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US 2010O226943A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0226943 A1 Brennan et al. (43) Pub. Date: Sep. 9, 2010

(54) SURFACE TOPOGRAPHIES FOR NON-TOXIC a continuation-in-part of application No. 1 1/202,532, BOADHESON CONTROL filed on Aug. 12, 2005, now Pat. No. 7,143,709, which is a continuation-in-part of application No. 10/780, (75) Inventors: Anthony B. Brennan, Gainesville, 424, filed on Feb. 17, 2004, now Pat. No. 7,117,807. FL (US); Christopher James Long, Titusville, FL (US); Joseph Publication Classification W. Bagan, Greenwood Village, CO (US); James Frederick (51) Int. Cl. Schumacher, Cumming, GA (US); A6IR 9/00 (2006.01) Mark M. Spiecker, Denver, CO B32B 3/00 (2006.01) (US) A 6LX 9/70 (2006.01) (52) U.S. Cl...... 424/400; 428/141; 428/143 Correspondence Address: CANTOR COLBURN, LLP (57) ABSTRACT 20 Church Street, 22nd Floor Hartford, CT 06103 (US) Disclosed herein is an article that includes a first plurality of spaced features. The spaced features are arranged in a plural (73) Assignee: UNIVERSITY OF FLORIDA, ity of groupings; the groupings of features include repeat Gainesville, FL (US) units; the spaced features within a grouping are spaced apart at an average distance of about 1 nanometer to about 500 (21) Appl. No.: 12/550,870 micrometers; each feature having a surface that is Substan tially parallel to a surface on a neighboring feature; each (22) Filed: Aug. 31, 2009 feature being separated from its neighboring feature; the groupings of features being arranged with respect to one Related U.S. Application Data another so as to define a tortuous pathway. The plurality of (63) Continuation-in-part of application No. 11/567,103, spaced features provide the article with an engineered rough filed on Dec. 5, 2006, now Pat. No. 7,650,848, which is ness index of about 5 to about 20.

130 111 U

Sea.

Patent Application Publication Sep. 9, 2010 Sheet 4 of 15 US 2010/0226943 A1

Depth Spacing Width Roughness (um) (um) (um) Factor

has c C O O S. s wn V Patent Application Publication Sep. 9, 2010 Sheet 5 of 15 US 2010/0226943 A1

Patent Application Publication Sep. 9, 2010 Sheet 7 of 15 US 2010/0226943 A1 FIG. 6A

FIG. 6B

Patent Application Publication Sep. 9, 2010 Sheet 8 of 15 US 2010/0226943 A1

FIG. 7A

Patent Application Publication Sep. 9, 2010 Sheet 10 of 15 US 2010/0226943 A1

FIG. 8A

800 8500 Reduction

4O O

Patent Application Publication Sep. 9, 2010 Sheet 11 of 15 US 2010/0226943 A1

FIG. 9 Ulva Settlement VSER Gradient Studies 800 7003 v=-27.431x+ 575,34 600 R2 = 0.83

500 400

ER Patent Application Publication Sep. 9, 2010 Sheet 12 of 15 US 2010/0226943 A1

FIG. 10

Balanus amphitrite Settlement 6500 Reduction

O 3 0. 2 O. 1 O

FIG. 1 1A Settlement of B. amphitrite ASSay 1 1 5

1 2 48 hrs 9

6

3

Glass Smooth 2OCH 40CH 2OSK 40SK Patent Application Publication Sep. 9, 2010 Sheet 13 of 15 US 2010/0226943 A1 FIG. 11B Settlement of B. amphitrite ASSay 2

1 O

O Glass Smooth 20OH 40CH 20SK 40SK

24 hrs O72 hrs FIG. 11C Settlement of B. amphitrite Assay 3

Smooth 20OH 40CH 20SK 40SK 24 hrs 48 hrs Patent Application Publication Sep. 9, 2010 Sheet 14 of 15 US 2010/0226943 A1

FG 12 50 um

FIG 13

Patent Application Publication Sep. 9, 2010 Sheet 15 of 15 US 2010/0226943 A1

FIG . 14A

FIG 14B US 2010/0226943 A1 Sep. 9, 2010

SURFACE TOPOGRAPHIES FOR NON-TOXC typically cuprous oxide or tributyltin, into the . The BOADHESON CONTROL biocides are either tethered to the coated surface or are released from the Surface into the Surrounding environment. CROSS-REFERENCE TO RELATED Use of these types of coatings has caused damage to the APPLICATIONS marine ecosystem, especially in shallow bays and harbors, 0001. This application is a continuation-in-part (CIP) where the biocides can accumulate. As such, the use of tribu application of U.S. patent application Ser. No. 11/567,103, tyltin has been banned in many parts of the world. These which is a continuation-in-part (CIP) application of U.S. products are effective for only approximately 2 to 5 years. patent application Ser. No. 1 1/202,532 entitled “SURFACE 0008 Foul release coatings present a hydrophobic, low TOPOGRAPHY FOR NON-TOXICBIOADHESION CON Surface energy, and resulting slippery Surface that minimizes TROL' which was filed on Aug. 12, 2005, now U.S. Pat. No. the adhesion of the biofouling organisms. The most com 7,143,709, which a CIP of U.S. patent application Ser. No. monly used and highly successful of these is a nontoxic 10/780,424 entitled “DYNAMICALLY MODIFIABLE silicone-based paint. The silicone-based coating requires sev POLYMER COATINGS AND DEVICES’ which was filed eral layers to make it effective, and therefore it can be quite on Feb. 17, 2004, now U.S. Pat. No. 7,117,807, each of which costly. Effectiveness lasts up to 5 years at which time recoat are incorporated by reference in their entirety into the present ing may become necessary. These products are considered to application. be more environmentally sound as compared to anti-fouling coatings because they do not leach toxins. However, they are STATEMENT REGARDING FEDERALLY subject to abrasion, and therefore their use is limited to areas SPONSORED RESEARCH ORDEVELOPMENT that are not Susceptible to damage caused by ice or debris. 0009 Biofouling is similarly a problem for surfaces used 0002 The United States Government has rights in this in biomedical applications. The accumulations of bacteria, invention pursuant to Office of Naval Research (ONR) Grant i.e. a biofilm, on implanted devices Such as orthopedic pros No. NOOO14-02-1-0325 theses present a significant risk of leading to com plications as severe as death. In cosmetic implants, devices FIELD OF THE INVENTION such as breast implants are fouled with fibroblasts and acel 0003. The invention relates to articles and related devices lular extracellular matrix resulting in a hard fibrous capsule and systems having Surface topography and/or surface elastic and Subsequent implant rupture. Blood contacting Surfaces properties for providing non-toxic bioadhesion control. Such as artificial heart Valves and artificial vascular grafts are fouled by proteins such as fibrinogen that initiate the coagu BACKGROUND lation cascade leading in part to heart attack and . The accumulated affect of bio fouling on chronic and acute dis 0004 Biofouling is the unwanted accumulation of organic ease states, its contribution to morbidity and its massive medi and inorganic matter of biological origin on Surfaces. For cal expenses places biofouling as one of the major issues example, in the marine environment bio fouling is the result of marine organisms settling, attaching, and growing on Sub facing modern medicine. merged marine Surfaces. The bio fouling process is initiated SUMMARY OF THE INVENTION within minutes of a Surface being Submerged in a marine environment by the absorption of dissolved organic materials 0010. An article has a surface topography for resisting which result in the formation of a conditioning film. Once the bioadhesion of organisms and includes a base article having a conditioning film is deposited, bacteria (e.g. unicellular Surface. The chemical composition of the Surface comprises a algae) colonize the surface within hours of submersion. The polymer. The Surface has a topography comprising a pattern resulting biofilm produced from the colonization of the bac defined by a plurality of spaced apart features attached to or teria is referred to as microfouling or slime and can reach projected into the base article. The plurality of features each thicknesses on the order of 500 um. have at least one microscale dimension and at least one neigh 0005 Biofouling is estimated to cost the U.S. Navy alone boring feature having a substantially different geometry. An over $1 billion per yearby increasing the hydrodynamic drag average spacing between adjacent ones of the features is of naval vessels. This in turn decreases the range, speed, and between 10um and 100 um in at least a portion of the surface. maneuverability of naval vessels and increases the fuel con 0011 Surface topographies according to the invention sumption by up to 30-40%. Thus, biofouling weakens the resist bioadhesion as compared to the base article. As used national defense. Moreover, biofouling is also a major eco herein, a Surface that provides a Surface topography accord nomical burden on commercial shipping, recreational craft, ing to the invention can be applied to a surface as either a as well as civil structures, bridges, and power generating printed patterned, adhesive coating containing the topogra facilities. phy, or applied directly to the surface of the device through 0006 Any substrate in regular contact with water is likely micromolding. In the case of micromolding, the Surface to become fouled. No surface has been found that is com topography will be monolithically integrated with the under pletely resistant to fouling. Due to the vast variety of marine lying article. organisms that form biofilms, the development of a single 0012. The feature spacing distance as used herein refers to Surface coating with fixed Surface properties for the preven the distance between adjacent features. Moreover, as used tion biofilm formation for all relevant marine organisms is a herein, “microscale features’ includes micron size or smaller difficult if not impossible task. features, thus including microscale and nanoscale. 0007 Anti-fouling and foul-release coatings are two main 0013. In one embodiment of the invention referred to as a approaches currently used for combating biofilm formation. hierarchical architecture, at least one multi-element plateau Anti-fouling coatings prevent or deter the settling of biofoul layer is disposed on a portion of the Surface. A spacing dis ing organisms on a Surface by the use of leached biocides, tance between elements of the plateau layer provides a second US 2010/0226943 A1 Sep. 9, 2010

feature spacing being Substantially different as compared to apart at an average distance of about 1 nanometer to about 500 the first feature spacing. The hierarchical architecture can micrometers; each feature having a surface that is Substan simultaneously repel organisms having Substantial different tially parallel to a surface on a neighboring feature; each sizes, such as spores and barnacles. In one embodiment the feature being separated from its neighboring feature; the surface is monolithically integrated with the base article, groupings of features being arranged with respect to one wherein a composition of the base article is the same as the another so as to define a tortuous pathway. composition of the Surface. In another embodiment, the Sur 0019 Disclosed herein too is an article comprising a plu face comprises a coating layer disposed on the base article. In rality of spaced features; the features arranged in a plurality of this coating embodiment, the composition of the coating layer groupings; the groupings of features comprising repeat units: is different as compared to a composition of the base article, the spaced features within a grouping being spaced apart at an and the polymer can comprise a non-electrically conductive average distance of about 1 nanometer to about 500 microme polymer, Such as selected from elastomers, rubbers, polyure ters; the groupings of features being arranged with respect to thanes and polysulfones. one another so as to define a tortuous pathway and wherein a 0014. The topography can provide an average roughness tangent to the tortuous pathway intersects with a spaced fea factor (R) of from 4 to 50 and an elastic modulus of between ture; the spaced feature being different from each nearest 10 kPa and 10 MPa. In another embodiment, the topography neighbor and not in contact with the nearest neighbor. is numerically representable using at least one sinusoidal function, such as two different sinusoidal waves. An example BRIEF DESCRIPTION OF THE DRAWINGS of a two different sinusoidal wave topography comprises a Sharklet topography. In another embodiment, the plurality of 0020. A fuller understanding of the present invention and spaced apart features can have a Substantially planar top Sur the features and benefits thereof will be obtained upon review face. In a preferred embodiment for controlling barnacles, the of the following detailed description together with the accom first feature spacing can be between 15 and 60 um. panying drawings, in which: 0015. In the multi-element plateau layer disposed on a 0021 FIG. 1(a) is a scanned SEM image of an exemplary portion of Surface embodiment, wherein a spacing distance "Sharklet' anti-algae Surface topography comprising a plu between elements of the plateau layer provide a second fea rality of raised surface features which project out from the ture spacing being Substantially different as compared to the Surface of a base article, according to an embodiment of the first feature spacing, the Surface can comprise a coating layer invention. disposed on the base article. The elastic modulus of the coat 0022 FIG. 1(b) is a scanned optical profilometry image of ing layer can be between 10 kPa and 10 MPa. a pattern having a plurality of features projecting into the 0016. The base article can comprise a roofing material. In Surface of a base article, according to another embodiment of another embodiment, the base article comprises a water pipe, the invention. wherein the surface is provided on an inner surface of a water 0023 FIG. 2(a)-(d) illustrate some exemplary surface inlet pipe. In this embodiment, the inlet pipe can be within a architectural patterns according to the invention. power plant in another embodiment, the base article com 0024 FIG.3 provides a table of exemplary feature depths, prises an implantable device or material. Such as a breast feature spacings, feature widths and the resulting roughness implant, a catheter or a heart Valve. factor (R) based on the patterns shown in FIGS. 2(a)-(d). 0017. In another embodiment of the invention, an article 0025 FIG. 4 is a depiction of an exemplary hierarchical has a Surface topography for resisting bioadhesion of organ Surface topography according to an embodiment of the inven isms, comprising a base article having a surface. The compo tion. sition of the Surface comprises a polymer, the Surface having 0026 FIG. 5(a) shows a sinusoidal wave beginning at the a topography comprising a pattern defined by a plurality of centroid of the smallest (shortest) of the four features com spaced apart features attached to or projected into the base prising the Sharklet pattern. article. The plurality offeatures each have at least one micros 0027 FIG. 5(b) shows sine and cosine waves describing cale dimension and at least one neighboring feature having a the periodicity and packing of the Sharklet pattern. Substantially different geometry, wherein an average first fea 0028 FIG. 6(a) shows two (of four) exemplary Sharklet ture spacing between adjacent ones of the features is micros elements, element 1 and element 2; the element 1 and element cale and topography is numerically representable using at 2 have different lengths and widths. least one sinusoidal function. The Surface can comprise a 0029 FIG. 6(b) shows the resulting layout after following coating layer disposed on the base article. In a first embodi limitations 3 & 4 (described below) and defining X. Ps ment the first feature spacing is between 0.5 and 5 um in at (y-spacing between Smaller element and larger element after least a portion of the Surface, while in a second embodiment packing), and FIG. 6(c) shows the resulting layout between the first feature spacing is between 15 and 60 Lum in at least a two elements by setting the spacing to 3 microns. portion of the Surface. The at least one sinusoidal function can 0030 FIG. 7(a) shows a space filled with elements that comprise two different sinusoidal waves, such as a Sharklet have a different periodicity: FIG. 7(b) shows the result of topography. The article can further comprise at least one applying sinusoidal waves to define aperiodic structures, multi-element plateau layer disposed on a portion of the Sur while FIG. 7(c) shows the resulting topographical structure face, wherein a spacing distance between elements of the over the full area of the desired surface. plateau layer provide a second feature spacing being Substan 0031 FIG. 8(a) shows settlement density data for algae tially different as compared to the first feature spacing. spores on a smooth control sample as compared to the settle 0018 Disclosed herein is an article comprising a plurality ment density on the Sharklet Surface architecture according to of spaced features; the spaced features arranged in a plurality the invention shown in FIG. 1(a); FIG. 8(b) is a scanned light of groupings; the groupings of features comprising repeat micrograph image showing algae spores on the Surface of the units; the spaced features within a grouping being spaced control sample, while FIG. 8(c) is a scanned light micrograph US 2010/0226943 A1 Sep. 9, 2010 image showing a dramatic reduction in algae spores on the and aperiodic. In another embodiment, the pathway between Surface of the Surface architecture according to the invention the features may be linear but of a varying thickness. The shown in FIG. 1(a). plurality of spaced features may be projected outwards from 0032 FIG. 9 shows a correlation between Ulva Spore a Surface or projected into the Surface. In one embodiment, settlement density and the corresponding Engineered Rough the plurality of spaced features may have the same chemical ness Index (ERI) for several topographical patterns according composition as the Surface. In another embodiment, the plu to the invention (shown in A-D above the correlation data). rality of spaced features may have a different chemical com 0033 FIG.10 shows settlement data from B. amphitrite on position from the Surface. various (PDMS elastomer (PDMSe) channel topographies. Mean values+1 standard error are shown. 0043. In one embodiment, an article having a surface 0034 FIG.11(a) is a chart showing barnacle cyprid settle topography for resisting bioadhesion of organisms, com ment for a first assay (assay 1). Cyprids were allowed to settle prises a base article having a Surface. The composition of the for 48 hrs on each of the test surfaces. Topographies used Surface and/or the base article comprises a polymer, a metal or included 20x20 channels (20CH), 20x20 Sharklet (20SK), an alloy, a ceramic. Combinations of polymers, metals and 20x40 channels (40CH) and 20x40 Sharklet (40SK). Error ceramics may also be used in the Surface or the base article. bars represent +1 standard error. The Surface having a topography comprising a plurality of 0035 FIG. 11(b) is a chart of barnacle cyprid settlement patterns; each pattern being defined by a plurality of spaced for a second assay (assay 2). Cyprids were allowed to settle apart features attached to or projected into the base article. for up to 72hrs on each of the test Surfaces. Topographies used The plurality of features each have at least one microscale included 20x20 channels (20CH), 20x20 Sharklet (20SK), (micrometer or nanometer sized) dimension and has at least 40x40 channels (40CH) and 40x40 Sharklet (40SK). Error one neighboring feature having a Substantially different bars represent +1 standard error. geometry. The average first feature spacing between the adja 0036 FIG. 11(c) is a chart of barnacle cyprid settlement cent features is between 10um and 100 um in at least a portion for a third assay (assay 3). Cyprids were allowed to settle for of the Surface, wherein said plurality of spaced apart features up to 48 hrs on each of the test Surfaces. Topographies used are represented by a periodic function. It is to be noted that included 20x20 channels (20CH), 20x20 Sharklet (20SK), each of the features of the plurality of features are separated 40x40 channels (40CH) and 40x40 Sharklet (40SK). Error bars represent +1 standard error. from each other and do not contact one another. 0037 FIG. 12 is a photograph showing the fractal dimen 0044. In one embodiment, the surface is monolithically sions measured parallel to the surface of the substrate. integrated with said base article, wherein a composition of the 0038 FIG. 13 is a photograph showing a pattern having base article is the same as the composition of the Surface. In nanometer sized features. another embodiment, the Surface comprises a coating layer 0039 FIG. 14 depicts how the degrees of freedom are disposed on the base article. In yet another embodiment, the calculated. FIG. 14(A) shows a pattern that results in two composition of the coating layer is different from the com degrees of freedom for an organism traveling along a channel. position of the base article. In one embodiment, the polymer FIG. 14(A) shows a pattern that results in one degree of comprises a non-electrically conducting polymer. freedom for an organism traveling along a channel. 0045. In another embodiment, the topography provides an average roughness factor (R) of from 4 to 50. The surface may DETAILED DESCRIPTION OF THE INVENTION comprise an elastomer that has an elastic modulus of about 10 0040. The present invention describes a variety of scalable kPa to about 10 MPa. Surface topographies for modification of biosettlement and 0046. As noted above, the pattern is separated from a bioadhesion, such as bioadhesion of biofouling organisms, neighboring pattern by a tortuous pathway. The tortuous path including, but not limited to, algae, bacteria and barnacles. As way may be represented by a periodic function. The periodic described in the Examples below, it has been proven through functions may be different for each tortuous pathway. In one experimental testing that Surface topographies according to embodiment, the patterns can be separated from one another the invention provide a passive and non-toxic Surface, which by tortuous pathways that can be represented by two or more through selection of appropriate feature sizes and spacing, periodic functions. The periodic functions may comprise a can significantly and generally dramatically reduce settle sinusoidal wave. In an exemplary embodiment, the periodic ment and adhesion of the most common fouling marine algae function may comprise two or more sinusoidal waves. known, as well as the settlement of barnacles. In one embodi 0047. In another embodiment, when a plurality of differ ment, the plurality of spaced features increase the effective ent tortuous pathways are represented by a plurality of peri ness of algaecides or . The algaecides and/or anti odic functions respectively, the respective periodic functions biotics can be contained in the Surface and can be released may be separated by a fixed phase difference. In yet another gradually when desired. embodiment, when a plurality of different tortuous pathways 0041 Disclosed herein are articles comprising a plurality are represented by a plurality of periodic functions respec of spaced features; the features arranged in a plurality of tively, the respective periodic functions may be separated by groupings; the groupings of features being arranged with a variable phase difference. respect to one another so as to define a tortuous pathway when 0048. In one embodiment, the plurality of spaced apart viewed in a first direction. When viewed in a second direction, features have a substantially planar top surface. In another the groupings of features are arranged to define a linear path embodiment, a multi-element plateau layer can be disposed way. on a portion of the Surface, wherein a spacing distance 0042. In one embodiment, when viewed in a second direc between elements of said plateau layer provide a second tion, the pathway between the features may be non-linear and feature spacing; the second feature spacing being Substan non-sinusoidal. In other words, the pathway can be non-linear tially different when compared to the first feature spacing. US 2010/0226943 A1 Sep. 9, 2010

0049. In one embodiment, the pattern comprises a coating chemical composition from that of the Surface. In one layer disposed on said base article. In other words, the coating embodiment, the features have similar geometries, while in layer comprises the pattern and is disposed on the base article. another embodiment, the features can have different geom 0050. In another embodiment, an article having a surface etries. As will be detailed below, the groupings show dila topography for controlling (e.g., resisting or facilitating) the tional symmetry. bioadhesion of organisms, comprises a base article having a 0056. The plurality of spaced features is applied to the Surface; wherein the composition of the Surface comprises a Surface in the form of a coating and can comprise an organic polymer, a ceramic or a metal. The Surface has a topography polymer, a ceramic or a metal. As noted above, the groupings comprising a pattern defined by a plurality of spaced apart of features are arranged with respect to one another so as to features attached to or projected into the base article. The define a linear pathway or a plurality of channels. The tortu plurality of features each have at least one microscale dimen ous pathway is defined by a sinusoidal function. sion and have at least one neighboring feature having a Sub stantially different geometry. The features are separated from 0057. In one embodiment, the features are periodic. In each other and the average feature spacing is about 1 nanom another embodiment, the features are aperiodic. The features eter to about 500 micrometers. The topography is numerically have a roughness factor (R) of about 2 to about 20. representable using at least one periodic function; the peri 0058 As can be seen in the FIGS. 1(a), 1(b), 2(a), 2(b), odic function being representable by a pathway situated Sub 2(c), 2Gd), 5,5(a), 7(a), 7(b) and 7(c), the article comprises a stantially between a plurality of patterns of the spaced apart plurality of spaced features; the spaced features being features. arranged in a plurality of groupings. The FIGS. 1(a), 1(b). 0051. In one embodiment, the first feature spacing is 2(a), 2Gb), 20c), 2(d), 5 (a), 5(b), 7(a), 7(b) and 7(c) show that between 0.5 micrometers (Lm) and 5 um in at least a portion the groupings of features comprise at least Some repeat units. of the surface. In another embodiment, the first feature spac As can be seen in these Figures, the groupings have patterns ing is between 15 and 60 um in at least a portion of said of features. As can also be seen in these figures, the groupings Surface. As noted above, the periodic function comprises two of features are arranged with respect to one another so as to different sinusoidal waves. In one embodiment, the topogra define a tortuous pathway when viewed in one direction and phy resembles the topography of shark-skin (e.g., a Sharklet). define linear pathways when viewed in other directions. In another embodiment, the pattern comprises at least one 0059. As can be seen in the FIGS. 5(a) and 5(b), the multi-element plateau layer disposed on a portion of the Sur tortuous pathway exists substantially between pluralities of face, wherein a spacing distance between elements of the groupings of such features. As can be seen in the FIG. 5(a), an plateau layer provides a second feature spacing; the second occasional feature may lie in the otherwise tortuous pathway. feature spacing being Substantially different when compared In one embodiment, a tangent to the tortuous pathway will to said first feature spacing. always intersect a single separated feature of the pattern. In 0052. In yet another embodiment, an article having a sur one embodiment, a frequency of intersection between the face topography for resisting bioadhesion of organisms, com tangent to the tortuous pathway and the spaced feature is prises a base article having a surface. The Surface has a periodic. In another embodiment, a frequency of intersection topography that comprises a pattern defined by a plurality of between a tangent to the tortuous pathway and a spaced spaced apart features attached to or projected into the base feature is aperiodic. In another embodiment, a frequency of article. The plurality of features comprise at least one feature intersection between a tangent to the tortuous pathway and a having a Substantially different geometry. The features are shared feature is periodic. In another embodiment, a fre separated from each other. One of these features that is a part quency of intersection between a tangent to the tortuous path of the pattern is shared by a neighboring pattern. The plurality way and the shared spaced feature is aperiodic. of spaced apart features has at least one microscale dimen 0060. It is generally desirable for the groupings of features Sion. The neighboring patterns are separated from each other to comprise at least one repeat unit and to share at least one by a tortuous pathway. The tortuous pathway has at least two common feature. For example, in the FIGS. 1(a), 1(b), the or more directions. groupings of feature have a repeat unit that has a diamond 0053. In another embodiment, an article comprises a plu shape. It can also be seen that the Smallest feature in each rality of spaced features. The features are arranged in a plu repeat unit is shared by two adjacent repeat units or by two rality of groupings; the groupings of features comprise repeat adjacent groups of features. The sharing of the feature by two units. The spaced features within a grouping are spaced apart or more groups of patterns results in the formation of the at an average distance of about 0.5 to about 200 micrometers. tortuous pathway. Similarly the FIGS. 2(a) and 20b) show at The groupings of features are arranged with respect to one least one feature that is shared by two adjacent repeat units. another so as to define a tortuous pathway, the groupings have 0061 The number of features in a given pattern can be odd patterns of features wherein one or more features are shared or even. In one embodiment, if the total number of features in between groupings. These are generally referred to as shared a given pattern are equal to an odd number, then the number features. The plurality of spaced feature extend outwardly of shared features are generally equal to an odd number. In from a surface. another embodiment, if the total number offeatures in a given 0054. In one embodiment, a sum of a number of features pattern are equal to an even number, then the number of shared by two neighboring groupings is equal to an odd features in the given pattern are equal to an even number. number. In another embodiment, a sum of a number of fea 0062. The spaced features can have variety of geometries tures shared by two neighboring groupings is equal to an even and can exist in one, two or three dimensions or any dimen number. sions therebetween. The spaced features can have similar 0055. In one embodiment, the plurality of spaced features geometries with different dimensions or can have different has a similar chemical composition to the Surface. In another geometries with different dimensions. For example, in the embodiment, the plurality of spaced features has a different FIG. 1(a), the spaced features are of a similar shape, with each US 2010/0226943 A1 Sep. 9, 2010

shape having a different sizes, while in the FIGS. 7(a), 7(b) cifically about 3.25 to about 3.95, more specifically about and 7(c), the spaced features have different geometries and 3.35 to about 3.85 in a plane measured perpendicular to the different dimensions. surface upon which the features are disposed. In other words, 0063. The geometries can be regular (e.g., described by the tortuous pathway or the surface of each feature may be Euclidean mathematics) or irregular (e.g., described by non textured with features similar to those of the pattern (albeit on Euclidean mathematics). Euclidean mathematics describes a smaller scale), thus creating micro-tortuous pathways and those structures whose mass is directly proportional to a nano-tortuous pathways within the tortuous pathway itself. characteristic dimension of the spaced feature raised to an 0070. In another embodiment, the spaced features may integer power (e.g., a first power, a second power or a third have multiple fractal dimensions in a direction parallel to the power). In one embodiment, the geometries can comprise Surface upon which the features are disposed. The spaced shapes that are described by Euclidean mathematics such as, features may be arranged to have 2 or more fractal dimen for example, lines, triangles, circles, quadrilaterals, polygons, sions, specifically 3 or more dimensions, specifically 4 or spheres, cubes, fullerenes, or combinations of Such geom more dimensions in a direction parallel to the Surface upon etries. which the features are disposed. As can be seen in the FIG. 12 0064. For example, the FIGS. 1(a) and 1(b) show that the (a), the features have 3 different fractal dimensions in a plane spaced features are almost elliptical, i.e., the cross-sectional parallel to the surface upon which the features are disposed. geometry of each feature when viewed from the top-down is The fractal dimensions created by the features in a direction similar to that which could be obtained by combining rect from the top to the bottom of the micrograph are 1.444 and angles with semi-circles. Similarly, the FIGS. 2(b), 2(c) and 1.519 respectively, while the fractal dimension created by the 2(d) show features that comprise circles, sections of circles features in a direction from left to right have dimensions of (e.g., semi-circles, quarter-circles), triangles, and the like. 1.557. The presence of the texture having multiple fractal 0065. In one embodiment, a repeat unit can be combined dimensions prevents bioadhesion of algae, bacteria, virus, with a neighboring repeat unit so as to produce a combination and other organisms. of spaced apart features that have a geometry that is described by Euclidean mathematics. As can be seen in the FIGS. 2(c) 0071. In yet another embodiment, the spaced features may and 2Cd), the respective repeat units can be combined to have multiple fractal dimensions in a direction perpendicular produce different geometries. For example in the FIG. 2(d). to the surface upon which the features are disposed. The the repeat unit can be combined with a single neighboring spaced features may be arranged to have 2 or more fractal repeat unit to produce a diamond shaped geometry. Similarly, dimensions, specifically 3 or more dimensions, specifically 4 3 or more neighboring repeat units can be combined to pro or more dimensions in a direction parallel to the surface upon duce a rhombohedral, while six repeat units can be combined which the features are disposed. to produce a hexagon. Thus repeat units may be combined to 0072. As will be noted below, the tortuous pathway may be produce structures whose geometries can be described by defined by a sinusoidal function, a spline function, a polyno Euclidean mathematics. mial function, or the like. The tortuous pathway generally 0066. In one embodiment, the spaced features can have exists between a plurality of groupings of spaced features and irregular geometries that can be described by non-Euclidean may occasionally be interrupted by the existence of a feature mathematics. Non-Euclidean mathematics is generally used or by contact between two features. For example, in the FIGS. to describe those structures whose mass is directly propor 5(a) and5(b), the sinusoidal tortuous pathway intersects with tional to a characteristic dimension of the spaced feature the commonly shared feature and is thereby interrupted by it. raised to a fractional power (e.g., fractional powers such as The frequency of the intersection between the tortuous path 1.34, 2.75, 3.53, or the like). Examples of geometries that can way and the spaced feature may be periodic or aperiodic. In be described by non-Euclidean mathematics include fractals one embodiment, the tortuous pathway may have a periodic and other irregularly shaped spaced features. ity to it. In another embodiment, the tortuous pathway may be 0067. In one embodiment, spaced features whose geom aperiodic. In one embodiment, two or more separate tortuous etries can be described by Euclidean mathematics may be pathways never intersect one another. combined to produce features whose geometries can be 0073. The tortuous pathway can have a length that extends described by non-Euclidean mathematics. In other words, the over the entire length of the surface upon which the pattern is groupings of features can have dilational symmetry. The frac disposed, if the features that act as obstructions in the tortuous tal dimension can be measured perpendicular to the Surface pathway are by-passed. The width of the tortuous pathway as upon which the features are disposed or may be measured measured between two adjacent features of two adjacent pat parallel to the surface upon which the features are disposed. terns are about 10 nanometers to about 500 micrometers, The fractal dimensions are measured in the inter-topographi specifically about 20 nanometers to about 300 micrometers, cal gaps. specifically about 50 nanometers to about 100 micrometers, 0068. In one embodiment, the fractal dimensions can have and more specifically about 100 nanometers to about 10 fractional powers of about 1.00 to about 3.00, specifically micrometers. about 1.25 to about 2.25, more specifically about 1.35 to 0074 The spaced features have linear pathways or chan about 1.85 in a plane measured parallel to the surface upon nels between them. In one embodiment, the spaced features which the features are disposed. In another embodiment, the can have a plurality of linear pathways or a plurality of chan fractal dimensions can have fractional powers of about 1.00 to nels between them. about 3.00, specifically about 1.25 to about 2.25, more spe 0075. The spaced features can be periodic or aperiodic. As cifically about 1.35 to about 1.85 in a plane measured perpen can be seen in the FIG. 1(a), the spaced features can be dicular to the surface upon which the features are disposed. periodic, while as seen in the FIGS. 7(a), 7(b) and 7(c), the 0069. In yet another embodiment, the fractal dimensions spaced features can be aperiodic. In a similar manner, the can have fractional powers of about 3.00 to about 4.00, spe patterns can be periodic or aperiodic. US 2010/0226943 A1 Sep. 9, 2010

0076. As noted above, the spaced features can have differ another embodiment, each pattern has at least four or more ent dimensions (sizes). The average size of the spaced fea neighboring patterns that have a different size or shape. tures can be nanoscale (e.g., they can be less than 100 nanom I0083. As noted above the chemical composition of the eters) or greater than or equal to about 100 nanometers. In one spaced features can be different from the surface. The spaced embodiment, the spaced features can have average dimen features and the surfaces from which these features are pro sions of 1 nanometer to 500 micrometers, specifically about jected or projected into can also comprise organic polymers 10 nanometers to about 200 micrometers, and more specifi or inorganic materials. cally about 50 nanometers to about 100 micrometers. I0084 Organic polymers used in the spaced features and/or 0077. In another embodiment, the average periodicity the surface can be may be selected from a wide variety of between the spaced features can be about 1 nanometer to thermoplastic polymers, blend of thermoplastic polymers, about 500 micrometers. In one embodiment, the periodicity thermosetting polymers, or blends of thermoplastic polymers between the spaced features can be about 2, 5, 10, 20, 50, 100 with thermosetting polymers. The organic polymer may also or 200 nanometers. In another embodiment, the average peri be a blend of polymers, copolymers, terpolymers, or combi odicity between the spaced features can be about 2, 5, 10, 20, nations comprising at least one of the foregoing organic poly 50, 100 or 200 nanometers. In another embodiment, the peri mers. The organic polymer can also be an oligomer, a odicity can be about 0.1, 0.2,0.5, 1, 5, 10, 20, 50, 100, 200, homopolymer, a copolymer, a block copolymer, an alternat 300, 400 or 450 micrometers. In yet another embodiment, the ing block copolymer, a random polymer, a random copoly average periodicity can be about 0.1, 0.2,0.5, 1, 5, 10, 20, 50. mer, a random block copolymer, a graft copolymer, a star 100, 200, 300, 400 or 450 micrometers. block copolymer, a dendrimer, a polyelectrolyte (polymers 0078. In one embodiment, the spaced features can have that have some repeat groups that contain electrolytes), a dimensions of 1 nanometer to 500 micrometers, specifically polyampholyte (a polyelectrolyte having both cationic and about 10 nanometers to about 200 micrometers, and more anionic repeat groups), an ionomer, or the like, or a combi specifically about 50 nanometers to about 100 micrometers. nation comprising at last one of the foregoing organic poly 0079. In another embodiment, the periodicity between the CS. spaced features can be about 1 nanometer to about 500 I0085 Examples of the organic polymers are polyacetals, micrometers. In one embodiment, the periodicity between the polyolefins, polyacrylics, polycarbonates, polystyrenes, spaced features can be up to about 2, 5, 10, 20, 50, 100 or 200 polyesters, polyamides, polyamideimides, polyarylates, pol nanometers. In another embodiment, the periodicity between yarylsulfones, polyetherSulfones, polyphenylene Sulfides, the spaced features can be about 2, 5, 10, 20, 50, 100 or 200 polyvinyl chlorides, polysulfones, polyimides, polyetherim nanometers. In another embodiment, the periodicity can be ides, polytetrafluoroethylenes, polyetherketones, polyether up to about 0.1, 0.2,0.5, 1, 5, 10, 20, 50, 100, 200,300, 400 or etherketones, polyether ketone ketones, polybenzoxazoles, 450 micrometers. In yet another embodiment, the periodicity polyphthalides, polyacetals, polyanhydrides, polyvinyl can be up to about 0.1, 0.2,0.5, 1, 5, 10, 20, 50, 100,200,300, , polyvinyl thioethers, polyvinyl , polyvinyl 400 or 450 micrometers. ketones, polyvinyl halides, polyvinyl nitriles, polyvinyl 0080. In one embodiment, each feature of a pattern has at esters, polysulfonates, polysulfides, polythioesters, polysul least one neighboring feature that has a different geometry fones, polysulfonamides, polyureas, polyphosphaZenes, pol (e.g., size or shape). A feature of a pattern is a single element. ysilaZanes, styrene acrylonitrile, acrylonitrile-butadiene-sty Each feature of a pattern has at least 2,3,4, 5, or 6 neighboring rene (ABS), polyethylene terephthalate, polybutylene features that have a different geometry from the feature. In terephthalate, polyurethane, propylene diene rubber one embodiment, there are at least 2 or more different features (EPR), polytetrafluoroethylene, perfluoroelastomers, fluori that form the pattern. In another embodiment, there are at nated ethylene propylene, perfluoroalkoxyethylene, poly least 3 or more different features that form the pattern. In yet chlorotrifluoroethylene, polyvinylidene fluoride, polysilox another embodiment, there are at least 4 or more different anes, or the like, or a combination comprising at least one of features that form the pattern. In yet another embodiment, the foregoing organic polymers. there are at least 5 or more different features that form the I0086 Examples of polyelectrolytes are polystyrene sul pattern. fonic acid, polyacrylic acid, pectin, carageenan, alginates, 0081. In another embodiment, at least two identical fea carboxymethylcellulose, polyvinylpyrrolidone, or the like, or tures of the pattern have at least one neighboring feature that a combination comprising at least one of the foregoing poly has a different geometry (e.g., size or shape). A feature of a electrolytes. pattern is a single element. In one embodiment, two identical I0087. Examples of thermosetting polymers suitable for features of the pattern have at least 2, 3, 4, 5, or 6 neighboring use in the polymeric composition include epoxy polymers, features that have a different geometry from the identical unsaturated polyester polymers, polyimide polymers, bisma features. In another embodiment, three identical features of leimide polymers, bismaleimide triazine polymers, cyanate the pattern have at least 2, 3, 4, 5, or 6 neighboring features ester polymers, vinyl polymers, benzoxazine polymers, ben that have a different geometry from the identical features. Zocyclobutene polymers, acrylics, alkyds, -formalde 0082 In another embodiment, each pattern has at least one hyde polymers, novolacs, resoles, melamine-formaldehyde or more neighboring patterns that have a different size or polymers, -formaldehyde polymers, hydroxymethyl shape. In other words, a first pattern can have a second neigh furans, isocyanates, diallyl , triallyl cyanurate, trial boring pattern that while comprising the same features as the lyl isocyanurate, unsaturated polyesterimides, or the like, or a first pattern can have a different shape from the first pattern. In combination comprising at least one of the foregoing thermo yet another embodiment, each pattern has at least two or more setting polymers. neighboring patterns that have a different size or shape. In yet I0088. Examples of blends of thermoplastic polymers another embodiment, each pattern has at least three or more include acrylonitrile-butadiene-styrene/nylon, polycarbon neighboring patterns that have a different size or shape. In yet ate/acrylonitrile-butadiene-styrene, acrylonitrile butadiene US 2010/0226943 A1 Sep. 9, 2010

