US 2003.0068365A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0068365A1 Suvanprakorn et al. (43) Pub. Date: Apr. 10, 2003

(54) COMPOSITIONS AND METHODS FOR Related U.S. Application Data ADMINISTRATION OF ACTIVE AGENTS USING LIPOSOME BEADS (60) Provisional application No. 60/327,643, filed on Oct. 5, 2001. (76) Inventors: Pichit Suvanprakorn, Bangkok (TH); Tanusin Ploysangam, Bangkok (TH); Publication Classification Lerson Tanasugarn, Bangkok (TH); Suwalee Chandrkrachang, Bangkok (51) Int. Cl." ...... A61K 9/127; A61K 35/78 (TH); Nardo Zaias, Miami Beach, FL (52) U.S. Cl...... 424/450; 424/725 (US) (57) ABSTRACT Correspondence Address: Law Office of Eric G. Masamori Compositions and methods for administration of active 6520 Ridgewood Drive agents encapsulated within liposome beads to enable a wider Castro Valley, CA 94.552 (US) range of delivery vehicles, to provide longer product shelf life, to allow multiple active agents within the composition, (21) Appl. No.: 10/264,205 to allow the controlled use of the active agents, to provide protected and designable release features and to provide (22) Filed: Oct. 3, 2002 Visual inspection for damage and inconsistency. US 2003/0068365A1 Apr. 10, 2003

COMPOSITIONS AND METHODS FOR toxic degradation of the products, leakage of the drug from ADMINISTRATION OF ACTIVE AGENTS USING the liposome and the modifications of the Size and morphol LPOSOME BEADS ogy of the phospholipid liposome vesicles through aggre gation and fusion. Liposome vesicles are known to be CROSS REFERENCE TO OTHER thermodynamically relatively unstable at room temperature APPLICATIONS and can Spontaneously fuse into larger, leSS Stable altered liposome forms. 0001) This application claims the benefit of U.S. Provi sional Patent Application No. 60/327,643 filed Oct. 5, 2001. 0007 Also adding to the potential instability of lipo Somes in conventional formulations is the pKa. The pKa of FIELD OF INVENTION compounds may be defined by the pH at which concentra tions of both the uncharged and charged forms of the 0002 The present invention relates to compositions and molecules are found. methods for administration of active agents, including but not limited to cosmetic, cosmeceuticals and pharmaceuti 0008 Various schemes have been devised to avoid some cals, to biological organisms in need thereof. More specifi the Stability and limitations of liposome formulations, Such cally, the present invention relates to aggregated or globu as freeze drying of the composition. The freeze dried com lized multiple encapsulations of active agents using position is reconstituted as required for use. conventionally prepared liposomes and aggregating or 0009 What is needed is a liposome formulation that globulizing those liposomes into globules or beads. avoids the disadvantages of pre-existing liposomes formu lations discussed above, that has a longer shelf-life, provides BACKGROUND OF THE INVENTION controlled and increased concentrations of active agents at 0003) When phospholipids and many other amphipathic or near the desired target administration site, allows Segre lipids are dispersed gently in an aqueous medium they gation of different active agents and provides the ability to hydrate and Spontaneously form multilamellar concentric Visually determine if the integrity of the lipoSome has been bilayer vesicles. The lipid bilayers are separated with layers affected by undesired alterations. of the aqueous media. These vesicles are commonly referred to as multilamellar liposomes or multilamellar vesicles and SUMMARY OF THE INVENTION usually have diameters of about 0.2 um to 5 Lim. Sonication 0010. The present invention contemplates the use of of the multilamellar vesicles results in the formation of liposome encapsulated materials made by any conventional smaller unilamellar vesicles with diameters usually in the means and Subsequently, or in addition to the encapsulation range of 20 to 100 nm, containing an aqueous Solution in the process, provides a System to Suspend these liposomes into core. Multivesicular liposomes differ from multilamellar discrete multilamellar vesicles or beads. The multilamellar liposomes in the random, non-concentric arrangement of the vesicles or beads are designed with Surface tensions of chambers within the liposome. Amphipathic lipids can form different Strengths to provide an improved delivery System a variety of Structures other than liposomes when dispersed of a drug or other active agent. The present invention in water, depending on the molar ratio of lipid to water, but provides compositions and methods of administration of at low ratios the liposome is the preferred Structure. globules or beads of liposomal formulations and active 0004. The physical characteristics of liposomes generally agents in predetermined sizes with Similar or different active depend on pH and ionic strength. They characteristically agents, thereby enhancing the use of the drug or active show low permeability to ionic and polar Substances, but at agents in a number of different ways. certain temperatures can undergo a gel-liquid crystalline 0011. Accordingly, the present invention provides a com phase transition dependent upon the physical properties of position and method of administration of active agents the lipids used in their manufacture which markedly alters which, when used in combination with liposomes, enables a their permeability. The phase transition involves a change wider range of vehicles, provides longer life of the product, from a closely packed, ordered Structure, known as the gel provides controlled and increased concentrations of active State, to a loosely packed, less ordered Structure, known as agents at or near the desired target administration Site, the liquid crystalline phase. provides protected and designable release features, allows 0005 Various types of lipids differing in chain length, Segregation of different active agents and allows the con Saturation, and head group have been used in liposomal drug trolled use of the active agent and their visual inspection for formulations for many years, including the unilamellar, damage and consistency. multilamellar and multivesicular liposomes described 0012. In general, the invention comprises a composition above. The major goal of the field is to develop liposomal and method for the administration of beads or globules of formulations for Sustained release of drugs and other com liposomal formulations and active agents. The active agents pounds of interest and to develop liposome formulations include but are not limited to cosmetics, cosmeceuticals and from which the rate of release of the encapsulated material pharmaceuticals. A liposomal Suspension of multilamellar can be controlled. vesicles encapsulating the active agent is prepared by con 0006 Various limitations on the shelf-life and use of ventional methods. The liposomal Suspension is placed into lipoSome compounds exist due to the relatively fragile a physical or physiochemical bonding Solution resulting in a nature of liposomes. Major problems encountered during liposomal first Solution. The resulting liposomal first Solu lipoSome drug Storage in vesicular Suspension are the chemi tion is then aliquoted into a Second Solution containing at cal alterations of the liposome compounds, Such as phos least one inorganic Salt. The at least one inorganic Salt of the pholipids, cholesterols, ceramides, leading to potentially Second Solution comprises 1-2% by weight of the Second US 2003/0068365A1 Apr. 10, 2003

