US 200700.93462A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0093462 A1 Rogers et al. (43) Pub. Date: Apr. 26, 2007

(54) MULTI-FUNCTIONAL IONIC LIQUID (22) Filed: Oct. 10, 2006 COMPOSITIONS FOR OVERCOMING POLYMORPHISMAND IMPARTING Related U.S. Application Data IMPROVED PROPERTIES FOR ACTIVE PHARMACEUTICAL, BIOLOGICAL, (60) Provisional application No. 60/764,850, filed on Feb. NUTRITIONAL AND ENERGETIC 2, 2006. Provisional application No. 60/724,604, filed INGREDIENTS on Oct. 7, 2005. Provisional application No. 60/724, 605, filed on Oct. 7, 2005. (76) Inventors: Robin D. Rogers, Tuscaloosa, AL (US); Daniel T. Daly, Tuscaloosa, AL (US); Publication Classification Richard P. Swatloski, Tuscaloosa, AL (US); Whitney L. Hough, Albertville, (51) Int. Cl. AL (US); James Hilliard Davis JR. A 6LX 3/555 (2006.01) Mobile, AL (US); Marcin Smiglak, A6II 3L/28 (2006.01) (52) U.S. Cl...... 514/184: 514/185: 514/492

Tuscaloosa, AL (US); Juliusz Pernak, Poznan (PL); Scott K. Spear, (57) ABSTRACT Bankston, AL (US) Disclosed are ionic liquids and methods of preparing ionic Correspondence Address: liquid compositions of active pharmaceutical, biological, NEEDLE & ROSENBERG, PC. nutritional, and energetic ingredients. Also disclosed are SUTE 1 OOO methods of using the compositions described herein to 999 PEACHTREE STREET overcome polymorphism, overcome solubility and delivery ATLANTA, GA 30309-3915 (US) problems, to control release rates, add functionality, enhance efficacy (synergy), and improve ease of use and manufac (21) Appl. No.: 11/545,938 ture. Patent Application Publication Apr. 26, 2007 Sheet 1 of 6 US 2007/0093462 A1 Figure 1

Hex)Sulfacetamide, HexCl & Na Sulfacetamide Dissolution

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Hex Sulfacetamide and DDA Sulfacetamide Dissolution

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Hex Sulfacetamide Time (min) m DDA Sulfacetamide Patent Application Publication Apr. 26, 2007 Sheet 3 of 6 US 2007/0093462 A1

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Figure 4B 100mMMPE

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MULTI-FUNCTIONAL IONIC LIOUID structures and is a widely used reference source in crystal COMPOSITIONS FOR OVERCOMING lography. One survey of the Cambridge Structural Database POLYMORPHISMAND IMPARTING IMPROVED shows that pharmaceutical compounds have been reported to PROPERTIES FOR ACTIVE PHARMACEUTICAL, exist as hemi-hydrates (0.5 water molecules) through BIOLOGICAL, NUTRITIONAL AND ENERGETIC decahydrates (10 water molecules). (Morris, “Structural INGREDIENTS Aspect of Hydrates and Solvates.' Ch. 4 in Polymorphism in Pharmaceutical Solids, in Brittain, H. G., Ed., Vol. 95 of CROSS-REFERENCE TO RELATED Drugs and the Pharmaceutical Sciences, Marcel Dekker, APPLICATIONS Inc., New York, N.Y., 1999, 125-181) 0001. This patent application claims the benefit of prior 0006 The possibility of polymorphism or pseudo-poly ity to U.S. Provisional Application No. 60/764,850, filed morphism may exist for any particular compound, but the Feb. 2, 2006, U.S. Provisional Application No. 60/724,604, conditions required to prepare as yet unknown polymorphs filed Oct. 7, 2005, and U.S. Provisional Application No. or pseudo-polymorphs are not easily determined (see e.g., 60/724,605, filed Oct. 7, 2005, which are each incorporated Bernstein, “Crystal Structure Prediction and Polymorphism, by reference herein in their entireties. Am Crystallographic Assoc Trans, 2004, 39:14-23). The knowledge that one type of polymorph or pseudo-poly FIELD morph of a crystalline form of a compound exists, or that a 0002 The subject matter disclosed herein generally given set of crystallization conditions leads to the production relates to ionic liquids and to methods of preparing ionic of one type of polymorph or pseudo-polymorph, does not liquid compositions of active pharmaceutical, biological, typically allow researchers to predict what other types of nutritional, and energetic ingredients. Also the Subject mat polymorph or pseudo-polymorph might exist, or what type ter disclosed herein generally relates to methods of using the of polymorph or pseudo-polymorph would be produced by compositions described herein to overcome polymorphism, other crystallization conditions (Guillory, “Generation of overcome solubility and delivery problems, to control Polymorphs, Hydrates, Solvates, and Amorphous Solids.” release rates, add functionality, enhance efficacy (synergy), Ch. 5 in Polymorphism in Pharmaceutical Solids, Brittain, and improve ease of use and manufacture. H. G., Ed., Vol. 95 of Drugs and the Pharmaceutical Sciences, Marcel Dekker, Inc., New York, N.Y., 1999, pp. BACKGROUND 183-226). 0003 Polymorphism is the ability of a substance to exist 0007. The existence of various polymorphs or pseudo in two or more crystalline forms that have a different polymorphs can greatly affect a pharmaceutical's perfor arrangement and/or conformation of molecules in a crystal mance since each form can have different physical and line lattice (see e.g., Chawla and Bansal, CRIPS 2004, chemical properties. For example, one particular polymorph 5(1):9-12; Bernstein, “Polymorphism in Molecular Crystals, pseudo-polymorph may be more bioavailable, more stable IUCR Monographs on Crystallography 14, Oxford Science (e.g., longer shelf life), or more easily formulated or tableted Publications, 2002, pp. 1-28, 240-256). It has been estimated than another polymorph. Similarly, one polymorph pseudo that a large number of pharmaceuticals exhibit polymor polymorph may be more active or less toxic than another. phism. For example, 70% of barbiturates, 60% of sulfona Some specific examples of the dramatic difference that can mides, and 23% of steroids are believed to exist in different exist between various pharmaceutical polymorphs are polymorphic forms or “polymorphs' (Haleblian et al., J described in, e.g., Brittain et al., J Pharm Sci 2002, 91: 1573 1580 and Morissette et al., Proc Natl Acad Sci USA 2003, Pharm Sci 1975, 64:1269-1288). 100:218O-21.84. 0004. In some cases, when crystals of a compound are forming (e.g., crystallizing from a solution), solvent mol 0008. The effects of polymorphism and pseudo-polymor ecules may become entrapped or bound within the crystal phism on quality and performance of a drug is widely lattice. The presence of the entrapped solvent molecules may recognized. The exact Solid State polymorph (or pseudo affect the three-dimensional crystal lattice that eventually polymorph) of a compound determines its physical proper crystallizes. The occurrence of a compound (target mol ties such as dissolution rate, Solubility, bioavailability, crys ecule) crystallizing in different three-dimensional lattices tal habit, mechanical strength, etc. (Datta et al., Nature based upon the presence of Solvent molecules has been Reviews-Drug Discovery, 2004, 3:42-57). The delivery of an termed “pseudo-polymorphism.” Akin to polymorphs, such exact dosage in manufacture and the manufacturing process “pseudo-polymorphs,” also known as “solvates’ (or itself often depend on which of several possible polymorphs “hydrates' when the solvent is water), are crystalline solids or pseudo-polymorphs are present. containing either stoichiometric (i.e., whole number ratios of 0009. The variation in properties among different poly target molecules to solvent molecules) or non-stoichiometric morphs (or pseudo-polymorphs) usually means that one (i.e., non-whole number ratios of target molecules to solvent crystalline form is desired or preferred over other forms. molecules) amounts of a solvent incorporated within the Obtaining a particular form can be difficult, however. Typi crystal structure. In general, different crystalline forms of cally, researchers have to experiment with a multitude of molecules (e.g., pharmaceutical compounds) can exist in the variables in crystallization conditions, such as aqueous same or different hydrated or solvated states. Solvent mixtures, amount of water, amount of target com 0005. The Cambridge Structural Database (Allen, “The pound, relative humidity, temperature of incubation, incu Cambridge Structural Database: a quarter of a million crys bation time, etc., in a process characterized by trial and error. tal structures and rising. Acta Crystallographica, 2002, Further, the search for salts of crystalline forms (usually B58, 380-388) is a database of over 300,000 organic crystal sought after to control dissolution rate and solubility) can US 2007/0093462 A1 Apr. 26, 2007 require extensive experimentation. Each salt of a drug or 0015. Another common problem that exists with many each different solvent used to crystallize the drug or a salt of pharmaceuticals is low solubility. Low solubility can make the drug may lead to polymorphs or pseudo-polymorphs that formulating a particular compound difficult, and generally have to be fully investigated and that have different prop low solubility translates into low bioavailability. Much erties (see e.g., Reutzel-Edens et al., “Anhydrates and research is conducted on finding ways to improve a com hydrates of olanzapine: Crystallization, Solid-state charac pounds solubility and availability. Typically methods terization, and structural relationships.'Crystal Growth & include complex delivery devices and chemical modifica Design, 2003, 3:897-907). tions of the drug. 0010 Moreover, the inadvertent production of an undes 0016 Given that polymorphism and pseudo-polymor ired polymorph (or pseudo-polymorph), or the spontaneous phism cannot be predicted; that the exact crystalline State transformation from the desired crystalline form to an affects chemical properties (e.g., dissolution rate, solubility), undesired form, can result in crystalline forms of a drug that biological properties (e.g., bioavailability, pharmacokinet are less effective or even toxic. Thus, the existence and ics), mechanical and physical properties, and manufacturing control of polymorphism and pseudo-polymorphism can be processes, and that polymorphs and pseudo-polymorphs can the biggest challenge to obtaining a drug product of constant inconveniently interconvert, what are needed are composi quality. tions that are at least effective for their intended purpose, but 0011 Another important issue regarding polymorphism can also have controlled and tunable chemical, biological, and pseudo-polymorphism is that there can be considerable and physical properties, are in a form that is not subject to regulatory hurdles for a drug that exists in various crystalline polymorphism, and for which controlled, tunable dissolution forms. The FDA's regulatory guidelines emphasize control and Solubility are possible. Methods of preparing and using of crystal form and the use of appropriate techniques to Such compositions are also needed. Further methods of detect and characterize different forms of a drug (see Guid converting a compound that is difficult to Solubilize into a ance for Industry ANDAS: Pharmaceutical Solid Polymor more soluble form are also desired. The compositions and phism Chemistry, Manufacturing, and Controls Information, methods disclosed herein meet these and other needs includ U.S. Department of Health and Human Services, FDA, ing the introduction of enhanced or new functionality. 2004). Thus, an applicant seeking FDA approval of a drug must demonstrate the ability to maintain a constant crystal SUMMARY line form throughout the life of the product. Such an endeavor is costly and can be extremely difficult or even 0017. In accordance with the purposes of the disclosed impossible. materials, compounds, compositions, devices, and methods, as embodied and broadly described herein, the disclosed 0012 Similar challenges can exist when one seeks Subject matter, in one aspect, relates to compounds and approval of a generic product by filing an Abbreviated New compositions and methods for preparing and using Such Drug Application (ANDA), in which case the applicant must compounds and compositions. In a further aspect, the dis show equivalence between the generic drug and an approved closed Subject matter relates to ionic liquid compositions drug. Such a showing can be complicated when various that can be used for or in biological, pharmaceutical, nutri polymorphic and/or pseudo-polymorphic forms exist for the tional, cosmetic, industrial, and commercial compositions. drug. Methods for making the disclosed ionic liquid compositions 0013 Amorphous forms of drugs are now being studied are also disclosed. Also disclosed are methods of preparing because they are higher energy forms that have higher ionic liquid compositions of active pharmaceutical, biologi dissolution rates and solubilities since there is no lattice cal, nutritional, and energetic ingredients. Also the disclosed structure to overcome or to inhibit solvation (Bernstein, are methods of using the compositions described herein to “Polymorphism in Molecular Crystals.IUCR Monographs overcome polymorphism, overcome solubility and delivery on Crystallography 14, Oxford Science Publications, 2002, problems, to control release rates, add functionality, enhance pp. 240-256). This increasing attention to amorphous forms efficacy (synergy), and improve ease of use and manufac has also shown, however, that the amorphous forms have a ture. tendency to crystallize spontaneously to a lower energy crystalline form, usually at inopportune times. 0018. Additional advantages will be set forth in part in 0014. The phenomenon of polymorphism and pseudo the description that follows, and in part will be obvious from polymorphism is not limited to pharmaceuticals as many the description, or may be learned by practice of the aspects other (if not all) organic and inorganic compounds can described below. The advantages described below will be crystallize into different forms. Thus, the existence of vari realized and attained by means of the elements and combi ous forms of a given compound (e.g., a pesticide, herbicide, nations particularly pointed out in the appended claims. It is nutraceutical, cosmetic, food additive, explosive, etc.) can to be understood that both the foregoing general description result in the same synthetic, analytical, regulatory, and and the following detailed description are exemplary and commercial difficulties that plague the pharmaceutical explanatory only and are not restrictive. industry because of polymorphic and pseudo-polymorphic drugs. In each of these industries, it is not currently possible BRIEF DESCRIPTION OF THE FIGURES to simply alter the chemical nature of the active compound 0019. The accompanying Figures, which are incorpo in order to tune the chemical (e.g., rate of dissolution and rated in and constitute a part of this specification, illustrate solubility) or physical (crystal habit, mechanical strength) several aspects described below. properties. Rather, it is often the strategy to search for polymorphs or pseudo-polymorphs that have the most desir 0020 FIG. 1 is a graph of absorbance at 258 nanometers able “obtainable properties. (nm) over time (minutes) for hexadecylpyridinium sulfac US 2007/0093462 A1 Apr. 26, 2007

etamide (Hex sulfacetamide), hexadecylpyridinium chlo liquid” includes mixtures of two or more Such ionic liquids, ride (HexCl), and sodium sulfacetamide dissolution. reference to “the compound includes mixtures of two or 0021 FIG. 2 is a graph of absorbance at 258 nm over time more such compounds, and the like. for hexadecylpyridinium sulfacetamide and didecyldim 0032) "Optional or “optionally’ means that the subse ethylammonium (DDA) sulfacetamide dissolution. quently described event or circumstance can or cannot 0022 FIG. 3 is a schematic of a computer model used to occur, and that the description includes instances where the identify ion combinations suitable for the disclosed ionic event or circumstance occurs and instances where it does liquid combinations. not. 0033 Ranges can be expressed herein as from “about 0023 FIG. 4A is a graph showing a comparison of one particular value, and/or to “about another particular lidocaine hydrochloride and lidocaine docusate at Imillimo value. When Such a range is expressed, another aspect lar concentration. FIG. 4B is a graph showing a comparison includes from the one particular value and/or to the other of lidocaine hydrochloride and lidocaine docusate at 100 particular value. Similarly, when values are expressed as millimolar concentration. approximations, by use of the antecedent “about, it will be 0024 FIG. 5 is a graph showing molar conductivity for understood that the particular value forms another aspect. It CamimCl solutions at variable temperature; () 291.0 K: will be further understood that the endpoints of each of the (D) 295.3 K; (V) 300.2 K; (A) 305.0 K in water and (()) in ranges are significant both in relation to the other endpoint, DMSO at 295.3 K. and independently of the other endpoint. It is also under stood that there are a number of values disclosed herein, and 0.025 FIG. 6 is a graph showing the difference in calcu that each value is also herein disclosed as “about that lated limiting slope and actually measured (D) CamimCl particular value in addition to the value itself. For example, in HO at 295.3 K: (()) CamimCl in DMSO at 295.3 K. if the value “10' is disclosed, then “about 10' is also disclosed. It is also understood that when a value is dis DETAILED DESCRIPTION closed, then “less than or equal to the value, “greater than 0026. The materials, compounds, compositions, articles, or equal to the value.” and possible ranges between values and methods described herein may be understood more are also disclosed, as appropriately understood by the skilled readily by reference to the following detailed description of artisan. For example, if the value “10” is disclosed, then specific aspects of the disclosed subject matter and the “less than or equal to 10' as well as “greater than or equal Examples included therein. to 10” is also disclosed. It is also understood that throughout the application data are provided in a number of different 0027. Before the present materials, compounds, compo formats and that this data represent endpoints and starting sitions, articles, devices, and methods are disclosed and points and ranges for any combination of the data points. For described, it is to be understood that the aspects described example, if a particular data point '10' and a particular data below are not limited to specific synthetic methods or point “15” are disclosed, it is understood that greater than, specific reagents, as such may, of course, vary. It is also to greater than or equal to, less than, less than or equal to, and be understood that the terminology used herein is for the equal to 10 and 15 are considered disclosed as well as purpose of describing particular aspects only and is not between 10 and 15. It is also understood that each unit intended to be limiting. between two particular units are also disclosed. For 0028. Also, throughout this specification, various publi example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 cations are referenced. The disclosures of these publications are also disclosed. in their entireties are hereby incorporated by reference into 0034. As used herein, by a “subject' is meant an indi this application in order to more fully describe the state of vidual. Thus, the “subject' can include domesticated ani the art to which the disclosed matter pertains. The references mals (e.g., cats, dogs, etc.), livestock (e.g., cattle, horses, disclosed are also individually and specifically incorporated pigs, sheep, goats, etc.), laboratory animals (e.g., mouse, by reference herein for the material contained in them that rabbit, rat, guinea pig, etc.), and birds. “Subject' can also is discussed in the sentence in which the reference is relied include a mammal. Such as a primate or a human. upon. 0035). By “reduce” or other forms of the word, such as General Definitions “reducing or “reduction,” is meant lowering of an event or characteristic (e.g., microorganism growth or Survival). It is 0029. In this specification and in the claims that follow, understood that this is typically in relation to Some standard reference will be made to a number of terms, which shall be or expected value, in other words it is relative, but that it is defined to have the following meanings: not always necessary for the standard or relative value to be 0030 Throughout the description and claims of this referred to. For example, “reduces bacteria growth' means specification the word “comprise' and other forms of the lowering the amount of bacteria relative to a standard or a word, Such as "comprising and "comprises,” means includ control. ing but not limited to, and is not intended to exclude, for 0036). By “prevent” or other forms of the word, such as example, other additives, components, integers, or steps. “preventing or “prevention,” is meant to stop a particular 0031. As used in the description and the appended event or characteristic, to stabilize or delay the development claims, the singular forms “a,”“an, and “the' include plural or progression of a particular event or characteristic, or to referents unless the context clearly dictates otherwise. Thus, minimize the chances that a particular event or characteristic for example, reference to “a composition' includes mixtures will occur. Prevent does not require comparison to a control of two or more such compositions, reference to “an ionic as it is typically more absolute than, for example, reduce. As US 2007/0093462 A1 Apr. 26, 2007

used herein, Something could be reduced but not prevented, herein to specifically refer to a molecule that can be con but something that is reduced could also be prevented. verted to an anion via a chemical reaction (e.g., deprotona Likewise, something could be prevented but not reduced, tion). but something that is prevented could also be reduced. It is understood that where reduce or prevent are used, unless 0044) The term “cation' is a type of ion and is included specifically indicated otherwise, the use of the other word is within the meaning of the term “ion. A “cation' is any also expressly disclosed. molecule, portion of a molecule (e.g., Zwitterion), cluster of molecules, molecular complex, moiety, or atom, that con 0037. By “treat” or other forms of the word, such as tains a net positive charge or that can be made to contain a “treated' or “treatment,” is meant to administer a composi net positive charge. The term “cation precursor is used tion or to perform a method in order to reduce, prevent, herein to specifically refer to a molecule that can be con inhibit, break-down, or eliminate a particular characteristic verted to a cation via a chemical reaction (e.g., protonation or event (e.g., microorganism growth or Survival). The term or alkylation). “control' is used synonymously with the term “treat.” 0045. As used herein, the term “substituted' is contem 0038. By “antimicrobial” is meant the ability to treat or plated to include all permissible Substituents of organic control (e.g., reduce, prevent, inhibit, break-down, or elimi compounds. In a broad aspect, the permissible Substituents nate) microorganism growth or Survival at any concentra include acyclic and cyclic, branched and unbranched, car tion. Similarly, the terms “antibacterial.”“antiviral.” and bocyclic and heterocyclic, and aromatic and nonaromatic “antifungal respectively mean the ability to treat or control Substituents of organic compounds. Illustrative Substituents (e.g., reduce, prevent, inhibit, break-down, or eliminate) include, for example, those described below. The permis bacterial, viral, and filmgal growth or Survival at any con sible Substituents can be one or more and the same or centration. different for appropriate organic compounds. For purposes of this disclosure, the heteroatoms, such as nitrogen, can 0039. It is understood that throughout this specification have hydrogen Substituents and/or any permissible Substitu the identifiers “first and “second are used solely to aid in ents of organic compounds described herein which satisfy distinguishing the various components and steps of the the valencies of the heteroatoms. This disclosure is not disclosed subject matter. The identifiers “first and “second intended to be limited in any manner by the permissible are not intended to imply any particular order, amount, Substituents of organic compounds. Also, the terms 'substi preference, or importance to the components or steps modi tution” or “substituted with include the implicit proviso that fied by these terms. Such substitution is in accordance with permitted Valence of the substituted atom and the substituent, and that the sub Chemical Definitions stitution results in a stable compound, e.g., a compound that 0040. References in the specification and concluding does not spontaneously undergo transformation Such as by claims to parts by weight of a particular element or com rearrangement, cyclization, elimination, etc. ponent in a composition denotes the weight relationship 0046) “A,”“A,”“A,” and “A” are used herein as between the element or component and any other elements generic symbols to represent various specific Substituents. or components in the composition or article for which a part These symbols can be any substituent, not limited to those by weight is expressed. Thus, in a compound containing 2 disclosed herein, and when they are defined to be certain parts by weight of component X and 5 parts by weight Substituents in one instance, they can, in another instance, be component Y. X and Y are present at a weight ratio of 2:5, defined as some other substituents. and are present in Such ratio regardless of whether additional components are contained in the compound. 0047 The term “aliphatic' as used herein refers to a non-aromatic hydrocarbon group and includes branched and 0041. A weight percent (wt.%) of a component, unless unbranched, alkyl, alkenyl, or alkynyl groups. specifically stated to the contrary, is based on the total weight of the formulation or composition in which the 0048. The term “alkyl as used herein is a branched or component is included. unbranched saturated hydrocarbon group of 1 to 24 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl. n-butyl, 0042. The term “ion,” as used herein, refers to any isobutyl, t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl. molecule, portion of a molecule, cluster of molecules, dodecyl, tetradecyl, hexadecyl, eicosyl, tetracosyl, and the molecular complex, moiety, or atom that contains a charge like. The alkyl group can also be substituted or unsubsti (positive, negative, or both (e.g., Zwitterions)) or that can be tuted. The alkyl group can be substituted with one or more made to contain a charge. Methods for producing a charge groups including, but not limited to, alkyl, halogenated in a molecule, portion of a molecule, cluster of molecules, alkyl, alkoxy, alkenyl, alkynyl, aryl, heteroaryl, aldehyde, molecular complex, moiety, or atom are disclosed herein and amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, can be accomplished by methods known in the art, e.g., nitro, silyl, Sulfo-oxo, Sulfonyl, Sulfone, Sulfoxide, or thiol, protonation, deprotonation, oxidation, reduction, alkylation, as described below. etc. 0049. Throughout the specification “alkyl is generally 0043. The term “anion' is a type of ion and is included used to refer to both unsubstituted alkyl groups and substi within the meaning of the term “ion.” An “anion' is any tuted alkyl groups; however, Substituted alkyl groups are molecule, portion of a molecule (e.g., Zwitterion), cluster of also specifically referred to herein by identifying the specific molecules, molecular complex, moiety, or atom that con Substituent(s) on the alkyl group. For example, the term tains a net negative charge or that can be made to contain a "halogenated alkyl specifically refers to an alkyl group that net negative charge. The term “anion precursor is used is Substituted with one or more halide, e.g., fluorine, chlo US 2007/0093462 A1 Apr. 26, 2007 rine, bromine, or iodine. The term “alkoxyalkyl specifically alkoxy, alkenyl, alkynyl, aryl, heteroaryl, aldehyde, amino, refers to an alkyl group that is substituted with one or more carboxylic acid, ester, ether, halide, hydroxy, ketone, nitro, alkoxy groups, as described below. The term “alkylamino” silyl, Sulfo-oxo, Sulfonyl, Sulfone, Sulfoxide, or thiol as specifically refers to an alkyl group that is substituted with described herein. The term “biary1' is a specific type of aryl one or more amino groups, as described below, and the like. group and is included in the definition of aryl. Biaryl refers When “alkyl is used in one instance and a specific term to two aryl groups that are bound together via a fused ring Such as “alkylalcohol is used in another, it is not meant to structure, as in naphthalene, or are attached via one or more imply that the term “alkyl does not also refer to specific carbon-carbon bonds, as in biphenyl. terms such as “alkylalcohol and the like. 0055. The term “cycloalkyl as used herein is a non 0050. This practice is also used for other groups aromatic carbon-based ring composed of at least three described herein. That is, while a term such as “cycloalkyl carbon atoms. Examples of cycloalkyl groups include, but refers to both unsubstituted and substituted cycloalkyl moi are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, eties, the Substituted moieties can, in addition, be specifi cyclohexyl, etc. The term "heterocycloalkyl is a cycloalkyl cally identified herein; for example, a particular substituted group as defined above where at least one of the carbon cycloalkyl can be referred to as, e.g., an “alkylcycloalkyl.” atoms of the ring is Substituted with a heteroatom Such as, Similarly, a substituted alkoxy can be specifically referred to but not limited to, nitrogen, oxygen, Sulfur, or phosphorus. as, e.g., a "halogenated alkoxy, a particular Substituted The cycloalkyl group and heterocycloalkyl group can be alkenyl can be, e.g., an “alkenylalcohol.” and the like. substituted or unsubstituted. The cycloalkyl group and het Again, the practice of using a general term, such as erocycloalkyl group can be substituted with one or more “cycloalkyl, and a specific term, such as “alkylcycloalkyl.” groups including, but not limited to, alkyl, alkoxy, alkenyl, is not meant to imply that the general term does not also alkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, include the specific term. ester, ether, halide, hydroxy, ketone, nitro, silyl, Sulfo-OXo, 0051. The term “alkoxy” as used herein is an alkyl group sulfonyl, sulfone, sulfoxide, or thiol as described herein. bound through a single, terminal ether linkage; that is, an 0056. The term “cycloalkenyl' as used herein is a non “alkoxy” group can be defined as —OA' where A' is alkyl aromatic carbon-based ring composed of at least three as defined above. carbon atoms and containing at least one double bound, i.e., 0.052 The term “alkenyl as used herein is a hydrocarbon C=C. Examples of cycloalkenyl groups include, but are not group of from 2 to 24 carbon atoms with a structural formula limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, containing at least one carbon-carbon double bond. Asym cyclopentadienyl, cyclohexenyl, cyclohexadienyl, and the metric structures such as (AA)C=C(AA) are intended like. The term "heterocycloalkenyl' is a type of cycloalkenyl to include both the E and Z isomers. This may be presumed group as defined above, and is included within the meaning in structural formulae herein wherein an asymmetric alkene of the term “cycloalkenyl, where at least one of the carbon is present, or it may be explicitly indicated by the bond atoms of the ring is Substituted with a heteroatom Such as, symbol C=C. The alkenyl group can be substituted with but not limited to, nitrogen, oxygen, Sulfur, or phosphorus. one or more groups including, but not limited to, alkyl, The cycloalkenyl group and heterocycloalkenyl group can halogenated alkyl, alkoxy, alkenyl, alkynyl, aryl, heteroaryl, be substituted or unsubstituted. The cycloalkenyl group and aldehyde, amino, carboxylic acid, ester, ether, halide, heterocycloalkenyl group can be substituted with one or hydroxy, ketone, nitro, silyl, Sulfo-oxo, Sulfonyl, Sulfone, more groups including, but not limited to, alkyl, alkoxy, sulfoxide, or thiol, as described below. alkenyl, alkynyl, aryl, heteroaryl, aldehyde, amino, carboxy lic acid, ester, ether, halide, hydroxy, ketone, nitro, silyl, 0053. The term “alkynyl' as used herein is a hydrocarbon sulfo-oxo, sulfonyl, sulfone, sulfoxide, or thiol as described group of 2 to 24 carbon atoms with a structural formula herein. containing at least one carbon-carbon triple bond. The alkynyl group can be substituted with one or more groups 0057 The term “cyclic group” is used herein to refer to including, but not limited to, alkyl, halogenated alkyl, either aryl groups, non-aryl groups (i.e., cycloalkyl, hetero alkoxy, alkenyl, alkynyl, aryl, heteroaryl, aldehyde, amino, cycloalkyl, cycloalkenyl, and heterocycloalkenyl groups), or carboxylic acid, ester, ether, halide, hydroxy, ketone, nitro, both. Cyclic groups have one or more ring systems that can silyl, Sulfo-oxo, Sulfonyl, Sulfone, Sulfoxide, or thiol, as be substituted or unsubstituted. A cyclic group can contain described below. one or more aryl groups, one or more non-aryl groups, or one or more aryl groups and one or more non-aryl groups. 0054 The term “aryl as used herein is a group that contains any carbon-based aromatic group including, but not 0.058. The term “aldehyde' as used herein is represented limited to, benzene, naphthalene, phenyl, biphenyl, phe by the formula —C(O)H. Throughout this specification noxybenzene, and the like. The term “aryl also includes “C(O) is a short hand notation for C=O. "heteroaryl, which is defined as a group that contains an 0059) The terms “amine” or “amino” as used herein are aromatic group that has at least one heteroatom incorporated represented by the formula NAAA, where A, A, and A within the ring of the aromatic group. Examples of heteroa can be, independently, hydrogen, an alkyl, halogenated toms include, but are not limited to, nitrogen, oxygen, Sulfur, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and phosphorus. Likewise, the term “non-heteroaryl, which cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group is also included in the term “aryl. defines a group that described above. contains an aromatic group that does not contain a heteroa tom. The aryl group can be substituted or unsubstituted. The 0060. The term “carboxylic acid as used herein is rep aryl group can be substituted with one or more groups resented by the formula—C(O)CH. A "carboxylate” as used including, but not limited to, alkyl, halogenated alkyl, herein is represented by the formula —C(O)O. US 2007/0093462 A1 Apr. 26, 2007

0061 The term “ester” as used herein is represented by group can optionally be substituted with a hydroxyl group, the formula—OC(O)A' or —C(O)OA', where A' can be an an alkoxy group, an amine group, an alkyl group, a halide, alkyl, halogenated alkyl, alkenyl, alkynyl, aryl, heteroaryl, and the like. Depending upon the groups that are selected, a cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocy first group can be incorporated within second group or, cloalkenyl group described above. alternatively, the first group can be pendant (i.e., attached) to 0062) The term “ether as used herein is represented by the second group. For example, with the phrase “an alkyl the formula A'OA, where A' and A can be, independently, group comprising an amino group, the amino group can be an alkyl, halogenated alkyl, alkenyl, alkynyl, aryl, het incorporated within the backbone of the alkyl group. Alter natively, the amino group can be attached to the backbone of eroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or het the alkyl group. The nature of the group(s) that is (are) erocycloalkenyl group described above. selected will determine if the first group is embedded or 0063. The term “ketone' as used herein is represented by attached to the second group. the formula A'C(O)A, where A' and A can be, indepen dently, an alkyl, halogenated alkyl, alkenyl, alkynyl, aryl, 0075) The term “bioactive property” is any local or heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or systemic biological, physiological, or therapeutic effect in a heterocycloalkenyl group described above. biological system. For example, the bioactive property can be the control of infection or inflammation, enhancement or 0064. The term “halide” as used herein refers to the Suppression of growth, action as an analgesic, anti-viral, halogens fluorine, chlorine, bromine, and iodine. pesticidal, herbicidal, or nutrientional action, etc. Many 0065. The term “hydroxyl as used herein is represented examples of bioactive properties are disclosed herein. by the formula —OH. 0076. The term “energetic' is used to described a com 0.066 The term "nitro” as used herein is represented by pound having a heat of combustion of greater than about 500 the formula —NO. kcal/mol (e.g., about 750, 1000, 1500 kcal/mol or more). 0067. The term “silyl as used herein is represented by 0077. Unless stated to the contrary, a formula with chemi the formula - SiAAA, where A, A, and A can be, cal bonds shown only as solid lines and not as wedges or independently, hydrogen, alkyl, halogenated alkyl, alkoxy, dashed lines contemplates each possible isomer, e.g., each alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, enantiomer, diastereomer, and meso compound, and a mix heterocycloalkyl, or heterocycloalkenyl group described ture of isomers, such as a racemic or scalemic mixture. above. 0078 Reference will now be made in detail to specific 0068 The term “sulfo-oxo' as used herein is represented aspects of the disclosed materials, compounds, composi by the formulas —S(O)A'. - S(O)A'. - OS(O).A", or tions, articles, and methods, examples of which are illus —OS(O).OA', where A' can be hydrogen, an alkyl, halo trated in the accompanying Examples. genated alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl group Materials and Compositions described above. Throughout this specification “S(O) is a 0079 Certain materials, compounds, compositions, and short hand notation for S=O. components disclosed herein can be obtained commercially 0069. The term “sulfonyl is used herein to refer to the or readily synthesized using techniques generally known to sulfo-oxo group represented by the formula –S(O)2A', those of skill in the art. For example, the starting materials where A' can be hydrogen, an alkyl, halogenated alkyl, and reagents used in preparing the disclosed compounds and alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, compositions are either available from commercial Suppliers heterocycloalkyl, or heterocycloalkenyl group described such as Aldrich Chemical Co., (Milwaukee, Wis.). Acros above. Organics (Morris Plains, N.J.), Fisher Scientific (Pittsburgh, Pa.), Sigma (St. Louis, Mo.), Pfizer (New York, N.Y.), 0070 The term “sulfonylamino” or “sulfonamide' as GlaxoSmithKline (Raleigh, N.C.), Merck (Whitehouse Sta used herein is represented by the formula —S(O)NH-. tion, N.J.), Johnson & Johnson (New Brunswick, N.J.), 0071. The term "sulfone' as used herein is represented by Aventis (Bridgewater, N.J.), AstraZeneca (Wilmington, the formula A'S(O).A., where A' and A can be, indepen Del.), Novartis (Basel, Switzerland), Wyeth (Madison, N.J.), dently, an alkyl, halogenated alkyl, alkenyl, alkynyl, aryl, Bristol-Myers-Squibb (New York, N.Y.), Roche (Basel, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or Switzerland), Lilly (Indianapolis, Id.), Abbott (Abbott Park, Ill.), Schering Plough (Kenilworth, N.J.), or Boehringer heterocycloalkenyl group described above. Ingelheim (Ingelheim, Germany), or are prepared by meth 0072 The term “sulfoxide’ as used herein is represented ods known to those skilled in the art following procedures by the formula A'S(O)A, where A' and A can be, inde set forth in references such as Fieser and Fieser’s Reagents pendently, an alkyl, halogenated alkyl, alkenyl, alkynyl, for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, 1991); Rodd's Chemistry of Carbon Compounds, Volumes or heterocycloalkenyl group described above. 1-5 and Supplementals (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 0073. The term “thiol” as used herein is represented by 1991); March's Advanced Organic Chemistry, (John Wiley the formula —SH. and Sons, 4th Edition); and Larock’s Comprehensive 0074) “R',”“R,”“R,”“R", etc., where n is some inte Organic Transformations (VCH Publishers Inc., 1989). ger, as used herein can, independently, possess one or more Other materials, such as the active pharmaceutical ingredi of the groups listed above. For example, if R is a straight ents, pesticides, herbicides, and other biological agents chain alkyl group, one of the hydrogen atoms of the alkyl disclosed herein can be obtained from commercial sources. US 2007/0093462 A1 Apr. 26, 2007

0080. In one aspect, disclosed herein are ionic liquid plary properties of ionic liquids are high ionic conductivity, compositions. The term "ionic liquid” has many definitions non-volatility, non-flammability, high thermal stability, wide in the art, but is used herein to refer to salts (i.e., composi temperature for liquid phase, highly Solvability, and non tions comprising cations and anions) that are liquid at a coordinating. For a review of ionic liquids see, for example, temperature of at or below about 150°C. That is, at one or Welton, Chem Rev. 1999, 99:2071-2083; and Carlin et al., more temperature ranges or points at or below about 150° C. Advances in Nonadueous Chemistry, Mamantov et al. Eds. the disclosed ionic liquid compositions are liquid; although, VCH Publishing, New York, 1994. it is understood that they can be solids at other temperature ranges or points. Since the disclosed ionic liquid composi 0085. The specific physical properties (e.g., melting tions are liquid, and thus not crystalline solids, at a given point, viscosity, density, water solubility, etc.) of ionic temperature, the disclosed compositions do not suffer from liquids are determined by the choice of cation and anion, as the problems of polymorphism associated with crystalline is disclosed more fully herein. As an example, the melting Solids. point for an ionic liquid can be changed by making structural 0081. The use of the term “liquid” to describe the dis modifications to the ions or by combining different ions. closed ionic liquid compositions is meant to describe a Similarly, the particular chemical properties (e.g., bioactiv generally amorphous, non-crystalline, or semi-crystalline ity, toxicity, pharmacokinetics, etc.), can be selected by state. For example, while some structured association and changing the constituent ions of the ionic liquid. packing of cations and anions can occur at the atomic level. 0086) The ionic liquid compositions disclosed herein are the disclosed ionic liquid compositions have minor amounts comprised of at least one kind of anion and at least one kind of such ordered structures and are therefore not crystalline of cation. The at least one kind of cation, the at least one kind solids. The compositions disclosed herein can be fluid and of anion, or both can be a pharmaceutical active, a pesticidal free-flowing liquids or amorphous solids Such as glasses or active, a herbicidal active, a food additive, a nutraceutical, or waxes at a temperature at or below about 150° C. In the like, including any combination thereof, as is disclosed particular examples disclosed herein, the disclosed ionic herein. It is contemplated that the disclosed ionic liquid liquid compositions are liquid at the body temperature of a compositions can comprise one kind of cation with more Subject. than one kind of anion (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, or more 0082 Further, the disclosed ionic liquid compositions are different kinds of anions). Likewise, it is contemplated that materials composed of at least two different ions; each of the disclosed ionic liquid compositions can comprise one which can independently and simultaneously introduce a kind of anion with more than one kind of cation (e.g., 2, 3, specific characteristic to the composition not easily obtain 4, 5, 6, 7, 8, 9, 10, or more different kinds of cations). able with traditional dissolution and formulation techniques. Further, the disclosed ionic liquids can comprise more than Thus, by providing different ions and ion combinations, one one kind of anion (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, or more can change the characteristics or properties of the disclosed different kinds of anions) with more than one kind of cation ionic liquid compositions in a way not seen by simply (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10 or more different kinds of preparing various crystalline salt forms. Examples of char cations). Specific examples include, but are not limited to, acteristics that can be controlled in the disclosed composi one kind of cation with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more tions include, but are not limited to, melting, Solubility kinds of anions, 2 kinds of cations with 1, 2, 3, 4, 5, 6, 7, 8, control, and rate of dissolution. It is this multi-nature? 9, 10, or more kinds of anions, 3 kinds of cations with 1, 2, functionality of the disclosed ionic liquid compositions 3, 4, 5, 6, 7, 8, 9, 10, or more kinds of anions, 4 kinds of which allows one to fine-tune or design in very specific cations with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more kinds of desired material properties. anions, 5 kinds of cations with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more kinds of anions, 6 kinds of cations with 1, 2, 3, 4, 5, 0083. It is further understood that the disclosed ionic 6, 7, 8, 9, 10, or more kinds of anions, 7 kinds of cations with liquid compositions can include solvent molecules (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more kinds of anions, 8 kinds water); however, these solvent molecules should not be of cations with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more kinds of present in excess in the sense that the disclosed ionic liquid anions, 9 kinds of cations with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or compositions are dissolved in the solvent, forming a solu more kinds of anions, 10 kinds of cations with 1, 2, 3, 4, 5, tion. That is, the disclosed ionic liquid compositions contain 6, 7, 8, 9, 10, or more kinds of anions, or more than 10 kinds no or minimal amounts of solvent molecules that are free of cations with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more kinds of and not bound or associated with the ions present in the ionic anions. liquid composition. Thus, the disclosed ionic liquid compo sitions can be liquid hydrates or Solvates, but not solutions. 0087. Other specific examples include, but are not limited to, one kind of anion with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more 0084 Ionic liquids have been of general interest because kinds of cations, 2 kinds of anions with 1, 2, 3, 4, 5, 6, 7, 8, they are environmentally-friendly alternatives to organic 9, 10, or more kinds of cations, 3 kinds of anions with 1, 2, Solvents for various chemical processes, e.g., liquid/liquid 3, 4, 5, 6, 7, 8, 9, 10, or more kinds of cations, 4 kinds of extractions, catalysis, separations, and electrochemistry. anions with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more kinds of Ionic liquids have also become popular alternative media for cations, 5 kinds of anions with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or chemical synthesis because of their low volatility and low more kinds of cations, 6 kinds of anions with 1, 2, 3, 4, 5, toxicity. See e.g., Wasserscheid and Keim, Angew Chen Int 6, 7, 8, 9, 10, or more kinds of cations, 7 kinds of anions with Ed Engl, 2000, 39:3772; and Wasserscheid, “Ionic Liquids 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more kinds of cations, 8 kinds in Synthesis,” 1 Ed., Wiley-VCH, 2002. Further, ionic of anions with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more kinds of liquids can reduce costs, disposal requirements, and hazards cations, 9 kinds of anions with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or associated with Volatile organic compounds. Other exem more kinds of cations, 10 kinds of anions with 1, 2, 3, 4, 5, US 2007/0093462 A1 Apr. 26, 2007