styrenefpolyvinyl chloride, polyphenylene /polysty and more preferably less than or equal to about 65 wt %, based rene, polyphenylene ether/nylon, polysulfone/acrylonitrile on the total weight of the coating. butadiene-styrene, polycarbonate/thermoplastic urethane, 0092. When the pattern is used in a medical device, the polycarbonate/polyethylene terephthalate, polycarbonate/ drug coating may be coated onto the medical device in a polybutylene terephthalate, thermoplastic elastomer alloys, variety of ways. In one embodiment, the drug coating may be nylon/elastomers, polyesterfelastomers, polyethylene tereph dissolved in a solvent such as water, , alcohols such thalate/polybutylene terephthalate,acetal/elastomer, styrene , isopropanol, , , dimethylforma maleicanhydride/acrylonitrile-butadiene-styrene, polyether mide, dimethylacetamide, hexane, and the like, and coated etherketone/polyethersulfone, polyether etherketone/poly onto the medical device in the form of the pattern. In another etherimide polyethylene/nylon, polyethylene/polyacetal, or embodiment, a monomer may be covalently bonded with the the like. biologically active agent and then polymerized to form the drug coating, which is then applied onto the medical device in 0089 Polymers that can be used for the pattern or the the form of the pattern. In yet another embodiment, the poly substrate include biodegradable materials. Suitable examples meric resin may first be applied as a coating (in the form of the of biodegradable polymers are as polylactic-glycolic acid pattern) onto the medical device, following which the coated (PLGA), poly-caprolactone (PCL), copolymers of polylac device is immersed into the biologically active agent, thus tic-glycolic acid and poly-caprolactone (PCL-PLGA copoly permitting diffusion into the coating to form the drug coating. mer), polyhydroxy-butyrate-valerate (PHBV), polyorthoe 0093. In one embodiment, a biologically active agent can ster (POE), polyethylene oxide-butylene terephthalate (PEO be added to the pattern. Te biologically active agent can be PBTP), poly-D.L--p-dioxanone-polyethylene disposed upon the Surface of the pattern or can be included in glycol block copolymer (PLA-DX-PEG), or the like, or com the pattern (e.g., mixed with the material forming the pattern). binations comprising at least one of the foregoing biodegrad It may also be desirable to have two or more biologically able polymers. The biodegradable polymers upon undergoing active agents dispersed in a single drug coating layer. Alter degradation can be consumed by the body without any unde natively, it may be desirable to have two or more layers of the sirable side effects. drug coating coated upon the medical device. Various meth 0090. In one embodiment, the pattern can comprise a poly ods of coating may be employed to coat the medical device meric resin that is blended with a biologically active agent to Such as spin coating, electrostatic painting, dip-coating, form a drug coating. The biologically active agent is then painting with a brush, and the like, and combinations com gradually released from the pattern, which simply acts as a prising at least one of the foregoing methods of coating. carrier. When the polymeric resin is physically blended (i.e., 0094. Various types of biologically active agents may be not covalently bonded) with the biologically active agent, the used in the drug coating, which is used to coat the medical release of the biologically active agent from the drug coating device. The coatings on the medical device may be used to is diffusion controlled. It is generally desirable for the pattern deliver therapeutic and pharmaceutically biologically active to comprise an amount of about 5 weight percent (wt %) to agents including anti- agents, anti-arrhythmic about 90 wt % of the biologically active agent based on the agents, anti-bacterial agents, anti- agents, anti total weight of the drug coating. Within this range, it is gen coagulant agents, anti-convulsant agents, anti- erally desirable to have the biologically active agent present agents, anti-diabetic agents, anti-diuretic agents, anti-fungal in an amount of greater than or equal to about 10, preferably agents, anti-hypertensive agents, anti-inflammatory agents, greater than or equal to about 20, and more preferably greater anti-malarial agents, anti-neoplastic agents, anti-nootropic than or equal to about 30 wt % based on the total weight of the agents, anti-Parkinson agents, anti-retroviral agents, anti-tu drug coating. Within this range it is generally desirable to berculosis agents, anti-tussive agents, anti-ulcerative agents, have the biologically active agent present in an amount of less anti-viral agents, or the like, or a combination comprising at than or equal to about 75, preferably less than or equal to least one of the foregoing therapeutic and pharmaceutically about 70, and more preferably less than or equal to about 65 biologically active agents. wt % based on the total weight of the drug coating. The drug 0.095 Examples of other suitable therapeutic and pharma coating may be optionally coated with an additional Surface ceutically biologically active agents are anti-proliferative/ coating if desired. When an additional Surface coating is used, antimitotic agents including natural products Such as Vinca the release of the biologically active agent is interfacially alkaloids (e.g., , , and ), controlled. The drug coating may be disposed only on the , epidipodophyllotoxins (e.g., , tenipo surface of the features or alternatively on the surface of the side), antibiotics (e.g., , actinomycin D, dauno tortuous pathway. rubicin, , V, penicillin G. amplicillin, 0091. In another exemplary embodiment, the biologically , , , doxycycline, active agent may be covalently bonded with a biodegradable , , , aminoglyco polymer to form the drug coating. The rate of release is then side antibiotics, polypeptide antibiotics, , griseoful controlled by the rate of degradation of the biodegradable vin, and ), , , bleomy polymer. Suitable examples of biodegradable polymers are cins, , mithramycin and mitomycin, provided above. Within this range, it is generally desirable to (L-, which systemically metabolizes L-aspar have the biologically active agent present in an amount of agine and deprives cells which do not have the capacity to greater than or equal to about 10, preferably greater than or synthesize their own ), antiplatelet agents such as equal to about 20, and more preferably greater than or equal G(GP) IIb/IIIa inhibitors and vitronectin antago to about 30 wt % based on the total weight of the drug coating. nists, anti-proliferative/antimitotic alkylating agents such as Within this range, it is also generally desirable to have the mustards (e.g., mechlorethamine, cyclophospha biologically active agent present in an amount of less than or mide and analogs, , ), ethylenimines equal to about 75, preferably less than or equal to about 70, and methylmelamines (e.g., hexamethylmelamine and US 2010/0226943 A1 Sep. 9, 2010 ), alkyl Sulfonates-, (e.g., car brequinar, bropirimine, brostallicin, budotitane, bullatacin, mustine (BCNU) and analogs, streptozocin), traZenes-dacar buserelin, buSulfan, , folinate, calcium bazinine (DTIC), anti-proliferative/antimitotic antimetabo levofolinate, , , canertinib, canfos lites Such as folic acid analogs (e.g., ), famide, cantharidin, , caracemide, carbetimer, analogs (e.g., , , cytara , (carboprost tromethamine), carbo bine), analogs and related inhibitors (e.g., mercap quone, , carglumic acid, , , topurine, thioguanine, and 2-chlorodeoxyadenos carzelesin, cedefingol, cemadotin, cetuximab, cevipabulin, ine }), platinum coordination complexes (e.g., chlorambucil, (mechlorethamine), chlorota , carboplatin), , hydroxyurea, , moxifen, , , cisplatin, cladribine, aminoglutethimide, hormones (e.g., ), anti-coagu clanfenur, , clofazimine, citrate, lants (e.g., heparin, synthetic heparin salts and other inhibi cordycepin, corosolic acid, crisinatol, , cyclocyti tors of thrombin), fibrinolytic agents (e.g., tissue plasmino dine, , , , D-aminole gen activator, Streptokinase and urokinase), , Vulinic acid, , damsin, daniquidone, danusertib, , , , abciximab, antimi daporinad, darinaparsin, , daunoblastin, daunorubi gratory, antisecretory (e.g., breveldin), anti-inflammatory: cin/daunomycin, , deferasiroX, deforolimus, deme Such as adrenocortical (e.g., , , colcine, denibulin, detorubicin, dexniguldipine, dexormapl , , , 6C.-methylpred atin, dezaguanine, dianhydrodulcitolum, dibrospidium nisolone, , , and dexametha chloride, , diflomotecan, dinalin, disermolide, doc sone), non-steroidal agents (e.g., derivatives etaxel, dolfequidar, mesylate, dovitinib, doxifluri Such as aspirin, para-aminophenol derivatives Such as dine, doxorubicin, dromoStanolone, duaZomycin, duocarmy acetaminophen, indole and indene acetic acids (e.g., cin, dynemicin, ecomustine, edatrexate, edotecarin, indomethacin, , etodalac), heteroaryl acetic acids edotreotide, , elacridar, eacytarabine, . (e.g., , , ), arylpropionic acids elinafide, elomotecan, , emitefur, enloplatin, (e.g., and derivatives), anthranilic acids (e.g., mefe enocitabine, enpromate, , , entricitabine, namic acid, ), enolic acids (e.g., piroxi enzastaurin, , eptaloprost, , erlotinib, Eso cam, , , oxyphenthatraZone), nabu rubicin, , , etanidazole, , etopo metone, gold compounds (e.g., auranofin, , side, , , exisulind, fadrozole, faZarabine, gold sodium thiomalate), immunosuppressives (e.g., fiacitabine, floxuridine, , , fluo cyclosporine, (FK-506), (e.g., rapamy rocitabine, , , forodesine, fosfluridine cin, , mycophenolate mofetil), angiogenic agents tidoxil, fosquidone, fostriecin, , fotretamine, full such as vascular endothelial growth factor (VEGF), fibroblast Vestrant, , galarubicin, galocitabine, gefitinib, growth factor (FGF), angiotensin receptor blockers, nitric , gemtuzumab ozogamicin, geroquinol, gigan oxide donors, anti-sense oligionucleotides and combinations tetronenin, gigantetroneninone, gimatecan, gimeracil, glox thereof, inhibitors, mTOR inhibitors, and growth aZone, glufosfamide, goniothalamicin, goniothalamicinone, factor receptor signal transduction kinase inhibitors, goserelin, HCl, gusperimus, hexarelin, homohar retenoids, cyclin/CDK inhibitors, HMG co- reduc ringtonine, hydrocamptothecine, hydroxy carbamide, tase inhibitors () or protease inhibitors. hydroxyurea, , ibandronate sodium, ibandronic 0096. The biologically active agents may also include can acid, idarubicin HCl, idronoxil, , ilmofosine, ima cer inhibitors. Suitable examples of cancer inhibitors are (-)- tinib, mesylate, imexon, improsulfan, incadronate, Ci-Cdp1, (-)-Ci-Cdp2, (-)-epigallocatechingallate, (+)-Cbi indibulin, indisulam, inolitaZone, inproduone, intiquinatine, Cdpi2, (+)-Ci-Cdp2, 10-Deacetylbaccatin Iii, 4-demethoxy intoplicine, iobenguane, hydrochloride, irofulven, , 5-azacytidine/5-aza-2'-deoxycytidine, 5-fluo , ispinesib, , ketotrexate, L-alanosine, rouracil, 5-iminodoxorubicin hydrochloride, 6-mercaptopu laniquidar, lapatinib ditosylate, laromustine, , ledox rine, , acodazole, actinomycin D, phos antrone, lenalidomide, lentinan, lestaurtinib, letrozole, leu phate, , aderbasib, adozelesin; U-73.975, prolide , leuprorelin, lexacalcitol, liarozole, lobapl afeletecan, alemtuzumab, alitreninoin, HCl, alphi atin, , lonafarnib, , , tolic acid, , alvespimycin, ambazone, amet Ly-83583, lysipressin, mafosfamide, mannomustine, manno antrone, amifostine, aminoglutethimide, HCl, Sulfan, marimastat, marinomycin A, masitinib, maslinic acid, amsilarotene, amygdalin, , anastroZole, anaxirone, , mechlorethamine, medorubicin, , ancitabine, annomontacin, annomuricin A, (C19/C20 , , mesna, methotrexate, methyl Erythro), annomuricin B, (C10/C11, C19/C20-Erythro), aminolevulinate, , metoprine, meturedepa, mibo annomuricin C, (All Threo) annomuricin E. annonacin, platin, midostaurin, mi?amurtide, milataxel, , annonacin-10-One, annonacin-A-One, annonidin B, annonin miriplatin, misonidazole, mitindomide, mitoflaxone, VI, annosquamosin A, annosquamosin B, antramycin, apazi , mitomycin, mitonafide, mitoquidone, mito quone, argimesna, aristoforin, , , tane, mitoxantrone, mitozolomide, mivobulin, mizoribine, ascomycin, asparaginase, , , axitinib, aza mofarotene, mopidamol, motesanib, motexafin, mubritinib, setron HCl, azatepa, azathioprine, azotomycin, bafetinib, bal muricapentocin, muricatacin, mustine HCl, mycophenolate amapimod, banoxantrone, batabulin, batimastat, Bbr-34384. mofetil, , medaplatin, nelZarabine, nemo becatecarin, , benaxibine, , ben rubicin, neocuproine, neptamustine, neratinib, , Zodepa, berubicin, betulin, betulinic acid, betulinic aldehyde, nilotinib, , , ninopterin, nitracrine, bevacizumab, , , , birico nogalamycin, nolatrexed, norcantharidine, nor-dihydroguai dar, bisantrene, bistramid A. bistratene A, bizelesin, bleomy aretic acid, nortopixantrone, novembichin, obatoclax, oct cin, A2 Sulfate, bleomycin A5, bleomycin Sul reotide, , oleanolic aldehyde, omacetaxine mepesuc fate, , , boSutinib, brequinar Sodium, cinate, ombrabulin, omtripolide, HCl, , US 2010/0226943 A1 Sep. 9, 2010

oteracil, oteracil potassium, , oxisuran, oxophe acitretin, acivicin, alcantate, aclarubicin, aclatonium napa narsine, paclitaxel ceribate, palifosfamide, , disilate, , aconiazide, , acotiamide, acox pamidronate disodium, pamidronic acid, panitumumab, atrine, acreoZast, , acriflavine, acrihellin, acrisorcin, , patubilone, paZelliptine, paZopanib, pegaspar , acroinonide, acronine, actaplanin, actarit, actino gase, peldesine, pelitinib, pelitrexol, disodium, quinol, actisolide, actodigin, acyclovir, , pentostatin, peplomycin, peretinoin, perfosfamide, perifos adamexine, adapalene, , , , ade ine, pibroZelesin hydrobromide, picoplatin, pinafide, pipo kalant, adelmidrol, ademitrionine, adenosine, adibendal, adi Sulfan, , pirfenidone, piritrexim, piroXantrone, cillin, , , adiphenine, aditeren, aditoprim, , plevitrexed, plicamycin, plitidepsin, , , adoZelesin, , adrenalone, adrogolide, , pomalidomide, , pralatrex afalanine, afeletecan, , afovirsen, , agano ate, prinomastat, procarbazine HCl, , pros dine, , , aklomide, alacepril, alafos pidium chloride, pumitepa, , , ouar falin, alagebrium, alamecin, alamifovir, , alanosine, floxin, raltegravir, , HCl, , , alatrofloxacin, alazanine triclofenate, albacona retaspimycin, retelliptine, riboprine, ritrosulfan, rituximab, Zole, albendazole, albuterol, , , alclometa , , ropidoxuridine, roquinimex, rosabu Sone, alcloxa, alcuronium, aldioxa, , alemcinal, lin, , Sabarubicin, Safingol, salirasib, Sapacitabine, alendronic acid, , alepride, , ale Saracatinib, Sardomozide, , Sebriplatin, , tamine, alexidine, alexitol, alexomycin, alfacalcidol, alfadex, Semaxanib, SU-5416, , sermorelin, simotaxel, alfidalone, alfaprostol, , aldaxalone, alfentranil, simtraZene, Sitagliptin, sizofuran, Soblitodin, Sobuzoxane, alfluZosin, algeldrate, , alibendol, aliconazole, Sodium phenylbutyrate, Sorafenib, Sparfosic acid, sparsomy , alifurane, alilusem, , alinastine, alinidine, cin, Spiroplatin, squalamine, Squamocin, streptonigrin, Strep alipaminde, alliskiren, alitame, , , alle tovarycin, Streptozocin, Sufosfamide, Sulofenur, Sunitinib, torphine, allobarbitol, allocamide, allocupreide, allomethadi Swainsonine, tacedinaline, tafluposide, tallabostat, talisomy one, , , , almecillin, alm cin, tallimustine, talotrexin, taltobulin, citrate, , , , , , tandutinib, tanespimycin, tariquidar, tasidotin, tasisulam, , almurtide, , , alonacic acid, tauromustine, , tegafur-, telantinib, telox alonimid, aloracetam, alosetron, , aloxidone, alox antrone, , , tenuaZonic acid, terame iprin, aloxistatin, aloZafone, alpertine, alphameprodine, procol, , , , tezacitabine, thia , alphamethyldopa, alphaprodine, , miprine, thioguanine, thiotepa, , tiaZoflurine, alpiropride, alprafenone, , , tilomisole, tillorone, timcodar, timonacic, , tira alprenoXime, alprostadil, alrestatin, , altapizone, paZamine, tocladesine, tomudex, hydrochloride, alteconazole, althiazide, , altoqualiine, altrenogast, citrate, tosedostat, toSitumomab, toxipantrone, altretamine, alvemeline, , , , ama trastuzumab, trenimon, , triciribine, , trime dinone, amafalone, amanozine, , amantocillin, trexate, triplatin tetranitrate, triptolide, triptorelin, trofosfa ambamustine, ambasilide, ambazone, ambenonium, mide, HCl, tubulozole, tylophorin, U-67786, ambenoxan, ambomycin, , ambroXol, ambruti U-68415, U-71184, U-76074, U-78057, , uramus cin, ambucaine, ambucetamide, , ambuside, tine, uredepa, urethane, , ursolic acid, ursolic alde ambutonium, , , , amdinocil hyde, VadimeZan, , Valspodar, Vandetanib, vap lin, amdoxovir, ambucort, , , amelt reotide, Vatalanib, PTK-787, , vildagliptin, olide, amelubant, , ametantrone, amethocaine, vinblastine Sulfate, Vincristine, , vinepidine, Vin amezapine, amezinium, , , amfetami flunine, vinformide, vinfosiltine, Vinleucinol, Vinleurosine, nil, , amfonelic, amicarbalide, amicloral, amicy vinorelbine Base, vinorelbine tartrate, vintriptol, Vinzoli cline, anidantel, amidapsone, , , ami dine, Voriconazole, , Vorozole, wilforlide A, Xan floverine, amifloxacin, amifostine, amiglumide, amikacin, thomycin A, Zalcitabine, Zeniplatin, Zilascorb, Zinostatin, amikhelline, , , aminacrine, amindocate, Zoledronic acid, , ZoSuquidar, or the like, or a com , aminoglutethimide, aminohippuric acid, ami bination comprising at least one of the foregoing cancer nolevulinic acid, aminometradine, aminopentamide, ami inhibitors. nophenaZone, , aminopromazine, aminop 0097. A more complete list of compounds, most of which terin, aminopyrine, aminoquinol, aminoquinuride, , are pharmaceutical or veterinary, which can be utilized in the aminosalicylic acid, aminothiazole, , amiperone, present invention includes, but is not limited to: abacavir, amphenazole, amipizone, amiprolose, amiquinsin, amisome abamectin, , abaperidone, abarelix, abecamil, abi tradine, amisulprode, amiterol, amithioZone, amitivir, ami raterone, abitesartan, , abunidazole, acadesine, traz, , amitriptyinoxide, amixetrine, , acamprosate, , , , acecamide, amlintide, , amocarzine, , amol , , , acedapsone, acedia anone, amonafide, amoproxan, amopyroquine, amorolfine, Sulfone, acedoben, , acefurtiamine, amoscanate, amosulatol, amotoSalen, amotriphene, amoxap clofibrol, acefylline , aceglatone, aceglutaminde, ine, amoxecaine, amoxicillin, amoxydramine, , , aceneuramicacid, acenocoumarol, acepeprone, anphechloral, amphenidone, , amphomycin, , , acequinoline, acesulfame, amphotalide, amphotericin, amplicillin, , acetaminosalol, , acetarSone, acetaminophen, amprenavir, amprolium, ampyrimine, ampyZine, amduinate, , acetiamine, acetiromate, , , amsacrine, amtolimetin, amustaline, amylobar acetophenaZone, acetophenetidin, , acetosulfone, bital, angestone, anagrelide, anakinra, anaritide, anastrozole, acetriozoic acid, , acetyldigitoxin, acetylleu anatibant, anaxirone, , anazolene, , ancit cine, acetyltributyl citrate, acetyltriethyl citrate, acevaltrate, abine, andolast, , , andulafun acexamin acid, acifran, , acitaZanolast, acitemate, gin, anecortave, anetholtrithion, angiotensin amide, andidox US 2010/0226943 A1 Sep. 9, 2010 10 amine, anidulafungin, anilamate, anilleridine, , Ziodarone, benzmalecene, benznidazole, , ben , , anirolate, anisacril, anisindione, Zocaine, benzoclidine, , benzodepa, anisopirol, anisotropine, anisperimus, , anpirto benzododecinium, benzonatate, benzopyrronium, benzo line, , antafenite, , antazonite, anthelmy quinonium, benzotript, benzoxiquine, benzoxonium, ben cin, anthralin, , antipyrine, , apado Zoylpas, , benzpiperylon, benzpyrinium, ben line, apafant, apalcillin, apaxafylline, apaziquone, apaZone, Zquercin, , benzthiazide, benztropine, apicycline, , , apovincamine, apra , benzylhydrochlorothiazide, benzylpenicillin, , apramycin, , aprakalim, , benzylsulfamide, bepafant, beperidium, bephenium, bepias aprinocarsine, apofene, aprosulate, , , tine, , beractant, , , , ber aptocaine, , aranotin, arbaprosil, arbekacin, arb genin, berlafenone, bermoprofen, bertosamil, berupipam, utamine, arclofenin, ardacin, ardeparin, , arfalasin, bervastatin, berythromycin, besigomsin, besipirdine, beson , , , argimeSna, argipres prodil, besulpamide, besunide, beta carotene, betacetylmeth sin, argiprestocin, arlidone, arimoclomol, , adol, , betaine, betameprodine, , , , , artinolol, arprinocid, arpro betamethasone, betamicin, betamipron, betaprodine, betax midine, arsanilic acid, arteflene, artemether, artemisinin, arte olol, , bethanacol, , betiatide, betox motil, artenimol, artesunate, , artilide, arundic acid, ycaine, , , beXarotene, , , ascorbic acid, arsenapine, aseripide, , , beztiramide, bialamicol, biapenem, bibeZonium, asobamast, asocainol, , aspartame, aspartocin, bibrocathol, bilcalutamide, bici fadine, bicoldil, biclofibrate, asperlin, aspirin, aspoxicillin, , astromicin, asula biclotymol, bicoZamycin, bidimazium, bidisomide, crine, , ataprost, ataquimast, atavanavir, . bietamiverine, bietaserpine, , bifepramide, , atibeprone, atilmotin, , atipromod, bifeprofen, , , , , , , atliprofen, atocalcitol, atolide, atomoxet , , bimoclomol, bimosiamose, bin ine, , atosiban, atovaquone, atracurium, atrasen darit, binedaline, binfioxacin, binfibrate, biniramycin, bini tan, atraleuton, atrimustine, atrinositol, atromepane, , Zolast, binodenosine, , bioallethrin, botin, bipen atropine oxide, auranofin, aurothioglucose, , ava amol, , biphenamine, biricodar, biriperone, simibe, avicatonin, avalamycin, aviptadil, , bisacodyl, bisantrene, bisaramil, bisbendazole, bisben , , azoparcin, avorelin, pyridine, axam tiamine, bisbutiamine, bisdequilinium, bisfenaZone, bisfenti ozide, axitirome, , azabon, azabuperone, azaciti dine, bisnafide, bisorbin, bisoctriazole, , bisorcic, dine, , azaclorzine, azaconazole, azacosrterol, aza bisoxatin, bispyrithione, bithonol, bithionoloxide, butipa cyclonol, azaftozine, , azalomycin, azaloxan, Zone, , bitoscanate, bivalirudin, bizelesin, bleomy aZamethiphos, azamethonium, azamulin, azanator, azanida cin, blonanserine, bluenSomycin, bofumustine, . Zole, , azapetine, azaquinzole, azaribine, azarole, , , , , , aZaserine, , azaspirium, azastene, , aza bometolol, , , , borelone, thioprine, , , aZelinnidipine, azepexole, borocaptaine, bortezomib, bosentan, botiacrine, boxidine, , azetepa, aZetirelin, azidamfenicol, azidocillin, , , brazergoline, , brema azimexon, , azintamide, azipramide, , Zocine, brequinar, , bretyllium, , bri aZlocillin, azlocillin, azolimine, azosemide, aztomycin, monidine, brinaZaprone, brindoXime, brinzolamide, brivu aztreonam, aZumolene, bacampicillin, bacitracin, , dine, brobactam, broclepride, brocrestine, brocrinat, bacmecillinam, bakeprofen, balaglitaZone, balaZipone, balo brodimoprim, , brofoxine, brolaconazole, brola floxacin, balsalazide, , bamaquimast, bambermy mfetamine, , bromamid, , bro cin, , , , , bamiras mchlorenone, bromebric acid, , bromete tine, bamidazole, banoxantrone, baduiloprim, , namine, , brom hexene, bomindione, , barixibat, barmastine, , barucamide, bromisovalum, bromociclen, , bromodiphe , basifungin, batalbulin, , batebulast, nylhydramine, bromofenfos, bromofos, , bro , batilol, batimastat, batoprozine, baxitoizine, moxanide, , , , , , becanthone, becatecarin, beclipar broperamol, bropirimine, broquinaldol, broSotaminde, bros cil, , becliconazole, beclobrate, beclomethasone, tallicin, broSuximide, brotianide, , brovanexine, beclotiamine, , befiperide, , brovincamine, broxaldine, , broxitalamide, broXu , , bekanamycin, belaperidone, belariz ridine, , bucamide, , buciclovir, bucil ine, belfosdil, belotecan, beloxamide, beloxepin, bemar lamine, , , , buclosaminde, inone, , , bemetizide, beminafil, bemi bucloxic acid, bucolme, bucricaine, bucromarone, bucu parin, bemetradine, bemoradan, , , molol, , , budotitane, budralazine, benafentrine, benapry Zine, benaxibine, benazepril, ben bufenadrine, bufeniode, , , bufezolac, cianol, bencisteine, benclonidine, , bendacalol, bufromedil, bufogentin, buformin, bufrolin, , bufyl bendamustine, , bendazol, benderizine, bendroflu line, bullaquine, , bumecaine, bumepidil, bumet methazide, benethamine penicillin, benexate, , anide, bumetriazole, , bunamidine, bunamiodyl, benfosformin, benfotiamine, benfluorodil, benhepazone, bunaprolast, , , bunolol, buparvaquone, , , benolizime, , , , , , , bupro benoxifos, , benoximate, benpenolisin, benperi pion, buquinerin, buquinolate, buquiterine, buramate, dol, benproperine, benrixate, bensalan, , bensul burodiline, buserelin, , busulfan, , dazic acid, , bentemazole, bentiamine, bentipi , butacetin, , butadiaZamide, butafosfan, mine, bentiromide, bentoquatam, benurestat, benzalkonium, , , , butamirate, butamisole, benzarone, , , , benze butamoxane, butanilicaine, butanserin, butantrone, butapera thonium, benzetimide, benzilonium, benZindopyrine, ben zine, butaprost, butaverine, butedronate, bytenafine, buteriz US 2010/0226943 A1 Sep. 9, 2010

ine, butenamate, buthiazide, butibufen, butifrine, butikacin, pyramine, chloroquine, chloroserpidine, , chlo butilfenin, , , butirosin, butixirate, rothiazide, chlorotrianisene, , chloroxylenol, , butobendine, , butocrolol, butocta chlorphenesin, chlorpheniramine, chlorphenoctium, chlor mide, butofiolol, butonate, butopamine, butopiprine, buto phenoxamine, , , chlor prozine, butopyrammonium, , butoxamine, proguanil, , , chlorprothix butoxylate, , butropium, butylscopolamine, ene, chlorpyrifos, chlortetracycline, chlorthalidone, butynamine, buZepide, cabastine, , cactinomycin, chlorthenoxazine, , cholecalciferol, choles , cadrofloxacin, cafaminol, , , terol, alfoscerate, choline, chromic chloride, chromo calcifediol, calciprotriene, calcitriol, calcobutrol, caldaret, nar, ciadox, ciaftalan, ciamexon, cianergoline, cianidanol, caldiamine, caloxetic acid, calteridol, clausterone, , ciapilome, cicaprost, cicarperone, ciclactate, , cambendazole, camaglibose, camiverine, camp , , , cleletanine, cicliomenol, tothecin and its analogues such as 9-amino camptothecin, , ciclonium, , , ciclopro 10-hydroxy camptothecin, 7-ethyl-10-hydroxy camptoth fen, , ciclosidomine, , ciclotropium, ecin, 9-nitro camptothecin and all other camptothecin ana cicloxilic acid, cicloxolone, , , cidox logues with six, seven and eight membered lactone rings, epin, cifenline, cifostodine, , ciheptolane, cila camonagrel, camo.stat, , canbisol, candesartan, can dopa, cilansertron, , cilaZapril, cilengitide, cilexin, dicidin, candocuronium, , candoXatrilat, caner , , cilobradine, cillofungin, , tinib, canfosfaminde, , cannabinol, canrenoate, can , , ciluprevir, cilutazoline, , renone, capectitabine, capobenate, capobenic acid, , , cimetropium, , capravirine, capreomycin, capromorelin, , cap , cinacalcet, cinalukast, cinametic acid, saicin, captamine, , , capuride, caraber , , cinaproxen, cinchophen, cinecromen, sat, caracemide, carafiban, , , carbadox, , , cinfenine, cinfenoac, cinfiumide, , carbentel, carbasone, carbaspirin, carbaz , , cinmetacin, cinnamaverine, cinnamed eran, carbazochrome, , cabenicillin, carbenox rine, , cinnofuradione, cinoctramide, cinodine, olone, , carbetapentane, , , , cinoquidox, cinoxacin, , cinoXolone, carbimazole, , carbiphene, carbofenotion, car cinoXopazide, cinperene, cinprazole, cinpropazide, cinprom boplatin, carboprost, , , , ide, cintaZone, cintriamide, cinuperone, cioteronel, cipamfyl , , carcainium, carebastine, carfenta line, cipemastat, ciprafamide, , cipraZafone, nil, carfimate, cargutocin, cariporide, , carman , , , , tadine, carmofur, , carmustine, camidazole, car ciprokiren, cipropride, ciprocquaZone, ciprestene, , nitine, carocamide, , , carperidine, , cirolemycin, , cisatracurium, cincona carperitide, carperone, carphenazine, . Zole, , cisplatin, cistinexine, , , carpraZidil, , capronium, carsalam, citatepine, citenamide, citenaZone, , citiolone, ciZo carsatirin, cartasteine, , , carubicin, caru lirtine, cladribine, clamidoxic acid, clamikalant, clamox monam, , carvotroline, carZelesin, carZenide, cas ycuin, clanfenur, clanobutin, clantifen, , cla anthranol, casokefaminde, caspofungin, , , Vulanate, , claZolimine, claZuril, , , cedefingol, cefaclor, cefadroxil, cefalonium, , , clemeprol, , , cefaloram, cefamandole, cefaparole, cefatriazine, cefazaflur, clenpirin, , cletoquine, , clevudine, cefazedone, cefazolin, cefbuperaZone, cefanel, cefcapene, clibucaine, clidafidine, clidanac, clindium, , cefclidin, cefdaloxime, cefdinir, cefditoren, cefedrolor, , climiqualine, clinafloxacin, , cli cefempidone, cefepime, cefetamet, cefetecol, cefetriaole, nofibrate, clinolamide, climprost, , clioxanide, clip cefivtril, cefixime, cefimatilen, cefimenoxine, cefimepidium, rofen, cliropamine, , clobenoside, , cefnetazole, ceminox, cefodizime, cefonicid, cefoperaZone, clobenorex, , , , clobuti ceforanide, cefoselis, cefotaxime, cefotetan, cefotiam, nol, clobuZarit, clocanfamide, , clociguanil, cefoVecin, cefoxazole, cofoxitin, cefoZopran, cefpimizole, , , clocoumarol, clodacaine, cefpiramide, cefpodoxime, cefprozil, cefauinome, cefrotil, clodanolene, clodazon, clodoxopone, clodronate, clofara cefroxadine, cefsulodin, cefsumide, ceftazidime, cefteram, bine, clofazimine, clofenamic acid, clofeniclan, clofen ceftezole, ceftibuten, ceftioflur, ceftiolene, ceftioxide, ceft etamine, clofenoxyde, clofevine, clofexamine, clofeZone, ioxime, ceftriaxone, cefuracetamime, cefuroxime, cefu , clofibric acid, , clofilium, clofucarba, Zonam, , celgosivir, , cemadotin, ceph clofoctol, , clofurac, , cloguanamil, clo acetrile, cephadrine, cephalexin, cephaloglycin. macrin, , clometacin, clometherone, clomethia , cephalothin, cephapirin, cepharanthine, ceph Zole, clometocillin, , , clomiphene, radine, , , ceronapril, ceruletide, ceta , clomocycline, clomoxir, , clona ben, cetalkonium, , cetefloxacin, cethexonium, Zoline, clonidine, clonitazine, clonixeril, , clopam cethromycin, , , , cetocycline, ide, , , cloperidone, clopidogrel, clo cetopheincol, cetotiamine, cetoxime, , cetrimo pidol, , clopipazan, clopirac, cloponone, nium, cetylpyridinium, , chaulmosulfone, cheno cloprendol, , cloprothiazole, cloquinate, clo diol, chinofon, chlofibrate, chlophendianol, chloracy Zine, quinozine, cloracetadol, , , cloraZepic , chlorambusil, chloramines-T, , acid, clorethane, chlorexolone, clorfenvinos, , clo chlorazanil, chlorbenoxamine, chlorbetamide, chlorcycliz ricromen, , clorindanic acid, clorindione, clo ine, chlordantoin, , chlordimorine, chlo rmecaine, cloroperone, clorophene, , clo rhexidine, chlorindanol, , chloramadione, rotepine, clorprenaline, clorSulon, , closantel, chlormerodrin, , chlormidazole, chlornaphaz closiramine, , clothiapine, clothixamide, clotiaz ine, chloroaZodin, , , chloro epam, , clotioxone, clotixamide, , US 2010/0226943 A1 Sep. 9, 2010