Solution. Upon entry into the Second Solution, the liposomal the group consisting of calcium chloride, calcium Sulfate, first Solution develops a hardened Surface and forms a bead. calcium carbonate, mangesium chloride, magnesiun Sulfate, The beads are then aggregated and washed with an inert barium chloride, or barium Sulfate. In alternate embodi Solution to remove any residual liposomal first Solution and ments, other inorganic Salts may be used in the Second Second Solution. The resulting liposomal beads are now Solution. In the preferred embodiment, the inorganic Salt ready for use. comprises about 1 to 2% by weight of the second solution. 0013 In the preferred embodiment, multiple portions of 0019. In the preferred embodiment, the liposomal first an empty acqueous liposome formulation are lyophilized and Solution is introduced into the inorganic Salt Solution hydrated with a Solution of active agent or other material that through a predetermined orifice which allows for a specific are to be encapsulated resulting in the formation of lipoSome Size or amount of liposomal first Solution to be introduced. multilamellar vesicles containing the active agent or mate In prototype development testing, the types of delivery rials. In the preferred embodiment, the active agent is Systems used included needle injection and disc Spinning. Selected from the group consisting of cosmetics, cosmeceu However, other types of delivery Systems, Such as Spraying, ticals and pharmaceuticals. However, in alternate embodi hydraulic pressure pump, gravitational dipping, pneumatic ment, it may be possible for one skilled in the art to use other pumping or liquidating methods may be used. The means of materials with different therapeutic characteristics. The por bead formation can be achieved by a number of alternative tions of liposome Solution are then Separated or pooled to embodiments, including but not limited to providing the form the final liposome preparation. Each batch may be liposome formulation through a spray, Spinning vessels, washed prior to pooling to remove unencapsulated active injection, pumping, dripping or aliquoting method. agent. In the preferred liposome encapsulation process, 50 to 0020. Upon entry of the liposomal first solution into the 95% of the total active agent or other material is entrapped inorganic Salt Solution, the liposomal first Solution develops or encapsulated. Alternative methods of preparing the lipo a hardened outer Surface and forms a bead. In the preferred Some preparation may be used, as will be readily apparent to embodiment, the beads are generally Spherical or irregular one skilled in the art. polygon in shape and their appearance allows for identifi 0.014. The liposome multilamellar vesicles are then cation and Verification of bead formation. The Shape, degree mixed into a vessel containing a pre-determined concentra of hardening and resulting force necessary to fracture the tion of a physical and/or potentially physiochemical bonding bead is determined by the formulation of the inorganic Salt Solution. This mixture results in a liposomal first Solution. In Solution, the pH of the inorganic Sal Solution, the time of the preferred embodiment, the bonding Solution contains at Submersion or contact with the inorganic Salt Solution, and least one organic compound Selected from the group con the relative temperature differentials between the liposome Sisting of aragrose, cellulose, Sodium alginate, chitosans, or formulation and the inorganic Salt Solution. polymeric Substances. In alternate embodiments, other com 0021. In the preferred embodiment, the pH of the inor pounds with the necessary characteristics of physical or ganic Salt Solution was 6-7, the length of time of Submersion physiochemical bonding may be used. was 30 to 45 minutes, and the solution temperature was 25 0.015. In another preferred embodiment, the liposomal to 30° C. first Solution is comprised of the multilamellar lipoSome 0022. The hardness of the bead is measured in "yield containing cosmetic or pharmaceutical actives mixed with a Strength', which is measured as the amount of weight micro-emulsion Solution composed of organic oils in one required to rupture the bead. The yield Strength is expressed phase and a group of organic compounds consisting of as grams per cubic millimeter (gm/mm). The preferred aragrose, cellulose, Sodium alginate, chitosans, or polymeric range of hardneSS or force necessary to fracture the bead is Substances at a pre-determined temperature. 1 to 4 gm/mm. However, the range of firmness may vary, 0016. The preferred bonding characteristics include the So long as the liposome formulation remains constituted in ability to form polymer network attraction, compatible with bead form. liposomes, able to form beads in the presence of inorganic 0023 The bead are physically separated by any means of Salts. The bonding may consist of polarity bonding, ionic Selection, Specific gravity or physical filtration and rinsed bonding, Van der Waals bonding and affinity bonding. with any conventional washing operation. In the preferred embodiment, the beads are Separated by a Sieve and washed 0.017. It is preferable that the bonding solution forms the with deionized water for 15 minutes and then rinsed again outer shell of the bead in the presence of inorganic Salts and with deionized water. The outer portions of the wetliposome holds the liposomal actives inside at the same time to embodiments, including liposome-micro emulsion Spheres, maintain the stability of the bead and enhance the stability are then dehydrated to remove the remaining water. Dehy of the liposomes. The bonding Solution can also protect the dration is accomplished by any chemical and/or physical inner microparticle liposomes when exposed to the inor means. The dried liposome micro-emulsion Spheres are then ganic Salts. The general concentration range of the bonding Stored in a pre-determined concentration of organic, inor Solution depends upon the type of the bead desired; however ganic, or aqueous aliquot of organic or inorganic compound the preferred concentration range is 1 to 1.5% by weight. Solution, ready to be further processed into finished prod Different beads require different concentrations of the bond uctS. ing Solution to provide the proper degree of hardness of the shell. 0024. The liposome beads can be used in any number of delivery vehicles. The variability and uses of the beaded 0.018. The liposomal first solution is then introduced into liposome are extensive with the physical characteristics and a Second Solution comprising one or more inorganic Salts. In applications being determined and designed by the physical the preferred embodiment, the organic Salt is Selected from characteristics of the bead wall and the contents of the bead. US 2003/0068365A1 Apr. 10, 2003

0.025 In one embodiment, carbopol gel will be used for the Suspension of the beads in vehicles, which would ordi oil-Soluble actives. The carbopol gels may be neutralized by narily adversely react with a liposome. means of alkaline Substances or buffered by a predetermined 0039 The ability to visually determine if any undesired pH buffer solution to yield clear gels. alterations or lack of integrity bead wall has affected the 0026. In another embodiment, silicone derivatives will be integrity of the liposome is also a benefit. A broken or used for water Soluble actives. The silicone derivatives distended bead can indicate the potential instability of the vehicles are designed Such that an anhydrous environment is liposomes. achieved and the clarity and/or Viscosity are adjusted 0040. The benefit of a hardened surface wall which can through the quantities of the organic Silicones or Solvents then be processed in various means for Special uses by comprising the Silicone bases of intended use. means and compounds that would otherwise have been 0027. The now prepared final bead formulation can be damaging or altering to the liposomal active agents. used for any of the desired embodiments. The variability and 0041. The benefit of easily designing and producing a uses of the beaded lipoSome are extensive with the physical variety of different bead walls and differently controlled characteristics and applications being determined and releases of active agents, released through a number of designed by the physical characteristics of the bead wall and different mechanisms for maintaining or delivering a lipo the contents of the bead. Some at the desired site of the delivery, which delivery can 0028. The benefits of defined beads of liposome include be released and controlled by the fracture of the bead wall one or more of the following for each use: through various means of wall release. Thus, the entire design becomes a tool for the effective delivery individually 0029. The therapeutic benefit of treating all types of or as part of a System which requires the addition of outside Dermatocytosis. energy or intervention. 