6, 7, 8, 9, 10, or more kinds of cations, or more than 10 kinds which they will be used or processed. For example, many of of anions with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more kinds of the disclosed ionic liquid compositions can be used for cations. therapeutic or nutritional purposes in a subject. In this case, 0088. In addition to the cations and anions, the ionic the disclosed ionic liquid compositions can be liquid at the liquid compositions disclosed herein can also contain non subject’s body temperature (e.g., about 37° C. for a human). ionic species, such as solvents, preservatives, dyes, colo Other examples include compositions that can be used as rants, thickeners, Surfactants, viscosity modifiers, mixtures herbicides or pesticides, which are liquid at the temperature and combinations thereof and the like. However, the amount of their use (e.g., ambient temperature). In still other of Such nonionic species is typically low (e.g., less than examples, the disclosed compositions can be liquid at the about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 wt.% based on the total temperature at which they are formulated or processed. weight of the composition). In some examples described 0092. It is understood, however, that the disclosed ionic herein, the disclosed ionic liquid compositions are neat; that liquid compositions can, though need not, be solubilized, is, the only materials present in the disclosed ionic liquids and Solutions of the disclosed ionic liquids are contemplated are the cations and anions that make up the ionic liquid herein. Further, the disclosed ionic liquid compositions can compositions. It is understood, however, that with neat be formulated in an extended or controlled release vehicle, compositions, some additional materials or impurities can for example, by encapsulating the ionic liquids in micro Sometimes be present, albeit at low to trace amounts (e.g., spheres or microcapsules using methods known in the art. less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 wt.% based on Still further, the disclosed ionic liquid compositions can the total weight of the composition). themselves be solvents for other solutes. For example, the 0089. The disclosed ionic liquid compositions are liquid disclosed ionic liquids can be used to dissolve a particular at some temperature range or point at or below about 150° nonionic or ionic pharmaceutical active. These and other C. For example, the disclosed ionic liquids can be a liquid formulations of the disclosed ionic liquids are disclosed at or below about 150, 149, 148, 147, 146, 145, 144, 143, elsewhere herein. 142, 141, 140, 139, 138, 137, 136, 135, 134, 133, 132, 131, 0093. In some examples, the disclosed ionic liquids are 130, 129, 128, 127, 126, 125, 124, 123, 122, 121, 120, 119, not solutions where ions are dissolved in a solute. In other 118, 117, 116, 115, 114, 113, 112, 111, 110, 109, 108, 107, examples, the disclosed ionic liquid compositions do not 106, 105,104, 103, 102, 101, 100, 99,98, 97,96, 95, 94, 93, contain ionic exchange resins. In still other examples, the 92, 91, 90, 89, 88, 87, 86, 85, 84, 83, 82, 81, 80, 79, 78, 77, disclosed ionic liquids are substantially free of water. By 76, 75, 74, 73,72, 71, 70, 69,68, 67, 66, 65, 64, 63, 62,61, substantially free is meant that water is present at less than 60, 59,58, 57, 56, 55, 54, 53, 52, 51, 50, 49, 48, 47, 46, 45, about 10,9,8,7,6, 5, 4, 3, 2, 1, 0.5, 0.25, or 0.1 wt.%, based 44, 43, 42, 41, 40, 39, 38, 37, 36, 35,34, 33, 32, 31, 30, 29, on the total weight of the composition. 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 0094. The disclosed ionic liquid compositions can be 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0, -1, -2, -3, -4, -5,-6, prepared by methods described herein. Generally, the par -7, -8, -9, -10, -11, -12, -13, -14, -15, -16, -17, -18, ticular cation(s) and anion(s) used to prepare the disclosed -19, -20, -21, -22, -23, -24, -25, -26, -27, -28, -29, or ionic liquids are selected as described herein. Then, with the -30°C., where any of the stated values can form an upper particular cation(s) and anion(s) in hand, they can be com or lower endpoint when appropriate. In further examples, the bined, resulting in ionic liquid compositions as disclosed disclosed ionic liquids can be liquid at any point from about herein. Additionally, the method for the preparation of the -30° C. to about 150° C., from about -20° C. to about 140° disclosed ionic liquid compositions can include the reaction C., -10°C. to about 130°C., from about 0°C. to about 120° in which two neutral species: an anion precursor (e.g., in the C., from about 10° C. to about 110° C., from about 20° C. form of an inorganic acid, carboxylic organic acid, non to about 100° C., from about 30° C. to about 90° C., from carboxylic acid, or Zwitterion species) and a cation precur about 40° C. to about 80°C., from about 50° C. to about 70° Sor (e.g., inorganic base, organic base, Zwitterion species) C., from about -30° C. to about 50° C., from about -30°C. are combined resulting in ionic liquid compositions as to about 90° C., from about -30° C. to about 110° C., from disclosed herein. about -30°C. to about 130°C., from about -30°C. to about 150° C. from about 30° C. to about 90° C., from about 30° 0095 Providing ions used to prepare the disclosed ionic C. to about 110° C., from about 30° C. to about 130° C., liquids depends, in one aspect, on the desired properties of from about 30° C. to about 150° C., from about 0° C. to the resulting ionic liquid composition. As described herein, about 100° C., from about 0°C. to about 70° C., from about the disclosed ionic liquid compositions can have multiple 0° to about 50° C., and the like. desired properties, which, at least in part, come from the properties of the cation(s) and/or anion(s) used to prepare 0090. Further, in some examples the disclosed ionic the ionic liquid. Thus, to prepare the disclosed ionic liquids, liquid compositions can be liquid over a wide range of one or more kinds of cations with a desired property(ies) are temperatures, not just a narrow range of, say, 1-2 degrees. provided. One or more kinds of anions with a desired For example, the disclosed ionic liquid compositions can be property(ies) that is similar or different to that of the liquids over a range of at least about 4, 5, 6, 7, 8, 9, 10, or cation(s) can likewise be provided. Of course, providing a more degrees. In other example, the disclosed ionic liquid desired anion(s) and cation(s) can be done in any order, compositions can be liquid over at least about a 11, 12, 13. depending on the preference and aims of the practitioner. For 14, 15, 16, 17, 18, 19, 20, or more degree temperature range. example, a particular cation(s) can be provided and then a Such temperature ranges can begin and/or end at any of the particular anion(s) can be provided. Alternatively, a particu temperature points disclosed in the preceding paragraph. lar anion(s) can be provided and then a particular cation(s) 0091. In many examples disclosed herein the disclosed can be provided. Further, the cation(s) and anion(s) can be ionic liquid compositions are liquid at the temperature at provided simultaneously. US 2007/0093462 A1 Apr. 26, 2007

0096. As noted, providing a suitable ion can be based on properties being combined with an ion having antibacterial selecting an ion that possesses a property that is desired properties. Ionic liquids resulting from Such combinations (e.g., the ion has a property that is desired to be possessed could find uses in wound repair, for example. Still other by the resulting ionic liquid). Examples of properties that examples of desirable combination include ions having could be desired in a Suitable cation and/or anion (and thus therapeutic or prophylactic efficacy being combined with the ionic liquid made therefrom) include, but are not limited ions having taste enhancement properties (i.e., taste modi to, biological, therapeutic, prophylactic, nutritional, pesti fiers). Ionic liquids resulting from this combination can be cidal, and/or herbicidal activity. Inertness, taste, Viscosity useful in enhancing the taste and palatability of medicines. modulation, solubility modulation, stability, and toxicity are Still further examples can include two differently charged other properties of a given ion that could be desired and ions each with similar uses but with different mechanisms of considered. While more specific properties are disclosed action. Specific examples of Such combinations can include, elsewhere herein, the disclosed methods and compositions but are not limited to, combinations of ions with antine are not limited to any particular combination of properties, oplastic properties or antiviral properties. Ionic liquids pre as Such will depend on the preferences and goals of the pared from Such ion combinations can be useful as drug practitioner. “cocktails, where two or more bioactive agents are present 0097. Typically, the desired properties of the cation(s) in a single ionic liquid combination. and anion(s) will be different or complimentary to one 0.100 According to the methods and compositions dis another. In this way, the resulting ionic liquid can possess closed herein, ion identification and combination, as dis multiple desired properties: those properties imparted by the closed herein, can involve any ion, not just ionic drugs, as cation(s) and those imparted by the anion(s). In other words, long as the combination results in an ionic liquid. For Some or all of the ions present in the disclosed ionic liquids example, ions that have pesticidal properties can be com can independently and simultaneously introduce a specific bined with oppositely charged ions having pesticidal, her functionality or property to the disclosed ionic liquid com bicidal, antimicrobial properties, and the like. In other positions. It is this multiple functionality characteristic that examples, ions with antibacterial properties can be com can allow one to fine-tune or design very specific physical, bined with oppositely charges ions that have preservative chemical, and bioactive properties in the disclosed ionic properties, taste modifiers, etc. In still other examples, anion liquid compositions. Additional functionality can be with one therapeutic or prophylactic property can be com obtained by using the disclosed ionic liquid compositions as bined with another therapeutic or prophylactic ion. As solvents to dissolve a solute(s) with another desired prop should be appreciated, the various combinations of ions erty, thus resulting in a solution where the ions of the ionic according to the disclosed methods are numerous, and liquid as well as the solute contribute desired properties to depend only on the desired combination of properties and the composition. General and specific examples of various whether the resulting ion combination is an ionic liquid as combinations of ions and their associated properties are defined herein. disclosed herein. 0101 Specific examples of properties that can be exhib 0098. In some particular examples, one or more ions in ited by the disclosed compositions include antibacterial, the disclosed ionic liquid composition (e.g., the anions, FDA approved dyes, anti-acne, antibiotic, UV blocker, wet cations, or both) can be a pharmaceutical active, e.g., an ting agents, preservative, emollient, anti-inflammatory, and existing drug that is ionic or that can be made ionic. Many Vitamin. drugs exist naturally or at physiological conditions as an ion, or they can be converted to ions via simple chemical 0102 Ions The disclosed ionic liquids contain at least one transformations (e.g., alkylation, protonation, deprotona kind of cation and at least one kind of anion. Examples of tion, etc.). As such, these drugs can be used to prepare an Suitable cations and anions are disclosed herein. It should be ionic liquid composition as disclosed herein. Such drugs can understood that when a particular compound is disclosed as possess any therapeutic or prophylactic activity, many of being a cation, for example, it can also, in other circum which are described herein. Combining such drugs with stances, be an anion and vice versa. Many compounds are other ions to prepare an ionic liquid, as is disclosed herein, known to exist as cations in Some environments and anions can result in the modification and/or enhancement of the in other environments. Further, many compounds are known drug's properties. For example, a first drug ion with a given to be convertible to cations and anions through various property can be combined with an oppositely charged sec chemical transformations. Examples of Such compounds are ond ion with another property to effect the controlled disclosed herein. release, controlled delivery, biological impact, taste, physi cal properties (Stability, Solubility, toxicity, melting point, 0103) The materials, compounds, compositions, and etc.), or to overcome polymorphism in the first drug ion. In components that can be used for, can be used in conjunction this way, new drug compositions can be created by forming with, can be used in preparation for, or are products of the disclosed methods and compositions are disclosed herein. It ionic liquids with functionality crafted into the combination is understood that when combinations, Subsets, interactions, of the ions, as disclosed herein. groups, etc. of these materials are disclosed that while 0099. As another example, the first drug ion may be specific reference of each various individual and collective combined with a second drug ion that has properties com combinations and permutation of these compounds may not plimentary to the first. Examples of this can include, but are be explicitly disclosed, each is specifically contemplated and not limited to, an ion having anesthetic properties being described herein. For example, if an ionic liquid composi combined with an ion having antibacterial properties, an ion tion is disclosed and a number of modifications that can be having anesthetic properties being combined with an ion made to a number of components of the ionic liquid com having coagulation properties, or an ion having coagulation position are discussed, each and every combination and US 2007/0093462 A1 Apr. 26, 2007 permutation that are possible are specifically contemplated 0108. In 1935, Domagk synthesized long-chain QACs, unless specifically indicated to the contrary. Thus, if a class including benzalkonium chloride, and characterized their of cations A, B, and C are disclosed as well as a class of antibacterial activities (Domagk, Deut Med Wochenschr, anions D, E, and F and an example of a ionic liquid A-D is 1935, 61:829). He showed that these salts are effective disclosed, then even if each is not individually recited, each against a wide variety of bacterial strains. This study of the is individually and collectively contemplated. Thus, in this use of QACs as germicides was greatly stimulated. example, each of the ionic liquids A-E, A-F B-D, B-E, B-F, 0.109 Many scientists have focused their attention on C-D, C-E, and C-F are specifically contemplated and should water soluble QACs because they exhibit a range of prop be considered disclosed from disclosure of A, B, and C, D, erties: they are surfactants, they destroy bacteria and fungi, E. and F., and the example ionic liquid A-D. Likewise, any they serve as a catalyst in phase-transfer catalysis, and they Subset or combination of these is also specifically contem show anti-electrostatic and anticorrosive properties. They plated and disclosed. Thus, for example, the Sub-group of exert antibacterial action against both Gram-positive and A-E, B-F, and C-E are specifically contemplated and should Gram-negative bacterial as well as against Some pathogen be considered disclosed from disclosure of A, B, and C, D, species of fungi and protozoa. These multifunctional salts E. and F; and the example combination A-D. This concept have also been used in wood preservation, their application applies to all aspects of this disclosure including, but not promoted in the papers of Oertel and Butcher et al. (Oertel, limited to, steps in methods of making and using the Holztechnologie, 1965, 6:243; Butcher et al., For Prod J. disclosed compositions. Thus, if there are a variety of 1977, 27:19: Butcher et al., J. For Sci, 1978, 8:403). additional steps that can be performed it is understood that each of these additional steps can be performed with any 0110 QACs are also widely used as skin antiseptics, specific aspect or combination of aspects of the disclosed disinfectants, fabric softeners, antistatic agents, cleaning methods, and that each Such combination is specifically agents, and preservatives. Detergent properties and antimi crobial activities of QACs have made them useful for contemplated and should be considered disclosed. general environmental sanitations, for examples, in hospitals 0104 Cations and food production facilities. In pharmacological prepara tions they are used such as mouth rinses, lozenges, sprays 0105 Particular examples of cationic compounds that and gels. can be present in the disclosed ionic liquid compositions are compounds that contain nitrogen atoms. Nitrogen atoms can 0111. In humans and animals QACs have been consid exist or can be converted to positively-charged quaternary ered too toxic for systematic applications, but are accepted ammonium species, for example, through alkylation or to be safe for topical applications. Furthermore, QACs have protonation of the nitrogen atom. Thus compounds that recently been used as penetration enhancers for transnasal possess a quaternary nitrogen atom (known as quaternary and transbuccal drug delivery, as well as in nasal vaccination ammonium compounds (QACs)) are typically cations. (Klinguer et al., Vaccine, 2001, 19:4236). This ability to According to the methods and compositions disclosed penetrate and open cell membrane has been widely used in herein, any compound that contains a quaternary nitrogen drug delivery via liposomes (mainly QACs with two long atom or a nitrogen atom that can be converted into a alkyl chains) and non-viral gene delivery (Liu and Huang, J quaternary nitrogen atom can be a suitable cation for the Contr Rel, 2002, 78:259). Many examples of compounds disclosed ionic liquid compositions. having nitrogen atoms, which exist as quaternary ammo nium species or can be converted into quaternary ammo 0106 QACs can have numerous biological properties nium species, are disclosed herein. that one may desire to be present in the disclosed ionic liquid 0112 In some examples, when the cation is a quaternary compositions. For example, many QACs are known to have ammonium compound, the anion is not an inorganic anion, antibacterial properties. The antibacterial properties of examples of which are disclosed herein. In other examples, QACs were first observed toward the end of the 19" century where the cation is a quaternary ammonium compound, the among the carbonium dyestuffs, such as auramin, methyl anion is not a halide. violet, and malachite green. These types of compounds are effective chiefly against the Gram-positive organisms. Aliphatic Heteroaryls Jacobs and Heidelberger first discovered QACs antibacterial effect in 1915 studying the antibacterial activity of substi 0113 Some specific QACs suitable for use herein are tuted hexamethylene-tetrammonium salts (Jacobs and aliphatic heteroaryls. An aliphatic heteroaryl cation is a Heidelberger, Proc Nat AcadSci USA, 1915, 1:226: Jacobs compound that comprises an aliphatic moiety bonded to a and Heidelberger, J Biol Chem, 1915, 20:659; Jacobs and heteroaryl moiety. In the aliphatic heteroaryl cation, the Heidelberger, J Exptl Med, 1916, 23:569). aliphatic moiety can be any alkyl, alkenyl, alkynyl, cycloalkyl, or cycloalkenyl group, as described herein. Gen 0107 Browning et al. found great and somewhat less erally, the aliphatic moiety can comprise at least 10, at least selective bactericidal powers among quaternary derivatives 12, at least 14, at least 16, at least 18, or at least 20 carbon of pyridine, quinoline, and phenazine (Browning et al., Proc atoms. In other examples, the aliphatic moiety can comprise Roy Soc London, 1922, 93B:329; Browning et al., Proc Roy a mixture of aliphatic groups having a range of carbon Soc London, 1926, 100B:293). Hartman and Kagi observed atoms. For example, the aliphatic moiety can comprise from antibacterial activity in QACs of acylated alkylene diamines 10 to 40, from 12 to 38, from 14 to 36, from 16 to 34, from (Hartman and Kagi, ZAngew Chem, 1928, 4:127). 18 to 32, from 14 to 18, or from 20 to 30 carbon atoms. In US 2007/0093462 A1 Apr. 26, 2007

Some specific examples, the aliphatic moiety can contain 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, -continued 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37,38, 39, 40, 41, 42, R4 R3 R4 R3 R3 R2 43, 44, or 45 carbon atoms, where any of the stated values can form an upper or lower endpoint when appropriate. N N N Y Y O. Y O. Examples of specific aliphatic moieties that can be used 11NZN 1 N2 - 11 NY n include, but are not limited to, decyl, dodecyl (lauryl), R2 tetradecyl (myristyl), hexadecyl (palmity1 or cetyl), octade 1,2,3-TRIAZOLIUM 1,2,4-TRIAZOLIUM cyl (Stearyl), eicosyl (arachidyl), and linolenyl groups, R5 R3 R4 R5 R4 including branched derivatives thereof and any mixtures thereof. In the aliphatic heteroaryl cations, the aliphatic moiety is bonded to a heteroatom in the heteroaryl moiety. Y (O),)-( R R5 J.-- RI -- R6 N R2 R7 N R6 / V 0114 In the aliphatic heteroaryl cation, the heteroaryl R4 R1 Ye R1 R2 moiety can be any heteroaryl moiety as described herein. For THIAZOLIUM PIPERIDINIUM PYRROLIDINIUM example, the heteroaryl moiety can be an aryl group having R5 R4 R4 R3 one or more heteroatoms (e.g., nitrogen, oxygen, Sulfur, phosphorous, or halonium). Examples of specific heteroaryl R6 R3 R R9 moieties that can be used in the aliphatic heteroaryl cations include, but are not limited to, pyrazole, pyridine, pyrazine, R7 C R9 R6 C D. NRI pyrimidine, pryidazine, indolizine, isoindole, indole, inda Zole, imidazole, oxazole, triazole, thiazole, purine, isoquino R8 RI R7 R8 line, quinoline, phthalazine, quinooxaline, phenazine, and QUINOLIUM ISOQUINOLIUM the like, including substituted derivatives and mixtures thereof. In the aliphatic heteroaryl cations, a heteroatom in wherein R' and Rare, independently, a C-C alkyl group the heteroaryl moiety is bonded to the aliphatic moiety. or a C-C alkoxyalkyl group, and R. R. R. R. R. R. When the heteroatom of the heteroaryl is nitrogen, this and R (R-R), when present, are independently H, a C-C, forms a quaternary ammonium cation, as described herein. alkyl, a C-C alkoxyalkyl group, a C-C alkoxy group, or an energetic Substituents such as nitro, amino, cyano, azido, 0115 Further examples of aliphatic heteroaryl cations are alkyl nitro, alkyl amino, alkyl cyano, alkyl azido, alkoxy those having the following structures: nitro, alkoxy amino, alkoxy cyano, and alkoxy azido. In other examples, both R" and R groups are C-C alkyl, with one being methyl, and R-R, when present, are H. Exem R4 R4 plary C-C alkyl groups and C-C alkyl groups include methyl, ethyl, propyl, iso-propyl, butyl, Sec-butyl, iso-butyl, pentyl, iso-pentyl, hexyl, 2-ethylbutyl, 2-methylpentyl, and the like. Corresponding C-C alkoxy groups contain the O R5 Or R5 above C-C alkyl group bonded to an oxygen atom that is R7 O R6 R6 O also bonded to the cation ring. An alkoxyalkyl group con tains an ether group bonded to an alkyl group, and here RI R1 contains a total of up to six carbon atoms. It is to be noted PYRIDINIUM PYRIDAZINIUM that there are two isomeric 1,2,3-triazoles. In some R4 examples, all R groups not required for cation formation can be H. R3 R3 N R4 0.116) The phrase “when present is often used herein in regard to Substituent R group because not all cations have all R6 R5 R6 R5 of the numbered R groups. All of the contemplated cations RI R1 contain at least four R groups, which can be H, although R PYRIMIDINIUM PYRAZINIUM need not be present in all cations. R4 R5 R3 R4 R5 R3 0.117) In one example, all R groups that are not required for cation formation; i.e., those other than R' and R for compounds other than the imidazolium, pyrazolium, and O. O. O. triazolium cations shown above, are H. - Yisry sers 0118. A cation that contains a single five-membered ring R3 R1 R4 that is free of fusion to other ring structures is suitable for IMIDAZOLIUM PYRAZOLIUM OXAZOLIUM use herein. Exemplary cations are illustrated below wherein R", R., and R-R, when present, are as defined before. US 2007/0093462 A1 Apr. 26, 2007 12

of a benzylalkyl amine moiety. The aliphatic moiety can be as described herein. The benzylalkylamine moiety can be a R4 R3 R4 R3 R3 R2 benzyl amine where the amine is bonded to an alkyl or cyclic M alkyl group, as described herein. One or more types of N aliphatic benzylalkyl ammonium cation can be used in the Y Y Y ionic liquid compositions disclosed herein. The aliphatic 11NION 2ns: ~N~- O 11'N,-O). R4 benzylalkyl ammonium cation Suitable for use herein can be prepared by methods known in the art or can be obtained k from commercial sources. 1,2,3-TRIAZOLIUM 1,2,4-TRIAZOLIUM R5 R3 R4 R5 R3 R4 0122) In one aspect, the aliphatic benzylalkyl ammonium cation can be represented by the following formula:

Y {O, Y O, Y {O R1 Y R1 Y YR2 R2 N R5 R4 R3 R1 THIAZOLIUM IMIDAZOLIUM PYRAZOLIUM R5 R3 wherein R' is an aliphatic group, as described above, R' (O), and R'' are, independent of one another, alkyl groups or cyclic alkyl groups as described herein. In some examples, R11 Y one or more of the “R” substituents can be a long chain alkyl R4 group (e.g., the number of carbon atoms is 10 or greater). In OXAZOLIUM other examples, one or more of the “R” substituents can be a short chain alkyl group (e.g., the number of carbon atoms 0119. Of the cations that contain a single five-membered is less than 10). In still other examples, one of the “R” ring free of fusion to other ring structures, an imidazolium Substituents is a long chain alkyl group and the other two cation that corresponds in structure to Formula A is also “R” substituents are short chain alkyl groups. suitable, wherein R', R, and R-R, are as defined before. 0123. In one aspect, the aliphatic benzylalkyl ammonium cation can have any of the aliphatic moieties disclosed herein bonded to any benzylalkyl amine moieties disclosed (A) herein. In some specific examples, R' in the formula of aliphatic benzylalkyl ammonium cation can be an aliphatic group of from 10 to 40 carbon atoms, e.g., a decyl, dodecyl (lauryl), tetradecyl (myristyl), hexadecyl (palmityl or cetyl), octadecyl(stearyl), or eicosyl (arachidyl)group, and R'' and R' can each be, independent of one another, a methyl, ethyl, propyl, butyl, pentyl, or hexyl group. 0.124. In another aspect, the aliphatic benzylalkyl ammo nium cation can include, but are not limited to, alkyl 0120 In a further example, an N,N-1,3-di-(C-C alkyl)- dimethyl benzyl ammonium cations. Specific examples of Substituted-imidazolium ion can be used; i.e., an imidazo lium cation wherein R-R of Formula A are each H, and R' alkyl dimethylbenzyl ammonium cations include, but are and R are independently each a C-C alkyl group or a not limited to, cetyl dimethyl benzyl ammonium, lauryl C-C alkoxyalkyl group. In yet another example, the cation dimethyl benzyl ammonium, myristyl dimethyl benzyl illustrated by a compound that corresponds instructure to ammonium, Stearyl dimethyl benzyl ammonium, and Formula B, below, wherein R-R of Formula A are each arachidyl dimethylbenzyl ammonium. hydrogen and R' is a C-C-alkyl group or a C-C alkoxy 0.125. In yet another aspect, the aliphatic benzylalkyl alkyl group. ammonium cation can include, but are not limited to, alkyl methylethyl benzyl ammonium cations. Specific examples of alkyl methylethylbenzyl ammonium cations include, but (B) are not limited to, cetyl methylethyl benzyl ammonium, lauryl methylethylbenzyl ammonium, myristyl methylethyl Y O benzyl ammonium, Stearyl methylethylbenzyl ammonium, RI N2 in CH and arachidyl methylethylbenzyl ammonium. Dialiphatic Dialkyl Ammonium Aliphatic Benzylalkyl Ammonium 0.126 Still further examples of QACs that can be used in 0121 The disclosed ionic liquid compositions can also the disclosed ionic liquid compositions are dialiphatic comprise an aliphatic benzylalkyl ammonium cation. An dialkyl ammonium cations. A dialiphatic dialkyl ammonium aliphatic benzylalkyl ammonium cation is a cation that cation is a compound that comprises two aliphatic moieties comprises an aliphatic moiety bonded to the nitrogen atom and two alkyl moieties bonded to a nitrogen atom. The US 2007/0093462 A1 Apr. 26, 2007

aliphatic moieties can be the same or different and can be 0.132. Futher examples of cations include (2-hydroxyeth any aliphatic group as described above. The alkyl moieties yl)dimethylundecyloxymethylammonium, (2-acetoxyethyl can be the same or different can be any alkyl group as )heptyloxymethyldimethylammonium, and (2-acetoxyethyl described above. In the disclosed dialiphatic dialkyl ammo )dodecyloxymethyldimethylammonium, mepenZolate, niums cations, the two aliphatic moieties can have 10 or Sulfathiazole, thimerosal, and valproic acid. more carbon atoms and the two alkyl moieties can have less 0133. In other examples, the cation can be an energetic than 10 carbon atoms. In another alternative, the two ali cation as disclosed in Katritzky et al., “ILs Based on phatic moieties can have less than 10 carbon atoms and the Energetic Imidazolium Cations: Nitro- and Nitrile-substi two alkyl moieties can have 10 or more carbon atoms. One tuted N,N' Dialkylimidazolium Salts' New J Chem 30:349, or more types of dialiphatic dialkyl ammonium cations can 2006, which is incorporated by reference herein at least for be used in the ionic liquid compositions disclosed herein. its teachings of energetic ions. 0127. In some particular examples, the dialiphatic dialkyl ammonium cation can be di-dodecyl dimethyl ammonium, 0134) Anions di-tetradecyl dimethyl ammonium, dihexadecyl dimethyl 0.135 Particular examples of anionic compounds that can ammonium, and the like, including combinations thereof. be present in the disclosed ionic liquids are compounds that contain oxygen atoms. Oxygen atoms can exist or can be Tetraalkyl Ammonium converted to negatively charged, anionic species, for example, through deprotonation of alcohols or acids, 0128. The disclosed ionic liquid compositions can also through saponification of esters, or through alkylation of comprise a tetraalkyl ammonium cation. Suitable tetraalkyl ketones. Likewise, compounds that contain Sulfur atoms can ammonium cations comprise four alkyl moieties, as dis also exist or be converted to anionic species through similar closed herein. In one example, a tetraalkyl ammonium reactions. Still further, compounds that contain nitrogen cation can comprise one long chain alkyl moiety (e.g., 10 or atoms, especially nitrogen atoms adjacent to electron with more carbon atoms in length) and three short chain alkyl drawing groups or resonance stabilizing structures, can be moieties (e.g., less than 10 carbon atoms in length). converted to anions through deprotonation. According to the 0129. Some specific examples of tetraalkyl ammonium methods and compositions disclosed herein, any compound cations that can be included in the disclosed ionic liquid that contains an oxygen, Sulfur, or nitrogen atom can be a compositions include, but are not limited to, cetyl trimethyl Suitable anion for the disclosed ionic liquid compositions. ammonium, lauryl trimethyl ammonium, myristyl trimethyl 0.136. Other suitable anions include, but are not limited ammonium, Stearyl trimethyl ammonium, arachidyl trim to, halides (e.g., fluoride, chloride, bromide, and iodide), ethyl ammonium, or mixtures thereof. Other examples Sulfates (SO), carbonates, bicarbonates, phosphates, phos include, but are not limited to, cetyl dimethylethyl ammo phates, nitrates (NO), nitrites (NO), acetates (CHCO nium, lauryl dimethylethyl ammonium, myristyl dimethyl ), and the like. Other examples of anions include, but are not ethyl ammonium, Stearyl dimethylethyl ammonium, limited to PF, that is immiscible in water and BF that is arachidyl dimethylethyl ammonium, or mixtures thereof. miscible in water depending on the ratio of ionic liquid to water, system temperature, and alkyl chain length of cation. Other Cations Other anions include triflate (TfG); CFSO), nonaflate (NfO; CF (CF)SO), bis(triflyl)amide (Tf,N: 0130. Other cations that are suitable for use in the dis (CFSO)N), trifluoroacetate (TA; CFCO), and hep closed methods and compositions are compounds that con taflurorobutanoate (HB; CF (CF)SO). Other types of tain metals. According to the methods and compositions ionic liquids include haloaluminates, such as chloroalumi disclosed herein, any compound that contains a metal atom nate. can be a Suitable cation. Organometallic compounds or metal complexes commonly have one or more metal atom in 0.137 Other suitable anions contemplated herein are sac a positive oxidation state. Examples of metals that can be charin and acesulfame. Saccharin, as an alkali metal salt, and present in a suitable cation include, but are not limited to, acesulfame (6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one lithium, Sodium, potassium beryllium, magnesium, calcium, 2,2-dioxide), which has previously only been offered as strontium, chromium, manganese, iron, cobalt, nickel, cop potassium salt, are in widespread use in foodstuffs as non per, and zinc. Silver nanoparticles can also be used. nutritive Sweeteners. Such anions can be used when one Examples of Suitable organometallic cations include, but are desires to prepare an ionic liquid composition that has not limited to, metallocenium, alkylgermanyl, alkyltin, or Sweetness as one of its desired properties. For example, alkylsilyl (e.g., trimethylsilylium, triethylsilylium, tris(trim saccharin and acesulfame can be combined with pharma ethylsilyl)silylium, tribenzylsilylium, triphenylsilylium, tri ceutically active cations to prepare Sweet tasting ionic cyclohexylsilylium, and dimethyloctadecylsilylium). liquids that have pharmaceutical activity. 0131) Another suitable group of quaternary ammonium 0.138 Specific examples of other anions include piper cations are those that have been prepared by esterifying a acillin, folic acid, ibuprofen, fast green FCF, docusate, compound containing a carboxylic acid moiety or transes acesulfamate, penicillin G, Colawet MA-80, salicylic acid, terifying a compound with an ester moiety with a choline saccharinate, Sulfacetamide, naproxen, benzoate, diclofenac, moiety. Such choline esters can be biofriendly, permanent and trans-cinnamic acid. ions that are amenable to being added to various compounds 0.139. Other suitable anions include, but are not limited while still being easily cleavable under physiological con to. Substituted and un-substituted imidazolates, 1,2,3-triaz ditions. The choline esters can be used to increase the olates, and 1,2,4-triazolates, benzimidazolates, benz-1.2.3- solubility and bioavailability of many neutral compounds. triazolates, as shown below: US 2007/0093462 A1 Apr. 26, 2007 14

active. Pharmaceutical actives that exist as ions or can be converted to ions, and which are suitable for use in preparing R13 R13 R 14 the disclosed ionic liquid compositions, include the follow N N N ing categories and specific examples. It is not intended that \ W { the category be limited by the specific examples. Those of ordinary skill in the art will be able to readily identify those R 14 > R 14 - -- pharmaceutical actives that can be used in the disclosed imidazolate 1,2,3-triazolate 1,2,4-triazolate methods and compositions. For example, one can identify a R13 R13 compound with a given property or activity by consulting various sources, such as the Merck Index (13" Edition, R 14 N R 14 N Wiley, 2001), The United States Pharmacopeia-National Formulary (USP-NF), and the FDA's Orange book, which MX- R17 MY are each incorporated by reference herein at least for their R15 N R15 N teachings of pharmaceutical actives. Once a compound with a desired property is identified, the skilled artisan can R 16 R 16 determine whether the compound is ionic or can be made benzimidazolate benz-1,2,3-triazolate ionic. Such determinations can be performed based on the compounds structure, which can readily be determined by consulting the sources mentioned herein or experimentally. wherein R', R', R', R', R'7, (R-7), when present, are Knowing a compounds structure can readily reveal if the independently H, a C-C alkyl, a C-C alkoxyalkyl group, compound is ionic. In fact, many pharmaceutical actives a C-C alkoxy group, or energetic Substituents like nitro, exist as salts and are thus Suitable for use in preparing the amino, cyano, azido, alkyl nitro, alkyl amino, alkyl cyano, disclosed ionic liquid compositions. Further, if a compound alkyl azido, alkoxy nitro, alkoxy amino, alkoxy cyano, and is not ionic, but contains an ion forming moiety (e.g., alkoxy azido. Exemplary C-C alkyl groups and C-C, nitrogen, oxygen, Sulfur, or metal atoms, as described alkyl groups include methyl, ethyl, propyl, iso-propyl, butyl, herein), the compound can be converted to an ion and then sec-butyl, iso-butyl, pentyl, iso-pentyl, hexyl, 2-ethylbutyl, combined with a suitable counterion to prepare the disclosed 2-methylpentyl, and the like. Corresponding C-C alkoxy ionic liquid compositions. Those of ordinary skill in the art groups contain the above C-C alkyl group bonded to an will recognize numerous other compounds that fall within oxygen atom that is also bonded to the cation ring. An the categories and that are usefull according to the disclosed alkoxyalkyl group contains an ether 10 group bonded to an compositions and methods. alkyl group, and here contains a total of up to six carbon atoms. It is to be noted that there are two isomeric 1,2,3- 0144. Some specific examples of pharmaceutical actives triazoles. In some examples, all R groups not required for that can be used in the disclosed ionic liquids include, but are anion formation can be H. not limited to, aspirin, LIBRIUMTM, isoniazid, penicillin, PRONTOSILTM, cisplatin, 6-mercaptopurine, RIT 0140. Further examples of suitable energetic anions are UXANTM, TAXOLTM, phenobarbital, PROZACTM, disclosed in Katritzky et al., “ILs Based on Energetic ALLEGRATM, VIOXXTM, quinine, ivermectin, L-dopa, Azolate Anions.'Chen Eur) 12:4630, 2006, which is incor THORAZINETM, salvarsan, TAGAMETTM, AZT, crixivan, porated by reference herein at least for its teachings of salbutamol, digoxin, fluride, LOVASTATINTM, erythropoi energetic anions. etin, hydrocortisone, insulin, oral contraceptives, oxytocin, PREMARINTM, RU-486, thyroxine, thalidomide, cyclospo Compound that Exist that as Both: Anion or Cation rine, fentanyl, methadone, morphine, botox, Vitamins, 01.41 Examples of compounds that exist as cations in FOSAMAXTM, RITALINTM, and VIAGRATM, including Some environments and anions in other environments ionic derivatives thereof. include, but are not limited to, 1,3-dimethylimidazolium, 0.145) Other examples of pharmaceutical active ions or 1-butyl-3-methylimidazolium, 1,2,3-triazolium, tetrazo pharmaceutical actives that can be made ionic include, but lium, 1,2,4-triazolium, 1,3-dimethyl-1,2,3-triazolium, and are not limited to, pantoprazole, sold under the trade names 1,3-dimethyl-4-nitroimidazolium, which exist as a cations, PROTONLXTM and PANTOZOLTM, and rabeprazole, sold and 4-nitroimidazolate, 4,5-dinitroimidazolate, 3,5-dinitro under the trade names ACIPHEXTM and PARIETTM, which 1,2,4-triazolate, tetraZolate, 5-aminotetraZolate, 2-nitroimi are used to treat gastrointestinal disorders. Risedronate, sold dazolate, which exist as an anion. Those separate ions can under the trade name ACTONELTM, and alendronate, sold still form single product ionic liquids. under the trade name FOSAMAXTM, are used to treat 0142. Examples of compounds that can change from an osteoporosis and are further examples of Suitable com anion in one environment to a cation in another environment pounds that can be used to prepare the disclosed ionic liquid due to chemical modifications are the sulfur ylides through compositions. Further examples include losartan, Sold under the reaction of a sulfide with methyliodide to form the the trade names NU-LOTANTM, COZAARTM, and HYZ Sulfonium ion. AARTM, and fosinopril, sold under the trade name MONO PRILTM, which are used to treat hypertension and are other Specific Examples of Pharmaceutical Actives examples of Suitable compounds that can be used to prepare the disclosed ionic liquid compositions. Atorvastatin, sold 0143. When pharmaceutical activity is a desired property under the trade name LIPITORTM, and pravastatin, sold of the disclosed ionic liquids, one or more of the ions in the under the trade name PRAVACHOLTM, are used to treat disclosed ionic liquid compositions can be a pharmaceutical cholesterol and are further examples of suitable compounds US 2007/0093462 A1 Apr. 26, 2007 15 that can be used to prepare the disclosed ionic liquid 0146 The following table illustrates further examples of compositions. A further example is montelukast, which is pharmaceutical actives that are ionic or can be made ionic used to treat asthma and is sold under the trade name and combined with other ions to form the disclosed ionic SINGULAIRTM. liquid compositions.