, cloxacepride, cloxacillin, , clox dexfosfoserine, , deximafen, dexindoprofen, , cloximate, , cloxypendyl, clox dexivacaine, , dexlofexidine, , ycuin, , cobalamide, , , , , , dexnafenodonee, cofistatin, , colchicines, colestolone, colfenamate, dexniguldipine, dexnorgestrel, dexormaplatin, , , colfosceril, colimecycline, , , dexpanthenol, dexpemedolac, dexpropranolol, dex.proxib , congaZone, , conorphone, cormetha utene, dexraZOxane, dexsecoverine, dexSotalol, dextilidine, Sone, , cortisone, , , cortodox dextiopronin, dextofisopam, , dextro one, , , coumaphos, coumaZolin, coumer femine, , , , mycin, coumetarol, creatinine, creatinolfosfate, cresotamide, , dexcerapimil, Sezaguanine, dezinamide, cridanimod, crilvastin, crisinatol, crobenetine, croconazole, , diacerein, diacetamate, , diamfenetide, , cromitrile, cromoglicate lisetil, cromolyn, cro diamocaine, , diamthiazole, diapamide, diar lom, cronidipine, cropropamide, crotamiton, crotetamide, barone, diathymosulfone, , diaveridine, , crotoniazide, crotoxyfos, crufomate, cuprimyxin, cuproXo diaziquone, , dibekacin, dibemethine, , line, cyacetacide, , cyanocobalamine, cyclacil dibenzothiophene, dibrompropamidine, bibromsalan, lin, cyclamate, cyclamic acid, , , dibrospidium, dibucaine, dibuprol, dibupyrone, dibusadol, , , cyclexanone, cyclindole, cyc dicarbine, dicarfen, , dichloramine, liramine, , , cyclobendazole, cycloben , dichlormeZanone, dichlorophen, dichlorphe Zaprine, cyclobutoic acid, cyclobutyrol, cyclocumarol, narsine, dichloroxylenol, dichlorphenamide, dichlovos, dici , cycloguanil, cycloheximide, cyclomenol, cyclom ferron, , , diclofenac, diclofenamide, ethycaine, , cyclopenthiazide, cyclopento , diclofutrime, diclometide, diclonixin, diclo late, cyclophenazine, cyclophosphamide, cyclopregnol, ralurea, , diclolinium, dicummol, dicyclomine, cyclopyrronium, , eyelothiazide, cyclovalone, didanosine, didrovaltrate, , , dienogest, cyclotiamine, , cyfluthrin, cyhalothrin, cyhepta diethadione, diethylphthalate, , dietyl mide, cyheptropine, cynarine, , , propion, , dethylthambutene, dietyltolua cypothrin, , , , cypro mide, dietifen, , , difemetorex, dife heptadine, cyprolidol, cyproduinate, , cyproxim namizole, difencloxazine, difenoximide, , ide, cyromazine, cysteamine, , cystine, cytarabine, , difeterol, diflomotecan, , difloxacin, cythiolate, dabelotine, dabigatran, dabu Zalgron, dacarbazine, difluanine, , diflumidone, , diflupred dacemazine, dacinostat, dacisteine, dacopafant, dactinomy nate, diftalone, digitalis, , digoxin, , cin, dacuronium, dagapamil, dagluril, dalbavancin, dalbrami , , , dihy nol, dalcotidine, , dalfopristin, dalteparin, dal drostreptomycin, dihydrotachysterol, diisobutylaminoben troban, dalvastatin, dametralast, damotepine, . Zoyloxypropyl , , diisopropanola daniquidone, danittracen, danofloxacin, danosteine, dan mine, diisopropylamine, , dilevalol, dilimefone, thron, dantrolene, , dapitant, dapivirine, dapoxet , , dimabefylline, dimadectin, dimecam ine, dapsone, daptomycin, darbufelone, darenzepine, dargli ine, dimeclonium, dimecrotic acid, dimefadane, dimefline, taZone, , , darunavir, , dimelazine, , , , dasantafil, datelliptium, daunorubicin, daxalipram, daZadrol, dimepranol, , dimepropion, dimeproZan, dime dazepinil, daZidamine, daZmegrel, dazolicine, , Sna, , , dimetamfetamine, dimethadi daZoquinast, , deboxament, debrisoquin, decame one, , dimethisoquin, , dimetholiz thonium, decimemide, decitabine, decitropine, declenper ine, dimethothizine, , dimethylaminoethyl one, declopramide, decloxizine, decominol, decoquinate, reserpilinate, dimethylthambutene, dimethyltubocurarinium, dectaflur, deditonium, deferasirox, deferiprone, deferoxam dimetipirium, , dimetridazole, diminaZene, ine, , defosfamine, defoslimod, degarelix, dehy , dimoxamine, dimoxaprost, dimoxyline, droacetic acid, dehydrocholic acid, , dimpylate, dinaline, dinaZafone, diniprofylline, dinitolmide, , delapril, , delquamine, deergotrile, dinoprost, dinoprostone, dinsed, diohippuric acid, dioSmin, delfantrine, delfaprazine, Selmadinone, delmetacin, delimpi diotyrosine, dioxadrol, dioxamate, , nol, , deloXolone, delprostenate, , dioxation, dioxethedrin, dioxifedrine, dioxybenazone, dioxy dembrexine, demecarium, demeclocycline, , line, dipenine, diperodon, diphemanil, diphenadione, demecycline, , demelverine, , diphenan, diphenchloxazine, , diphenidol. democonazole, , , denatonium, , diphenylpiperidinomethyldioxolan, diphe denaverine, denbufylline, denipride, denofungin, denopam nylpyraline, diphenoxazide, , dipiproverine, ine, denotivir, denpidaZone, , denZimol, depelestat, dipivefrin, , , diprobutine, dipro , depreotide, , deprostil, , fene, diprogulic acid, diproleandomycin, diprofylline, dipro , , , deriglidole, derpan qualone, , diprotrizoate, diproxadol, dipy icaine, derSalazine, desapidin, desciclovir, , ridamole, dipyrithione, , dipyrone, diduafosol, , , deeslanoside, desloratidine, dirithomycin, , disermolide, disquonium, disob deslorelin, desmeninol, , , utamide, Sidofenin, Sdisogluside, , disoxaril. desocriptine, , desmorphine, , des distigmine, disufenton, disulergine, disulfamide, disulfuram, Oximetasone, desoxycorticosterone, , detaj disupraZoole, ditazole, ditekiren, ditercalinium, dithiaanine, mium, detanosal, , detirelix, detiviciclovir, detromi ditiocade, ditiocarb, ditiomustane, ditolamide, ditophal, div dine, detorubicin, detrothyronine, , , abuterol, divalproex, , dixanthogen, dizatrifone, , dexamisole, , dex dizcilpine, dobesilate, dobupride, dobutamide, , budesonide, , dexclamol, dexecadotril, docarpamine, docebenone, , doconazole, doconex dexefaroxan, , dexetoZoline, , ent, docosanol, , dodeclonium, dodicin, dofamium, US 2010/0226943 A1 Sep. 9, 2010 13 dofecquidar, dolfetilide, dolasetron, doliracetam, domazoline, diol, estramustine, , , , estrone, domiodol, domiphen, domipizone, domitroban, domopred estropipaten esupone, esZopclone, etabenzarone, etacepride, nate, domoxin, , , donetidine, doni , , etalocib, etamestrol, etaminile, etami , dopamantine, , , dopropidil, phylline, etamocycline, etanidazole, etanterol, , doqualast, dorampimod, doramectin, doranidazole, doras etarotene, etasuline, , , etebenecid, eter tine, Soreptidei, doretinel, doripenem, dorzolamide. dosergo obarb, etersalate, ethacridine, ethacrynic acid, ehtambutol, side, doSmalfate, , dotefonium, dothiepin, doxacu ethamivan, ethamsylate, ethaverine, ethenZameide, ethiazide, rium, doxapram, doxaprost, , , , ethinyl estradiol, ethionamide, , etho doxenitoin, doxepine, doxergocalciferol, , doxi heptazine, ethomoxane, ethonam, ethopabate, ethopro fluridine, , doxorubicin, , doxycy pazine, , , ethoxazene, ethoxazoruto cline, , drafiazine, dramedilol, draquinolo, drazi side, , ethybenztropine, ethyl biscoumacetate, , dribendazolew, drimidene, drobuline, , , ethyl cartrizoate, ethyl , ethyl droclidinium, , , drometrizole, dromo dirazepate, , , ethylhydrocu stanolone, , drinedarone, dropempine, . preine, , , ethylnore droprenilamine, , , , pinepherine, ethylstilbamine, ethylnerone, ethylnodil, , droxacin, droxicamide, , , ethypicone, etibendazole, , , eti droximavir, droxypropine, duaZomycin, dulofibrate, dulloxet docaine, etidronate, etidronic acid, etifelmine, etifenin, eti ine, duloZafone, dumorelin, dumetacin, duoperone, duprac foXine, , etillefrine, , etinidine, etam, , dyclonine, dyhydrogestrone, dymanthine, etipirium, etiprendol, etiproston, , etiroXate, etisa dyphylline, , , eberconazole, ebiratide, Zole, etisomicin, etisulergine, , etocarlide, etoc , ebselen, ecabapide, ecabet, , ecalcidene, rylene, , , etofamide, , , , ecenofloxacin, echothiophate, eciprami etofemprox, , etofermin, etofuradine, etofylline, eto dil, , eclaZolast, ecomustine, , ecopi glucid, eorolex, etolotifen, etoloxamine, , etomido pam, ecraprost, ectylurea, edaglitaZone, edaravone, edatrex line, etomoxir, etomitaZene, , , eto ate, edelfosine, edetol, edifolone, , edonentan, poside, etoprindole, etoprine, , , edotecarin, edotreotide, , edratide, edronocaine, etosalamide, , , etoZolin, etrabamine, edrophonium, , , , efegatran, etravirine, etretinate, etriciguat, etryptamine, , efepristin, efetozole, efletirizine, eflornithine, , eflu eucaine, eucalyptol, eugenol, euprocin, evandamine, evern cimibe, elfiumast, , efrotomycin, eganoprost, imicin, , evicromil, exalamide, exametazime, eglumetad, egtazic acid, equalen, elacridar, elantrine, elan examorelin, , exatecan, exemestane, exepanol, exi Zepine, elaarofiban, elbanizine, eldacimibe, , elf fone, exiprofen, exisulind, , eZlopitant, fadolmi azepam, elgotipine, elinafide, , elisartan, , dine, fadrozole, falecalcitriol, fallintolol, , elliptinium, elmustine, elnadipine, , elsamitru falnidamol, , famirapinium, , famo cin, eltanolone, eltenac, , elucaine, elvucitabine, tine, fampridine, , fampronil, , , elziverine, emakalim, emapunil, , , fandofloxacin, fandoSentan, , fantofar embusartan, , , emepronium, emet one, fantridone, fargilitazar, fasidotril, , , ine, emeglitate, emilium, emiteflur, emiverine, emodepside, faudil, fazadinium, fazarabine, febantel, , febu , emorfaZone, emitricitabine, , enado prol, febuverine, , feclemine, feclobuzone, fedot line, enalapril, enalaprilat, enalkiren, enaZadrem, enbucrilate, ozine, fedrilate, , , felipyrine, , encamide, , enclomiphene, encyprate, endix feloprentan, fely pressin, , fenabutene, fenace aprine, endomide, , endrysone, enecadin, enefex tinol, fenaclon, , fenaftic acid, femalamide, femal ine, , enfenamic acid, enfluvirtide, englitaZone, eni comine, fenamifuril, fenamole, fenaperone, , clobrate, enilconazole, , eniluracil, eniporide, fenbenicillin, , fenbutreazate, , fenci enisoprost, enloplatin, enocitabine, enofelast, enolicam, butirol, fencleXonium, fleclofenac, , fenclorac, enoxacin, enoxamast, enoxaparin, , , fenclozic acid, , fendizoate, fendosal, feneritrol, enipiprazole, empiroline, , , enpro , , , fenetradil, fenflumizole, mate, , enramycin, enrasentan, enrofloxacin, , flenfluthrin, , fenharmane, fenimide, ensacillin, , , entecavir, entisulfon, feniodium, fenipentol, fenirfibrate, , fenitrothion, enviomycin, enviradene, enviroxime, enZacamene, anZastau , , fenmetraminde, fenobam, fenocinol, rin, epalrestat, , eperezolid, , eperVudine, fenocitimine, , , , fenot , epicamide, epicillin, , , erol, fenoerine, fenoxazoline, fenoxedil, , fenpen , , epinephrine, epinepheryl, epipropi tadiol, femperate, fenprpalone, fenpipramide, , fen dine, epirizole, apiroprim, epirubicin, epitetracycline, epithi piverinium, fenprinast, , fenprostalene, azide, , eplerenone, elivanserin, epoprostenol, fenduiaone, fenretinide, , , fenthion, fen epostane, eprazinone, eprinomectin, , , tiazac, fenticlor, fenticonazolem, fentonium, fenvalerate, eprosartan, eprovafen, eproXindine, , epsipranel, fenyripol, fepentolic acid, fepitrizol, fepradinol, feprazone, epaloprost, , eptaplatin, eptastigmine, eptazocin, fepromide, , ferpifosate, , fetoxy eptifibatide, equillin, erbuloZole, erdosteine, ergo calciferol, late, fexicaine, fexinidazole, , fezatione, fezola ergonovine, , eritoran, erizepine, erlotinib, erca mine, fiacitabine, fialuridine, fibracillin, fidarestat, fidexaban, mide, , ertapenem, ertiprotafib, erythrity tetrni fiduXosin, figopitant, , filenadol, filipin, finafloxa trate, erythromycin, esafloxacin, esaprazole, esatenolol, esci cin, , fingolimod, fipamezole, , . , esculamine, eseridine, esflurbiprofen, , , flavamine, flavodic acid, flavodilol, , escarbazepine, esmolol, , esonarimod, esorubi flazalone, flecamide, flerobuterol, fleroxacin, , cin, esoxybutynin, espatropate, esproquin, , estra , , flezelastine, , flindokalner, US 2010/0226943 A1 Sep. 9, 2010 flocalcitriol, , flomoxe?, floptopione, floranty , glaspimod, glatiramer acetate, , glen rone, flordipine, floredil, florfenicol, florifenine, flosatidil, vastatin, gliamilide, glibotnuride, glibutimine, , , flosulide, flotrenizine, floverine, floxacillin, glicetanide, , glicondamine, glidaZamide, glifiu floxacrine, floXuridine, flucizine, fluialamine, fluianisone, flu mide, , glipalamide, , , azacort, fluaZuron, flubanilate, flubendazole, flubepride, flu glisamuride, glisentide, glisindamine, glisolamide, glisox carbril, flucetorex, , flucinprazine, flucloronide, epide, gloxazone, gloXimonam, glucametacin, glucosamine, fluconazole, flucrylate, flucytosine, fludalanine, fludarabine, gluronolactone, glucuronamide, glunicate, glyburide, gly fludazonium, fludeoxyglucose, , fluidorex, flu buthiazole, glubuZole, gycopyrrolate, glycylamide, glyhexa doxopone, fludrocortisone, , flufenisal, flu mide, glymidine, glyoctamide, glyparamide, glypinamide, fosal, flufylline, , fluindarol, fluindione, flumaze glyprothiazole, gly Sobuzole, goralatide, goserelin, gramici nil, flimecinol, , flumequine, flumeridone, din, granisetron, grepafloxacin, , guabenXan, flumethasone, flumethiazole, flumetramide, , , guafecainol, guaiactamine, guaiapate, guaietolin, , , , , flunamine, , guaimeSal, guaisteine, guaithylline, , , flunidazole, , , , guanacline, , , guanclofine, guancy flunoprost, , , , fluo dine, , , guanisoquin, guanoclor, gua cortin butyl, , fluorescein, fluoresone, fluoro noctine, , , guanoxyfen, gusperimus, dopa, , fluorosalan, fluorouracil, , , halaZone, , halethazole, halobetasol, , fluoxymesterone, , , flu halocortolone, halofantrine, halofenate, halofuginone, peramide, , , flupheazine, flupi , halonamine, halopemide, halopenium, halo mazine, , flupranone, , , flu peridol, , , , halox prednisolone, fluprofen, fluprofylline, fluproduaZone, aZolam, haloxon, haloqionol, hamycin, hedaquinium, helio fluprostenol, fluquaZone, fluradoline, flurandrenolide, fluran mycin, hepronicate, heptabarbital, heptaverine, heptolamide, tel, , , fluretofen, flurithromycin, fluo , , , hetaflur, heteronium, hexachlo rocitabine, fluorofamide, fluorogestone, , fluspip rophene, , hexacy prone, hexadiline, hexafluo erone, , flutamide, , , renium, , hexaminolevulinate, hexapradol, flutiazin, , flutizenol, flutomidate, flutonidine, flu hexaprofen, , hexasonium, hexazole, hexe toprazepam, , flutroline, flutropium, , dine, , hexetidine, , , hexo , fluzinamide, fluZoperine, fodipir, folic acid, cyclium, , hexopyrronium, heylcaine, hista fomepizole, fomidacillin, , fomiversen, mine, , , homarylamine, , fomocaine, fonazine, fondaparinux, fopiirtoline, forasartan, homidium, , homofenazine, forfenimex, , formestane, formetorex, formini homopipramol, , , hopantenic trazole, , , forodesine, foropafant, fos acid, hoquizil, hycanthone, hydracarbazine, , amprenavir, fosarilate, , foSenazide, fosflucona hydragaphen, hydrobentizide, , hydroc Zole, foSfocreatinine, fosfomycin, foSfonet, fosfosal, odone, , hydroflumethiazide, , fosfructose, , fosinoprilat, foSmenic acid, fosmido , , , hydroxy mycin, fosopamine, fosphenyloin, fospirate, fosquidone, indasate, hydroxyindasol, hydro Xocobalamin, hydroxyam , foSrtriecin, fosveset, fotemustine, fortrenamine, phetamine, hydroxychloroquin, , hydroxy fozivudine, frabuprofen, fradafiban, , framycetin, , , hydroxyprocaine, frentizole, freselestat, fronepidil, fropenem, , hydroxyprogesterone, hydroxypyridine tartrate, hydroxys froxiprost, ftaxilide, ftivazide, formetazine, forpropazine, tenozole, hydroxyStilbamidine, hydroxytetracaine, hydrox fubrogonium, fudosteine, fuladectin, , fumagillin, yZine, hymecromone, , ibafloxacin, ibandr fumoxicillin, fungimycin, fuprazole, furacrinic acid, furafyl onate, , , , ibrotamide, line, furalazine, furaltadone, furaprofen, , furazoli ibudalast, ibufenac, ibuprofen, , ibutamoren, done, furazolium, furbicillin, furcloprofen, furegrelate, fure ibuterol, , ibuverine, icaridin, , iclaprim, thidine, , furidarone, furmethoxadone, furnidipine, icazepam, icodulinium, icofungipen, ifometaSone, icopezil, furobufen, furodazole, furofenac, furomazine, furomine, icosapent, icospiramide, icotidine, icrocaptide, idarubicin, , , fursalan, fursultiamine, fur idaverine, , idebenone, idenast, , idoxuri therene, furtrethonium, fusafungine, fusidate, fusidic acid, dine, idralfidine, idramantone, idraparinux, idrapril, idiremci fuZlocillin, , gabapexate, , , nal, idrociliamide, idronoxil, , iferanserin, gadobenate, , gadocolectic acid, gadodiamine, , ifosfamide, , iganidipine, , igu gadofosveset, gadomelitol, gadopenamide, gadopentetate, ratimod, , ilatreotide, ilepcimide, iliparcil, ilmofos , , , gadoxetate, ine, illoomastat, illonidap, illoperidone, imafen, imanixil, ima gadoxeticaicid, galamustine, galntamine, galarubicin, gala tinib, imaZodan, imcarbofos, imiclopazine, , Somite, galdansetron, , , imidapril, imidaprilat, imidocarb, imidoline, imidurea, imi galocitabine, galosemide, galtifenin, gamfexine, gamolenic glitazar, , iminophenimide, , , acid, gamaXolone, , ganefromycin, ganglefene, , , imirestat, imitrodast, imola ganstigmine, gantacurium, gantofiban, gapicomine, gapro mine, imoxiterol, impacarzine, implitapide, , midine, garenoxacin, gatifloxacin, , geclosporin, improSulfan, , inamirone, inaperisone, incad , , gefitinib, , gemcabene, ronic acid, , indacrinone, , indanazoline, gemcadiol, gemcitabine, , genfibtrozil, gemifloxa , , indapamide, , indecamide, cin, gemopatrilat, gentamicin, , , gero , , indibulin, indigotindisulfonate, quinol, , gestadienol, , gestonorone, , , indisetron, indobufen, indocate, indocya , , gimatecan, gimeracil, giparmen, nine green, indolapril, indolidan, indomethacin, . giracodazole, giractide, , gitaloxin, gitoformate, indopine, , , , indoxole, US 2010/0226943 A1 Sep. 9, 2010 15 indriline, inecalcitol, ingliforib, inicarone, inocterone camitine, levodopa, , levofacetoperane, acetate, inogatran, , , improquoone, intopli levofenfluramine, , levofluraltadone, levoleuco cine, intrazole, , inulin, iobenguane, iobenzamic Vorin, levomenol, , , acid, , iobutoic acid, icanlidic acid, , levomethadyl acetate, , levometiomeprazine, , iodamine, iodipamide, , iodoantipy , levomoramide, , levonordefrin, rine, iodocholesterol, iodohippurate, iodoquinol, iodothiou , , levopropoxyphene, racil, idoxamic acid, , , iofratol, ioglicic levopropylcilline, levopropuylhexedrine, levoprotiline, acid, ioglucol, ioglunide, ioglycamic acid, iogulaamide, levorin, , , , iohexyl, iolidonic acid, iolixanic acid, iolopride, . levosemotiadil, , , , iomeglamic acid, , iomethin, iometopane, iomorinic levotofisopam, levoxadrol, lexipafant, lexithromycin, lex acid, , , , iophendylate, iophe ofenac, liarozole, libecillide, libenzapril, , noxic acid, , iopronic acid, , iopydone, iosa , , lidadronic acid, lidamine, , rcol, isofenamic acid, io.seric acid, iosimenol, iosimide, ioSu , lidoferin, lidorestat, lifariaine, lifibrate, lifibrol, lamide, ioSumetic acid, iotasul, ioteric acid, iothalamate, , limaprost, limazocic acid, linarotene, lincomy iothalamic acid, iotranic acid, iotriside, iotrizoic acid, iotro cin, , linetastine, , linogliride, , lan, , iotyrosine, iovesol, ioxabrolic acid, ioxa linotroban, lisinidomine, lintitript, lintopride, liothyronine, glic acid, , , ioxotrizoic acid, ioZomic , , liranaftate, , lirexapride, lir acid, ipamorelin, ipazilide, ipenoxazone, ipexidine, ipida imilast, liroldine, lisadimate, lisinopril, , , crine, ipodate, iprgratine, ipramidil, ipratropium, ipra litomeglovir, , , lividomycin, lixazinone, lix vacaine, , ipriflavone, , ipocinidine, ivaptan, lobapolatin, , lobendazole, lobenzarit, lobu , iprocrodol, iprofenin, , iproniazide, cavir, lobuprofen, locicortolone, lodaxaprine, lodaZecar, ipronidazole, iproplatin, iprotiaZem, iproxamine, iprozil lodelaben, lodenosine, Iodinixil, lodiperone, lodoxamide, amine, ipsalazide, , iquindamine, iralukast, iram lofemizole, , , , , panel, irbesartan, irindalone, irinotecan, irloxacin, irofulven, loflucarban, lombazole, lomefloxacin, lomeguarib, lomeriZ irolapride, iroXanadine, irsogladine, irtemazole, isalidole, ine, lometraline, lometrexol, lomevactone, lomifylline, lomo isalsteine, isamfaZone, isamoltan, isamoxole, isatoribine, fungin, lomustine, lonafarnib, lonapalene, lonaprofen, lona isaxonine, isbogrel, isbufylline, ispamicin, isoamilinile, iso Zolac, lonidamine, , lopinavir, , bromindione, isobucaine, isobutamben, , iso lopobutan, , loracarbef, , lorapride, conazole, isocromil, isoetharine, , isofluo , , lorcamide, lorcinadol, , rophate, isomazole, isomerol, isometamidium, , , , lopiprazole, lorta , , isomolpan, isoamylamine, lamine, lorZafone, , losigamone, losindole, loSmipro , isonixin, isoprazole, , isoprofen, iso fen, losoxantrone, losulazine, , lotrafiban, lot propamide, isopropicillin, isoproterenol, isoSrbide, isospa rifen, lotucaine, , loviride, loxanast, , glumic acid, isosulfan blue, isosulpride, , iso loxiglumide, , loxoribine, lozilurea, , tiquimide, , , isoxepac, , , , , lucartamide, lucimy , , , istrdefylline, itameline, cin, lufenuron, lufironil, , luliconazole, lumira itanoXone, itasetron, itaZigrel, , , itriglu coxib, , luprostiol, , lurosetron, lurotote mide, itrocamide, , iturelix, ivbradine, ivarimod, can, lusaperidone, luxabendazole, lydimycin, lymecycline, , ivoqualine, ixabepilone, izonsteride, josamycin, , lypressin, mabuprofen, , madurami , kalafungin, kanamycin, kebuZone, keracyanin, cin, mafenide, mafoprazine, mafosfamide, malathion, maley , , , , kethoxal, lsulfathiazole, malotilate, , , mani ketipramine, , , ketocainol, ketocona faxine, mannomustine, manoZodil, mantabegron, Zole, , , ketorolac, , ketotrexate, mapinastine, , maraviroc, marbofloxacin, marib , khelloside, kitasamycin, , labradimil, avir, maridomycin, marimastat, mariptiline, , mar lachesine, , , lactalfate, lactilol, lactu oxepin, masoprocol, maxacalcitol, maytansine, , lose, ladirubicin, , laflunimus, lafutine, laidlomycin , , , maZokalim, , propionate, lamifiban, , , lamitidine, mebendazole, menbenoside, , mebeZonium, meb lanatoside, , , , laniquidar, hydrolin, mebiquine, , mebrofenin, , lanoconazole, lanperisone, lanproston, lanreotide, lanSopra mebutizide, , mecarbinate, mecetronium, Zole, lapatinib, , laprafylline, lapyrium, lacquini meciadanil, mecinarone, , , meclocy mod, , lasinavir, , , lau cline, meclofenamaic acid, , , dexium, laurcetium, laurocapram, lauroguadine, laurolinium, , dibutyrate, mecloxamine, meco lauryl isoquinolinium, , , lecimibide, balamin, , medazomide, , mediba ledazerol, ledoxantrone, , leflunomide, Zine, , medorinone, medorubicin, lefradafiban, leiopyrrole, lemidosul, lemidipine, leminopra medrogestrone, medronic acid, , medroxyproges Zole, lemoxinol, lemuteporfin, lanalidomine, lenampicillin, terone acetate, , , mefeclorazine, lenapenem, leniquisin, leuperone, leptacline, , , mefenidil, mefenidramium, , , , lesoptiron, lestaurtinib, leteprinim, lete mefeserpine, , , mefruside, megalo prinim, letimide, letosteine, letraZuril, letrozole, leucino mycin, megestrol, megace, meglitinide, meglucycline, caine, leucocianidol, leucovorin, leurubicin, levalbuterol, meglumine, , meladrizine, melagatran, melarsom , levamfetamine, , levcromakalim, ine, melarsonyl, melarsoprol, meldonium, levcycloserine, levdobutamine, levemoamil, , acetate, meletimide, , melinamide, , levisoprenaline, levlofexidine, levmetamfetamine, levobe melizame, , , melphalan, melduinast, taxolol, , levobupiacaine, , levo meluadrine, mamantine, memotine, menabitan, menadiol. US 2010/0226943 A1 Sep. 9, 2010 16 menadione, menadoxime, , menbutone, men , , mindodilol, mindoperone, minepen fegol, menglytate, , menoctone, menogaril. tate, minocromil, minocycline, minodronic acid, minopafant, menobentine, mepazine, , meperidine, mephen , mioflaazine, mipitroban, mipragoside, miproX esin, , , mephenyloin, ifene, , mirincamycin, miripirium, miriplatin, mephobarbital, mebaral, , mepiperphenidol. mirisetron, miristalkonium, , mirosamicin, , mepiroXol, mepitioStane, , mepix mirostipen, , misonidazole, , mitem anox, mepramidil, , , meprochol, cinal, , mitindomine, , mitocarcin, meproscillarin, meprotixol, , , meduli mitoclomine, mitocromin, mitoflaxone, mitogillin, mitogua dox, meduinol, meduitamium, meduitazine, meradimqate, Zone, mitolactol, mitomalcin, mitomycin, mitonafide, mito , merafloxacin, meralein, meralluride, podozide, mitoquidone, mitosper, mitolane, mitotenamine, merbaphen, merbromin, mercaptomerin, mercaptopurine, mitoxantrone, mitoZolomide, mitradipide, mivacurium, mercuderamide, mercufenol, mercumatilin, mergocriptine, mivobulin, mivotilate, mixidine, , mizoribine, meribendan, merimepodib, meropenem, mersalyl, mer mobecarb, mobenzoxamine, mocimycin, mociprazine, tialide, , mesalamine, meseclaZone, , moclonemide, moctamide, , modaline, modecam , mesipiperone, , , ide, modipafant, moexipril, moexiprilat, mofarotene, , , meSudipine, , mesulfa mofebtaZone, , , mofloverine, mofoX mide, meSulfen, meSuprine, metabromsalan, met ine, mofuisteine, molfarnate, molinaZone, , mol butethamine, metabutoxycaine, metacetamol, meta , , , monalaZone, clazepam, metacresol, , , , monesin, , monoctanoin, metalkonium, metalol, metamelfalan, metamfaZone, metam monometacrine, monophosphothiamine, monoxerutin, mon fenpramone, metampicillin, metanixin, , metap telukast, monterelin, , mopidamol, mopidralazine, roterenol, , , metaZamide, metazide, , moquizone, , , morclofone, matazocine, metbufen, meteneprost, , metergota , moricizine, morinamide, , moro mine, metescufylline, metesculetol, metesind, metethohep cromen, , , , morSuxim tazine, , , methacycline, , ide, , , motapizone, motexafin, methadyl acetate, , methallibure, methalthiaz , motrtinide, moveltipril, moxadolen, moxalac ide, , , methandrostenolone, tam, moxaprindine, , , , , , , methapy , moxicoumone, moxidectin, moxifloxacin, moxi rilene, , , methastyridone, meth lubant, moxipraquine, moxirapine, moxisylate, moxnida aZolamide, , methenamine, methenolone, meth Zole, moXonidine, , moZenavir, mubritnib, mupi eptazine, , methetoin, methikcillin, methimazole, rocin, murabutide, muraglitazar, mureletecan, murocamide, , methiomeprazine, , methisaZone, muZolimine, mycophenolic acid, my fadol, , , methixene, , methocidin, metho myrtecaine, nabazenil, , , naboctate, nabume hexital, methopholone, methoprene, methoserpidine, meth tone, nacartocin, nadide, nadiofloxacin, , . otrexate, methotrimeprazine, , methoXSalen, nafagrel, nafamo.stat, nafarelin, nafazatrom, nafcaproic acid, methoxyphedrine, , methoxypromazine, , nafenodone, , nafetolol, nafimidone, methScopolamine, methSuximide, methyclothiazide, methyl nafiverine, , nafomine, nafoxadol, , aminolevulinate, methyl palmoxirate, , nafronyl, naftalofos, naftaZone, naftifine, , naftox , methylbenactyzium, methylbenzethonium, ate, naftypamide, naglivan, , malfurafine, nalidixic methylcromone, , methyldihydromor acid, , , , , naltrex phine, , methylene blie, methylephedrine, meth one, naminidil, naminterol, namirotene, namoXyrate, nana ylergometrine, methylergonovine, methyllparaben, meth frocin, , nanterinone, nantradol, napactadine, ylphenidate, , , napamezole, naphazaoline, naphthonone, napirimus, napi methylthiouracil, methynodiol, , , tane, naproxime, , naproXol, napsagatran, , , , metiazinic acid, metibride, meticrane, narasin, , nardetoterol, naroparcil, , metildigoxin, metindizate, metioprim, metioxate, metipirox, , navuridine, naxagolide, naxaprosteine, naxifyl metiprenaline, , metizoline, metkephamid, line, , nebantan, nebidrazine, , metochalcone, metocinium, , , , , nebramycin, , nedapl metofenazate, , metolaZone, metomidate, metopi atin, , , , neflumozide, mazine, , metoprine, , metoquizine, , , , neleZaprine, nelfinavir, metoserpate, metostilenol, metoxepin, metrafazoline, metral neltenexine, nelZarabine, nemadectin, nemaZoline, nemi indole, metrazifone, metrenperone, , metri fitide, , memorubicin, neocinchophen, neomy fonate, metrifudil, , metrizoate, metronidiazole, cin, neostigmine, , nepafenac, nepaprazole, nepi meturedepa, , metyrosine, , mexafyl castat, , nequinate, , neraminol, line, , , , mexiprosil, mexo nerbacadol, neridronic acid, nerisopam, nesapidil, , profen, mexrenoate, meZacopride, meZepine, mezilamine, nesosteine, nestifylline, neticonazole, netilmicin, netivudine, meZlocillin, miaanserin, , , miboplatin, netobimin, netoglitaZone, , neutramycin, nevi micafungin, , micronomicin, , midafotel, parine, , nexopamil, , niacinamide, niala midaglizole, midamaline, midaxifylline, midazogrel, mida mide, , nibroxane, nicafenine, nicainoprol, nica Zolam, midecamycin, midestein, , midostaurin, metane, nicanartine, nicaraven, nicarbazin, , mifentidine, , mifobate, miglitol, miglustat, , niceritol, niceverine, niclofolan, niclosamide, mikamycin, milacamide, millacemide, , milataxel, nicoboxil, nicoclonate, nicocodine, , nicocido milemperone, milfasartan, millipertine, miloxacin, , dine, nicoduozide, nicofibrate, , nifurate, miltefosine, milverine, mimbane, minalrestat, minamestane, nicogrelate, nicomol, , nicopholine, nicorac US 2010/0226943 A1 Sep. 9, 2010 17 etam, , nicothiaZone, nicotredole, nicoXamat, nic Zole, oxidapamine, oxidronic acid, Oxfentorex, oxifungin, tiazem, nictindole, nidroxy Zone, , , nife oxigluttione, , , oXimonam, OXindanac, malol, , , nifungin, nifiradene, oxiniacic acid, Oxperomide, , oxiramide, oxiso nifuraldezone, nifuralide, , nifuratrone, nifurdazil, pred. Oxisuran, oxitefonium, oxitriptan, , oxtri nifurethaZone, nifurfoline, nifurimide, nifurizone, nifurma ponium, , , , oxolamine, Zole, nifurmerone, nifuroquine, nifuroxazide, nifuroxime, , oXomermazine, oXonazine, Oxophenarsine, nifurpipone, nifurpirinol, nifirprazine, nifurquinazol. Oxoprostol, , oXprenoate, , Oxtriph nifursemizone, nifursol, nifurthiazole, nifurtimox, nifurtoi ylline, oxbenZone, , oxychlorosene, oxycin nol, nifurvidine, nifurzide, nigludipine, nihydraZone, chophen, oxyclipine, oxyclozanide, , oxydipento , nileprost, nilprazole, , nilutamide, nium, , , , , nimaZone, , , nimidane, oxymethalone, , oxypendyl, , , , nimustane, neometacin, niperoti , , oxyphenisatin, dine, nipradillol, niprofaZone, nitavoline, nirdazole, nis oxyphenonium, oxypurinol, oxypurronium, oxyquinoline, buterol, , , , , nitar oxyridazine, oxysonium, , , , Sone, nitazoxanide, , nithiamide, nitisinone, oZagamicin, oZolindone, paclitaxel, pacrindolol, pactimibe, nitracrine, nitrafudan, nitralamine, nitramisole, nitradua padimate A, padimate Q, , , paldimycin, Zone, , nitrefazole, , nitrocefin, nitro palinavir, , palmidrol, palmoxirate, palonid clofene, nitrocycline, nitrodan, nitrofurantoin, nitrofuraZone, ipine, palonosertron, palosuran, pamabron, pamaqueside, nitromersol, nitromide, , nitroscanate, nitrovin, pamaquin, , pamidronic acid, , pan nitroXinil, nitroxoline, nivaZol. nivimedone, , amesine, pancopride, pancuronium, panipenem, , nizofenone, noberastine, nocloprost, nocodazole, nofecam pantenicate, pantethine, panthenol, , ide, nogalamycin, nolatrexed, nolinium, nolomirole. nolpi , papverine, papveroline, parachlorphenol, tantium, , nomelidine, , nonabine, parafiutizide, , acetate, nonaperone, nonapyrimine, nonathymulin, nonivamide, paranitrosulfathiazole, paranyline, parapenzolate, para , norbolethone, norbudroine, norcholestenol, propamol, pararosaniline, , parbendazole, parc , , , nordefrin, , etasal, parconazole, , pareptide, parethoxycaine, , norepinepherine, , noethin pargeverine, , , paricalcitol, paridocaine, drone, norethynodrel, noreximide, , norfloxacin, parodilol, , , , , , , , norg parsalmide, particin, parvaquone, pasiniazid, pasireotide, estrieneone, norletimol, norlevorphenol, , nor patamostat, patupilone, paulomycin, paxamate, paZelliptine, morphine, , , nortopixantrone, , paZOxide, paZufloxacin, pecilocin, pecocycline, , , noSantine, , nosihep pefloxocin, , peldesine, peliomycin, pelitinib, peli tide, novobiocin, , noxytiolin, nuclomedone, trexol, pelretin, pelrinone, pelubiprofen, pemedolac, nuclotixene, , nupafant, nuvenZepine, nylestriol, pemerid, pemetrexed, pemirolast, , penamecillin, nylidrin, nystatin, obidoxime, , , ocilt , , pendecamine, pendetide, penfluri ide, , octacaine, octafonium, , octapinol, dol, penflutizide, pengitoxin, penicillamine, penicillin G, octatine, octaverine, octaZamide, octenidine, Octicizer, penicillin V, penimepicycline, penimocycline, penirolol, pen octimibate, Octinoxate, octisalate, , , mesterol, penoctonium, penprostene, , penta , octotiamine, , , octriazole, cynium, pentfluranol, , , pentala odalprofen, odapipam, odiparcil, , oftomine, oftas mide, pentamethonium, , , ceine, oglu fanide, olaflur, olamufloxacin, olanexidine, olan pentamoxane, pentamustine, pentapiperide, pentapiperium, Zapine, olaquindox, , oleandomycin, oletimol, pentaquine, , pentetic acid, pentreotide, olmesartan, , olpadronic acid, olpimedone, , penthrichloral, pentiapine, , pen , olradipine, olsalazine, oltipraz, olvanil, omaciclo tigetide, pentisomicin, pentisomeide, pentizidone, pentobar Vir, omapartrilat, , omidoline, omigapil, omilox bital, , pentolonium, , pentopril, pen etine, , omonasteine, , ondansetron, torex, pentosalen, pentostatin, , , ontazolast, ontianil, opanixil, opaviraline, opiniazide, pentrinitrol, , peplomycin, pepstatin, pera , opratonium, oraZamide, oraZipone, orbofiban, clopone, peradoxime, , peralopride, peramivir, orbutopril, orconazole, orientiparcin, oritavancin, , peraquisin, perastine, peratizole, , perbufylline, per ormaplatin, , ormetoprin, , orni fomedil, perfosfamide, pegolide, perhexyline, , preessin, , ornoprostil, orotic acid, orotirelin, orpan perifosine, perimetazine, perindopril, perindoprilat, oxin, , ortataxel, orteteamine, , osater perisoxal, , , , , one, oseltamivir, , osmadizone, ospennifene, persilic acid, , , peXantel, phanquone, ostreogrycin, OSutidine, otamixaban, , oteracil, phenacaine, , , phenactropinium, otilonium, otimerate, ouabain, oxabolon, oxabrexine, , , phenamaZoline, phenampro , oxacillin, oxadimedine, , oxaflu mide, phenaphthazine, phenarsone, , mazine, oxagrelate, oxalinast, oxaliplatin, oXamarin, oxam , phenbutaZone, phencarbamide, phencycli etacin, oxamisole, oxaminiquinem , , dine, , , , phenethicil oxantel, oxapadol, oxapium, Oxaprazine, , lin, , phenylglutarimide, phenicarbazide, phenin , oXcarbazole, , oxazafone, , damine, phenindione, , , oxazidone, , oxazorone, , oxdrala phenisonone, , , phenobutiodil, Zine, Oxeclosporin, oxedrine, Oxeglitazar, OXeladin, oxen , , , phenoxyben dolone, oxepinac, oxetacillin, oxethazine, , Zamine, , , phenprocou oxfendazole, Oxfenicine, Oxibendazole, oxibetaine, oxiconi mon, , , , phen US 2010/0226943 A1 Sep. 9, 2010 tolamine, phenyl aminosalicylic acid, , acid, , profexalone, proflavine, , proga phenylbutaZone, , , phe bide, , , , prohep nylthiolone, , pheny racillin, phenyramidol. tazine, , praline, , prolonium, pro phenyloin, pnetharbital, , , phoxim, mazine, , , , promo phthalofyne, phthylsulfacetamide, phthalylsulfamethiazole, late, promoxo lane, prontalol, , , phthalylsulfathiazole, physostigmine. , phytona propagermanium, propamidine, , propanocaine, dione, pibaxizine, pibecarb, , , pibroZe propantheline, proparacaine, propatyl , propaZola lesin, pibutidien, picafibrate, picartamide, , picil mide, , proprintofylline, propenZolate, properi orex, piclaimilast, piclonidine, piclopastine, picloxydine, dine, propetamide, propetamfos, , propicillin, picobenzide, picodralazine, picolamine, piconol, picoperine, propikacin, propinetidine, , propiocaine, propi picoplatin, picoprazole, , picotrin, picumast, picu ram, propisergide, , , , pro meterol, pidobenzone, pidolacetamol, pidolicaica, pidoti poxate, propoXur, , propoxyphene, . mod, pifamine, pifinate, pifexole, piflutiXol, piketoprofen, propyl docetrizoate, propyl gallate, , propy , , pilsicamide, , pime liodone, propylthiouracil, propyperone, , clone, , pimethylline, pimelautide, pimetacin, propyromazine, produaZone, produinolate, prorenoate, , pimetine, imetremide, pimilprost, , proroXan, prScillardin, prospidium, prostalene, proSulpride, , pimonidazole, , , pinadoline, proSultiamine, proterguride, protheobromine, . pinafide, pinaverium, , pincamide, . prothixene, , protionamide, protirelin, protizinic pinokalant, pinolcaine, pinoxepine, pioglitaZone, pipacy acid, , protoporphyrin, , proXZole, cline, , , pipazethate, pipebuZone, proxibarbal, proxibutene, proxicromil, proxifeZone, proXor pipecuronium, pipemidicacid, , pipenZolate, phan, , , proZapine, prucalo , , piperacillin, piperamide, piperi pride, prulifloxacin, , , puma dolate, piperilate, , piperonyl butoxide, piper fentrine, pumaprazole, pumitepa, pumosetrag, puromycin, oxan, piperphenidol, piperylone, , pipoctanone, pyrabrom, , pyrathiazine, pyrazinamide, pyrazofu , piposulfan, , , pipoxolan, rin, pyricarbate, pyridarone, pyridinol, pyridofylline, pyri pipradimadol, , pipramadol, pipratecol, piprinhydri dostigmine, pyridoxal, pyridoxamine, pyridoxine, pyril nate, pipocurarium, piprofurol, piproZolin, , amine, pyrimethamine, pyrimate, pyrinoline, pyrithione, piquizil, , , pirarubicin, piraxelate, , pyritidium, , pyrophenindane, pyrov pirzmonam, pirazolac, pirbenicillin, , pirdonium, alerone, pyroxamine, , pyrrocaine, pyrrolif pirenoxine, piremperone, pirezepine, pirepolol, , ene, pyrroliphene, pyrrolnitrin, pyrroxane, pyrvinium, pirfenidone, pirbendil, piridicillin, , piridoxilate, pytamine, , , quatacaine, , piridironic acid, pirifibrate, pirimiphos-ethyl, pirindazole, , quaZodine, quaZolast, , , pirinixic acid, pirinixil, piriprost, piriqualone, , quiflapon, quillifoline, quilostigmine, quinacainol, quinacil , piritrexin, pirlimycin, , pirmagrel, pir lin, quinacrine, , quinaldine blue, quinapril, menol, pirnabine, piroctone, pirodavir, priodomast, pirog quinaprilat, , quibolone, quincarbate, quindecam liride, , , pirolazamide, piromidic acid, ine, quindonium, quindoxin, , , piroXantrone, , piroxicillin, piroXimone, pirozadil, , quinethaZone, quinetolate, quinezamide, quinfa , pirquinozol, pirralkonium, pirsidomine, pirteni mide, acetate, , , quinine, dine, pitenodil, pitofenone, pituxate, , pivampicil quinotolast, , quinterenol, quitiofos, quinuclium, lin, pivenfrine, pivopril, , pixantrone, pizoty , quinupristin, , quisultazine, line, plafbride, plaunotol, plauracin, pleconaril, pleuromulin, , , , , rafoxanide, plevitrexed, plicamuycin, plomestane, pobilukast, podilfen, ragaglitazar, ralitoline, , raltitrexed, raluridine, podofilox, , polymixin, polythiazide, pomisartan, , ramciclane, , ramifenaZone, ramipril, ponalrestat, ponaZuril, ponfibrate, porfiromycin, posacona ramiprilat, ramixotidine, ramnodigin, ramnoplanin, ramo Zole, posatirelin, posiZolid, poskine, , pradolfoxa relix, ramosetron, ranelic acid, ranimustine, ranimycin, ranir cin, prajmalium, , pralidoxime, prailmorelin, pral estat, , ranolaine, rapacuronium, , rasbu nacasan, , , pramoxine, prampine, ricase, rathyronine, ravuconazole, raZaxaban, razinodil, pranazepide, , prankulast, pranolium, pranopro raZobazam, razoxane, rebimastat, , recainam, fen, pranosal, , , pratosartan, pravadoline, , , reglitazar, , relomycin, , praxadine, praZarelix, , prazepine, , , remikiren, remiprostol, remoX praziquantel, , prazocillin, , preclamol. ipride, , rentiapril, , , rep , , , , arixin, , repirinast, repromicin, , rescime , prednisolone, prednisone, prednival, pred tol, rescinnamine, resequinil, , residuimod, nylidene, , pregnadiol, , premafloxa resocortolbutyrate, resorantel, , retapamulin, retel cin, , , prenisteine, prenoverine, liptine, , retinol, , revatropate, revenast, prenoxdiazine, , pretamazium, pretiadoil, preza reviparin, revizinone, , , riboflavin, ribo tide, pribecaine, , prideperone, , prifelone, prine, ribostamuycin, , , ridogrel, rifabu pri?inium, prifuroline, pilocalne, primaperone, primaquine, tin, rifalazil, rifametane, rifamexil, rifamide, rifampin, rifap , , primycin, prinomastat, prinomide, entine, , rilapine, rilmakalim, , prinoXodan, pristinol, pristinamycin, prizidilol, , rillmenidine, rilopirox, riloZarone, rilpovorine, , , probenecid, probicromil, , procaina , rimazolium, , , , mide, , procarbazine, , , , rimoprogin, , rioprostil, , rip , , proclonol, procromil, , isartan, risarestat, risedronicacid, , risotilide, rispen , prodeconium, , prodipine, prodolic Zepine, , ristianol, ristocetin, , ritometan, US 2010/0226943 A1 Sep. 9, 2010 19 ritipenem, ritobegron, , ritolukast, , ritropir cinylsulfathiazole, Succisulfone, Suclofenide. , ronium, ritrosulfan, rivaroXaban, rivastigmine, rivoglitaZone, Sucralose. Sucrose octaacetate. SucroSufate, Sudexanox, , , robenidine, rocastine, rocepafant, Sudoxicam, Sufenatil, , Sufugolix, , rociclovir, rocuronium, rodocaine, rodorubicin, , Sulamserod, , SulaZuril, Sulbactam, Sulbenicillin, rofelodine, rofileponide, roflumilast, rogletimide, rokitamy Sulbenox, Sulbentine, Sulbutiamine, Sulclamine, Sulconazole, cin, rollafagrel, roletamide, rolgamidine, , roli Sulfabenz, Sulfabenzamide, Sulfabromomethazine, Sulfacar cyprine, , rollitetracycline, rolodine, , bamide, Sulfacecole, Sulfacetamide, Sulfachlorpyridazine, romazarit, romergoline, romifenone, , romurtide, Sulfachrysoidine, Sulfaclomide, Sulfaclorazole, Sulfaclozine, ronactolol, ronidazole, , ronipamil, runnel, ropin Sulfacytine, Sulfadiazine, Sulfadimethoxine, Sulfadoxine, Sul irole, ropitoin, , ropizine, roquinimex, rosapros faethidole, Sulfaguanidine, Sulfaguanole, Sulfalene, Sulfa tol, rosaramicin, , rosiglitaZone, roSoxacin, ros loxic acid, SulfamaZone, Sulfamerazine, Sulfameter, Sulfamet tafuroxin, rostaporfin, rosterolone, , rotamicillin, hazine, sulfamethizole, Sulfamethoxazole, , rotoxamine, rotaxate, roXadimate, roXarsone, Sulfamethoxypyridazine, Sulfametmidline, Sulfametrole, Sul , roXibolone, roxifiban, , roXithro famonomethoxine, Sulfamoxole, Sulfanilamide, Sulfanilate, mycin, roXolonium, roXoperone, rubitecan, rubOXistaurin, Sulfaanitran, Sulfaperin, Sulfaphenazole, Sulfaproxyline, Sul , rufloxacin, , rupintrivir, rutamycin, fapyridine, Sulfaquinoxaline, Sulfarsphenamine, Sulfasala ruvaZone, ruzadolane, Sabarubicin, , , Zine, Sulfasomizole, SulfaSuccinamide, Sulfasymazine, Sul Sabiporide, Saccharin, Safingol, Safirinol, Sagandipine, salac fathiazole, Sulfathiourea, , Sulfatroxazole, etamide, Salafibrate, Salantel, Salazodine, Salazosulfadimi Sulfatrozole, Sulfazamet, Sulfinaolol, Sulfinpyrazone, Sul dine, Salazosulfamide, Salazosulfathiazole, Salcaprozoic furam, Sulfisomidine, Sulfisoxazole, Sulfobromophthalein, acid, Salcolex, Salethamide, Salflucerine, Salicyl , Sali Sulfonterol, , Sulfosalicylic acid, Sulfoxone, Sul cylamide, Salicylic acid, Salinazid, Salinomycin, Salmefamol. crinat, Sulindac, Sulisatin, , Sulmarin, Sulma , Salmisteine, Salnacedin, Salprotoside, , Zole, Sulmepride, Sulnidazole, Sulocarbilate, , Sulo , Samixogrel, Sampatrilat, sampirtine, Sancycline, dexide, Sulofenur, Sulopenem, Sulosemide, Sulotroban, Sanfetrinem, sanguinarium, Saperconazole, Saprisartan, Suloxifen, , Sulprosal, , Sultamicillin, Sul sapropterin, saquinavir, Sarafloxacin, Sarakalim, Saralasin, tiame, , Sultosilic acid, Sultroponium, Sulukast, Sul sarcolysin, Sardomozide, , Saripedem, , Verapride, Sumacetamol, , Sumarotene, Sumatrip . Samoxicillin, Sarpicillin, , tan, Sumetizide, Sunagrel, Suncillin, , Supidimide, saterinone, satigrel, satranidazole, satraplatin, saviprazole, Supalast, , , , Suricamide, Suri savoxepin, scopafungin, scopinast, , Secalcif clone, , Suronacrine, Susalimod, SuXemerid, Sux erol, seclaZone, , , , sede ethonium, SuxibuZone, Symclosene, Synetine, tabilautide, camycin, Sedoxantrone, Seganserin, , Seglitide, tabimorelin, tacalcitol, tacapenem, tacedinaline, taclamine, Selamectin, Selgiline, , Soldenoson, selprazine, Sampi , tacrolimus, , tafluposide, taglutamine, tago mod, sematilide, Semaxanib, semduramicin, , rizine, , talampicillin, , , talb Semotiadil, Semustine, SenaZodan, Seocalcitol, sepazonium, utal, , talibegron, , , talisomycin, seperidol, sepimostat, Seprilose, , sequifenadine, tallimustine, talmetacin, talmetoprim, , talniflumate, , , serfibrate, , sermetacin, talopram, talsalate, toloXimine, , , , , , setzindol, Setipafant, setip , taltobulin, taltrimide, taludipine, talviraline, tiline, , Sevitropium, Sevopramide, Sezalamide, tameridone, tameticillin, , tamibarotene, tamiti Sagoside, Sibenadet. Sibopirdine, sibrafiban, , sic nol, tanolarizine, tamoxifen, , , canin, Sifrprazine, , , , silibi , , , tandutinib, taniplon, nin, Silcristin, sildianin, , silodrate, , , , taprizosin, taprostene, tarazepide, siltenZepine, simendan, simetride, , simtraZene, tariquindar, tasosartan, tasuldine, taurolidine, tauromustine, , sincalide, sinefungin, sinitrodil, sintropium, tauroselcholic acid, taurosteine, tazadolene, taZanolast, taZ sipatrigine, , Siratiazem, sirolimus, sisomicin, Sita arotene, taZaSubrate, tazeprofen, tazifylline, taZiprinone, floxacin, Sitalidone, Sitamaquine, , sitofibrate, sito taZobactam, taZofelone, , taZometime, , glusoide, sivelestat, Soblidotin, Sobuzoxane, , tebatizole, tebipenem, tebufelone, tebuquine, tecadenoson, Solifenasin, Solimastat, Solpecainol, Solypertine, Somatadine, tecalcet, tecastemizole, teclthiazide, , , tefa soneclosan, , sopitazine, Sopromidine, Soqui Zoline, tefenperate, teflufazine, tefiutiXol, tegafur, , nolol, Sorafenib, Soraprazan, Sorbinicate, Sorbinil, , teglicar, teicopamin, telavancin, , , Sornidipine, , Soterenol, spaglumic acid, sparfloxacin, telinavir, tellithromycin, telmesteine, , telox sparfosate, sparsomycin, , spectinomycin, antrone, teludipine, temafioxacin, temarotene, tematropium, spiclamine, , , , spiramycin, , temefos, temelastine, temiverine, temocapril, spirapril, spiraprilat, , spirgetine, spirilene, spir temocaprilat, temocillin, temodox, , temozolo iprostil, Spirofylline, spirogermanium, Spiroglumide, spiro mide, temisirolimus, temurtide, tenamfetamine, tenatopra mustine, , Spiroplatin, , spirotriaz Zole, tendamistat, , , , ine, , , spiroXepin, Spizofurone, tenilsetam, teniposide, tenivastatin, , tenofovir, Sprodiamine, squalamine, squalane, stacofylline, stillimycin, , , tenosal, tenosiprol, Stannsoprfin, stanolone, stanoaolol, stavudine, Stearylsulfa tenoxicam, tenylidone, teoprantil, teoprolol, tepirindole, tep mide, Steffimycin, , strpronin, Stercuronium, Stev oxalin, , teprotide, , terbequinil, terbin aladil, Stibamine, stilbophen, Stilbamidine, Stilbazium, stilo afine, , terbucromil, terbufirol, terbuficin, terbuprol, nium, Strimazole, , stirocamide, Stirofos, , terciprazine, , terdecamycin, teeres streptomycin, streptonicozid, Streptonigrin, Streptozocin, tigmine, terfeadine, terfiavoxate, terfuranol, , teri styramine, SubathiaZone, Subendazole, Succinylcholine, suc flunomide, terikalant, terizidone, terlakiren, , US 2010/0226943 A1 Sep. 9, 2010 20 ternidazole, , terofenamate, teroxalene, teroxirone, tranexamic acid, tranilast, transcamide, trantelinium, trany , tesaglitazar, tesicam, tesimide, tesimilifene, cypromine, trapencaine, , , traXanox, traXo , testolactone, , tetomilst, tetrabar prodil, traZitiline, , , traZolopride, treben bital, , , tetracycline, tetrahydroZo Zomine, trecadrine, trecetilide, , trelnarizine, line, tetramethrin, tetramisole, tetraxetan, , tetra treloxinate, , , trenizine, , Zolast, tetriprofen, tetrofosmin, tetronasin, tetroquinone, , , trepirium, , treptilamine, tetroxoprin, tetrydamine, teverelix, texacromil, tezacitabine, terquisin, tresperimus, , trethinium, trethocanoic , , , , thenium, the acid, tretinoin, tretinoin tocoferil, , triacetin, tri nyldiamine, , , theofibrate, theo afungin, triamcinolone, , triamcino phylline, thiabendazole, thiacetarsamide, , thia lone benetonide, , triampyZine, tri mazole, thiamine, thiamiprine, , thamylal, amternem , , tribendilol, tribenoside, thiaZesim, thiazinamium, thiazolsulfone, thiethyperazine, tribromsalan, tribuZone, tricaprilin, tricetamide, trichlorfon, thihexinol ethylbromide, thimerfonate, thimerosal, thio trichlormethiazide, trichlomethine, triciribine, triclabenda colchicoside, thioctic acid, thiofuradene, thioguanine, thio Zole, triclacetamol, triclazate, triclobisonium, , hexamide, thioinosine, thiopental, thiophanate, thiopro triclodazol, triclofenol, , triclofyllin, , tri pazate, , , thiosalan, thiostrpton, closan, tricyclamol, , tridolgosir, trientine, tri thiotepa, , thiothixene, thiphenamil, thiphen ethylenemelamine, trifenagrel, trifezolac, triflocin, trifluba cillin, thiram, thonzonium, , , threo Zam, triflumidate, triflomeprazine, trifluperazine, nine, thymocartin, thymoctonan, , thymopentin, thy , , trifluidine, , trifosmin, motrinan, thyromedan, thyropropic acid, thyroxin, tiacrilast, trigeVolol, trihexylpheidyl, triletide, triloStane, , , tiafibrate, , , tiametomnium, , trimecain, trimedoxime, , trimep tiamulin, tianafac, , tiapamil, tiapirinol, , eridine, trimeprazine, , trimethadone, trimetha , tiaprost, tiaramide, , tiaZuril, tia mide, trimethaphan, trimethidinium, , tri balosin, tibeglisene, tibenelast, tibenzate, tibeZonium, methoprim, , trimetrexZate, trimexiline, , tibric acid, tibrofan, ticabesine, ticalopride, ticarbo , trimoprostil, trimoxamine, , triox dine, ticarcillin, ticlatone, ticlopidine, ticolubant, ticrynafen, salen, tripalmitin, tripamide, , , tri tidembersat, tidiacic acid, tiemonium, tienocarbine, tieno platin, , triptorelin, , trixolane, tri pramine, , tifemoxone, tifenaZoxide, tiflamizole, Zoxime, trocimine, troclosene, trodusquemine, , tiflorex, , tiflucarbine, tiformin, tifurac, tigecycline, , , tromanttadine, tropabazate, tigemonam, , , tillargenine, , tili , tropapride, , tropenZiline, tropicam dine, tiliquinol, , , tilmicosin, tilnoprofen, ide, tropigline, tropirine, tropisetron, tropodifene, troquida tilomisole, tillorone, tilozepine, tilsuprost, tiludonic acid, tim Zole, trospectomycin, trospium, trovafloxacin, troVirdine, codar, timefurone, timegadine, timelotem, timepidium, timi troxacitabine, troXerutin, , troXolamide, troxonium, perone, timirdine, acetate, timofibrate, . troxypyrrolium, truXicurium, truXipicurium, tryparsamide, timonacic, , tinabinol, tinazoline, timidazole, tubocurarine, tubulozole, tucaresol, , tulathromy tinisulpride, tinofedrine, tinoridine, tiocarlide, tioclomarol, cin, , tulopafant, , tuvatidine, , , tioctilate, , tiodonium, tiomergine, tylosin, tymazolin, tyropanoate, , tyrothricin, uben , tioperidone, tiopinate, tiopronin, tiopropam imex, ubidecarenone, ubisindine, ufenamate, ufiprazole, ine, , tiotidine, tiotropium, tioxacin, tioXamast, , ulifloxacin, uliprisnil, , undecylenic tioxaprofen, tioxidazole, tioXolone, tipentosin, , acid, , upenazime, upidosin, uracil, uracil mus tipetropium, , tipindole, tipranavir, , tipre tard, , uredepa, uredofos, urefibrate, ursodiol. nolol, tiprinast, tiprodil, tiprostanide, tiportimod, tiqueside, urulcholic acid, utibapril, utibaprilat, Vadocaine, , tiquinamide, tiquizium, tiracizine, tirapazamine, , Valconazole, , Valdetamide, Valdipromide, Vale , tirofiban, tiropramine, tisartan, tisocalcitate, thamate, vlaganiciclovir, Valine, Valnemulin, Vlanoctamide, tisocromide, , tisoquone, tivanidazole, tiviciclovir, , Valomaciclovir, , , Vlaproicacid, tivirapine, tixadil, tixanox, , tiZabrin, , , Valrocemide, valrubicin, Valsartan, Valorcitab tizolemide, tizoprolic acid, tobicillin, toborinone, tobramy ine, Valtrate, Vamicamide, Vancomycin, Vandetanib, Vanep cin, tocamide, tocamphyl, tocladesine, tocofenoxate, tocofi rim, Vanitiolide, , Vanyldisulfamide, Vapiprost, brate, tocophersolan, todralazine, , tofetridine, Vapreotide, Vardenfanil, , Varespladib, Vatalanib, tofimilast, tofisoline, tofisppam, tolafentrine, . Vatanidipine, Vebufloxacin, vecuronium, , , tolboxane, , tolvapone, tolciclate, , Velaresol, Velnacrine, , Venritidine, toldimfos, tolfamide, , , tolimidone, Verodoline, , , Verazide, Verilopam, Ver tolindate, toliodium, , tolmesoxide, tometin, tolnaf lukast, Verofylline, versetamide, Verteporfin, , tate, tolnapersine, tolnidamine, toloconium, , tolo , Vetrabutine, , , , nium, , toloxychlorinol, tolpadol, tolpentamide, Vildaglipin, , , vinblastine, , , tolpiprazole, tolpronine, tolpropamide, tolpyrra , Vincanol, Vincofos, Vinconate, Vincristine, Vinde mide, tolduinzole, tolrestat, , toltraZuril, tolu burnol, Vindesine, Vinpidine, , Vinformide, Vinfos fazepam, , tolycaine, tomeglovir, tomelukast, tomo iltine, Vinglycinate, Vinleucinol, Vinleurosine, Vinmegallate, glumide, tomoxiprole, tonabersat, , , Vinorelbine, , Vinpoline, Vinrosidine, Vintiamol. , topixantrone, topotecan, toprilidine, , Vintoperol, Vintriptol, , Vinzolidine, Viomycin, toquizine, torbafylline, , torcitabine, toremifene, Viprostol, Vicqualine, Viquidil, Virginiamycin, viridofulvin, , torsemide, tosagestin, tosifen, to Sufioxacin, ViroXime, , Visnafylline, Vofopiitant, Voglibose, to Sulur, , traboXopine, , tradecamide, , Volpristin, Voriconazole, Vorozole, Voxergolide, , , tramaZoline, trandolapril, trandolaprilat, , , , Xanoxic acid, , US 2010/0226943 A1 Sep. 9, 2010