0030 The therapeutic benefit from the user being able to provide controlled and increased concentration of active 0042. The benefit of a designed indicator of any liposome agent released at or near the desired target Site of adminis degradation, infiltration or loss of bead wall integrity. tration on or in the Skin. DETAILED DESCRIPTION OF THE 0031. The therapeutic benefit of allowing the user to INVENTION Visually determine the location and amount of the active 0043. The present invention contemplates the use of agent applied to the treatment area thus enabling the user to liposome encapsulated materials made by any conventional control the locus and levels of agent where the active means and Subsequently, or in addition to the encapsulation ingredient is most needed. process, provides a composition to Suspend these liposomes into discrete multilamellar vesicles or beads. The multila 0.032 The benefit of having active agents in bead form, mellar vesicles or beads are designed with Surface tensions and thus not in direct contact with other active or inert of different Strengths to provide an improved delivery Sys Suspensions including other liposomes. This includes Second tem of a drug or other active agent. The present invention is and third levels of bead formation and levels of hardening a composition and method of administration of globules or encapsulation. beads of liposomal formulations and active agents in pre 0033. The benefit of being able to produce liposome determined sizes with Similar or different active agents, beads of discrete and predetermined size for more accurate thereby enhancing the use of the drug or active agents in a administration of drugs or other active agents. number of different ways. 0034. The benefit of having different types of delivery 0044) The present invention provides a composition and vehicles, containing the beads, to deliver the treatment, method of administration which, when added to any other whether inert or containing active agents, thereby effectively active or inactive delivery of liposomes, enables a wider allowing for the vehicle to be an active agent. range of vehicles, provides longer life of the product, allows additional active agents within the compound, provides 0035. The benefit of having more than one active agent protected and designable release features, and allows the encapsulated within the bead membrane itself, thereby pro controlled use of the active agent and their visual inspection Viding a multiple active agent liposomal mixture which only for damage and consistency. The active agents being becomes interactive when the dynamics of the beads are Selected from the group consisting of cosmetics, cosmeceu affected to release their encapsulated agents. ticals and pharmaceuticals. 0.036 The benefit of being able to define the physical 004.5 The present invention is compatible with all known characteristics of the Semi-rigid wall of the bead for Specific and anticipated liposomal Structures and results in predeter protection and delivery of the liposomic compound or mined sizes of globulized beads allowing for a Second and compounds, including a slow and/or continuous delivery of additional level of control, shelf life and application ease. the active agent. Liposome compositions, which have this additional Step of placing the liposome into beads, have been shown to be 0037. The benefit of a bead protecting the liposomal more effective in the delivery of the active agent in Several formulation from physically changing forces Such as ultra means. They also enjoy Superior or increased shelf life of the Sound, Vibration, light, microwaves and other energy pro active agent, and allow different active agents to remain Viding Sources, by both the Semi-rigid wall and the type of Segregated until release upon fracture of the bead Surface. vehicles used. They also allow for the storage of normally incompatible 0.038. The benefit of designing extended shelf life and active agents in one composition to be delivered to the protection of the lipoSome through various means including biological organism. US 2003/0068365A1 Apr. 10, 2003

0046. In the preferred embodiment, the intended lipo that the bonding Solution contains at least one organic Some is made by any known means of formation. Typical compound Such as aragrose, cellulose, Sodium alginate, lipoSome manufacturing processes comprise the following chitosans, polymeric Substances or other compounds with Steps: multiple portions of an "empty' aqueous lipoSome the necessary characteristic of physical or physiochemical formulation are provided, each portion is lyophilized and bonding. The resulting Solution is hereinafter referred to as hydrated with a Solution of the active agents or materials that the “liposomal first solution”. are to be encapsulated, resulting in the formation of lipo Somes which have trapped the active agent or material. 0054. In another preferred embodiment, the liposomal These portions are then Separated or pooled to form a batch first Solution comprises the multilamellar lipoSome contain of material, which typically constitutes the final lipoSome ing cosmetic or pharmaceutical actives mixed with a micro preparation. Each batch may be washed prior to pooling to emulsion Solution composed of organic oils in one phase and remove unencapsulated material. a group of organic compounds consisting of aragrose, cel lulose, Sodium alginate, chitosans, or polymeric Substances 0047 Alternatively, liposomes are prepared using an at a pre-determined temperature. organic Solution of lipids which are dried and hydrated with water to form "empty' liposome formulations. Each portion 0055. The preferred physical or physiochemical bonding is then lyophilized and hydrated with a solution of the characteristics include the ability to form polymer network material to be encapsulated. attraction, compatible with liposomes, able to form beads in the presence of inorganic Salts. The bonding may consist of 0.048. In another alternative procedure, liposome formu polarity bonding, ionic bonding, Van der Waals bonding and lation compounds are made by lyophilizing an empty lipo affinity bonding. Some formulation and aliquoting the lyophilized material into a plurality of portions prior to lyophilization. Each 0056. It is preferable that the bonding solution forms the lyophilized portion is then hydrated with a solution of the outer shell of the bead in the presence of inorganic Salts and material that is to be encapsulated, and may be washed to holds the liposomal actives inside at the same time to remove unencapsulated material. maintain the stability of the bead and enhance the stability of the liposomes. The Solution bonding can also protect the 0049. In a fourth alternative procedure, a plurality of inner microparticle liposomes when exposed to the inor portions of an organic Solution of lipids is provided in a ganic Salts. The general concentration range of the bonding plurality of containers, and the organic Solvents are evapo Solution depends upon the type of the bead; however the rated from each portion, resulting in the formation of a thin preferred concentration range is 1 to 1.5% by Wieght. lipid film on the walls of each container. The evaporation Different beads require different