TABLE 1.

Name Compound MP Patent No. Other Names Function: Abortifacient Interceptive 66-68 U.S. Pat. PGE2, U-12062, No. Cerviprost, 3598858 Minprostin E2, Prepidil, Propess, Prostarmon-E, Prostin

Prosta 25-35 U.S. Pat. PGF2A, U-14583, glandin No. Enzaprost F. F2A 3657327 Glandin, Prostarmon F

Sulprostone U.S. Pat. Nalador No. 4024179

Function: ACE-Inhibitor (Antihypertensive)

Cetapril 155- U.S. Pat. Alacepril 1560 No. 4248883

Benzaepril 148– U.S. Pat. 149 No. 441052O

Captopril 103- U.S. Pat. Acediur, Acepril, 104° Nos. Alopresin, 4046889 Acepress, 4105776 Capoten, Captolane, Captoril, Cesplon, Dilabar, Garranil, Hipertil, Lopirin, Lopril, Tensobon, Tensoprel US 2007/0093462 A1 Apr. 26, 2007 16

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: A-Adrenergic Agonist

Methyl U.S. Pat. Forthane hexaneamine Nos. 23S0318 2386273

Synephrine OH 184– DE 566578 Analeptin, 1850 Ethaphene, Oxedrine, Parasympatol, CH3 Simpalon, Synephrin, Synthenale HO

Function: B-Adrenergic Agonist

Isoetharine 212– DE 6386SO WIN-3046, 213 Dilabron, Neoisuprel

97 990 JP 612921

CH

Function: A-Adrenergic Blocker

Tamsulosin 228 U.S. Pat. Flomaz, Harnali, 230° No. Omnic, Pradif 4703063

Tolazoline 1749 U.S. Pat. H Lambral, Priscol, N No. Priscoline, Vasco 2161938 Dilatan HCI N

Function: B-Adrenergic Blocker

Bufuralol 146 U.S. Pat. Angium No. 3929836 US 2007/0093462 A1 Apr. 26, 2007 17

TABLE 1-continued

Name Compound MP Patent No. Other Names

Nadoxolol 1889 U.S. Pat. Bradyl No. 3819702

Function: Analgesic (non-narcotic)

Acetylsalicyl 1549 Salicylic acid

Ammonium Salicylate COONH4+

OH

Function: Anesthetic (Intravenous)

Buthalital Baytinal, Buthaliton Sodium Sodium, Thialiso bumalnatrium, Transithal, Ulbreval

Thiopental U.S. Pat. Sodium Nos. 2153729 2876225 3109001

Function: Anesthetic (Local)

Isobutyl p- 65o Cycloform, Isobutyl Amino- O Kelofom, Isocaine benzo ate O~ CH3 NH US 2007/0093462 A1 Apr. 26, 2007 18

TABLE 1-continued

Name Compound MP Patent No. Other Names Phenol OH

Function: Anorexic

Clortermine 116– U.S. Pat. NH2 118 No 3415937 CH, CH C

Fenproporexprop 126 U.S. Pat. 127C No. N-1NN 3485924 CH

Function: Antacid

Dermatol

Function: Anthelmintic (Cesodes) Nicosamide 225 U.S. Pat. OH 230° Nos. C 3079297 H 3 113067 N C

O NO

Pelletierine H Punicine N CH

O

Function: Anthelimintic (Nematodes) Dithiazanine U.S. Pat. Anelmid, Iodide No. Anguifugan, 2412815 Delvex, Dejo, Deselmine, Dilombrin, Dizan, Nectocyd, Partel, Telmicid, Telmid

Thia 3O4 U.S. Pat. Thibenzole, bendazole 305 No. Equizole, 3O17415 Mertect, Storite, TBZ, Tecto US 2007/0093462 A1 Apr. 26, 2007 19

TABLE 1-continued

Name Compound MP Patent No. Other Names Function: Anthelmintic (Schistosoma) Antimony Sodium Thio glycolate

Niridazole 260- BE 632989 Ba-32644, Ciba 262 32644-Ba, Ambilinar

Function: Antiacne

Isotretinoin 174 U.S. Pat. Accitame, Isotrex, 175o No. Oratane, Roaccutane 45565.18

Function: Antiallergic

Lodoxamide 2120 U.S. Pat. No. 39936.79

Ramatroban 134- U.S. Pat. 135° No. 4965258

Function: Antialopecia Agent

Finasteride -2S7 U.S. Pat. Chibro-Proscar, No Finasid, Propecia, 476OO71 Proscar, Prostide US 2007/0093462 A1 Apr. 26, 2007 20

TABLE 1-continued

Name Compound MP Patent No. Other Names

Minoxidi 248 U.S. Pat. Alopexil, Alostil, Nos. Loniten, Lonolox, 3382247 Minoximen, 3644364 Normoxidil, Prexidil, Regaine, Rogaine, Tricoxidi

Function: Antiamebic

Carbarisone 1749 JP S84418 Amabevan, Amebian, Amibiarson, Arsambide, Carb-O- Selo, Histocarb, Fenarsone, Leucarsone, Aminarsone, Amebarsone

Diphetarsone Amebarsin, Bemarsal, Rodameb

Function: Antiandrogen

Flutamide 1115- U.S. Pat. Drogenil, Eulexin, 112.5° No. Euflex, Flucinom, 384.7988 Flutamin, Fugerel

Nilutamide 149° U.S. Pat. RU-23908, No. Anandron, 4097578 Nilandron US 2007/0093462 A1 Apr. 26, 2007 21

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: Antianginal

Nicorandil 92-93 U.S. Pat. Adamcor, Ikorel, No. Perisalol, Sigmart 42OO640

OZagrel 223 224

Bunitrolol 163- U.S. Pat. 1650 No. 3541130

Ipratropium 230– U.S. Pat. Atem, Atrovent, Bromide 232 o No. Bitrop, 3505337 Itrop, Narilet, Inatec

Function: Anti-arteriosclerotic

Pyridinol 136 Anginin, Carbamate 1370 Angioxione, Aterosan, Atower, Cicloven, Colesterinex, Duvaline, Morecil, Prodectin, Ravenil, Sospitan, Vasagin, Vasapril, Vasocil, Vasoverin US 2007/0093462 A1 Apr. 26, 2007 22

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: Antiarthritic? Antiheumatic

Bucillamine 139– U.S. Pat. Rimatil 140° No. 4305958

Diacerein 217 U.S. Pat. Artrodar, Fisiodar 218 No 4244968

Amlexanox >300 U.S. Pat. Aphthasol, No. Elics, Solfa 4143042

Cromolyn Aarane, Alercrom, Alerion, Allegocrom, Colimune, Cromoret, Firent, Gastro frenal, Inostral, Intal, Introl, Irtan Lomudal, Lomupren, Lomusol, Lomuspray, Nalcrom, Nalcron, Nasalcrom, Nasmil,Opticrom, Opticron, Rynacrom, Sofro, Vicrom, Vividrin

Function: Antibacterial (Antibiotics)

AZidam 1070 U.S. Pat. Berlicetin, fenicol No. Leukomycin-N, 2882275 Posifenicol, Thilocanifol US 2007/0093462 A1 Apr. 26, 2007 23

TABLE 1-continued

Name Compound MP Patent No. Other Names Thi- 1643- U.S. Pat. Hyrazin, Igralin, amphenicol 166.3° Nos. Neomyson, Rigelon, 2759927 Thiamcol, 2759970 Thionicol, 2759971 Thiophenicol, 2759972 Urfamycine, 2759976 Urophenil

Function: Antibacterial (Synthetic) Brodimo- 225- U.S. Pat. Hyprim, Unitrim prim 228 No. 4024145

Tetroxoprim 153- U.S. Pat. 156° No. 39923.79

Acetosulfone -285 U.S. Pat. Sodium No. 2358365

Dapsone 175 FR 829926 Avlosulfon, 1760 Croysulfone, Diphenasone, Disulone, Dumitone, Eporal, Novophone, Sulfona-Mae, Sulphadione, Udolac Function: Antibacterial (Tuberculostatic) Benzoylpas 260- GB 6.76363 261

HO

COOH US 2007/0093462 A1 Apr. 26, 2007 24

TABLE 1-continued

Name Compound MP Patent No. Other Names Cyamelide

Function: Anticoagulant

Picotamide 1249 U.S. Pat. No. 3973O26

Acetylphen- 100- U.S. Pat. Crampol eturide 1010 No. 3110728

Albutoin 21O- Euprax 211o

Function: Antidepressant

Caroxazone 2O3- U.S. Pat. Timostenil 2050 No. 3427313

Indalpine U.S. Pat. Upstene H N No. 4O642SS

NH

Function: Antidiabetic

Calcium Dec. JP 524157 Mesoxan Mesoxalate 21O- JP 6O7463 220° C. US 2007/0093462 A1 Apr. 26, 2007 25

TABLE 1-continued

Name Compound MP Patent No. Other Names Buformin U.S. Pat. No. 2.961377

Function: Antidiarrheal

Alkofanone Dec. U.S. Pat. Alfone 221– No. V/ 223° C. 2421836 S

O HN

Metformin U.S. Pat. DMG5, LA-6023 No. 3174901

Function: Antidote (Curare) Edrphomium Dec. U.S. Pat. Antirex, Enlon, Chloride 162- No. Reversol, Tensiolon 1630 2647924

Neostigmine Dec. U.S. Pat -167° No. 1905990

Function: Antidote (Cyanide) p-Aminopro- O 140° DMSO piophenon CH3

HN

Methylene Blue US 2007/0093462 A1 Apr. 26, 2007 26

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: Antidote (Folic Acid Antagonists)

Folinic Acid Dec. U.S. Pat. 240– No. 2500 2741608

Function: Antidote (Heavy Metal Poisoning)

Tiopronin 95-97 Acadione, Capen, Epatiol, Mucolysin, Thiola, Thiosol

Function: Antidote (Methanol and Ethylene Glycol Poisoning)

Fomepizole H 15.5- NS 18.5 \ f HC

Function: Antidote (Organophophate poisoning)

AsOxime 145- U.S. Pat. Chloride 1470 No. 3773775

Obidoxime Syn: U.S. Pat. Toksobidin, Chloride "C- "C- 23S- No. Toxogonin 4YS-11SJ1s 236° 3137702 Anti: N 2 218 HON 220

Function: Antidyskinetic

Chloride 130° U.S. Pat. C y- C 32O2660No. US 2007/0093462 A1 Apr. 26, 2007 27

TABLE 1-continued

Name Compound MP Patent No. Other Names

Tiapride 123- GB 125° C. 1394.563

Function: Antiemetic

Alizapride 1390 U.S. Pat. No. 4O93672

Bromopride U.S. Pat. Emepride, Emoril, No. Vladi 3177252

Function: Antifibrotic

Potassium p COOK Potaba Amino benzo ate

NH2

Function: (synthetic)

Chlordantoin

Bromo 238- U.S. Pat. Multifungin Salicylchlor OH 243 No. anilide 28O2O29

Br

C US 2007/0093462 A1 Apr. 26, 2007 28

TABLE 1-continued

Name Compound MP Patent No. Other Names Function: Antiglaucoma

Aceta 2S8 U.S. Pat. Acetamox, Zolamide 2590 No. Atenezol, 2554816 Defiltran, Diamox, Didoc, Diuriwas, DonmoX, Edemox, Fonurit, Glaupax

Benfunolol 160° U.S. Pat. Versus, Zildasac No. 34701.94

Function: Antigout

Allopurinol above U.S. Pat. 360° No. 3474O98

Carprofen 197 U.S. Pat. Imadyl, Rimadyl H N COOH 1989 No. 38961.45

C

Function: Antihistaminic

Acrivastine Dec. U.S. Pat. Semprex 222 o No. 45O1893

Metron S 84-85 US 2007/0093462 A1 Apr. 26, 2007 29

TABLE 1-continued

Name Compound MP Patent No. Other Names Function: Anti-hyperlipoproteininemic

Acifran 1760 U.S. Pat. Reductol No. 424.4958

Benfluorex U.S. Pat. No. CH3 36O7909

ON-1a N CF H O

Function: Anti-hypertensive

Chlorisoncl 2S8 U.S. Pat. Ecolid, Ecolid amine 265 No. Chloride Chloride /-/ Cl (CH3)3 3O2S294

N CH3

Penta Penthonium, methon- (HC). Br 1N1\-1\,. Br (CH3) Lytensium ium Bromide

Function: Anti-hyperthyroid

2-Amino U.S. Pat. No. thiazole y- NH2 2242237

Methylthio H Dec. Alkiron, Antibason, 326 Basecil, Basethyrin, uracil CH NY 3310 Methiacil, Methicil, Methiocil, Muracil, Prostrumyil, Strumacil, Thimecil, Thyreostat I

Function: Anti-hypotensive

Amexinium 1760 U.S. Pat. Regulton, Risumic, Methyl No. Supratonin Sulfate 363.1038 US 2007/0093462 A1 Apr. 26, 2007 30

TABLE 1-continued

Name Compound MP Patent No. Other Names

Dopamine Dec. Cardiosteril, Hydro HO 241 Dopastat, chloride Dynatra, Inovan, HCI Inotropin HO

Function: Anti-Inflammatory (Gastrointestinal)

Balsalazide U.S. Pat. No. 4412992

Mesalamine dec. GB 751386 Asacol, Ascolitin, COOH 280° Claversal, Lixacol, Mesasal, Pentasa, OH Rowasa, Salofalk

HN

Function: Anti-Inflammatory (Nonsteroidal)

Enfenamic 116– IN 103066 Tromaril Acid COOH 117o IN 114805

Menfenamic Acid

Flufenamic COO Alfenamin, Opyrin Acid Aluminum Salt

Function: Antimalarial

Berberine 145° US 2007/0093462 A1 Apr. 26, 2007 31

TABLE 1-continued

Name Compound MP Patent No. Other Names

Chloguanide H H H 1290 FR NSN." 1 OO1548 NH NH CH3

Function: Antimanic Valproic liquid Convulex, Acid H3C Depakene, Mylproin OH H3C O

Function: Antimigraine

Lisuride 186°

Naratriptan 170 U.S. Pat. 1710 No. 4997841

Function: Antimuscarinic

Ambutonium 228 Bromide 229°

Benzilonium 2O3- GP 821436 Minelsin, Minelcin, Bromide 204° Portyn, Ulcoban US 2007/0093462 A1 Apr. 26, 2007 32

TABLE 1-continued

Name Compound MP Patent No. Other Names Function: Antineoplastic

9-Amino- 300° JP KoKai camptothecin 59.51289 (to Yakult Honsha)

TenuaZonic Acid

Function: Antiobsessional

Clometo- U.S. Pat. Rixapen cillin No. 3OO792O

Fluoxetine 157 U.S. Pat. Adofen, Fluctin, Hydro- 158° No. Fluoxeren, Fontex, chloride 4314081 Foxetin, Lovan, Prozac, Reneuron, Sarafem

Function: Antiosteoporotic

Pamidronic U.S. Pat. Acid No. 4327039

Risedronate U.S. Pat. Acetonel, Optinate Sodium No 5583122 US 2007/0093462 A1 Apr. 26, 2007 33

TABLE 1-continued

Name Compound MP Patent No. Other Names Function: Antiparkinsonian

Benserazide 146– U.S. Pat. Hydro- 148 No. chloride 3.178476

Carbidopa 2O3- U.S. Pat. Lodosyn 2050 No. 3462S36

Function: Antipheochromoc-ytoma Metyrosine 31O- U.S. Pat. Demser 315o No. 28688.18

Phentol- 174 U.S. Pat. amine 175o No. 2503059

N OH

HC

Function: Anti-pneumocystic

Elfornithine 1830 Hydro chloride monohydrate

Sulfa- 1670 U.S. Pat. Gantanol, Sinomin methox- No. azole 28884S5

Function: Antiprostatic Hypertrophy

Tamsulosin 228- U.S. Pat. Flomax, Harnal, Hydro- 230° No. Omnic Pradif chloride 4703063 US 2007/0093462 A1 Apr. 26, 2007 34

TABLE 1-continued

Name Compound MP Patent No. Other Names

Terazosin 272 U.S. Pat. 274 No. 4026894 U.S. Pat. No. 42S1532

Function: Antiprotozoal Cryptosporidium

Nitazoxanide U.S. Pat. CryptaZ No. 39SO3S1

Function: Antiprotozoal (Giardia)

Acrani 237 U.S. Pat. 238° No. 2113357

Function: Antiprotozoal (Leishmania)

Hydroxystill 235o U.S. Pat. bamidine No. 2S10047 US 2007/0093462 A1 Apr. 26, 2007 35

TABLE 1-continued

Name Compound MP Patent No. Other Names

Pentamidine dec. U.S. Pat. 186° No. 2394,003

Function: Antiprotozoal (Toxoplasma)

Pyri- 233- U.S. Pat. Chloridin, methamine 234 No. Daraprim, 268.0740 Malcoide, Tindurin

Function: Antiprotozoal (Trichomonas) AcetarSone 240– Gynoplix, Orarsan, 2500 Spirocid, Stovarsol

Aminitrozole 264– U.S. Pat. Tritheon, Trichorad, 265 No. Enheptin-A 253,1756

Function: Antiprotozoal (Trypanosoma)

Benzinida- 188- GB Radani zole 190° 1138,529 US 2007/0093462 A1 Apr. 26, 2007 36

TABLE 1-continued

Name Compound MP Patent No. Other Names

Eflornithine 1830 Ornidyl Hydro chloride

Acitretin 228 U.S. Pat. Neotigason, 230° No. Soriatane 4105681

6-AZauridine 160 1619

Function: Antipsychotic

Amisulpride 126 U.S. Pat. Deniban, Socian, 127C No. Solian, Sulamide 4401822

Remoxipride 1730 U.S. Pat. Roxiam Hydro No. chloride 4232O37 Monohydrate US 2007/0093462 A1 Apr. 26, 2007 37

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: Antipyretic

Bufexamac 153 U.S. Pat. Droxaryl, Feximac, 1550 No. Malipuran, 3479396 Mofenar, Norfemae, Parfenac, Parfenal

Bumadizon 116– U.S. Pat. 117o No. 3455999

Ol N COOH CH N1 H O

Function: Antirickettsial

Chloram- 1SO U.S. Pat. phenicol 1510 No. 2839577

Function: Antiseptic/Disinfectant

Benzox- 107 CH3O6648 Absonal, Bactofen, onium 109° Bialcol Chloride

Cetalkonium 590 U.S. Pat. Banicol, Acetoquate Chloride No. CDAC, 2075958 Ammonyx G, Zettyn, Ammonyx T. Cetol

Function: Antispasmodic

Alibendol O 95o U.S. Pat. Cebera No. 3668.238 HO n1n N H

HO OCH US 2007/0093462 A1 Apr. 26, 2007 38

TABLE 1-continued

Name Compound MP Patent No. Other Names

Ambutonium 228 Bromide 229°

Function: Antisyphilitic

Arsh- U.S. Pat. Ehrlich 606, penamine No. Salvarsan 98.6148

Sodium O Arsamin, Atoxyl, Arsanilate Nuarsol, Protoxyl, Soamin AS-O- s S Sonate, Piglet OH Pro-Gen V, Trypoxyl HN

Function: Antithrom-boxythemic

Anagrelide >280 U.S. Pat. Agrylin No. 4146718

Function: Antihrombotic

Beraprost U.S. Pat. Dorner, Procylin No US 2007/0093462 A1 Apr. 26, 2007 39

TABLE 1-continued

Name Compound MP Patent No. Other Names

Cilostazol 159 BE 878548 Pletal 160°

Function: Antitussive

Bibenzonium 144 U.S. Pat. Sedobex, Bromide 1470 No. Lysobex, 291.3459 Lysibex, Thoragol, Lysbex, Medipectol

Sodium dec. O Labaz, Dibunate >300° Becantal, N-1\,. (CH3)3 Becantex, Dibunafon, Keuten, Linctussal

Function: Antiulcerative

Aldioxa. 230° U.S. Pat. Alanetorin, Alusa, No. Arlanto, 276.1867 Ascomp, Chlokale, Isalon, Nische, Peptilate

Cimetidine 141– U.S. Pat. Acibilin, Acinil, 1439 No. Cimal, Cimetag, 395.0333 Cimetum, Edalene, Dyspamet, Eureceptor, Gastromet, Peptol

Function: Antiurolithic

Allopurinol U.S. Pat. No. 3474O98

Succinimide 125 Orotric 127C US 2007/0093462 A1 Apr. 26, 2007 40

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: Antiviral

Foscarnet >250 U.S. Pat. Foscavir Sodium No. 421.5113

Efavirenz 139– U.S. Pat. 141 No. 5519021

Function: Anxiolytic

Etifoxine 90-92 U.S. Pat. No. 372S4O4

Val- 113- Axiquel, Nirvanil noctamide 114

Function: Atriopeptidase Inhibitor

Cannabinol 76. 17o US 2007/0093462 A1 Apr. 26, 2007 41

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: Bronchodilator

Oxitropium 2O3- U.S. Pat. Oxivent, Tersigat, Bromide 204° No. Ventilat 3472861

Tiotropium 218 EP 418716 Bromide 220

Function: Calcium Channel Blocker

Fendiline 204– U.S. Pat. Cordan, Fendilar, Hydro 2050 No. Sensit chloride 3262977 H N

CH HCI

Prenylamine 36-37 U.S. Pat. Elecor No. H 3152173 N

CH3

Function: Carbonic Anhydrase Inhibitor

Aceta 2S8 U.S. Pat. Acetamox, Zolamide 2590 No. Atenezol, 2554816 Diamox, Didoc, Diuriwas, Donmox, Edemox, Fonurit, Glaupax US 2007/0093462 A1 Apr. 26, 2007 42

TABLE 1-continued

Name Compound MP Patent No. Other Names Flumeth- 3OS- U.S. Pat. Ademol, Fludemil iazide 307 No. 3040042

Function: Cardioprotective Acadesine 213- Arasine, Protara 214

Cariporide 90-949 U.S. Pat. No. 5591754

Function: Cardotonic

Levo- 21O- U.S. Pat. Simdax simendan 214 No. 5569657

Pimobendan 311o U.S. Pat. Hydro- No. chloride 4361S63 US 2007/0093462 A1 Apr. 26, 2007 43

TABLE 1-continued

Name Compound MP Patent No. Other Names Function: Cholelitholytic Agent

Ursodiol 2O3 Actigall, Arsacol, Cholit-Ursan, Delursan, Desol, Destolit, Deursil, Litursol, Lyeton, Peptarom, Solutrat, Urdes, Ursacol, Urso, Ursochol, Ursofalk, Ursolvan.

Chenodiol 119° Chendol, Chenix, Chenocedon, Chenocol, Chenodex, Chenofaulk, Chenossil, Chenosaure, Cholanorm, Fluibil, Hekbilin, Ulmenide

Function: Choleretic

Cholic Acid 1989 Colalin Monohydrate

Clanobutin 115 U.S. Pat. Bykahepar 116 No. 3780095

Function: Cholinergic

Echo- 138° U.S. Pat. thiophate No. Iodide 2911430 US 2007/0093462 A1 Apr. 26, 2007 44

TABLE 1-continued

Name Compound MP Patent No. Other Names Edro- 162- U.S. Pat. Antirex, Enlon, phonium 1630 No. Eversol, Tensilon Chloride 2647924

Function: Cholinesterase Inhibitor

Amben- 196 DE Mytelase onium 1990 1024517 Chloride

Distigmine dec U.S. Pat. Ubretide Bromide 1439 No. 2789981

Function: Cholinesterase Reactivator

AsOxime 145- U.S. Pat. Chloride 1470 No. 3773775

Obidoxime dec U.S. Pat. Toksobidin, Chloride 225o No. Toxogonin 3137702

Function: CNS Stimulant

Pemoline 2S6 U.S. Pat. AZOkSodon, Cylert, 257o No. Deltamine, 2892753 Hyton Asa, Kethamed, Nitan, Pioxol, Pondex, Senior, Sigma dyn, Stimul, Tradon, Wolital

Phen- liquid U.S. Pat. metrazine No 283,5669

N CH3 H US 2007/0093462 A1 Apr. 26, 2007

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: Cyclooxygenase-2 Inhibitor

Celecoxib 157 WO Celebrex 1590 9515316

Function: Cytoprotectant (Gastric)

Cetraxate 2OO- U.S. Pat. 280° No. 3699149

Irsogladine 268- U.S. Pat. 269 No. 3.966728

Function: Decongestant

Naphazoline 255 U.S. Pat. Ak-con, Albalon, Hydro- N 260° No. Clera, chloride 2161938 Coldan, Iridina, N Naphcon, Niazol, H OpconRhinantin, HCI Phinoperd, Sanorin, Sanorin-Spofa, Strictylon

Nordefrin 178 U.S. Pat. Corbasil, Cobefrin Hydro- OH 179° No. chloride HO NH2 1948.162

CH3 HO US 2007/0093462 A1 Apr. 26, 2007 46

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: Dermatitis Herpetiformis Suppressant

Dapsone 175 Avlosulfon, 1760 Croysulfone, Diphenasone, Disulone, Dumitone, Eporal, Novophone, Sulfona-Mae, Sulphadine, Udolac

Sulfa- 190- U.S. Pat. Isopiridina, pyridine 1910 No. Soludagenan Sodium Salt 22753.54

Function: Diuretic

Mercapto- 1SO U.S. Pat. merin 1550 No. Sodium 2576349

Mercuma- 155 U.S. Pat. tilin 160° No. Sodium 2667442

Function: Dopamine Receptor Agonist

Pergolid 2O6- U.S. Pat. 209 No. 4166182

Pramipexole 296 U.S. Pat. Mirapex, Mirapexin, Dihydro- 298 No. Sifrol chloride 488.6812 US 2007/0093462 A1 Apr. 26, 2007 47

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: Dopamine Receptor Antagonist

Amisulpride 126 U.S. Pat. 127C No. 4401822

Sulpiride 178 U.S. Pat. Alilit, Aiglonyl, 180° No Coolspan, Dobren, 3342826 Dogmatil, Dogmatyl, Dolmatil, Guastil, Meresa, Miradol, Mierbanil, Misulvan, Neogama, Omperan, Pyrikappl, Sernevin, Splotin, Sulpitil, Sursumid, Trilan

Function: Emetic

Cephaeline 115 116

Function: Expectorant

Bromhexine 237 BE 625022 238°

Br

CH3

Br US 2007/0093462 A1 Apr. 26, 2007 48

TABLE 1-continued

Name Compound MP Patent No. Other Names

Ambroxol 233- U.S. Pat. Abramen, Ambril, Hydro 234 No. Bronchopront, chloride 3.536713 Duramucal, Fluibron, Fluixol, Frenopect, Lindoxyl, Motosol, Mucofar, Muscolvan, Mucoclear, Mucovent, Pect.Solvolan, Stas Hustenloser, Surbronc, Surfactal

Function: Gastric & Pancreatic Secretion Stimulant

Carnitine U.S. Pat. Nos. 42SS449 4315944

Function: Gastroprokinetic

Cinitapride U.S. Pat. Tartate, Cidine No. SO26858

Cisapride 109.8 U.S. Pat. Acenalin, Alimix, No Cipril, Prepulsick, 4.962115 Propulside, Risamol US 2007/0093462 A1 Apr. 26, 2007 49

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: Glucocorticoid

Cortivazol 160- U.S. Pat. 1650 No. 306.7194f U.S. Pat. No. 3300483

Enoxolone 296 GB 833 184

Function: Gonad-Stimulating Principle

Clomiphene 116– U.S. Pat. Citrate, Clomid, 118 No. Clomphid, Clomricl, 2914563 Clostilbeggit, Dyneric, Ikaclomine, Pergotime, Serophene C

Function: Hemorheologic Agent

Pentoxi 1050 U.S. Pat. Oxpentifylline, fylline No. Vasofirin, 3422107 AZOpentat, Dorapental, Rentglin, Torental, Trental US 2007/0093462 A1 Apr. 26, 2007 50

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: Hemostatic

Adrenalone CH 235o DE 152814 Adrenone, Stryphon N DE 277540

OH

OH

Carbazo 227 GB 795184 AC17, Adenaron, chrome 228 Adona, Carbazon, Sodium Donaseren, Emex, Sulfonate Odanon, Tazin

Function: Hepatoprotectant

Thioctic U.S. Pat. Biletan, Thioctacid, Acid Nos. Thioctan, Tioctan 2980716 3O49549 3223712

Timonacid FR 1731.84 Norgemen, Thioproline, Detokepa, Hepalidine, Heparegen, HOOCS. Thiazolidin

Function: Immono modulator

Pidotimod 194 U.S. Pat. 1989 No. 4839387

Bucillamine 139– U.S. Pat. Rimatil 140° No. 4305958

Function: Immono Suppressant

6-Mercapto 313 U.S. Pat. Leuberin, purine 3149 Nos. Mercaleubin 2697709 2721866 US 2007/0093462 A1 Apr. 26, 2007 51

TABLE 1-continued

Name Compound MP Patent No. Other Names Brequinar 315- U.S. Pat. 317o No. 468O299

F

N n

F 2 CH3

COOH

Function: Keratolytic

Retinoic 18O- U.S. Pat. Aberd, Airol, Arite, Acid 1810 No. Eudgna, Kerlocal, 3746730 Renova

Salicylic 1590 Acnisal, Duofilm, Acid Duoplant, Keralyt, OH Occlusal, Verrugon

Function: Lexative? Cathartic

Docusate U.S. Pat. Sofale Calcium Nos. (Sodium) 3035973 2028091

Picosolfate 272 U.S. Pat. Guttalax-Fher, Sodium 275o Nos. Laxoberal, 3528986 Laxoberon, 3SS8643 Neopax, Pico-Salax

-OSO OSO3 Function: Leukotriene Antagonist

Ibudilast 53-54° U.S. Pat. Ketas No. 3850941 US 2007/0093462 A1 Apr. 26, 2007 52

TABLE 1-continued

Name Compound MP Patent No. Other Names

Zafirlukast 138 U.S. Pat. Accolate 140° No. 4859692

Function: Lipotropic

Choline U.S. Pat. Biocolina, Chloride No. Hepacholine, 2623901 Lipotril

Methionine 280– Acimethin 282°

Function: Lupos Erythematosos Suppressant

Bismuth U.S. Pat. Bistrimate Sodium No. Tri 2348,984 glycollam ate

Chloroquine C 193– U.S. Pat. Aralen, Articlin, 1950 No. Bemaphate, 2233970 Capquin, Nivaquine B, Reamachlor, Sanoquin

Function: Matrix Metallo-proteinase Inhibitor

Prinomastat 149.8° WO 972O824

Function: Miotic

Carbachol 2070 U.S. Pat. Doryl, Isopto No. Carbachol, Zestryl, 1894.162 Miostat US 2007/0093462 A1 Apr. 26, 2007 53

TABLE 1-continued

Name Compound MP Patent No. Other Names

Neostigmine 1670 U.S. Pat. No. 1905990

Function: Mucolytic

Acetyl- 109– U.S. Pat. Bronac, Fabrol, cysteine 110 No. Fluimueil, Mocosil, 31.8450S Moeret

Bromhexine 237.59 BE 625022

Br N

NH2 Br

Function: Muscle Relaxant (Skeletal)

Tetrazepam 144 U.S. Pat. Muscaril, Muokelat, No. Myolastan 3426O14

Tizanidine 221– U.S. Pat. 223 No. 3843668 US 2007/0093462 A1 Apr. 26, 2007 54

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: Mydriatic

Tropicamide 96-97 U.S. Pat. Mydriacyl, No. Mydriaticum 2726245

140– U.S. Pat. Phenyl OH Adrianol, Ak-Dilate, ephrine 145° No. Alc-Nefrin, 1932347. Hydro HO Isophirin, chloride U.S. Pat. m-Sympatol, CH3 No. Neophryn 1954.389

Function: Naroctic Antagonist

Cyclazocine BE 611OOO

HO

CH

Ami 163 Dizol, Daptazole, phenazole 1649 Daptazile, Fenamizol

Function: Neuraminidase Inhibitor

Zanamivir 256° WO 911632O

Function: Neuromuscular Blocking Agent

Succinyl 156 choline 1630 US 2007/0093462 A1 Apr. 26, 2007 55

TABLE 1-continued

Name Compound MP Patent No. Other Names

Fazadinium 2150 U.S. Pat. Fazadon Bromide No. 3773746

Function: Neutral Endopetidase Inhibitor

Omapatrilat 218 U.S. Pat. Vauler 220 No. 5508272

Function: Neuroprotective

Riluzole 119° U.S. Pat. Rilutek No. 4370338

Repinotan 192- U.S. Pat. 1949 No. 5137901

Function: Nootropic

Indeloxazine U.S. Pat. Elen, Noin Hydro- No chloride 4109088 US 2007/0093462 A1 Apr. 26, 2007 56

TABLE 1-continued

Name Compound MP Patent No. Other Names

Donepezil 211– U.S. Pat. Aricept N 2120 No. O 4895841 HCO

H3CO

Function: Oxytocic

Carboprost SS-S6 U.S. Pat. No. 3728.382

Function: Potassium Channel Activator/Opener

Pinacidil 164- U.S. Pat. Pindac 1650 No. 4057636

Nicorandil 92-93 U.S. Pat. Adamcor, Ikorel, No. Perisalol, Sigmart 42OO640

Function: Potassium Channel Blocker

Fampridine N 158 n 1590 2

NH2

Tedisamil 195- U.S. Pat. 1970 No. 45SO112 US 2007/0093462 A1 Apr. 26, 2007 57

TABLE 1-continued

Name Compound MP Patent No. Other Names

Function: Prolactin Inhibitor

Cabergoline 102 U.S. Pat. Cabaser, Dostinex No. 4526892

Function: Prostaglandin

Beraprost U.S. Pat. No. 44798O2

Function: Respiratory Stimulant

Dimefline 213- U.S. Pat. 214 No. 3147258

Fominoben 122– U.S. Pat. 123° No. 3661903 US 2007/0093462 A1 Apr. 26, 2007 58

TABLE 1-continued

Name Compound MP Patent No. Other Names Function: Sclerosing Agent 2-Hexyl- 140– decanoic HC 1500 Acid COOH

CH3

Sodium Sotradecol, Tergitol Tetradecyl OSO3 Sulfate

Function: Sedative? Hypnotic

Flurazepam 77-82 U.S. Pat. Felmeme, Nos. Noctosom, 3299053 Stacuroderm 3567710

Etodroxizine liquid GB 8172321

Function: Succinylcholine Synergist

Hexafluor- 188- U.S. Pat. Mylexen enium 1890 No. Bromide 2783.237 US 2007/0093462 A1 Apr. 26, 2007 59

TABLE 1-continued

Name Compound MP Patent No. Other Names Function: Tocolytic

Ritodrine 88-90° U.S. Pat. OH No. 3410944

CH HO OH

Terbutaline CH3 119 U.S. Pat. 1220 No. 393,7838 HO N

OH

Function: Ultraviolet Screen p-Amino 187 U.S. Pat. Pabanol benzoic Acid COOH 187.5o Nos. 2878282 2947781 2735.865

Soliso 145° GB Songard, Uvinol benzone SOH 1136525 OCH

Function: UricoSuric

Ticrynafen 148 U.S. Pat. No. 3758506

Orotic Acid 345° U.S. Pat. Oropor, Orotyl Nos. 2937175 3O86917 US 2007/0093462 A1 Apr. 26, 2007 60

TABLE 1-continued

Name Compound MP Patent No. Other Names Function: Vasodilator (Cerebral) Nafronyl 190° U.S. Pat. Dubimax, Gevatran No. 3334096

Nicametate 155 Eucast 157o

Function: Vasodilator (Coronary)

Perhexiline 243– GB 245.5° 1025578 H N

Cloricromen 147- U.S. Pat. 148 No. 4452811

Function: Vasodilator (Peripheral)

Ciclonicate 127 DE 128° 1910481 24O6849 US 2007/0093462 A1 Apr. 26, 2007 61

TABLE 1-continued

Name Compound MP Patent No. Other Names

Cinepazide 135° U.S. Pat. No. 3634411

Function: Vasprotectant

Chromocarb 2SO U.S. Pat. O COOH 251 o No. 381.6470

O

Dobesilate >300 U.S. Pat. Calcium OH No. 3509207

HO SO3

Function: Vitamin Vitamin Source

Thiamine dec (Vit. B) 248

Pyridoxine 20S- U.S. Pat. Hydro- 2120 Nos. chloride 268.0743 (Vit. Bs) 2734O63 29O4SS1 3O24244

Function: Vulnerary

Oxaceprol 133- U.S. Pat. 1349 Nos. 38606O7 38.91765 3932638 US 2007/0093462 A1 Apr. 26, 2007 62

TABLE 1-continued

Name Compound MP Patent No. Other Names Acetyl- 109– U.S. Pat. Brunac, Fabrol, cysteine 110 No. Fluimucil, 31.8450S Fluprowit, Mucomgst, Mocosil, Tixair