Xantifibrate, Xantocillin, Xanto?yl palmitate, Xemilofiban, oxide (CaO), manganese dioxide (MnO and MnO), or Xenalipin, Xenazoic acid, Xenbucin, Xenipentone, Xenothio combinations comprising at least one of the foregoing inor rate, Xenygloxal, Xenylhexenicacid, Xenylropium, . ganic oxides. Examples of inorganic carbides include silicon Xibornol, Xidecaflur, Xilobam, Ximelagatran, Ximoprofen, carbide (SiC), titanium carbide (TiC), tantalum carbide Ximidamine, Xinomiline, sipamide, . , (TaC), tungsten carbide (WC), hafnium carbide (HfC), or the , , Xylocoumarol. , Xylox like, or a combination comprising at least one of the foregoing emine, yohimbic acid, Zabicipril, Zabiciprilat, , carbides. Examples of suitable nitrides include silicon , Zafiuleptine, Zalcitabine, Zalderide, , nitrides (SiN.), titanium nitride (TiN), or the like, or a com , Zalitidine, , Zamifenacin, Zanamivir, bination comprising at least one of the foregoing. Examples Zanapezil, Zankiren, , , , Zard of suitable borides are boride (LaB), chromium averine, Zatebradine, , Zelandopam, Zenarestat, borides (CrB and CrB), molybdenum borides (MoB. , Zeniplatin, Zepastine, , Zetidoline, Zidapa MoBs and MoB), tungsten boride (WBs), or the like, or mide, Zidometacin, Zidovudine, Zifrostilone, Zilantel, Zilas combinations comprising at least one of the foregoing corb, , , Zimeldine, Zimidoben, Zindotrine, borides. Exemplary inorganic Substrates are those that com , Zinconazole, Zinostatin, , ZinviroXime, prise naturally occurring or synthetically prepared silica and/ , Ziprsidone, Zocainone, Zofenopril. Zofenoprilat, or alumina. Metals used in the spaced features and/or the Zoficonazole, , Zolasartan, , Zolendronic Surface can be transition metals, alkali metals, alkaline earth acid, Zolenzepine, , , Zoliprofen, Zolmi metals, rare earth metals, or the like, or a combination com triptan, Zoloperone, , , , prising at least one of the foregoing metals. Examples of , , ZonicleZole, Zoniporide, Zonisa metals are iron, copper, aluminum, tin, tungsten, chromium, mide, , Zopolrestat, Zorbamycin, Zorubicin, ZoSu gold, silver, titanium, or a combination comprising at least quidar, , ZoticaSone, , Zucapsaicin, one of the foregoing metals. Zuclomiphene, , Zylofuramine, or the like, or a 0102 The pattern can be aligned such that linear channels combination comprising at least one of the foregoing phar between respective features in a pattern can be arranged to be maceutical or veterinary compounds. perpendicular and/or parallel to an average direction of fluid 0098 Algaecides may also be disposed upon the patternor flow, when the pattern is disposed on a Surface that contacts a blended in with the material used to form the pattern. flowing fluid. In one embodiment, the pattern may be dis Examples of suitable algaecides are 2,2-dibromo-3-nitrilo posed on the substrate so that the linear channels between propionamide (DNP), methylene bis-thiocyanate (MBT), respective features in a pattern can be arranged to occupy an 5-chloro-2-methyl-4-isothiazolin-3-one/2-methyl-4-isothia angle of 1 to about 360 degrees, specifically about 5 to about Zol in-3-one (CMI), tetrahydro-3,5-dimethyl-2H, 1,3,5-thia 270 degrees, and more specifically about 10 to about 200 diazine-2-thione (TDD), sodium dimethyldithiocarbamate/ degrees, and more specifically about 20 to about 200 degrees sodium ethylene bis dithiocarbamate (SDT), alkyl with respect to the average direction of fluid flow. dimethylbenzyl amonium chloride family, polyoxyethylene 0103) In one embodiment, the pattern can be dynamically (dimethyliminio)ethylene (dimethyliminio)ethylene dichlo modified during use. In other words, the Surface can comprise ride, copper Sulfate, or the like, or a combination comprising a material Such as, for example, a shape memory alloy, a at least one of the foregoing algaecides. shape memory polymer, a magnetorheological fluid, an elec 0099. In one embodiment, the biologically active agents trorheological fluid, and the like, that can be activated when may be encapsulated in microballoons and incorporated into desired to either inhibit or to facilitate bioadhesion. the pattern as part of the drug coating. In another embodi 0104. In an exemplary embodiment, when the pattern ment, the biologically active agents may be encapsulated in comprises an organic polymer, the organic polymer can be microballoons and incorporated on the Surface of the pattern filled with an electrically conducting filler thereby making the or incorporated into the channels that form the tortuous path Surface electrically conductive. By passing an electrical sig way. The microballoons may serve to release the gradu nal to the Surface, the pattern can be heated and consequently ally over a period of time. In other words the pattern can serve the dimensions of the features and those of the patterns can be as a time-release coating for the drugs. In one embodiment, changed during use. the pattern can release drugs after being Subjected to a stress. 0105. Although not required to practice the present inven 0100. The inorganic materials used in the spaced features tion, Applicants not seeking to be bound by the mechanism and/or the Surface can comprise ceramics and/or metals. The believed to be operable to explain the efficacy of the present inorganic materials can comprise inorganic oxides, inorganic invention, provide the following. The efficacy of surfaces carbides, inorganic nitrides, inorganic hydroxides, inorganic according to the invention is likely to be due to physically oxides having hydroxide coatings, inorganic carbonitrides, interfering with the settlement and adhesion of microorgan inorganic oxynitrides, inorganic borides, inorganic borocar isms. Such as algae, bacteria and barnacles. Properly spaced bides, or the like, or a combination comprising at least one of features (such as "ribs) formed on or formed in the surface the foregoing inorganic materials. Examples of suitable inor can be effective for organisms from Small bacteria (<1 um, ganic materials are metal oxides, metal carbides, metal such as 200 to 500 nm), to large tube worms (>200 um, such nitrides, metal hydroxides, metal oxides having hydroxide as 200 to 500 um), provided the feature spacing scales with coatings, metal carbonitrides, metal oxynitrides, metal the organism size. Specifically, bioadhesion is retarded when borides, metal borocarbides, or the like, or a combination the specific width of closely packed, yet dissimilar features comprising at least one of the foregoing inorganic materials. (e.g. ribs) in the pattern is too narrow to support settlement on 0101 Examples of suitable inorganic oxides include silica top, yet the ribs are too closely packed to allow settlement in (SiO2), alumina (Al2O), titania (TiO), Zirconia (ZrO2), between. However, a feature spacing too small is believed to ceria (CeO), manganese oxide (MnO), oxide (ZnO), make the Surface look flat to the settling organism, i.e. like the iron oxides (e.g., FeC), Y-Fe2O, Fe-O, or the like), calcium base Surface, and thus ineffective. Accordingly, a feature US 2010/0226943 A1 Sep. 9, 2010 22 spacing that scales with 25 to 75% of the settling organism’s polymeric elements that contribute to the viscoelastic and Smallest physical dimension has been found to be generally topographical properties. A “feature' as used herein is effective to resist bioadhesion. Various different surface defined a volume (L, Wand H) that projects out the base plane topographies can be combined into a hierarchical multi-level of the base material or an indented volume (L, W and H) Surface structure to provide a plurality of spacing dimensions which projects into the base material. The claimed architec to deter the settlement and adhesion of multiple organisms ture is not limited to any specific length. For example, two having multiple and wide ranging sizes simultaneously. Such ridges of an infinite length parallel to one another would as algae, spores and barnacles. define a channel in between. In contrast, by reducing the 0106 Topographies according to the invention can gener overall lengths of the ridges one can form individual pillars. ally be applied to a wide variety of surfaces for a wide variety Although the Surface is generally described as a coating, of desired applications. Applications for inhibiting bioadhe which is generally a different material as compared to the sion using the invention described in more detail below base article, as noted above, the invention includes embodi include base articles used in marine environments or bio ments where the coating and base layer are formed from the medical or other applications which may be exposed to con same material. Such as provided by a monolithic design, tamination by biological organisms, such as roofs on build which can be obtainable by micromolding. ings, water inlet in power plants, catheters, cosmetic 0111. In the case of a Surface coating, the coating can implants, and heart valves. As described below, Surfaces comprise a non-electrically conductive material, defined as according to the invention can be formed on a variety of having an electrical conductivity of less than 1x10 S/cm at devices and over large areas, if required by the application. room temperature. The coating layer can comprise elas 0107 Barnacles are known to be generally elliptically tomers, rubbers, polyurethanes and polysulfones. The elastic shaped have a nominal length of about 100 um, and a nominal modulus of the coating layer can be between 10 kPa and 10 width of about 30 Lum. Algae are also generally elliptically MPa. In the case of 10 to 100 kPa materials, the coating can shaped and have a nominal length of about 7 um, and a comprise hydrogels such as polyacrylic acid and thermo sen nominal width of about 2 um, while spores are generally sitive hydrogels such as poly isopropylacrylamide. The coat elliptically shaped have a nominal length of about 5um, and ing layer can be various thicknesses, such as 1 um to 10 mm, a nominal width of about 1.5 Lum. Features according to the preferably being between 100 um to 1 mm. invention are generally raised Surfaces (volumes) which 0112 Each of the features have at least one microscale emerge from a base level to provide a first feature spacing, or dimension. In some embodiments, the top surface of the in the case of hierarchical multi-level surface structures features are generally substantially planar. Although feature according to the invention also include the a second feature spacing has been found to be the most important design spacing being the spacing distance between neighboring pla parameter, feature dimensions can also be significant. In a teaus, which themselves preferably include raised features preferred embodiment of the invention, each of the features thereon or features projected into the base article. includes at least one neighboring feature having a 'substan 0108. As noted above, if the feature spacing is smaller than tially different geometry”. “Substantially different geom the Smaller dimension of the organism or cell, it has been etry” refers to at least one dimension being at least 10%, more found that the growth is generally retarded, such between preferably 50% and most preferably at least 100% larger than 0.25 and 0.75 of the smaller dimension of the cell or organ the Smaller comparative dimension. The feature length or ism. A feature spacing of about /2 the Smaller dimension of a width is generally used to provide the substantial difference. given organism to be repelled has been found to be near 0113. The feature spacing in a given pattern should gen optimum. For example, for an algae spore 2 to 5um in width, erally be consistent. Studies by the present Inventors have to retard adhesion, a feature spacing of from about 0.5 to 3.75 indicated that Small variations in micrometer scale spacing of um, preferably 0.75 to 2 um is used. For example, to repel the ribs that compose the surface features have demonstrated barnacles 20 to 50 um in width, a feature spacing of between that less than 1 um changes (10% or less than the nominal 5 and 200 um, preferably 10 to 100 um, has been found to be spacing) can significantly degrade coating performance. For effective. For repelling both barnacles and spores, a hierar example, the consistency of a2um nominal spacing should be chical multi-level Surface structure according to the invention within +0.2 um for best retardation of Ulva settlement. can include a raised surfaces (volumes) which emerge from or 0114. The composition of the patterned coating layer may are projected into a base level having a feature spacing of also provide surface elastic properties, which also can pro about 2 Lim, and a plurality of striped plateau regions spaced vide some bioadhesion control. In a preferred embodiment 20 um apart, the plateau regions also including raised surfaces when bioadhesion is desired to be minimized, the coated (volumes) which emerge from or are projected into the pla Surface distributes stress to several Surrounding features teau having a spacing of about 2 Lum. One or more additional when stress is applied to one of the features by an organism to plateau regions can be used to repel additional organisms be repelled from the surface. having other sizes. The additional plateau regions can be 0115 The roughness factor (R) is a measure of surface aligned (parallel) with the first plateau, or oriented at various roughness. R is defined herein as the ratio of actual Surface other angles. area (R) to the geometric Surface area (R), R-R/R). 0109 Although generally described for deterring bioad An example is provided for a 1 cm piece of material. If the hesion, the invention can also be used to encourage bioadhe sample is completely flat, the actual Surface area and geomet Sion, such as for bone growth. Feature dimensions of at least ric surface area would both be 1 cm. However if the flat equal to about the size of the larger dimension of bioorganism Surface was roughened by patterning, Such as using photoli or cells to be attached have been found to be effective for this thography and selective etching, the resulting actual Surface purpose. area becomes much greater that the original geometric Sur 0110. Although the surface is generally described herein face area due to the additional surface area provided by the as being an entirely polymeric, the coating can include non sidewalls of the features generated. For example, if by rough US 2010/0226943 A1 Sep. 9, 2010

ening the exposed surface area becomes twice the Surface a ceramic. The coating layer is also typically hydrophobic, area of the original flat surface, the R value would thus be 2. but can also be neutral or hydrophilic. 0116. The typography generally provides a roughness fac I0123. As noted above, the patterned surface layer may also tor (R) of at least 2. It is believed that the effectiveness of a provide Surface elastic properties which can influence the patterned coating according to the invention will improve degree of bioadhesion directly, an in Some cases, also modu with increasing pattern roughness above an R value of about late surface chemistry of the surface layer. It is believed that 2, and then likely level off upon reaching some higher value of a low elastic modulus of the patterned coating layer tends to R. In a preferred embodiment, the roughness factor (R) is at retard bioadhesion, while a high elastic modulus tends to least 4, such as 5, 6, 7, 8, 9, 10 11, 12, 13, 14, 15, 16, 17, 18, promote bioadhesion. A low elastic modulus is generally 19, 20, 25 or 30. Assuming deeper and more closely spaced from about 10 kPa and 10 MPa, while a high elastic modulus features can be provided, R values can be higher than 30. is generally at least 1 GPa. 0117 FIG. 1(a) is a scanned SEM image of an exemplary 0.124. The patterned surface can be formed or applied “Sharklet' topography according to an embodiment of the using a number of techniques, which generally depend on the invention sized to resistalgae adhesion and growth. The Shar klet topography is based on the topography of a shark's skin. area to be covered. For Small area polymer layer applications, Shark skin is a prominent example of a low friction Surface in Such as on the order of square millimeters, or less, techniques water. Unlike real shark skin which has fixed topographical Such as conventional photolithography, wet and dry etching, feature dimensions based on the species, the Sharklet topog and ink-jet printing can be used to form a desired polymer raphy is scalable to any topographical feature dimension pattern. When larger area layers are required. Such as on the including feature width, feature height, feature geometry, and order of square centimeters, or more, spray, dipcoat, hand spacing between features. The composition of real shark skin paint or a variant of the well known “applique' method be is limited to the natural composition of the skin. The Sharklet used. These larger area techniques would effectively join a topography according to the invention can be produced in a plurality of Smaller regions configured as described above to variety of material including synthetic polymers, ceramics, provide a polymer pattern over a large area region, Such as the and metals, as well as composites. region near and beneath the waterline of a ship. 0118. The Sharklet and related topographies according to 0.125. A paper by Xia et al entitled “Soft Lithography the invention can be described quantitatively using two sinu discloses a variety of techniques that may be suitable for soidal functions. This description is provided below. forming comparatively large area Surfaces according to the 0119 Surface layer comprises a plurality of features 111 invention. Xia et al. is incorporated by reference into the which are attached to and project out from base surface 130. present application. These techniques include microcontact Base surface 130 can be a roofing material, the inner surface printing, replica molding, microtransfer molding, micro of a water inlet pipe for a power or water treatment plant, an molding in capillaries, and solvent-assisted micromolding, implantable medical device or material. Such as a breast which can all generally be used to apply or form topographies implant, a catheter or a heart valve. Each of the features 111 according to the invention to Surfaces. This surface topogra have at least one microscale dimension, with a width of about phy according to the invention can thus be applied to devices 3 um, lengths of from about 3 to about 16 um, and a feature as either a printed patterned, adhesive coating containing the spacing of about 1.5 Lum. The thickness (height) of features topography, or applied directly to the Surface of the device 111 comprising coating layer is about three (3) microns. The through micromolding. first feature spacing can be less than or equal to about 200 0.126 Another tool that can be used is the Anvik HexS nanometers as can be seen in the FIG. 13. can R) 1010 SDE micro lithography system which is a com 0120 Features adjacent to a given feature 111 generally mercially available system manufactured by Anvik Corpora provide Substantially different dimensions, in the arrange tion, Hawthorne, N.Y. 10532. Such a tool could be used to ment shown in FIG. 1(a), feature lengths. The top surface of produce Surface topographies according to the invention over the features is shown as being planar. The patterned coating a large area very quickly. It has a 1 micron resolution which layer generally resists algae as compared to a generally planar can produce our Smallest pattern at a speed of approximately base surface as described in the Examples and shown in FIGS. 90 panels (10" by 14") per hour. 8(a)-(c). I0127 FIGS. 2(a)-(d) illustrate some exemplary architec 0121 FIG. 1(b) is a scanned optical profilometry image of tural patterns (unit cells) that can be used with the invention. a pattern having a plurality of features 161 projecting into a FIG. 2(a) shows a riblet pattern fabricated from PDMS elas base surface 180, according to another embodiment of the tomer having features spaced about 2 um apart on a silicon invention. Features 161 comprise indented void volumes into wafer. The features were formed using conventional photo base surface 180. Although not shown, a surface can include lithographic processing. FIG. 2(b) shows a star/clover pat regions having raised features 111 shown in FIG. 1(a) tern, FIG. 2(c) a gradient pattern, while FIG. 2(d) shows a together with regions having indented features 161 shown in triangle? circle pattern. FIG. 1(b). I0128 FIG.3 provides a table of exemplary feature depths, 0122) The composition of the patterned surface shown in feature spacings, feature widths and the resulting roughness FIGS. 1(a) and 1(b) is generally a polymer Such as polym factor (R) based on the patterns shown in FIGS. 2(a)-(d). ethylsiloxane (PDMS) elastomer SILASICT2(R) provided by Regarding the riblet pattern shown in FIG. 2(a) for the depth, Dow Corning Corp, which is an elastomer of a relative low spacing and widths shown, the resulting pattern roughness elastic modulus. The features 111 need not be formed from a factor (R) ranged from 5.0 to 8.9. Similar data for the star/ single polymer. Features can beformed from copolymers and clover pattern (FIG. 2(b)), gradient pattern (FIG. 2(c)), and polymer composites. In another embodiment, the Surface or triangle/circle (FIG. 2(d)) are also shown in FIG. 3. Regard coating comprises of a material Such as, Steel or aluminum, or ing the triangle? circle arrangement (FIG. 2(d)), for a feature US 2010/0226943 A1 Sep. 9, 2010 24 depth of 10um, feature spacing of 1 Jum, and feature width of graphs below, a sinusoidal description of Sharklet and related 1 um (circles) and 5um (triangles), a roughness factor (R) of topographies is provided. The Sharklet and related topogra 13.9 is obtained. phies can be numerically representing using two (2) sinusoi 0129 FIG. 4(a) is a scanned SEM image of an exemplary dal waves. A general equation is provided which the only hierarchical (multi-layer) Surface architecture according to an topographical restriction is that two elements with at least a embodiment of the invention. The first feature spacing dis one dimensional length discrepancy must be selected and tance of about 2 Lim between features 412 and its neighboring periodic throughout the structure. The smallest feature of the features including feature 411 is for deterring a first organism, two being related to the size of the smallest dimension (the or organism in a size range of about 5 um, or less. For width) of the organism of interest. All the elements and fea example, as noted above, an algae spore is nominally 5 um tures in-between and/or around the two periodic features wide. A patterned second layer comprising a plurality of become irrelevant. Examples of each of these instances are striped plateau regions 420 is disposed on the first layer. A presented and the generalized equation is then developed. spacing distance between elements of the plateau layer pro I0133. The Sharklet shown in FIG. 1(a) will be used for this vides a second feature spacing, which is substantially differ example. The dimensions are not relevant as this point. The ent as compared to the first feature spacing. As used herein, a Sharklet shown in FIG. 1(a) is a 4-C element (repeating) “substantially different spacing distance' is at least 50% Structure. larger, and is preferably at least 100% larger than the smaller 0.134 FIG. 5(a) shows a sinusoidal wave beginning at the first feature spacing distance. In FIG. 4, the architecture centroid of the smallest of the four Sharklet features. By shown provides a spacing distance between the second pat inspection of the periodicity of the Sharklet features, a sine tern strips of about 20 um, or about 900% greater than the first wave of the form y=A sin(wx) can be used to describe this spacing distance. The 20 um spacing is approximate /2 the periodicity as shown in FIG. 5(a). It can be noticed that the width (Smallest dimension) of a nominal barnacle thus repel repeating structure above the section described by the sine ling barnacles. Thus, hierarchical (multi-layer) Surface archi wave is out of phase from that structure by 90 degrees or n/2 tectures according to the invention can simultaneously repel radians, which happens to be a cosine wave. That periodicity multiple organisms covering a significant range of sizes. and packing can be represented using a cosine wave in the 0130. In one embodiment, the hierarchical surface archi form y=B+A cos(wX) (as shown in FIG. 5(b)). tecture comprises a first plurality of spaced features upon 0.135 The entire surface area of the topography can be which are disposed a second plurality of spaced features. FIG. numerically represented by a numerical Summation of both 4(b) depicts a hierarchical surface architecture comprising a sinusoidal waves in the form: first plurality of spaced features upon which are disposed a second plurality of spaced features. The spaced features of the first plurality of spaced features arranged in a plurality of y=cN+B+A cos(wx) where N=0,1,2,3 ... n. groupings. The groupings of the first plurality of spaced fea 0.136 The area of coverage of the topography is thus tures comprise repeat units. The spaced features within a described by the limits of n and X. grouping being spaced apart at an average distance of about 1 0.137 The Sharklet and related topographies can thus be nanometer to about 500 micrometers. Each feature may have defined by the following limitations: a Surface that is Substantially parallel to a Surface on a neigh 0.138 (i) Two geometric features of at least one dimen boring feature. In one embodiment, each feature may have a sional discrepancy must be periodic throughout the structure. Surface that is not parallel to a surface on a neighboring 0.139 (ii) The smallest of the two geometric features is feature. Each feature is separated from the neighboring fea related to the Smallest dimension of the fouling organism or tures. The groupings of features are arranged with respect to cell of interest. one another so as to define a tortuous pathway; the plurality of 0140 (iii) In a standard Cartesian coordinate system rep spaced features provide the article with an engineered rough resented by Xandy, with the origin positioned at start of each ness index of about 5 to about 30. sin and cosine wave, the Smaller of the two features is periodic 0131 The second plurality of spaced features are disposed where the waves cross y=0. The waves pass through the area upon the first plurality of spaced features. The spaced features centroid of the feature (a) y=0. of the second plurality of spaced features are arranged in a 0141 (iv) In a standard Cartesian coordinate system rep plurality of groupings. The groupings of features of the sec resented by X and y with the origin positioned at start of each ond plurality of spaced features comprise repeat units. The sine and cosine wave, the larger of the two features is periodic spaced features within a grouping being spaced apart at an where the waves cross reaches it's maximum amplitude. The average distance of about 1 nanometer to about 50 microme wave intersects the center of the tallest part of the feature (a) ters; specifically at an average distance of about 10 nanometer y=max and the X-moment of inertia of the feature (a) y=0. to about 30 micrometers; and more specifically at an average 0.142 General Form of Sinusoids distance of about 20 nanometer to about 10 micrometers. The groupings of features in the second plurality of spaced fea tures are arranged with respect to one another so as to define a tortuous pathway; the plurality of spaced features providing the article with an engineered roughness index of about 5 to 0.143 whereN=0,1,2,3 ... n. about 30. The second plurality of spaced features may have 0144. The following equations define the values for the disposed thereon a third plurality of spaced features, and so variables A, B, c and w: O 0132. In one embodiment of the invention, the surface topography is a topography that can be numerically repre Ly-dimension of larger of two elements sented using at least one sinusoidal function. In the para US 2010/0226943 A1 Sep. 9, 2010

0146 S, y-dimension of smaller of two elements Thiele U, Quéré D. 2002. Wetting of textured surfaces. Col 0147 Psy-spacing between the two elements after pack loids Surf A: Physicochem Eng Aspects 206:41-46; Quéré D. ing c-L+2*(Ps)+S, 2002. Rough ideas on wetting. Physica A: Stat Theoret Phys 0148 w 27tf-(21)/(T)->w: angular frequency (rad), f: 313:32–46) and f is the solid-liquid interface term of the frequency (HZ), T: wave period Cassie-Baxter relationship for wetting (Cassie ABD, Baxter S. 1944. Wettability of porous surfaces, Trans Faraday Soc 0149 X, X-dimensions from centroid of smaller feature 40:546-551). to the center of the tallest point on the larger feature 0159. The degree of freedom for movement relates to the tortuosity of the surface and refers to the ability of an organ Example Units=microns ism (e.g. Ulva spore or barnacle) to follow recesses (i.e., 0150 FIG. 6(a) shows element 1 and element 2. FIG. 6(a) grooves) between features within the topographical Surface. shows that the two elements can have different sizes. In the If the recesses form a continuous and intersecting grid, move FIG. 6(a), the element 1 has a shorter length and a greater ment in both the X and y coordinates on a plane Surface is width than the element 2. FIG. 6(b) shows the resulting layout permitted and the degree of freedom will be 2. Alternatively, after following limitations 3 & 4 and defining X. The FIG. if the grooves are individually isolated (e.g. as in channel 6(b) depicts that the spacing between elements can be varied. topographies) then movement is only allowed in one coordi 0151. Variables are then calculated: nate direction, the degree of freedom will be 1. The calcula tion of degrees of freedom can be seen in the FIG. 14. FIG. 14A contains a pattern where an organism traveling in a channel between two raised features can, upon arriving at the point X migrate in either the direction A-B or the direction C-D. It therefore has two degrees of freedom available to it. In the FIG. 14B, an organism travelling can only travel in the 0152 Sinusoids are then defined. direction A-B along the channel. The organism therefore has y=33N+9 sin((J/20.5)x) (1) only one degree of freedom. 0160. In addition to being able to control bioadhesion, it is y=33N+15+9 cos((J/20.5)x) (2) desirable for the Surface to function as a non-wetting Surface 0153. N=0,1,2,3 ... n. to any fluid. This is accomplished by minimizing the value of 0154) The space is then filled with elements between f, in the Equation (3) above. In minimizing the ERI value, the defined elements as shown in FIG. 7(a). Sinusoidal waves are value of r/?, is increased, thereby increasing the ERI value. then applied to define periodic repeat definitions as shown in 0.161. As such, as shown in FIG. 9 described in detail FIG. 7(b) to create the desired topographical structure over below, larger ERI values correlate with reduced settlement. It the desired surface area shown in FIG. 7(c). is generally desirable to have ERI values of about 5 to about 0155 Another method for describing surface topogra 40, specifically about 7 to about 30, and more specifically phies according to the invention involves a newly devised about 9 to about 20. In a preferred embodiment, the ERI is at engineered roughness index (ERI), first conceived of and least 5, preferably 8 or more, preferably 10 or more, prefer used by the present Inventors. The ERI can characterize the roughness of an engineered surface topography. The ERI was ably 15 or more. developed to provide a more comprehensive quantitative 0162. A related surface description according to another description of engineered Surface topography that expands on embodiment of the invention comprises a polymer layer hav Wenzel’s roughness factor (Wenzel RN. 1936, Resistance to ing a surface. The polymer layer is an elastomer containing a solid surfaces to wetting by water. Ind Eng Chem 28:988 plurality of dissimilar neighboring protruding non-planar Sur 944). It has been found that Wenzel's description alone does face features where for repelling algae, the features are not adequately capture the tortuosity of the engineered topog spaced between 0.5 and 5.0 microns. The features are such that the stress required to bend the feature is 10% greater than raphies studied. ERI is expressed as follows in the Equation the stress required to strain a cell wall and where the features (3): have a greater than 10% bending modulus difference in the ERI=(rdf)/f (3) bending modulus between two neighboring features, or in the 0156 wherein the ERI encompasses three variables asso case of three or more neighboring features, their vector ciated with the size, geometry, and spatial arrangement of the equivalence difference of greater than 10%. Preferably, the topographical features: Wenzel’s roughness factor (r), Surface features exist on the Surface at a features per area depressed Surface fraction (f), and degree of freedom for concentration of greater than 0.1 square microns. movement (d). 0163 The invention provides numerous benefits to a vari 0157 Wenzel’s roughness factor refers to the ratio of the ety of applications since Surface properties can be customized actual Surface area to the projected planar Surface area. The for specific applications. The invention can provide reduced actual Surface area includes areas associated with feature energy and cost required to clean Surfaces of biofouling by tops, feature walls, and depressed areas between features. The reducing biofouling in the first place. As a result, there can be projected planar Surface area includes just the feature tops and longer times between maintenance/cleaning of Surfaces. As depressions. explained below, the invention can also provide non-capsule 0158. The depressed surface fraction (f) is the ratio of the formation due to foreign body response in the case of coated recessed surface area between protruded features and the implanted articles. The invention can also be configured to projected planar Surface area. This depressed surface fraction provide enhanced adhesion to Surfaces. term is equivalent to both 1-ps and 1-f where (psis the Surface 0164. The present invention is thus expected to have broad solid fraction as described by Quéré and colleagues (Bico J. application for a variety of products. Exemplary products that US 2010/0226943 A1 Sep. 9, 2010 26 can benefit from the bioadhesion resistance provided by coat central venous devices such as, for example, a urinary cath ing architectures according to the invention include, but are eter, Surfaces of implanted devices such as, for example, not limited to, the following: pacemakers, artificial pancreas, and the like; ports on cath 0.165 a.biomedical implants, such as breast plant shells eters such as, for example, feeding tube ports, implanted or other fluid filled implant shells; venous access ports. It is to be noted that the patterns can be (0166 b. biomedical instruments, such as heart valves: varied to permit bioadhesion or to resist bioadhesion. These 0.167 c. Hospital surfaces, e.g., consider film (electro variations include geometrical variations, dimensional varia static) applications to Surfaces that can be readily tions, variations in Surface chemistry, or the like. These varia replaced between Surgeries; tions may be static or dynamic variations. 0168 d. Clothing/protective personal wear; 0181. As noted above, the pattern can be disposed on the 0169 e. Biomedical packaging; Surfaces of bone implants, such as, for example, an orthope (0170 f. Clean room surfaces, such as for the semicon dic implant or other implant in a hip joint replacement or ductor or biomedical industry; repair, knee replacement or repair, shoulder replacement or 0171 g. Food industry, including for packaging, food repair, elbow replacement or repair, and an ankle replacement preparation Surfaces; or repair. The pattern can also be used as a Surface in implant 0172 h. Marine industry-including exterior surfaces of able medical devices where the goal is to cause cells (e.g., marine vessels including ships and associated bilge progenitor and/or stem cells) to differentiate themselves; the tanks and gray water tanks and water inlet/outlet pipes; topography of the patterned surface causing this differentia 0173 i. Water treatment plants including pumping sta tion to occur. As noted above, these medical devices may be tions; implanted permanently or temporarily. (0174 j. Power plants; 0182. The pattern can be used on outer and inner surfaces (0175 k. Airline industry: of devices, instruments, furniture, and the like used in hospi 0176 1. Furniture industry, such as for children's cribs; tals, healthcare centers, dental offices, dispensaries, gymna 0177 m. Transportation industry, such as for ambu siums, rehabilitation facilities, bathrooms, waiting rooms, lances, buses, public transit, and and the like. As listed below, the pattern can be used in 0.178 n. Swimming pools hospitals, healthcare centers, dental offices, dispensaries, 0179 The articles may find utility in biomedical implants, gymnasiums, rehabilitation facilities, bathrooms, waiting such as breast plant shells or other fluid filled implant shells; rooms, and the like. The patterns can be used on the Surfaces biomedical instruments, such as heart Valves; hospital Sur of an electrostatic film applied to operating room surfaces faces (e.g., consider film (electrostatic) applications to Sur between Surgeries; on the Surfaces of Surgical drapes used to faces that can be readily replaced between Surgeries); cloth cover patients and/or shield doctors from fluids; on the sur ing/protective personal wear, biomedical packaging, such as, faces of waiting room chairs and waiting room furniture; on for example, the outside Surface of sterilized packaging; clean the Surfaces of operating room instruments; on the Surfaces of room Surfaces, such as, for example, the semiconductor or operating room instrument trays; on high tough surfaces in biomedical industry; food industry, Such as, for example, hospital rooms; on bedside table surfaces; on bedrail switch food packaging, food preparation Surfaces; marine industry, panel (e.g., control panels) Surfaces; on cover Surfaces (poly Such as, for example, exterior Surfaces of marine vessels mer covers of various thicknesses and dimensions) such as including ships and associated bilge tanks, gray water tanks bed sheets and on other Surfaces where keeping the Surface and water inlet/outlet pipes; water treatment plants, such as, clean is important. The surfaces of the aforementioned for example, pumping stations; powerplants; airline industry; devices, instruments and furniture may be textured, or alter furniture industry. Such as, for examples, for children's cribs, natively a film having a textured Surface can be attached to the handles on exercise equipment, and exercise equipment; in device, instrument and furniture using permanent or tempo the transportation industry, Such as, for example, in ambu rary means of attachment such as adhesives, static electricity, lances, buses, public transit; Swimming pools and other struc mechanical interlocking devices such as nails, Screws, nuts, tures that are used in aquatic environments; and the like. clips, bevel joints, dove tail joints, and the like. Additional details of the types of articles and surfaces upon 0183 The pattern can also be used to protect the surfaces which the pattern can be disposed are provided below. of all touch screens Such as, for example, a computer Screen 0180. The pattern may be used in articles that include cover—especially a touch screen cover where keeping the medical devices, medical implants, medical instruments that surface clean is desirable. The film used to protect the touch are used internal or external to the body of living beings. The screen can contact the screen or its frame using the permanent term “living beings' can include warm blooded animals, cold or temporary means of attachment discussed above. blooded animals, trees, plants, mammals, fishes, reptiles, 0.184 The pattern can also be disposed on the inner and amphibians, crustaceans, and the like. The medical devices, outer Surfaces of medical packaging Such as the Surfaces of a medical implants and medical instruments may be tempo sterile package. It can also be disposed for example, on all bed rarily or permanently inserted into the body of the living rail coverings in hospitals, medical facilities and nursing sta being. Examples of medical devices, medical implants and tions. The pattern can also be disposed on all bathroom, medical instruments are endotracheal tubes; stents; shells locker room and waiting room surfaces, especially on all used to encapsulate implants such as, for example, breast bathroom and waiting room Surfaces in hospitals, office implant shells; breast implants; ear tubes; heart valves; Sur buildings, Schools, colleges, stadiums, and other places faces of bone implants; Surfaces of grafted tissues; Surfaces of where mass gatherings of people take place and where there is contact lens; components and Surfaces of dialysis manage an increased probability of disease transmission. ment devices such as, for example, a dialysis line; compo 0185. For example, in bathroom, locker room and waiting nents and Surfaces of urinary management devices such as, room surfaces, it can be disposed on the Surfaces of toilets, for example, a urinary catheter, components and Surfaces of sinks, hand washing areas, hand drying areas, mirrors, doors, US 2010/0226943 A1 Sep. 9, 2010 27 door handles, door locks, push plates located on door Sur 0193 The pattern can also be disposed on surfaces used in faces, Supporting rails in the bathrooms, Surfaces of Sources the transportation of food-stuffs such as plastics, textiles, of illumination (e.g., the overhead lighting in a dentists textile nets, serrated plastics, and the like. The pattern can also office), and the like. The pattern can also be used as a filter for be disposed on food packaging, packaging for fruits and filtering particles in the nanometer and micrometerranges. In Vegetables (e.g., carrots, tomatoes, potatoes, corn, apples, one embodiment, the pattern can be used for filtering hydro grapes, mangoes, cauliflower, oranges, peaches, tangerines, carbons and polymers. nectarines, lettuce, cabbage, eggplant, okra, onions, nuts, 0186 The pattern can also be disposed on all surfaces of an dates, figs, lemons, lime, grapefruit, walnuts, cashew, pecans, ambulance. For example, it can be disposed on all work and the like). Surfaces that are contacted by the health care provider (e.g., 0194 The pattern can also be disposed on surfaces used in emergency medical technicians, doctors, nurses, laboratory water filtration used in fresh and saline water treatment facili technicians) or by the patient. In another embodiment, the ties. For example, it can be used on the inner and outer pattern can also be disposed on all Surface of Class I medical Surfaces of pipes and hoses used to transfer water or other devices Such as, for example, thermometer tips, pens and fluids, filters, nozzles, valves, heaters, granular particles, and other stationary, doctor/nurse gowns and clothing used by the like. health care providers. 0.195. It can also be used in devices that are used to trans 0187. In one embodiment, the pattern can be disposed on form fluids from a first state to a second state. For example, it the Surface of ploughs that are used to collect and shovel Snow can be used on Surfaces of devices that are used to transform (e.g., Snow ploughs). The Snow plough can be rendered self liquids to gases, gases to solids, Solids to liquids and gases to cleaning. Ice that normally adheres to the Snowplough will be liquids. It can also be used on the Surfaces of devices that easily removed, providing for a clean ploughed surface. contact flowing fluids. It can be used on the Surfaces of ice 0188 The pattern can also be disposed upon viewing sur makers, vaporizers, humidifiers, air conditioners, fans, pro faces Such as window panes, wind shields, eyeglasses, and pellers, airfoils (e.g., the leading edge and trailing edges of the like. Since the features of the pattern can be smaller than airplane wings), wind tunnels, exterior body panels of auto the wavelength of visible light, the viewing surface will not mobiles, ships, airplanes, Solar panels, wind turbines, turbine scatter light. In addition, the presence of the texture will blades, siding (e.g., metallic siding Such as aluminum, Steel, render the Surface self cleaning. wooden siding and plastic siding) used on the exterior and 0189 In one embodiment, the pattern can be disposed on interior Surfaces of buildings, ducts that transport air inside the surfaces of laboratory culture dishes where the attachment buildings, and the like. The pattern can be used on packaging of organisms to any surface inside the dish is not desired (e.g., for thermal insulation used in the interior of structures (e.g., the pattern causes lesser attachment rate than would other buildings, airplanes, ships, and the like), construction Sur wise be the case). In another embodiment, the pattern can be faces (e.g., the Surface of woodenbeams, metal beams, plastic disposed on a laboratory culture dish where the attachment of beams, bricks, dry wall, and the like), and the like, to prevent an organism to any surface inside the dish is desired (e.g., the the buildup of spores and mold when Such surfaces contact pattern causes greater attachment rate than would otherwise moisture over extended periods of time. be the case). 0196. The pattern can also be used on the internal and 0190. In one embodiment, the pattern can be disposed on external surfaces of electronic devices used for entertain a Surface of devices that can be used to carry or to transport ment; communications; signal transmission; capturing medical equipment or medical components (e.g., a contact images; capturing and transmitting auditory signals; and the lens carrying case, packaging for catheters, packaging for like. Examples of entertainment devices are solid-state musi guidewires, packaging for needles, packaging for Syringes, cal devices (e.g., iPODS(R), Solid-state gaming devices and and the like). electronic toys (e.g., NINTENDO DSR, LEAPSTER(R), and 0191 In another embodiment, the pattern can be disposed the like. Examples of communication devices are cellphones on Surfaces that are contacted by living beings both inside and (e.g., Motorola i870, iPhone, and the like), personnel digital outside of hospital or health care facilities. The surfaces can assistant (PDA) phones (e.g., Blackberry), laptops, iBooks, be metallic or non-metallic. For example, it can be disposed and the like. Examples of image capturing devices are optical on the Surfaces of bathroom fixtures such as toilet seats, lenses, digital cameras, infrared cameras, infrared scopes, shower tiles, towel racks, shower curtains, and the like. It can night vision goggles, and the like. Examples of devices for also be disposed on the Surfaces of kitchens and dining halls capturing auditory signals are bluetooth headsets, earphones, (e.g., kitchens in restaurants, homes, hospitals, and the like) and the like. and instruments used in kitchens such as, for example, coun 0197) The pattern can also be disposed on surfaces that tertops, sinks, refrigerator Surfaces, microwave Surfaces, contact the mucous membranes of living beings. For oven Surfaces, stove top surfaces, food trays (e.g., those used example, it can be used on all Surfaces that are contacted by in airlines, ships and on buses), the Surfaces of knives, forks, the human mouth especially those Surfaces that contact the spoons, ventilators, and the like. mouths of toddlers. Examples of surfaces that are contacted 0.192 The pattern can also be disposed on instruments by the mouths of toddlers are high chair trays, pacifiers, and/or surfaces used in an office, gymnasium or laboratory diaper changing pads, crib frames and rails, reusable and environment such as, for example, work table Surfaces (e.g., disposable water bottles, cups and mugs, coffee thermos, metallic or non-metallic), chair surfaces, handles of chairs, toys, blocks, coins, and the like. computer Surfaces, keyboards, Surfaces of a mouse, Surfaces 0198 The pattern can also be disposed on the surface of a of memory Sticks, clean room Surfaces, exercise equipment variety of miscellaneous items such as, for example, clothing Surfaces, Surfaces of public buses and trains (e.g., grab rails or and accessories, Sunglass lenses, frames of Sunglasses, eye other Surfaces such as push bars on doors that are contacted by glass lenses, Surfaces and frames of aquariums, outdoor living beings), and the like. clothing, water resistantjackets, coats, sports clothing, Swim US 2010/0226943 A1 Sep. 9, 2010 28