concentrations of the bond proceSS may be any conventional evaporation process, Such ing Solution to provide the proper degree of hardness of the as rotary evaporation. An acqueous Solution of the material to shell. be encapsulated is then added to each portion and the container is agitated. The resulting Solution is the formation 0057 The liposomal first solution is preferably intro of a plurality of portions of liposomes that have trapped the duced into a Second Solution comprising one or more material. These portions are then pooled to form the final inorganic Salts through a predetermined orifice which allows lipoSome preparation. for a specific Size or amount of liposomal first Solution one to be introduced into the Second Solution. The inorganic Salt 0050. In an adaptation of the fourth alternative process preferably comprises about 1 to 2% by weight of the second described above, an aqueous Solution of a material to be solution. The effect of the interaction of the liposomal first encapsulated is added to one the plurality of containers Solution with the Second Solution is to harden the outer most which have the thin lipid film on the walls, and this container exposed areas of the introduced liposomal first Solution. In is agitated to hydrate the lipid film and form a lipoSome prototype testing the Second Solution was comprised of Suspension. This Suspension is then added to another con calcium chloride or Sodium hydroxide, although other types tainer having the thin lipid film on the walls thereof. This container is agitated to hydrate the lipid film. This proceSS is of inorganic Salts can be used Such as calcium Sulfate, repeated until all of the containers having the thin lipid film calcium carbonate, magnesium chloride, magnesium Sulfate, have been hydrated, resulting in the formation of the final barium chloride, barium Sulfate or other salts. lipoSome preparation. 0058. In the preferred embodiment, the liposomal first Solution is introduced into the inorganic Salt Solution by 0051. Other conventional approaches to making lipo dripping the liposomal first Solution through a Small needle Some mixtures may be used, Such as rotating Systems to or predetermined orifice or by Spinning the liposomal first encapsulate the active form in a Suspension or the use of an Solution with a centrifugal force via a rotating disc. The aqueous Solution, which is under pressure, and is injected predetermined orifice allows for a specific size or amount of with the active agent into a lipid Solution to form liposomes, liposome Solution to be introduced. In prototype develop referred to as “reverse phasing method”. ment testing, other types of delivery System also used 0.052 It is preferable that the selected liposome encap included Spraying, hydraulic pressure pump, gravitational sulation process traps or encapsulates 50 to 95% of the dipping, pneumatic pumping or liquidating methods. available total active agents. It is preferable that the active agent comprise 0.01 to 5 weight percent of the lipoSome 0059. In another preferred embodiment, the liposomal composition. first Solution comprises the multilamellar lipoSome contain ing cosmetic or pharmaceutical activce mixed with a micro 0053. The prepared liposome is then mixed into a vessel emulsion Solution composed of organic oils in one phase and containing a predetermined concentration of a physical and a group of organic compounds consisting of aragrose, cel potentially physiochemical bonding Solution. It is preferable lulose, Sodium alginate, chitosans or polymeric Substances. US 2003/0068365A1 Apr. 10, 2003

The liposome-micro-emulsion Solution is then introduced 0068 (b) a therapeutically effective amount of a into the inorganic Salt Solution through a predetermined Second active agent encapsulated in a liposome Sus orifice which allows for a specific size or amount of lipSome pension of multilamellar vesicles micro-emulsion Solution to be introduced. 0069 (c) in admixture with the liposome suspension 0060. Upon entry into the second solution, the liposomal of multilamellar vesicles a physical bonding Solution first Solution develops a hardened Surface and forms a bead, typically 1 to 4 mm in size. Differing appearances allow for 0070 wherein each active agents comprises 0.01 to 5% identification and Verification of the formation and size of by weight of the total composition and wherein the admix the bead. The Shape, degree of hardening and resulting force ture is Subsequently encapsulated within at least one inor necessary to fracture the bead in order to release its active ganic Salt. ingredient is determined by the formulation of the Second solution, the pH of the second solution, the time of submer 0071. In another embodiment, the invention relates to a Sion or contact with the Second Solution, and the relative composition and method of administering one or more temperature differentials. active agents to a Subject comprising the Steps of 0061 The preferred general shape of the formed bead is 0072) (a) providing a liposome encapsulated bead generally spherical or irregular polygon. The hardness of the composition containing at least one active agent, and bead is measured in "yield Strength', which is measured as the amount of weight required to rupture the bead. The yield 0073) (b) contacting an area of skin or mucous Strength is expressed as grams per cubic millimeter (gm/ membrane of a Subject with the composition to mm). The preferred range of hardness or force necessary to administer the at least one active agent fracture the bead is 1 to 4 gm/mm. However, the range of 0074 The term active agent as used in the specification firmness may vary, So long as the liposome formulation sections entitled “Summary of the Invention” and “Detailed remains constituted in bead form. Description of the Invention” and in the above examples is 0062) The beads are physically separated by any means intended to include the following therapeutic categories: of Selection, Specific gravity or physical filtration and rinsed topically applied antifungals, Such as Terbinafine, Ketocona with any conventional washing operation. In the preferred Zole, Climbazole, Tolnaftate; anti-inflammatories (nonste embodiment, the beads are Separated by a Sieve and washed roidal); antiarthritics; corticosteroids, Such as Clobetasone, with deionized water for 15 minutes and then rinsed again Triancinolone acetonide, Betamethasone; Vitamins, Such as with deionized water. The outer portions of the wetliposome Retinoic Acid, Vitamin K1, Nicotinamide, Vitamin E, whit embodiments, including liposome-micro emulsion spheres, ening agents, Such as Arbutin, AHAS, antioxidants, Such as are then dehydrated to remove the remaining water. The Tranexamic Acid, Polyphenols, nitrus oxide, moisturizers, dehydration process is accomplished by any chemical and/or Such as Aloe Vera and Evening primrose oil; anabolics, physical means. The dried lipoSome micro-emulsion spheres analgesics (dental, narcotic and non-narcotic); anesthetics are then Stored in a pre-determined concentration of organic, (local); antiasthmatics (nonbronchodilator, Steroidal, inhal inorganic, or aqueous aliquot of organic or inorganic com ant); antibacterial (antibiotics); antihistaminics; antineoplas pound Solution, ready to be further processed into finished tics, antiparasitics, vasodilators, vasoconstrictors, anti-tu products. mor, i.e., Seborrheic keratosis to malignant tumors Such as 0.063. Depending upon the designed use of the liposome basal cell carcinoma, anti-Viral (warts and molluscum con bead, various compositions are achieved by changes to the tagiosum); anti Seborrheic, anti-vertigo Such as compazine; Surface thickness of the bead, the Size of the bead, the shape anti insects (anti lice); deliverance of toxins, Such as botox of the bead, and any additional compounds which are added (nerve paralysis); deliverance of hormones Such as estrogen; to the