Function: Wilson's Disease Treatment

Penicill- SH 2O2- Depen, Distamine, amine COOH 2O6 Mercaptyl, Sofortan, Trolovo NH,

Function: Xanthine Oxidase Inhibitor

Allopurinol >350 U.S. Pat. Adenoal, Aloral, Nos. CoSonic, Remid, 28688O3 Riball 3474O98

0147 Further examples of pharmaceutical actives that acetate, lysine hydrochloride, methionine, phenylalanine, are ionic or can be made ionic and combined with other ions proline, serine, threonine, tryptophan, tyrosine, Valine. to form the disclosed ionic liquid compositions are detailed 0154 Ammonia detoxicant: arginine: arginine glutamate, below, along with their typically pharmaceutical use. arginine hydrochloride. 0148 Adrenergic: adrenalone, amidephrine mesylate, apraclonidine hydrochloride, brimonidine tartrate, dapipra 0.155 Anabolic: bolandiol dipropionate, bolasterone, Zole hydrochloride, deterenol hydrochloride, diplivefrin, boldenone undecylenate, bolenol, bolnantalate, ethylestre dopamine hydrochloride, ephedrine Sulfate, epinephrine, nol, methenolone acetate, methenolone enanthate, mibole epinephrine bitartrate, epinephryl borate, esprocquin hydro rone, nandrolone cyclotate, norbolethone, pizotyline, quin chloride, etafedrine hydrochloride, hydroxyamphetamine bolone, Stenbolone acetate, tibolone, Zeranol. hydrobromide, levonordefrin, mephentermine sulfate, met 0156 Analeptic: modafinil. araminol bitartrate, metizoline hydrochloride, naphazoline hydrochloride, norepinephrine bitartrate, oxidopamine, 0157 Analgesic: acetaminophen, alfentanil hydrochlo oxymetazoline hydrochloride, phenylephrine hydrochloride, ride, aminobenzoate potassium, aminobenzoate Sodium, ani phenylpropanolamine hydrochloride, phenylpropanolamine doXime, anilleridine, anilleridine hydrochloride, anilopam polistirex, prenalterol hydrochloride, propylhexedrine, pseu hydrochloride, anirolac, antipyrine, aspirin, benoxaprofen, doephedrine hydrochloride, tetrahydrozoline hydrochloride, benzydamine hydrochloride, bici fadine hydrochloride, tramazoline hydrochloride, Xylometazoline hydrochloride. brifentanil hydrochloride, bromadoline maleate, bromfenac 0149 Adrenocortical steroid: ciprocinonide, desoxycor Sodium, buprenorphine hydrochloride, butacetin, butixirate, ticosterone acetate, desoxycorticosterone pivalate, dexam butorphanol, butorphanol tartrate, carbamazepine, carbaspi ethasone acetate, fludrocortisone acetate, flumoxonide, rin calcium, carbiphene hydrochloride, carfentanil citrate, hydrocortisone hemisuccinate, methylprednisolone ciprefadol Succinate, ciramadol, ciramadol hydrochloride, clonixeril, clonixin, codeine, codeine phosphate, codeine hemisuccinate, naflocort, procinonide, timobesone acetate, Sulfate, conorphone hydrochloride, cyclazocine, dexoxadrol tipredane. hydrochloride, dexpemedolac, dezocine, diflunisal, dihydro 0150 Adrenocortical suppressant: aminoglutethimide, codeine bitartrate, dimefadane, dipyrone, doxpicomine triloStane. hydrochloride, drinidene, enadoline hydrochloride, epiri Zole, ergotamine tartrate, ethoxazene hydrochloride, etofe 0151. Alcohol deterrent: disulfiram. namate, eugenol, fenoprofen, fenoprofen calcium, fentanyl 0152 Aldosterone antagonist: canrenoate potassium, citrate, floctafenine, flufenisal, fluniXin, flunixin meglumine, canrenone, dicirenone, mexrenoate potassium, prorenoate flupirtine maleate, fluproduaZone, fluradoline hydrochloride, potassium, spironolactone. flurbiprofen, hydromorphone hydrochloride, ibufenac, 0153 Amino acid: alanine, aspartic acid, cysteine hydro indoprofen, ketazocine, ketorfanol, ketorolac tromethamine, chloride, cystine, histidine, isoleucine, leucine, lysine, lysine letimide hydrochloride, levomethadyl acetate, levomethadyl US 2007/0093462 A1 Apr. 26, 2007 acetate hydrochloride, levonantradol hydrochloride, levor 0.161 Anorectic compounds including dexfenfluramine. phanol tartrate, lofemizole hydrochloride, lofentanil oxalate, 0162 Anorexic: aminorex, amphecloral, chlorphenter lorcinadol, lomoxicam, magnesium salicylate, mefenaamic mine hydrochloride, clominorex, clortermine hydrochloride, acid, menabitan hydrochloride, meperidine hydrochloride, diethylpropion hydrochloride, fenfluramine hydrochloride, meptazinol hydrochloride, methadone hydrochloride, meth fenisorex, fluidorex, fluminorex, levamfetamine Succinate, adyl acetate, methopholine, methotrimeprazine, metkepha mazindol, mefenorex hydrochloride, phenmetrazine hydro mid acetate, mimbane hydrochloride, mirfentanil hydrochlo chloride, phentermine, sibutramine hydrochloride. ride, molinaZone, morphine Sulfate, moxazocine, nabitan hydrochloride, nalbuphine hydrochloride, nalmexone 0.163 Antagonist: atipamezole, atosiban, bosentan, cime hydrochloride, namoxyrate, nantradol hydrochloride, tidine, cimetidine hydrochloride, clentiazem maleate, detire naproxen, naproxen Sodium, naproXol, nefopam hydrochlo lix acetate, devaZepide, donetidine, etintidine hydrochloride, famotidine, fenmetozole hydrochloride, flumazenil, icati ride, nexeridine hydrochloride, noracymethadol hydrochlo bant acetate, icotidine, isradipine, metiamide, nadide, ride, ocfentanil hydrochloride, octaZamide, olvanil, oxetor nalmefene, nalmexone hydrochloride, naloxone hydrochlo one fluimarate, oxycodone, oxycodone hydrochloride, ride, naltrexone, nilvadipine, oxilorphan, oxmetidine hydro oxycodone terephthalate, oxymorphone hydrochloride, chloride, oxmetidine mesylate, quadazocine mesylate, ran pemedolac, pentamorphone, pentazocine, pentazocine itidine, ranitidine bismuth citrate, ranitidine hydrochloride, hydrochloride, pentazocine lactate, phenazopyridine hydro sufotidine, teludipine hydrochloride, tiapamil hydrochlo chloride, phenyramidol hydrochloride, picenadol hydro ride, tiotidine, vapiprost hydrochloride, Zaltidine hydrochlo chloride, pinadoline, pirfenidone, piroXicam olamine, pra ride. vadoline maleate, prodilidine hydrochloride, profadol hydrochloride, propirarn fumarate, propoxyphene hydro 0.164 Anterior pituitary activator: epimestrol. chloride, propoxyphene napsylate, proxazole, proxazole cit 0.165 Anterior pituitary suppressant: danazol. rate, proXorphan tartrate, pyrroliphene hydrochloride, 0166 Anthelmintic: albendazole, anthelmycin, bromox remifentanil hydrochloride, Salcolex, Salethamide maleate, anide, bunamidine hydrochloride, butonate, cambendazole, salicylamide, Salicylate meglumine, Salsalate, Sodium sali carbantel lauryl Sulfate, clioxanide, closantel, cyclobenda cylate, spiradoline mesylate, Sufentanil, Sufentanil citrate, Zole, dichlorvos, diethylcarbamazine citrate, dribendazole, talmetacin, talniflumate, talosalate, taZadolene Succinate, dymanthine hydrochloride, etibendazole, fenbendazole, tebufelone, tetrydamine, tifurac sodium, tilidine hydrochlo furodazole, hexylresorcinol, mebendazole, morantel tartrate, ride, tiopinac, tonazocine mesylate, tramadol hydrochloride, niclosamide, nitramisole hydrochloride, nitrodan, oxantel trefentanil hydrochloride, trolamine, Veradoline hydrochlo pamoate, Oxfendazole, oxibendazole, parbendazole, pipera ride, Verilopam hydrochloride, Volazocine, Xorphanol mesy mide maleate, piperazine, piperazine citrate, piperazine ede late, Xylazine hydrochloride, Zenazocine mesylate, Zomepi tate calcium, proclonol, pyrantel pamoate, pyrantel tartrate, rac sodium, Zucapsaicin. pyrvinium pamoate, rafoxanide, stilbazium iodide, tetrami sole hydrochloride, thiabendazole, ticarbodine, tioxidazole, 0158 Androgen: fluoxymesterone, mesterolone, methylt triclofenol piperazine, Vincofos, Zilantel. estosterone, nandrolone decanoate, nandrolone phenpropi onate, nisterime acetate, Oxandrolone, oxymetholone, silan 0.167 Anti-acne: adapalene, erythromycin salnacedin, drone, stanozolol, testosterone, testosterone cypionate, inocoterone acetate, accutane. testosterone enanthate, testosterone ketolaurate, testosterone 0168 Anti-adrenergic: acebutolol, alprenolol hydrochlo phenylacetate, testosterone propionate, trestolone acetate. ride, atenolol, bretylium tosylate, bunolol hydrochloride, carteolol hydrochloride, celiprolol hydrochloride, cetamolol 0159 Anesthesia, adjunct to: sodium oxybate. hydrochloride, cicloprolol hydrochloride, dexpropranolol 0160 Anesthetic: alliflurane, benoximate hydrochloride, hydrochloride, diacetolol hydrochloride, dihydroergotamine benzocaine, biphenamine hydrochloride, bupivacaine mesylate, dilevalol hydrochloride, esmolol hydrochloride, hydrochloride, butamben, butamben picrate, chloroprocaine exaprolol hydrochloride, fenspiride hydrochloride, flestolol hydrochloride, cocaine, cocaine hydrochloride, cyclopro sulfate, labetalol hydrochloride, levobetaxolol hydrochlo pane, desflurane, dexivacaine, diamocaine cyclamate, ride, levobunolol hydrochloride, metalol hydrochloride, dibucaine, dibucaine hydrochloride, dyclonine hydrochlo metoprolol, metoprolol tartrate, nadolol, pamatolol Sulfate, ride, enflurane, ether, ethyl chloride, etidocaine, etoxadrol penbutolol Sulfate, phentolamine mesylate, practolol, pro hydrochloride, euprocin hydrochloride, fluroxene, hal pranolol hydrochloride, proroXanhydrochloride, Solypertine othane, isobutamben, isoflurane, ketamine hydrochloride, taitrate, sotalol hydrochloride, timolol, timolol maleate, levoxadrol hydrochloride, lidocaine, lidocaine hydrochlo tiprenolol hydrochloride, tolamolol, Zollertine hydrochloride. ride, mepivacaine hydrochloride, methohexital Sodium, 0.169 Anti-allergic: amlexanox, astemizole, azelastine methoxyflurane, midazolam hydrochloride, midazolam hydrochloride, eclaZolast, minocromil, nedocromil. maleate, minaxolone, nitrous oxide, norflurane, octodrine, nedocromil calcium, nedocromil Sodium, nivimedone oxethazaine, phencyclidine hydrochloride, pramoxine Sodium, pemirolast potassium, pentigetide, pirquinozol, poi hydrochloride, prilocaine hydrochloride, procaine hydro Sonoak extract, probicromil calcium, proxicromil, repirinast, chloride, propanidid, proparacaine hydrochloride, propofol. tetraZolast meglumine, thiazinamium chloride, tiacrilast, tia propoxycaine hydrochloride, pyrrocaine, risocaine, crilast Sodium, tiprinast meglumine, tixanoX. rodocaine, roflurane, salicyl alcohol, sevoflurane, teflurane, tetracaine, tetracaine hydrochloride, thiamylal, thiamylal 0170 Anti-amebic: berythromycin, bialamicol hydro Sodium, thiopental Sodium, tiletamine hydrochloride, Zola chloride, chloroquine, chloroquine hydrochloride, chloro mine hydrochloride. quine phosphate, clamoxyquin hydrochloride, clioquinol, US 2007/0093462 A1 Apr. 26, 2007 64 emetine hydrochloride, iodoquinol, paromomycin Sulfate, mindione, dalteparin Sodium, desirudin, dicumnarol, heparin quinfamide, Symetine hydrochloride, teclozan, tetracycline, calcium, heparin Sodium, lyapolate Sodium, nafamoStat tetracycline hydrochloride. mesylate, phenprocoumon, tinzaparin Sodium, warfarin 0171 anti-androgen: benorterone, cioteronel, cyproter Sodium. one acetate, delmadinone acetate, Oxendolone, topterone, ZanoterOne. 0182 Anticoccidal: maduramicin. 0172 Anti-anemic: epoetin alfa, epoetin beta, ferrous 0183 Anticonvulsant: albutoin, ameltolide, atolide, bura Sulfate, dried, leucovorin calcium. mate, carbamazepine, cinromide, citenamide, clonazepam, cyheptamide, dezinamide, dimethadione, divalproex 0173 Anti-anginal: amlodipine besylate, amlodipine Sodium, eterobarb, ethoSuximide, ethotoin, flurazepam maleate, betaxolol hydrochloride, bevantolol hydrochloride, hydrochloride, fluzinamide, fosphenytoin Sodium, gabapen butoprozine hydrochloride, carvedilol, cinepaZet maleate, tin, ilepcimide, lamotrigine, magnesium Sulfate, mepheny metoprolol Succinate, molsidomine, monatepil maleate, toin, mephobarbital, methetoin, methSuximide, millacemide primidolol, ranolazine hydrochloride, tosifen, Verapamil hydrochloride, nabazenil, nafimidone hydrochloride, hydrochloride. nitrazepam, phenacemide, phenobarbital, phenobarbital 0174 Anti-anxiety agent: adatanserin hydrochloride, Sodium, phensuximide, phenytoin, phenytoin Sodium, primi alpidem, binospirone mesylate, bretazenil, glemanserin, done, progabide, ralitoline, remacemide hydrochloride, rop ipsapirone hydrochloride, mirisetron maleate, ocinaplon, izine, sabeluzole, stiripentol, Sulthiame, thiopental Sodium, ondansetron hydrochloride, panadiplon, pancopride, paZina tiletamine hydrochloride, topiramate, trimethadione, Val clone, Serazapine hydrochloride, tandospirone citrate, proate sodium, Valproic acid, vigabatrin, ZonicleZole hydro Zalospirone hydrochloride. chloride, Zonisamide. 0175 Anti-arthritic: lodelaben. 0.184 Antidepressant: adatanserin hydrochloride, adina 0176 Anti-asthmatic: ablukast, ablukast sodium, azelas Zolam, adinazolam mesylate, alaproclate, aletamine hydro tine hydrochloride, bunaprolast, cinalukast, crornitrile chloride, amedalin hydrochloride, amitriptyline hydrochlo Sodium, cromolyn Sodium, enofelast, isamoxole, ketotifen ride, amoxapine, aptazapine maleate, azaloxan fluimarate, fumarate, levcromakalim, lodoxamide ethyl, lodoxamide azepindole, azipramine hydrochloride, bipenamol hydro tromethamine, montelukast sodium, OntaZolast, oxarbazole, chloride, bupropion hydrochloride, butacetin, butriptyline oXatomide, piriprost, piriprost potassium, pirolate, pobi hydrochloride, caroxazone, cartazolate, ciclazindol, cidox epin hydrochloride, cilobamine mesylate, clodazon hydro lukast edamine, quaZolast, repirinast, ritolukast, Sulukast, chloride, clomipramine hydrochloride, cotinine fumarate, tetraZolast meglumine, tiaramide hydrochloride, tibenelast cyclindole, cypenamine hydrochloride, cyprolidol hydro Sodium, tomelukast, tranilast, Verlukast, Verofylline, Zar chloride, cyproximide, daledalin tosylate, dapoxetine hydro irlukast. chloride, dazadrol maleate, dazepinil hydrochloride, 0177 Anti-atherosclerotic: mifobate, timefuronc. desipramine hydrochloride, dexamisole, deximafen, diben Zepin hydrochloride, dioxadrol hydrochloride, dothiepin 0178 Anticholelithic: monoctanoin. hydrochloride, doxepin hydrochloride, dulloxetine hydro 0179 Anticholelithogenic: chenodiol, ursodiol. chloride, eclanamine maleate, encyprate, etoperidone hydro 0180 Anticholinergic: alverinc citrate, anisotropine chloride, fantridone hydrochloride, fehmetozole hydrochlo methylbromide, atropine, atropine oxide hydrochloride, ride, fenmetramide, fezolamine fumarate, fluotracen atropine Sulfate, belladonna, benapry Zine hydrochloride, hydrochloride, fluoxetine, fluoxetine hydrochloride, flupar benzetimide hydrochloride, benzilonium bromide, oxan hydrochloride, gamfexine, guanoxyfen Sulfate, imafen biperiden, biperiden hydrochloride, biperiden lactate, clid hydrochloride, imiloxan hydrochloride, imipramine hydro inium bromide, cyclopentolate hydrochloride, dexetimide, chloride, indeloxazine hydrochloride, intriptyline hydro dicyclomine hydrochloride, dihexyverine hydrochloride, chloride, iprindole, isocarboxazid, ketipramine fumarate, domaZoline fumarate, elantrine, elucaine, ethybenztropine, lofepramine hydrochloride, lortalamine, maprotiline, eucatropine hydrochloride, glycopyrrolate, heteronium bro maprotiline hydrochloride, melitracen hydrochloride, mila mide, homatropine hydrobromide, homatropine methylbro cemide hydrochloride, minaprine hydrochloride, mirtazap mide, hyoscyamine, hyoscyamine hydrobromide, hyos ine, moclobemide, modaline Sulfate, napactadine hydrochlo cyamine Sulfate, isopropamide iodide, mepenZolate ride, napamezole hydrochloride, nefazodone hydrochloride, bromide, methylatropine nitrate, metoquizine, oxybutynin nisoxetine, nitrafudam hydrochloride, nomifensine maleate, chloride, parapenzolate bromide, pentapiperium methylsul nortriptyline hydrochloride, octriptyline phosphate, fate, phencarbamide, poldine methylsulfate, proglumide, opipramol hydrochloride, oxaprotiline hydrochloride, propantheline bromide, propenZolate hydrochloride, Scopo oxypertine, paroxetine, phenelZine Sulfate, pirandamine lamine hydrobromide, tematropium methylsulfate, tiquina hydrochloride, pizotyline, pridefine hydrochloride, prolin mide hydrochloride, tofenacin hydrochloride, toguizine, tri tane hydrochloride, protriptyline hydrochloride, quipazine ampyzine sulfate, trihexyphenidyl hydrochloride, maleate, rolicyprine, seproxetine hydrochloride, Sertraline tropicamide. hydrochloride, sibutramine hydrochloride, Sulpiride, Surito Zole, tametraline hydrochloride, tampramine fimarate, tan 0181 Anticoagulant: ancrod, anticoagulant citrate dex damine hydrochloride, thiazesim hydrochloride, thozali trose solution, anticoagulant citrate phosphate dextrose none, tomoxetine hydrochloride, traZodone hydrochloride, adenine solution, anticoagulant citrate phosphate dextrose trebenzomine hydrochloride, trimipramine, trimipramine Solution, anticoagulant heparin solution, anticoagulant maleate, venlafaxine hydrochloride, viloxazine hydrochlo Sodium citrate solution, ardeparin sodium, bivalirudin, bro ride, Zimeldine hydrochloride, Zometapine. US 2007/0093462 A1 Apr. 26, 2007

0185 Antidiabetic: acetohexamide, buformin, butoxam narium chloride, Saperconazole, scopafungin, selenium Sul ine hydrochloride, camiglibose, chlorpropamide, ciglita fide, sinefungin, Sulconazole nitrate, terbinafine, Zone, englitaZone sodium, etoformin hydrochloride, gliamil terconazole, thiram, ticlatone, tioconazole, tolciclate, tolin ide, glibornuride, glicetanile sodium, gliflumide, glipizide, date, tolnaftate, triacetin, triafungin, undecylenic acid, virido glucagon, glyburide, glyhexamide, glymidine sodium, gly fulvin, Zinc undecylenate, Zinoconazole hydrochloride. One octamide, glyparamide, insulin, insulin, dalanated, insulin specific antifungal that is Suitable is itraconazole. human, insulin human, isophane, insulin human Zinc, insulin 0.195 Antiglaucoma agent: alprenoxime hydrochloride, human Zinc, extended, insulin, isophane, insulin lispro, colforsin, dapiprazole hydrochloride, diplivefrin hydrochlo insulin, neutral, insulin Zinc, insulin Zinc, extended, insulin Zinc, prompt, linogliride, linogliride fumarate, metformin, ride, naboctate hydrochloride, pilocarpine, pimabine. methyl palmoxirate, palmoxirate sodium, pioglitaZone 0.196 Antihemophilic: antihemophilic factor. hydrochloride, pirogliride tartrate, proinsulin human, seg litide acetate, tolaZamide, tolbutamide, tolpyrramide, trogli 0.197 Antihemorrhagic: poliglusam. taZone, Zopolrestat, and Sitagliptin. 0198 Antihistaminic: acrivastine, antazoline phosphate, astemizole, azatadine maleate, barmastine, bromodiphenhy 0186 Antidiarrheal: rolgamidine, diphenoxylate hydro dramine hydrochloride, brompheniramnine maleate, carbi chloride (lomotil), metronidazole (flagyl), methylpredniso noxamine maleate, cetirizine hydrochloride, chlorphe lone (medrol), SulfaSalazine (aZulfidine). niramine maleate, chlorpheniramine polistirex, cinnarizine, 0187 Antidiuretic: argipressin tannate, desmopressin clemastine, clemastine fluimarate, closiramine aceturate, acetate, lypressin. cycliramine maleate, cyclizine, cyproheptadine hydrochlo ride, dexbrompheniramnine maleate, dexchlorpheniramine 0188 Antidote: dimercaprol, edrophonium chloride, maleate, dimethindene maleate, diphenhydramine citrate, fomepizole, leucovorin calcium, levoleucovorin calcium, diphenhydramnine hydrochloride, dorastine hydrochloride, methylene blue, protamine Sulfate. doxylamine Succinate, ebastine, levocabastine hydrochlo 0189 Antidyskinetic: selegiline hydrochloride. ride, loratadine, mianserin hydrochloride, noberastine, 0.190 Anti-emetic: alosetron hydrochloride, batanopride orphenadrine citrate, pyrabrom, pyrilamine maleate, pyrox hydrochloride, bemesetron, benzquinamide, chlorprom amnine maleate, rocastine hydrochloride, rotoxamine, tazi azine, chlorpromazine hydrochloride, clebopride, cyclizine fylline hydrochloride, temelastine, terfenadine, tripelen hydrochloride, dimenhydrinate, diphenidol, diphenidol namine citrate, tripelennamine hydrochloride, triprolidine hydrochloride, diphenidol pamoate, dolasetron mesylate, hydrochloride, Zolamine hydrochloride. domperidone, dronabinol, fluidorex, flumeridone, 0199 Antihyperlipidemic: cholestyramine resin, clofi galdansetron hydrochloride, granisetron, granisetron hydro brate, colestipol hydrochloride, crilvastatin, dalvastatin, chloride, lurosetron meSylate, meclizine hydrochloride, dextrothyroxine Sodium, fluvastatin Sodium, gemfibrozil, metoclopramide hydrochloride, metopimazine, ondansetron lecimibide, lovastatin, niacin, pravastatin Sodium, probucol, hydrochloride, pancopride, prochlorperazine, prochlorpera simvastatin, tiqueside, Xenbucin. Zine edisylate, prochlorperazine maleate, promethazine hydrochloride, thiethylperazine, thiethylperazine malate, 0200 Antihyperlipoproteinemic: acifran, beloxamide, bezafibrate, boxidine, butoxamine hydrochloride, cetaben thiethylperazine maleate, trimethobenzamide hydrochloride, Sodium, ciprofibrate, gemcadiol, halofenate, lifibrate, Zacopride hydrochloride. meglutol, nafenopin, pimetine hydrochloride, theofibrate, 0191 Anti-epileptic: felbamate, loreclezole, tolgabide. tibric acid, treloxinate. 0192 Anti-estrogen: clometherone, dehnadinone acetate, 0201 Antihypertensive: alfuzosin hydrochloride, alipa nafoxidine hydrochloride, nitromifene citrate, raloxifene mide, althiazide, amidulinsin hydrochloride, amlodipine hydrochloride, tamoxifen citrate, toremifene citrate, triox besylate, amlodipine maleate, anaritide acetate, atiprosin ifene mesylate. maleate, belfosdil, bemitradine, bendacalol mesylate, ben droflumethiazide, benzthiazide, betaxolol hydrochloride, 0193 Antifibrinolytic: na?amostat mesylate. bethanidine sulfate, bevantolol hydrochloride, biclodil 0194 Antifungal: acrisorcin, ambruticin, amphotericinb. hydrochloride, bisoprolol, bisoprolol fumarate, bucindolol aZaconazole, azaserine, basifuingin, bifonazole, biphe hydrochloride, bupicomide, buthiazide: candoXatril, can namine hydrochloride, bispyrithione magSulfex, butocona doXatrilat, captopril, carvedilol, ceronapril, chlorothiazide Zole nitrate, calcium undecylenate, candicidin, carbol-fuich Sodium, cicletanine, cilaZapril, clonidine, clonidine hydro sin, chlordantoin, ciclopiroX, ciclopiroX olamine, cillofungin, chloride, clopamide, cyclopenthiazide, cyclothiazide, dar cisconazole, clotrimazole, cuprimyxin, denofungin, dipy odipine, debrisoquin Sulfate, delapril hydrochloride, diapa rithione, doconazole, econazole, econazole nitrate, enilcona mide, diazoxide, dilevalol hydrochloride, diltiazem malate, Zole, ethonam nitrate, fenticonazole nitrate, filipin, flucona ditekiren, doxazosin mesylate, ecadotril, enalapril maleate, Zole, flucytosine, fingimycin, griseofulvin, hamycin, enalaprilat, enalkiren, endralazine mesylate, epithiazide, isoconazole, itraconazole, kalafungin, ketoconazole, eprosartan, eprosartan mesylate, fenoldopam mesylate, fla lomofimgin, lydimycin, mepartricin, miconazole, micona Vodilol maleate, flordipine, floSequinan, fosinopril Sodium, Zole nitrate, monensin, monensin Sodium, naftifine hydro fosinoprilat, guanabenz, guanabenZ acetate, guanacline Sul chloride, neomycin undecylenate, nifuratel, nifulrmerone, fate, guanadrel Sulfate, guancydine, guanethidine monosul nitralamine hydrochloride, nystatin, octanoic acid, orcona fate, guanethidine Sulfate, guanfacine hydrochloride, Zole nitrate, oxiconazole nitrate, oxifungin hydrochloride, guanisoquin Sulfate, guanoclor Sulfate, guanoctine hydro parconazole hydrochloride, partricin, potassium iodide, pro chloride, guanoxabenz, guanoxan Sulfate, guanoxyfen Sul clonol, pyrithione Zinc, pyrrolnitrin, rutamycin, sangui fate, hydralazine hydrochloride, hydralazine polistirex, US 2007/0093462 A1 Apr. 26, 2007 66 hydroflumethiazide, indacrinone, indapamide, indolaprif diflorasone diacetate, diflumidone sodium, diflunisal, diflu hydrochloride, indoramin, indoramin hydrochloride, prednate, diftalone, dimethyl sulfoxide, drocinonide, end indorenate hydrochloride, lacidipine, leniquinsin, levcro rysone, enlimomab, enolicam Sodium, epirizole, etodolac, makalim, lisinopril, lofexidine hydrochloride, losartan etofenamate, felbinac, fenamole, fenbufen, fenclofenac, fen potassium, losulazine hydrochloride, mebutamate, mecamy clorac, fendosal, fenpipalone, fentiazac, flazalone, fluaza lamine hydrochloride, medroxalol, medroxalol hydrochlo cort, flufenamic acid, flumizole, flunisolide acetate, flunixin, ride, methalthiazide, methyclothiazide, methyldopa, meth flunixin meglumine, fluocortin butyl, fluorometholone yldopate hydrochloride, metipranolol, metolaZone, acetate, fluguaZone, flurbiprofen, fluretofen, fluticaSone pro metoprolol fumarate, metoprolol Succinate, metyrosine, pionate, furaprofen, furobufen, halcinonide, halobetasol pro minoxidil , monatepil maleate, muZolimine, nebivolol. pionate, halopredone acetate, ibufenac, ibuprofen, ibuprofen nitrendipine.ofomine, pargyline hydrochloride, paZoxide, aluminum, ibuprofen piconol, illonidap, indomethacin, pelanserin hydrochloride, perindopril erbumine, phenoxy indomethacin Sodium, indoprofen, indoxole, intrazole, isof benzamine hydrochloride, pinacidil, pivopril, polythiazide, lupredone acetate, isoxepac, isoxicam, ketoprofen, lofemi prazosin hydrochloride, primidolol, prizidilol hydrochlo Zole hydrochloride, lomoxicam, loteprednol etabonate, ride, quinapril hydrochloride, quinaprilat, quinazosin hydro meclofenamate Sodium, meclofenamic acid, meclorisone chloride, quinelorane hydrochloride, quinpirole hydrochlo dibutyrate, mefenamic acid, mesalamine, meseclaZone, ride, quinuclium bromide, ramipril, rauwolfia Serpentina, methylprednisolone Suleptanate, momiflumate, nabume reserpine, saprisartan potassium, Saralasin acetate, sodium tone, naproxen, naproxen Sodium, naproXol, nimaZone, nitroprusside, Sulfinalol hydrochloride, tasosartan, telu olsalazine sodium, orgotein, orpanoxin, oxaprozin, dipine hydrochloride, temocapril hydrochloride, terazosin oxyphenbutaZone, paranyline hydrochloride, pentosan hydrochloride, terlakiren, tiamenidine, tiamenidine hydro polysulfate sodium, phenbutaZone sodium glycerate, pir chloride, ticrynafen, tinabinol, tiodaZosin, tipentosin hydro fenidone, piroXicam, piroxicam cinnamate, piroXicam ola chloride, trichlormethiazide, trimazosin hydrochloride, tri mine, pirprofen, prednazate, prifelone, prodolic acid, pro methaphan camsylate, trimoxaamine hydrochloride, quaZone, proxazole, proxazole citrate, rimexolone, tripamide, Xipamide, Zankiren hydrochloride, Zofenoprilat romazarit, Salcolex, Salnacedin, Salsalate, Sanguinarium arginine. chloride, seclaZone, sermetacin, Sudoxicam, Sulindac, Supro fen, talmetacin, talniflumate, talosalate, tebufelone, tenidap, 0202 Antihypotensive: ciclafrine hydrochloride, mido tenidap Sodium, tenoxicam, tesicam, tesimide, tetrydamine, drine hydrochloride. tiopinac, tiXocortol pivalate, tolmetin, tolmetin Sodium, tri 0203 Anti-infective: difloxacin hydrochloride, lauryl clonide, triflumidate, Zidometacin, Zomepirac sodium. isoquinolinium bromide, moxalactam disodium, omidazole, 0206 Antikeratinizing agent: doretinel, linarotene, pel pentisomicin, Sarafloxacin hydrochloride, protease inhibi retin. tors of hiv and other retroviruses, integrase inhibitors of hiv and other retroviruses, cefaclor (CECLORTM), acyclovir 0207 Antimalarial: acedapsone, amodiaquine hydro (ZOVIRAXTM), norfloxacin (NOROXINTM), cefoxitin chloride, amduinate, arteflene, chloroquine, chloroquine (MEFOXINTM), cefuroxime axetil (CEFTINTM), ciprofloxa hydrochloride, chloroquine phosphate, cycloguanil pamo cin (CIPROTM). ate, empiroline phosphate, halofantrine hydrochloride, hydroxychloroquine Sulfate, mefloquine hydrochloride, 0204 Anti-infective, topical: alcohol, aminacrine hydro menoctone, mirincamycin hydrochloride, primaquine phos chloride, benzethonium chloride: bithionolate sodium, bro phate, pyrimethamine, quinine Sulfate, tebuquine. mchlorenone, carbamide peroxide, cetalkonium chloride, cetylpyridinium chloride: chlorhexidine hydrochloride, clio 0208 Antimicrobial: aztreonam, chlorhexidine glucon quinol. domiphen bromide, fenticlor, fludazonium chloride, ate, imidurea, lycetamine, nibroxane, piraZmonam Sodium, fuchsin, basic, furazolidone, gentian violet, halquinols, propionic acid, pyrithione sodium, Sanguinarium chloride, hexachlorophene: hydrogen peroxide, ichthammol, imidecyl tigemonam dicholine. iodine, iodine, isopropyl alcohol, mafenide acetate, meralein 0209 Antimigraine: dolasetron mesylate, naratriptan Sodium, mercufenol chloride, mercury, ammoniated, meth hydrochloride, Sergolexole maleate, Sumatriptan Succinate, ylbenzethonium chloride, nitrofuraZone, nitromersol, Zatosetron maleate. octenidine hydrochloride, oxychlorosene, oxychlorosene Sodium, parachlorophenol, camphorated, potassium per 0210 Antimitotic: podofilox. manganate, povidone-iodine, sepazonium chloride, silver nitrate, Sulfadiazine, silver, Symclosene, thimerfonate 0211 Antimycotic: amorolfine. Sodium, thimerosal: troclosene potassium. 0212 Antinauseant: buclizine hydrochloride, cyclizine 0205 Anti-inflammatory: acetominophen, alclofenac, lactate, naboctate hydrochloride. aldlometasone dipropionate, algestone acetonide, alpha 0213 Antineoplastic: acivicin, aclarubicin, acodazole amylase, amcinafal, amcinafide, amfenac sodium, ami hydrochloride, acronine, adoZelesin, aldesleukin, altre prilose hydrochloride, anakinra, anirolac, anitraZafen, apa tamine, ambomycin, ametantrone acetate, aminoglutethim Zone, balsalazide disodium, bendazac, benoxaprofen, ben ide, amsacrine, anastroZole, anthramycin, asparaginase, Zydamine hydrochloride, bromelains, broperamole, asperlin, azacitidine, azetepa, azotomycin, batimastat, ben budesonide, carprofen, cicloprofen, cintaZone, cliprofen, Zodepa, bicalutamide, bisantrene hydrochloride, bisnafide clobetasol propionate, clobetaSone butyrate, clopirac, cloti dimesylate, bizelesin, bleomycin Sulfate, brequinar Sodium, casone propionate, cormethasone acetate, cortodoxone, bropirimine, buSulfan, cactinomycin, calusterone, carace deflazacort, desonide, desoximetaSone, dexamethasone mide, carbetimer, carboplatin, carmustine, carubicin hydro dipropionate, diclofenac potassium, diclofenac sodium, chloride, carZelesin, cedefingol, chlorambucil, cirolemycin, US 2007/0093462 A1 Apr. 26, 2007 67 cisplatin, cladribine, crisinatol mesylate, cyclophosphamide, betaclamycin B, betulinic acid, bFGF inhibitor, bicaluta cytarabine, dacarbazine, dactinomycin, daunorubicin hydro mide, bisantrene, bisaziridinylspermine, bisnafide, bis chloride, decitabine, dexormaplatin, dezaguanine, dezagua tratene A, bizelesin, breflate, bropirimine, budotitane, nine mesylate, diaziquone, docetaxel, doxorubicin, doxoru buthionine Sulfoximine, calcipotriol, callphostin C, camp bicin hydrochloride, droloxifene, droloxifene citrate, tothecin derivatives, canarypox IL-2, capecitabine, carboxa dromostanolone propionate, duaZomycin, edatrexate, eflo mide-amino-triazole, carboxyamidotriazole, CaRest M3. mithine hydrochloride, elsamitrucin, enloplatin, empromate, CARN 700, cartilage derived inhibitor, carzelesin, casein epipropidine, epirubicin hydrochloride, erbulozole, esorubi kinase inhibitors (ICOS), castanospermine, cecropin B, cin hydrochloride, estramustine, estramustine phosphate sodium, etanidazole, ethiodized oil I 131, etoposide, etopo cetrorelix, chlorins, chloroquinoxaline Sulfonamide, cica side phosphate, etoprine, fadrozole hydrochloride, faZara prost, cis-porphyrin, cladribine, clomifene analogues, clot bine, fenretinide, floxuridine, fludarabine phosphate, fluo rimazole, collismycin A, collismycin B, combretastatin A4. rouracil, flurocitabine, fosquidone, fostriecin Sodium, combretastatin analogue, conagenin, crambescidin 816, cri gemcitabine, gemcitabine hydrochloride, gold au 198, Snatol, cryptophycin 8, cryptophycin A derivatives, curacin hydroxyurea, idarubicin hydrochloride, ifosfamide, ilmofos A cyclopentanthraquinones, cycloplatam, cypemycin, cyt ine, interferon alfa-2a, interferon alfa-2b, interferon alfa-N1, arabine ocfosfate, cytolytic factor, cytostatin, dacliximab, interferon alfa-N3, interferon beta-la, interferon gamma-Ib, decitabine, dehydrodidemnin B, deslorelin, dexifosfamide, iproplatin, irinotecan hydrochloride, lanreotide acetate, dexraZoxane, dexVerapamil, diaziquone, didemnin B, didox, letrozole, leuprolide acetate, liarozole hydrochloride, lom diethylnorspermine, dihydro-5-azacytidine, dihydrotaxol. etrexol Sodium, lomustine, losoxantrone hydrochloride, 9-dioxamycin, diphenyl spiromustine, docosanol, dolas masoprocol, maytansine, mechlorethamine hydrochloride, etron, doxifluridine, droloxifene, dronabinol, duocannycin megestrol acetate, melengestrol acetate, melphalan, menog SA, ebselen, ecomustine, edelfosine, edrecolomab, eflo aril, mercaptopurine, methotrexate, methotrexate Sodium, mithine, elemene, emitefur, epirubicin, epristeride, estra metoprine, meturedepa, mitindomide, mitocarcin, mitocro mustine analogue, estrogen agonists, estrogen antagonists, min, mitogillin, mitomalcin, mitomycin, mitosper, mitotane, etanidazole, etoposide phosphate, exemestane, fadrozole, mitoxantrone hydrochloride, mycophenolic acid, nocoda fazarabine, fenretinide, filgrastim, finasteride, flavopiridol. Zole, nogalamycin, ormaplatin, oxiSuran, paclitaxel, pegas flezelastine, fluasterone, fludarabine, fluorodaunorunicin pargase, peliomycin, pentamustine, peplomycin Sulfate, per hydrochloride, forfenimex, formestane, fostriecin, fotemus fosfamide, pipobroman, piposulfan, piroXantrone tine, gadolinium texaphyrin, gallium nitrate, galocitabine, hydrochloride, plicamycin, plomestane, porfimer Sodium, ganirelix, gelatinase inhibitors, gemcitabine, glutathione porfiromycin, prednimustine, procarbazine hydrochloride, inhibitors, hepsulfam, heregulin, hexamethylene bisaceta puromycin, puromycin hydrochloride, pyrazofurin, ribo mide, hypericin, ibandronic acid, idarubicin, idoxifene, idra prine, rogletimide, Safmgol, Safingol hydrochloride, Semus mantone, ilmofosine, illomastat, imidazoacridones, imiqui tine, simtraZene, sparfosate sodium, sparsomycin, Spiroger mod, immunostimulant peptides, insulin-like growth manium hydrochloride, Spiromustine, spiroplatin, factor-1 receptor inhibitor, interferon agonists, interferons, streptonigrin, streptozocin, strontium chloride Sr 89. interleukins, iobenguane, iododoxorubicin, ipomeanol, Sulofenur, talisomycin, taxane, taxoid, tecogalan Sodium, 4-irinotecan, iroplact, irsogladine, isobengaZole, isohomo tegafur, teloxantrone hydrochloride, temoporfin, teniposide, halicondrin B, itasetron, jasplakinolide, kahalalide F. lamel teroxirone, testolactone, thiamiprine, thioguanine, thiotepa, larin-N triacetate, lanreotide, leinamycin, lenograstim, len tiazofurin, tirapazamine, topotecan hydrochloride, tinan Sulfate, leptolstatin, letrozole, leukemia inhibiting toremifene citrate, trestolone acetate, triciribine phosphate, factor, leukocyte alpha interferon, leuprolide+estrogen trimetrexate, trimetrexate glucuronate, triptorelin, tubulo progesterone, leuprorelin, levamisole, liarozole, linear Zole hydrochloride, uracil mustard, uredepa, Vapreotide, polyamine analogue, lipophilic disaccharide peptide, lipo verteporfin, vinblastine sulfate, Vincristine sulfate, vin philic platinum compounds, lissoclinamide 7, lobaplatin, desine, Vindesine Sulfate, vinepidine Sulfate, Vinglycinate lombricine, lometrexol, lonidamine, losoxantrone, lovasta sulfate, Vinleurosine sulfate, vinorelbine tartrate, Vinrosidine tin, loxoribine, lurtotecan, lutetium texaphyrin, lysofylline, Sulfate, Vinzolidine Sulfate, Vorozole, Zeniplatin, Zinostatin, lytic peptides, maitansine, mannostatin A, marimastat, Zorubicin hydrochloride. masoprocol, maspin, matrilysin inhibitors, matrix metallo proteinase inhibitors, menogaril, merbarone, meterelin, 0214. Other anti-neoplastic compounds include: 20-epi methioninase, metoclopramide, MIF inhibitor, mifepristone, 1.25 dihydroxyvitamin D3, 5-ethynyluracil, abiraterone, miltefosine, mirimostim, mismatched double stranded RNA, aclarubicin, acylfuilvene, adecypenol, adoZelesin, aldesleu mitoguaZone, mitolactol, mitomycin analogues, mitonafide, kin, ALL-TK antagonists, altretamine, ambamustine, ami mitotoxin fibroblast growth factor-Saporin, mitoxantrone, doX, amifostine, aminolevulinic acid, amrubicin, atrsacrine, mofarotene, molgramostim, monoclonal antibody, human anagrelide, anastrozole, andrographolide, angiogenesis chorionic gonadotrophin, monophosphoryl lipid A +myo inhibitors, antagonist D, antagonist G, antarelix, anti-dor bacterium cell wall sk, mopidamol, multiple drug resistance salizing morphogenetic protein-1, antiandrogen, prostatic genie inhibitor, multiple tumor Suppressor 1-based therapy, carcinoma, antiestrogen, antineoplaston, antisense oligo mustard anticancer agent, mycaperoxide B, mycobacterial nucleotides, aphidicolin glycinate, apoptosis gene modula cell wall extract, myriaporone, N-acetyldinaline, N-substi tors, apoptosis regulators, apurinic acid, ara-CDP-DL tuted benzamides, nafarelin, nagrestip, naloxone +pentaZo PTBA, arginine deaminase, asulacrine, atamestane, cine, napavin, naphterpin, nartograstim, medaplatin, nemo atrimustine, axinastatin 1, axinastatin 2, axinastatin 3, aza rubicin, neridronic acid, neutral endopeptidase, nilutamide, setron, azatoxin, azatyrosine, baccatin III derivatives, bal nisamycin, nitric oxide modulators, nitroxide antioxidant, anol, batimastat, BCR/ABL antagonists, benzochlorins, ben nitrullyn, 06-benzylguanine, octreotide, okicenone, oligo Zoylstaurosporine, beta lactam derivatives, beta-alethine, nucleotides, onapristone, ondansetron, ondansetron, oracin, US 2007/0093462 A1 Apr. 26, 2007 oral cytokine inducer, ormaplatin, osaterone, oxaliplatin, 0216) Antineutropenic: filgrastim, lenograstim, molgra oxaunomycin, paclitaxel analogues, paclitaxel derivatives, mostim, regramostim, Sargramostim. palauamine, palmitoylrhizoxin, pamidronic acid, panax ytriol, panomifene, parabactin, paZelliptine, pegaspargase, 0217 Antiobsessional agent: fluvoxamine maleate. peldesine, pentosan polysulfate sodium, pentostatin, pentro 0218 Antiparasitic: abamectin, clorsulon, ivermectin. Zole, perflubron, perfosfamide, perillyl alcohol, phenazino 0219 Antiparkinsonian: benztropine meSylate, mycin, phenylacetate, phosphatase inhibitors, picibanil, biperiden, biperiden hydrochloride, biperiden lactate, car pilocarpine hydrochloride, pirarubicin, piritrexim, placetin mantadine, ciladopa hydrochloride, dopamantine, ethopro A, placetin B, plasminogen activator inhibitor, platinum pazine hydrochloride, lazabemide, levodopa, lometraline complex, platinum compounds, platinum-triamine complex, hydrochloride, mofegiline hydrochloride, naxagolide hydro porfimer Sodium, porfiromycin, propyl bis-acridone, pros chloride, pareptide sulfate, procyclidine hydrochloride, taglandin J2, proteasome inhibitors, protein A-based quinetorane hydrochloride, ropinirole hydrochloride, sel immune modulator, protein kinase C inhibitor, protein egiline hydrochloride, tolcapone, trihexyphenidyl hydro kinase C inhibitors, microalgal, protein tyrosine phosphatase chloride. antiperistaltic: difenoximide hydrochloride, inhibitors, purine nucleoside phosphorylase inhibitors, pur difenoxin, diphenoxylate hydrochloride, fluperamide, lida purins, pyrazoloacridine, pyridoxylated hemoglobin poly midine hydrochloride, loperamide hydrochloride, male oxyethylene conjugate, raf antagonists, raltitrexed, ramo thamer, nufenoXole, paregoric. setron, ras famesyl protein transferase inhibitors, ras Antipneumocystic: atovaquone. inhibitors, ras-GAP inhibitor, retelliptine demethylated, rhe 0220) nium Re 186 etidronate, rhizoxin, ribozymes, RII retina 0221) Antiproliferative agent: piritreximisethionate. mide, rogletimide, rohitukine, romurtide, roquinimex, Antiprostatic hypertrophy: sitogluside. rubiginone B1, ruboxyl, Safingol, Saintopin, SarCNU, sar 0222 cophytol A, SargramoStim, Sdi 1 mimetics, semustine, Senes 0223 Antiprotozoal: amodiaquine, azanidazole, bam cence derived inhibitor 1, sense oligonucleotides, signal nidazole, carnidazole, chlortetracycline bisulfate, chlortet transduction inhibitors, signal transduction modulators, racycline hydrochloride, flubendazole, flunidazole, single chain antigen binding protein, sizofiran, Sobuzoxane, halofuginone hydrobromide, imidocarb hydrochloride, Sodium borocaptate, Sodium phenylacetate, solverol, ipronidazole, metronidazole, misonidazole, moXnidazole, Somatomedin binding protein, Sonermin, sparfosic acid, nitarSone, partricin, puromycin, puromycin hydrochloride, spicamycin D. Spiromustine, splenopentin, spongistatin 1, ronidazole, Sulnidazole, tinidazole. squalamine, stem cell inhibitor, stem-cell division inhibitors, stipiamide, Stromelysin inhibitors, Sulfinosine, Superactive 0224) Antipruritic: cyproheptadine hydrochloride, meth vasoactive intestinal peptide antagonist, Suradista, Suramin, dilazine, methdilazine hydrochloride, trimeprazine tartrate. Swainsonine, synthetic glycosaminoglycans, tallimustine, 0225. Antipsoriatic: acitretin, anthralin, azaribine, calci tamoxifen methiodide, tauromustine, tazarotene, tecogalan potriene, cycloheximide, enaZadrem phosphate, etretinate, Sodium, tegafur, tellurapyrylium, telomerase inhibitors, liaroZole fumarate, lonapalene, tepoxalin. temoporfin, temozolomide, teniposide, tetrachlorodecaox ide, tetraZomine, thaliblastine, thalidomide, thiocoraline, 0226 Antipsychotic: acetophenazine maleate, alentemol thrombopoietin, thrombopoietin mimetic, thymalfasin, thy hydrobromide, alpertine, azaperone, batelapine maleate, mopoietin receptoragonist, thymotrinan, thyroid stimulating benperidol, benzindopyrine hydrochloride, brofbxine, bro hormone, tin ethyl etiopurpurin, tirapazamine, titanocene mperidol, bromperidol decanoate, butaclamol hydrochlo dichloride, topotecan, top sentin, toremifene, totipotent stem ride, butaperazine, butaperazine maleate, carphenazine cell factor, translation inhibitors, tretinoin, triacetyluridine, maleate, carvotroline hydrochloride, chlorpromazine, chlo triciribine, trimetrexate, triptorelin, tropisetron, turosteride, rpromazine hydrochloride, chlorprothixene, cinperene, cin tyrosine kinase inhibitors, tyrphostins, UBC inhibitors, ube triamide, clomacran phosphate, clopenthixol, clopimozide, nimex, urogenital sinus-derived growth inhibitory factor, clopipazan meSylate, cloroperone hydrochloride, clothiap urokinase receptor antagonists, vapreotide, variolin B. vec ine, clothixamide maleate, clozapine, cyclophenazine tor system, erythrocyte gene therapy, velaresol, Veramine, hydrochloride, droperidol, etazolate hydrochloride, fenim Verdins, verteporfin, Vinorelbine, Vinxaltine, vitaxin, Voro ide, flucindole, flumeZapine, fluiphenazine decanoate, Zole, Zanoterone, Zeniplatin, Zilascorb, Zinostatin Sti fluphenazine enanthate, fluphenazine hydrochloride, flus malamer. piperone, fluspirilene, flutroline, gevotroline hydrochloride, halopemide, haloperidol, haloperidol decanoate, illoperi 0215 Anti-cancer supplementary potentiating agents: tri done, imidoline hydrochloride, lemperone, mazapertine Suc cyclic anti-depressant drugs (e.g., imipramine, desipramine, cinate, mesoridazine, mesoridazine besylate, metiapine, amitryptyline, clomiprainine, trimipramine, doxepin, milemperone, millipertine, molindone hydrochloride, naranol nortriptyline, protriptyline, amoxapine and maprotiline), hydrochloride, neflumozide hydrochloride, ocaperidone, non-tricyclic anti-depressant drugs (e.g., Sertraline, traZ olanzapine, OXiperomide, penfluridol, pentiapine maleate, odone and citalopram), Ca' antagonists (e.g., Verapamil, perphenazine, pimozide, pinoxepin hydrochloride, pipam nifedipine, nitrendipine and caroverine), calmodulin inhibi perone, piperacetazine, pipotiazine palniitate, piquindone tors (e.g., prenylamine, trifluoroperazine and clomi hydrochloride, prochlorperazine edisylate, prochlorperazine pramine), amphotericin B, triparanol analogues (e.g., tamox maleate, promazine hydrochloride, remoxipride, remoX ifen), antiarrhythmic drugs (e.g., quinidine), ipride hydrochloride, rimcazole hydrochloride, seperidol antihypertensive drugs (e.g., reserpine), thiol depleters (e.g., hydrochloride, sertindole, Setoperone, spiperone, thior buthionine and sulfoximine) and Multiple Drug Resistance idazine, thioridazine hydrochloride, thiothixene, thiothixene reducing agents such as Cremaphor EL. hydrochloride, tioperidone hydrochloride, tiospirone hydro US 2007/0093462 A1 Apr. 26, 2007 69 chloride, trifluoperazine hydrochloride, trifluperidol, triflu hydrochloride, reproterol hydrochloride, rimiterol hydrobro promazine, triflupromazine hydrochloride, Ziprasidone mide, Salmeterol, Salmeterol Xinafoate, Soterenol hydrochlo hydrochloride. ride, sulfonterol hydrochloride, Suloxifen oxalate, terbuta 0227 Antirheumatic: auranofin, aurothioglucose, bin line Sulfate, theophylline, Xanoxate sodium, Zindotrine, darit, lobenzarit sodium, phenylbutaZone, piraZolac, prino Zinterol hydrochloride. mide tromethamine, Seprilose. 0240 Carbonic anhydrase inhibitor: acetazolamide, 0228 Antischistosomal: becanthone hydrochloride, acetazolamide Sodium, dichlorphenamide, dorzolamide hycanthone, lucanthone hydrochloride, niridazole, oxam hydrochloride, methazolamide, sezolamide hydrochloride. niquine, pararosaniline pamoate, teroxalene hydrochloride. 0241 Cardiac depressant: acecainide hydrochloride, ace 0229 Antiseborrheic: chloroxine, piroctone, piroctone tylcholine chloride, actisomide, adenosine, amiodarone, olamine, resorcinol monoacetate. antisecretory: arbaprostil, aprindine, aprindine hydrochloride, artilide fumarate, azi deprostil, fenoctimine Sulfate, octreotide, octreotide acetate, milide Dihydrochloride, bidisomide, bucainide maleate, omeprazole sodium, rioprostil, trimoprostil. bucromarone, butoprozine hydrochloride, capobenate Sodium, capobenic acid, cifenline, cifenline Succinate, clo 0230 Antispasmodic: stilonium iodide, tizanidine hydro filium phosphate, disobutamide, disopyramide, disopyra chloride. mide phosphate, dofetilide, drobuline, edifolone acetate, emilium tosylate, encainide hydrochloride, flecainide 0231 Antithrombotic: anagrelide hydrochloride, biva acetate, ibutilide fluimarate, indecainide hydrochloride, ipa lirudin, dalteparin Sodium, danaparoid sodium, daZOXiben Zilide fumarate, lorajmine hydrochloride, lorcainide hydro hydrochloride, efegatran Sulfate, enoxaparin Sodium, chloride, meobentine sulfate, mexiletine hydrochloride, ifetroban, ifetroban Sodium, tinzaparin Sodium, trifenagrel. modecainide, moricizine, oxiramide, pirmenol hydrochlo 0232 Antitussive: benzonatate, butamirate citrate, chlo ride, pirolaZamide, pranolium chloride, procainamide phedianol hydrochloride, codeine polistirex, codoxime, dex hydrochloride, propafenone hydrochloride, pyrinoline, quin tromethorphan, dextromethorphan hydrobromide, dex donium bromide, quinidine gluconate, quinidine Sulfate, tromethorphan polistirex, ethyl dibunate, guaiapate, recainam hydrochloride, recainam tosylate, risotilide hydro hydrocodone bitartrate, hydrocodone polistirex, levopro chloride, ropitoin hydrochloride, sematilide hydrochloride, poxyphene napsylate, noscapine, pemerid nitrate, Suricainide maleate, tocainide, tocainide hydrochloride, pipazethate, SuXemerid Sulfate. transcainide. 0233 Anti-ulcerative: aceglutamide aluminum, cadex 0242 Cardioprotectant: dexrazoxane, draflazine. omer iodine, cetraxate hydrochloride, enisoprost, isotiquim ide, lanSoprazole, lavoltidine Succinate, misoprostol, nizati 0243 Cardiotonic: actodigin, amrinone, bemoradan, dine, nolinium bromide, pantoprazole, pifarnine, butopamine, carbazeran, carsatirin Succinate, deslanoside, pirenzepine hydrochloride, rabeprazole sodium, remipros digitalis, digitoxin, digoxin, dobutamine, dobutamine hydro chloride, dobutamine lactobionate, dobutamine tartrate, tol, roXatidine acetate hydrochloride, Sucralfate. Sucrosofate enoXimone, imaZodan hydrochloride, indolidan, isomazole potassium, tolimidone. hydrochloride, levdobutamine lactobionate, lixazinone sul 0234 Anti-urolithic: cysteamine, cysteamine hydrochlo fate, medorinone, milrinone, pelrinone hydrochloride, ride, tricitrates. pimobendan, piroXimone, prinoXodan, proscillaridin, quazi 0235 Appetite suppressant: dexfenfluramine hydrochlo none, tazolol hydrochloride, Vesnarinone. ride, phendimetrazine tartrate, phentermine hydrochloride. 0244 Cardiovascular agent: dopexamine, dopexamine 0236 Benign prostatic hyperplasia therapy agent: tamsu hydrochloride. losin hydrochloride. 0245 Choleretic: dehydrocholic acid, fencibutirol, 0237 Blood glucose regulators: human insulin, gluca hymecromone, piprozolin, sincalide, tocamphyl. gon, tolaZamide, tolbutamide, chloropropamide, acetohexa 0246 Cholinergic: aceclidine, bethanechol chloride, car mide and glipizide. bachol, demecarium bromide, dexpanthenol, echothiophate iodide, isoflurophate, methacholine chloride, neostigmine 0238 Bone resorption inhibitor: alendronate sodium, bromide, neostigmine methylsulfate, physostigmine, phys etidronate disodium, pamidronate disodium. ostigmine salicylate, physostigmine Sulfate, pilocarpine, 0239 Bronchodilator: albuterol, albuterol sulfate, azana pilocarpine hydrochloride, pilocarpine nitrate, pyridostig tor maleate, bamifylline hydrochloride, bitolterol mesylate, mine bromide. butaprost, carbuterol hydrochloride, clorprenaline hydro chloride, colterol mesylate, doxaprost, doxofylline, dyphyl 0247 Cholinergic agonist: Xanomeline, Xanomeline tar line, enprofylline, ephedrine, ephedrine hydrochloride, trate. fenoterol, fenprinast hydrochloride, guaithylline, hexopre 0248 Cholinesterase deactivator: obidoxime chloride, naline Sulfate, hoquizil hydrochloride, ipratropium bromide, pralidoxime chloride, pralidoxime iodide, pralidoxime isoetharine, isoetharine hydrochloride, isoetharine mesylate, mesylate. isoproterenol hydrochloride, isoproterenol sulfate, metapro terenol polistirex, metaproterenol sulfate, nisbuterol mesy 0249 Coccidiostat: arprinocid, narasin, semduramicin, late, oxtriphylline, picumeterol fumarate, piquizil hydro semduramicin Sodium. chloride, pirbuterol acetate, pirbuterol hydrochloride, 0250) Dognition adjuvant: ergoloid mesylates, piracetam, procaterol hydrochloride, pseudoephedrine Sulfate, quaZod pramiracetam hydrochloride, pramiracetam Sulfate, tacrine ine, quinterenol sulfate, racepinephrine, racepinephrine hydrochloride. US 2007/0093462 A1 Apr. 26, 2007 70