Suits, wetsuits, Surfboards, outdoor equipment, tents, lan device Surfaces, magnetic resonance imaging (MRI) Sur terns, lamps, tickets (e.g., to sporting events, airline tickets, faces, echo cardiogram Surfaces, cat-scan Surfaces, scales, train and ship tickets), shirt and dress collars, textile Surfaces clipboards, and the like. that contact armpits and other private parts of the body, and 0203 The pattern can be disposed on hospital surfaces. the like. Such surfaces can be marketed as being antimicro For example, it can be used as a film to be applied to Surfaces bial surfaces. that can be readily replaced between Surgeries. For example, it can be applied to such surfaces as listed below using elec 0199 The pattern can also be disposed on the surfaces of trostatic adhesion, mechanical interlocking or adhesives. The camping equipment (e.g., tents, poles, lamps, and the like), film can be used on table tops, MRI/CAT scan surfaces, X-ray camping gear, sports equipment (e.g., parachutes, parachute Surfaces, scales, operating tables, door push panels, devices rigs, parachute bags, insides and outsides of shoes, insoles, or articles that are contacted by human beings Such as, for and the like), and the like. Such equipment can be marketed as example, light Switches, control panels, beds, incubators, water resistant equipment that deters microorganism aggre monitors, remote controls, call buttons, door push bars, gation. It can also be marketed as deterring the buildup of preparation Surfaces, instrument trays, pharmacy Surfaces, odor in shoes and underwear. pathology tables, outside Surfaces of bed pans, identification 0200. The pattern can also be disposed on the surfaces of Surfaces on walls, clothing/protective personal wear, gloves, marine vessels and other devices that contact water. For cling films to attach temporary in public rest rooms/areas, example, it can be used on boat hulls, intake and outlet pipes baby changing cling films, films for attaching to bottoms of for industrial and power plants, drilling rig for underwater purses/bags/Suitcases, biomedical packaging, Such as the out Surfaces, fish tanks and aquariums, boat Surfaces (above the side Surface of Sterilized packaging; vacuum formed trayS/ hull), bilge tanks, water treatment plants and pumping station films, cling films for short and long term use, clean room Surfaces—any surface inside such a water treatment plant and Surfaces, such as, for example, those used for the semicon pumping station where organism growth and colonization is ductor or biomedical industry, table tops, push bars, door an issue. The pattern can be disposed on the Surfaces of bags panels, control panels, instruments, entrance/exit points, food used to grow algae, for example, it can be used on the Surface industry, including for packaging, food preparation Surfaces, of a bag used to grow any microorganism but prevent attach counter tops, cutting boards, trays, entrance/exit points, ment of the microorganism onto the Surface of bag (medical Switches, control panels, Scales, packaging equipment opera or marine—e.g., blood bags where it is desirable to deter tor contact points, marine industry, exterior Surfaces of organism attachment to bag). Alternatively, by varying the marine vessels including ships, bilge tanks, gray water tanks, surface texture or the size of the texture dimensions, it can be water inlet/outlet pipes, power drive systems, propellers, jet used on the Surface of a bag used to grow any microorganism ports, water treatment plants including pumping stations, and encourage attachment of the microorganism to Surface of inlet/outlet pipes, control panel Surfaces, laboratory Surfaces, the bag (e.g., a stem cell culture where it is desirable to power plants, inlet/outlet pipes, control Surfaces, airline encourage growth and attachment to Surface). industry, trays on seatbacks, entry/exit push Surfaces, bath 0201 The pattern can also be disposed on a variety of room doors, service carts, arm rests, furniture industry, chil other items: bags, handbags, garbage bags, bags that are used dren's cribs, handles on exercise equipment, exercise equip for carrying tissue, fluids from living beings, waste and other ment contact Surfaces, changing tables, high chairs, table byproducts from living beings, and the like. Examples of tops, food prep surfaces, transportation industry, ambulances, tissue, fluids, waste from living beings are urine, blood, buses, public transit, Swimming pools. saline, glucose, feces, fluids from the mucous membranes, and the like. EXAMPLES 0202 The pattern can also be used on the surfaces of body 0204. It should be understood that the Examples described parts that are used in Surgeries such as, for example, in a below are provided for illustrative purposes only and do not in colostomy, and the like. It can also be used in replacement any way define the scope of the invention. joints, plates, tendon and ligament ends for enhanced tissue 0205 An experiment was performed to compare the per adaptation, vascular implants, grafts, shunts, access, and the formance of an exemplary Surface architecture according to like. The pattern may also be used on the inner and outer the invention having features formed from a PDMS elastomer Surfaces of periodontal dressings; intravenous catheters and as compared to a planar uncoated control Surface (the same ports; foley catheters; Surfaces in contact with tissues such as, PDMS elastomer) against bioadhesion of algae spores. The for example, plates; adhesive tapes, patches, bandages, and inventive surface topography was the Sharklet shown in FIG. the like; electronic leads; dental implants; orthodontia 1(a). Following 45 minutes of exposure, as shown in FIG. devices; iols (intraocular lenses); hydrogel films for tissue 8(a), the settlement density of algae spores on the Smooth enhancement, skin grafting, isolation of bacteria from tissues; control sample was about 720/mm, while the settlement heart-lung machine Surfaces to reduce infection, clotting/ density for the Surface architecture according to the invention thrombosis, enhance flow; tissue constructs for organ/tissue was only about 100/mm, or only about 15% of the settlement genesis; dialysis machine components, tubing and control density of the control. FIG. 8(b) is a scanned light micrograph panels; cochlearfotolaryngology implants and electronic image of the surface of the control, while FIG. 8(c) is a devices; pace maker leads and body; fibrillator leads and scanned light micrograph image of the Surface of the Surface body; heart valve flow surfaces and fixation surfaces; spinal architecture according to the invention. implants; cranial/facial implants; biomedical instruments 0206. A further set of Ulva spore settlement assays were Such as, for example, heart valves; Scalpels; tongs; forceps; conducted to evaluate the impact of ERI. All pattern designs saws; reamers; grippers; spreaders; pliers; hammers; drills; tested were transferred to photoresist-coated silicon wafers laryngoscopes; bronchoscopes; oesophagoscopes; stetho using previously described photolithographic techniques. Scopes, mirrors, oral/ear speculum, Xray plates/frames, X-ray Patterned silicon wafers were reactive etched, utilizing US 2010/0226943 A1 Sep. 9, 2010 29 the Bosch process, to a depth of approximately 3 um creating topographical areas. Ten ml of spore Suspension (adjusted to a topographical negative. Wafers were then stripped of pho 2x10 spores per ml) were added to each dish and placed in toresist and cleaned with an O. plasma etch. Hexamethyld darkness for 60 minutes. The slides were then rinsed and fixed isilaZane was vapor deposited on the processed silicon wafers with 2% glutaraldehyde in artificial seawater as described in to methylate the surfaces in order to prevent adhesion. Callow et al. (1997). 0207 Topographical surfaces were transferred to PDMSe 0215 Spore counts were quantified using a Zeiss epifluo from replication of the patterned silicon wafers. The resultant rescence microscope attached to a Zeiss Kontron 3000 image topographies contain features projecting from the Surface at a analysis system (Callow et al. 2002). Thirty images and height of approximately 3 um. Pattern fidelity was evaluated counts were obtained from each of three replicates at 1 mm with light and scanning electron microscopy. intervals along both the vertical (15) and horizontal (15) axes 0208 Ulva spore settlement assays were conducted with of the slide. 76 mmx25 mm glass microscope slides coated with Smooth 0216 Spore density was reported as the mean number of and topographically modified PDMSe surfaces. Glass slides settled spores per mm from 30 counts on each of three rep coated with PDMSe topographies were fabricated using a licate slides itstandard error (n=3). Statistical differences two-step curing process as previously described (Carman et between Surfaces were evaluated using a nested analysis of al. 2006). The resultant slide (~ 1 mm thickness) contained an variance (ANOVA) followed the SNK (Student-Newman adhered PDMSe film with a 25mmx25mm area containing Kuels) test for multiple comparisons. Replicate slides (3) of topography bordered on both sides by 25mmx25mm smooth each surface (5) were treated as a nested variable within each (no topography) areas. Surface. 0209 Three replicates of each topographically-modified 0217. The mean spore density measured for each of the PDMSesample, permanently adhered to glass microscope studied PDMSe surfaces was plotted against the calculated slides, were evaluated for settlement of Ulva spores. Topog engineered roughness index (ERI) to determine if any corre raphies included the Sharklet (inset A: upper left), 2 um lations existed. It must be noted that these ERI values are for diameter circular pillars (inset C: lower left), 2 um wide a fixed feature spacing of 2 um and depth of 3 Lum. ridges (inset D; lower right), and a multi-feature topography 0218 Spores were calculated to settle at a mean density of containing 10 um equilateral triangles and 2 um diameter 671-66 spores/mm on the smooth PDMSe surface. All circular pillars (inset B; upper right). A uniformly smooth topographies showed a statistically significant reduction in PDMSesample was included in the assay and served as a spore density relative to this smooth surface as evaluated by control for direct comparison. ANOVA analysis followed by the SNK multiple comparison 0210 Regarding the Sharklet, 2 um ribs of various lengths test. A lower mean spore density was measured on the tri were combined centered and in parallel at a feature spacing of angles/pillars (279-66) compared to both the pillars 2 um. The features were aligned in the following order as (430+81) and ridges (460-54). The Sharklet topography had indicated by feature length (Lm): 4, 8, 12, 16, 12, 8, and 4. the lowest spore density (152+32) compared to all other sur This combination of features formed a diamond and was the faces. repeat unit for the arrayed pattern. The spacing between each 0219 For the 2um wide ridges, the majority of the settled diamond unit was 2 um. Similar to that of the skin of a shark spores were bridged between the top edges of neighboring in terms of feature arrangement, this pattern was designed ridges. A few smaller spores were found Squeezed within the Such that no single feature is neighbored by a feature similar 2 um wide channels between ridges. to itself. 0220 Spores remained atop the hexagonal packed 2 um 0211 Regarding the 2 um diameter circular pillars shown diameter pillars. No settled spores were observed on flat areas in inset C, patterns of 2 um pillars and 2 um ridges were between pillars. For the multi-feature topography containing designed at an analogous feature spacing of 2 um. The pillars both 10 um triangles and 2 um pillars, spores completely were hexagonally packed so that the distance between any avoided settling on the flat top surface of the triangle. Most two pillars was 2 um. Regarding the 2um wide ridges shown spores appeared to have settled on top of a pillar while leaning in inset D, the ridges were continuous in length and spaced by against the edge of the triangle feature. The table below 2 um channels (D). provides the calculated ERI values for the studied topographi 0212 Regarding the multi-feature pattern shown in inset cal patterns. B, the pattern was designed by combining 10um triangles and 2 um pillars. Pillars were arranged in the same hexagonal TABLE packing order as in the uniform structure. At periodic inter vals, a 10 um equilateral triangle replaced a set of six 2 um Feature Geometry Engineered Roughness Index pillars forming the outline of a 10 um triangle. Thus, this depth spacing width ERI design maintained a 2 um feature spacing between each edge (Lm) r df f (r'df)/f of the triangle and pillars. Ridges 3 2 2 2.5 1 OSO 5 0213 Fertile plants of Ulva linza were collected from Pillars 3 2 2 2.36 2 0.77 6.1 Wembury beach, UK (latitude 50°18' N; 4°02'W). Ulva Triangles 3 2 2, 10 2.23 2 O.S1 8.7 Zoospores were released and prepared for attachment experi Pillars ments as documented previously (Callow et al. 1997). Sharklet 3 2 2 2.5 2 O.S3 9.5 0214 Topographical samples were pre-soaked in nan Smooth na na na 1 2 1 2 opure water for several days prior to the assay in order for the surfaces to fully wet. Samples were transferred to artificial 0221 Calculated engineered roughness index (ERI) val seawater (TROPIC MARINR) for 1 hour prior to experimen ues for the studied topographical Surfaces. tation without exposure to air. Samples were then rapidly 0222. The mean spore density measured on each tested transferred to assay dishes to minimize any dewetting of the PDMSe surface was plotted against the calculated engineered US 2010/0226943 A1 Sep. 9, 2010 30 roughness index (ERI) as shown in FIG. 9. A correlation was tocol. The results collected at 24 and 48 hrs from the initial observed and a linear regression model was fit to the data. A assay are referred to in the following sections as “assay 1. fairly strong (R2=0.69, p<0.001) inverse linear relationship 0228. In assay 1, settlement on all surfaces was negligible existed between meanspore density and ERI by the following after 24 hrs, but the 48 hr results shown in FIG.11(a) appear equation: to indicate that all of the studied topographies reduce barnacle Spore Density(spores/mm)=796–63.5*(ERI) (2) cyprid settlement. The 40SK topography completely inhib ited barnacle settlement. However, because the overall settle 0223) The Sharklet had highest ERI (9.5) and lowest mean ment counts were quite low (-10% on glass), accurate statis spore density. Following the trend, the triangles/pillars topog tical interpretation of the data was not possible. raphy had the second highest ERI (8.7) and the second lowest 0229. Due to low overall cyprid settlement in assay 1, the mean spore density. Both the uniform ridges and pillars decision was made to "clean' the test surfaces and repeat the topographies had lower ERI values (5.0 and 6.1 respectively) process. Briefly, Surfaces were rinsed in an excess of nan and higher mean spore densities than both the Sharklet and opure water, gently agitated in 90% ethanol on an orbital triangles/pillars. There were no statistical differences in the shaker over night, and Subsequently rinsed in nanopure water mean spore densities of uniform ridges and pillars topogra and allowed to dry in air. On all PDMSe surfaces there was phies. still a vague droplet outline evident following this procedure. 0224 Since feature width and spacing were the same for Closer inspection Suggested that this deposit may be bacterial all these topographies, differences in ERI values were asso biofilm. Assay 2 droplets were deposited on areas of the ciated only with differences in feature geometry and tortuos samples not previously used for assay. The results of this ity. This indicated that the geometric shape and arrangement second round of testing will be referred to as “assay 2' in of the individual features of Sharklet was likely critical which readings were taken after 24 and 72 hrs. Cyprids were because it enhanced anti-settlement effectiveness over topog allowed to explore for longerinassay 2 to increase settlement, raphies of equivalent dimensions. but the 48 hr reading was removed to prevent the potential loss 0225. Not all topographically modified or roughened sur of test droplets during transfer to and from the incubator. faces have anti-settlement properties for Ulva spores. Spore After the 24hr reading, salinity in most of the test droplets had settlement results on topographies presented here and previ increased through evaporation from ~33 ppt to ~40 ppt So ously have indicated that a critical interaction must be reverse osmosis (RO) water was added to each droplet to achieved between individual topographical features and the return the salinity back to ~33 ppt. For assay 2, significant spore for the entire surface to be an effective inhibitory sur results were found between glass and all PDMSe surfaces as face. Although trends with ERI values and spore settlement shown in have been ascertained, it was only after topographic Surfaces 0230 FIG. 11(b) shows barnacle settlement after both 24 were designed at a feature spacing of 2Lum. This indicated that and 72 hrs. The 20SK topography completely inhibited bar there exists an interaction between roughness measures and nacle settlement. However, there were still no significant feature spacing that must be considered when designing topo differences detected between the smooth PDMSecontrol and graphic Surfaces. the textured inventive surfaces. A repeat experiment with a 0226. In another round of testing, sharklet surfaces fresh cyprid batch and new test Surfaces was sought so that a according to the invention were prepared and tested for effi definitive conclusion could be reached. cacy against barnacle adhesion. In the study, a Surface com 0231. After the completion of assay 2, fresh samples were prising 20 Lumx5um, 20 Lumx20 um, 200 umx5 um and 200 used to replicate the study. Using the same protocolas before, umx20 um PDMSe channels were evaluated for B. amphitrite settlement was evaluated at 24 and 48 hrs for this study (assay (barnacle) settlement and release. The convention used herein 3). All topographies yielded significantly lower settlement is WXD, where W represents both the width and spacing compared to smooth after 24hrs as shown in FIG.11(c). After between features and D represents the depth (height) of fea 48 hrs, the 20OH and 40SK topographies both showed a tures. Although equal in this particular example, the invention significant inhibitory affect on settlement. The 40SK topog is in no way limited to the width equaling the spacing. Incu raphy almost completely inhibited settlement of the cyprids, bation time was approximately 48 hours. All four topogra which is consistent with assay 1 results. No significant dif phies reduced settlement relative to a surface of smooth ferences were detected between the various topographies PDMSe. The most significant reduction in barnacle settle according to the invention. ment of about 65% was provided by the 20x20 channels as 0232. Additional tests were performed to evaluate critical shown in FIG. 10. surface dimensions for bacteria. Recent literature on the rela 0227 Based on the results of this study, surfaces were tionship between Zoospores and bacteria cells suggest that designed to probe the antifouling properties of topographical Zoospores of eukaryote alga can sense a chemical signal features with ~20 um dimensions. Four replicates each of the produced by bacteria by utilizing a bacterial sensory system. following PDMSe topographies were prepared: smooth, As such, bacterial biofilms have a direct influence on the 20x20 Channels (20CH), 20x40 Channels (40CH), 20x20 development of algal communities. Work by the present Sharklet (20SK) and 20x40 Sharklet (40SK). Four 0.5 cm Inventors with barnacle cyprids as discussed above has also drops of artificial sea water (ASW) were deposited on each shown the presence of something resembling a bacterial bio sample and then 10 cyprids dispersed in -0.5 cm ASW were film that was found to remain after washing. These findings added to each drop, bringing the total Volume per drop to 1 Suggest that disrupting the bacterial colonization of Surfaces cm. Samples were next placed in a humidified incubator at can in turn disrupt the settlement of larger organisms such as 28° C. for 24 hrs. Samples were inspected and settlement Zoospores or cyprids. numbers (cyprids attached-cyprids metamorphosed) were 0233. In the investigation with the bacteria Staphylococ counted. Samples were then returned to the incubator and cus aureus, Sharklet topography with 2 um spacing dimen read after Subsequent 24 hr periods following the same pro sions was chosen to accommodate isolated, individual bacte US 2010/0226943 A1 Sep. 9, 2010

rium (cell size ~1-2 um) to prohibit connectivity between 16. The article of claim 1, wherein the features are periodic. bacteria cells thus prohibiting the formation of a confluent 17. The article of claim 1, wherein the features are aperi biofilm. Samples of 2 um Sharklet PDMSe, smooth PDMSe, odic. and glass were statically exposed to 107 CFU/mL in growth 18. The article of claim 1, wherein the features have a depth medium for up to 12 days to promote biofilm formation. to height ratio of about 1 to about 10 micrometers. Samples were removed on the 2nd, 4th, 7th, and 12th days, 19. The article of claim 1, wherein the features have an gently rinsed by immersion in de-ionized water, and air-dried average surface roughness of about 4 to about 50. for characterization. 20. The article of claim 6, wherein the organic polymer is 0234. After 12 days, scanning electron micrographs a polyacetal, a polyolefin, a polyacrylic, a polycarbonate, a (SEM) revealed abundant biofilm on glass and slightly less on polystyrene, a polyester, a polyamide, a polyamideimide, a the smooth PDMSe, but no evidence of biofilm on the Shar polyarylate, a polyarylsulfone, a polyetherSulfone, a klet Surface. The SEM images acquired also Suggest inhibi polyphenylene Sulfide, a polyvinyl chloride, a polysulfone, a tion of bacterial cell settlement on the Sharklet surface. polyimide, a polyetherimide, a polytetrafluoroethylene, a 0235. It is to be understood that while the invention has polyetherketone, a polyether etherketone, a polyether ketone been described in conjunction with the preferred specific ketone, a polybenzoxazole, a polyphthalide, a polyacetal, a embodiments thereof, that the foregoing description as well polyanhydride, a polyvinyl ether, a polyvinyl thioether, a as the examples, which follow are intended to illustrate and polyvinyl alcohol, a polyvinyl ketone, a polyvinyl halide, a not limit the scope of the invention. Other aspects, advantages polyvinyl nitrile, a polyvinyl ester, a polysulfonate, a polysul and modifications within the scope of the invention will be fide, a polythioester, a polysulfone, a polysulfonamide, a apparent to those skilled in the art to which the invention polyurea, a polyphosphaZene, a polysilaZane, a polyurethane, pertains. an ethylene propylene diene rubber, a polytetrafluoroethyl 1. An article comprising: ene, a perfluoroelastomer, a fluorinated ethylene propylene, a a first plurality of spaced features; the spaced features perfluoroalkoxyethylene, a polychlorotrifluoroethylene, a arranged in a plurality of groupings; the groupings of polyvinylidene fluoride, a polysiloxane, combination com features comprising repeat units; the spaced features prising at least one of the foregoing organic polymers. within a grouping being spaced apart at an average dis 21. The article of claim 1, wherein the spaced features tance of about 1 nanometer to about 500 micrometers; comprise an inorganic material, and wherein the inorganic each feature having a surface that is substantially paral material is an inorganic oxide, an inorganic carbides, an inor lel to a surface on a neighboring feature; each feature ganic nitride, an inorganic hydroxide, an inorganic oxide being separated from its neighboring feature; the group having a hydroxide coating, an inorganic carbonitride, an ings of features being arranged with respect to one inorganic oxynitride, an inorganic boride, an inorganic boro another so as to define a tortuous pathway; the plurality carbide, or a combination comprising at least one of the of spaced features providing the article with an engi foregoing inorganic materials or wherein the inorganic mate neered roughness index of about 5 to about 30. rial is a metal oxide, a metal carbide, a metal nitride, a metal 2. The article of claim 1, wherein the plurality of spaced hydroxide, a metal oxide having a hydroxide coating, a metal feature extend outwardly from a surface. carbonitride, a metal oxynitride, a metal boride, a metal boro 3. The article of claim 2, wherein the plurality of spaced carbide, or a combination comprising at least one of the features has a similar chemical composition to the Surface. foregoing inorganic materials. 4. The article of claim 2, wherein the plurality of spaced 22. The article of claim 1, wherein the spaced features features has a different chemical composition from that of the comprise a metal, the metal being iron, copper, aluminum, tin, Surface. gold, titanium, silver, tungsten, platinum, palladium, chro 5. The article of claim 2, wherein the plurality of spaced mium, or a combination comprising at least one of the fore features is applied to the Surface in the form of a coating. going metals. 6. The article of claim 1, wherein the plurality of spaced 23. The article of claim 1, wherein the article has an engi features comprises an organic polymer, a ceramic or a metal. neered roughness index of greater than or equal to about 5. 7. The article of claim 1, wherein the groupings of features 24. The article of claim 1, where the article has an engi are arranged with respect to one another so as to define a neered roughness index of greater than or equal to about 10. linear pathway or a plurality of channels. 25. The article of claim 1, where the article has a drug 8. The article of claim 1, wherein the tortuous pathway is coating disposed thereon. defined by a sinusoidal curve. 26. The article of claim 1, where the article comprises 9. The article of claim 1, wherein the tortuous pathway is biologically active agents. defined by a spline function. 27. The article of claim 1, where the article comprises a 10. The article of claim 1, wherein one or more features are bio-degradable polymer. shared between groupings. 28. The article of claim 26, where the biologically active 11. The article of claim 1, wherein the groupings have agents comprise anti-proliferative/antimitotic agents, Vinca patterns of features. alkaloids, vinblastine, Vincristine, Vinorelbine, paclitaxel, 12. The article of claim 1, wherein the features have similar epidipodophyllotoxins, etoposide, teniposide, antibiotics, geometries. doxycycline, dactinomycin, actinomycin D, daunorubicin, 13. The article of claim 1, wherein the features have dif doxorubicin and idarubicin, anthracyclines, mitoxantrone, ferent geometries. , plicamycin, mithramycin, mitomycin, enzymes, 14. The article of claim 1, wherein the features have dif L-asparaginase, antiplatelet agents, G(GP) IIb/IIIa inhibitors, ferent dimensions. vitronectin receptor antagonists, anti-proliferative/antimi 15. The article of claim 1, wherein the groupings show totic alkylating agents, nitrogen mustards, mechlorethamine, dilational symmetry. cyclophosphamide and analogs, melphalan, chlorambucil, US 2010/0226943 A1 Sep. 9, 2010 32 ethylenimines, methylmelamines, hexamethylmelamine, a waiting room; on a Surface of an electrostatic film applied to thiotepa, alkyl Sulfonates-buSulfan, nitrosoureas, carmustine operating room Surfaces between Surgeries; on a Surface of and analogs, streptozocin, traZenes-dacarbazinine, anti-pro Surgical drapes used to cover patients and/or shield a doctor liferative/antimitotic , folic acid analogs, from fluids; on a surface of waiting room chairs and waiting methotrexate, pyrimidine analogs, fluorouracil, floXuridine, room furniture; on a Surfaces of operating room instruments; cytarabine, purine analogs, mercaptopurine, thioguanine, on a surface of operating room instrument trays; on a high pentostatin, 2-chlorodeoxyadenosine, platinum coordination complexes, cisplatin, carboplatin, procarbazine, hydrox tough Surface in hospital rooms; on bedside table Surfaces; on yurea, mitotane, aminoglutethimide, hormones, estrogen, a bedrail Switch panel Surfaces; on a Surface of control panels; anti-coagulants, heparin, synthetic heparin salts, inhibitors of on cover Surfaces; on a bed sheet Surface; on bathroom, locker thrombin, fibrinolytic agents, tissue plasminogen activator, room and/or waiting room surfaces; on outer and/or inner streptokinase, urokinase, aspirin, dipyridamole, ticlopidine, Surfaces of an electronic device; on Surfaces of toilets, sinks, clopidogrel, abciximab, antimigratory agents, antisecretory hand washing areas, hand drying areas, mirrors, doors, door agents, breveldin, anti-inflammatory agents, adrenocortical handles, door locks, push plates located on door Surfaces: steroids, Cortisol, cortisone, fludrocortisone, prednisone, Supporting rails in the bathrooms; Surfaces of bathroom fix prednisolone, 6C.-methylprednisolone, triamcinolone, tures; Surfaces of shower tiles; Surfaces of towel racks; Sur betamethasone, dexamethasone, non-steroidal agents, Sali faces of shower curtains; Surfaces of sources of illumination; cylic acid derivatives, aspirin, para-aminophenol derivatives, a work Surface on all Surfaces that are contacted by a health acetominophen, indole, indene acetic acids, indomethacin, care provider and/or a patient; on all Surface of Class I medi Sulindac, etodalac, heteroaryl acetic acids, tolmetin, cal devices, thermometer tips, pens, stationary, doctor and/or diclofenac, ketorolac, arylpropionic acids, ibuprofen and nurse gowns, and/or clothing used by health care providers; derivatives, anthranilic acids, mefenamic acid, meclofenamic on a surface of laboratory culture dishes where attachment of acid, enolic acids, piroXicam, tenoxicam, phenylbutaZone, organisms to a surface inside the dish is not desired; on the oxyphenthatraZone, , gold compounds, aurano Surfaces of kitchens and dining halls; Surfaces of countertops; fin, aurothioglucose, gold sodium thiomalate, immunosup Surfaces of sinks; refrigerator Surfaces; microwave Surfaces: pressives, cyclosporine, tacrolimus, sirolimus, rapamycin, oven Surfaces; Stove top surfaces; Surfaces of food trays used azathioprine, mycophenolate mofetil, angiogenic agents, in airlines, ships and on buses; Surfaces of knives; Surfaces of vascular endothelial growth factor, fibroblast growth factor, forks; Surfaces of spoons; surfaces of ventilators; Surfaces of angiotensin receptor blockers, donors, anti-sense an office; surfaces of a gymnasium; Surfaces of a laboratory; oligionucleotides, cell cycle inhibitors, mTOR inhibitors, work table surfaces; chair surfaces; handles of chairs; com signal transduction kinase inhibitors, puter Surfaces; keyboard Surfaces; Surfaces of a mouse; Sur retenoids, cyclin/CDK inhibitors, statins, protease inhibitors, faces of memory sticks; clean room Surfaces; exercise equip or a combination comprising at least one of the foregoing ment Surfaces; Surfaces of public buses and trains; grab rail biologically active agents. Surfaces; push bar Surfaces; hand rail Surfaces; on a Surface of a device used for the transportation of food; an inner and/or 29. The article of claim 25, where the drug coating is a time outer surface of a device that is used to transfer fluids, water, release coating. saline water or granular particles; as packaging for thermal 30. The article of claim25, where the article is a biomedical insulation used in the interior of structures, buildings, air implant, a breast implant shell, a fluid filled implant shell; a planes and ships; as a construction Surface; on Surfaces to biomedical instrument; a biomedical device; a heart valve; a prevent the buildup of spores and mold on Surfaces that con hospital Surface; clothing/protective personal wear, biomedi tact water or moisture over extended periods of time; on cal packaging; an outside Surface of sterilized packaging; a internal and external surfaces of electronic devices used for clean room surface; a Surface of a semiconductor, food pack entertainment; communications; on Surfaces of signal trans aging; a food preparation Surface; an exterior Surface of a mission devices; on Surfaces of devices for capturing images; marine vessel; an interior Surface of a marine vessel; an exte on Surfaces for capturing and transmitting auditory signals; rior Surface of a ship; a bilge tank; an inlet or an outlet to a on internal and external Surfaces of electronic devices; the water pipe; an inner Surface of a pipe or hose; a surface in a electronic devices being solid-state musical devices, Solid water treatment plant; a part of a pumping station; a surface of state gaming devices and electronic toys, cellphones, person a power plant; a Surface of a child's crib, a Surface on handles nel digital assistant phones, laptops, digital cameras, infrared of exercise equipment; a Surface on an ambulance, a Surface cameras, infrared scopes, night vision goggles, an optical on a bus, a surface on a public transit vehicle; or a part of a lens, blue tooth headsets or earphones; as a Surface of a filter, Swimming pool. nozzle, valve, heater, aspirator, decanter, jar, cup, vaporizer, 31. The article of claim 1, where the article is affixed to a humidifier, air conditioner, fan, propeller, wind tunnel, exte Surface by an adhesive, by electrostatic forces, by mechanical rior body panel of automobile, ship, airplane, Solar panel, interlocking devices, or a combination comprising at least wind turbine, turbine blade, sidings for buildings, airfoil or one of an adhesive, electrostatic forces or mechanical inter siphons; on of Surfaces that are contacted by the mouths of locking devices. babies or toddlers; the Surfaces being high chair trays, paci 32. The article of claim 1, where the article is used as an fiers, diaper changing pads, crib frames and rails, reusable outer and/or an inner Surface of a device; an outer and/or an and disposable water bottles, cups and mugs, coffee thermos, inner Surface of an instrument; an outer and/or an inner Sur toys, blocks, coins or nipples; as Surfaces on clothing and face of furniture; a Surface on and/or in a hospital; a surface on accessories, Sunglass lenses, frames of Sunglasses, eyeglass and/or in a healthcare center, a Surface on and/or in a dental lenses, Surfaces and frames of aquariums, outdoor clothing, office; a Surface on and/or in a dispensary; a surface on and/or water resistantjackets, coats, sports clothing, Swimsuits, wet in a gymnasium; a surface on and/or in a rehabilitation facil Suits, Surfboards, outdoor equipment, tents, lanterns, lamps, ity; a Surface on and/or in a bathroom; a surface on and/or in tickets, shirt and dress collars, or textile Surfaces that contact US 2010/0226943 A1 Sep. 9, 2010

armpits and other private parts of the body; as Surfaces of 42. The article of claim 34, wherein the tortuous pathway is camping equipment, tents, poles, lamps, camping gear, sports defined by a periodic function. equipment, parachutes, parachute rigs, parachute bags, 43. The article of claim 34, wherein the groupings show insides and outsides of shoes or insoles; on Surfaces of marine dilational symmetry. vessels; on Surfaces of boat hulls; on intake and outlet pipes 44. The article of claim 34, wherein the features are peri for industrial and powerplants; on drilling rigs for underwater odic. Surfaces; on fish tanks and aquariums; on boat Surfaces above 45. The article of claim 34, wherein the article comprises the hull; on Surfaces of bilge tanks; water treatment plants or an organic polymer. pumping station Surfaces; on Surfaces of bags that are used to 46. The article of claim 34, wherein the article comprises grow algae; on the Surfaces of bags that are used to deter the an inorganic material. growth of algae; on Surfaces of a bag, a handbag, a garbage 47. The article of claim 34, wherein the article has an bag, or a bag that is used for carrying tissue, fluids from living engineered roughness index of greater than or equal to about beings, waste and other byproducts from living beings. 5. 33. The article of claim 1, where the article is used in 48. The article of claim 34, where the article comprises a replacement joints; plates; tendon and ligament ends for drug coating. enhanced tissue adaptation; vascular implants; grafts; shunts; 49. The article of claim 34, where the article comprises a inner and outer Surfaces of periodontal dressings; intravenous biologically active agent. catheters; ports for intravenous catheters; foley catheters; 50. The article of claim 34, where the article comprises a plates; adhesive tapes; patches; bandages; electrical leads: bio-degradable polymer. dental implants; orthodontia devices; intraocular lens; hydro 51. The article of claim 49, where the biologically active gel films for tissue enhancement; skin grafting, isolation of agent comprises anti-proliferative/antimitotic agents, Vinca bacteria from tissues; heart-lung machine Surfaces to reduce alkaloids, vinblastine, Vincristine, Vinorelbine, paclitaxel, infection; clotting/thrombosis; tissue constructs for organ/ epidipodophyllotoxins, etoposide, teniposide, antibiotics, tissue genesis; dialysis machine components; tubing and con doxycycline, dactinomycin, actinomycin D, daunorubicin, trol panels; cochlearfotolaryngology implants and electronic doxorubicin and idarubicin, anthracyclines, mitoxantrone, devices; pace maker leads and body; fibrillator leads and bleomycins, plicamycin, mithramycin, mitomycin, enzymes, body; heart valve flow surfaces and fixation surfaces; spinal L-asparaginase, antiplatelet agents, G(GP) IIb/IIIa inhibitors, implants; cranial/facial implants; biomedical instruments; vitronectin receptor antagonists, anti-proliferative/antimi heart valves; scalpels; tongs; forceps; saws; reamers; grip totic alkylating agents, nitrogen mustards, mechlorethamine, pers; spreaders; pliers; hammers; drills; laryngoscopes; bron cyclophosphamide and analogs, melphalan, chlorambucil, choscopes; oesophagoscopes; stethoscopes; mirrors; oral/ear ethylenimines, methylmelamines, hexamethylmelamine, speculum; X-ray plates/frames: Xray device surfaces; mag thiotepa, alkyl Sulfonates-buSulfan, nitrosoureas, carmustine netic resonance imaging Surfaces; echo cardiogram Surfaces: and analogs, streptozocin, traZenes-dacarbazinine, anti-pro cat-scan Surfaces; scales; or on clipboards. liferative/antimitotic antimetabolites, folic acid analogs, 34. An article comprising: methotrexate, pyrimidine analogs, fluorouracil, floXuridine, a plurality of spaced features; the features arranged in a cytarabine, purine analogs, mercaptopurine, thioguanine, plurality of groupings; the groupings of features com pentostatin, 2-chlorodeoxyadenosine, platinum coordination prising repeat units; the spaced features within a group complexes, cisplatin, carboplatin, procarbazine, hydrox ing being spaced apart at an average distance of about 1 yurea, mitotane, aminoglutethimide, hormones, estrogen, nanometer to about 500 micrometers; the groupings of anti-coagulants, heparin, synthetic heparin salts, inhibitors of features being arranged with respect to one another so as thrombin, fibrinolytic agents, tissue plasminogen activator, to define a tortuous pathway and whereina tangent to the streptokinase, urokinase, aspirin, dipyridamole, ticlopidine, tortuous pathway intersects with a spaced feature; the clopidogrel, abciximab, antimigratory agents, antisecretory spaced feature being different from at least one nearest agents, breveldin, anti-inflammatory agents, adrenocortical neighbor and not in contact with the nearest neighbor. steroids, Cortisol, cortisone, fludrocortisone, prednisone, 35. The article of claim 34, wherein a feature of the group prednisolone, 6C.-methylprednisolone, triamcinolone, ing is shared between a pair of neighboring groupings. betamethasone, dexamethasone, non-steroidal agents, Sali 36. The article of claim 35, wherein a frequency of inter cylic acid derivatives, aspirin, para-aminophenol derivatives, section between a tangent to the tortuous pathway and the acetominophen, indole, indene acetic acids, indomethacin, grouping is periodic. Sulindac, etodalac, heteroaryl acetic acids, tolmetin, 37. The article of claim 35, wherein a frequency of inter diclofenac, ketorolac, arylpropionic acids, ibuprofen and section between a tangent to the tortuous pathway and the derivatives, anthranilic acids, mefenamic acid, meclofenamic grouping is aperiodic. acid, enolic acids, piroXicam, tenoxicam, phenylbutaZone, oxyphenthatraZone, nabumetone, gold compounds, aurano 38. The article of claim 35, wherein a sum of a number of fin, aurothioglucose, gold sodium thiomalate, immunosup features in a grouping is equal to an odd number. pressives, cyclosporine, tacrolimus, sirolimus, rapamycin, 39. The article of claim 35, wherein a sum of a number of azathioprine, mycophenolate mofetil, angiogenic agents, features in a grouping is equal to an even number. vascular endothelial growth factor, fibroblast growth factor, 40. The article of claim 35, wherein a sum of a number of angiotensin receptor blockers, nitric oxide donors, anti-sense features shared by two neighboring groupings is equal to an oligionucleotides, cell cycle inhibitors, mTOR inhibitors, odd number. growth factor receptor signal transduction kinase inhibitors, 41. The article of claim 35, wherein a sum of a number of retenoids, cyclin/CDK inhibitors, statins, protease inhibitors, features shared by two neighboring groupings is equal to an or a combination comprising at least one of the foregoing even number. biologically active agents. US 2010/0226943 A1 Sep. 9, 2010 34