delivery vehicle. delivery of nicotine, prophylactic uses of many of the above; for anti cold; for release of heat; and prevention of contact 0064. The now prepared final bead composition can be dermatitis and irritants. used in a multitude of applications. The variability and uses of the beaded liposome are extensive with the physical 0075. The term active agent is also intended to include characteristics and applications being determined and the following categories: designed by the physical characteristics of the bead wall and 0076 Vitamins, such as: Vitamin A/Beta-Carotene, the contents of the bead. Vitamin B1 (Thiamin), Vitamin B3 (Niacin), Vitamin 0065. In one preferred embodiment the liposome encap B6, Vitamin B12, Biotin, Folic Acid, Pantothenic Acid Sulated bead composition is used for topical application. The and Pantethine, Vitamin C, Vitamin D, Vitamin E, lipoSome encapsulated bead composition comprises a thera Vitamin K peutically effective amount of an active agent encapsulated in a liposome Suspension of multilamellar vesicles in an 0077 Minerals, such as: Boron, Calcium, Chromium, amount from about 0.01 to 5 weight percent based on the Copper, Fluorine, Germanium, Iodine, Iron, Magne weight of the whole composition, in admixture with a sium, Manganese, Molybdenum, Phosphorus, Potas physical bonding Solution wherein the admixture is Subse sium, Selenium, Silicon, Vanadium, Zinc quently encapsulated within at least one inorganic Salt. 0078 Amino Acids, such as: L-Arginine, L-Aspartic 0.066. In another preferred embodiment, the invention Acid, Branched-Chain Amino Acids, L-Cysteine (and relates to a composition and method of administering: Glutathione), L-Glutamine/L-Glutamic Acid, Glycine, 0067 (a) a therapeutically effective amount of a first L-Histidine, L-Lysine, L-Methionine and Taurine, active agent encapsulated in a liposome Suspension L-Phenylalanine, D-Phenylalanine, DL-Phenylalanine, of multilamellar vesicles L-Tryptophan, L-Tyrosine US 2003/0068365A1 Apr. 10, 2003

0079 Lipids, such as: AL, Fish Oils/EPA and DHA, 0088 Another embodiment provides for the size of the Gamma-Linolenic Acid and Oil of Evening Primrose, liposome beads to change in response to any changes to the Glycosphingolipids, Inositol (Myo-Inositol) and Phos liposome occurring within the bead wall, thereby indicating phatidylinositol, Lecithin/Phosphatidylcholine/Cho a potentially compromised liposome bead. line, Liposomes, Lipotropes/Activated Lipotropes, Monolaurin and Caprylic Acid, Phosphatidylserine and 0089 Another embodiment provides for the liposome Phosphatidylethanolamine beads to be Suspended in chronologically degrading walls, or bead walls that are altered by enzymatic or pH factors, 0080 Herbs, such as: Aconite, Alfalfa, Aloe Vera and Such as the enzymes and pH changes found when adminis Derivatives, Angelica/Dong Quai, Astragalus, Bay tered Systemically. The lipoSome bead can be designed to berry Root Bark, Black Cohosh, Blessed Thistle, allow the active agents to remain protected until fracture or Buchu, Burdock, Butcher's Broom, Capsicum/Hot Surface tension release by the appropriate enzyme, chrono Peppers, Cascara Sagrada, Catnip, Chamomile, Chap logical passage, or pH change. arral, Chickweed, Comfrey/Allantoin, Cruciferous 0090 Another embodiment provides for various degrees Vegetables, Damiana, Dandelion, Devil's Claw, of hardening of the lipoSome bead wall, the degree of Echinacea, Ephedra/Ma-Huang, Euphorbia, Eyebright, hardening being predetermined to provide for greater or Fennel, Fenugreek, Feverfew, Forskolin, Fo-Ti, Garlic lesser forces to cause the degradation of the bead wall and and Onions, Ginger, Ginkgo, Ginseng, Goldenseal, release of its contents at distinct intervals or levels. Gotu Kola, Hawthorn, Herbal Analbesic Ointments and Oils, Herbal Fiber, Horsetail Grass, Juniper, Kava 0091 Another embodiment provides for coating the lipo Kava, Licorice, LiguStrum, Melaleuca, Marshmallow, Some beads with various compounds, which are reactive to Mexican Wild Yam, Milk Thistle, Mistletoe/Iscador, the active agent. The incompatible agents are separated by Mullein, Myrrh, Nettle, Oats, Parsley, Pau d’arco, the hardened shell, and only become interactive upon the Quinine, Red Clover, Red Raspberry, Saint John's fracture or softening of the bead wall. Wort, Sarsaparilla, Schizandra, Senna, Skullcap, Slip 0092 Anther embodiment provides for mechanical pery Elm, Triphala, Uva Ursi, Valerian, Walnuts, Wheat means of release on the using of apparel, for example shoes, Grass/Barley Grass, White Oak, Yellow Dock, Yohim to activate the fracture or destruction of the bead wall, So as bine to release the active agent. 0081 Metabolite Supplements, such as: Acidophilus/ 0093. Another embodiment provides for the use of a Yogurt/Kefir, Bioflavonoids, Brewer’s Yeast/Skin Res photoactive Suspension of the vehicle So as to release the piratory Factor/Glucan, Coenzyme Q, Dietary Fiber, liposome from the bead on the event of a predetermined Enzymes, L-Carnitine, Lipoic Acid, Mushrooms: Shii condition or level of light or other waveform, or any other take and Rei-Shi, PABA, Panagamic Acid/DMG energy transmission, Such as ultrasound, microwave, light or (“Vitamin B-15”), Royal Jelly, Seaweeds and Deriva percussion forces. tives, Spirulina and Chlorella, Succinates and Cyto chromes, Wheat Germ/Wheat-Germ. Oil/Octacosanol. 0094. Another embodiment provides for the use of a chemically reactive vehicle compound which, upon the 0082 The term “administering” is intended to mean any event of the vehicle coming into contact with its reactive mode of application to a tissue, which results in the physical counterpart, the liposome bead wall is fractured and the contact of the composition with an anatomical Site. The term liposome released. “Subject' is intended to include all biological organisms. 0095) Another embodiment provides for the fracture 0.083. In accordance with one embodiment, the liposome through temperature Sensitive bead walls, with relative tem beads are introduced into an inert delivery vehicle or Solu peratures providing relative release points. tion, Such as lotions, ointments, creams or Sprays, for its use. 0096. The foregoing list of therapeutic categories and 0084 Another embodiment provides for the liposome various embodiments are illustrative of the invention and are beads to be contained in an inert delivery solution which is merely exemplary. A perSon Skilled in the art may make translucent or opaque to the desired level of light reduction. variations and modifications without departing from the 0085 Another embodiment provides for the liposome Spirit and Scope of the invention. All Such modifications and beads to be fractured by a mechanical means as the delivery variations are intended to be included within the scope of the Solution is metered or dispensed from a device. The pre invention as described in this specification. ferred fracturing means can be an orifice which is signifi 0097 Indeed, the present invention is intended to encom cantly Smaller than the Size of the particular bead, however pass and be Suitable for use by Substituting any of the any known fracturing means may be utilized. following drugs for the active agent in the composition and 0.086 Another embodiment provides for the liposome methods for administration of the Same: bead walls to be degraded by nonphysical chemical means, 0098) alpha-ADRENERGIC AGONIST such as including both pre-existing chemical conditions or the intro Adrafinil, Adrenolone, Amidephrine, Apraclonidine, duction of a degrading chemical through other means Such Budralazine, Clonidine, Cyclopentamine, Detomidine, as within the delivery vehicle, or with other liposome beads. Dimetofrine, Dipivefrin, Ephedrine, Epinephrine, 0.087 Another embodiment provides for the liposome Fenoxazoline, Guanabenz, Guanfacine, Hydroxyam beads to be coated with a particular color or pattern of phetamine, Ibopamine, Indanazoline, Isometheptene, recognition So as to allow the user to meter and judge the Mephentermine, Metaraminol, Methoxamine, Methyl amount of active reagent without unnecessary dilution. hexaneamine, Metizolene, Midodrine, Modafinil, Mox US 2003/0068365A1 Apr. 10, 2003