0251 Cognition enhancer: besipirdine hydrochloride, 0260 Fibrinolytic: anistreplase, bisobrin lactate, brino linopirdine, Sibopirdine. lase. 0252) Depressant: omeprazole. 0261 Free oxygen radical scavenger: pegorgotein. 0253 Diagnostic aid: aminohippurate sodium, anazolene 0262 Gastrointestinal motility agents: cisapride (PRO Sodium, arclofenin, arginine, bentiromide, benzylpenicilloyl PULSIDTM), metoclopramide (REGLANTM), hyoscyamine polylysine, butedronate tetrasodium, butilfenin, coccidioi (LEVSINTM). din, corticorelin ovine triflutate, corticotropin, repository, corticotropin Zinc hydroxide, diatrizoate meglumine, diatri 0263 Glucocorticoid: amcinonide, beclomethasone Zoate sodium, diatrizoic acid, diphtheria toxin for Schick dipropionate, betamethasone, betamethasone acetate, test, disofenin, edrophonium chloride, ethiodized oil, etife betamethasone benzoate, betamethasone dipropionate, nin, exametazime, ferristenc, ferumoxides, ferumoXsil, fluo betamethasone sodium phosphate, betamethasone Valerate, rescein, fluorescein Sodium, gadobenate dimeglumine, carbenoXolone sodium, clocortolone acetate, clocortolone gadoteridol, gadodiamide, gadopentetate dimeglumine, pivalate, cloprednol, corticotropin, corticotropin, repository, gadoversetamide, histoplasmin, impromidine hydrochlo corticotropin Zinc hydroxide, cortisone acetate, cortivaZol. ride, indigotindisulfonate Sodium, indocyanine green, loben descinolone acetonide, dexamethasone, dexamethasone guane sulfate I'', iobenzamic acid, iocarmate meglumine, Sodium phosphate, diflucortolone, diflucortolone pivalate, locarmic acid, iocetamic acid, iodamide, lodamide flucloronide, flumethasone, flumethasone pivalate, megiumine, iodipamide meglumine, iodixanol, iodoxamate flunisolide, fluocinolone acetonide, fluocinonide, fluocor meglumine, iodoxamic acid, ioglicic acid, ioglucol, ioglu tolone, fluocortolone caproate, fluorometholone, fluperolone comide, ioglycamic acid, iogulamide, lohexol, iomeprol, acetate, fluprednisolone, fluprednisolone Valerate, flurandre iopamidol, iopanoic acid, iopentol, iophendylate, iprofenin, nolide, formocortal, hydrocortisone, hydrocortisone acetate, iopronic acid, ioprocemic acid, iopydol, iopydone, iose hydrocortisone buteprate, hydrocortisone butyrate, hydro famic acid, io.seric acid, ioSulamide meglumine, iosumetic cortisone sodium phosphate, hydrocortisone sodium Succi acid, iotasul, iotetric acid, iothalamate meglumine, iothala nate, hydrocortisone Valerate, medrysone, methylpredniso mate sodium, iothalamic acid, iotrolan, iotroXic acid, iover lone, methylprednisolone acetate, methylprednisoloime Sol, ioxaglate meglumine, ioXagiate Sodium, ioxaglic acid, Sodium phosphate, methylprednisolone sodium Succinate, ioXilan, ioxotrizoic acid, ipodate calcium, ipodate Sodium, nivaZol, paramethasone acetate, prednicarbate, predniso isosulfan blue, leukocyte typing serum, lidofenin, mebrofe lone, prednisolone acetate, prednisolone hemisuccinate, nin, meglumine, metrizamide, metrizoate Sodium, prednisolone sodium phosphate, prednisolone sodium suc metyrapone, metyrapone tartrate, mumps skin test antigen, cinate, prednisolone tebutate, prednisone, prednival, ticabe pentetic acid, propyliodone, quinaldine blue, sermorelin Sone propionate, tralonide, triamcinolone, triamcinolone acetate, sodium iodide I'', sprodiamide, stannous pyro acetonide, triamcinolone acetonide sodium, triamcinolone phosphate, Stannous Sulfur colloid. Succimer, teriparatide diacetate, triamcinolone hexacetonide. acetate, tetrofosmin, tolbutamide Sodium, tuberculin, tyro 0264 Gonad-stimulating principle: buserelin acetate, panoate Sodium, Xylose. clomiphene citrate, ganirelix acetate, gonadorelin acetate, 0254 Diuretic: ambuphylline, ambuside, amiloride gonadorelin hydrochloride, gonadotropin, chorionic, hydrochloride, azolimine, aZosemide, brocrinat, bumet menotropins. anide, chlorothiazide, chlorthalidone, clazolimine, clorex 0265 Hair growth stimulant: minoxidil. olone, ethacrynate sodium, ethacrynic acid, etoZolin, fen quizone, furosemide, hydrochlorothiazide, isosorbide, 0266 Hemostatic: aminocaproic acid, oxamarin hydro mannitol, mefruside, oZolinone, piretanide, SpiroXasone, chloride, Sulmarin, thrombin, tranexarnic acid. torsemide, triamterene, triflocin, urea. 0267. Histamine H2 receptor antagonists: ranitidine 0255 Dopaminergic agent: ibopamine. (ZANTACTM), famotidine (PEPCIDTM), cimetidine (TAG AMETM), nizatidine (AXIDTM). 0256 Ectoparasiticide: nifluridide, permethrin. 0268 Hormone: diethylstilbestrol, progesterone, 17 0257 Emetic: apomorphine hydrochloride. hydroxy progesterone, medroxyprogesterone, norgestrel, 0258 Enzyme inhibitor: acetohydroxamic acid, alrestatin norethynodrel, estradiol, megestrol (megace), norethin Sodium, aprotinin, benazepril hydrochloride, benazeprilat, drone, levonorgestrel, ethyndiol, ethinyl estradiol, mestra benurestat, bromocriptine, bromocriptine mesylate, cilasta nol, estrone, equilin, 17 alpha dihydroequilin, equilenin, 17 tin Sodium, flurofamide, lergotrile, lergotrile mesylate, lev alpha dihydroequilenin, 17 alpha estradiol, 17 beta estradiol, cycloserine, libenZapril, pentopril, pepstatin, perindopril, leuprolide (LUPRONTM), glucagon, testolactone, clomi phene, human menopausal gonadotropins, human chorionic polignate Sodium, Sodium amylosulfate, Sorbinil, spirapril gonadotropin, urofollitropin, bromocriptine, gonadorelin, hydrochloride, spiraprilat, taleranol, teprotide, tolfamide, luteinizing hormone releasing hormone and analogs, gona Zofenopril calcium. dotropins, danazol, testosterone, dehydroepiandrosterone, 0259 Estrogen: chlorotrianisene, dienestrol, diethylstil androstenedione, dihydroestosterone, relaxin, oxytocin, bestrol, diethylstilbestrol diphosphate, equilin, estradiol, vasopressin, folliculostatin, follicle regulatory protein, estradiol cypionate, estradiol enanthate, estradiol undecy gonadoctrinins, oocyte maturation inhibitor, insulin growth late, estradiol valerate, estraZinol hydrobromide, estriol, factor, follicle stimulating hormone, luteinizing hormone, estrofurate, estrogens, conjugated, estrogens, esterified, tamoxifen, corticorelin ovine trifiutate, cosyntropin, estrone, estropipate, ethinyl estradiol, fenestrel, mestranol, metogest, pituitary, posterior, seractide acetate, Somalapor, nylestriol, quinestrol. Somatrem, somatropin, Somenopor, somidobove. US 2007/0093462 A1 Apr. 26, 2007

0269) Hypocholesterolemic: lifibrol. 0285 Memory adjuvant: dimoxamine hydrochloride, rib 0270. Hypoglycemic: dargilitazone sodium: glimepiride. aminol. 0271 Hypolipidemic: azalanstat dihydrochloride, coles 0286 Mental performance enhancer: aniracetam. tolone, Surfomer, Xenalipin. 0287 Mood regulator: fengabine. 0272 Hypotensive: viprostol. 0288 Mucolytic: acetylcysteine, carbocysteine, domi odol. 0273 Hmgcoa reductase inhibitors: lovastatin (MEVA CORTM), simvastatin (ZOCORTM), pravastatin (PRAVA 0289 Mucosal protective agents: misoprostol (CYTO CHOLTM), fluvasatin (LESCOLTM). TECTM). 0274 Immunizing agent: antirabies serum, antivenin 0290 Mydriatic: berefrine. (latrodectus mactans), antivenin (micrurus filvius), antive 0291 Nasal decongestant: nemazoline hydrochloride, nin (crotalidae) polyvalent, BCG vaccine, botulism anti pseudoephedrine polistirex. toxin, cholera vaccine, diphtheria antitoxin, diphtheria tox Neuroleptic: duoperone fumarate, risperidone. oid, diphtheria toxoid adsorbed, globulin, immune, hepatitis 0292) b immune globulin, hepatitis B virus vaccine inactivated, 0293 Neuromuscular blocking agent: atracurium besy influenza virus Vaccine, measles virus vaccine live, menin late, cisatracurium besylate, doxacurium chloride, gallamine gococcal polysaccharide vaccine group A, meningococcal triethiodide, metocurine iodide, mivacurium chloride, pan polysaccharide vaccine group C, mumps virus vaccine live, curonium bromide, pipecuronium bromide, rocuronium bro pertussis immune globulin, pertussis vaccine, pertussis vac mide, Succinylcholine chloride, tubocurarine chloride, vecu cine adsorbed, plague vaccine, poliovirus vaccine inacti ronium bromide. vated, poliovirus vaccine live oral, rabies immune globulin, 0294 Neuroprotective: dizocilpine maleate. rabies vaccine, Rh, (D) immune globulin, rubella virus vaccine live, Smallpox vaccine, tetanus antitoxin, tetanus 0295). NMDA antagonist: selfotel. immune globulin, tetanus toxoid, tetanus toxoid adsorbed, typhoid vaccine, yellow fever vaccine, vaccinia immune 0296 Non-hormonal sterol derivative: pregnenolone suc globulin, varicella-Zoster immune globulin. cinate. 0297. Oxytocic: carboprost, carboprost methyl, carbo 0275 Immunomodulator: dimepranolacedoben, imiqui prost tromethamine, dinoprost, dinoprost tromethamine, mod, interferon beta-lb., lisofylline, mycophenolate mofetil, dinoprostone, ergonovine maleate, meteneprost, methyler prezatide copper acetate. gonovine maleate, oxytocin, Sparteine Sulfate. 0276. Immunoregulator: azarole, fanetizole mesylate, 0298 Plasminogen activator: alteplase, urokinase. frentizole, oxamisole hydrochloride, ristianol phosphate, thymopentin, tilomisole. 0299 Platelet activating factor antagonist: lexipafant. 0300 Platelet aggregation inhibitor: acadesine, bera 0277 Immunostimulant: loxoribine, teceleukin. prost, beraprost sodium, ciprostene calcium, itaZigrel, 0278 Immunosuppressant: azathioprine, azathioprine lifarizine, oxagrelate. Sodium, cyclosporine, daltroban, gusperimus trihydrochlo 0301 Post-stroke and post-head trauma treatment: citi ride, sirolimus, tacrolimus. coline Sodium. 0279) Impotence therapy adjunct: deleguamine hydro 0302 Potentiator: pentostatin, talopram hydrochloride. chloride. 0303 Progestin: algestone acetophenide, amadinone 0280 Inhibitor: acarbose, atorvastatin calcium, benser acetate, anagestone acetate, chlormadinone acetate, cinges azide, brocresine, carbidopa, clavulanate potassium, tol, clogestone acetate, clomegestone acetate, desogestrel, daZmegrel, docebenone, epoprostenol, epoprostenol dimethisterone, dydrogesterone, ethynerone, ethynodiol sodium, epristeride, finasteride, flurbiprofen sodium, fure diacetate, etonogestrel, flurogestone acetate, gestaclone, grelate sodium, lufironil, miglitol, orlistat, pimagedine gestodene, gestonorone caproate, gestrinone, haloprogester hydrochloride, pirmagrel, ponalrestat, ridogrel, Sulbactam one, hydroxyprogesterone caproate, levonorgestrel, benZathine, Sulbactampivoxil, Sulbactam Sodium, Surona lynestrenol, medrogestone, medroxyprogesterone acetate, crine maleate, taZobactam, taZobactam Sodium, ticlopidine methynodiol diacetate, norethindrone, norethindrone hydrochloride, tirilazad mesylate, tolrestat, Velnacrine male acetate, norethynodrel, norgestimate, norgestomet, norg ate, Zifrosilone, Zileuton. estrel, oxogestone phenpropionate, progesterone, quingestanol acetate, quingestrone, tigestol. 0281 Keratolytic: alcloxa, aldioxa, benzoyl peroxide, dibenzothiophene, etarotene, isotretinoin, motretinide, 0304 Prostaglandin: cloprostenol sodium, fluprostenol picotrin diolanine, resorcinol, resorcinol monoacetate, sali Sodium, gemeprost, prostalene, Sulprostone. cylic acid, Sumarotene, tazarotene, tetroquinone, tretinoin. 0305 Prostate growth inhibitor: pentomone. 0282 LHRL agonist: deslorelin, goserelin, histrelin, 0306 Prothyrotropin: protirelin. lutrelin acetate, nafarelin acetate. 0307 Psychotropic: minaprine. 0283 Liver disorder treatment: malotilate. 0308 Pulmonary surface: beractant, colfosceril palmi 0284 Luteolysin: femprostalene. tate. US 2007/0093462 A1 Apr. 26, 2007 72