52. The article of claim 48, where the drug coating is a time a device used for the transportation of food; an inner and/or release coating. outer surface of a device that is used to transfer fluids, water, 53. The article of claim34, where the article is a biomedical saline water or granular particles; as packaging for thermal implant, a breast implant shell, a fluid filled implant shell; a insulation used in the interior of structures, buildings, air biomedical instrument; a biomedical device; a heart valve; a planes and ships; as a construction Surface; on Surfaces to hospital Surface; clothing/protective personal wear, biomedi prevent the buildup of spores and mold on Surfaces that con cal packaging: tact water or moisture over extended periods of time; on an outside Surface of sterilized packaging; a clean room internal and external surfaces of electronic devices used for Surface; a Surface of a semiconductor; food packaging; a entertainment; communications; on Surfaces of signal trans food preparation Surface; an exterior Surface of a marine mission devices; on Surfaces of devices for capturing images; vessel; an interior Surface of a marine vessel; an exterior on Surfaces for capturing and transmitting auditory signals; Surface of a ship; a bilge tank; an inlet or an outlet to a on internal and external Surfaces of electronic devices; the water pipe; an inner Surface of a pipe or hose; a Surface electronic devices being solid-state musical devices, Solid in a water treatment plant; a part of a pumping station; a state gaming devices and electronic toys, cellphones, person Surface of a power plant; a Surface of a child's crib, a nel digital assistant phones, laptops, digital cameras, infrared Surface on handles of exercise equipment; a surface on cameras, infrared scopes, night vision goggles, blue tooth an ambulance, a Surface on a bus, a Surface on a public headsets or earphones; as a surface of a filter, nozzle, valve, transit vehicle; or a part of a Swimming pool. heater, aspirator, decanter, jar, cup, Vaporizer, humidifier, air 54. The article of claim 34, where the article is affixed to a Surface by an adhesive, by electrostatic forces, by mechanical conditioner, fan, propeller, wind tunnel, exterior body panel interlocking devices, or a combination comprising at least of automobile, ship, airplane, Solar panel, wind turbine, tur one of an adhesive, electrostatic forces or mechanical inter bine blade, sidings for buildings, airfoil or siphons; on of locking devices. surfaces that are contacted by the mouths of babies or tod 55. The article of claim 34, where the article is used as an dlers; the Surfaces being high chair trays, pacifiers, diaper outer and/or an inner Surface of a device; an outer and/or an changing pads, crib frames and rails, reusable and disposable inner Surface of an instrument; an outer and/or an inner Sur water bottles, cups and mugs, coffee thermos, toys, blocks, face of furniture; a Surface on and/or in a hospital; a surface on coins or nipples; as Surfaces on clothing and accessories, and/or in a healthcare center, a Surface on and/or in a dental Sunglass lenses, frames of Sunglasses, eye glass lenses, Sur office; a surface on and/or in a dispensary; a surface on and/or faces and frames of aquariums, outdoor clothing, water resis in a gymnasium; a surface on and/or in a rehabilitation facil tantjackets, coats, sports clothing, Swimsuits, wetsuits, Surf ity; a Surface on and/or in a bathroom; a surface on and/or in boards, outdoor equipment, tents, lanterns, lamps, tickets, a waiting room; on a Surface of an electrostatic film applied to shirt and dress collars, or textile Surfaces that contact armpits operating room Surfaces between Surgeries; on a Surface of and other private parts of the body; as Surfaces of camping Surgical drapes used to cover patients and/or shield a doctor equipment, tents, poles, lamps, camping gear, sports equip from fluids; on a Surface of waiting room chairs and waiting ment, parachutes, parachute rigs, parachute bags, insides and room furniture; on a surfaces of operating room instruments; outsides of shoes or insoles; on Surfaces of marine vessels; on on a surface of operating room instrument trays; on a high surfaces of boat hulls; on intake and outlet pipes for industrial tough Surface in hospital rooms; on bedside table Surfaces; on and power plants; on drilling rigs for underwater Surfaces; on a bedrail Switch panel Surfaces; on a Surface of control panels; fish tanks and aquariums; on boat Surfaces above the hull; on on cover Surfaces; on a bed sheet Surface; on bathroom, locker Surfaces of bilge tanks; water treatment plants or pumping room and/or waiting room surfaces; on Outer and/or inner station Surfaces; on Surfaces of bags that are used to grow Surfaces of an electronic device; on Surfaces of toilets, sinks, algae; on the Surfaces of bags that are used to deter the growth hand washing areas, hand drying areas, mirrors, doors, door of algae, on Surfaces of a bag, a handbag, a garbage bag, or a handles, door locks, push plates located on door Surfaces: bag that is used for carrying tissue, fluids from living beings, Supporting rails in the bathrooms; Surfaces of bathroom fix waste and other byproducts from living beings. tures; Surfaces of shower tiles; Surfaces of towel racks; Sur 56. The article of claim 34, where the article is used in faces of shower curtains; surfaces of Sources of illumination; replacement joints; plates; tendon and ligament ends for a work Surface on all Surfaces that are contacted by a health enhanced tissue adaptation; vascular implants; grafts; shunts; care provider and/or a patient; on all Surface of Class I medi inner and outer Surfaces of periodontal dressings; intravenous cal devices, thermometer tips, pens, stationary, doctor and/or catheters; ports for intravenous catheters; foley catheters; nurse gowns, and/or clothing used by health care providers; plates; adhesive tapes; patches; bandages; electrical leads: on a surface of laboratory culture dishes where attachment of dental implants; orthodontia devices; iols (intraocular organisms to a surface inside the dish is not desired; on the lenses); hydrogel films for tissue enhancement; skin grafting: Surfaces of kitchens and dining halls; Surfaces of countertops; isolation of bacteria from tissues; heart-lung machine Sur Surfaces of sinks; refrigerator Surfaces; microwave Surfaces: faces to reduce infection; clotting/thrombosis; tissue con oven Surfaces; Stove top surfaces; Surfaces of food trays used structs for organ/tissue genesis; dialysis machine compo in airlines, ships and on buses; Surfaces of knives; Surfaces of nents; tubing and control panels; cochlearfotolaryngology forks; Surfaces of spoons; surfaces of ventilators; Surfaces of implants and electronic devices; pace maker leads and body; an office; surfaces of a gymnasium; Surfaces of a laboratory; fibrillator leads and body; heart valve flow surfaces and fixa work table surfaces; chair surfaces; handles of chairs; com tion Surfaces; spinal implants; cranial/facial implants; bio puter Surfaces; keyboard Surfaces; Surfaces of a mouse; Sur medical instruments; heart Valves; Scalpels; tongs; forceps; faces of memory sticks; clean room surfaces; exercise equip saws; reamers; grippers; spreaders; pliers; hammers; drills; ment Surfaces; Surfaces of public buses and trains; grab rail laryngoscopes; bronchoscopes; oesophagoscopes; stetho Surfaces; push bar Surfaces; hand rail Surfaces; on a Surface of Scopes; mirrors; oral/ear speculum; X-ray plates/frames: Xray US 2010/0226943 A1 Sep. 9, 2010

device Surfaces; magnetic resonance imaging Surfaces; echo elomotecan, elsamitrucin, emitefur, enloplatin, enocitabine, cardiogram Surfaces; cat-scan Surfaces; Scales; or clipboards. empromate, entecavir, entinostat, entricitabine, enZastaurin, 57. The article of claim 1, where the surfaces that are epirubicin, eptaloprost, eribulin, erlotinib, Esorubicin, estra Substantially parallel to the Surfaces of neighboring features mustine, etalocib, etanidazole, etoglucid, etoposide, exate are both vertical surfaces. can, exemestane, exisulind, fadrozole, faZarabine, fiacitab 58. The article of claim 1, wherein the article comprises a ine, fioxuridine, fiudarabine, fiuoxymesterone, thermoplastic polymer, a blend of thermoplastic polymers, a fluorocitabine, fiutamide, formestane, forodesine, fosfiuri thermosetting polymer, a blend of thermoplastic polymers dine tidoxil, fosquidone, fostriecin, fotemustine, fotretamine, with thermosetting polymers, a copolymer, a terpolymer, an fulvestrant, fumagillin, galarubicin, galocitabine, gefitinib, oligomer, a homopolymer, a block copolymer, an alternating gemcitabine, gemtuzumab ozogamicin, geroquinol, gigan block copolymer, a random copolymer, a random block tetronenin, gigantetroneninone, gimatecan, gimeracil, glox copolymer, a graft copolymer, a star block copolymer, a den aZone, glufosfamide, goniothalamicin, goniothalamicinone, drimer, a polyelectrolyte, a polyampholyte, an ionomer, or a goserelin, granisetron HCl, gusperimus, hexarelin, homohar combination thereof. ringtonine, hydrocamptothecine, hydroxy carbamide, 59. The article of claim 26, where the biologically active hydroxyurea, hypericin, ibandronate sodium, ibandronic agents comprise a cancer inhibitors. acid, idarubicin HCl, idronoxil, ifosfamide, ilmofosine, ima 60. The article of claim 59, where the cancer inhibitors are tinib, imatinib mesylate, imexon, improsulfan, incadronate, (-)-Ci-Cdp1, (-)-Ci-Cdp2, (-)-, (+)- indibulin, indisulam, inolitaZone, inproduone, intiquinatine, Cbi-Cdpi2, (+)-Ci-Cdp2, 10-Deacetylbaccatin Iii, intoplicine, iobenguane, irinotecan hydrochloride, irofulven, 4-demethoxy daunorubicin, 5-azacytidine/5-aza-2'-deoxycy irsogladine, ispinesib, ixabepilone, ketotrexate, L-alanosine, tidine, 5-fluorouracil, 5-iminodoxorubicin hydrochloride, laniquidar, lapatinib ditosylate, laromustine, larotaxel, ledox 6-mercaptopurine, aclarubicin, acodazole, actinomycin D, antrone, lenalidomide, lentinan, lestaurtinib, letrozole, leu adenine phosphate, adenosine, aderbasib, adoZelesin; U-73, prolide acetate, leuprorelin, lexacalcitol, liarozole, lobapl 975, afeletecan, alemtuzumab, alitreninoin, alosetron HCl, atin, lomustine, lonafarnib, lonidamine, losoxantrone, alphitolic acid, altretamine, alvespimycin, ambazone, amet Ly-83583, lysipressin, mafosfamide, mannomustine, manno antrone, amifostine, aminoglutethimide, amsacrine HCl, Sulfan, marimastat, marinomycin A, masitinib, maslinic acid, amsilarotene, amygdalin, anagrelide, anastroZole, anaxirone, masoprocol, mechlorethamine, medorubicin, megestrol, ancitabine, annomontacin, annomuricin A, (C19/C20 mepitioStane, mercaptopurine, mesna, methotrexate, methyl Erythro), annomuricin B, (C10/C11, C19/C20-erythro), aminolevulinate, metomidate, metoprine, meturedepa, mibo annomuricin C, annomuricin E, annonacin, annonacin-10 platin, midostaurin, mi?amurtide, milataxel, miproxifene, One, annonacin-A-One, annonidin B, annonin VI, annosqua miriplatin, misonidazole, mitindomide, mitoflaxone, mosin A, annosquamosin B, antramycin, apaziquone, mitoguaZone, mitomycin, mitonafide, mitoquidone, mito argimesna, aristoforin, arsenic trioxide, artemisinin, ascomy tane, mitoxantrone, mitozolomide, mivobulin, mizoribine, cin, asparaginase, atosiban, atrimustine, axitinib, aZasetron mofarotene, mopidamol, motesanib, motexafin, mubritinib, HCl, azatepa, azathioprine, azotomycin, bafetinib, balamapi muricapentocin, muricatacin, mustine HCl, mycophenolate mod, banoxantrone, batabulin, batimastat, Bbr-34384, mofetil, mycophenolic acid, medaplatin, nelZarabine, nemo becatecarin, belotecan, benaxibine, bendamustine, ben rubicin, neocuproine, neptamustine, neratinib, nigericin, Zodepa, berubicin, betulin, betulinic acid, betulinic aldehyde, nilotinib, nilutamide, nimustine, ninopterin, nitracrine, bevacizumab, beXarotene, bicalutamide, bietaserpine, birico nogalamycin, nolatrexed, norcantharidine, nor-dihydroguai dar, bisantrene, bistramid A. bistratene A, bizelesin, bleomy aretic acid, nortopixantrone, novembichin, obatoclax, oct cin, bleomycin A2, bleomycin A5, bleomycin Sulfate, bort reotide, olaparib, oleanolic aldehyde, omacetaxine mepesuc eZomib, bosentan, boSutinib, brequinar Sodium, brequinar, cinate, ombrabulin, omtripolide, ondansetron HCl, ortataxel, bropirimine, brostallicin, budotitane, bullatacin, buserelin, oteracil, oteracil potassium, oxaliplatin, OXisuran, oxophe buSulfan, cabazitaxel, calcium folinate, calcium levofolinate, narsine, paclitaxel ceribate, palifosfamide, palonosetron, calusterone, camptothecin, canertinib, canfosfamide, pamidronate disodium, pamidronic acid, panitumumab, cantharidin, capecitabine, caracemide, carbetimer, carbopl panobinostat, patubilone, paZelliptine, paZopanib, pegaspar atin, carboprost (carboprost tromethamine), carboquone, car gase, peldesine, pelitinib, pelitrexol, pemetrexed disodium, filzomib, carglumic acid, carmofur, carmustine, carZelesin, pentostatin, peplomycin, peretinoin, perfosfamide, perifos cedefingol, cemadotin, cetuximab, cevipabulin, chloram ine, pibroZelesin hydrobromide, picoplatin, pinafide, pipo bucil, chlormethine (mechlorethamine), chlorotamoxifen, Sulfan, pirarubicin, pirfenidone, piritrexim, piroXantrone, chlorotrianisene, cioteronel, cisplatin, cladribine, clanfenur, pixantrone, plevitrexed, plicamycin, plitidepsin, plomestane, clofarabine, clofazimine, clomifene citrate, cordycepin, coro podophyllotoxin, pomalidomide, porfimer Sodium, pralatrex Solic acid, crisinatol, curcumin, cyclocytidine, cyclophospha ate, prinomastat, procarbazine HCl, propamidine, pros mide, cytarabine, cytidine, D-, dacarba pidium chloride, pumitepa, puromycin, pyrazofurin, ouar Zine, damsin, daniquidone, danusertib, daporinad, floxin, raltegravir, raltitrexed, ramosetron HCl, ranimustine, darinaparsin, dasatinib, daunoblastin, daunorubicin/dauno retaspimycin, retelliptine, riboprine, ritrosulfan, rituximab, mycin, decitabine, deferasiroX, deforolimus, demecolcine, roflumilast, romidepsin, ropidoxuridine, roquinimex, rosabu denibulin, detorubicin, dexniguldipine, dexormaplatin, deza lin, rubitecan, Sabarubicin, Safingol, salirasib, Sapacitabine, , dianhydrodulcitolum, dibrospidium chloride, Saracatinib, Sardomozide, satraplatin, Sebriplatin, Seliciclib, dienogest, diflomotecan, dinalin, disermolide, docetaxel, Semaxanib, SU-5416, semustine, sermorelin, simotaxel, dofecquidar, dolasetron mesylate, dovitinib, , simtraZene, Sitagliptin, sizofuran, Soblitodin, Sobuzoxane, doxorubicin, dromostanolone, duaZomycin, duocarmycin, Sodium phenylbutyrate, Sorafenib, Sparfosic acid, sparsomy dynemicin, ecomustine, edatrexate, edotecarin, edotreotide, cin, Spiroplatin, squalamine, Squamocin, streptonigrin, Strep eflornithine, elacridar, eacytarabine, elesclomol, elinafide, tovarycin, Streptozocin, Sufosfamide, Sulofenur, Sunitinib, US 2010/0226943 A1 Sep. 9, 2010 36

Swainsonine, tacedinaline, tafluposide, tallabostat, talisomy melatine, aklomide, alacepril, alafosfalin, alagebrium, ala cin, tallimustine, talotrexin, taltobulin, tamoxifen citrate, mecin, alamifovir, alanine, alanosine, alaproclate, tandutinib, tanespimycin, tariquidar, tasidotin, tasisulam, alatrofloxacin, alazanine triclofenate, albaconazole, albenda tauromustine, tegafur, tegafur-uracil, telantinib, telox Zole, albuterol, albutoin, alclofenac, , alcloxa, antrone, temozolomide, teniposide, tenuaZonic acid, terame alcuronium, aldioxa, aldosterone, alemcinal, alendronic acid, procol, teriparatide, tesetaxel, testolactone, tezacitabine, thia alentemol, alepride, alestramustine, aletamine, alexidine, miprine, thioguanine, thiotepa, thymopoietin, tiazofurine, alexitol, alexomycin, alfacalcidol, alfadex, alfidalone, tilomisole, tillorone, timcodar, timonacic, tioguanine, tira alfaprostol, alfatradiol, aldaxalone, alfentranil, alfluZosin, paZamine, tocladesine, tomudex, topotecan hydrochloride, algeldrate, algestone, alibendol, aliconazole, allifedrine, ali toremifene citrate, tosedostat, toSitumomab, toxipantrone, furane, alilusem, alimadol, alinastine, alinidine, alipaminde, trastuzumab, trenimon, tretinoin, triciribine, triloStane, trime aliskiren, alitame, alitretinoin, alizapride, , allo trexate, triplatin tetranitrate, triptolide, triptorelin, trofosfa barbitol, allocamide, allocupreide, allomethadione, allopu mide, tropisetron HCl, tubulozole, tylophorin, U-67786, rinol, allylestrenol, allylprodine, almecillin, , U-68415, U-71184, U-76074, U-78057, ubenimex, uramus alminoprofen, almitrine, almokalant, almotriptan, tine, uredepa, urethane, uridine, ursolic acid, ursolic alde almoxatone, almurtide, alnespirone, alniditan, alonacic acid, hyde, VadimeZan, valrubicin, Valspodar, Vandetanib, vap alonimid, aloracetam, alosetron, alovudine, aloxidone, alox reotide, Vatalanib, PTK-787, verteporfin, vildagliptin, iprin, aloxistatin, aloZafone, alpertine, alphameprodine, vinblastine Sulfate, Vincristine, Vindesine, vinepidine, Vin alphamethadol, alphamethyldopa, alphaprodine, alpidem, flunine, vinformide, vinfosiltine, Vinleucinol, Vinleurosine, alpiropride, alprafenone, alprazolam, alprenolol, vinorelbine Base, vinorelbine tartrate, vintriptol, Vinzoli alprenoXime, alprostadil, alrestatin, altanserin, altapizone, dine, Voriconazole, Vorinostat, Vorozole, wilforlide A, Xan alteconazole, althiazide, altinicline, altoqualiine, altrenogast, thomycin A, Zalcitabine, Zeniplatin, Zilascorb, Zinostatin, altretamine, alvemeline, alverine, alvimopan, alvocidib, ama Zoledronic acid, Zorubicin, ZoSuquidar, or the like, or a com dinone, amafalone, amanozine, amantadine, amantocillin, bination comprising at least one of the foregoing cancer ambamustine, ambasilide, ambazone, ambenonium, inhibitors. ambenoxan, ambomycin, ambrisentan, ambroXol, ambruti 61. The article of claim 1, further comprising a second cin, ambucaine, ambucetamide, ambuphylline, ambuside, plurality of spaced features; the second plurality of spaced ambutonium, amcinafal, amcinafide, amcinonide, amdinocil features being disposed upon the first plurality of spaced lin, amdoxovir, ambucort, amedalin, amelometasone, amelt features; the spaced features of the second plurality of spaced olide, amelubant, amesergide, ametantrone, amethocaine, features being arranged in a plurality of groupings; the group amezapine, amezinium, amfenac, amfepentorex, amfetami ings of features of the second plurality of spaced features nil, amfiutizole, amfonelic, amicarbalide, amicloral, amicy comprising repeat units; the spaced features within a group cline, anidantel, amidapsone, amidephrine, amifiamine, ami ing being spaced apart at an average distance of about 1 floverine, amifioxacin, amifostine, amiglumide, amikacin, nanometer to about 50 micrometers; the groupings of features amikhelline, amiloride, amiloxate, aminacrine, amindocate, being arranged with respect to one another so as to define a amineptine, aminoglutethimide, aminohippuric acid, ami tortuous pathway; the plurality of spaced features providing nolevulinic acid, aminometradine, aminopentamide, ami the article with an engineered roughness index of about 5 to nophenaZone, aminophylline, aminopromazine, aminop about 30. terin, aminopyrine, aminoquinol, aminoquinuride, aminorex, 62. The article of claim 26, where the biologically active aminosalicylic acid, aminothiazole, amiodarone, amiperone, agent is abacavir, abamectin, abanoquil, abaperidone, amphenazole, amipizone, amiprolose, amiquinsin, amisome abarelix, abecamil, abiraterone, abitesartan, ablukast, tradine, amisulprode, amiterol, amithioZone, amitivir, ami abunidazole, acadesine, acamprosate, acaprazine, acebro traz, amitriptyline, amitriptyinoxide, amixetrine, amlexanox, chol, acebutolol, acecamide, acecarbromal, aceclidine, ace amlintide, amlodipine, amocarzine, amodiaquine, amol clofenac, acedapsone, acediasulfone, acedoben, acefluranol, anone, amonafide, amoproxan, amopyroquine, amorolfine, acefurtiamine, acefylline clofibrol, acefylline piperazine, amoscanate, amosulatol, amotoSalen, amotriphene, amoxap aceglatone, aceglutaminde, acemetacin, aceneuramicacid, ine, amoxecaine, amoxicillin, amoxydramine, amperozide, acenocoumarol, acepeprone, acepromazine, aceprometazine, anphechloral, amphenidone, amphetamine, amphomycin, aceduinoline, acesulfame, acetaminosalol, acetanilide, amphotalide, amphotericin, amplicillin, ampiroxicam, acetarSone, acetaminophen, acetazolamide, acetiamine, ace amprenavir, amprolium, ampyrimine, ampyZine, amduinate, tiromate, acetohexamide, acetophenaZone, acetophenetidin, amrubicin, amsacrine. amtolimetin, amustaline, amylobar acetorphine, acetosulfone, acetriozoic acid, acetylcysteine, bital, angestone, anagrelide, anakinra, anaritide, anastrozole, acetyldigitoxin, acetylleucine, acetyltributyl citrate, acetyl anatibant, anaxirone, anazocine, anazolene, ancarolol, ancit triethylcitrate, acevaltrate, acexamin acid, acifran, acipimox, abine, andolast, androstenediol, androstenedione, andulafun acitazanolast, acitemate, acitretin, acivicin, alcantate, aclaru gin, anecortave, anetholtrithion, angiotensin amide, andidox bicin, aclatonium napadisilate, acolbifene, aconiazide, amine, anidulafungin, anilamate, anilleridine, anilopam, aconitine, acotiamide, acoXatrine, acreoZast, acridorex, acri anipamil, aniracetam, anirolate, anisacril, anisindione, flavine, acrihellin, acrisorcin, acrivastine, acroinonide, acro anisopirol, anisotropine, anisperimus, anitraZafen, anpirto nine, actaplanin, actarit, actinoquinol, actisolide, actodigin, line, ansoxetine, antafenite, antazoline, antazonite, anthelmy acyclovir, adafenoxate, adamexine, adapalene, adaprolol. cin, anthralin, anthramycin, antipyrine, antrafenine, apado adatanserin, adefovir, adekalant, adelmidrol, ademitrionine, line, apafant, apalcillin, apaxafylline, apaziquone, apaZone, adenosine, adibendal, adicillin, adimolol, adinazolam, apicycline, aplindore, apomorphine, apovincamine, apra adiphenine, aditeren, aditoprim, adosopine, adoZelesin, clonidine, apramycin, aprepitant, aprakalim, aprindine, adrafinil, adrenalone, adrogolide, afalanine, afeletecan, aflo aprinocarsine, apofene, aprosulate, aptazapine, aptiganel, qualone, afovirsen, afurolol, aganodine, aglepristone, ago aptocaine, aranidipine, aranotin, arbaprosil, arbekacin, arb US 2010/0226943 A1 Sep. 9, 2010 37 utamine, arclofenin, ardacin, ardeparin, arecoline, arfalasin, bervastatin, berythromycin, besigomsin, besipirdine, beson arfendazam, arformoterol, argatroban, argimeSna, argipres prodil, besulpamide, besunide, beta carotene, betacetylmeth sin, argiprestocin, arlidone, arimoclomol, aripiprazole, adol, betahistine, betaine, betameprodine, betamethadol, armodafinil, arnolol, arofylline, artinolol, arprinocid, arpro betamethasone, betamicin, betamipron, betaprodine, betax midine, arsanilic acid, arteflene, artemether, artemisinin, arte olol, betazole, bethanacol, bethanidine, betiatide, betox motil, artenimol, artesunate, articaine, artilide, arundic acid, ycaine, bevantolol, bevonium, beXarotene, bexlosteride, arZoxifene, ascorbic acid, arsenapine, aseripide, asimadoline, bezafibrate, beztiramide, bialamicol, biapenem, bibeZonium, asobamast, asocainol, asoprisnil, aspartame, aspartocin, bibrocathol, bilcalutamide, bici fadine, bicoldil, biclofibrate, asperlin, aspirin, aspoxicillin, astemizole, astromicin, asula biclotymol, bicoZamycin, bidimazium, bidisomide, crine, atameStane, ataprost, ataquimast, atavanavir, atenolol. bietamiverine, bietaserpine, bifemelane, bifepramide, atevirdine, atibeprone, atilmotin, atipamezole, atipromod, bifeprofen, bifeprunox, bifluranol, bifonazole, bilastine, atiprosin, atizoram, atliprofen, atocalcitol, atolide, atomoxet bimakalim, bimatoprost, bimoclomol, bimosiamose, bin ine, atorvastatin, atosiban, atovaquone, atracurium, atrasen darit, binedaline, binfloxacin, binfibrate, biniramycin, bini tan, atraleuton, atrimustine, atrinositol, atromepane, atropine, Zolast, binodenosine, binospirone, bioallethrin, botin, bipen atropine oxide, auranofin, aurothioglucose, avanafil, ava amol, biperiden, biphenamine, biricodar, biriperone, simibe, avicatonin, avalamycin, aviptadil, avitriptan, bisacodyl, bisantrene, bisaramil, bisbendazole, bisben avizafone, avobenzone, azoparcin, avorelin, pyridine, axam tiamine, bisbutiamine, bisdequilinium, bisfenaZone, bisfenti ozide, axitirome, axomadol, azabon, azabuperone, azaciti dine, bisnafide, bisorbin, bisoctriazole, bisoprolol, bisorcic, dine, azacitidine, azaclorzine, azaconazole, azacoSrterol, aza bisoxatin, bispyrithione, bithonol, bithionoloxide, butipa cyclonol, azaftozine, azalanstat, azalomycin, azaloxan, Zone, bitolterol, bitoscanate, bivalirudin, bizelesin, bleomy aZamethiphos, azamethonium, azamulin, azanator, azanida cin, blonanserine, bluenSomycin, bofumustine, bolandiol. Zole, azaperone, azapetine, azaquinzole, azaribine, azarole, bolasterone, bolazine, boldenone, bolenol, bolmantalate, aZaserine, aZasetron, azaspirium, azastene, azatadine, aza bometolol, bopindolol, bornaprine, bornaprolol, borelone, thioprine, azelaic acid, azelastine, aZelinnidipine, azepexole, borocaptaine, bortezomib, bosentan, botiacrine, boxidine, azepindole, azetepa, aZetirelin, azidamfenicol, azidocillin, brallobarbital, brasofensine, brazergoline, brefonalol, brema azimexon, azimilide, azintamide, azipramide, azithromycin, Zocine, brequinar, bretazenil, bretyllium, brifentanil, bri aZlocillin, azlocillin, azolimine, azosemide, aztomycin, monidine, brinaZaprone, brindoXime, brinzolamide, brivu aztreonam, aZumolene, bacampicillin, bacitracin, baclofen, dine, brobactam, broclepride, brocrestine, brocrinat, bacmecillinam, bakeprofen, balaglitazone, balazipone, balo brodimoprim, brofaromine, brofoxine, brolaconazole, brola floxacin, balsalazide, bamaluzole, bamaquimast, bambermy mfetamine, bromadoline, bromamid, bromazepam, bro cin, bambuterol, bamethan, bamifylline, bamipine, bamiras mchlorenone, bromebric acid, bromerguride, bromete tine, bamidazole, banoxantrone, baduiloprim, barbexaclone, namine, bromfenac, brom hexene, bomindione, barbital, barixibat, barmastine, barnidipine, barucamide, bromisovalum, bromociclen, bromocriptine, bromodiphe barusiban, basifungin, batalbulin, batanopride, batebulast, nylhydramine, bromofenfos, bromofos, bromopride, bro batelapine, batilol, batimastat, batoprozine, baxitoizine, moxanide, bromperidol, brompheniramine, broparestrol, baZedoxifene, bazinaprine, becanthone, becatecarin, beclipar broperamol, bropirimine, broquinaldol, broSotaminde, bros cil, beclamide, becliconazole, beclobrate, beclomethasone, tallicin, broSuximide, brotianide, brotizolam, brovanexine, beclotiamine, befetupitant, befiperide, befloxatone, brovincamine, broxaldine, broXaterol, broxitalamide, broXu befunolol, befuraline, bekanamycin, belaperidone, belariz ridine, broxyquinoline, bucamide, bucetin, buciclovir, bucil ine, belfosdil, belotecan, beloxamide, beloxepin, bemar lamine, bucindolol, bucladesine, buclizine, buclosaminde, inone, bemegride, bemesetron, bemetizide, beminafil, bemi bucloxic acid, bucolme, bucricaine, bucromarone, bucu parin, bemetradine, bemoradan, bemotrizinol, benactyzine, molol, budesonide, budipine, budotitane, budralazine, benafentrine, benapry Zine, benaxibine, benazepril, ben bufenadrine, bufeniode, bufetolol, bufexamac, bufezolac, cianol, bencisteine, benclonidine, bencyclane, bendacalol, bufromedil, bufogentin, buformin, bufrolin, bufuralol, bufyl bendamustine, bendazac, bendaZol, benderizine, bendrofiu line, bullaquine, bumadizone, bumecaine, bumepidil, bumet methazide, benethamine penicillin, benexate, benfluorex, anide, bumetriazole, bunaftine, bunamidine, bunamiodyl, benfosformin, benfotiamine, benfluorodil, benhepazone, bunaprolast, bunaZosin, bunitrolol, bunolol, buparvaquone, benidipine, benmoxin, benolizime, benorilate, benorterone, bupicomide, bupivacaine, bupranolol, buprenorphine, bupro benoxifos, benoxaprofen, benoximate, benpenolisin, benperi pion, buquinerin, buquinolate, buquiterine, buramate, dol, benproperine, benrixate, bensalan, benserazide, bensul burodiline, buserelin, buspirone, busulfan, butobarbital, dazic acid, bentazepam, bentemazole, bentiamine, bentipi butacaine, butacetin, butaclamol, butadiaZamide, butafosfan, mine, bentiromide, bentoquatam, benurestat, benzalkonium, butalamine, butalbital, butamben, butamirate, butamisole, benzarone, benzbromarone, benzestrol, benzethidine, benze butamoxane, butanilicaine, butanserin, butantrone, butapera thonium, benzetimide, benzilonium, benZindopyrine, ben zine, butaprost, butaverine, butedronate, bytenafine, buteriz Ziodarone, benzmalecene, benznidazole, benzobarbital, ben ine, butenamate, buthiazide, butibufen, butifrine, butikacin, Zocaine, benzoclidine, benzoctamine, benzodepa, butilfenin, butinazocine, butinoline, butirosin, butixirate, benzododecinium, benzonatate, benzopyrronium, benzo butixocort, butobendine, butoconazole, butocrolol, butocta quinonium, benzotript, benzoxiquine, benzoxonium, ben mide, butofiolol, butonate, butopamine, butopiprine, buto Zoylpas, benzphetamine, benzpiperylon, benzpyrinium, ben prozine, butopyrammonium, butorphanol, butoxamine, Zquercin, benzquinamide, benzthiazide, benztropine, butoxylate, butriptyline, butropium, butylscopolamine, benzydamine, benzylhydrochlorothiazide, benzylpenicillin, butynamine, buZepide, cabastine, cabergoline, cactinomycin, benzylsulfamide, bepafant, beperidium, bephenium, bepias cadralazine, cadrofloxacin, cafaminol, cafedrine, caffeine, tine, bepridil, beractant, beraprost, berberine, berefrine, ber calcifediol, calciprotriene, calcitriol, calcobutrol, caldaret, genin, berlafenone, bermoprofen, bertosamil, berupipam, caldiamine, caloxetic acid, calteridol, clausterone, US 2010/0226943 A1 Sep. 9, 2010