onidine, Naphazoline, Norepinephrine, Norfenefrine, phine Derivatives, Myrophine, Nalbuphine, Narceline, Octodrine, Octopamine, Oxymetazoline, Phenyleph Nicomorphine, Norlevorphanol, Normethadone, Nor rine, Phenylpropanolamine, Phenylpropylmethy morphine, Norpipanone, Opium, Oxycodone, Oxymor lamine, Pholedrine, Propylhexedrine, Pseudoephe phone, Papaveretum, Pentazocine, Phenadoxone, drine, Rilmenidine, Synephrine, Talipexole, Phenazocine, Phenoperidine, Piminodine, Piritramide, Tetrahydrozoline, Tiamenidine, TramaZoline, Tuami Proheptazine, Promedol, Propiram, Propoxyphene, noheptane, Tymazoline, Tyramine, Xylometazoline Remefentanil, Sufentanil, Tilidine 0099 beta-ADRENERGIC AGONIST such as 01.07 ANALGESIC (NON-NARCOTIC) such as Ace Albuterol, Bambuterol, Bitolterol, Carbuterol, Clen clofenac, Acetaminophen, AcetaminoSalol, Acetanil buterol, Clorprenaline, Denopamine, Ephedrine, Epi ide, Acetylsalicylsalicylic Acid, Alclofenac, Almino nephrine, Etafedrine, Ethylnorepinephrine, Fenoterol, profen, Aloxiprin, Aluminum Bis(acetylsalicylate), Formoterol, HeXoprenaline, Ibopamine, Isoetharine, Aminochlorthenoxazin, 2-Amino-4-picoline, Amino Isoproterenol, Mabuterol, Metaproterenol, Methox propylon, Aminopyrine, Ammonium Salicylate, Amtol yphenamine, Oxyfedrine, Pirbuterol, Prenalterol, Pro metin Guacil, Antipyrine, Antipyrine Salicylate, caterol, Protokylol, Reproterol, Rimiterol, Ritodrine, Antrafenine, ApaZone, Aspirin, Benorylate, Benox Salmerterol, Soterenol, Terbutaline, Tretoquinol, aprofen, BenZpiperylon, BenZydamine, Bermoprofen, Tulobuterol, Xamoterol Bromofenac, p-Bromoacetanilide, 5-BromoSalicylic Acid Acetate, Bucetin, BufeXamac, Bumadizon, Buta 0100 alpha-ADRENERGIC BLOCKER such as cetin, Calcium Acetylsalicylate, Carbamazepine, Car AmoSulalol, Arotinilol, Dapiprazole, Doxazosin, biphene, CarSalam, Chloralantipyrine, Chlorthenox Ergoloid MeSylates, Fenspiride, Indoramine, Labetalol, azin(e), Choline Salicylate, Cinchophen, Ciramadol, Naftopidil, Nicergoline, Prazosin, Tamsulosin, Tera Clometacin, Clonixin, Cropropamide, Crotethamide, Zosin, Tolazoline, Trimazosin, Yohimbine Dexoxadrol, Difenamizole, Diflunisal, Dihydroxyalu 0101 beta-ADRENERGIC BLOCKER such as Ace minum Acetylsalicylate, Dipyrocetyl, Dipyrone, Emor butolol, Alprenolol, AmoSulalol, Arotinolol, Atenolol, faZone, Enfenamic Acid, Epirizole, EterSalate, Ethen Befunolol, Betaxolol, Bevantolol, Bisoprolol, Bopin Zamide, Ethoxazene, Etodolac, Felbinac, Fenoprofen, dolol, Bucumolol, Bufetolol, Bufuralol, Bunitrolol, Floctafenine, Flufenamic Acid, Fluoresone, Flupirtine, Bupranolol, Butidrine, Butofilolol, Carazolol, Car FluproduaZone, Flurbiprofen, Fosfosal, Gentisic Acid, teolol, Carvedilol, Celiprolol, Cetamolol, Cloranolol, Glafenine, Ibufenac, Imidazole Salicylate, Indometha Dilevalol, Epanolol, Esmolol, Indenolol, Labetalol, cin, Indoprofen, IsofeZolac, Isoladol, Isonixin, Keto Levobunolol, Mepindolol, Metipranolol, Metoprolol, profen, Ketorolac, p-Lactophenetide, Lefetamine, Lor Moprolol, Nadolol, Nadoxolol, Nebivalol, Nifenalol, noxicam, Loxoprofen, Lysine Acetylsalicylate, Nipradillol, Oxprenolol, Penbutolol, Pindolol, Prac Magnesium Acetylsalicylate, Methotrimeprazine, tolol, Pronethalol, Propranolol, Sotalol, Sulfinalol, Tali Metofoline, Mofezolac, Morazone, Morpholine Salicy nolol, Tertatolol, Tilisolol, Timolol, Toliprolol, late, Naproxen, Nefopam, Nifenazone, 5' Nitro-2' pro Xibenolol poxyacetanilide, Parsalmide, Perisoxal, Phenacetin, Phenazopyridine, Phenocoll, Phenopyrazone, Phenyl 0102) ALCOHOL DETERRENT such as Calcium Acetylsalicylate, Phenyl Salicylate, Phenyramidol, Cyanamide Citrated, Disulfiram, Nitrefazole Pipebuzone, Piperylone, Propacetamol, Propy 0103) ALDOSE REDUCTASE INHIBITOR such as phenaZone, RamifenaZone, Rimazolium Metilsulfate Epalrestat, Sorbinil, Tolrestat, Zopolrestat Salacetamide, Salicin, Salicylamide, Salicylamide O-Acetic Acid, Salicylsulfuric Acid, Salsalate, Salver 0104 ANABOLIC Such as Androisoxazole, Andros ine, Simetride, Sodium Salicylate, Suprofen, Talniflu tenediol, Bolandiol, Bolasterone, Clostebol, Ethylestre mate, Tenoxicam, Terofenamate, Tetradrine, Tinori nol, Formebolone, Methandriol, Methenolone, Meth dine, Tolfenamic Acid, Tramadol, Tropesin, Viminol, yltrienolone, Nandrolone, Norbolethone, Oxabolone, Xenbucin, Zomepirac Oxymesterone, Pizotyline, Quinbolone, Stenbolone, Trenbolone 0108) ANDROGEN such as Boldenone, Cloxotest Osterone, Fluoxymesterone, Mestanolone, Mester 01.05 ANALGESIC (DENTAL) such as Chlorobu olone, Methandrostenolone, 17-Methyltestosterone, 17 tanol, Clove, Eugenol alpha-Methyl-testosterone 3-Cyclopentyl Enol Ether, 01.06 ANALGESIC (NARCOTIC) such as Alfentanil, Norethandrolone, Normethandrone, Oxandrolone, Allyiprodine, Alphaprodine, Anileridine, Benzylmor Oxymesterone, Oxymetholone, Prasterone, Stanlolone, phine, Bezitramide, Buprenorphine, Butorphanol, Stanozolol, Testosterone, Tiomesterone ClonitaZene, Codeines, DeSomorphine, Dextromora 0109) ANESTHETIC such as Acetamidoeugenol, mide, DeZocine, Diampromide, Dihydrocodeine, Dihy Alfadolone Acetate, Alfaxalone, Ambucaine, Amol drocodeinone Enol Acetate, Dihydromorphine, anone, Amylocaine, BenoXinate, Benzocaine, Betox Dimenoxadol, Dimepheptanol, Dimethylthiambutene, ycaine, Biphenamine, Bupivacaine, Butacaine, Butam Dioxaphetyl Butyrate, Dipipanone, Eptazocine, Etho ben, Butanilicaine, Butethamine, Buthalital, heptazine, Ethylmethlythiambutene, Ethylmorphine, Butoxycaine, Carticaine, Chloroprocaine, Cocaethyl EtonitaZene, Fentanyl, Hydrocodone, Hydromorphone, ene, Cocaine, Cyclomethycaine, Dibucaine, Dime Hydroxypethidine, Isomethadone, Ketobemidone, thisoquin, Dimethocaine, Diperadon, Dyclonine, Levorphanol, Lofentanil, Meperidine, Meptazinol, Ecgonidine, Ecgonine, Ethyl Chloride, Etidocaine, Metazocine, Methadone, Metopon, Morphine, Mor Etoxadrol, beta-Eucaine, Euprocin, Fenalcomine, US 2003/0068365A1 Apr. 10, 2003

Fomocaine, Hexobarbital, Hexylcaine, Hydroxydione, Phanquinone, Polybenzarsol, Propamidine, Quinfa Hydroxyprocaine, Hydroxytetracaine, Isobutyl p-Ami mide, Secnidazole, Sulfarside, Teclozan, Tetracycline, nobenzoate, Ketamine, Leucinocaine MeSylate, Thiocarbamizine, ThiocarbarSone, Tinidazole LeVOXadrol, Lidocaine, Mepivacaine, Meprylcaine, Metabutoxycaine, Methohexital, Methyl Chloride, 0117. ANTIANDROGEN such as Bicalutamide, Midazolam, Myrtecaine, Naepaine, Octacaine, Bifluranol, Cioteronel, Cyproterone, Delmadinone Orthocaine, Oxethazaine, Parethoxycaine, Phenacaine, Acetate, Flutamide, Nilutamide, OSaterone, Oxen Phencyclidine, Phenol, Piperocaine, Piridocaine, Poli dolone docanol, Pramoxine, Prilocaine, Procaine, Propanidid, 0118 ANTIANGINAL Such as Acebutolol, Alpre Propanocaine, Proparacaine, Propipocaine, Propofol, nolol, Amiodarone, Amlodipine, Arotinolol, Atenolol, Propoxycaine, Pseudococaine, Pyrrocaine, Ropiv Barnidipine, Bepridil, Bevantolol, Bucumolol, Bufe acaine, Salicyl Alcohol, Sodium Oxybate, Tetracaine, tolol, Bufuralol, Bunitrolol, Bupranolol, Carazolol, Thialbarbital, Thiamylal, Thiobutabarbital, Thiopental, Carteolol, Celiprolol, Cinepazet Maleate, Diltazem, Tolycaine, Trimecaine, Zolamine Elgodipine, Epanolol, Felodipine, Gallopamil, Imola 0110 ANOREXIC such as Aminorex, Amphecloral, mine, Indenolol, ISOSorbide Dinitrate, Isradipine, Amphetamine, BenZaphetamine, Chlorphentermine, Limaprost, Mepindolol, Metoprolol, Molsidomine, Clobenzorex, Cloforex, Clortermine, Cyclexedrine, Nadolol, Nicardipine, Nicorandil, Nifedipine, Nife Dextroamphetamine, Diethylpropion, Diphemethoxi malol, Nilvadipine, Nipradillol, Nitroglycerin,Oxpre dine, N-Ethylamphetamine Fenbutrazate, Fenflu nolol, Oxyfedrine, OZagrel, Penbutolol, Pentaerythritol