0309 Radioactive agent: fibrinogen ". fludeoxyglucose fos Sodium, trimetozine, uldazepam, Zaleplon, Zolazepam F', fluorodopa F, insulin I'', insulin I'', iobenguane hydrochloride, Zolpidem tartrate. I', iodipamide sodium I'', iodoantipyrine I'', iodocho lesterol I'', iodohippurate sodium I'', iodohippurate 0318 Selective adenosine all antagonist: apaxifylline. sodium I', iodohippurate sodium I'', iodopyracet I'', 0319 Serotonin antagonist: altanserin tartrate, ameser iodopyracet I'', iofetamine hydrochloride I'', iomethin gide, ketanserin, ritanserin. I', iomethin I'', iothalamate sodium I', iothalamate sodium I'', iotyrosine I'', liothyronine I'', liothyronine 0320 Serotonin inhibitor: cinanserin hydrochloride, fen I'', merisoprol acetate Hg'7, merisoprol acetate Hg', clonine, fonazine mesylate, Xylamidine tosylate. merisoprol Hg', selenomethionine Se7, technetium Tc'" 0321 Serotonin receptor antagonist: tropanserin hydro antimony trisulfide colloid, technetium Tc'" bicisate, tech chloride. netium Tc" disofenin, technetium Tc'" etidronate, tech netium Tc" exametazime, technetium Tc" furifosmin, 0322 Steroid: dexamethasone aceflrate, mometasone technetium Tc’" gluceptate, technetium Tc" lidofenin, furoate. technetium Tc" mebrofenin, technetium Tc’" medronate, 0323 Stimulant: amfonelic acid, amphetamine sulfate, technetium Tc’" medronate disodium, technetium Tc'" ampyZine Sulfate, arbutamine hydrochloride, azabon, caf mertiatide, technetium Tc'" oxidronate, technetium Tc 99. feine, ceruletide, ceruletide diethylamine, cisapride, dazo pentetate, technetium Tc" pentetate calcium trisodium, pride fluimarate, dextroamphetamine, dextroamphetamine technetium Tc" sestamibi, technetium Tc'" siboroxime, sulfate, difluanine hydrochloride, dimefline hydrochloride, technetium Tc'" succimer, technetium Tc" sulfur colloid, doxapram hydrochloride, etryptamine acetate, ethamivan, technetium Tc’" teboroxime, technetium Tc’" tetrofos fenethylline hydrochloride, flubanilate hydrochloride, min, technetium Tc’" tiatide, thyroxine I'', thyroxine I'', flurothyl, histamine phosphate, indriline hydrochloride, tolpovidone I'', triolein I'', triolein I''. mefexamide, methanphetamine hydrochlo ride, meth ylphenidate hydrochloride, pemoline, pyrovalerone hydro 0310 Regulator: calcifediol, calcitonin, calcitriol, clo dronic acid, dihydrotachysterol, etidronic acid, oxidronic chloride, Xamoterol. Xamoterol fumarate. acid, piridronate Sodium, risedronate Sodium, Secalciferol. 0324 Suppressant: amfliutizole, coxchicine, tazofelone. 0311 Relaxant: adiphenine hydrochloride, alcuronium 0325 Symptomatic multiple sclerosis: fampiridine. chloride, aminophylline, azumolene sodium, baclofen, ben Zoctamine hydrochloride, carisoprodol, chlorphenesin car 0326 Synergist: proadifen hydrochloride. bamate, chlorZoxaZone, cinflumide, cinnamedrine, 0327 Thyroid hormone: levothyroxine sodium, liothyro clodanolene, cyclobenzaprine hydrochloride, dantrolene, nine Sodium, liotrix. dantrolene sodium, femalamide, fenyripol hydrochloride, fetoxylate hydrochloride, flavoxate hydrochloride, fle 0328 Thyroid inhibitor: methimazole, propyithiouracil. taZepam, flumetramide.-flurazepam hydrochloride, 0329. Thyromimetic: thyromedan hydrochloride. hexafluorenium bromide, isomylamine hydrochloride, lor 0330 Tranquilizer: bromazepam, buspirone hydrochlo bamate, mebeverine hydrochloride, mesuprine hydrochlo ride, chlordiazepoxide, claZolam, clobazam, cloraZepate ride, metaxalone, methocarbamol, methixene hydrochloride, dipotassium, cloraZepate monopotassium, demoxepam, nafomine malate, neleZaprine maleate, papaverine hydro dexmedetomidine, enciprazine hydrochloride, gepirone chloride, pipoxolan. hydrochloride, hydroxyphenamate, hydroxy Zine 0312 Hydrochloride, quinctolate, ritodrine, ritodrine 0331 Hydrochloride, hydroxyzine pamoate, ketazolam, hydrochloride, rolodine, theophylline sodium glycinate, lorazepam, lorZafone, loxapine, loxapine Succinate, thiphenamil hydrochloride, xilobam. medazepam hydrochloride, nabilone, nisobamate, 0313 Repartitioning agent: cimaterol. oxazepam, pentabamate, piremperone, ripazepam, rolipram, Sulazepam, taciamine hydrochloride, temazepam, trifluba 0314 Scabicide: amitraz, crotamiton. Zam, tybamate, valnoctamide. 0315) Sclerosing agent: ethanolamine oleate, morrhuate 0332 Amyotrophic lateral sclerosis agents: riluzole. Sodium, tribenoside. 0333 Cerebral ischemia agents: dextrorphan hydrochlo 0316 Sedative: propiomazine. ride. 0317 Sedative-hypnotic: allobarbital, alonimid, alpra 0334 Paget’s disease agents: tiludronate disodium. Zolam, amobarbital sodium, bentazepam, brotizolam, but 0335 Unstable angina agents: tirofiban hydrochloride. abarbital, butabarbital sodium, butalbital, capuride, car bocloral, chloral betaine, chloral hydrate, chlordiazepoxide 0336 Uricosuric: benzbromarone, irtemazole, hydrochloride, cloperidone hydrochloride, clorethate, probenecid, Sulfinpyrazone. cyprazepam, dexclamol hydrochloride, diazepam, dichloral phenaZone, estaZolam, ethchlorVynol, etomidate, fenobam, 0337 Vasoconstrictor: angiotensin amide, fely pressin, flunitrazepam, fosazepam, glutethimide, halazepam, methysergide, methysergide maleate. lormetazepam, mecloqualone, meprobamate, methaqualone, 0338 Vasodilator: alprostadil, azaclorzine hydrochloride, midaflur, paraldehyde, pentobarbital, pentobarbital sodium, bamethan sulfate, bepridil hydrochloride, buterizine, cetiedil perlapine, prazepam, quazepam, reclazepam, roletamide, citrate, chromonar hydrochloride, clonitrate, diltiazem secobarbital, secobarbital sodium, Suproclone, thalidomide, hydrochloride, dipyridamole, droprenilamine, erythrity1 tet tracazolate, trepipam maleate, triazolam, tricetamide, triclo ranitrate, felodipine, flunarizine hydrochloride, fostedil, US 2007/0093462 A1 Apr. 26, 2007 hexobendine, inositol niacinate, iproxamine hydrochloride, budipine, budotitane, bunaprolast, bunaZosin, butenafine, isosorbide dinitrate, isosorbide mononitrate, isoXSuprine buthionine Sulfoximine, butiXocort propionate, cadeXomer hydrochloride, lidoflazine, mefenidil, mefenidil fumarate, iodine, calanolide A, calcipotriol, calphostin C, camonagrel, mibefradil dihydrochloride, mioflazine hydrochloride, mixi candesartan, candesartan cilexetil, candoXatril, candoXatri dine, nafronyl oxalate, nicardipine hydrochloride, nicer lat, capecitabine, capromab, capsaicin, captopril, carbazo goline, nicorandil, nicotinyl alcohol, nifedipine, nimodipine, mycin C, carbetocin, carbovir, carboxamide-amino-triazole, nisoldipine, Oxfenicine, Oxprenolol hydrochloride, pen carboxyamidotriazole, carboxymethylated B-1,3-glucan, taerythritol tetranitrate, pentoxifylline, pentrinitrol, perhex carperitide, carteolol, carumonam, carvedilol, carvotroline, iline maleate, pindolol, pirsidomine, prenylamine, propatyl carzelesin, castanospermine, cebaracetan, cecropin B, cef nitrate, Suloctidil, terodiline hydrochloride, tipropidil hydro capene pivoxil, cefdaloXime pentexil tosilate, cefdinir, chloride, tolazoline hydrochloride, Xanthinol niacinate. cefditoren pivoxil, cefepime, cefetamet, cefetamet pivoxil, 0339) Vulnerary: allantoin. cefixime, cefluprenam, cefinnetazole, cefinninox, cefodiz ime, cefoselis, cefotetan, cefotiam, cefotiam hexetil, cefo 0340 Wound healing agent: ersofermin. Zopran, cefpimizole, ce?piramide, cefpirome, cefpodoxime 0341 Xanthine oxidase inhibitor: allopurinol, oxypu proxetil, cefprozil, cefsulodin, cefteram, ceftibuten, cefiri rinol. axone, cefuroxime axetil, celastrol, celikalim, celiprolol. cepacidine A, cericlamine, cerivastatin, ceronapril, certo 0342. Other pharmaceutical agents include: 1-decpyrro parin Sodium, cetiedil, cetirizine, chloroorienticin A, chlo lidinone, 1-dodecpyrrolidinone, 16C.-fluoroestradiol, 16-epi roorienticin B, chloroquinoxaline Sulfonamide, cibenzoline, estriol, 16C.-gitoxin, 17C. estradiol, 17 B estradiol. 1 alpha cicaprost, ciclesonide, cicletanine, cicloprolol, cidofovir, hydroxyvitamin D2,2'-nor-cGMP 20-epi-1,25 cilansetron, cilaZapril, cilnidipine, cilobradine, cilostaZol. dihydroxyvitamin D3, 22-oxacalcitriol, 2CVV, 3-isobutyl cimetropium bromide, cinitapride, cinolazepam, cioteronel, GABA, 6-FUDCA, 7-methoxytacrine, abamectin, abano ciprofibrate, ciprofloxacin, ciprostene, cis-porphyrin, quil, abecarnil, abiraterone, acadesine, acamprosate, acar cisapride, cisatracurium besilate, cistinexine, citalopram, bose, aceclofenac, acemannan, acetomepregenol, acetyl-L- citicoline, citreamicin alpha, cladribine, clarithromycin, carnitine, acetylcysteine, N-acetylmethadol, acifran, clausenamide, clebopride, clinafloxacin, clobazam, clobeta acipimox, acitemate, acitretin, aclarubicin, aclatonium, Sone butyrate, clodronic acid, clomethiazole, clopidogrel, napadisilate, aconiazide, acrivastinet, adafenoxate, ada clotrimazole, colestimide, colfosceril palmitate, collismycin palene, adatanserin, adecypenol, adefovir dipivoxil, adelm A, collismycin B, combretastatin A4, complestatin, conage idrol, ademetionine, adinazolam, adiposin, adoZelesin, nin, contignasterol, contortrostatin, cosalane, costatolide, adrafinil, alacepril, aladapcin, alaptide, albendazole, albola cotinine, coumermycin A1, cucumariosid, curacin A, curd brin, aldecalmycin, aldesleukin, alendronic acid, alentemol. lan sulfate, curiosin, cyclazosin, cyclic HPMPC, cycloben alfacalcidol, alfuizosin, alglucerase, alinastine, alosetron, Zaprine, cyclobut A, cyclobut G, cyclocapron, cycloplatam, alpha idoSone, alprostadil, altretamine, altromycin B. amba cyclosin, cyclothialidine, cyclothiazomycin, cypemycin, mustine, amelometasone, ameSergide, ameZinium metilsul cyproterone, cytarabine ocfosfate, cytochalasin B, daclix fate, amfebutamone, amidox, amifloxacin, amifostine, amio imab, dactimicin, daidzein, daidzin, dalfopristin, dalteparin darone, amisulpride, amlexanoX, amlodipine, amlodipine, Sodium, danaparoid, daphnodorin A, dapiprazole, dapitant, ampiroXicam, aminone, amrubicin, amsacrine, amylin, darifenacin, darlucin A, darsidomine, ddOTP, decitabine, amythiamicin, anagrelide, anakinra, ananain, anaritide, deferiprone, deflazacort, dehydrodidemrnin B, dehydroepi anastroZole, andrographolide, anordrin, apadoline, apafant, androsterone, delapril, delequamine, delfaprazine, delmopi apaxifylline, aphidicolin glycinate, apraclonidine, aproSu nol, delphinidin, deoxypyridinoline, deprodone, depsidomy late Sodium, aptiganel, apurinic acid, aranidipine, arbekacin, cin, deramciclane, dermatan Sulfate, desflurane, desirudin, arbidol, arbutamine, ardeparin Sodium, arecatannin B1, deslorelin, desmopressin, desogestrel, desoxoamiodarone, argatroban, aripiprazol, arotinolol, asimadoline, aspalatone, detajmium bitartrate, dexifosfamide, dexketoprofen, dex asperfuran, aspoxicillin, astemizole, asulacrine, atameStanie, loxiglumide, dexmedetomidine, dexpemedolac, dexraZOX atenolol, S-atevirdine, atosiban, atovaquone, atpenin B, atri ane, dexSotalol, dextrin 2-sulphate, dexVerapamil, dezina mustine, atrinositol, aureobasidin A. azadirachtine, aza mide, dezocine, diaziquone, diclofenac digolil, diclofenac setron, azatyrosine, azelaic acid, azelastine, aZelnidipine, potassium, dicranin, didemnin B, didox, dienogest, diethyl azimilide, azithromycin, aZosemide, aztreonam, baccatin III, homospermine, diethylnorspermine, dihydrexidine, dihy bacoside A, bacoside B, bactobolamine, balazipone, balhi dro-5-azacytidine, dimethyl prostaglandin A1, dimethylho mycin, balofloxacin, balsalazide, bambuterol, baohuoside 1. mospennine, dimiracetam, dioxamycin, diphency prone, bamidipine, basifingin, batebulast, batimastat, beauvericin, diphenyl spiromustine, diprafenone, dipropylnorspermine, becaplermin, becliconazole, befloxatone, belfosdil, bellena dirithromycin, discodermolide, disulfiram, ditekiren, docar mine, benflumetol, benidipine, benzisoxazole, benzochlor pamine, docosanol. 1-dofetilide, dolasetron, domitroban, ins, benzoidazoxan, benzoylstaurosporine, benztropine, dopexamine, dorzolamide, doSmalfate, dotarizine, doxacu bepridil, beractant, beraprost, berlafenone, bertosamil, rium chloride, doxazosin, doxifluridine, doxofylline, dracu besipirdine, beta-alethine, betaclamycin B, betamipron, lin, draflazine, droloxifene, dronabinol, drosperidone, dro betaxolol, betulinic acid, bevantolol, bicalutamide, bife taverine acephyllinate, droxicam, ebiratide, ebrotidine, melane, bimakalim, bimithil, binospirone, bioxalomycin ebselen, ecabapide, ecabet, ecadotril, ecdlisteron, echicetin, alpha2, biriperone, bis-benzimidazole A, bis-benzimidazole echistatin, ecomustine, ecteinascidin 722, ecteinascidin 729, B, bisantrene, bisaramil, bisaziridinylspermine, bisnafide, ecteinascidin 743, edaravone, edelfosine, edobacomab, bisoprolol, bistramide D, bistramide K, bistratene A, bol edrecolomab, efegatran, eflornithine, efonidipine, egualen, dine, bopindolol, brefeldin, breflate, brimonidine, bro elcatonin, eletriptan, elgodipine, eliprodil, eltenac, mfenac, bromperidol, bropirimine, bucindolol, budesonide, emakalim, emedastine, emiglitate, emitefur, emoctakin, ena US 2007/0093462 A1 Apr. 26, 2007 74 doline hydrochloride, enalapril, enaZadrem, englitaZone, lorglumide, lomoxicam, losartan, losigamone, losoxantrone, enlimomab, enoxacin, enoxaparin sodium, enoXimone, enta loteprednol, loviride, loxoribine, lubeluzole, lurtotecan, capone, enterostatin, epoprostenol, epoxymexrenone, epris luteinizing hormone, lutetium, luZindole, lydicamycin, teride, eprosartan, eptastigmine, erdosteine, ersentilide, lysofylline, lysostaphin, magainin 2 amide, magnolol, mal erSofermin, erytlritol, esuprone, etanidazole, etanterol, etha lotochromene, mallotojaponin, malotilate, mangafodipir, cizin, ethinylestradiol, etizolam, etodolac, etoposide phos manidipine, maniwamycin A, mannostatin A, manumycin E, phate, etrabamine, everninomicin, examorelin, exemestane, manumycin F. mapinastine, marimastat, masoprocol, fadrozole, faerieflungin, famciclovir, fampiridine, fantofar maspin, massetolide, meterelin, methoxatone, methylhista one, faropenem, fasidotril, fasudil, fazarabine, fedotozine, mine, R-alpha, methylinosine monophosphate, methylpred felbamate, fenofibrate, fenoldopam, fenretinide, fenspiride, nisolone aceponate, methylprednisolone Suleptanate, meti fenticonazole, fepradinol, ferpifosate Sodium, ferristene, fer pamide, metoclopramide, metoprolol. S-metrifonate, rixan, ferumoxsil, fexofenadine, flavopiridol, flecainide, fle mibefradil, michellamine B, microcolin A, midodrine, mife robuterol, fleroxacin, flesinoxan, flezelastine, flobufen, flo pristone, miglitol, millacemide, milameline, mildronate, mil moxef, florfenicol, florifenine, flosatidil, fluasterone, nacipran, mihinone, miltefosine, minaprine, miokamycin, fluconazole, fludarabine, flumazenil, flumecinol, flume mipragoside, mirfentanil, mirimostim, mirtazapine, miso quine, flunarizine, fluocalcitriol, fluorodaunorunicin hydro prostol, mitoguaZone, mitolactol, mitonafide, mitoxantrone, chloride, fluoxetine, R-fluoxetine, S-fluparoxan, flupirtine, mivacurium chloride, mivaZerol, mixanpril, mizolastine, flurbiprofen axetil, flurithromycin, fluticasone propionate, mizoribine, moclobemide, modafinil, moexipril, mofaro flutrimazole, fluvastatin, fluvoxamine, forasartan, forfen tene, mofeZolac, molgramoStim, mometaSone, montirelin, imex, formestane, formoterol, formoterol, R.R-fosfomycin, mopidamol, moracizine, mosapramine, mosapride, motilide, trometamol, fosinopril, fosphenytoin, fostriecin, fotemus moxiraprine, moXonidine, nadifloxacin, nadroparin calcium, tine, gabapentin, gadobenic acid, gadobutrol, gadodiamide, nafadotride, nafamo.stat, nafarelin, naftopidil, naglivan, gadodiamnide-EOB-DTPA, gadolinium texaphyrin, gadot nagrestip, nalmefene, naphterpin, napsagatran, naratriptan, eric acid, gadoteridol, gadoversetamide, galantamine, nartograstim, nasaruplase, nateplase, niperotidine, nirav galdansetron, gallopamil, galocitabine, gamolenic acid, oline, nisamycin, nisin, nisoldipine, nitazoxanide, niteca ganirelix, gepirone, gestrinone, girisopam, glaspimod, glau pone, nitrendipine, nitrendipine, S-nitrofurantoin monohy cocalyxin A, glutapyrone, glycopine, glycopril, granisetron, drate, nitrullyn, nizatidine, ofloxacin, okicenone, grepafloxacin, halichondrin B, halofantrine, halomon, halo olanzapine, olopatadine, olprinone, olSalazine, omeprazole, predone, hatomamicin, hatomarubigin A, hatomarubigin B, onapristone, ondansetron, ondansetron, R-ontazolast, ora hatomarubigin C, hatomarubigin D, ibogaine, ibopamine, cin, otenZepad, oxaliplatin, oxamisole, Oxandrolone, ibudilast, illimaquinone, ilmofosine, illomastat, illoperidone, oxaprozin, oxaunomycin, oXcarbazepine, oxiconazole, iloprost, imidapril, imidazenil, indinavir, indolidan, oxiracetam, oxodipine, oZagrel, palauamine, palinavir, indometacin farnesil, indometacin, tropine ester, indoramin, palmitoylrhizoxin, pamaqueside, pamicogrel, pamidronic inocoterone, inogatran, inolimomab, interferon alfa, inter acid, panamesine, panaxytriol, panipenem, panipenum, pan feron alfa-2a, interferon alfa-2B, interferon alfa-N 1, inter norin, panomifene, pantethine, pantoprazole, parabactin, feron alfa-N3, interferon B, interferon B-1 A1, interferon pamaparin Sodium, paroxetine, parthenolide, paZelliptine, B-1B, interferon gamma-1A, interferon gamma-1B, inter paZufloxacin, pefloxacin, pegaspargase, peldesine, pemed feron omega, interferon, consensus, interleukin-1, interleu olac, pemirolast, penciclovir, pentafuside, pentamidine, pen kin-1 alpha, interleukin-1 f, interleukin-10, interleukin-11, tamorphone, pentigetide, pentosan, pentostatin, pentrozole, interleukin-12, interleukin-12, interleukin-15, interleukin-2, perflubron, perfosfamide, pergolide, perindoprilat, per interleukin-3, interleukin-4, interleukin-5, interleukin-7, oSpirone, phenaridine, phenazinomycin, phenserine, phen interleukin-8, iobenguane, iobitridol, iodoamiloride, iodo Succinal, phentolamine mesilate, phenylacetate, phenylala doxorubicin, iofratol, iomeprol, iopentol, iopromide, iopy nyl ketoconazole, picenadol, picibanil, picroliv, rol, iotriside, ioversol, ioXilan, ipazilide, IpdR, ipenoxazone, picumeterol, pidotimod, pilocarpine hydrochloride, pilsic ipidacrine, ipomeanol, 4-ipriflavone, ipsapirone, irbesartan, ainide, pimagedine, pimilprost, pimobendan, pinacidil, irinotecan, irloxacin, irsogladine, irtemazole, isalsteine, pinocebrin, pioglitaZone, pipecuronium bromide, pirarubi isbogrel, isepamicin, isobengaZole, isofloxythepin, iso cin, piretanide, pirfenidone, piritrexim, pirlindole, pirma homohalicondrin B, isopropyl unoprostone, isradipine, ita grel, pirmenol, pirodavir, pirodomast, piroXicam cinnamate, meline, itasetron, itopride, itraconazole, ketoprofen, R-ke propagermanium, propentofylline, propionylcamitine, toprofen, S-ketorolac, lacidipine, lactitol, lactivicin, laennec, L-propiram, propiram +paracetamol, propiverine, propyl lafutidine, lamelrarin-N triacetate, lamifiban, lamivudine, bis-acridone, prostaglandin J2, prostratin, protegrin, proto lamotrigine, lanoconazole, lanperisone, lanreotide, lanSo Sufloxacin, prulifloxacin, pyrazoloacridine, quazepam, que prazole, latanoprost, lateritin, laurocapram, lazabemide, tiapine, quiflapon, quinagolide, quinapril, quinfamide, lemefloxacin, lemildipine, leminoprazole, lenercept, quinupristin, raloxifene, raltitrexed, ramatroban, ramipril, lenograstim, lentinan Sulfate, leptin, leptolstatin, lercanid ramosetron, ranelic acid, ranitidine bismuth citrate, ranola ipine, lerisetron, lesopitron, letraZuril, letrozole, leu Zine, recainam, regavirumab, relaxin, repirinast, resinfera comyzin, leuprorelin, levcromakalim, levetiracetam, levo toxin, reticulon, reviparin sodium, revizinone, ricasetron, betaxolol, levobunolol, levobupivacaine, levocabastine, ridogrel, rifabutin, rifapentine, rifaximin, rilopiroX, riluzole, levocamitine, levodropropizine, levofloxacin, levomoprolol. rimantadine, rimexolone, rimoprogin, riodipine, ripisartan, levonorgestrel, levormeloxifene, levosimendan, levo risedronic acid, rispenzepine, risperidone, ritanserin, riti Sulpiride, linotroban, linsidomine, lintitript, lintopride, lio penem, ritipenem acoxil, ritolukast, ritonavir, rizatriptan thyronine Sodium, lirexapride, lisinopril, lobaplatin, lobu benzoate, rohitukine, rokitamycin, ropinirole, ropivacaine, cavir, lodoxamide, lombricine, lomefloxacin, lomerizine, roquinimex, roXatidine, roXindole, roXithromycin, rubigi lometrexol, lonazolac, lonidamine, loracarbef, loratadine, none B1, ruboxyl, rufloxacin, rupatidine, ruzadolane, Safin US 2007/0093462 A1 Apr. 26, 2007

gol, Safironil, Saintopin, Salbutamol, R-Salmeterol, Salme cin, avoparcin, azithromycin, aZlocillin, azlocillin Sodium, terol, R-Sainacedin, sameridine, Sampatrilat, Sanfetrinem, bacampicillin hydrochloride, bacitracin, bacitracin methyl Saprisartan, sapropterin, saquinavir, sarcophytol A Sargra ene disalicylate, bacitracin Zinc, bambermycins, benzoylpas mostim, Sarpogrelate, Saruplase, Saterinone, satigrel, Satu calcium, berythromycin, betamicin Sulfate, biapenem, momab pendetide, Selegiline, selenium thiosemicarbazone, biniramycin, biphenamine hydrochloride, bispyrithione sematilide, semduramicin, Semotiadil, Semustine, sermore magSulfex, butikacin, butirosin Sulfate, capreomycin Sulfate, lin, Sertaconazole, sertindole, Sertraline, setiptiline, carbadox, carbenicillin disodium, carbenicillin indanyl Sevirumab, sevoflurane, Sezolamide, silipide, silteplase, sim Sodium, carbenicillin phenyl sodium, carbenicillin potas endan, simvastatin, sinitrodil, sinnabidol, sipatrigine, siroli sium, carumonam sodium, cefaclor, cefadroxil, cefaman mus, sizofiran, Somatomedin B, Somatomedin C, somatrem, Somatropin, Sonermin, Stalol, staurosporine, stavudine, dole, cefamandole nafate, cefamandole sodium, cefaparole, stepronin, stipiamide, Stiripentol, Stobadine, Succibun, cefatrizine, cefazaflur Sodium, cefazolin, cefazolin Sodium, Sucralfate, Sulfasalazine, Sulfmnosine, Sulfoxamine, cefbuperaZone, cefdinir, cefepime, cefepime hydrochloride, Sulopenem, Sultamicillin, Sultopride, Sulukast, Sumatriptan, cefetecol, cefixime, cefinenoxime hydrochloride, cefimeta Symakalim, tandospirone, tapgen, taprostene, tasosartan, Zole, cefimnetazole Sodium, cefonicid monosodium, taZanolast, tazarotene, teicoplanin, telenzepine, tellurapyry cefonicid sodium, cefoperaZone sodium, ceforanide, cefo lium, telmesteine, telmisartan, temocapril, temoporfin, taxime Sodium, cefotetan, cefotetan disodium, cefotiam temozolomide, tenidap, teniposide, tenosal, tenoxicam, hydrochloride, cefoxitin, cefoxitin Sodium, cefpimizole, cef tepirindole, tepoxalin, teraZosin, terbinafine, terfenadine, pimizole Sodium, ce?piramide, ce?piramide Sodium, cef terflavoxate, terguride, terlakiren, terlipressin, terodiline, pirome Sulfate, cefpodoxime proxetil, cefprozil, cefroxa tertatolol, testosterone buciclate, tetrachlorodecaoxide, tet dine, cefsulodin Sodium, ceftazidime, ceftibuten, razomine, thaliblastine, thalidomide, thiocoraline, ceftizoxime sodium, ceftriaxone sodium, cefuroxime, thiofedrine, thiomarinol, thioperamide, thyroid stimulating cefuroxime axetil, cefuroxime pivoxetil, cefuroxime hormone, tiagabine, tianeptine, tiapafant, tibolone, ticlopi Sodium, cephacetrile sodium, cephalexin, cephalexin hydro dine, tienoxolol, tilisolol, tilnoprofen arbamel, tiludronic chloride, cephaloglycin, cephaloridine, cephalothin Sodium, acid, tinzaparin Sodium, tiotropium bromide, tipredane, cephapirin Sodium, cephradine, cetocycline hydrochloride, tiqueside, tirandalydigin, tirapazamine, tirilazad, tirofiban, cetophenicol, chloramphenicol, chloramphenicol palmitate, tiropramide, topsentin, torasemide, toremifene, toSufloxacin, chloramphenicol pantothenate complex, chloramphenicol trafermin, trandolapril, traxanox, tretinoin, tretinoin tocof Sodium Succinate, chlorhexidine phosphanilate, chloroxyle eril, triacetyluridine, tricaprilin, trichohyalin, trichosanthin, nol, chlortetracycline bisulfate, chlortetracycline hydrochlo alpha, triciribine, trientine, triflavin, trimegestone, triptore ride, cinoxacin, ciprofloxacin, ciprofloxacin hydrochloride, lin, troglitaZone, trombodipine, tropisetron, trospectomycin, cirolemycin, clarithromycin, clinafloxacin hydrochloride, trovafloxacin, troVirdine, tucaresol, tulobuterol, tylogenin, clindamycin, clindamycin hydrochloride, clindamycin urapidil, uridine triphosphate, Valaciclovir, Valproate mag palmitate hydrochloride, clindamycin phosphate, clofaz nesium, Valproate semisodium, Valsartan, Vamicamide, imine, cloxacillin benzathine, cloxacillin Sodium, cloxyquin, Vanadeine, Vaninolol, Vapreotide, variolin B. velaresol, ven colistimethate sodium, colistin Sulfate, coumermycin, lafaxine, Veramine, Verapamil, S-Verdins, Veroxan, Vertepor coumermycin sodium, cyclacillin, cycloserine, dalfopristin, fin, Vesnarinone, Vexibinol, vigabatrin, vinbumine citrate, dapsone, daptomycin, demeclocycline, demeclocycline Vinburnine resinate, Vinconate, vinorelbine, Vinpocetine, hydrochloride, demecycline, denofungin, diaveridine, Vinpocetine citrate, Vintoperol, Vinxaltine, Voriconazole, dicloxacillin, dicloxacillin Sodium, dihydrostreptomycin Vorozole, Voxergolide, Xemilofiban, Ximoprofen, yan Sulfate, dipyrithione, dirithromycin, doxycycline, doxycy gambin, Zabicipril, Zacopride, Zacopride, R-Zafirlukast, Zal cline calcium, doxycycline fosfatex, doxycycline hyclate, citabine, Zaleplon, Zalospirone, Zaltoprofen, Zanamivir, droxacin sodium, enoxacin, epicillin, epitetracycline hydro Zankiren, Zanoterone, Zatebradine, Zatosetron, Zenarestat, chloride, erythromycin, erythromycin acistrate, erythromy Zeniplatin, Zifrosilone, Zilascorb, Zileuton, Zinostatin Sti cinestolate, erythromycin ethylsuccinate, erythromycin glu malamer, Ziprasidone, Zoledronic acid, Zolmitriptan, Zolpi ceptate, erythromycin lactobionate, erythromycin dem, Zonisamide, Zopiclone, Zopiclone, S-Zopolrestat, propionate, erythromycin Stearate, ethambutol hydrochlo Zotepine. ride, ethionamide, fleroxacin, floxacillin, fludalanine, flume quine, fosfomycin, fosfomycin tromethamine, fumoxicillin, furazolium chloride, furazolium tartrate, fusidate Sodium, Specific Examples of Antibacterials fusidic acid, gentamicin Sulfate, gloXimonam, gramicidin, 0343. When antibacterial activity is a desired property of haloprogin, hetacillin, hetacillin potassium, hexedine, iba the disclosed ionic liquids, one or more of the ions in the floxacin, imipenem, isoconazole, isepamicin, isoniazid, disclosed ionic liquids can be an antibacterial. That is the josamycin, kanamycin Sulfate, kitasamycin, levofuralta one or more kinds of cations, one or more kinds of anions, done, levopropylcillin potassium, lexithromycin, lincomy or both cations and anions can be an antibacterial. Many of cin, lincomycin hydrochloride, lomefloxacin, lomefloxacin suitable antibacterial have already been disclosed herein hydrochloride, lomefloxacin meSylate, loracarbef mafenide, (e.g., many QACs have antibacterial properties). Further meclocycline, meclocycline Sulfosalicylate, megalomicin examples of Suitable antibacterial agents include, but are not potassium phosphate, medulidox, meropenem, methacycline, limited to, acedapsone, acetosulfone sodium, alamecin, methacycline hydrochloride, methenamine, methenamine alexidine, amdinocillin, amdinocillin pivoxil, amicycline, hippurate, methenamine mandelate, methicillin Sodium, amifloxacin, amifloxacin mesylate, amikacin, amikacin Sul metioprim, metronidazole hydrochloride, metronidazole fate, aminosalicyhc acid, aminosalicylate sodium, amoxicil phosphate, mezlocillin, meZlocillin sodium, minocycline, lin, amphomycin, amplicillin, amplicillin Sodium, apalcillin minocycline hydrochloride, mirincamycin hydrochloride, Sodium, apramycin, aspartocin, astromicin Sulfate, avilamy monensin, monensin Sodiumr, nafcillin Sodium, nalidixate US 2007/0093462 A1 Apr. 26, 2007 76

Sodium, nalidixic acid, natainycin, nebramycin, neomycin Specific Examples of Antiviral palmitate, neomycin Sulfate, neomycin undecylenate, 0345 When antiviral activity is a desired property of the netilmicin Sulfate, neutramycin, nifuradene, nifuraldeZone, disclosed ionic liquids, one or more of the ions in the nifuratel, nifuratrone, nifurdazil, nifurimide, nifiupirinol, disclosed ionic liquids can be an antiviral. Examples of nifurquinazol, nifurthiazole, nitrocycline, nitrofurantoin, suitable antiviral actives include, but are not limited to, nitromide, norfloxacin, novobiocin Sodium, ofloxacin, acemannan, acyclovir, acyclovir Sodium, adefovir, aloVu onnetoprim, oxacillin Sodium, oximonam, oximonam dine, alvircept Sudotox, amantadine hydrochloride, aranotin, Sodium, oxolinic acid, oxytetracycline, oxytetracycline cal arildone, atevirdine mesylate, avridine, cidofovir, cipamfyl cium, Oxytetracycline hydrochloride, paldimycin, parachlo line, cytarabine hydrochloride, delavirdine mesylate, desci rophenol, paulomycin, pefloxacin, pefloxacin mesylate, clovir, didanosine, disoxaril, edoxudine, enviradene, penamecillin, penicillin G benzathine, penicillin G potas enviroxime, famciclovir, famotine hydrochloride, fiacitab sium, penicilling procaine, penicilling sodium, penicillin V. ine, fialuridine, fosarilate, foScamet Sodium, fosfonet penicillin V benzathine, penicillin V hydrabamine, penicillin Sodium, ganciclovir, ganciclovir Sodium, idoxuridine, V potassium, pentizidone sodium, phenyl aminosalicylate, kethoxal, lamivudine, lobucavir, memotine hydrochloride, piperacillin Sodium, pirbenicillin Sodium, piridicillin methisaZone, nevirapine, penciclovir, pirodavir, ribavirin, Sodium, pirlimycin hydrochloride, pivampicillin hydrochlo rimantadine hydrochloride, saquinavir mesylate, Somanta dine hydrochloride, Sorivudine, statolon, stavudine, tillorone ride, pivampicillin pamoate, pivampicillin probenate, poly hydrochloride, trifluridine, Valacyclovir hydrochloride, myxin B sulfate, porfiromycin, propikacin, pyrazinamide, Vidarabine, Vidarabine phosphate, Vidarabine Sodium phos pyrithione Zinc, quindecamine acetate, quinupristin, raceph phate, viroXime, Zalcitabine, Zidovudine, ZinviroXime, and enicol, ramoplanin, ranimycin, relomycin, repromicin, Tamiflu. rifabutin, rifametane, rifamexil, rifamide, rifampin, rifapen tine, rifaximin, rollitetracycline, rollitetracycline nitrate, rosa 0346) These and other suitable antivirals can be identified ramicin, rosaramicin butyrate, rosaramicin propionate, rosa based on the desired properties of the antiviral and whether ramicin Sodium phosphate, rosaramicin Stearate, roSoxacin, the antiviral is or can be converted into an ion. As noted, roXarsone, roXithromycin, Sancycline, Sanfetrinem Sodium, identification of whether an antiviral is an ion or can be Sarmoxicillin, Sarpicillin, scopafungin, Sisomicin, sisomicin converted into an ion can be done by a skilled artisan Sulfate, sparfloxacin, spectinomycin hydrochloride, spira inspecting the chemical structure of the antiviral. mycin, stallimycin hydrochloride, Steflimycin, streptomycin Specific Examples of Pesticidal Actives Sulfate, Streptonicozid, Sulfabenz, Sulfabenzamide, Sulfac 0347 When pesticidal activity is a desired property of the etamide, Sulfacetamide Sodium, Sulfacytine, Sulfadiazine, disclosed ionic liquids, one or more of the ions in the Sulfadiazine sodium, Sulfadoxine, Sulfalene, Sulfamerazine, disclosed ionic liquids can be a pesticide. Included within Sulfameter, Sulfamethazine, Sulfamethizole, Sulfamethox the meaning of "pesticide' are insecticides and fingicides. azole, Sulfamonomethoxine, Sulfamoxole, Sulfanilate Zinc, Examples of suitable pesticides include, but are not limited to, carfentraZone-ethyl, SulfentraZone, clomaZone, diclofop Sulfanitran, Sulfasalazine, Sulfasomizole, Sulfathiazole, Sul methyl, oxamyl propargite, prosulfuron, pyridate, pyriftalid, faZamet, Sulfisoxazole, Sulfisoxazole acetyl, Sulfisboxazole S-metolachlor, simazine, terbuthylazine, terbutryn, triasul diolamine, Sulfomyxin, Sulopenem, Sultamricillin, Suncillin furon, trifloxysulfuron, trinexapac-ethyl, ametryn, atrazine, Sodium, talampicillin hydrochloride, teicoplanin, temafloxa benoxacor, bifenthrin, butafenacil, choline azide, chlortolu cin hydrochloride, temocillin, tetracycline, tetracycline ron, cinosulfuron, clodinafop, cloquintocet, DEET, desm hydrochloride , tetracycline phosphate complex, tetroX etryn, dicamba, dimethachlor, dimethametryn, DTPA NaFe, oprim, thiamphenicol, thiphencillin potassium, ticarcillin EDDHA NaFe, fenclorim, flumetralin, fluometuron, fluthi cresyl Sodium, ticarcillin disodium, ticarcillin monosodium, acetmethyl, halosulfuron, isoproturon, metobromuron, ticlatone, tiodonium chloride, tobramycin, tobramycin Sul metolachlor, norflurazon, oxasulfuron, piperophos, preti fate, to Sufloxacin, trimethoprim, trimethoprim Sulfate, trisul lachlor, primisulfuron, prometryn, propaquizafop, aciben fapyrimidines, troleandomycin, trospectomycin Sulfate, Zolar-s-methyl, chlorothalonil, cyproconazole, cyprodinil, tyrothricin, Vancomycin, Vancomycin hydrochloride, Virgin difenoconazole, fempropidin, fenpropimorph, furalaxyl, iamycin, and Zorbamycin. Penicillin G, which is used as an metalaxyl, metalaxyl-m, oxadixyl, penconazole, propicona antibacterial agent for infections including pneumonia, men Zole, pyrifenox, thiabendazol, abamectin, bromopropylate, ingitis, and skin, bone, joint, stomach, blood, and heart valve cypermethrin, cypermethrin high-cis, cyromazine, diafenthi infections, is a particular example Suitable for use herein. uron, diazinon, dichlorvos, disulfoton, emamectinbenzoate, taZobactum, sold under the trade names ZOSYNTM and fenoxycarb, formothion, furathiocarb, lufenuron, methi TAZOCINTM, ceftrioxone, sold under the trade name dathion, permethrine, codilemone, phosphamidon, profeno ROCEPHINTM, and metronidazol, sold under the trade name fos, pymetrozine, quinalphos, terrazole, thiamethoxam, thio FLAGYLTM, are also used to treat bacterial infections and cyclam, thiometon, triallate, trifloxystrobin, VincloZolin, are further examples of Suitable compounds that can be used Zetacypermethrin, and the like. Prohexadione is a FDA to prepare the disclosed ionic liquids. approved reduced risk fungicide and is also useful for the 0344) These and other suitable antibacterials can be iden disclosed ionic liquids. Further examples of suitable pesti tified based on the desired properties of the antibacterial and cides can be found in The Pesticide Manual, 11" Edition, whether the antibacterial active is or can be converted into British Crop Protection Council, 1997, which is incorpo an ion. As noted, identification of whether an antibacterial rated by reference herein at least for its teaching of pesti active is an ion or can be converted into an ion can be done cides. by a skilled artisan inspecting the chemical structure of the 0348 These and other suitable pesticides can be identi antibacterial. fied based on the desired properties of the pesticide and US 2007/0093462 A1 Apr. 26, 2007 77 whether the pesticide is or can be converted into an ion. As Specific Examples of Energetics noted, identification of whether a pesticide is an ion or can 0352. The disclosed ionic liquid compositions can also be converted into an ion can be done by a skilled artisan include high energy ingredients as well as explosive mate inspecting the chemical structure of the pesticide. rials. The ability to prepare a particular composition with high energy content Substituents (fuel) on one ion and high Specific Examples of Herbicidal Actives oxygen balance (oxidizers) on the other ion opens wide 0349 When herbicidal activity is a desired property of applicability in today's high energy compounds industry. the disclosed ionic liquids, one or more of the ions in the The ability to independently form differentially functional disclosed ionic liquids can be a herbicide. Examples of ized groups of ions, then chose two of interest and combin suitable herbicides include, but are not limited to, carfen ing them on demand to form desired strength energetic traZone, imazapyr, benefin, acifluorfen, and 2-2-chloro-3- material (Scheme 1) opens the doors for the quick prepara (2.2.2-trifluoroethoxymethyl)-4-methylsulfonylbenzoylcy tion of customizable energetic materials (e.g., explosives with pre-designed power) and more safe storage technique clohexane-1. of those energetic materials since the components are sepa 0350 Other suitable herbicides include inhibitors of the rated before usage. The disclosed compositions can be biosynthesis of branched amino acids Such as ethoxysulfu prepared according to one of the following reaction proto ron, flumetSulam, halosulfuron, imaZamox, imazapyr, cols. imaZaquin, imazethapyr, metoSulam, nicosulfuron, primisul furon, prosulfuron, rimsulfuron, thifensulfuron-methyl, tri flusulfuron, N-(4,6-dimethoxypyrimidin-2-yl)aminocarbo Scheme 1: Protocol 1. nyl-2-dimethylaminocarbonyl-5- formylaminobenzenesulfonamide (Foramsulfuron), and the like. Still further, suitable herbicides include inhibitors of the e/ photosynthesis electron transport such as ametryne, atrazine, En f y IAC I. bromoxynil, cyanazine, diuron, hexaZinone, metribuzin, N pyridate, terbuthylazine, and the like. In yet further examples, suitable herbicides for the disclosed ionic liquids R include synthetic auxins such as copyralid, dicamba, diflufenzopyr, fluroxypyr, and the like. Inhibitors of fatty En En G. ambient conditions acid biosynthesis, such as butylate, EPTC, fenoxaprop-P- y y IC Heharmless solvent ethyl, and the like, can also be used in the disclosed ionic N-N (e.g. H2O, EtOH) liquid compositions. In other examples, Suitable herbicides can include inhibitors of cell division such as acetochlor, R alachlor, dimethenamid, flufenacet, mefenacet, metolachlor, ey 9 S-metolachlor, thenylchlor, and the like. In still other tify En N En examples, the herbicide can be an inhibitor of protoporphy &y || "Y Y rinogen oxidase. Such as fluthiacet-methyl, carfentraZone N-N ethyl, and the like. Inhibitors of hydroxyphenylpyruvate R dioxygenase, Such as isoxaflutole, mesotrione, Sulcotrione, 4-(4-trifluoromethyl-2-methylsulfonylbenzoyl)-5-hydroxy 1-methyl-3-methylpyrazole, and the like, can also be used. Ice ise Further examples of suitable herbicides include, but are not limited to, glyphosate, pendimethalin, trifluralin, asulam, triaziflam, diflufenican, glufosinate-ammonium, and the where En is an energetic functional group containing either like. Clofencet, fluroxpyr, mesosulfuron, diflufenzopyr are high oxygen or nitrogen content (including but not limited further examples of suitable herbicides and they are FDA to: nitro, amino, cyano, azido, alkyl nitro, alkyl amino, alkyl approved. cyano, alkyl azido, alkoxy nitro, alkoxy amino, alkoxy cyano, and alkoxy azido), IA is an innocuous anion, IC+ is Specific Examples of Other Ions an innocuous cation, and ICIIA) is an easily removable and harmless byproduct from the metathesis reaction. The reac 0351. In addition to the pharmaceutical, antibacterial, tion proceeds via ion exchange reaction in solvent system antiviral, pesticidal, and herbicidal actives disclosed herein, media (solvent system is the solvent or the mixture of the other compounds that are ions or can be converted to ions Solvents in which at least one of the starting materials can be used in the disclosed ionic liquid compositions. dissolves). The solvents (or solvent) with substrates dis Specific examples of these include, but are not limited to, the Solved in them separately are being combined, the byproduct food additives Allura Red AC (FD&C Red No.40), Tartra is being separated from the product (by solvent extraction or zine (FD&C Yellow No. 5), Indigotine (FD&C Blue No.2), precipitation) (Katritzky et al., “1-Butyl-3-methylimidazo Erythrosine (FD&C Red No.3), and Sunset Yellow (FD&C lium 3,5-dinitro-1,2,4-triazolate: a Novel IL Containing a Yellow No. 6), which are FDA-approved color additives for Rigid, Planar Energetic Anion, 'Chem Commun 868, 2005, food use. Further, nutraceuticals such as fatty acids, choles which is incorporated by reference herein). terols, vitamins, minerals, and trace elements can be suitable ions for the disclosed ionic liquid compositions. SEA-NIN 0353 Examples of those ionic liquid compositions 211 is an antifoulant that can be used as an ion id the include, but are not limited to, the mixture of at least two disclosed compositions. components of functionalized 5- and 6-membered, and bicy US 2007/0093462 A1 Apr. 26, 2007 clic fused ring heterocyclic cations and anions containing 1. 2, 3, 4, or 5 atoms of nitrogen in the ring structure, where all -continued R4 R3 R4 R3 carbon and nitrogen atoms in the ring structure can be V M V M functionalized with additional substituents such as alkyl, N-N N-N allyl, aryl, nitro, nitrile, azido, hydroxyl, carboxylic acid, ester, amide, amine, aldehyde, ketone, epoxy, or function ( \, ( \, alized alkyl and aryl groups (with any functional mentioned R5 N1 NR2 R51 Y NR2 above). Examples of Such components (cations and/or l, R anions) are shown below. R R7 R R 7 R2 \ R2 \ M R4 R4 2- R6 N-R R R3 R3 R3 R3 N R3 N N N R4 Rs R4 Rs 2 2 N R6 R2 R6 NR2 RI RI where R', R. R. R. R. and R', are, independent of one R4 R4 another, not present, H, alkyl, alkenyl, alkynyl, allyl, aryl, nitro, amino, cyano, azido, alkyl nitro, alkyl amino, alkyl R R3 R l R3 cyano, alkyl azido, alkoxy nitro, alkoxy amino, alkoxy n Y n cyano, and alkoxy azido, nitrile, isonitrile, carboxylic acid, ester, ether, CONR, CONHR, CONH, amine, NHR, R6 als R2 R6 2 R2 NR, ketone, aldehyde, or epoxy, wherein R is H, alkyl alkenyl, alkynyl, allyl, aryl, carboxylic acid, ester, ether, RI RI ketone, or aldehyde. R4 R4