camazepam, cambendazole, camaglibose, camiverine, camp ciclafrine, ciclazindol, ciclesonide, cleletanine, cicliomenol, tothecin and its analogues, 9-amino camptothecin, 10-hy ciclonicate, ciclonium, ciclopiroX, ciclopramine, ciclopro droxy camptothecin, 7-ethyl-10-hydroxy camptothecin, 9-ni fen, cicloprolol, ciclosidomine, ciclotizolam, ciclotropium, tro camptothecin and all other camptothecin analogues with cicloxilic acid, cicloxolone, cicortonide, cidofovir, cidox six, seven and eight membered lactone rings, camonagrel, epin, cifenline, cifostodine, ciglitaZone, ciheptolane, cila camo.stat, camylofin, canbisol, candesartan, , can dopa, cilansertron, cilastatin, cilaZapril, cilengitide, cilexin, docuronium, candoXatril, candoXatrilat, canertinib, canfosfa cilnidipine, cilobamine, cilobradine, cillofungin, cilomilast, minde, cangrelor, cannabinol, canrenoate, , capec cilostamide, cilostazol, ciluprevir, cilutazoline, cimaterol, titabine, capobenate, capobenic acid, capravirine, cimemoxin, cimetidine, cimetropium, cimicoxib, capreomycin, capromorelin, caproxamine, , cimoxatone, cinacalcet, cinalukast, cinametic acid, captamine, captodiame, captopril, capuride, carabersat, cara cinamolol, cinanserin, cinaproxen, cinchophen, cinecromen, cemide, carafiban, caramiphen, carbachol, carbadox, car cinepazet, cinepazide, cinfenine, cinfenoac, cinflumide, bamazepine, carbentel, carbasone, carbaspirin, carbaZeran, cingestol, cinitapride, cinmetacin, cinnamaverine, cinnamed carbazochrome, carbazocine, cabenicillin, , rine, cinnarizine, cinnofuradione, cinoctramide, cinodine, carbenzide, carbetapentane, carbetocin, carbidopa, carbima cinolazepam, cinoquidox, cinoxacin, cinoxate, cinoXolone, Zole, carbinoxamine, carbiphene, carbofenotion, carboplatin, cinoXopazide, cinperene, cinprazole, cinpropazide, cinprom carboprost, carboquone, carbubarb, carburazepam, carbuta ide, cintaZone, cintriamide, cinuperone, cioteronel, cipamfyl mide, carbuterol, carcainium, carebastine, , carfi line, cipemastat, ciprafamide, cipralisant, cipraZafone, mate, cargutocin, cariporide, carisoprodol, carmantadine, ciprefadol, ciprocinonide, ciprofibrate, ciprofloxacin, carmofur, carmoterol, carmustine, camidazole, carnitine, ciprokiren, cipropride, ciprocquaZone, ciprestene, ciramadol, carocamide, caroverine, caroXaZone, carperidine, carperitide, cirazoline, cirolemycin, cisapride, cisatracurium, cincona carperone, carphenazine, carpindolol, carpipramine, car Zole, cismadinone, cisplatin, cistinexine, citalopram, praZidil, carprofen, capronium, carsalam, carsatirin, car citatepine, citenamide, citenaZone, citicoline, citiolone, ciZo tasteine, cartazolate, carteolol, carubicin, carumonam, lirtine, cladribine, clamidoxic acid, clamikalant, clamox carvedilol, carvotroline, carzelesin, carzenide, casanthranol, ycuin, clanfenur, clanobutin, clantifen, clarithromycin, cla casokefaminde, caspofungin, cathine, cathinone, cebarac Vulanate, claZolam, claZolimine, claZuril, clebopride, etam, cedefingol, cefaclor, cefadroxil, cefalonium, cefalo clefamide, clemastine, clemeprol, clemizole, clenbuterol, ram, cefamandole, cefaparole, cefatriazine, cefazaflur, clenpirin, clentiazem, cletoquine, clevidipine, clevudine, cefazedone, cefazolin, cefbuperaZone, cefanel, cefcapene, clibucaine, clidafidine, clidanac, clindium, climazolam, cefclidin, cefdaloxime, cefdinir, cefditoren, cefedrolor, climbazole, climiqualine, clinafloxacin, clindamycin, cli cefempidone, cefepime, cefetamet, cefetecol, cefetriaole, nofibrate, clinolamide, climprost, clioquinol, clioxanide, clip cefivtril, cefixime, cefimatilen, cefinenoxine, cefinepidium, rofen, cliropamine, clobazam, clobenoside, clobenzepam, cefinetazole, ceminox, cefodizime, cefonicid, cefoperaZone, clobenorex, clobenztropine, clobetasol, clobetasone, clobuti ceforanide, cefoselis, cefotaxime, cefotetan, cefotiam, nol, clobuZarit, clocanfamide, clocapramine, clociguanil, cefoVecin, cefoxazole, cofoxitin, cefoZopran, cefpimizole, clocinizine, clocortolone, clocoumarol, clodacaine, cefpiramide, cefpodoxime, cefprozil, cefauinome, cefrotil, clodanolene, clodazon, clodoxopone, clodronate, clofara cefroxadine, cefsulodin, cefsumide, ceftazidime, cefteram, bine, clofazimine, clofenamic acid, clofeniclan, clofen ceftezole, ceftibuten, ceftioflur, ceftiolene, ceftioxide, ceft etamine, clofenoxyde, clofevine, clofexamine, clofeZone, ioxime, ceftriaxone, cefuracetamime, cefuroxime, cefu clofibrate, clofibric acid, clofibride, clofilium, clofucarba, Zonam, celecoxib, celgosivir, celiprolol, cemadotin, ceph clofoctol, cloforex, clofurac, clogestone, cloguanamil, clo acetrile, cephadrine, cephalexin, cephaloglycin. macrin, clomegestone, clometacin, clometherone, clomethia Cephaloridine, cephalothin, cephapirin, cepharanthine, ceph Zole, clometocillin, clomifenoxide, clominorex, clomiphene, radine, cericlamine, cerivastatin, ceronapril, ceruletide, ceta clomipramine, clomocycline, clomoxir, clonazepam, clona ben, cetalkonium, cetamolol, cetefloxacin, cethexonium, Zoline, clonidine, clonitazine, clonixeril, clonixin, clopam cethromycin, cetiedil, cetilistat, cetirizine, cetocycline, ide, clopenthixol, cloperastine, cloperidone, clopidogrel, clo cetopheincol, cetotiamine, cetoxime, cetraxate, cetrimo pidol, clopimozide, clopipazan, clopirac, cloponone, nium, cetylpyridinium, cevimeline, chaulmosulfone, cheno cloprendol, cloprostenol, cloprothiazole, cloquinate, clo diol, chinofon, chlofibrate, chlophendianol, chloracy Zine, quinozine, cloracetadol, cloranolol, cloraZepate, cloraZepic chloralose, chlorambusil, chloramines-T, chloramphenicol, acid, clorethane, chlorexolone, clorfenvinos, clorgiline, clo chlorazanil, chlorbenoxamine, chlorbetamide, chlorcycliz ricromen, cloridarol, clorindanic acid, clorindione, clo ine, chlordantoin, chlordiazepoxide, chlordimorine, chlo rmecaine, cloroperone, clorophene, cloroqualone, clo rhexidine, chlorindanol, chlorisondamine, chloramadione, rotepine, clorprenaline, clorSulon, clortermine, closantel, chlormerodrin, chlormeZanone, chlormidazole, chlornaphaz closiramine, clostebol, clothiapine, clothixamide, clotiaz ine, chloroaZodin, chloroprednisone, chloroprocaine, chloro epam, cloticaSone, clotioxone, clotixamide, clotrimazole, pyramine, chloroquine, chloroserpidine, chlorothen, chlo clovoxamine, cloxacepride, cloxacillin, cloxazolam, clox rothiazide, chlorotrianisene, chloroxine, chloroxylenol, estradiol, cloximate, cloXotestosterone, cloxypendyl, clox chlorphenesin, chlorpheniramine, chlorphenoctium, chlor ycuin, clozapine, cobalamide, cocaine, codeine, codoxime, phenoxamine, chlorphentermine, chlorproethazine, chlor cofistatin, cogaZocine, colchicines, colestolone, colfenamate, proguanil, chlorpromazine, chlorpropamide, chlorprothix colforsin, colfosceril, colimecycline, colterol, coluracetam, ene, chlorpyrifos, chlortetracycline, chlorthalidone, conessine, congaZone, conivaptan, conorphone, cormetha chlorthenoxazine, chlorZoxazone, cholecalciferol, choles Sone, corticorelin, cortisone, cortisuZol, cortivaZol, cortodox terol, choline alfoscerate, choline, chromic chloride, chromo one, cotinine, cotriptyline, coumaphos, coumazolin, coumer nar, ciadox, ciaftalan, ciamexon, cianergoline, cianidanol, mycin, coumetarol, creatinine, creatinolfosfate, cresotamide, cianopramine, ciapilome, cicaprost, cicarperone, ciclactate, cridanimod, crilvastin, crisinatol, crobenetine, croconazole, US 2010/0226943 A1 Sep. 9, 2010 39 cromakalim, cromitrile, cromoglicate lisetil, cromolyn, cro diamocaine, diampromide, diamthiazole, diapamide, diar lom, cronidipine, cropropamide, crotamiton, crotetamide, barone, diathymosulfone, diatrizoate, diaveridine, diazepam, crotoniazide, crotoxyfos, crufomate, cuprimyxin, cuproXo diaziquone, diaZOxide, dibekacin, dibemethine, dibenzepin, line, cyacetacide, cyamemazine, cyanocobalamine, cyclacil dibenzothiophene, dibrompropamidine, bibromsalan, lin, cyclamate, cyclamic acid, cyclandelate, cyclarbamate, dibrospidium, dibucaine, dibuprol, dibupyrone, dibusadol, cyclazocine, cyclazodone, cyclexanone, cyclindole, cyc dicarbine, dicarfen, dichloralphenaZone, dichloramine, liramine, cyclizine, cyclobarbital, cyclobendazole, cycloben dichlorisone, dichlormeZanone, dichlorophen, dichlorphe Zaprine, cyclobutoic acid, cyclobutyrol, cyclocumarol, narsine, dichloroxylenol, dichlorphenamide, dichlovos, dici cyclofenil, cycloguanil, cycloheximide, cyclomenol, cyclom ferron, dicirenone, diclaZuril, diclofenac, diclofenamide, ethycaine, cyclopentamine, cyclopenthiazide, cyclopento diclofensine, diclofutrime, diclometide, diclonixin, diclo late, cyclophenazine, cyclophosphamide, cyclopregnol, ralurea, dicloxacillin, diclolinium, dicummol, dicyclomine, cyclopyrronium, cycloserine, eyelothiazide, cyclovalone, didanosine, didrovaltrate, dieldrin, dienestrol, dienogest, cyclotiamine, cycrimine, cyfluthrin, cyhalothrin, cyhepta diethadione, diethylphthalate, diethylcarbamazine, dietyl mide, cyheptropine, cynarine, cypenamine, cypermethrin, propion, diethylstilbestrol, dethylthambutene, dietyltolua cypothrin, cyprazepam, cyprenorphine, cyprodenate, cypro mide, dietifen, difebarbamate, difemerine, difemetorex, dife heptadine, cyprolidol, cyproduinate, cyproterone, cyproxim namizole, difencloxazine, difenoximide, difenoxin, ide, cyromazine, cysteamine, cysteine, cystine, cytarabine, difetarsone, difeterol, diflomotecan, diflorasone, difloxacin, cythiolate, dabelotine, dabigatran, dabu Zalgron, dacarbazine, difluanine, diflucortolone, diflumidone, diflunisal, diflupred dacemazine, dacinostat, dacisteine, dacopafant, dactinomy nate, diftalone, digitalis, digitoxin, digoxin, dihexyverine, cin, dacuronium, dagapamil, dagluril, dalbavancin, dalbrami dihydralazine, dihydrocodeine, dihydroergotamine, dihy nol, dalcotidine, daledalin, dalfopristin, dalteparin, dal drostreptomycin, dihydrotachysterol, diisobutylaminoben troban, dalvastatin, dametralast, damotepine, danazol. Zoyloxypropyl theophylline, diisopromine, diisopropanola daniquidone, danittracen, danofloxacin, danosteine, dan mine, diisopropylamine, dilaZep, dilevalol, dilimefone, thron, dantrolene, dapiprazole, dapitant, dapivirine, dapoxet diloxanide, diltiazem, dimabefylline, dimadectin, dimecam ine, dapsone, daptomycin, darbufelone, darenzepine, dargli ine, dimeclonium, dimecrotic acid, dimefadane, dimefline, taZone, darifenacin, darodipine, darunavir, darusentan, dimelazine, dimenhydrinate, dimenoxadol, dimepheptanol, dasantafil, datelliptium, daunorubicin, daxalipram, daZadrol, dimepranol, dimepregnen, dimepropion, dimeproZan, dime dazepinil, daZidamine, daZmegrel, dazolicine, dazopride, Sna, dimesone, dimetacrine, dimetamfetamine, dimethadi dazoquinast, dazoxiben, deboxament, debrisoquin, decame one, dimethazan, dimethisoquin, dimethisterone, dimetholiz thonium, decimemide, decitabine, decitropine, declenper ine, dimethothizine, dimethoxanate, dimethylaminoethyl one, declopramide, decloxizine, decominol, decoquinate, reserpilinate, dimethylthambutene, dimethyltubocurarinium, dectaflur, deditonium, deferasirox, deferiprone, deferoxam dimetipirium, dimetofrine, dimetridazole, diminaZene, ine, deflazacort, defosfamine, defoslimod, degarelix, dehy dimiracetam, dimoxamine, dimoxaprost, dimoxyline, droacetic acid, dehydrocholic acid, dehydroemetine, dimpylate, dinaline, dinaZafone, diniprofylline, dinitolmide, delanterone, delapril, delavirdine, delquamine, deergotrile, dinoprost, dinoprostone, dinsed, diohippuric acid, dioSmin, delfantrine, delfaprazine, Selmadinone, delmetacin, delimpi diotyrosine, dioxadrol, dioxamate, dioxaphetyl butyrate, nol, delorazepam, deloXolone, delprostenate, delucemine, dioxation, dioxethedrin, dioxifedrine, dioxybenazone, dioxy dembrexine, demecarium, demeclocycline, demecolcine, line, dipenine, diperodon, diphemanil, diphenadione, demecycline, demegestone, demelverine, demexiptiline, diphenan, diphenchloxazine, diphenhydramine, diphenidol. democonazole, demoxepam, demoxytocin, denatonium, diphenoxylate, diphenylpiperidinomethyldioxolan, diphe denaverine, denbufylline, denipride, denofungin, denopam nylpyraline, diphenoxazide, dipipanone, dipiproverine, ine, denotivir, denpidaZone, denufosol, denZimol, depelestat, dipivefrin, diprafenone, diprenorphine, diprobutine, dipro depramine, depreotide, deprodone, deprostil, deptropine, fene, diprogulic acid, diproleandomycin, diprofylline, dipro dequalinium, deracoxib, deramciclane, deriglidole, derpan qualone, diproteverine, diprotrizoate, diproxadol, dipy icaine, derSalazine, desapidin, desciclovir, descinolone, ridamole, dipyrithione, dipyrocetyl, dipyrone, diduafosol, deserpidine, desipramine, deeslanoside, desloratidine, dirithomycin, dirlotapide, disermolide, disquonium, disob deslorelin, desmeninol, desmethylmoramide, desmopressin, utamide, Sidofenin, Sdisogluside, disopyramide, disoxaril. desocriptine, desogestrel, desmorphine, desonide, des distigmine, disufenton, disulergine, disulfamide, disulfuram, Oximetasone, desoxycorticosterone, desvenlafaxine, detaj disupraZoole, ditazole, ditekiren, ditercalinium, dithiaanine, mium, detanosal, deterenol, detirelix, detiviciclovir, detromi ditiocade, ditiocarb, ditiomustane, ditolamide, ditophal, div dine, detorubicin, detrothyronine, devapamil, devaZepide, abuterol, divalproex, divaplon, dixanthogen, dizatrifone, dexamethasone, dexamisole, dexbrompheniramine, dex dizcilpine, dobesilate, dobupride, dobutamide, dobutamine, budesonide, dexchlorpheniramine, dexclamol, dexecadotril, docarpamine, docebenone, docetaxel, doconazole, doconex dexefaroxan, dexetimide, dexetoZoline, dexfenfluramine, ent, docosanol, docusate, dodeclonium, dodicin, dofamium, dexfosfoserine, dexibuprofen, deximafen, dexindoprofen, dofecquidar, dolfetilide, dolasetron, doliracetam, domaZoline, dexivacaine, dexketoprofen, dexlofexidine, dexloxiglumide, domiodol, domiphen, domipizone, domitroban, domopred dexmedetomidine, dexmethylphenidate, dexnafenodonee, nate, domoxin, domperidone, donepezil, donetidine, doni dexniguldipine, dexnorgestrel, dexormaplatin, dexoxadrol, triptan, dopamantine, dopamine, dopexamine, dopropidil, dexpanthenol, dexpemedolac, dexpropranolol, dex.proxib doqualast, dorampimod, doramectin, doranidazole, doras utene, dexraZoxane, dexsecoverine, dexSotalol, dextilidine, tine, Soreptide, doretinel, doripenem, dorZolamide. dosergo dextiopronin, dextofisopam, dextroamphetamine, dextro side, doSmalfate, dotarizine, dotefonium, dothiepin, doxacu femine, dextromethorphan, dextromoramide, dextrorphan, rium, doxapram, doxaprost, doxazosin, doxefazepam, dextrothyroxine, dexcerapimil, Sezaguanine, dezinamide, doxenitoin, doxepine, do Xergo calciferol, doxibetasol, doxi dezocine, diacerein, diacetamate, diacetolol, diamfenetide, fluridine, doxofylline, doxorubicin, doxpicomine, doxycy US 2010/0226943 A1 Sep. 9, 2010 40 cline, doxylamine, draflazine, dramedilol, draquinolo, drazi side, ethoXZolamide, ethybenztropine, ethyl biscoumacetate, dox, dribendazolew, drimidene, drobuline, drocinonide, ethyl carfluzepate, ethyl cartrizoate, ethyl dibunate, ethyl droclidinium, drofenine, droloxifene, drometrizole, dromo dirazepate, ethyl loflazepate, ethylestrenol, ethylhydrocu stanolone, dronabinol, drinedarone, dropempine, droperidol. preine, ethylmethylthiambutene, ethylmorphine, ethylnore droprenilamine, dropropizine, drospirenone, drotaverine, pinepherine, ethylstilbamine, ethylnerone, ethylnodil, drotebanol, droxacin, droxicamide, droxicam, droxidopa, ethypicone, etibendazole, eticlopride, eticyclidine, eti droximavir, droxypropine, duaZomycin, dulofibrate, dulloxet docaine, etidronate, etidronic acid, etifelmine, etifenin, eti ine, duloZafone, dumorelin, dumetacin, duoperone, duprac foXine, etilamfetamine, etillefrine, etilevodopa, etinidine, etam, dutasteride, dyclonine, dyhydrogestrone, dymanthine, etipirium, etiprendol, etiproston, etiracetam, etiroXate, etisa dyphylline, ebalZotan, ebastine, eberconazole, ebiratide, Zole, etisomicin, etisulergine, etizolam, etocarlide, etoc ebrotidine, ebselen, ecabapide, ecabet, ecadotril, ecalcidene, rylene, etodolac, etodroxizine, etofamide, etofenamate, ecamsule, ecastolol, ecenofloxacin, echothiophate, eciprami etofemprox, etofibrate, etofermin, etofuradine, etofylline, eto dil, eclanamine, eclaZolast, ecomustine, econazole, ecopi glucid, eorolex, etolotifen, etoloxamine, etomidate, etomido pam, ecraprost, ectylurea, edaglitaZone, edaravone, edatrex line, etomoxir, etomitaZene, etonogestrel, etoperidone, eto ate, edelfosine, edetol, edifolone, edogestrone, edonentan, poside, etoprindole, etoprine, etoricoxib, etorphine, edotecarin, edotreotide, edoxudine, edratide, edronocaine, etosalamide, etoxadrol, etoxeridine, etoZolin, etrabamine, edrophonium, efaproxiral, efaroxan, efavirenz, efegatran, etravirine, etretinate, etriciguat, etryptamine, etymemazine, efepristin, efetozole, efletirizine, eflornithine, efloxate, eflu eucaine, eucalyptol, eugenol, euprocin, evandamine, evern cimibe, elfiumast, efonidipine, efrotomycin, eganoprost, imicin, everolimus, evicromil, exalamide, exametazime, eglumetad, egtazic acid, equalen, elacridar, elantrine, elan examorelin, exaprolol, exatecan, exemestane, exepanol, exi Zepine, elaarofiban, elbanizine, eldacimibe, eletriptan, elf fone, exiprofen, exisulind, eZetimibe, eZlopitant, fadolmi azepam, elgotipine, elinafide, eliprodil, elisartan, ellagic acid, dine, fadrozole, falecalcitriol, fallintolol, falipamil, elliptinium, elmustine, elnadipine, elopiprazole, elsamitru falnidamol, famciclovir, famirapinium, famotidine, famo cin, eltanolone, eltenac, eltoprazine, elucaine, elvucitabine, tine, fampridine, famprofaZone, fampronil, fananserin, elzasonan, elziverine, emakalim, emapunil, embramine, fanapanel, fandofloxacin, fandoSentan, fanetizole, fantofar embusartan, embutramide, emedastine, emepronium, emet one, fantridone, fargilitazar, fasidotril, fasiplon, fasoracetam, ine, emeglitate, emilium, emiteflur, emiverine, emodepside, faudil, fazadinium, fazarabine, febantel, febarbamate, febu emopamil, emorfaZone, emitricitabine, emylcamate, enado prol, febuverine, febuxostat, feclemine, feclobuzone, fedot line, enalapril, enalaprilat, enalkiren, enazadrem, enbucrilate, ozine, fedrilate, felbamate, felbinac, felipyrine, felodipine, encamide, enciprazine, enclomiphene, encyprate, endix feloprentan, fely pressin, femoxetine, fenabutene, fenace aprine, endomide, endralazine, endrysone, enecadin, enefex tinol, fenaclon, fenadiazole, fenaftic acid, femalamide, femal ine, enestebol, enfenamic acid, enfluvirtide, englitaZone, eni comine, fenamifuril, fenamole, fenaperone, fenbendazole, clobrate, enilconazole, eniloSpirone, eniluracil, eniporide, fenbenicillin, fenbufen, fenbutreazate, fencamfamin, fenci enisoprost, enloplatin, enocitabine, enofelast, enolicam, butirol, fencleXonium, fleclofenac, fenclonine, fenclorac, enoxacin, enoxamast, enoxaparin, enoXimone, enoXolone, fenclozic acid, fendiline, fendizoate, fendosal, feneritrol, enipiprazole, empiroline, enprazepine, enprofylline, enpro fenestrel, fenethazine, fenethylline, fenetradil, fenflumizole, mate, enprostil, enramycin, enrasentan, enrofioxacin, fenfluramine, flenfluthrin, fengabine, fenharmane, fenimide, ensacillin, ensulizole, entacapone, entecavir, entisulfon, feniodium, fenipentol, fenirfibrate, fenisorex, fenitrothion, enviomycin, enviradene, enviroxime, enZacamene, anZastau fenleuton, fenmetoZole, fenmetraminde, fenobam, fenocinol, rin, epalrestat, epanolol, eperezolid, eperisone, eperVudine, fenocitimine, fenofibrate, fenoldopam, fenoprofen, fenot ephedrine, epicamide, epicillin, epicriptine, epiestriol, erol, fenoerine, fenoxazoline, fenoxedil, fenozolone, fenpen epimestrol, epinastine, epinephrine, epinepheryl, epipropi tadiol, femperate, fenprpalone, fenpipramide, fenpiprane, fen dine, epirizole, apiroprim, epirubicin, epitetracycline, epithi piverinium, fenprinast, fenproporex, fenprostalene, azide, epitiostanol, eplerenone, elivanserin, epoprostenol, fenduiaone, fenretinide, fenspiride, fentanyl, fenthion, fen epostane, eprazinone, eprinomectin, epristeride, eprobemide, tiazac, fenticlor, fenticonazolem, fentonium, fenvalerate, eprosartan, eprovafen, eproXindine, eproZinol, epsipranel, fenyripol, fepentolic acid, fepitrizol, fepradinol, feprazone, epaloprost, eptapirone, eptaplatin, eptastigmine, eptazocin, fepromide, feprosidnine, ferpifosate, fesoterodine, fetoxy eptifibatide, equillin, erbuloZole, erdosteine, ergo calciferol, late, fexicaine, fexinidazole, fexofenadine, fezatione, fezola ergonovine, ergotamine, eritoran, erizepine, erlotinib, erca mine, fiacitabine, fialuridine, fibracillin, fidarestat, fidexaban, mide, ersentilide, ertapenem, ertiprotafib, erythrity tetrni fiduXosin, figopitant, filaminast, filenadol, filipin, finafloxa trate, erythromycin, esafloxacin, esaprazole, esatenolol, esci cin, finasteride, fingolimod, fipamezole, fipexide, fipronil. talopram, esculamine, eseridine, esflurbiprofen, esketamine, firocoxib, fiavamine, flavodic acid, fiavodilol, fiavoxate, escarbazepine, esmolol, esomeprazole, esonarimod, esorubi flazalone, fiecamide, fierobuterol, fleroxacin, flesinoxan, cin, esoxybutynin, espatropate, esproquin, estazolam, estra fiestolol, fietazepam, fiezelastine, flibanserin, findokalner, diol, estramustine, estraZinol, estriol, estrofurate, estrone, fiocalcitriol, floctafenine, flomoxe?, fioptopione, floranty estropipaten esupone, esZopclone, etabenzarone, etacepride, rone, flordipine, floredil, florfenicol, fiorifenine, fiosatidil, etafedrine, etafenone, etalocib, etamestrol, etaminile, etami fiosequinan, flosulide, flotrenizine, floverine, floxacillin, phylline, etamocycline, etanidazole, etanterol, etaqualone, floxacrine, floXuridine, fiucizine, fluialamine, fiuanisone, flu etarotene, etasuline, etazepine, etazolate, etebenecid, eter azacort, fluaZuron, flubanilate, fiubendazole, fiubepride, flu obarb, etersalate, ethacridine, ethacrynic acid, ehtambutol, carbril, flucetorex, flucindole, fiucinprazine, flucloronide, ethamivan, ethamsylate, ethaverine, ethenZameide, ethiazide, fluconazole, flucrylate, flucytosine, fludalanine, fludarabine, ethinamate, ethinyl estradiol, ethionamide, ethisterone, etho fludazonium, fludeoxyglucose, fludiazepam, fluidorex, flu heptazine, ethomoxane, ethonam, ethopabate, ethopro doxopone, fludrocortisone, tolfenamic acid, flufenisal, flu pazine, ethoSuximide, ethotoin, ethoxazene, ethoxazoruto fosal, flufylline, flugestone, fluindarol, fluindione, flumaze US 2010/0226943 A1 Sep. 9, 2010

nil, flimecinol, flumedroxone, flumequine, flumeridone, din, granisetron, grepafloxacin, griseofulvin, guabenXan, flumethasone, flumethiazole, flumetramide, flumexadol, guacetisal, guafecainol, guaiactamine, guaiapate, guaietolin, flumeZapine, fluminorex, flumizole, flumoxonide, flunamine, guaifenesin, guaimeSal, guaisteine, guaithylline, guanabenz, flunarizine, flunidazole, flunisolide, flunitrazepam, flunixin, guanacline, guanadrel, guanaZodine, guanclofine, guancy flunoprost, flunoxaprofen, fluocinolone, fluocinonide, fluo dine, guanethidine, guanfacine, guanisoquin, guanoclor, gua cortin butyl, fluocortolone, fluorescein, fluoresone, fluoro noctine, guanoXabenz, guanoxan, guanoxyfen, gusperimus, dopa, fluorometholone, fluorosalan, fluorouracil, fluotracen, halazepam, halaZone, halcinonide, halethazole, halobetasol, fluoxetine, fluoxymesterone, fluparoxan, flupentiXol, flu halocortolone, halofantrine, halofenate, halofuginone, peramide, fluperlapine, fluperolone, flupheazine, flupi halometaSone, halonamine, halopemide, halopenium, halo mazine, flupirtine, flupranone, fluprazine, fluprednidene, flu peridol, halopredone, haloprogesterone, haloprogin, halox prednisolone, fluprofen, fluprofylline, fluproduaZone, aZolam, haloxon, haloqionol, hamycin, hedaquinium, helio fluprostenol, fluquaZone, fluradoline, flurandrenolide, fluran mycin, hepronicate, heptabarbital, heptaverine, heptolamide, tel, flurazepam, flurbiprofen, fluretofen, flurithromycin, fluo hepzidine, heroin, hetacillin, hetaflur, heteronium, hexachlo rocitabine, fluorofamide, fluorogestone, flusoxolol, fluspip rophene, hexacyclonate, hexacy prone, hexadiline, hexafluo erone, fluspirilene, flutamide, flutazolam, flutemazepam, renium, hexamethonium, hexaminolevulinate, hexapradol, flutiazin, fluticasone, flutizenol, flutomidate, flutonidine, flu hexaprofen, hexapropymate, hexasonium, hexazole, hexe toprazepam, flutrimazole, flutroline, flutropium, fluvastatin, dine, hexestrol, hexetidine, hexobarbital, hexobendine, hexo fluvoxamine, fluzinamide, fluZoperine, fodipir, folic acid, cyclium, hexoprenaline, hexopyrronium, heylcaine, hista fomepizole, fomidacillin, fominoben, fomiversen, mine, histapyrrodine, histidine, homarylamine, homatropine, fomocaine, fonazine, fondaparinux, fopiirtoline, forasartan, homidium, homochlorcyclizine, homofenazine, forfenimex, formebolone, formestane, formetorex, formini homopipramol, homosalate, homprenorphine, hopantenic trazole, formocortal, formoterol, forodesine, foropafant, fos acid, hoquizil, hycanthone, hydracarbazine, hydralazine, amprenavir, fosarilate, fosazepam, foSenazide, fosflucona hydragaphen, hydrobentizide, hydrochlorothiazide, hydroc Zole, foSfocreatinine, fosfomycin, foSfonet, fosfosal, odone, hydrocortisone, hydroflumethiazide, hydromadinone, fosfructose, fosinopril, fosinoprilat, foSmenic acid, fosmido hydromorphinol, hydromorphone, hydroquinone, hydroxy mycin, fosopamine, fosphenyloin, fospirate, fosquidone, indasate, hydroxyindasol, hydro Xocobalamin, hydroxyam fostedil, foSrtriecin, fosveset, fotemustine, fortrenamine, phetamine, hydroxychloroquin, hydroxydione, hydroxy fozivudine, frabuprofen, fradafiban, frakefamide, framycetin, pethidine, hydroxyphenamate, hydroxyprocaine, frentizole, freselestat, fronepidil, fropenem, froVatriptan, hydroxyprogesterone, hydroxypyridine tartrate, hydroxys froxiprost, ftaxilide, ftivazide, formetazine, forpropazine, tenozole, hydroxyStilbamidine, hydroxytetracaine, hydrox fubrogonium, fudosteine, fuladectin, fulvestrant, fumagillin, yZine, hymecromone, hyoscyamine, ibafloxacin, ibandr fumoxicillin, fungimycin, fuprazole, furacrinic acid, furafyl onate, ibazocine, ibopamine, ibrolipim, ibrotamide, line, furalazine, furaltadone, furaprofen, furazabol, furazoli ibudalast, ibufenac, ibuprofen, ibuproxam, ibutamoren, done, furazolium, furbicillin, furcloprofen, furegrelate, fure ibuterol, ibutilide, ibuverine, icaridin, icatibant, iclaprim, thidine, furfenorex, furidarone, furmethoxadone, furnidipine, icazepam, icodulinium, icofungipen, ifometaSone, icopezil, furobufen, furodazole, furofenac, furomazine, furomine, icosapent, icospiramide, icotidine, icrocaptide, idarubicin, furosemide, furostilbestrol, fursalan, fursultiamine, fur idaverine, idazoxan, idebenone, idenast, idoxifene, idoxuri therene, furtrethonium, fusafungine, fusidate, fusidic acid, dine, idralfidine, idramantone, idraparinux, idrapril, idiremci fuZlocillin, gabapentin, gabapexate, gaboxadol, gacyclidine, nal, idrociliamide, idronoxil, idropranolol, iferanserin, gadobenate, gadobutrol, gadocolectic acid, gadodiamine, ifetroban, ifosfamide, ifoxetine, iganidipine, igmesine, igu gadofosveset, gadomelitol, gadopenamide, gadopentetate, ratimod, ilaprazole, ilatreotide, ilepcimide, iliparcil, ilmofos gadoteric acid, gadoteridol, gadoversetamide, gadoxetate, ine, illoomastat, illonidap, illoperidone, imafen, imanixil, ima gadoxeticaicid, galamustine, galntamine, galarubicin, gala tinib, imaZodan, imcarbofos, imiclopazine, imidafenacin, Somite, galdansetron, gallamine triethiodide, gallopamil, imidapril, imidaprilat, imidocarb, imidoline, imidurea, imi galocitabine, galosemide, galtifenin, gamfexine, gamolenic glitazar, imiloxan, iminophenimide, imipenem, imipramine, acid, gamaXolone, ganciclovir, ganefromycin, ganglefene, imipraminoxide, imiquimod, imirestat, imitrodast, imola ganstigmine, gantacurium, gantofiban, gapicomine, gapro mine, imoxiterol, impacarzine, implitapide, impromidine, midine, garenoxacin, gatifloxacin, gavestinel, geclosporin, improSulfan, imuracetam, inamirone, inaperisone, incad gedocarnil, gefarnate, gefitinib, gemazocine, gemcabene, ronic acid, indacaterol, indacrinone, indalpine, indanazoline, gemcadiol, gemcitabine, gemeprost, genfibtrozil, gemifloxa indanidine, indanorex, indapamide, indatraline, indecamide, cin, gemopatrilat, gentamicin, gepefrine, gepirone, gero indeloxazine, indenolol, indibulin, indigotindisulfonate, quinol, gestaclone, gestadienol, gestodene, gestonorone, indinavir, indiplon, indisetron, indobufen, indocate, indocya gestrinone, geVotroline, gimatecan, gimeracil, giparmen, nine green, indolapril, indolidan, indomethacin, indopanolol. giracodazole, giractide, girisopam, gitaloxin, gitoformate, indopine, indoprofen, indoramin, indorenate, indoxole, glafenine, glaspimod, glatiramer acetate, glemanserin, glen indriline, inecalcitol, ingliforib, inicarone, inocterone vastatin, gliamilide, glibotnuride, glibutimine, glicaramide, acetate, inogatran, inosine, inositol, improquoone, intopli glicetanide, gliclazide, glicondamine, glidaZamide, gliflu cine, intrazole, intriptyline, inulin, iobenguane, iobenzamic mide, glimepiride, glipalamide, glipizide, gliquidone, acid, iobitridol, iobutoic acid, icanlidic acid, iocarmic acid, glisamuride, glisentide, glisindamine, glisolamide, glisox iocetamic acid, iodamine, iodipamide, iodixanol, iodoantipy epide, gloxazone, gloXimonam, glucametacin, glucosamine, rine, iodocholesterol, iodohippurate, iodoquinol, iodothiou gluronolactone, glucuronamide, glunicate, glyburide, gly racil, idoxamic acid, iofetamine, ioflupane, iofratol, ioglicic buthiazole, glubuzole, gycopyrrolate, glycylamide, glyhexa acid, ioglucol, ioglunide, ioglycamic acid, iogulaamide, mide, glymidine, glyoctamide, glyparamide, glypinamide, iohexyl, iolidonic acid, iolixanic acid, iolopride, iomazenil. glyprothiazole, gly Sobuzole, goralatide, goserelin, gramici iomeglamic acid, iomeprol, iomethin, iometopane, iomorinic US 2010/0226943 A1 Sep. 9, 2010 42 acid, iopamidol, iopanoic acid, iopentol, iophendylate, iophe ofenac, liarozole, libecillide, libenzapril, licarbazepine, noxic acid, iopromide, iopronic acid, iopydol, iopydone, iosa licofelone, licostinel, lidadronic acid, lidamine, lidanserin, rcol, isofenamic acid, io.seric acid, iosimenol, iosimide, ioSu lidocaine, lidoferin, lidorestat, lifariaine, lifibrate, lifibrol, lamide, ioSumetic acid, iotasul, ioteric acid, iothalamate, lilopristone, limaprost, limazocic acid, linarotene, lincomy iothalamic acid, iotranic acid, iotriside, iotrizoic acid, iotro cin, lindane, linetastine, lineZolid, linogliride, linopirdine, lan, iotroXic acid, iotyrosine, iovesol, ioxabrolic acid, ioxa linotroban, lisinidomine, lintitript, lintopride, liothyronine, glic acid, ioxilan, ioxitalamic acid, ioxotrizoic acid, ioZomic lipoic acid, liraglutide, liranaftate, lirequinil, lirexapride, lir acid, ipamorelin, ipazilide, ipenoxazone, ipexidine, ipida imilast, liroldine, lisadimate, lisinopril, lisofylline, lisuride, crine, ipodate, iprgratine, ipramidil, ipratropium, ipra litomeglovir, litoxetine, litracen, lividomycin, lixazinone, lix vacaine, iprazochrome, ipriflavone, iprindole, ipocinidine, ivaptan, lobapolatin, lobeline, lobendazole, lobenzarit, lobu iproclozide, iprocrodol, iprofenin, iproheptine, iproniazide, cavir, lobuprofen, locicortolone, lodaxaprine, lodaZecar, ipronidazole, iproplatin, iprotiaZem, iproxamine, iprozil lodelaben, lodenosine, Iodinixil, lodiperone, lodoxamide, amine, ipsalazide, ipsapirone, iquindamine, iralukast, iram lofemizole, lofendazam, lofentanil, lofepramine, lofexidine, panel, irbesartan, irindalone, irinotecan, irloxacin, irofulven, loflucarban, lombazole, lomefloxacin, lomeguarib, lomeriZ irolapride, iroXanadine, irsogladine, irtemazole, isalidole, ine, lometraline, lometrexol, lomevactone, lomifylline, lomo isalsteine, isamfaZone, isamoltan, isamoxole, isatoribine, fungin, lomustine, lonafarnib, lonapalene, lonaprofen, lona isaxonine, isbogrel, isbufylline, ispamicin, isoamilinile, iso Zolac, lonidamine, loperamide, lopinavir, lopirazepam, bromindione, isobucaine, isobutamben, isocarboxazid, iso lopobutan, loprazolam, loracarbef, lorajmine, lorapride, conazole, isocromil, isoetharine, isoflupredone, isofluo lorazepam, lorbamate, lorcamide, lorcinadol, lorecleZole, rophate, isomazole, isomerol, isometamidium, lorglumide, lormetazepam, lornoxicam, lopiprazole, lorta isomethadone, isometheptene, isomolpan, isoamylamine, lamine, lorZafone, losartan, losigamone, losindole, loSmipro isoniazid, isonixin, isoprazole, isoprednidene, isoprofen, iso fen, losoxantrone, losulazine, loteprednol, lotrafiban, lot propamide, isopropicillin, isoproterenol, isoSrbide, isospa rifen, lotucaine, lovastatin, loviride, loxanast, loxapine, glumic acid, isosulfan blue, isosulpride, isothipendyl, iso loxiglumide, loxoprofen, loxoribine, lozilurea, lubazodone, tiquimide, isotretinoin, isoxaprolol, isoxepac, isoxicam, lubeluzole, lubiprostone, lucanthone, lucartamide, lucimy isoXSuprine, isradipine, israpafant, istrdefylline, itameline, cin, lufenuron, lufironil, lufuradom, luliconazole, lumira itanoXone, itasetron, itaZigrel, itopride, itraconazole, itriglu coxib, lupitidine, luprostiol, lurasidone, lurosetron, lurotote mide, itrocamide, itrocinonide, iturelix, ivbradine, ivarimod, can, lusaperidone, luxabendazole, lydimycin, lymecycline, ivermectin, ivodualine, ixabepilone, izonsteride, josamycin, lynestrenol, lypressin, mabuprofen, mabuterol, madurami kainic acid, kalafungin, kanamycin, kebuZone, keracyanin, cin, mafenide, mafoprazine, mafosfamide, malathion, maley ketamine, ketanserin, ketazocine, ketazolam, kethoxal, lsulfathiazole, malotilate, mangafodipir, manidipine, mani ketipramine, ketobemidone, ketocaine, ketocainol, ketocona faxine, mannomustine, manoZodil, mantabegron, Zole, ketoprofen, ketorfanol, ketorolac, ketotifen, ketotrexate, mapinastine, maprotiline, maraviroc, marbofloxacin, marib khellin, khelloside, kitasamycin, labetalol, labradimil, avir, maridomycin, marimastat, mariptiline, maropitant, mar lachesine, lacidipine, lacosamide, lactalfate, lactilol, lactu oxepin, masoprocol, maxacalcitol, maytansine, mazapertine, lose, ladirubicin, ladostigil, laflunimus, lafutine, laidlomycin maZaticol, mazindol, maZipredone, maZokalim, mebanazine, propionate, lamifiban, lamivudine, lamotrigine, lamitidine, mebendazole, menbenoside, mebeverine, mebeZonium, meb lanatoside, landiolol, lanepitant, lanicemine, laniquidar, hydrolin, mebiquine, mebolazine, mebrofenin, mebutamate, lanoconazole, lanperisone, lanproston, lanreotide, lanSopra mebutizide, mecamylamine, mecarbinate, mecetronium, Zole, lapatinib, lapisteride, laprafylline, lapyrium, lacquini meciadanil, mecinarone, meclinertant, meclizine, meclocy mod, lasalocid, lasinavir, lasofoxifene, latanoprost, lau cline, meclofenamaic acid, meclofenoxate, meclonazepam, dexium, laurcetium, laurocapram, lauroguadine, laurolinium, mecloqualone, meclorisone dibutyrate, mecloxamine, meco lauryl isoquinolinium, lavoltidine, lazabemide, lecimibide, balamin, medazepam, medazomide, medetomidine, mediba ledazerol, ledoxantrone, lefetamine, leflunomide, Zine, medifoxamine, medorinone, medorubicin, lefradafiban, leiopyrrole, lemidosul, lemidipine, leminopra medrogestrone, medronic acid, medroxalol, medroxyproges Zole, lemoxinol, lemuteporfin, lanalidomine, lenampicillin, terone acetate, medrylamine, medrysone, mefeclorazine, lenapenem, leniquisin, leuperone, leptacline, lercanidipine, mefenamic acid, mefenidil, mefenidramium, mefenorex, lergotrile, lerisetron, lesoptiron, lestaurtinib, leteprinim, lete mefeserpine, mefexamide, mefloquine, mefruside, megalo prinim, letimide, letosteine, letraZuril, letrozole, leucino mycin, megestrol, megace, meglitinide, meglucycline, caine, leucocianidol, leucovorin, leurubicin, levalbuterol, meglumine, meglutol, meladrizine, melagatran, melarsom levallorphan, levamfetamine, levamisole, levcromakalim, ine, melarsonyl, melarsoprol, meldonium, melengestrol levcycloserine, levdobutamine, levemoamil, levetiracetam, acetate, meletimide, melevodopa, melinamide, melitracen, levisoprenaline, levlofexidine, levmetamfetamine, levobe melizame, meloxicam, melperone, melphalan, melduinast, taxolol, levobunolol, levobupiacaine, levocabastine, levo meluadrine, mamantine, memotine, menabitan, menadiol. camitine, levodopa, levodropropizine, levofacetoperane, menadione, menadoxime, menatetrenone, menbutone, men levofenfluramine, levofloxacin, levofluraltadone, levoleuco fegol, menglytate, menitrazepam, menoctone, menogaril. Vorin, levomenol, levomepromazine, levomethadone, menobentine, mepazine, mepenZolate, meperidine, mephen levomethadyl acetate, levomethorphan, levometiomeprazine, esin, mephenoxalone, mephentermine, mephenyloin, levomoprolol, levomoramide, levonantradol, levonordefrin, mephobarbital, mebaral, mepindolol, mepiperphenidol. levonorgestrel, levophenacylmorphan, levopropoxyphene, mepiprazole, mepiroXol, mepitioStane, mepivacaine, mepix levopropylcilline, levopropuylhexedrine, levoprotiline, anox, mepramidil, meprednisone, meprobamate, meprochol, levorin, levormeloxifene, levorphanol, levosalbutamol, meproscillarin, meprotixol, meprylcaine, meptazinol, meduli levosemotiadil, levosimendan, levoSulpiride, levothyroxine, dox, meduinol, meduitamium, meduitazine, meradimqate, levotofisopam, levoxadrol, lexipafant, lexithromycin, lex menthyl anthranilate, merafloxacin, meralein, meralluride, US 2010/0226943 A1 Sep. 9, 2010