ramine, FenproporeX, Furfurylmethylamphetamine, Tetranitrate, Pindolol, Pronethalol, Propranolol, Rano Levophacetoperate, Mazindol, Mefenorex, Metam lazine, Semotiadil, Sotalol, Terodiline, Timolol, Tolip feproamone, Metamphetamine, Norpseudoephedrine, rolol, Trolnitrate Phosphate, Verapamil, Zatebradine Pentorex, Phendimetrazine, Phenmetrazine, Phenpen 0119) ANTIARRHYTHMIC such as Acebutolol, termine, Phenylpropanolamine, Picilorex, Sibutramine Acecainide, Adenosine, Ajmaline, Alprenolol, Amio ANTHELMINTIC (CESTODES) such as Arecoline, darone, Amoproxan, Aprindine, Arotinolol, Atenolol, Aspidin, Aspidinol, Dichlorophen(e), Embelin, Kosin, Azimilide, Bevantolol, Bidisomide, Bretylium Tosy Napthalene, Niclosamide, Pellertierine, Quinacrine late, Bucumolol, Bufetolol, Bunaftine, Bunitrolol, 0111 ANTHELMINTIC (NEMATODES) such as Bupranolol, Butidrine, Butobendine, Capobenic Acid, Alantolactone, Amocarzine, Amoscanate, AScaridole, Carazolol, Carteolol, Cifenline, Disopyramide, Dofetil Bephenium, Bitoscanate, Carbon Tetrachloride, Car ide, Encainide, Esmolol, Flecainide, Hydroquinidine, vacrol, Cyclobendazole, Diethylcarbamazine, Ibutilide, Indecainide, Indenolol, Ipratropium, Diphenane, Dithiazanine Iodide, Dymanthine, Gentian Lidocaine, Lorajmine, Lorcainide, Meobentine, Mexi Violet, 4-Hexylresorcinol, Ivermectin, Kainic Acid, letine, Moricizine, Nadoxolol, Nifenalol, Oxprenolol, Levamisole, Mebendazole, 2-Napthol, Oxantel, Penbutolol, Pilsicainide, Pindolol, Pirmenol, Practolol, Papain, Piperazines, Pyrantel, Pyrvinium Pamoate, Prajmaline, Procainamide, Pronethalol, Propafenone, alpha-Santonin, Stilbazium Iodide, Tetrachloroethyl Propranolol, Pyrinoline, Quinidine, Sematilide, ene, Thiabendazole, Thymol, Thymyl N-Isoamylcar Sotalol, Talinolol, Tlisolol, Timolol, Tocainide, Vera bamate, Triclofenol Piperazine, Urea Stibamine pamil, Vicquidil, Xibenolol 0112 ANTHELMINTIC (SCHISTOSOMA) such as 0120 ANTIARTERIOSCLEROTIC such as Pyridinol Amoscanate, Amphotalide, Antimony(s) and Deriva Carbamate tives, Becanthone, Hycanthone, Lucanthone, Nirida 0121 ANTIARTHRITIC/ANTIRHEUMATIC such as Zole, Oxamniquine, Praziquantel, Stibocaptate, Sti Actarit, Allocupreide Sodium, Auranofin, Aurothioglu bophen, Urea Stibamine cose, Aurothioglycanide, AZathioprine, Bucillamine, 0113 ANTHELMINTIC (TREMATODES) such as Calcium 3-Aurothio-2propanol-1-Sulfonate, Cloro Anthiolimine, Tetrachloroethylene quine, Clobu Zarit, CuproXoline, Diacerein, Glu 0114 ANTIACNE Such as Algestone Acetophenide, cosamine, Gold Sodium Thiomalate, Gold Sodium Azelaic Acid, Benzoyl Peroxide, Cioteronel, Cyproter Thiosulfate, Hydroxychloroquine, KebuZone, Loben one, Motretinide, Resorcinol, Retinoic Acid, Tazaro Zarit, Melittin, Methotrexate, Myoral, Penicillamine tene, Tetroquinone, Tioxolone 0122) Antiarteriosclerotic (Antibiotic) 0115 ANTIALLERGIC such as Amlexanox, Astemi 0123 Aminoglycosides Such as Amikacin, Apramycin, Zole, AZelastine, Cromolyn, Fenpiprane, Ibudilast, Arbekacin, Bambermycins, Butirosin, Dibekacin, Dih Lodoxamide, Nedocromil, Oxatomide, Pemirolast, drostreptomycin, Fortimicin(s), Fradiomycin, Gen Pentigetide, Picumast, Repirinast, Suplast Tosylate, tamicin, Ispamicin, Kanamycin, Micronomicin, Neo Tranilast, TraxanoX mycin, Neomycin Undecylenate, Netilmicin, 0116. ANTIAMEBIC such as Arsthinol, Bialamicol, Paromomycin, Ribostamycin, Sisomicin, Spectinomy Carbarsone, Cephaeline, Chlorbetamide, Chloro cin, Streptomycin, Tobramycin, Trospectomycin quinone, Chlorphenoxamide, Chlorotetracycline, 0.124 Amphenicols such as Azidamfenicol, Chloram Dehydroemetine, Dibromopropamidine, Diloxanide, phenicol, Florfenicol, Thiamphenicol DephetarSone, Emetine, Fumagillin, Glaucarubin, Gly cobiarsol, 8-Hydroxy-7-iodo-5-quinolinesulfonic Acid, 0.125 Ansamycins such as Rifamide, Rifampin, Rifa Iodochlorhydroxyquin, Iodoquinol, Paromomycin, mycin, Rifapentine, Rifaximin beta-Lactams US 2003/0068365A1 Apr. 10, 2003

0.126 Carbapenems Such as Biapenem, Imipenem, cline, Minocycline, Oxytetracycline, Penimepicycline, Meropenem, Panipenem Pipacycline, Rolitetracycline, Sancycline, Tetracycline 0127 Cephalosporins such as Cefaclor, Cefadroxil, 0.136. Others such as Cycloserine, Mupirocin, Tuberin, Cefamandole, Cefatrizine, Cefazedone, Cefazolin, Cef 0137 Antibacterial (Synthetic) capene Pivoxil, Cefclidin, Cefdinir, Cefditoren, 0.138 2,4-Diaminopyrimidines such as Brodimoprim, Cefepime, Cefetamet, Cefixime, CefnmenoXime, Cefo Tetroxoprim, Trimethoprim dizime, Cefonicid, CefoperaZone, Ceforanide, Cefo taxime, Cefotiam, CefoZopran, Cefpimizole, Cefpira 0.139 Nitrofurans such as Furaltadone, Furazolium, Nifuradene, Nifuratel, Nifurfoline, Nifurpirinol, Nifur mide, Cefpirome, Cefpodoxime Proxetil, Cefprozil, prazine, Nifurtoinol, Nitrofurantoin Cefroxadine, CefSulodin, Ceftazidime, Cefteram, Ceft eZole, Ceftibuten, Ceftizoxime, Ceftriaxone, 0140 Quinolones and Analogs such as Cinoxacin, Cefuroxime, CefuZonam, Cephacetrile Sodium, Ceph Ciprofloxacin, Clinafloxacin, Difloxacin, Enoxacin, alexin, Cephaloglycin, Cephaloridine, Cephalosporin, Fleroxacin, Flumequine, Grepafloxacin, Lomefloxacin, Cephalothin, Cephapirin Sodium, Cephradine, Pivee Miloxacin, Nalidixic Acid, Norfloxacin, Ofloxacin, Oxolinic Acid, Pazufloxacin, Pefloxacin, Pipemidic falexin Acid, Piromidic Acid, RoSoxacin, Rufloxacin, Spar 0128 Cephamycins such as Cefbuperazone, Cefneta floxacin, Temafloxacin, ToSufloxacin, Travafloxacin Zole, Cefnminox, Cefetan, Cefoxitin 0141 Sulfonamides such as Acetyl Sulfamethoxypyra zine, Benzylsulfamide, Chloramine-B, Chloramine-T, 0.129 Monobactams such as Aztreonam, Carumonam, Dichloramine T, N'-Formyl-sulfisomidine, N'-beta-D- Tigemonam Glucosylsulfanilamide, Mafenide, 4'-(Methyl-sulfa moyl)sulfanilanilide, Noprylsulfamide, Phthalylsulfac 0.130 Oxacephems such as Flomoxef, Moxolactam etamide, Phthalylsulfathiazole, Salazosulfadimidine, 0131 Penicillins such as Amidinocillin, Amdinocillin Succinylsulfathiazole, Sulfabenzamide, Sulfacetamide, Pivoxil, Amoxicillin, Ampicillan, Apalcillin, Sulfachlorpyridazine, Sulfachrysoidine, Sulfacytine, ASpoxicillin, AZidocillan, AZlocillan, Bacampicillin, Sulfadiazine, Sulfadicramide, Sulfadimethoxine, Sul Benzylpenicillinic Acid, Benzylpenicillin, Carbenicil fadoxine, Sulfaethidole, Sulfaguanidine, Sulfaguanol, lin, Carindacillin, Clometocillin, Cloxacillin, Cyclacil Sulfalene, Sulfaloxic Acid, Sulfamerazine, Sulfameter, lin, Dicloxacillin, Epicillin, Fenbenicillin, Floxicillin, Sulfamethazine, Sulfamethizole, Sulfamethomidine, Hetacillin, Lenampicillin, Metampicillin, Methicillin, Sulfamethoxazole, Sulfamethoxypyridazine, Sulfame trole, Sulfamidochrysoidine, Sulfamoxole, Sulfanil Mezlocillin, Nafcillin, Oxacillin, Penamecillin, Peneth amide, 4-Sulfanilamidosalicylic Acid, N'-Sulfanilyl amate Hydriodide, Penicillin G Benethamine, Penicil Sulfanilamide, Sulfanily lurea, N-Sulfanillyl-3,4- lin G BenZathine, Penicillin G Benzhydrylamine, Peni Xylamide, Sulfanitran, Sulfaperine, Sulfaphenazole, cillin G Calcium, Penicillin G Hydrabamine, Penicillin Sulfaproxyline, Sulfapyrazine, Sulfapyridine, Sulfa GPotassium, Penicillin G Procaine, Penicillin N, Peni Somizole, Sulfasymazine, Sulfathiazole, Sulfathiourea, cillin O, Penicillin V, Penicillin V BenZathine, Penicil Sulfatolamide, Sulfisomidine, Sulfisoxazole lin V Hydrabamine, Penimepicycline, Phenethicillin, Piperacillin, Pivapicillin, Propicillin, Quinacillin, Sul 0.142 Sulfones Such as Acedapsone, Acediasulfone, benicillin, Sultamicillin, Talampicillin, Temocillin, Acetosulfone, DapSone, DiathymoSulfone, Glucosul fone, Solasulfone, Succisulfone, Sulfanilic Acid, p-Sul Ticarcillin fanilylbenzylamine, Sulfoxone, Thiazolsulfone 0.132. Others such as Ritipenem Lincosamides such as 0143. Others such as Clofoctol, Hexedine, Meth Clindamycin, Lincomycin enamine, Methenamine Anhydromethylene-citrate, 0.133 Macrollides such as Azithromycin, Carbomycin, Methenamine Hippurate, Methenamine