R R3 R3 l R3 Scheme 1: Protocol 2 N 2. N 2 N * ON 2 NO R6 NR2 R6 NR2 N-N f HN-N RI RI proton transfer R4 R4 in MeOH R l R3 R3 l R3

s2 N iss2 N R6 YR2 R6 NR2 1 i RI RI MR R4 R4 N-N R 1. R3 R3 l R3 & > ser OH R6 l 2 N NR2 R6 2. N NR2 3

RI RI A 120° C. 4 ii O -CO2 R4 R3 R4 R3 rt. DMSO R N R3

N l a Na, R N R2 R5 N /N R N R6 R2 ty Ne -" RI R R N-N R4 R3 R4 R3 R4 R3 M M V N N N

R5 ( ) R2 R5 - \s,YR2 R5 4 NR2 0354) Utilizing this protocol, model compounds (4), R R R which may undergo further modification in terms of intro duced functions (on the cation precursor (1), anion precur US 2007/0093462 A1 Apr. 26, 2007 79 sors (2), and homologous heterocycle core (both 1, and 2) 0362. Examples of such components (cation precursors (e.g., but not limited to: imidazole, triazole, tetrazole, ben and/or anion precursors) are shown below. Zimidazole, and benztriazole systems) can be formed. 0355 The protocol for the formation of azolium azolate salts via the reaction of two neutral components requires: R4 R4 Zwitterionic cation precursor (1) with carboxylate group R R3 R3 R3 appended on the heterocycle core, and neutral heterocycle N N (2) with the pKa value lower then that of carboxylate group 2 2 N in cation precursor (1). The reaction can be carried in any R6 R2 R6 NR2 Solvent systems (pure solvent or mixture of Solvents) that allows for the dissolution of both components, or without RI R1 solvents at all. The reaction protocol comprises the follow R4 R4 ing steps: R R3 R3 l R3 0356. Proton transfer reactions (protonation of carboxy nN.1 DC late group in Zwitterionic cation precursor (1): (step i) which als 2 is thermodynamically favored due to the difference in the R6 R2 R6 R2 pKa values of the Zwitterionic salt carboxylate group and RI R1 aZolate anion (formed from deprotonation of anion precursor R4 R4 (2)). R R3 R3 l R3 0357 Decarboxylation of the system containing the pro tonated carboxylic acid group on the cation precursor in the 2 N 2 N intermediate (cationic part of compound 3) (step ii). The R6 C YR2 R6 C NR2 decarboxyaltion may be performed in the presence of either polar solvents (e.g., but not limited to, DMSO, DMF, THF, RI R1 trialkylamine, H2O) or heat (temp between 25°C.-150° C.). R4 R4 0358) Additionally, the driving force for this conversion R R3 R3 R3 is the production of gaseous CO which, upon removal from the reaction mixture, shifts the thermodynamic equilibrium s2 N n2 N in favor of product formation. R6 NR2 R6 NR2 0359 Examples of those ionic liquid compositions made RI R1 utilizing above protocol include, but are not limited to, the R4 R4 mixture of at least two components of functionalized 5-, 6-membered, and bicyclic fused ring heterocyclic cation R 1. R3 R3 l R3 precursors and anion precursors containing 1, 2, 3, 4, or 5 n s atoms of nitrogen in the ring structure. R6 l 2 N NR2 R6 l 2 N NR2 0360 The cation precursors are neutral, Zwitterionic spe RI R1 cies (neutral molecule that within itself contains both: cation 4 and anion species) containing at least one cationic site (e.g., R4 R3 R4 R3 but not limited to, protonated or alkylated nitrogen atom) R N R3 and one anionic site (carboxylate (COO-) group). In the N cation precursors all carbon and nitrogen atoms in the ring 1 n structure can be functionalized with additional substituents -sels, R5 R2 R5 R2 Such as alkyl, allyl, aryl, nitro, nitrile, azido, hydroxyl, carboxylic acid, ester, amide, amine, aldehyde, ketone, k R R epoxy, or functionalized alkyl and aryl groups (with any R4 R3 R4 R3 R4 R3 functional mentioned above). \ \ ( 0361 The anion precursors are neutral, substituted, or not Substituted, heterocyclic species containing at least one R5 ( ) R2 R5 - N1 isYR2 R5 a 1NR2 acidic proton site on any of the nitrogen atoms. This hydrogen atom will be utilized for the proton transfer R R R reaction and consecutive decarboxylation reaction to form R4 R3 R4 R3 final azolium azolate product (4) as described in the protocol V M V M above. In the anion precursors all carbon and nitrogen atoms in the ring structure can be functionalized with additional \ | \ Substituents such as alkyl, allyl, aryl, nitro, nitrile, azido, f Nin N Nin hydroxyl, carboxylic acid, ester, amide, amine, aldehyde, R5 N1 R2 R5 Y R2 ketone, epoxy, or functionalized alkyl and aryl groups (with R R any functional mentioned above). US 2007/0093462 A1 Apr. 26, 2007 80

respective charges, the disclosed ionic liquids can have a -continued cation to anion ratio of 1:1:, 2:1, 3:1, 4:1, 1:3, 2:1, 3:2, 2:3, R R7 R R7 and the like. R2 \ R2 \ 0367 Many of the ionic liquid compositions disclosed herein can also have more than one different kind of cation A) R 6 MM N R6 and/or more than one different kind of anion. The use of R N R3 N more than one kind of cation and/oranion can be particularly Rs Rs beneficial when one prepares an ionic liquid composition R4 R4 comprising two or more bioactive ions that are not desired to be in a 1:1 relationship. In other words, according to the disclosed methods, ionic liquid compositions that contain where for the cation precursor: at least one of the R'-R varying effective amounts (or doses) of active substances Substituent groups (only among the ones directly appended can be prepared by varying the ratios of ions in the com to carbon in heterocyclic ring) can be a carboxylate anion position, as long as the total amount of cations is balanced group. The remaining groups can be, independent of one by the total amount of anions. For example, an ionic liquid another, not present, H, alkyl, alkenyl, alkynyl, allyl, aryl, composition disclosed herein can contain one type of cation nitro, amino, cyano, azido, alkyl nitro, alkyl amino, alkyl with a given property and two different anions (e.g., a first cyano, alkyl azido, alkoxy nitro, alkoxy amino, alkoxy and second anion), each with another different property. The cyano, and alkoxy azido, isonitrile, carboxylic acid, ester, resulting ionic liquid in this example will be 1 part cation, ether, CONR, CONHR, CONH, amine, NHR, NR, 0.5 part first anion, and 0.5 part second anion. Another ketone, aldehyde, epoxy, wherein R is H. alkyl, alkenyl, example of this adjustment in ion amounts can arise when alkynyl, allyl, aryl, carboxylic acid, ester, ether, ketone, or one ion is particularly potent and thus dilution is desired. For aldehyde. example, a first cation that is particularly potent can be 0363 And, where for the anion precursor: at least one of combined with a second (or third, forth, etc.) cation that is the R'-R substituent groups (only among the once directly inert or has so other property that is desired. When these appended to nitrogen in heterocyclic ring) can be an H atom cations are combined with one or more kinds of anions to suitable for deprotonation to form stable heterocyclic azolate form an ionic liquid, the amount of the first cation is diluted anion. The remaining groups can be, independent of one by the other the cation(s). As will be appreciated, many other another, not present, H, alkyl, alkenyl, alkynyl, allyl, aryl, such variations in the amount of cations and anions can be nitro, amino, cyano, azido, alkyl nitro, alkyl amino, alkyl present in the disclosed methods and compositions. Thus, cyano, alkyl azido, alkoxy nitro, alkoxy amino, alkoxy while specific ionic liquid compositions having particular cyano, and alkoxy azido, isonitrile, carboxylic acid, ester, combinations of cations and anions are disclosed herein, it ether, CO2NR, CONHR, CONH, amine, NHR, NR, is understood that the ratio of the particular ions can be ketone, aldehyde, or epoxy, wherein R is H, alkyl, alkenyl, varied or adjusted by adding other ions, so long as there is alkynyl, allyl, aryl, carboxylic acid, ester, ether, ketone, or a balance of charge and the final composition is an ionic aldehyde. liquid. 0364 Specific Ionic Liquids 0368 When the disclosed ionic liquid compositions have two or more ions with a bioactive property (e.g., pharma 0365 Because the disclosed ionic liquid compositions ceutical active ingredients, pesticidal actives, herbicidal can have multiple functionalities or properties, each arising actives, and the like), these compositions can be particularly from the various ions that make up the ionic liquid, the desired because each of the active ingredients in the com disclosed ionic liquid compositions can be custom designed position would have the same solubility and would dissolve for numerous uses. As disclosed herein, any combination of together when formulated or administered. This can be cations and anions, as disclosed herein, can be made as long particularly useful when overcoming formulation, Solubility, as the combination results in an ionic liquid as described bioavailability, size, and polymorphism issues. Further, herein. That is, any compound or active disclosed herein that when exact dosages of an active ingredient are needed, the has a given charge or can be made to have a given charge active ingredient as an ion can be combined with a counte (the “first ion(s)) can be combined with any other com rion that is innocuous or GRAS (generally recognized as pound or active disclosed herein having a charge opposite to safe). As noted above, for example, if one active ingredient that of the first ion(s) or any compound that can be made to (cation) is needed at half the dosage of another active have a charge opposite to that of the first ion(s). Thus, in ingredient (anion), then an innocuous cation could be used many examples, the ionic liquid compositions can have one as filler to balance the charges. This same concept applies if type of cation and one type of anion, in a 1:1 relationship, more cation is needed than anion. so that the net charge of the ionic liquid is Zero. 0369 A few specific examples of ionic liquid composi 0366 Furthermore, many of the ions disclosed herein can tions prepared from combinations of quaternary ammonium have multiple charges. Thus, when one ion having a multiple compounds and saccharinates or acesulfamates have been charge is used, more counterion(s) is needed, which will demonstrated. Burgard disclosed a process for preparing affect the ratio of the two ions. For example, if a cation hexadecylpyridinium acesulfamate and its use in the oral having a plus 2 charge is used, then twice as much anion hygiene sector (Eur Pat Appl 2003-1270580 A1: US Pat having a minus 1 charge is needed. If a cation having a plus Appl 2003-023084 A1). Hydrophilic quaternary ammonium 3 charge is used, then three times as much anion having a sacchrinates and acesulfamates and hydrophobic phospho minus 1 charge is needed, and so on. While the particular nium acesulfamates have been recently published (Carter et ratio of ions will depend on the type of ion and their al., Chem Comm, 2004, 630-631; Pernak et al., Eur J Org US 2007/0093462 A1 Apr. 26, 2007

Chem, 2005, 650-652). Saccharin, acting as a weak acid, can form salts with basic active pharmaceutical ingredients including tertiary amines to form quaternary nitrogen atoms XI (Bhatt et al., Chem Comm, 2005, 1073-1075). Also known O in the literature is N-hexadecylpyridinium saccharinate Colline-CH HN e-coch (CAS No. 7428-34-4). CH.1 YCH, 2 | 3 O 0370. Some other specific examples of the disclosed ionic liquids include, but are not limited to, ionic liquids where any of the cations in the ionic liquid are aliphatic benzylalkyl Still another example is the combination of N-hexadecylpy ammonium cations (e.g., benzalkonium), dialiphatic dialkyl ridinium sulfacetamide, which is shown in formula XII. ammonium cations (e.g., didecyldimethylammonium), and aliphatic heteroaryl cations (e.g., hexadecylpyridinium) are combined with any of the anions of sulfacetamide, ibupro XII fen, and saccharinate. \ N-CH

0371 Benzalkonium (BA) is used chiefly as an antiseptic O and disinfectant. It is found in many over the counter and | e prescription eye products, disinfectants, shampoos, and deodorants. It also acts as a preservative in many pharma HN -n-coch, ceutical preparations. Didecyldimethylammonium (DDA) is O used as an antiseptic and Surfactant. N-hexadecylpyridinium (HEX) is used as an antiseptic agent alone or in combination Such antiseptic/antibacterial compositions can be used in the with other drugs for oral and throat care. HEX is essentially treatment of wounds, for example, wounds near the scalp nontoxic and can be applied to the skin or mucous mem where a composition with both disinfectant and antibacterial branes. properties is desirable. Such compounds could also be used for skin care, e.g., to treat acne. 0372 Sulfacetamide is used to control antibacterial activ 0375. In still further examples, an ion that is antibacterial ity and is sold under the trade name KLARONTM in the can be combined with an anti-inflammatory and/or pain treatment of acne. Ibuprofen is used as an anti-inflammatory reliever. Such compositions can be used as a disinfectant and and pain reliever. Saccharinate is used as a Sweetener. for pain relief. For example, an ionic liquid can comprise 0373) Some specific examples of suitable ionic liquids benzalkonium and ibuprofen, which is shown in formula include, but are not limited to, benzalkonium Sulfacetamide XIII. (BA-Sulfacetamide), didecyldimethylammonium sulfaceta mide (DDA-sulfacetamide), N-hexadecylpyridinium sulfac XIII etamide (HEX-sulfacetamide), benzalkonium ibuprofen C12H25 (BA-ibuprofen), didecyldimethylammonium ibuprofen (DDA-ibuprofen), N-hexadecylpyridinium ibuprofen / V (HEX-ibuprofen), and benzalkonium acesulfamate, dide cyldimethylammonium acesulfamate, N-hexadecylpyri CH dinium acesulfamate, and benzalkonium saccharinate (BA SAC). CH 0374. In other examples, an ion that is antiseptic can be combined with an ion that is antibacterial agent. For HC 8 example, an ionic liquid can comprise benzalkonium and sulfacetamide, which is shown in formula X. Also, the ionic liquid composition can comprise didecyldim ethylammonium and ibuprofen, which is shown in formula XIV.

XIV CH3 C10H21Nell-CH3 O N CH3 C10H2 1 n CH O H3C O Further, the ionic liquid composition can comprise N-hexa Another example is the combination of didecyldimethylam decylpyridinium and ibuprofen, which is shown in formula monium sulfacetamide, which is shown in formula XI. XV. US 2007/0093462 A1 Apr. 26, 2007

-continued XX XV O CH C10H2 ing-CH3 N C / O M \, N N-CH3 CH C10H2 CH3 M MS \, O O H3 C 3 XXI O GE) \ / N-CH NC / 0376. In other examples of ionic liquid compositions 7\ disclosed herein, an ion that is an antibacterial can be O O combined with an ion that is a Sweetener. Such compositions can be used to improve the taste of medicines and hygiene 0377. In still other examples, the ionic liquid composition products and can be used in, for example, toothpaste, and can comprise an ion that is an antibacterial agent with an ion children's medicine. Some specific examples of Such ionic that is a UV-blocker. Such as trans-cinnamate. Such com liquids is prepared by combining the antibacterial agents positions can be used as disinfectants and for protection benzalkonium, didecyldimethylammonium, or N-hexade against UV radiation, as would be desirable for treating cylpyridinium and the Sweeteneracesulfamate, as shown in wounds exposed to the Sun's radiation. Specific examples of formulas XVI, XVII, and XVIII, respectively. Such composition include, but are not limited to, composi tions where the cation is an antibacterial agent such as benzalkonium, didecyldimethylanimonium, or N-hexade XVI cylpyridinium, and the anion is trans-cinnamate, as is shown O in formulas XXII, XXIII, and XXIV respectively. ( - C12H25 1 O XXII H3 / Y-h3 2O O O -Š O XVII GE)--12H25C3H 8 O - / V o C10H21 Sell-CH3 6 H3C CH3 -NN N C10H2 CH3 leo S Sa XXIII o1 no O XVIII 9 O O C10H21 nG-CH3 N o G CH.1 n CH \ N-CH N

M le.S. o1 No XXIV O

The antibacterial agents benzalkonium, didecyldimethylam monium, and N-hexadecylpyridinium can also be combined with the sweetener saccharinate, as shown in formulas XIV, XX, and XXI, respectively. 0378. In still other examples, the disclosed ionic liquids XIX can comprise an ion that is an antibacterial and an ion that O can provide wetting and controls reaction rate, particle size, G) -C2H25 $1 C Viscosity, polymer molecular weight, and stability in emul / V N sion polymerization systems, e.g., Sodium dihexylsulfo Suc H3C CH3 M cinate (e.g., Colawet MA-80 from Colonial Chemicals, S South Pittsburg, Tenn.)). Specific examples of such compo sitions include, but are not limited to, compositions where the cation is an antibacterial agent Such as benzalkonium, US 2007/0093462 A1 Apr. 26, 2007 83 didecyldimethylammonium, or n-hexadecylpyridinium, and the anion is Colawet MA-80, as shown in formulas XXV, -continued XXVI, and XXVII, respectively. XXIX C10H2NG-CH3N C10H2 1 n CH XXV O e- C12H2s C6H13 No

H3 / Y-h3 O CH-1 Sg O XXVI O C6H13 C10H2NG-CH3 No N XXX CoH.1 n CH3 -O C6H13 Sg O XXVII O o C6H13 No \ -edia CH-1 O Sg O

0379. In further examples, the disclosed ionic liquid compositions can comprise an ion that is antibacterial and an ion that is a food colorant. Examples of Such ionic liquid compositions include, but are not limited to, compositions 0380. In still further examples, the disclosed ionic liquid where the cation is an antibacterial agent Such as benzalko compositions can comprise a cation that is an antibacterial nium, didecyldimethylammonium, or N-hexadecylpyri and an anion that is an antibacterial. For example, the dinium, and the anion is Fast Green FCF, an FDA approved cationic antibacterial agents disclosed herein can be com color additive that provides a sea green hue and is used in bined with the anionic piperacillin, which is an extended products such as beverages, puddings, ice cream, sherbet, spectrum penicillin. Piperacillin is primarily used in the cherries, confections, baked goods, and dairy products. treatment of Susceptible infections such as septicemia, acute Other food coloring anions, which are well known in the art, and chronic respiratory tract infections, skin and Soft tissue can be used as well. infections, and urinary tract infections.

Gel-C12H25,N C10H2 inel-CH3,N or XXVIII / V CH C10H2 CH3

Cation

GE) \ -ed. O CO C2H5N O N O N CH H N N V CH O N S H H O O Ph US 2007/0093462 A1 Apr. 26, 2007

0381 Still further specific examples of the disclosed tomycin docusate, and isoniazide docusate. Docusate com ionic liquid compositions are those where the anion is bined with any of the cationic 5 and 6 membered quaternary benzoate and the cation comprises one or more of (2-ac ammonium ring compounds disclosed herein are also con etoxyethyl)-dodecyloxymethyldimethylammonium, (2-ac templated herein. etoxyethyl)-heptyloxymethyldimethylammonium, (2-hy droxyethyl)-cyclododecyloxymethyldimethylammonium, or 0389 Still further examples include a cation that is an (2-hydroxyethyl)-dimethylundecyloxymethylammonium. anticholinergic like mepenZolate and the anion is docusate. 0390 Another example comprises itraconazole, which 0382 Other examples of the disclosed ionic liquid com inhibits cytochrome p540 oxidase mediated snthesis of positions are those where the cation comprises benzalko ergosterol. Itraconazole is a 1:1:1 racemic mixture offour nium, didecyldimethylammonium, or N-hexadecylpyri diastereomers comprising 2 enantiomeric pairs. Generally, it dinium and the anion comprises one or more of has poor adsorption especially when givenin capsule form. acesulfamate, benzoate, colawet ma-80, fast green FCF, This is though to occur because 99.8% of the drug becomes ibuprofen, penicillin G, piperacillin, saccharinate, Salicylate, bound to proteins in the body. It has been shown that salicylate, Sulfacetamide, trans-cinnamate, Sulfathiazole, absorption is improvedwit acid as the pKa is 3.70; therefore, thimerosal, Valproic acid, mepenZolate, docusate. In three it is recommended that this drug be taken with orange juice. specific examples, benzalkonium is combined with mepen The compound is insoluble in water, slightly soluble in Zolate and docusate in a 1:1:2 ratio, a 2:1:3 ratio, or a 1:2:3 alcohol, and freely soluble in dichloromethane. This com ration. In another example, benzalkonium is combined with pound can be combined with any of the anions disclosed Sulfathiazole and saccharinate in a 2:1:1 ratio. herein, for example, sulfacetamide, colawet MA-80, and 0383. Further specific examples of the disclosed ionic docusate. liquid compositions are those where the cation is dide cyldimethylammonium and the anion comprises one or more 0391 Also contemplated are ionic liquids that are pro of saccharinate, (S)-6-methoxy-C.-methyl-2-naphthaleneac drugs. A prodrug is a pharmacologically inactive compound etate, 2-(2,6-dichlorophenyl)amino-benzeneacetate, 2-(2. that is converted to an active drug by a metabolic biotrans formation. Prodrugs are used when there are concerns 6-dichlorophenyl)amino-benzeneacetate, 2-acetoxyben regarding a drugs solubility, absorption and distribution, site Zoate, acesulfamate, benzoate, colawet ma-80, fast green specificity, stability, prolonged release, toxicity, patient FCF, ibuprofen, mandelate, N-4-(2-amino-1,4-dihydro-4- acceptability, and formulation concerns. Carrier linked pro oxo-6-pteridinyl)methylaminobenzoyl-L-glutamate, drugs are also contemplated. A carrier linked prodrug is a nicotinate, penicillin G, piperacillin, p-toluenesulfonate, compound thatcontains an active drug linked to a carrier salicylate, Sulfacetamide, or trans-cinnamate. group that can be removed enzymatically, such as an ester, 0384 Other specific examples of the disclosed ionic which is hydrolyzed to an active carboxylicacid containing liquid compositions are those where the cation is hexade drug. Other types of carrier linkages include alcohols and cylpyridinium and the anion comprises one or more of carboxylic acids, amines, and carbonyl compounds. Also colawet ma-80, fast green FCF, penicillin G, piperacillin, or contemplatedare mutual prodrugs, which comprise two Sulfacetamide. drugs attached to each other where one is the carrier for the 0385) Still further specific examples of the disclosed other and vice versa. ionic liquid compositions are those where the cation is 0392 Still further examples include compositions com hexadecylpyridinium and the anion comprises one or more prising lidocaine and silver. This composition has a com of clofencet, fluroxypyr, diflufenZopyr, mesosulfuron, pro ponent that is functional for topical anesthesia (lidocaine) hexadione, pantoprazole, risedronate, losartan, rabeprazole, with one Ag+ that has antimicrobial properties. This can be fosinopril, ceftioXone, atorvastatin, pravastatin, alendronate, used in conjunction with lidocaine docusate, as described montelukast, taZobactam, Allura Red AC, tartrazine, indigo herein, to create ointments or bandage materials that are tine, erythrosine, or Sunset Yellow. capable of providing a palliative effect as well as Suppres 0386 Further specific examples of the disclosed ionic sion of microorganism growth. Similarly, silver docusate liquid compositions are those where the cation is dide can be prepared, which can provide a lipophilic salt of silver cyldimethylamirnonium and the anion comprises one or that would be soluble in lidocaine docusate, other ILS, or more of clofencet, fluroxypyr, diflufenZopyr, mesosulfuron, even non-IL creme bases, for end-use as a topical antimi prohexadione, pantoprazole, risedronate, losartan, rabepra crobial agent. Zole, fosinopril, ceftioxone, atorvastatin, pravastatin, allen 0393 Still further examples include compositions com dronate, montelukast, taZobactam, Allura Red AC, tartra prising ranitidine and docusate. This compound can generate Zine, indigotine, erythrosine, or Sunset Yelow. a rather lipophilic, hydrophobic version of ranitidine, which 0387. Other specific examples of the disclosed ionic would be both non-crystalline and Sufficiently sluggish in its liquid compositions are those where the cation is benzalko rate of dissolution against biofluids that it could serve as a nium and the anion comprises one or more of clofencet, slow-release form of the drug. Lidocain docusate is another fluroxypyr, diflufenZopyr, mesosulfuron, prohexadione, pan example contemplated herein. toprazole, risedronate, losartan, rabeprazole, fosinopril, ceft Methods ioxone, atorvastatin, pravastatin, alendronate, montelukast, 0394 The disclosed ionic liquid compositions can be taZobactam, Allura Red AC, tartrazine, indigotine, eryth prepared by combining one or more kinds of cations or rosine, or Sunset Yellow. cation precursors with one or more kinds of anions or anion 0388 Still further examples include the compositions precursor. Providing of the particular ions is largely based on docusate lidocaine, miconazole?econazole docusate, Strep the identifying desired properties of the ion (e.g., its charge US 2007/0093462 A1 Apr. 26, 2007 and whether it has a particular bioactivity that is desired to 0400. Once the desired ions are provided, the ions can be be present in the resulting ionic liquid). Methods of identi combined to form the disclosed ionic liquids. There are fying Suitable ions are disclosed herein, for example, by generally two methods for preparing an ionic liquid: (1) considering the chemical structure and charge of the com metathesis of a salt of the desired cation (e.g., a halide salt) pounds and whether the ion combination will produce an with a salt of the desired anion (e.g., transition metal, like ionic liquid. Ag, salt, Group I or II metal salt, or ammonium salt). Such 0395 Typically, when preparing an ionic liquid compo reactions can be performed with many different types of sition as disclosed herein, an ion that minimizes coulombic salts; and (2) an acid-base neutralization reaction. Another interactions by diffusing its charge over several atoms in the method for forming the disclosed ionic liquid compostions ion is identified. An example of this is the alkylheteroaryl involves a reaction between a salt of a desired cation, say cations disclosed herein where the positive charge is spread CationX where X is an appropriate balancing anion (includ over the atoms of the heteroaryl ring. Then a weakly ing but not necessarily a halide), and an acid to yield the coordinating counterion, which also delocalizes charge over ionic liquid and HX byproduct. Conversely, the disclosed several atoms, is chosen. In general, more-complex and ionic liquid compositions can be formed by reacting a salt of higher molecular weight cations and anions have a greater a desired anion, Say YAnion where Y is an appropaite number of intermolecular contacts, which serves to raise balancing cation, with a base to yield the ionic liquid and melting point and increase the Viscosity of the ionic liquid Ybase byproduct. composition. 0401 Many of the bioactive compounds (e.g., pharma 0396 Further, when preparing an ionic liquid composi ceutical actives, pesticidal actives, herbicidal actives, etc.) tion as disclosed herein, molecular asymmetry can be par and energetic compounds disclosed herein are cationic or ticularly desired. Low-symmetry cations and anions typi can be made cationic, the identification of which can be cally reduce packing efficiency in the crystalline State and made by simple inspection of the chemical structure as lower melting points. disclosed herein. Further, many of these compounds are commercially available as their halide salts or can be con 0397. It is also desirable that the cation should not be verted to their halide salts by reactions with acids (e.g., HF, more nucleophilic than the neutral form of the cation. If this HCl, HBr, or HI) or by treating a halogenated compound is the case, then Suitable anions can be selected by consid ering their pKa. For example, by utilizing the pKa of acid with a nucleophile Such as an amine. Further many of the functionalized compounds and the pKb of base functional anions disclosed herein are commercially available as metal ized compounds, one can combine the neutral species of salts, Group I or II metal salts, or ammonium salts. Com acids and bases into one neutral compound possessing the bining Such cations and anions in a solvent with optional functions of both compounds. To Successfully produce an heating can thus produce the ionic liquid compositions. For ionic liquid by this method, the pKa or pKb of compound A a review of the synthesis of ionic liquids see, for example, should be different by approximately 5 orders of magnitude Welton, Chem Rev 1999, 99:2071-2083, which is incorpo from the pKa or pKb of compound B. This insures that the rated by reference herein for at least its teachings of ionic acidity or basicity at that hydrogen is sufficient to remove or liquid synthesis. add a hydrogen at that position. This will then produce an 0402 Ionic liquids which are immiscible with water are anion on the acidic compound and a cation on the basic often conveniently prepared by the combination of aqueous compound. Solutions of two precursor salts, each of which contains one 0398. One method for identifying a suitable ion combi of the two requisite ions of the targeted ionic liquids. On nation for preparing an ionic liquid as disclosed herein is by combination, the desired salt forms a separate phase from computer program. It is also possible to use a computer to the aqueous admixture. Such phases are readily washed free select various cation and anion combinations. For example, of byproduct salts with additional water, and may Subse the program called ERWINTM, sold by Computer Associates quently Subjected to other procedures (e.g., as disclosed in (Islandia, N.Y.), can be used. This computer program is the Examples) to separate them from non-water soluble comprised of two models: a forward model which predicts impurities. In certain cases, it is also possible to prepare the melting points and drug delivery rates of a formulation water immiscible ionic liquids by the addition to a neutral of ionic liquids, and a backwards model will allow the user amine-containing compound (e.g., an active pharmaceutical to select which type of pharmaceutical agents that are ingredient) of an acid such as aqueous HTf.N. Certain Tf.N. desired along with liquid range and delivery rates and the salts of N-H containing cations are known to be water program will give all the formulations which meet these immiscible. criterion. 0403. The purification of ionic liquids can be accom 0399 FIG. 3 illustrates how the two models interact. plished by techniques familiar to those skilled in the art of CODESSATM (Semichem, Inc. Shawnee Mission, Kans.) organic and inorganic synthesis, with the notable exception can be used to calculate the descriptors that can be used to of purification by distillation of the ionic liquid. One par construct the forward model. For example, if a researcher ticularly useful approach is the use of conventional or desires a formulation to have antibacterial and painkilling reverse-phase chromatography to separate the salt of interest therapeutic agents as well as the formulation to exist as a from other ionic or non-ionic materials, followed by the liquid at room temperature and have a delivery rate of 1 separation of the ionic liquid from the eluting solvent, gram absorbed per minute, the researcher would feed this commonly by evaporation of the latter. In some cases, ionic request into the program and all of the formulations meeting liquids can be purified by crystallization or thermal Zone these requirements and being composed entirely of a bal crystallization at appropriate conditions of temperature and anced ionic liquid formula would be suggested to the pressure. Such techniques can include the use of a solvent researcher. from which the ionic liquid can be crystallized at an appro US 2007/0093462 A1 Apr. 26, 2007 priate temperature. Other purification techniques include bandages. Liquid bandages are available from commercial exchange column chromatography and Supercritical CO Suppliers such as Johnson and Johnson. By dissolving the fluid extraction. disclosed ionic liquid compositions into a liquid bandage, Uses the various ions in the ionic liquid (e.g., antiinfective, 04.04 The disclosed ionic liquid compositions have many steroidal, anesthetic, etc. ions) can be released into a wound uses. For example, the disclosed ionic liquid compositions and provide beneficial effects. can be used to allow fine tuning and control of the rate of 04.09 Further, the disclosed ionic liquids can be coated dissolution, solubility, and bioavailability, to allow control onto a cellulosic bandage (e.g., a gauze or dressing). Thus, over physical properties and mechanical strength, to by soaking, spraying, or otherwise contacting a bandage improve homogenous dosing, and to allow easier formula with the disclosed ionic liquid compositions, the bandage tions. The disclosed ionic liquid compositions also make will contain the various active ions of the ionic liquid along having compositions with additional functionality possible. with their associated functionality. In this regard, it may be 04.05 One notable advantage of the disclosed ionic liquid desirable to use an ionic liquid composition that melts at or compositions is that they can be used to alleviate the around body temperature. In this way, the ionic liquid problems associated with polymorphism. For example, a composition can “leach out of the bandage and onto the site compound Subject to polymorphism can be used as an ion in contacted by the bandage. the disclosed ionic liquid compositions. In this way, the 0410 Additionally, the disclosed ionic liquids can be compound will become part of the ionic liquid composition melted by a consumer or physician (e.g., with hot water) and and thus not a crystalline Solid that is Subject to polymor then “painted onto an area of interest. It would then cool as phism. Alternatively, polymorphism can be prevented by a thin, Solid coating of the ionic liquid. This use can provide dissolving the compound in the ionic liquid. An advantage a slow release form of the API in the ionic liquid or impart of having ionic liquid compositions is that the Solubility and a desirable barrier on the area of interest. bioavailability can be known and predicted. This allows homogeneous and predictable dosing and tableting. 0411 Depending on the particular ions, the disclosed 0406 Another notable advantage is that the disclosed ionic liquid compositions can be used to treat a subject ionic liquid compositions can be used to alleviate side effects diagnosed with, for example, endocrine disorders, diabetes, associated with various compounds. For example, the dis infertility, hormone deficiencies, osteoporosis, ophthalmo closed ionic liquid compositions can contain an ion from a logical disorders, neurodegenerative disorders, Alzheimer's drug known to have an undesirable side effect along with a disease, dementia, Parkinson's disease, multiple sclerosis, counterion that is a drug known to alleviate or counteract Huntington's disease, cardiovascular disorders, atheroscle that side effect. An example of this is an ionic liquid rosis, hyper-coagulable states, hypo-coagulable states, coro composition that comprises the ions of morphine and docu nary disease, cerebrovascular events, metabolic disorders, sate. Such a composition can be used to treat pain due to the obesity, Vitamin deficiencies, renal disorders, renal failure, presence of morphine and relieve constipation due to the haematological disorders, anemia of different entities, presence of docusate. Along the same lines, many pharma immunologic and rheumatologic disorders, autoimmune dis ceuticals are known to cause constipation, and ionic liquids eases, immune deficiencies, infectious diseases, viral infec of these compounds with docusate or other laxatives are tions, bacterial infections, fungal infections, parasitic infec contemplated herein. tions, neoplastic diseases, multi-factorial disorders, 04.07 Generally, any use that exists for one or more of the impotence, chronic pain, depression, and different fibrosis ionic components in the ionic liquid is also a use for the ionic States. liquid composition itself. For example, if one of the ions in 0412 Similarly, with herbicidal and pesticidal actives, an ionic liquid composition disclosed herein is a pharma the ionic liquid compositions disclosed herein that contain ceutical active, then the ionic liquid composition can also be ionic pesticidal and herbicidal actives can be used in the used for the same indication as the pharmaceutical active. In same way as the actives themselves. Thus, any use contem fact, many of the compounds disclosed herein as being plated for a pesticidal and herbicidal active is contemplated suitable ions for the disclosed ionic liquids have already herein for an ionic liquid composition containing that active. been proven to be effective alone or in some other prepa ration. Many of the disclosed compounds are even FDA 0413 Furthermore, because the disclosed ionic liquid approved. When Such compounds are prepared as part of an compositions are liquid at a given temperature, they avoid ionic liquid, as disclosed herein, they can still maintain their problems associated with polymorphism. For example, one efficacy, and can even have their efficacy enhanced by being can vary the individual ions and the combination of ions to part of the ionic liquid composition. For example, when an fine tune the characteristics of the compositions, thus obtain ionic liquid having a pharmaceutical active as one or more ing a composition with desired properties (e.g., better dis of its cations or anions is administered to a subject, the solution, solubility, or bioavailability). This can lead to pharmaceutical active will dissociate from the ionic liquid easier dosing and formulating of the actives in the compo and be available to the subject in the same way as had a solid sitions. By preparing and using the disclosed ionic liquid form (e.g., tablet) or solution of the pharmaceutical active compositions, one need not need to prepare, Screen, and been administered. This effect is also observed for the characterize numerous crystalline forms of the actives. antibacterial, antiviral, pesticidal, herbicidal, nutritional, 0414. In one aspect, disclosed herein are methods for food additives and other compounds and actives disclosed using ionic liquid compositions that comprise administering herein. an effective amount of at least one ionic liquid composition 0408. Other uses of the disclosed ionic liquid composi as disclosed herein. By the term “effective amount of a tions include the dissolution of the ionic liquid into liquid compound as provided herein is meant a nontoxic but US 2007/0093462 A1 Apr. 26, 2007