merbaphen, merbromin, mercaptomerin, mercaptopurine, mitoxantrone, mitoZolomide, mitradipide, mivacurium, mercuderamide, mercufenol, mercumatilin, mergocriptine, mivobulin, mivotilate, mixidine, mizolastine, mizoribine, meribendan, merimepodib, meropenem, mersalyl, mer mobecarb, mobenzoxamine, mocimycin, mociprazine, tialide, mesabolone, mesalamine, meseclaZone, mesocarb, moclonemide, moctamide, modafinil, modaline, modecam mesoridazine, mesipiperone, mespirenone, mestanolone, ide, modipafant, moexipril, moexiprilat, mofarotene, mesterolone, mestranol, meSudipine, meSulergine, mesulfa mofebtaZone, mofegiline, mofeZolac, mofloverine, mofoX mide, meSulfen, meSuprine, metabromsalan, met ine, mofuisteine, molfarnate, molinaZone, molindone, mol butethamine, metabutoxycaine, metacetamol, meta racetam, molsidomine, mometaSone, monalaZone, clazepam, metacresol, metaglycodol, metahexamide, monatepil, monesin, monobenzone, monoctanoin, metalkonium, metalol, metamelfalan, metamfaZone, metam monometacrine, monophosphothiamine, monoxerutin, mon fenpramone, metampicillin, metanixin, metapramine, metap telukast, monterelin, moperone, mopidamol, mopidralazine, roterenol, metaraminol, metaxalone, metaZamide, metazide, moprolol, moquizone, morantel, moraZone, morclofone, matazocine, metbufen, meteneprost, metergoline, metergota morforex, moricizine, morinamide, morniflumate, moro mine, metescufylline, metesculetol, metesind, metethohep cromen, moroxydine, morpheridine, morphine, morSuxim tazine, metformin, methacholine, methacycline, methadone, ide, mosapramine, mosapride, motapizone, motexafin, methadyl acetate, methallenestril, methallibure, methalthiaz motrazepam, motrtinide, moveltipril, moxadolen, moxalac ide, methamphetamine, methandriol, methandrostenolone, tam, moxaprindine, moxastine, moXaverine, moxazocine, methaniazide, methantheline, methaphenilene, methapy moxestrol, moxicoumone, moxidectin, moxifloxacin, moxi rilene, methaqualone, metharbital, methastyridone, meth lubant, moxipraquine, moxirapine, moxisylate, moXnida aZolamide, methdilazine, methenamine, methenolone, meth Zole, moXonidine, moZavaptan, moZenavir, mubritnib, mupi eptazine, methestrol, methetoin, methikcillin, methimazole, rocin, murabutide, muraglitazar, mureletecan, murocamide, methiodal, methiomeprazine, methionine, methisaZone, muZolimine, mycophenolic acid, my fadol, myrophine, methitural, methixene, methocarbamol, methocidin, metho myrtecaine, nabazenil, nabilone, nabitan, naboctate, nabume hexital, methopholone, methoprene, methoserpidine, meth tone, nacartocin, nadide, nadiofloxacin, nadolol, nadoxolol. otrexate, methotrimeprazine, methoxamine, methoXSalen, nafagrel, nafamo.stat, nafarelin, nafazatrom, nafcaproic acid, methoxyphedrine, methoxyphenamine, methoxypromazine, nafcillin, nafenodone, nafenopin, nafetolol, nafimidone, methScopolamine, methSuximide, methyclothiazide, methyl nafiverine, nafiocort, nafomine, nafoxadol, nafoxidine, aminolevulinate, methyl palmoxirate, methyl salicylate, nafronyl, naftalofos, naftaZone, naftifine, naftopidil, naftox methylatropine, methylbenactyzium, methylbenzethonium, ate, naftypamide, naglivan, nalbuphine, , nalidixic methylcromone, methyldesorphine, methyldihydromor acid, nalmefene, nalmexone, nalorphine, naloxone, naltrex phine, methyldopa, methylene blie, methylephedrine, meth one, naminidil, naminterol, namirotene, namoXyrate, nana ylergometrine, methylergonovine, methyllparaben, meth frocin, nandrolone, nanterinone, nantradol, napactadine, ylphenidate, methylprednisolone, methyltestosterone, napamezole, naphazaoline, naphthonone, napirimus, napi methylthiouracil, methynodiol, methyprylon, methysergide, tane, naproxime, naproxen, naproXol, napsagatran, naranol, metiamide, metiapine, metiazinic acid, metibride, meticrane, narasin, naratriptan, nardetoterol, naroparcil, natamycin, metildigoxin, metindizate, metioprim, metioxate, metipirox, nateglinide, navuridine, naxagolide, naxaprosteine, naxifyl metiprenaline, metitepine, metizoline, metkephamid, line, nealbarbital, nebantan, nebidrazine, nebivolol, metochalcone, metocinium, metoclopramide, metocurine, neboglamine, nebracetam, nebramycin, necopidem, nedapl metofenazate, metogest, metolaZone, metomidate, metopi atin, nedocromil, nefazodone, nefiracetam, neflumozide, mazine, metopon, metoprine, metoprolol, metoquizine, nefopam, nelarabine, neldaZosin, neleZaprine, nelfinavir, metoserpate, metostilenol, metoxepin, metrafazoline, metral neltenexine, nelZarabine, nemadectin, nemaZoline, nemi indole, metrazifone, metrenperone, metribolone, metri fitide, nemonapride, memorubicin, neocinchophen, neomy fonate, metrifudil, metrizamide, metrizoate, metronidiazole, cin, neostigmine, nepadutant, nepafenac, nepaprazole, nepi meturedepa, metyrapone, metyrosine, mevastatin, mexafyl castat, nepinalone, nequinate, neramexane, neraminol, line, mexazolam, mexenone, mexiletine, mexiprosil, mexo nerbacadol, neridronic acid, nerisopam, nesapidil, nesiritide, profen, mexrenoate, meZacopride, meZepine, mezilamine, nesosteine, nestifylline, neticonazole, netilmicin, netivudine, meZlocillin, miaanserin, mibefradil, mibolerone, miboplatin, netobimin, netoglitaZone, netupitant, neutramycin, nevi micafungin, miconazole, micronomicin, midaflur, midafotel, parine, nexeridine, nexopamil, niacin, niacinamide, niala midaglizole, midamaline, midaxifylline, midazogrel, mida mide, niaprazine, nibroxane, nicafenine, nicainoprol, nica Zolam, midecamycin, midestein, midodrine, midostaurin, metane, nicanartine, nicaraven, nicarbazin, nicardipine, mifentidine, mifepristone, mifobate, miglitol, miglustat, nicergoline, niceritol, niceverine, niclofolan, niclosamide, mikamycin, milacamide, millacemide, milameline, milataxel, nicoboxil, nicoclonate, nicocodine, nicocortonide, nicocido milemperone, milfasartan, millipertine, miloxacin, milrinone, dine, nicoduozide, nicofibrate, nicofuranose, nifurate, miltefosine, milverine, mimbane, minalrestat, minamestane, nicogrelate, nicomol, nicomorphine, nicopholine, nicorac minaprine, minaxolone, mindodilol, mindoperone, minepen etam, nicorandil, nicothiaZone, nicotredole, nicoXamat, nic tate, minocromil, minocycline, minodronic acid, minopafant, tiazem, nictindole, nidroxy Zone, nifedipine, nifekalant, nife minoxidil, mioflaazine, mipitroban, mipragoside, miproX malol, nifenaZone, niflumic acid, nifungin, nifiradene, ifene, mirfentanil, mirincamycin, miripirium, miriplatin, nifuraldezone, nifuralide, nifuratel, nifuratrone, nifurdazil, mirisetron, miristalkonium, miroprofen, mirosamicin, nifurethaZone, nifurfoline, nifurimide, nifurizone, nifurma mirostipen, mirtazapine, misonidazole, misoprostol, mitem Zole, nifurmerone, nifuroquine, nifuroxazide, nifuroxime, cinal, mitiglinide, mitindomine, mitobronitol, mitocarcin, nifurpipone, nifurpirinol, nifirprazine, nifurquinazol. mitoclomine, mitocromin, mitoflaxone, mitogillin, mitogua nifursemizone, nifursol, nifurthiazole, nifurtimox, nifurtoi Zone, mitolactol, mitomalcin, mitomycin, mitonafide, mito nol, nifurvidine, nifurzide, nigludipine, nihydraZone, podozide, mitoquidone, mitosper, mitolane, mitotenamine, nikethamide, nileprost, nilprazole, niludipine, nilutamide, US 2010/0226943 A1 Sep. 9, 2010 44 nilvadipine, nimaZone, nimeSulide, nimetazepam, nimidane, oxymethalone, oxymorphone, oxypendyl, oxypertine, nimodipine, nimorazole, nimustane, neometacin, niperoti oxyphenbutaZone, oxyphencyclimine, oxyphenisatin, dine, nipradillol, niprofaZone, nitavoline, nirdazole, nis oxyphenonium, oxypurinol, oxypurronium, oxyquinoline, buterol, nisobamate, nisoldipine, nisoxetine, nisterime, nitar oxyridazine, oxysonium, oxytetracycline, oxytocin, OZagrel, Sone, nitazoxanide, nitecapone, nithiamide, nitisinone, oZagamicin, oZolindone, paclitaxel, pacrindolol, pactimibe, nitracrine, nitrafudan, nitralamine, nitramisole, nitradua padimate A, padimate Q, pafenolol, pagoclone, paldimycin, Zone, nitrazepam, nitrefazole, nitrendipine, nitrocefin, nitro palinavir, paliperidone, palmidrol, palmoxirate, palonid clofene, nitrocycline, nitrodan, nitrofurantoin, nitrofuraZone, ipine, palonosertron, palosuran, pamabron, pamaqueside, nitromersol, nitromide, nitromifene, nitroscanate, nitrovin, pamaquin, pamicogrel, pamidronic acid, panadiplon, pan nitroXinil, nitroxoline, nivaZol. nivimedone, nizatidine, amesine, pancopride, pancuronium, panipenem, panomifene, nizofenone, noberastine, nocloprost, nocodazole, nofecam pantenicate, pantethine, panthenol, pantoprazole, ide, nogalamycin, nolatrexed, nolinium, nolomirole. nolpi panuramine, papverine, papveroline, parachlorphenol, tantium, nomegestrol, nomelidine, nomifensine, nonabine, paraflutizide, paramethadione, , nonaperone, nonapyrimine, nonathymulin, nonivamide, paranitrosulfathiazole, paranyline, parapenzolate, para noracymethadol, norbolethone, norbudroine, norcholestenol, propamol, pararosaniline, paraxaZone, parbendazole, parc norclostebol, norcodeine, nordazepam, nordefrin, nordinone, etasal, parconazole, parecoxib, pareptide, parethoxycaine, norelgestromin, norepinepherine, norethandrolone, noethin pargeverine, pargolol, pargyline, paricalcitol, paridocaine, drone, norethynodrel, noreximide, norfenefrine, norfloxacin, parodilol, paromomycin, paroxetine, paroxypropione, norgesterone, norgestimate, norgestomet, norgestrel, norg parsalmide, particin, parvaquone, pasiniazid, pasireotide, estrieneone, norletimol, norlevorphenol, normethadone, nor patamostat, patupilone, paulomycin, paxamate, paZelliptine, morphine, norpipanone, nortetrazepam, nortopixantrone, paZinaclone, paZOxide, paZufloxacin, pecilocin, pecocycline, nortriptyline, norvinisterone, noSantine, noscapine, nosihep pefloxocin, pelanserin, peldesine, peliomycin, pelitinib, peli tide, novobiocin, noxiptiline, noxytiolin, nuclomedone, trexol, pelretin, pelrinone, pelubiprofen, pemedolac, nuclotixene, nufenoXole, nupafant, nuvenZepine, nylestriol, pemerid, pemetrexed, pemirolast, pemoline, penamecillin, nylidrin, nystatin, obidoxime, Ocaperidone, ocfentanil, ocilt penbutolol, penciclovir, pendecamine, pendetide, penfluri ide, ocinaplon, octacaine, octafonium, octamoxin, octapinol, dol, penflutizide, pengitoxin, penicillamine, penicillin G, octatine, octaverine, octaZamide, octenidine, Octicizer, penicillin V, penimepicycline, penimocycline, penirolol, pen octimibate, Octinoxate, octisalate, octocrylene, octodrine, mesterol, penoctonium, penprostene, pentabamate, penta octopamine, octotiamine, octreotide, octriptyline, octriazole, cynium, pentfluranol, pentagastrin, pentagestrone, pentala odalprofen, odapipam, odiparcil, ofloxacin, oftomine, oftas mide, pentamethonium, pentamidine, pentamorphone, ceine, oglu fanide, olaflur, olamufloxacin, olanexidine, olan pentamoxane, pentamustine, pentapiperide, pentapiperium, Zapine, olaquindox, olcegepant, oleandomycin, oletimol, pentaquine, pentazocine, pentetic acid, pentreotide, olmesartan, olopatadine, olpadronic acid, olpimedone, penthienate, penthrichloral, pentiapine, pentifylline, pen olprinone, olradipine, olsalazine, oltipraz, olvanil, omaciclo tigetide, pentisomicin, pentisomeide, pentizidone, pentobar Vir, omapartrilat, omeprazole, omidoline, omigapil, omilox bital, pentolinium, pentolonium, pentomone, pentopril, pen etine, omoconazole, omonasteine, onapristone, ondansetron, torex, pentosalen, pentostatin, pentoxifylline, pentoxyverine, ontazolast, ontianil, opanixil, opaviraline, opiniazide, pentrinitrol, pentylenetetraZol, peplomycin, pepstatin, pera opipramol, opratonium, oraZamide, oraZipone, orbofiban, clopone, peradoxime, perafensine, peralopride, peramivir, orbutopril, orconazole, orientiparcin, oritavancin, orlistat, peraquisin, perastine, peratizole, perazine, perbufylline, per ormaplatin, ormeloxifene, ormetoprin, ornidazole, orni fomedil, perfosfamide, pegolide, perhexyline, periciazine, preessin, ornithine, ornoprostil, orotic acid, orotirelin, orpan perifosine, perimetazine, perindopril, perindoprilat, oxin, orphenadrine, ortataxel, orteteamine, osanetant, osater perisoxal, perlapine, permethrin, peroSpirone, perphenazine, one, oseltamivir, osemoZotan, osmadizone, ospennifene, persilic acid, perZinfotel, petrichloral, peXantel, phanquone, ostreogrycin, OSutidine, otamixaban, otenZepad, oteracil, phenacaine, phenacemide, phenacetin, phenactropinium, otilonium, otimerate, ouabain, oxabolon, oxabrexine, phenadoxone, phenaglycodol, phenamaZoline, phenampro oxaceprol, oxacillin, oxadimedine, oxafloZane, oxaflu mide, phenaphthazine, phenarsone, phenazocine, mazine, oxagrelate, oxalinast, oxaliplatin, oXamarin, oxam phenaZopyridine, phenbutaZone, phencarbamide, phencycli etacin, oxamisole, oxaminiquinem oxanamide, Oxandrolone, dine, phendimetrazine, phenelzine, pheneridine, phenethicil oxantel, oxapadol, oxapium, Oxaprazine, oxaprotiline, lin, pheneturide, phenylglutarimide, phenicarbazide, phenin oxaprozin, oXcarbazole, oxatomide, oxazafone, oxazepam, damine, phenindione, pheniprazine, pheniramine, oxazidone, oxazolam, oxazorone, oXcarbazepine, oxdrala phenisonone, phenmetrazine, phenobarbital, phenobutiodil, Zine, Oxeclosporin, oxedrine, Oxeglitazar, OXeladin, oxen phenomorphan, phenothiazine, phenothrin, phenoxyben dolone, oxepinac, oxetacillin, oxethazine, oxetorone, Zamine, phenoxypropazine, phenprobamate, phenprocou oxfendazole, Oxfenicine, Oxibendazole, oxibetaine, oxiconi mon, phenpromethamine, phensuXimide, phentermine, phen Zole, oxidapamine, oxidronic acid, Oxfentorex, oxifungin, tolamine, phenyl aminosalicylic acid, phenylalanine, oxigluttione, oxilofrine, OXilorphan, oXimonam, OXindanac, phenylbutaZone, phenylephrine, phenylpropanolamine, phe oxiniacic acid, Oxperomide, oxiracetam, oxiramide, oxiso nylthiolone, phenyltoloxamine, phenyracillin, phenyramidol. pred. Oxisuran, oxitefonium, oxitriptan, oxitriptyline, oXtri phenyloin, pnetharbital, pholcodine, pholedrine, phoxim, ponium, OXmetidine, oxodipine, oxogestone, oxolamine, phthalofyne, phthylsulfacetamide, phthalylsulfamethiazole, oXolinic acid, oXomermazine, oXonazine, Oxophenarsine, phthalylsulfathiazole, physostigmine. Phytic acid, phytona Oxoprostol, oxpheneridine, oXprenoate, oXprenolol, Oxtriph dione, pibaxizine, pibecarb, piberaline, piboserod, pibroZe ylline, oxbenZone, Oxybutynin, oxychlorosene, oxycin lesin, pibutidien, picafibrate, picartamide, picenadol, picil chophen, oxyclipine, oxyclozanide, oxycodone, oxydipento orex, piclaimilast, piclonidine, piclopastine, picloxydine, nium, oxyfedrine, Oxymesterone, Oxymetazoline, picobenzide, picodralazine, picolamine, piconol, picoperine, US 2010/0226943 A1 Sep. 9, 2010 picoplatin, picoprazole, picotamide, picotrin, picumast, picu ram, propisergide, propiverine, propizepine, propofol, pro meterol, pidobenzone, pidolacetamol, pidolicaica, pidoti poxate, propoXur, propoxycaine, propoxyphene, propranolol. mod, pifamine, pifinate, pifexole, piflutiXol, piketoprofen, propyl docetrizoate, propyl gallate, propylhexedrine, propy pildralazine, pilocarpine, pilsicamide, pimagedine, pime liodone, propylthiouracil, propyperone, propyphenaZone, clone, pimecrolimus, pimethylline, pimelautide, pimetacin, propyromazine, produaZone, produinolate, prorenoate, pimethixene, pimetine, imetremide, pimilprost, piminodine, proroXan, prScillardin, prospidium, prostalene, proSulpride, pimobendan, pimonidazole, pimozide, pinacidil, pinadoline, proSultiamine, proterguride, protheobromine, prothipendyl. pinafide, pinaverium, pinazepam, pincamide, pindolol. prothixene, protiofate, protionamide, protirelin, protizinic pinokalant, pinolcaine, pinoxepine, pioglitaZone, pipacy acid, protokylol, protoporphyrin, protriptyline, proXZole, cline, pipamazine, pipamperone, pipazethate, pipebuZone, proxibarbal, proxibutene, proxicromil, proxifeZone, proXor pipecuronium, pipemidicacid, pipendoxifene, pipenZolate, phan, proxymetacaine, proxyphylline, proZapine, prucalo pipequaline, piperacetazine, piperacillin, piperamide, piperi pride, prulifloxacin, pruvanserin, pseudoephedrine, puma dolate, piperilate, piperocaine, piperonyl butoxide, piper fentrine, pumaprazole, pumitepa, pumosetrag, puromycin, oxan, piperphenidol, piperylone, pipobroman, pipoctanone, pyrabrom, pyrantel, pyrathiazine, pyrazinamide, pyrazofu pipofezine, piposulfan, pipotiazine, pipOXizine, pipoxolan, rin, pyricarbate, pyridarone, pyridinol, pyridofylline, pyri pipradimadol, pipradrol, pipramadol, pipratecol, piprinhydri dostigmine, pyridoxal, pyridoxamine, pyridoxine, pyril nate, pipocurarium, piprofurol, piproZolin, piquindone, amine, pyrimethamine, pyrimate, pyrinoline, pyrithione, piquizil, piracetam, pirandamine, pirarubicin, piraxelate, pyrithyldione, pyritidium, pyritinol, pyrophenindane, pyrov pirzmonam, piraZolac, pirbenicillin, pirbuterol, pirdonium, alerone, pyroxamine, pyrrobutamine, pyrrocaine, pyrrolif pirenoxine, piremperone, pirezepine, pirepolol, piretanide, ene, pyrroliphene, pyrrolnitrin, pyrroxane, pyrvinium, pirfenidone, pirbendil, piridicillin, piridocaine, piridoxilate, pytamine, quadazocine, quadrosilan, quatacaine, quaZepam, piridironic acid, pirifibrate, pirimiphos-ethyl, pirindazole, quaZinone, quaZodine, quaZolast, quetiapine, quifenadine, pirinixic acid, pirinixil, piriprost, piriqualone, piriSudanol, quiflapon, quillifoline, quilostigmine, quinacainol, quinacil piritramide, piritrexin, pirlimycin, pirlindole, pirmagrel, pir lin, quinacrine, quinagolide, quinaldine blue, quinapril, menol, pirnabine, piroctone, pirodavir, priodomast, pirog quinaprilat, quinaZosin, quibolone, quincarbate, quindecam liride, piroheptine, pirolate, pirolazamide, piromidic acid, ine, quindonium, quindoxin, quinelorane, quinestradol, piroXantrone, piroXicam, piroxicillin, piroXimone, pirozadil, quinestrol, quinethaZone, quinetolate, quinezamide, quinfa pirprofen, pirquinozol, pirralkonium, pirsidomine, pirteni mide, , quingestrone, quinidine, quinine, dine, pitenodil, pitofenone, pituxate, pivagabine, pivampicil quinotolast, quinpirole, quinterenol, quitiofos, quinuclium, lin, pivenfrine, pivopril, pivoxazepam, pixantrone, pizoty quinupramine, quinupristin, quipazine, quisultazine, line, plafbride, plaunotol, plauracin, pleconaril, pleuromulin, rabeprazole, raclopride, ractopamine, radafaxine, rafoxanide, plevitrexed, plicamuycin, plomestane, pobilukast, podilfen, ragaglitazar, ralitoline, raloxifene, raltitrexed, raluridine, podofilox, poldine, polymixin, polythiazide, pomisartan, ramatroban, ramciclane, ramelteon, ramifenaZone, ramipril, ponalrestat, ponaZuril, ponfibrate, porfiromycin, posacona ramiprilat, ramixotidine, ramnodigin, ramnoplanin, ramo Zole, posatirelin, posiZolid, poskine, practolol, pradolfoxa relix, ramosetron, ranelic acid, ranimustine, ranimycin, ranir cin, prajmalium, pralatrexate, pralidoxime, prailmorelin, pral estat, ranitidine, ranolaine, rapacuronium, rasagiline, rasbu nacasan, pramipexole, pramiracetam, pramoxine, prampine, ricase, rathyronine, ravuconazole, raZaxaban, razinodil, pranazepide, pranidipine, prankulast, pranolium, pranopro raZobazam, razoxane, rebimastat, reboxetine, recainam, fen, pranosal, prasterone, praSugrel, pratosartan, pravadoline, reclazepam, regadenoson, reglitazar, relcovaptan, relomycin, pravastatin, praxadine, praZarelix, prazepam, prazepine, remacemide, remifentanil, remikiren, remiprostol, remoX praziquantel, praZitone, prazocillin, prazosin, preclamol. ipride, renanolone, rentiapril, renzapride, repaglinide, rep prednazate, prednazoline, prednicarbate, prednimustine, arixin, repinotan, repirinast, repromicin, reproterol, rescime prednisolamate, prednisolone, prednisone, prednival, pred tol, rescinnamine, resequinil, reserpine, residuimod, nylidene, pregabalin, pregnadiol, pregnenolone, premafloxa resocortolbutyrate, resorantel, resorcinol, retapamulin, retel cin, premazepam, prenalterol, prenisteine, prenoverine, liptine, retigabine, retinol, revaprazan, revatropate, revenast, prenoxdiazine, prenylamine, pretamazium, pretiadoil, preza reviparin, revizinone, revospirone, ribavirin, riboflavin, ribo tide, pribecaine, pridefine, prideperone, pridinol, prifelone, prine, ribostamuycin, ricasetron, ridazolol, ridogrel, rifabu pri?inium, prifuroline, pilocalne, primaperone, primaquine, tin, rifalazil, rifametane, rifamexil, rifamide, rifampin, rifap primidolol, primidone, primycin, prinomastat, prinomide, entine, rifaximin, rilapine, rilmakalim, rilmazafone, prinoXodan, pristinol, pristinamycin, prizidilol, proadifen, rillmenidine, rilopirox, riloZarone, rilpovorine, riluzole, probarbital, probenecid, probicromil, probucol, procaina rimantadine, rimazolium, rimcazole, rimexolone, rimiterol, mide, procaine, procarbazine, procaterol, prochlorperazine, rimonabant, rimoprogin, riodipine, rioprostil, ripazepam, rip procinolol, procinonide, proclonol, procromil, procyclidine, isartan, risarestat, risedronicacid, risocaine, risotilide, rispen procymate, prodeconium, prodilidine, prodipine, prodolic Zepine, risperidone, ristianol, ristocetin, ritanserin, ritometan, acid, profadol, profexalone, proflavine, proflazepam, proga ritipenem, ritobegron, ritodrine, ritolukast, ritonavir, ritropir bide, progesterone, proglumetacin, proglumide, prohep ronium, ritrosulfan, rivaroXaban, rivastigmine, rivoglitaZone, tazine, proligestone, praline, prolintane, prolonium, pro rizatriptan, robalZotan, robenidine, rocastine, rocepafant, mazine, promegestone, promestriene, promethazine, promo rociclovir, rocuronium, rodocaine, rodorubicin, rofecoxib, late, promoxo lane, prontalol, propacetamol, propafenone, rofelodine, rofileponide, roflumilast, rogletimide, rokitamy propagermanium, propamidine, propanidid, propanocaine, cin, rollafagrel, roletamide, rolgamidine, rolicyclidine, roli propantheline, proparacaine, propatyl nitrate, propazola cyprine, rolipram, rollitetracycline, rolodine, rolziracetam, mide, propenidazole, proprintofylline, propenZolate, properi romazarit, romergoline, romifenone, romifidine, romurtide, dine, propetamide, propetamfos, propetandrol, propicillin, ronactolol, ronidazole, ronifibrate, ronipamil, runnel, ropin propikacin, propinetidine, propiomazine, propiocaine, propi irole, ropitoin, ropivacaine, ropizine, roquinimex, rosapros US 2010/0226943 A1 Sep. 9, 2010 46 tol, rosaramicin, rose bengal, rosiglitaZone, roSoxacin, ros loxic acid, SulfamaZone, Sulfamerazine, Sulfameter, Sulfamet tafuroxin, rostaporfin, rosterolone, rosuvastatin, rotamicillin, hazine, sulfamethizole, Sulfamethoxazole, rotigotine, rotoxamine, rotaxate, roXadimate, roXarsone, Sulfamethoxypyridazine, Sulfametmidline, Sulfametrole, Sul roXatidine acetate, roXibolone, roxifiban, roXindole, roXithro famonomethoxine, Sulfamoxole, Sulfanilamide, Sulfanilate, mycin, roXolonium, roXoperone, rubitecan, rubOXistaurin, Sulfaanitran, Sulfaperin, Sulfaphenazole, Sulfaproxyline, Sul rufinamide, rufloxacin, rupatadine, rupintrivir, rutamycin, fapyridine, Sulfaquinoxaline, Sulfarsphenamine, Sulfasala ruvaZone, ruzadolane, Sabarubicin, sabcomeline, sabeluzole, Zine, Sulfasomizole, SulfaSuccinamide, Sulfasymazine, Sul Sabiporide, Saccharin, Safingol, Safirinol, Sagandipine, salac fathiazole, Sulfathiourea, Sulfatolamide, Sulfatroxazole, etamide, Salafibrate, Salantel, Salazodine, Salazosulfadimi Sulfatrozole, Sulfazamet, Sulfinaolol, Sulfinpyrazone, Sul dine, Salazosulfamide, Salazosulfathiazole, Salcaprozoic furam, Sulfisomidine, Sulfisoxazole, Sulfobromophthalein, acid, Salcolex, Salethamide, Salflucerine, Salicyl alcohol, Sali Sulfonterol, Sulforidazine, Sulfosalicylic acid, Sulfoxone, Sul cylamide, Salicylic acid, Salinazid, Salinomycin, Salmefamol. crinat, Sulindac, Sulisatin, Sulisobenzone, Sulmarin, Sulma salmeterol, Salmisteine, Salnacedin, Salprotoside, Salsalate, Zole, Sulmepride, Sulnidazole, Sulocarbilate, Suloctidil, Sulo sameridine, Samixogrel, Sampatrilat, sampirtine, Sancycline, dexide, Sulofenur, Sulopenem, Sulosemide, Sulotroban, Sanfetrinem, sanguinarium, Saperconazole, Saprisartan, Suloxifen, Sulpiride, Sulprosal, Sulprostone, Sultamicillin, Sul sapropterin, saquinavir, Sarafloxacin, Sarakalim, Saralasin, tiame, Sultopride, Sultosilic acid, Sultroponium, Sulukast, Sul sarcolysin, Sardomozide, Saredutant, Saripedem, Sarizotan, Verapride, Sumacetamol, Sumanirole, Sumarotene, Sumatrip SarmaZenil. Samoxicillin, Sarpicillin, Sarpogrelate, tan, Sumetizide, Sunagrel, Suncillin, Sunepitron, Supidimide, saterinone, satigrel, satranidazole, satraplatin, saviprazole, Supalast, Suproclone, Suprofen, Suramin, Suricamide, Suri savoxepin, scopafungin, scopinast, Scopolamine, Secalcif clone, SuritoZole, Suronacrine, Susalimod, SuXemerid, Sux erol, seclaZone, secnidazole, secobarbital, securinine, sede ethonium, SuxibuZone, Symclosene, Synetine, tabilautide, camycin, Sedoxantrone, Seganserin, Segesterone, Seglitide, tabimorelin, tacalcitol, tacapenem, tacedinaline, taclamine, Selamectin, Selgiline, selfotel, Soldenoson, selprazine, Sampi tacrine, tacrolimus, tadalafil, tafluposide, taglutamine, tago mod, sematilide, Semaxanib, semduramicin, semorphone, rizine, talampanel, talampicillin, talaporfin, talastine, talb Semotiadil, Semustine, SenaZodan, Seocalcitol, sepazonium, utal, taleranol, talibegron, talinolol, talipexole, talisomycin, seperidol, sepimostat, Seprilose, seproxetine, sequifenadine, tallimustine, talmetacin, talmetoprim, talnetant, talniflumate, seratrodast, Serazapine, serfibrate, Sergolexole, sermetacin, talopram, talsalate, toloXimine, talsaclidine, talsupram, sertindole, Sertraline, setastine, setzindol, Setipafant, setip taltirelin, taltobulin, taltrimide, taludipine, talviraline, tiline, setoperone, sevitropium, sevopramide, sezalamide, tameridone, tameticillin, tametraline, tamibaroteine, tamiti Sagoside, Sibenadet. Sibopirdine, sibrafiban, Sibutramine, sic nol, tanolarizine, tamoxifen, tampramine, tamsulosin, canin, Sifrprazine, siguaZodan, silandrone, sildenafil, silibi tanaproget, tandamine, tandospirone, tandutinib, taniplon, nin, Silcristin, sildianin, silodosin, silodrate, silperisone, tanomastat, tapentadol, taprizosin, taprostene, tarazepide, siltenZepine, simendan, simetride, Simfibrate, simtraZene, tariquindar, tasosartan, tasuldine, taurolidine, tauromustine, simvastatin, sincalide, sinefungin, sinitrodil, sintropium, tauroselcholic acid, taurosteine, tazadolene, taZanolast, taZ sipatrigine, siramesine, Siratiazem, sirolimus, sisomicin, Sita arotene, taZaSubrate, tazeprofen, tazifylline, taZiprinone, floxacin, Sitalidone, Sitamaquine, sitaxentan, sitofibrate, sito taZobactam, taZofelone, tazolol, taZometime, tebanicline, glusoide, sivelestat, Soblidotin, Sobuzoxane, Solabegron, tebatizole, tebipenem, tebufelone, tebuquine, tecadenoson, Solifenasin, Solimastat, Solpecainol, Solypertine, Somatadine, tecalcet, tecastemizole, teclthiazide, teclozan, tedisamil, tefa soneclosan, Sonepiprazole, sopitazine, Sopromidine, Soqui Zoline, tefenperate, teflufazine, teflutiXol, tegafur, tegaserod, nolol, Sorafenib, Soraprazan, Sorbinicate, Sorbinil, Sorivudine, teglicar, teicopamin, telavancin, telbivudine, telenzepine, Sornidipine, Sotalol, Soterenol, spaglumic acid, sparfloxacin, telinavir, tellithromycin, telmesteine, telmisartan, telox sparfosate, sparsomycin, Sparteine, spectinomycin, antrone, teludipine, temafloxacin, temarotene, tematropium, spiclamine, spiperone, spiradoline, spiramide, spiramycin, temazepam, temefos, temelastine, temiverine, temocapril, spirapril, spiraprilat, spirendolol, spirgetine, spirilene, spir temocaprilat, temocillin, temodox, temoporfin, temozolo iprostil, Spirofylline, spirogermanium, Spiroglumide, spiro mide, temisirolimus, temurtide, tenamfetamine, tenatopra mustine, spironolactone, Spiroplatin, spirorenone, spirotriaz Zole, tendamistat, tenidap, tenilapine, teniloxazine, ine, spiroXasone, spiroXatrine, spiroXepin, Spizofurone, tenilsetam, teniposide, tenivastatin, tenocyclidine, tenofovir, Sprodiamine, squalamine, squalane, stacofylline, stillimycin, tenofovir disoproxil, tenonitrozole, tenosal, tenosiprol, Stannsoprfin, stanolone, stanoaolol, stavudine, Stearylsulfa tenoxicam, tenylidone, teoprantil, teoprolol, tepirindole, tep mide, Steffimycin, Stenbolone, strpronin, Stercuronium, Stev oxalin, teprenone, teprotide, teraZosin, terbequinil, terbin aladil, Stibamine, stilbophen, Stilbamidine, Stilbazium, stilo afine, terbogrel, terbucromil, terbufirol, terbuficin, terbuprol, nium, Strimazole, Stiripentol, stirocamide, Stirofos, terbutaline, terciprazine, terconazole, terdecamycin, teeres streptomycin, streptonicozid, Streptonigrin, Streptozocin, tigmine, terfeadine, terfiavoxate, terfuranol, terguride, teri styramine, SubathiaZone, Subendazole, Succinylcholine, suc flunomide, terikalant, terizidone, terlakiren, terlipressin, cinylsulfathiazole, Succisulfone, Suclofenide. Sucralfate, ternidazole, terodiline, terofenamate, teroxalene, teroxirone, Sucralose. Sucrose octaacetate. SucroSufate, Sudexanox, tertatolol, tesaglitazar, tesicam, tesimide, tesimilifene, Sudoxicam, Sufenatil, Sufotidine, Sufugolix, Sugammadex, tesofensine, testolactone, testosterone, tetomilst, tetrabar Sulamserod, Sulazepam, SulaZuril, Sulbactam, Sulbenicillin, bital, tetrabenazine, tetracaine, tetracycline, tetrahydrozo Sulbenox, Sulbentine, Sulbutiamine, Sulclamine, Sulconazole, line, tetramethrin, tetramisole, tetraxetan, tetrazepam, tetra Sulfabenz, Sulfabenzamide, Sulfabromomethazine, Sulfacar Zolast, tetriprofen, tetrofosmin, tetronasin, tetroquinone, bamide, Sulfacecole, Sulfacetamide, Sulfachlorpyridazine, tetroxoprin, tetrydamine, teverelix, texacromil, tezacitabine, Sulfachrysoidine, Sulfaclomide, Sulfaclorazole, Sulfaclozine, tezosentan, thalidomide, thebacon, thenalidine, thenium, the Sulfacytine, Sulfadiazine, Sulfadimethoxine, Sulfadoxine, Sul nyldiamine, theobromine, theodrenaline, theofibrate, theo faethidole, Sulfaguanidine, Sulfaguanole, Sulfalene, Sulfa phylline, thiabendazole, thiacetarsamide, thialbarbital, thia US 2010/0226943 A1 Sep. 9, 2010 47 mazole, thiamine, thiamiprine, thiamphenicol, thamylal, amternem triaziquone, triazolam, tribendilol, tribenoside, thiaZesim, thiazinamium, thiazolsulfone, thiethyperazine, tribromsalan, tribuZone, tricaprilin, tricetamide, trichlorfon, thihexinol ethylbromide, thimerfonate, thimerosal, thio trichlormethiazide, trichlomethine, triciribine, triclabenda colchicoside, thioctic acid, thiofuradene, thioguanine, thio Zole, triclacetamol, triclazate, triclobisonium, triclocarban, hexamide, thioinosine, thiopental, thiophanate, thiopro triclodazol, triclofenol, triclofos, triclofyllin, triclonide, tri pazate, thioproperazine, thioridazine, thiosalan, thiostrpton, closan, tricyclamol, tridihexethyl, tridolgosir, trientine, tri thiotepa, thiotetrabarbital, thiothixene, thiphenamil, thiphen ethylenemelamine, trifenagrel, trifezolac, triflocin, trifluba cillin, thiram, thonzonium, thonZylamine, thoZalinone, threo Zam, triflumidate, triflomeprazine, trifluperazine, nine, thymocartin, thymoctonan, thymol, thymopentin, thy trifluperidol, triflupromazine, trifluidine, triflusal, trifosmin, motrinan, thyromedan, thyropropic acid, thyroxin, tiacrilast, trigeVolol, trihexylpheidyl, triletide, triloStane, trimaZosin, tiadenol, tiafibrate, tiagabine, tiamenidine, tiametomnium, trimebutine, trimecain, trimedoxime, trimegestone, trimep tiamulin, tianafac, tianeptine, tiapamil, tiapirinol, tiapride, eridine, trimeprazine, trimetazidine, trimethadone, trimetha tiaprofenic acid, tiaprost, tiaramide, tiazofurin, tiaZuril, tia mide, trimethaphan, trimethidinium, trimethobenzamide, tri balosin, tibeglisene, tibenelast, tibenzate, tibeZonium, methoprim, trimetozine, trimetrexZate, trimexiline, tibolone, tibric acid, tibrofan, ticabesine, ticalopride, ticarbo trimipramine, trimoprostil, trimoxamine, trioxifene, triox dine, ticarcillin, ticlatone, ticlopidine, ticolubant, ticrynafen, salen, tripalmitin, tripamide, triparanol, tripelennamine, tri tidembersat, tidiacic acid, tiemonium, tienocarbine, tieno platin, triprolidine, triptorelin, tritoqualine, trixolane, tri pramine, tienoxolol, tifemoxone, tifenaZoxide, tiflamizole, Zoxime, trocimine, troclosene, trodusquemine, trofosfamide, tiflorex, tifluadom, tiflucarbine, tiformin, tifurac, tigecycline, troglitaZone, troleandomycin, tromanttadine, tropabazate, tigemonam, tigestol, tigloidine, tillargenine, tiletamine, tili tropanserin, tropapride, tropatepine, tropenZiline, tropicam dine, tiliquinol, tilisolol, tilmacoxib, tilmicosin, tilnoprofen, ide, tropigline, tropirine, tropisetron, tropodifene, troquida tilomisole, tillorone, tilozepine, tilsuprost, tiludonic acid, tim Zole, trospectomycin, trospium, trovafloxacin, troVirdine, codar, timefurone, timegadine, timelotem, timepidium, timi troxacitabine, troXerutin, troXipide, troXolamide, troxonium, perone, timirdine, timobesone acetate, timofibrate, timolol. troxypyrrolium, truXicurium, truXipicurium, tryparsamide, timonacic, timoprazole, tinabinol, tinazoline, timidazole, tubocurarine, tubulozole, tucaresol, tuclazepam, tulathromy tinisulpride, tinofedrine, tinoridine, tiocarlide, tioclomarol, cin, tulobuterol, tulopafant, turosteride, tuvatidine, tybamate, tioconazole, tioctilate, tiodaZosin, tiodonium, tiomergine, tylosin, tymazolin, tyropanoate, tyrosine, tyrothricin, uben tiomesterone, tioperidone, tiopinate, tiopronin, tiopropam imex, ubidecarenone, ubisindine, ufenamate, ufiprazole, ine, tiospirone, tiotidine, tiotropium, tioxacin, tioxamast, uldazepam, ulifloxacin, uliprisnil, lumespirone, undecylenic tioxaprofen, tioxidazole, tioXolone, tipentosin, tipepidine, acid, unoprostone, upenazime, upidosin, uracil, uracil mus tipetropium, tipifarnib, tipindole, tipranavir, tipredane, tipre tard, urapidil, uredepa, uredofos, urefibrate, ursodiol. nolol, tiprinast, tiprodil, tiprostanide, tiportimod, tiqueside, urulcholic acid, utibapril, utibaprilat, Vadocaine, Valaciclovir, tiquinamide, tiquizium, tiracizine, tirapazamine, tiratricol, Valconazole, Valdecoxib, Valdetamide, Valdipromide, Vale tirilazad, tirofiban, tiropramine, tisartan, tisocalcitate, thamate, vlaganiciclovir, Valine, Valnemulin, Vlanoctamide, tisocromide, tisopurine, tisoquone, tivanidazole, tiviciclovir, valofane, Valomaciclovir, Valperinol, Valproate, Vlaproicacid, tivirapine, tixadil, tixanox, tiXocortol, tiZabrin, tizanidine, valpromide, Valrocemide, valrubicin, Valsartan, Valorcitab tizolemide, tizoprolic acid, tobicillin, toborinone, tobramy ine, Valtrate, Vamicamide, Vancomycin, Vandetanib, Vanep cin, tocamide, tocamphyl, tocladesine, tocofenoxate, tocofi rim, Vanitiolide, VanoXerine, Vanyldisulfamide, Vapiprost, brate, tocophersolan, todralazine, tofenacin, tofetridine, Vapreotide, Vardenfanil, Varenicline, Varespladib, Vatalanib, tofimilast, tofisoline, tofisppam, tolafentrine, tolamolol. Vatanidipine, Vebufloxacin, vecuronium, Vedaclidine, tolaZamide, tolboxane, tolbutamide, tolvapone, tolciclate, Vedaprofen, Velaresol, Velnacrine, Venlafaxine, Venritidine, toldimfos, tolfamide, tolfenamic acid, tolgabide, tolimidone, Verodoline, Veralipride, Verapamil, Verazide, Verilopam, Ver tolindate, toliodium, toliprolol, tolmesoxide, tometin, tolnaf lukast, Verofylline, versetamide, Verteporfin, Vesnarinone, tate, tolnapersine, tolnidamine, toloconium, tolonidine, tolo vestipitant, Vetrabutine, Vidarabine, vigabatrin, VilaZodone, nium, toloxatone, toloxychlorinol, tolpadol, tolpentamide, Vildaglipin, Viloxazine, vinbarbital, vinblastine, vinburnine, tolperisone, tolpiprazole, tolpronine, tolpropamide, tolpyrra Vincamine, Vincanol, Vincofos, Vinconate, Vincristine, Vinde mide, tolduinzole, tolrestat, tolterodine, toltraZuril, tolu burnol, Vindesine, Vinpidine, Vinflunine, Vinformide, Vinfos fazepam, tolvaptan, tolycaine, tomeglovir, tomelukast, tomo iltine, Vinglycinate, Vinleucinol, Vinleurosine, Vinmegallate, glumide, tomoxiprole, tonabersat, tonazocine, topilutamide, Vinorelbine, Vinpocetine, Vinpoline, Vinrosidine, Vintiamol. topiramate, topixantrone, topotecan, toprilidine, topterone, Vintoperol, Vintriptol, vinylbital, Vinzolidine, Viomycin, toquizine, torbafylline, torcetrapib, torcitabine, toremifene, Viprostol, Vicqualine, Viquidil, Virginiamycin, viridofulvin, toripristone, torsemide, tosagestin, tosifen, toSufloxacin, ViroXime, Visnadine, Visnafylline, Vofopiitant, Voglibose, to Sulur, trabectedin, traboXopine, tracazolate, tradecamide, Volazocine, Volpristin, Voriconazole, Vorozole, Voxergolide, tralonide, tramadol, tramaZoline, trandolapril, trandolaprilat, Xaliproden, Xamoterol, Xanomeline, Xanoxic acid, Xanthinol, tranexamic acid, tranilast, transcamide, trantelinium, trany Xantifibrate, Xantocillin, Xanto?yl palmitate, Xemilofiban, cypromine, trapencaine, trapidil, travoprost, traXanox, traXo Xenalipin, Xenazoic acid, Xenbucin, Xenipentone, Xenothio prodil, traZitiline, trazium, traZodone, traZolopride, treben rate, Xenygloxal, Xenylhexenicacid, Xenylropium, Xibenolol. Zomine, trecadrine, trecetilide, trefentanil, trelnarizine, Xibornol, Xidecafiur, Xilobam, Ximelagatran, Ximoprofen, treloxinate, trenbolone, trengestone, trenizine, treosulfan, Ximidamine, Xinomiline, sipamide, Xipranolol. Xorphanol, trepibutone, trepipam, trepirium, treprostinil, treptilamine, Xylamidine, Xylazine, Xylocoumarol. Xylometazoline, Xylox terquisin, tresperimus, trestolone, trethinium, trethocanoic emine, yohimbic acid, Zabicipril, Zabiciprilat, Zacopride, acid, tretinoin, tretinoin tocoferil, tretoquinol, triacetin, tri Zafirlukast, Zafiuleptine, Zalcitabine, Zalderide, Zaleplon, afungin, triamcinolone, triamcinolone acetonide, triamcino Zalospirone, Zalitidine, Zaltoprofen, Zamifenacin, Zanamivir, lone benetonide, triamcinolone furetonide, triampyZine, tri Zanapezil, Zankiren, Zanoterone, Zapizolam, Zaprinast, Zard US 2010/0226943 A1 Sep. 9, 2010 48 averine, Zatebradine, Zatosetron, Zelandopam, Zenarestat, 63. The article of claim 1, where the article comprises an Zenazocine, Zeniplatin, Zepastine, Zeranol, Zetidoline, Zidapa algaecide. mide, Zidometacin, Zidovudine, Zifrostilone, Zilantel, Zilas corb, Zileuton, Zilpaterol, Zimeldine, Zimidoben, Zindotrine, 64. The article of claim 63, where the algaecide is 2.2- Zindoxifene, Zinconazole, Zinostatin, Zinterol, ZinviroXime, dibromo-3-nitrilopropionamide (DNP), methylene bis-thio Zipeprol, Ziprsidone, Zocainone, Zofenopril. Zofenoprilat, cyanate, 5-chloro-2-methyl-4-isothiazolin-3-one/2-methyl Zoficonazole, Zolamine, Zolasartan, Zolazepam, Zolendronic 4-isothiazol in-3-one, tetrahydro-3,5-dimethyl-2H, 1,3,5- acid, Zolenzepine, Zolertine, Zolimidine, Zoliprofen, Zolmi thiadiazine-2-thione, sodium dimethyldithiocarbamate/ triptan, Zoloperone, Zolpidem, Zomebazam, Zomepirac, sodium ethylene bis dithiocarbamate, alkyl dimethylbenzyl Zometapine, Zonampanel, ZonicleZole, Zoniporide, Zonisa amonium chloride family, polyoxyethylene (dimeth mide, Zopiclone, Zopolrestat, Zorbamycin, Zorubicin, ZoSu yliminio) ethylene (dimethyliminio) ethylene dichloride, quidar, Zotepine, ZoticaSone, Zoxazolamine, Zucapsaicin, copper Sulfate, or a combination comprising at least one of the Zuclomiphene, Zuclopenthixol, Zylofuramine, or a combina foregoing algaecides. tion comprising at least one of the foregoing biologically active agents.