sufficient amount to provide the desired result. As will be 0417 Examples of pharmaceutically-acceptable carriers pointed out below, the exact amount required will vary from include, but are not limited to, Saline, Ringer's solution and Subject to Subject, depending on the species, age, and dextrose solution. The pH of the solution is preferably from general condition of the subject, the severity of the disease about 5 to about 8, and more preferably from about 7 to that is being treated, the particular compound used, its mode about 7.5. Further carriers include sustained release prepa of administration, and the like. Thus, it is not possible to rations such as semipermeable matrices of Solid hydropho specify an exact “effective amount.” However, an appropri bic polymers containing the disclosed compounds, which ate effective amount can be determined by one of ordinary matrices are in the form of shaped articles, e.g., films, skill in the art using only routine experimentation. The dose, liposomes, microparticles, or microcapsules. It will be schedule of doses, and route of administration can be varied. apparent to those persons skilled in the art that certain 0415. The efficacy of administration of a particular dose carriers can be more preferable depending upon, for of the ionic liquid compositions according to the methods instance, the route of administration and concentration of described herein can be determined by evaluating the par composition being administered. Other compounds can be ticular aspects of the medical history, signs, symptoms, and administered according to standard procedures used by those objective laboratory tests that are known to be useful in skilled in the art. evaluating the status of a subject in need of attention for the 0418 Pharmaceutical formulations can include addi treatment of a disease and/or condition. These signs, symp tional carriers, as well as thickeners, diluents, buffers, pre toms, and objective laboratory tests will vary, depending servatives, Surface active agents and the like in addition to upon the particular disease or condition being treated or the compounds disclosed herein. Pharmaceutical formula prevented, as will be known to any clinician who treats Such tions can also include one or more additional active ingre patients or a researcher conducting experimentation in this dients such as antimicrobial agents, anti-inflammatory field. For example, if based on a comparison with an agents, anesthetics, and the like. appropriate control group and/or knowledge of the normal 0419. The pharmaceutical formulation can be adminis progression of the disease in the general population or the tered in a number of ways depending on whether local or particular individual: (1) a Subject's physical condition is systemic treatment is desired, and on the area to be treated. shown to be improved, (2) the progression of the disease or Administration may be topically (including ophthalmically, condition is shown to be stabilized, or slowed, or reversed, vaginally, rectally, intranasally), orally, by inhalation, or or (3) the need for other medications for treating the disease parenterally, for example by intravenous drip, Subcutaneous, or condition is lessened or obviated, then a particular treat intraperitoneal or intramuscular injection. The disclosed ment regimen will be considered efficacious. compounds can be administered intravenously, intraperito 0416 Many of the disclosed ionic liquid compositions neally, intramuscularly, Subcutaneously, intracavity, or can be used therapeutically as neat ionic liquids. Also, the transdermally as is described more fully elsewhere herein. disclosed ionic liquids can be used in combination with a 0420 Administration and Delivery pharmaceutically acceptable carrier. By “pharmaceutically acceptable' is meant a material that is not biologically or 0421. In one aspect, disclosed herein are uses of a deliv otherwise undesirable, i.e., the material may be administered ery device to deliver an ionic liquid composition as dis to a subject without causing any undesirable biological closed herein to a subject. Further, disclosed are methods for effects or interacting in a deleterious manner with any of the delivering an ionic liquid composition to a Subject by other components of the pharmaceutical formulation in administering to the Subject any of the nutritional Supple which it is contained. The carrier would naturally be selected ments, pharmaceutical formulations, controlled release to minimize any degradation of the active ingredient and to vehicles, delivery and/or devices. minimize any adverse side effects in the subject, as would be 0422 The compositions described herein can be admin well known to one of skill in the art. In another aspect, many istered to the Subject in a number of ways depending on of the disclosed ionic liquids can be used prophylactically, whether local or systemic treatment is desired, and on the i.e., as a preventative agent, either neat or with a pharma area to be treated. Thus, for example, a composition ceutically acceptable carrier. The ionic liquid compositions described herein can be administered as an ophthalmic disclosed herein can be conveniently formulated into phar solution and/or ointment to the surface of the eye. Moreover, maceutical compositions composed of neat ionic liquid or in a compound or pharmaceutical composition can be admin association with a pharmaceutically acceptable carrier. See istered to a subject vaginally, rectally, intranasally, orally, by e.g., Remington's Pharmaceutical Sciences, latest edition, inhalation, or parenterally, for example, by intradermal, by E. W. Martin Mack Pub.Co., Easton, Pa., which discloses Subcutaneous, intramuscular, intraperitoneal, intrarectal, typical carriers and conventional methods of preparing phar intraarterial, intralymphatic, intravenous, intrathecal and maceutical compositions that can be used in conjunction intratracheal routes. Parenteral administration, if used, is with the preparation of formulations of the compounds generally characterized by injection. Injectables can be described herein and which is incorporated by reference prepared in conventional forms, either as liquid solutions or herein. Such pharmaceutical carriers, most typically, would Suspensions, Solid forms Suitable for solution or Suspension be standard carriers for administration of compositions to in liquid prior to injection, or as emulsions. A more recently humans and non-humans, including Solutions such as sterile revised approach for parenteral administration involves use water, saline, and buffered solutions at physiological pH. of a slow release or Sustained release system such that a Other compounds can be administered according to standard constant dosage is maintained. In one example an ionic procedures used by those skilled in the art. For example, liquid composition Such as lidocaine docusate is contacted to pharmaceutical compositions can also include one or more the skin of a subject to provide an anesthetic effect. additional active ingredients such as antimicrobial agents, 0423 Preparations for parenteral administration include anti-inflammatory agents, anesthetics, and the like. sterile aqueous or non-aqueous solutions, Suspensions, and US 2007/0093462 A1 Apr. 26, 2007

emulsions which can also contain buffers, diluents and other 0428 The disclosed compounds can be incorporated into Suitable additives. Examples of non-aqueous solvents are liposomes. AS is known in the art, liposomes are generally propylene glycol, polyethylene glycol, vegetable oils such as derived from phospholipids or other lipid substances. Lipo olive oil, and injectable organic esters such as ethyl oleate. somes are formed by mono- or multi-lamellar hydrated Aqueous carriers include water, alcoholic/aqueous solu liquid crystals that are dispersed in an aqueous medium. Any tions, emulsions or Suspensions, including saline and buff non-toxic, physiologically acceptable and metabolizable ered media. Parenteral vehicles include sodium chloride lipid capable of forming liposomes can be used. The dis Solution, Ringer's dextrose, dextrose and Sodium chloride, closed compositions in liposome form can contain, in addi lactated Ringer's, or fixed oils. Intravenous vehicles include tion to a compound disclosed herein, stabilizers, preserva fluid and nutrient replenishers, electrolyte replenishers (such tives, excipients, and the like. Examples of Suitable lipids are as those based on Ringer's dextrose), and the like. Preser the phospholipids and the phosphatidylcholines (lecithins), Vatives and other additives, such as antimicrobials, anti both natural and synthetic. Methods of forming liposomes oxidants, chelating agents, and inert gases and the like, can are known in the art. See, e.g., Prescott, Ed., Methods in Cell also be present. Biology, Volume XIV. Academic Press, New York, p. 33 et 0424 Formulations for topical administration can include seq., 1976, which is hereby incorporated by reference herein ointments, lotions, creams, gels, drops, Suppositories, for its teachings of liposomes and their preparation. sprays, liquids and powders. The disclosed ionic liquid 0429. In other examples, the liposomes can be cationic compositions having hydrophobic ions can be particularly liposomes (e.g., DOTMA, DOPE, DC cholesterol) or useful in Such applications because they can adhere to the anionic liposomes. Liposomes can further comprise proteins surface longer when exposed to water or other fluids than to facilitate targeting a particular cell, if desired. Adminis would a similar hydrophilic salt. Likewise, ionic liquids tration of a composition comprising a compound and a comprising disinfectant, herbicide, or pesticide ions and cationic liposome can be administered to the blood afferent hydrophobic counterions can be expected to resist erosion to a target organ or inhaled into the respiratory tract to target from rainfall. Conventional pharmaceutical carriers, aque cells of the respiratory tract. Regarding liposomes, see, e.g., ous, powder or oily bases, thickeners and the like can be Brigham, et al., Am J Resp Cell Mol Biol. 1:95-100, 1989: necessary or desirable. When applied to skin or mucous Felgner, et al., Proc Natl AcadSci USA 84:7413-7, 1987; and tissues (e.g., oral applications) ionic liquid compositions U.S. Pat. No. 4,897,355, which are incorporated by refer containing pharmaceutical actives formulated with highly ence herein for their teachings of liposomes. As one hydrophobic anions or cations (as appropriate) can have example, delivery can be via a liposome using commercially longer durations of adhesion when exposed to water or other available liposome preparations such as LIPOFECTIN, fluids than would similar hydrophilic salts applied in these LIPOFECTAMINE (GIBCO-BRL, Inc., Gaithersburg, environments. This would be particularly beneficial for sun Md.), SUPERFECT (Qiagen, Inc. Hilden, Germany) and screens. It should also be noted that disinfectants, pesticides, TRANSFECTAM (Promega Biotec, Inc., Madison, Wis.), as or herbicides applied to plant leaves can be less prone to be well as other liposomes developed according to procedures lost by rain even if it follows application. standard in the art. Liposomes where the diffusion of the 0425. When one or more ions in the disclosed ionic liquid compound or delivery of the compound from the liposome compositions are an antibacterial, an effective amount of the is designed for a specific rate or dosage can also be used. composition can be contacted (i.e., administered) to any Surface that has bacteria. Similarly, when one or more ions 0430. As described herein, niosomes are delivery devices in the disclosed ionic liquid composition are a pesticidal that can be used to deliver the compositions disclosed active, an effective amount of the composition can be herein. Noisomes are multilamellar or unilamellar vesicles administered to an area to control pests. When one or more involving non-ionic Surfactants. An aqueous solution of ions in the disclosed ionic liquid composition are a herbi Solute is enclosed by a bilayer resulting from the organiza cidal active, an effective amount of the composition can be tion of Surfactant macromolecules. Similar to liposomes, administered to an area to control plants. Techniques for noisomes are used in targeted delivery of for example, contacting Such surfaces and areas with the disclosed ionic anticancer drugs, including methotrexate, doxorubicin, and liquid compositions can include, spraying, coating, dipping, immunoadjuvants. They are generally understood to be immersing, or pouring the composition into or onto the different from transferosomes, vesicles prepared from Surface or area. The precise technique will depend on Such amphiphilic carbohydrate and amino group containing poly factors as the type and amount of infestation or contamina mers, e.g., chitosan. tion, the size of the area, the amount of composition needed, 0431. As described herein, nanoerythrosomes are deliv preference, cost and the like. ery devices that can be used to deliver the compositions 0426 Delivery Devices disclosed herein. NanoerythroSomes are nano-vesicles made of red blood cells via dialysis through filters of defined pore 0427. Any of the compounds described herein can be size. These vesicles can be loaded with a diverse array of incorporated into a delivery device. Examples of delivery biologically active molecules, including proteins and the devices include, but are not limited to, microcapsules, compositions disclosed herein. They generally serve as ideal microspheres, nanospheres or nanoparticles, liposomes, noi carriers for antineoplastic agents like bleomycin, actinomy Some, nanoerythroSome, Solid-liquid nanoparticles, gels, gel capsules, tablets, lotions, creams, sprays, emulsions, or cin D, but can be used for steroids, other lipids, etc. powders. Other examples of delivery devices that are suit 0432 Artificial red blood cells, as described herein, are able for non-oral administration include pulmospheres. further delivery devices that can be used to deliver the Examples of particular delivery devices usefuil herein are compositions disclosed herein. Artificial red blood cells can described below. be generated by interfacial polymerization and complex US 2007/0093462 A1 Apr. 26, 2007

emulsion methods. Generally, the “cell' wall is made of tants like egg lecithin triglycerides and miglyol. They are polyphtaloyl L-lysine polymer/polystyrene and the core is Suitable for passive and active targeting. made of a hemoglobin solution from sheep hemolysate. Hemoglobin loaded microspheres typically have particle 0436 There are other oral delivery systems under inves tigation that are based on osmotic pressure modulation, pH sizes of from about 1 to about 10 mm. Their size, flexibility, modulation, Swelling modulation, altered density and float and oxygen carrying capacity is similar to red blood cells. ing systems, mucoadhesiveness etc. These formulations and 0433 Solid-lipid nanoparticles, as described herein, are time-delayed formulations to deliver drugs in accordance other delivery devices that can be used to deliver the with circadian rhythm of disease that are currently in use or compositions disclosed herein. Solid-lipid nanoparticles are investigation can be applied for delivery of the compositions nanoparticles, which are dispersed in an aqueous Surfactant disclosed herein. solution. They are comprised of a solid hydrophobic core having a monolayer of a phospholipid coating and are 0437. It is also contemplated that the disclosed ionic usually prepared by high-pressure homogenization tech liquid compositions can be formulated as part of a controlled niques. Immunomodulating complexes (ISCOMS) are release vehicle. For example, microspheres and microcap examples of Solid-lipid nanoparticles. They are cage-like 40 Sules, implants, and the like containing liquid bioactive nm Supramolecular assemblies comprising of phospholipid, agents are well known, as are methods for their preparation. cholesterol, and hydrophobic antigens and are used mostly As such, these methods can be used with the disclosed ionic as immunoadjuvants. For instance, ISCOMs are used to liquid compositions to produce controlled release vehicles prolong blood-plasma levels of Subcutaneously injected that can release the disclosed ionic liquid composition with cyclosporine. a desired release profile. 0434 Microspheres and micro-capsules, as described 0438 Also contemplated are pills prepared from the herein, are yet other delivery devices that can be used to disclosed ionic liquid compositions that are glasses. For deliver the compositions disclosed herein. In contrast to example, a glass ionic liquid composition can be cooled to liposomal delivery systems, microspheres and micro-cap form a pill. That is, glasses are “cast-able' above their glass Sules typically do not have an aqueous core but a solid transition temperature (T,) into shapes with specific surface polymer matrix or membrane. These delivery devices are areas, allowing predictable release/pharmacokinetic proper obtained by controlled precipitation of polymers, chemical ties. Below T. these disclosed glass ionic liquid composi cross-linking of soluble polymers, and interfacial polymer tion can be milled into specific shapes and sizes. Alterna ization of two monomers or high-pressure homogenization tively, the disclosed ionic liquid compositions can be techniques. The encapsulated compound is gradually tableted as liquids that upon cooling form glasses. Such a released from the depot by erosion or diffusion from the method can allow the homogeneous distribution of a phar particles. Successful formulations of short acting peptides, maceutical active into the tablet. such as LHRH agonists like leuprorelin and triptoreline, 0439 A particular example includes ionic liquid compo have been developed. Poly(lactide co-glycolide (PLGA) sitions that are in the glass form but melt at or slightly above microspheres are currently used as monthly and three body temperature. Such compositions can allow formulation monthly dosage forms in the treatment of advanced prostrate as a solid, but have known solubility, bioavailability, etc. as cancer, endometriosis, and other hormone responsive con a liquid. These compositions can have uses in, for example, ditions. Leuprolide, an LHRH Superagonist, was incorpo bandages, patches, or wound dressings. Further, glass com rated into a variety of PLGA matrices using a solvent positions that “melt slightly above room temperature can be extraction/evaporation method. As noted, all of these deliv "melted by a consumer or physician with, e.g., hot water or ery devices can be used in the methods disclosed herein. body heat, and “painted onto an area of interest (infected 0435 Pulmospheres are still other examples of delivery area). Cooling of the composition can then provide a thin, devices that can be used herein. Pulmospheres are hollow solid coating of material which is both a slow release form porous particles with a low density (less than about 0.1 of an active ingredient ion (e.g., anti-infective, steroid, gm/mL). Pulmospheres typically have excellent re-dispers anesthetic, or combination thereof), plus serve as a physical ibility and are usually prepared by supercritical fluid con barrier. densation technology. Co-spray-drying with certain matri 0440 Further, the disclosed ionic liquids can be used as ces, such as carbohydrates, human serum albumin, etc., can carriers for other active compounds, many of which are improve the stability of proteins and peptides (e.g., insulin) disclosed herein. For example, prodrugs, ionic and neutral and other biomolecules for pulmonary delivery. This type of active molecules can be dissolved in the disclosed ionic delivery could be also accomplished with micro-emulsions liquid compositions. and lipid emulsions, which are ultra fine, thin, transparent oil-in-water (ofw) emulsions formed spontaneously with no 0441 Further methods of administration can include significant input of mechanical energy. In this technique, an incorporating the disclosed ionic liquid composition in to a emulsion can be prepared at a temperature, which should be food stuff or beverage, which can be ingested by a subject. higher than the phase inversion temperature of the system. At elevated temperature the emulsion is of water-in-oil (w/o) 0442. The disclosed ionic liquids can also be encapsu type and as it cools at the phase inversion temperature, this lated in a polymer matrix by methods known in the art. emulsion is inverted to become of w. Due to their very small 0443 Also, the disclosed ionic liquid compositions can inner phase, they are extremely stable and used for Sustained be dissolved in a suitable solvent or carrier as are disclosed release of steroids and vaccines. Lipid emulsions comprise herein. This method can enhance the delivery of one or more a neutral lipid core (i.e., triglycerides) stabilized by a mono active ions in the ionic liquid. Further, as is disclosed herein, layer of amphiphilic lipid (i.e., phospholipid) using Surfac this method can create a synergistic effect among the various US 2007/0093462 A1 Apr. 26, 2007 90 ions present. While not wishing to be bound by theory, the experimental values C=68.78%, H=10.69%, N=5.31%. H dissociate coefficient of various ions in an ionic liquid can be NMR (DMSO-d) cation: 3.22 (m, 4H); 3.00 (s, 6H); 1.63 different in different solvents. Thus, ions in an ionic liquid (m, 4H); 1.24 (m. 28H): 0.85 (t, J=7 Hz, 6H); anion: 7.58 (m, can dissociate freely in one solvent and cluster in another. 4H); C NMR cation: 62.7; 49.9; 31.2: 28.8; 28.7; 28.6; This phenomenon can be utilized to provide formulations of 28.4; 25.6; 22.0: 21.6; 13.8; anion: 167.7: 145.2: 134.8; compound that are difficult to deliver (e.g., increase the 131.3,130.8; 122.3; 118.9. water solubility of steroids). That is, compounds can be formed into an ionic liquid, as described herien, and then TABLE 2 dissolved in a suitable solvent to provide an easily deliver able solution. A synertistic effect can be observed upon Thermal stability data of synthesized salts administration to a Subject, when ions cluster and act together, rather than independently. Temperature BAISac DDAISac BAAce DDAIAce Tg -52.5 -58 EXAMPLES T 21.5 18.0 26.4 -45.5 s-s 65.5 0444 The following examples are set forth below to i. 82.5 22.5 89 -29 Tonset(5%) 176 184 186 182 illustrate the methods and results according to the disclosed Tonset 2O6 211 (203)258 2O1 subject matter. These examples are not intended to be Td 227 221 (225)273 245 inclusive of all aspects of the subject matter disclosed T - glass transition. herein, but rather to illustrate representative methods and T - crystallization temperature recorded by the DSC. results. These examples are not intended to exclude equiva T - solid-solid transitions recorded by the DSC. lents and variations of the present invention which are T - melting point recorded by the DSC. apparent to one skilled in the art. Tecso.) - onset temperature for 5% of the decomposition, T - onset temperature of the decomposition, 0445 Efforts have been made to ensure accuracy with T - temperature of total decomposition. respect to numbers (e.g., amounts, temperature, etc.) but some errors and deviations should be accounted for. Unless 0448 indicated otherwise, parts are parts by weight, temperature is in C. or is at ambient temperature, and pressure is at or near TABLE 3 atmospheric. There are numerous variations and combina tions of reaction conditions, e.g., component concentrations, MIC values for investigated salts temperatures, pressures and other reaction ranges and con ditions that can be used to optimize the product purity and BA DDA BA DDA yield obtained from the described process. Only reasonable culture Sac Sac Ace Ace BAC** DDAC*** and routine experimentation will be required to optimize S. airetts 4 4 4 8 2 2 E. faecium 8 8 8 8 4 4 Such process conditions. All chemicals used were of ana E. coi 16 16 31.2 16 8 8 lytical grade, purchased from Sigma-Aldrich (Milwaukee, C. albicans 16 16 16 16 8 8 Wis.), and used without further purification unless otherwise Average 11 11 14.8 12 5.5 5.5 noted. value *in ppm. Example I **benzalkonium chloride. *** didecyldimethylammonium chloride Didecyidimethylammonium Saccharinate DDAISac 0449) 0446. To the reaction flask, equipped with stirring bar and thermometer, 0.03 mol of didecyldimethylammonium bro TABLE 4 mide and 0.03 mol of saccharin sodium salt, and 50 mL of water were put in. The mixture was intensively stirred for MBC values for investigated Salts. one hour at room temperature. Afterwards 50 mL of chlo BA DDA BA DDA roform was added. After phases separated, chloroform phase Culture Sac Sac Ace Ace BAC** DDAC*** was isolated (separated), and washed with fresh distilled S. airetts 31.2 62.5 31.2 16 62.5 31.2 water (so many times) until all chloride ions were washed E. faecium 16 16 31.2 31.2 31.2 31.2 out (removed). Chloroform was distilled off (evaporated) E. coi 62.5 16 125 62.5 62.5 31.2 and the residue (remains) was dried at 60° C. in vacuum. C. albicans 31.2 16 31.2 16 16 16 Saccharinate in form of liquid, with high viscosity was Average 35.2 27.6 54.7 31.4 43.1 27.4 obtained in 95% yield. It is hydrophobic liquid (fluid), value lighter than water, poorly dissolvable in cold and warm *in ppm. water. Thermal stability of this salt is presented in Table 2. **benzalkonium chloride. Synthesized salt appear to be Sweet and active against *** didecyldimethylammonium chloride microorganisms. The activity is high in comparison with starting material, didecyldimethylammonium chloride, Example II which is confirmed by MIC and MBC values (Table 3 and Table 4). Benzalkonium Saccharinate BASac 0447 Elemental analysis: CHN: CHNOS (508.80) 0450. To the saturated water solution of saccharin calculated values: C=68.46%, H = 10.30% i N=5.51%: sodium, the water solution of benzalkonium chloride (alkyl US 2007/0093462 A1 Apr. 26, 2007 substituent—dodecyl and tetradecyl) was added in the molar (6.04 g) of acesulfamate potassium salt were put in (placed) ratio of 1:1.5. The mixture was stirred for 1 h at the into the reactor. The mixture was stirred for 1 h at the room temperature of 60°C. After the mixture was cooled down to temperature. Afterwards 50 mL of chloroform was added. the room temperature, white wax was formed. The wax was Water phase was separated and chloroform phase was dissolved in chloroform. Chloroform phase was washed washed with fresh distilled water (so many times) util all with fresh distilled water (so many times) until all chloride chloride ions were washed out (removed). The progress was ions were washed out (removed). The progress was moni monitored by using water solution of AgNO. After the tored by using water solution of AgNO. Afterwards chlo chloroform was evaporated, the liquid (fluid) was obtained roform was distilled off (evaporated) and the residue with 94% yield, and dried at 65° C. in vacuum. (remains) wax was dried at 50° C. in vacuum. Synthesized 0456. The hydrophobic, sweet liquid, with high viscosity, benzalkonium saccharinate was obtained with 98% yield. It lighter than water and thermally stable was obtained (Table is very sweet in taste. Obtained wax is poorly dissolvable in 2). Calculated MIC and MBC values are shown in the Table cold and warm water. Crystalline benzalkonium sacchari 3 and Table 4. Comparing average values of MIC and MBC nate, with the melting point of 80-82°C., was obtained form for the synthesized salt with the values for didecyldimethy the mixture of dry (no water) acetone and diethylether in the lammonium chloride the only slight difference in the bio volume ratio of 10:1. logical activity is seen (recorded). 0451) "H NMR (DMSO-d) 7.59 (m, 9H), 4.53 (s. 2H), 04.57 Elemental analysis: CHN: CHNOS (488.77) 3.24 (m, 2H), 2.95 (s, 6H), 1.77 (m, 2H), 1.24 (m, 20H), 0.85 calculated values C=63.89%, H=10.72% i N=5.73%; experi (t, J=7 Hz, 3H); 'CNMR cation: 132.8, 130. 1, 128.8, 128.0, mental values C=64.09%, H=10.99%, N=5.41%. "H NMR 66.1, 63.4, 49.0, 31.2, 28.9, 28.85, 28.7, 28.6, 28.4, 25.7, (DMSO-d) cation: 3.22 (m, 4H), 2.99 (s, 6H), 1.63 (m, 4H), 22.0, 21.7, 13.8, anion: 167.7, 145.2, 134.8, 1314, 130.8, 1.26 (m. 28H), 0.86 (t, J=7 Hz, 6H), anion: 5.26 (q, J= 1 Hz, 122.3, 118.9. 1H), 1.89 (d, J-2 Hz, 3H); 'CNMR cation: 62.7, 49.8, 31.2, Example III 28.8, 28.7, 28.6, 28.4, 25.7, 22.0, 21.6, 13.8, anion: 167.6, 159.4, 102.0, 19.3. Benzalkonium Acesulfamate BAAce 0458 In the biological activity measurements (tests) fol 0452 To the reactor the water solution of 1 mol of lowing bacteria were used: Staphylococcus aureus ATCC benzalkonium chloride (alkyl substituent is the mixture of the following groups: octyl, decyl, dodecyl, tetradecyl, hexa 6538, Enterococcus faecium ATCC 49474, Escherichia coli decyl and octydecyl) and water solution of 1.5 mol of ATCC 25922 and fungi Candida albicans ATCC 10231. acesulfamate sodium were put in (placed). The mixture was 0459 Microbiological activity tests were performed stirred for 1 h at the temperature of 60° C. After the mixture using dissolution method. Determinations were performed was cooled down to the room temperature. Formed wax was on liquid base (background): Mueller-Hinton for bacteria dissolved in chloroform and separated water phase was and Sabouraud for fungi. Starting Solution had the concen removed. Chloroform phase was washed with fresh distilled tration of 1 g/cm. From this solution, all other solutions water (so many times) until all chloride ions were washed (lower concentrations) were prepared. To those solutions, out (removed). The progress was monitored by using water 0.1 cm of the suspensions of standard microorganisms at a solution of AgNO. Chloroform was distilled off (evapo concentration of 10° cfu cm were added. The samples with rated) and the product dried at 60°C. in vacuum. Obtained bacteria were incubated for 24h at the temperature of 37°C., wax, with the 95% yield, was crystallized out (re-crystal and with fungi there were incubated for 48 h at the tem lized) from the mixture of THF, acetone and diethylether in perature of 22°C. After incubation time the MIC, Minimal the volume ratio of 10:10:1. Crystalline benzalkonium Inhibitory Concentration, minimal concentration of the acesulfamate, which has sweet taste, melts between 90 and investigated compound at which the growth of the micro 91 ° C. The melting point recorded on the by the DSC organisms is stopped (visually), was specified (recorded) for (diffraction scanning calorimeter) was 89° C. This salt is every sample. To define the MBC, Minimal Bactericidal poorly dissolvable in cold and warm water. Concentration, additionally to each solution the 10 cm of the inactivator was added on the base (background) (0.3% 0453 Measured thermal decomposition temperature of lecithin, 3% polysorbate 80 and 0.1% L-cysteine). The obtained salt are placed in Table 2, while biological activity samples with bacteria were incubated for 48 h in the data in Table 3 and Table 4. Calculated average values for temperature of 37°C. The fungi samples were incubated for MIC and MBC indicate high activity of the salt, slightly 5 days at the temperature of 22° C. MBC values were lower than that of the starting benzalkonium chloride defined (specified) as the concentration at which the level of 0454) "H NMR (DMSO-d) cation: 7.52 (m, 5H), 4.53 (s, the reduction of the microorganisms was not lower than 2H), 3.24 (m, 2H), 2.95 (s, 6H), 1.78 (m, 2H), 1.25 (m, 20H), 99.99%. 0.85 (t, J=7 Hz, 3H), anion: 5.28 (s, 1H), 1.90 (s, 3H); 'C NMR cation: 132.8, 130.1, 128.8, 128.0, 66.1, 63.4, 49.0, Example V 31.2, 28.9, 28.87, 28.7, 28.6, 28.4, 25.7, 22.0, 21.7, 13.8, anion: 167.6, 159.5, 102.0, 19.3. Benzalkonium Sulfacetamide Example IV 0460 Benzalkonium chloride (0.001 mol) was dissolved in 60 mL of distilled water by gentle heating and stirring. Didecyldimethylammonium Acesulfamate Sodium sulfacetamide (0.001 mol) was dissolved in 60 mL DDAAce of distilled water by gentle heating and stirring. The two 0455 0.03 mol of didecyldimethylammonium bromide, Solutions were combined and the reaction mixture was in form of gel (75%) in water, and water solution of 0.03 mol heated and stirred for 30 minutes. The reaction mixture US 2007/0093462 A1 Apr. 26, 2007 92 cooled to room temperature and then 60 mL of chloroform for 30 minutes. The reaction mixture cooled to room tem was added. The reaction mixture was stirred for an addi perature and then 60 mL of chloroform was added. The tional 30 minutes. The two phases were separated and the reaction mixture was stirred for an additional 30 minutes. chloroform phase was washed several times with cool The two phases were separated and the chloroform phase distilled water to remove any inorganic salt. The presence of was washed several times with cool distilled water to chloride anions was monitored by silver nitrate test. A rotary remove any inorganic salt. The presence of chloride anions evaporator removed the chloroform and a yellowish gel was was monitored by silver nitrate test. A rotary evaporator obtained in 76.99% yield. H and 'C NMR (DMSO) were removed the chloroform and a % yield. "H and 'C NMR obtained. Melting point (hot plate apparatus)=35-40° C. (DMSO) were obtained. Melting point (hot plate appara Thermal data determined by thermalgravimetric analysis tus)=°C. Thermogravimetric analysis: T=-41.1° C., T (TGA): Tonsets-6 = 164° C. and T conset= 181° C. setsoo-133° C. and Tconset = 153° C. Example VI Example IX Didecyldimethylammonium Sulfacetamide Didecyldimethylammonium Ibuprofen 0461 Didceyldimethylammonium bromide (0.001 mol) 0464) Didecyldimethylammonium bromide (0.001 mol) was dissolved in 60 mL of distilled water by gentle heating was dissolved in 60 mL of distilled water by gentle heating and stirring. Sodium sulfacetamide (0.001 mol) was dis and stirring. Ibuprofen (0.001 mol) was dissolved in 60 mL solved in 60 mL of distilled water by gentle heating and of distilled water by gentle heating and stirring. The two stirring. The two solutions were combined and the reaction Solutions were combined and the reaction mixture was mixture was heated and stirred for 30 minutes. The reaction heated and stirred for 30 minutes. The reaction mixture mixture cooled to room temperature and then 60 mL of cooled to room temperature and then 60 mL of chloroform chloroform was added. The reaction mixture was stirred for was added. The reaction mixture was stirred for an addi an additional 30 minutes. The two phases were separated tional 30 minutes. The two phases were separated and the and the chloroform phase was washed several times with chloroform phase was washed several times with cool cool distilled water to remove any inorganic salt. The distilled water to remove any inorganic salt. The presence of presence of chloride anions was monitored by silver nitrate chloride anions was monitored by silver nitrate test. A rotary test. A rotary evaporator removed the chloroform and a evaporator removed the chloroform and a % yield. H and yellowish gel was obtained in 87.74% yield. H and 'C 'C NMR (DMSO) were obtained. Melting point (hot plate NMR (DMSO) were obtained. Melting point (hot plate apparatus)=°C. Thermogravimetric analysis: T=-57.1° C. apparatus)=25-30°C. Thermal data determined by thermal Tesoconset = 153 C. and T=172°C.conset gravimetric analysis (TGA): Tso-183.3°C. and T onset 2OO.2° C. Example X Example VII Didecyldimethylammonium trans-Cinnamate Hexadecylpyridinium Sulfacetamide 0465 Didecyldimethylammonium bromide (0.001 mol) was dissolved in 50 mL of hot distilled water. trans-Cin 0462 Hexadecylpyridinium chloride (0.001 mol) was namic acid (0.001 mol) was added to the didecyldimethy dissolved in 60 mL of distilled water by gentle heating and lammonium solution. The reaction Solution was stirred at stirring. Sodium sulfacetanide (0.001 mol) was dissolved in 90° C. for 4 h. The reaction solution was cooled to room 60 mL of distilled water by gentle heating and stirring. The temperature and then 60 mL of chloroform was added. The two solutions were combined and the reaction mixture was two phases were separated and the chloroform phase was heated and stirred for 30 minutes. The reaction mixture washed several times with cool distilled water to remove any cooled to room temperature and then 60 mL of chloroform inorganic salt. The presence of chloride anions was moni was added. The reaction mixture was stirred for an addi tored by silver nitrate test. A rotary evaporator removed the tional 30 minutes. The two phases were separated and the chloroform and a wax was obtained in 93% yield. H and chloroform phase was washed several times with cool 'C NMR (DMSO) were obtained. Melting point (hot plate distilled water to remove any inorganic salt. The presence of apparatus)=54-55° C. chloride anions was monitored by silver nitrate test. A rotary evaporator removed the chloroform and an orange wax was Example XI obtained in 99.22% yield. H and 'C NMR (DMSO) were obtained. Melting point (hot plate apparatus)=30-40° C. Benzalkonium trans-Cinnamate Thermal data determined by thermalgravimetric analysis 0466 Benzalkonium chloride (0.001 mol) was dissolved (TGA): Teso =211° C. and T=219Set C. in warm distilled water trans-Cinnamic acid (0.001 mol) Example VIII was added to the benzalkonium solution. The reaction solution was stirred at 90° C. for 4 hours. The reaction Benzalkonium Ibuprofen solution was cooled to room temperature then 60 mL of chloroform was added. The two phases were separated and 0463 Benzalkonium chloride (0.001 mol) was dissolved the chloroform phase was washed several times with cool in 60 mL of distilled water by gentle heating and stirring. distilled water to remove any inorganic salt. The presence of Ibuprofen (0.001 mol) was dissolved in 60 mL of distilled chloride anions was monitored by silver nitrate test. A rotary water by gentle heating and stirring. The two solutions were evaporator removed the chloroform and an orange viscous combined and the reaction mixture was heated and stirred liquid was obtained in 90% yield. H and 'C NMR US 2007/0093462 A1 Apr. 26, 2007

(DMSO) were obtained. Melting point (hot plate appara cool distilled water to remove any inorganic salt. The tus)=liquid at room temperature. presence of chloride anions was monitored by silver nitrate test. A rotary evaporator removed the chloroform and a clear Example XII viscous liquid was obtained in 75.56% yield. H and 'C NMR (DMSO) were obtained. Melting point (hot plate Hexadecylpyridinium Cola wet MA-80 apparatus)=liquid at room temperature. Thermal data deter mined by thermalgravimetric analysis (TGA): Tso 0467 Hexadecylpyridinium chloride (0.001 mol) was 223° C. and T =262° C. dissolved in 60 mL of distilled water by gentle heating and conset stirring. Sodium dihexylsulfosuccinate (Colawet MA-80 from Colonial Chemicals, South Pittsburg, Tenn., 0.001 Example XV mol) was dissolved in 60 mL of distilled water by gentle Didecyldimethylammonium Fast Green FCF heating and stirring. The two solutions were combined and the reaction mixture was heated and stirred for 30 minutes. 0470 Didecyldimethylammonium bromide (0.003 mol) The reaction mixture cooled to room temperature and then was dissolved in 100 mL of distilled water by gentle heating 60 mL of chloroform was added. The reaction mixture was and stirring. Fast Green FCF (0.001 mol) was dissolved in stirred for an additional 30 minutes. The two phases were 60 mL of distilled water by gentle heating and stirring. The separated and the chloroform phase was washed several two solutions were combined and the reaction mixture was times with cool distilled water to remove any inorganic salt. heated and stirred for 30 minutes. The reaction mixture The presence of chloride anions was monitored by silver cooled to room temperature and then 60 mL of chloroform nitrate test. A rotary evaporator removed the chloroform and was added. The reaction mixture was stirred for an addi a yellowish viscous liquid was obtained in 96.93% yield. "H tional 30 minutes. The two phases were separated and the and 'C NMR (DMSO) were obtained. Melting point (hot chloroform phase was washed several times with cool plate apparatus)=liquid at room temperature. Thermal data distilled water to remove any inorganic salt. The presence of determined by thermalgravimetric analysis (TGA): T chloride anions was monitored by silver nitrate test. A rotary sets 96=248° C. and T=262°conset C. evaporator removed the chloroform and a dark blue liquid was obtained in 65.54% yield. Melting point (hot plate Example XIII apparatus)=liquid at room temperature. Thermal data deter mined by thermalgravimetric analysis (TGA): Tso Didecyldimethylammonium Cola wet MA-80 194° C. and T=200°conset C. 0468 Decyldimethylammonium bromide (0.001 mol) Example XVII was dissolved in 60 mL of distilled water by gentle heating and stirring. Sodium dihexylsulfosuccinate (Colawet Hexadecylpyridinium Fast Green FCF MA-80 from Colonial Chemicals, South Pittsburg, Tenn.; 0.001 mol) was dissolved in 60 mL of distilled water by 0471 Hexadecylpyridinium chloride (0.003 mol) was gentle heating and stirring. The two solutions were com dissolved in 100 mL of distilled water by gentle heating and bined and the reaction mixture was heated and stirred for 30 stirring. Fast Green FCF (0.001 mol) was dissolved in 60 mL minutes. The reaction mixture cooled to room temperature of distilled water by gentle heating and stirring. The two and then 60 mL of chloroform was added. The reaction Solutions were combined and the reaction mixture was mixture was stirred for an additional 30 minutes. The two heated and stirred for 30 minutes. The reaction mixture phases were separated and the chloroform phase was washed cooled to room temperature and then 60 mL of chloroform several times with cool distilled water to remove any inor was added. The reaction mixture was stirred for an addi ganic salt. The presence of chloride anions was monitored tional 30 minutes. The two phases were separated and the by silver nitrate test. A rotary evaporator removed the chloroform phase was washed several times with cool chloroform and a yellowish viscous liquid was obtained in distilled water to remove any inorganic salt. The presence of 96.93% yield. H and 'C NMR (DMSO) were obtained. chloride anions was monitored by silver nitrate test. A rotary Melting point (hot plate apparatus)=liquid at room tempera evaporator removed the chloroform and a dark blue soild ture. Thermal data determined by thermalgravimetric analy was obtained in 28.14% yield. Melting point (hot plate sis (TGA): Tso-218° C. and T=226°C.conset apparatus)=40-50° C. Thermal data determined by thermal gravimetric analysis (TGA): Tso-216° C. and T onset Example XIV 2180 C/307 C.F5040 C. Benzalkonium ColawetMA-80 Example XVIII 0469 Benzalkonium chloride (0.001 mol) was dissolved in 60 mL of distilled water by gentle heating and stirring. Benzalkonium Fast Green FCF Sodium dihexylsulfosuccinate (Colawet MA-80 from Colo 0472 Benzalkonium chloride (0.003 mol) was dissolved nial Chemicals, South Pittsburg, Tenn., 0.001 mol) was in 100 mL of distilled water by gentle heating and stirring. dissolved in 60 mL of distilled water by gentle heating and Fast Green FCF (0.001 mol) was dissolved in 60 mL of stirring. The two solutions were combined and the reaction distilled water by gentle heating and stirring. The two mixture was heated and stirred for 30 minutes. The reaction Solutions were combined and the reaction mixture was mixture cooled to room temperature and then 60 mL of heated and stirred for 30 minutes. The reaction mixture chloroform was added. The reaction mixture was stirred for cooled to room temperature and then 60 mL of chloroform an additional 30 minutes. The two phases were separated was added. The reaction mixture was stirred for an addi and the chloroform phase was washed several times with tional 30 minutes. The two phases were separated and the