Mandelate, Clarithromycin, Dirithromycin, Erythromycin(s) and Methenamine Sulfosalicylate, Nitroxoline, Taurolidine, Derivatives, Josamycin, Leucomycins, Midecamycins, Xibornol Miokamycin, Oleandomycin, Primycin, Rokitamycin, 0144). ANTICHOLINERGIC such as Adiphenine, Rosaramicin, Roxithromycin, Spiramycin, Troleando Alverine, Ambutonomium, Aminopentamide, Amix mycin etrine, Amprotropine Phosphate, Anisotropine Methyl bromide, Apoatropine, Atropine, Atropine N-Oxide, 0.134 Polypeptides such as Amphomycin, Bacitracin, Benactyzine, Benapry Zine, BenZetimide, BenZilonium, Capreomycin, Colistin, Enduracidin, Enviomycin, Benztropine Mesylate, Bevonium Methyl Sulfate, Fusafungine, Gramicidin(S), Gramicidin S, Mikamy Biperiden, Butropium, N-Butylscopolammonium Bro cin, Polymyxin, Pristinamycin, Ristocetin, Teicoplanin, mide, BuZepide, Camylofine, Caramiphen, Chlorben Thiostrepton, Tuberactinomycin, Tyrocidine, Tyrothri Zoxamine, Chlorphenoxamine, Cimetropium, Clid cin, Vancomycin, Viomycin(s), Virginiamycin, Zinc inium, Cyclodrine, Cyclonium, Cycrimine, Deptropine, Bacitracin Dexetimide, Dibutoline Sulfate, Dicyclomine, Diethaz ine, Difemerine, Dihexyverine, Diphemanil Methylsul 0.135 Tetracyclines such as Apicycline, Chlortetracy fate, N-(1,2-Diphenylethyl)nicotinamide, Dipiprover cline, Clomocycline, Demeclocycline, Doxycycline, ine, Diponium, Emepronium, Endobenzyline, Guamecycline, Lymecycline, Meclocycline, Methacy Ethopropazine, Ethybenztropine, Ethylbenzhydramine, US 2003/0068365A1 Apr. 10, 2003 10

Etomidoline, Eucatropine, Fenpiverinium, Fentonium, Fluvoxamine, Hematoporphyrin, Hypercinin, Flutropium, Glycopyrrolate, Heteronium, Hexocyc Levophacetoperane, Medifoxamine, Milnacipran, lium Methyl Sulfate, Homatropine, Hyoscyamine, Minaprine, Moclobemide, Nefazodone, Oxaflozane, Ipratropium, Isopropamide, Levomepate, Mecloxam Piberaline, Prolintane, Pyrisuccideanol, Ritaserin, ine, MepenZolate, Metcaraphen, Methantheline, RopXindole, Rubidium, Sulpiride, TandoSpirone, Methixene, Methscopolamine, Octamylamine, Oxybu Thozalinone, Tofenacin, ToloXatone, Tranylcypromine, tynin, Oxyphencyclimine, Oxyphenonium, Pentapip L-Tryptophan, Venlafaxine, Viloxazine, Zimeldine eride, Penthienate, Phencarbamide, Phenglutarimide, Pipenzolate, Piperidolate, Piperilate, Poldine Methys 0153 Antidiabetic ulfate, Pridinol, Prifinium, Procyclidine, Propantheline, 0154 Biguanides such as Buformin, Metformin, Phen Propenzolate, Propiverine, Propyromazine, Scopola formin mine, Scopolamine N-Oxide, Stramonium, Sultropo nium, Thiphenamil, Tiemonium, Timepidium, Tiqui O155 Sulfonylurea Derivatives such as Acetohexam Zium, Tridihexethyl Iodide, Trihexyphenidyl ide, 1-Butyl-3-metanily lurea, Carbutamide, Chlorpro Hydrochloride, Trimebutine, Tropacine, Tropenzile, pamide, Glibornuride, Gliclazide, Glimepiride, Glipiz Tropicamide, TroSpium, Valethamate, Vamicamide, ide, Gliquidone, Glisoxepid, Glyburide, Xeny tropium Glybuthiazol(e), Glybuzole, Glyhexamide, Glymidine, Glypinamide, Phenbutamide, Tolazamide, Tolbuta 0145 ANTICONVULSANT such as Acetylphenetu mide, Tolcyclamide ride, Albutoin, Aloxidone, Aminoglutethimide, 0156. Others such as Acarbose, Calcium Mesoxalate, 4-Amino-3-hydroxybutyric Acid, Atrolactamide, Bec Miglitol, Repaglinide lamide, Buramate, Calcium Bromide, Carbamazepine, Cinromide, Clomethiazole, Clonazepam, Decimenide, 0157. ANTIDIARRHEAL such as Acetorphan, Diethadione, Dimethadione, Doxenitoin, Eterobarb, Acetyltannic Acid, Alkofanone, Aluminum Salicylates, Ethadione, Ethosuximide, Ethotoin, Felbamate, Fluo Catechin, DilfenoXin, Diphenoxylate, Lidamidine, Lop resone, Gabapentin, 5-Hydroxytryptophan, Lamot eramide, Mebiquine, Trillium, Uzarin, Zaldaride rigine, Magnesium Bromide, Magnesium Sulfate, Mephenytoin, Methobarbital, Metharbital, Methetoin, 0158 ANTIDIURETIC such as Desmopressin, Fely Methsuximide, 5-Methyl-5-(3-phenanthryl)-hydantoin, pressin, Lypressin, Ornipressin, Oxycinchophen, Terli 3-Methyl-5-phenylhydantoin, Narcobarbital, pressin, Vasopressin Nimetazepam, Nitrazepam, OXcarbazepine, 0159 ANTIESTROGEN such as Centchroman, Del Paramethadione, Phenacemide, Phenetharbital, Phene madinone Acetate, Tamoxifen, Toremifene turide, Phenobarbital, Phensuximide, Phenylmethyl barbituric Acid, Phenytoin, Phethenylate Sodium, 0160 Antifungal (Antibiotics) Potassium Bromide, Primidone, Progabide, Sodium 0.161 Polyenes such as Amphotericin-B, Candicidin, Bromide, Solanum, Strontium, Suclofenide, Sulthiame, Dermostatin, Filipin, Fungichromin, Hachimycin, Tetrantoin, Tiagabine, Topiramate, Trimethadione, Val Hamycin, Lucensomycin, Mepartricin, Natamycin, proic Acid, Valpromide, Vigabatrin, Zonisamide Nystatin, Pecilocin, Perimycin 0146 Antidepressant 0162. Others such as AZaserine, Griseofulvin, Oligo 0147 Bicyclics such as Binedaline, Caroxazone, Cit mycins, Neomycin Undecylenate, Pyrrolnitrin, Sicca allopram, Dimethazan, Indalpine, Fencamine, Indelox nin, Tubercidin, Viridin azine, Nefopam, Nomifensine, Oxitriptan, Oxypertine, 0163 Antifungal (Synthetic) Paroxetine, Sertraline, Thiazesim, Trazodone 0.164 Allylamines such as Butenafine, Naftifine 0.148 Hydrazides/Hydrazines such as Benmoxine, Iproclozide, Iproniazid, Isocarboxazid, Nialamide, 0.165 Imidazoles such as Bifonazole, Butoconazole, Octamoxin, Phenelzine Chlordantoin, Chlormidazole, Cloconazole, Clotrima Zole, Econazole, Enilconazole, Fenticonazole, Flutri 0149 Pyrrolidones such as Cotinine, Rolicyprine, mazole, ISOconazole, Ketoconazole, Lanoconazole, Rolipram Miconazole, Omoconazole, Oxiconazole Nitrate, 0150 Tetracyclics such as Maprotiline, Metralindole, Sertaconazole, Sulconazole, Tioconazole Mianserin, Oxaprotiline 0166 Triazoles such as Fluconazole, Itraconazole, 0151 Tricyclics such as Adinazolam, Amitriptyline, Saperconazole, Terconazole Amitriptylinoxide, Amoxapine, Butriptyline, Clomi 0167. Others such as Acrisorcin, Amorolfine, Biphe pramine, Demexiptiline, Desipramine, Dibenzepin, namine, BromoSalicylchloranilide, Buclosamide, Cal Dimetracrine, Dothiepin, DOXepin, Fluacizine, Imi cium Propionate, Chlophenesin, CiclopiroX, Clox pramine, Imipramine N-Oxide, Iprindole, yguin, Coparaffinate, Diamthazole, Dihydrochloride, Lofepramine, Melitracen, Metapramine, Nortriptyline, Exalamide, Flucytosine, Halethazole, Hexetidine, Lof Noxiptilin, Opipramol, Pizotyline, Propizepine, Prot lucarban, Nifuratel, Potassium Iodide, Propionates, riptyline, Quinupramine, Tianeptine, Trimipramine Propionic Acid, Pyrithione, Salicylanilide, Sulbentine, 0152. Others such as Adrafinil, Benactyzine, Bupro Tenonitrozole, Triacetin, Ujothion, Undecylenic Acid pion, Butacetin, Dioxadrol, Duloxetine, Etoperidone, 0168 ANTIGLAUCOMA such as Acetazolamide, Febarbamate, Femoxetine, Fenpentadiol, Fluoxetine, Befunolol, Betaxolol, Brimonidine, Bupranolol, Car US 2003/0068365A1 Apr. 10, 2003 11

teolol, Dapiprazoke, Dichlorphenamide, Dipivefrin, 0186. Others such as Acifran, AZacosterol, Benfluorex, Dorzolamide, Epinephrine, Latanoprost, Levobunolol, beta-Benzalbutyramide, Carnitine, Chondroitin Sul Methazolamide, Metrpranolol, Pilocarpine, Pindolol, fate, Clomestone, Detaxtran, Dextran Sulfate Sodium, Timolol, Unoprostone 5,8,11,14,17-Eicosapentaenoic Acid, Eritadenine, Furazbol, Meglutol, Melinamide, Mytatrienediol, Orni 0169 ANTIGONADOTROPIN such as Danazol, thine, gamma-Oryzanol, Pantethine, Penataerythritol Gestrinone, Paroxypropione Tetraacetate, alpha-Phenylbutyramide, Phylate Acids 0170 ANTIGOUT such as Allopurinol, Carpofen, and Salts, Pirozadil, Probucol, beta-Sitosterol, Sulto Colchicine, Probenecid, Sulfinpyrazone Silic Acid, Tiadenol, Triparanol, Xenbucin 0171 Antihistaminic 0187 Antihypertensive 0172 Alkylamine Derivatives such as Acrivastine, 0188 Benzothiadiazine Derivatives such as Althiaz Bamipine, Brompheniramine, Chlorpheniramine, ide, Bendroflumethiazide, Benzthiazide, Benzylhydro Dimethindene, Metron S, Pheniramine, Pyrrobutamine, chlorothiazide, Buthiazide, Chlorothiazide, Chlorthali Thenaldine, Tolpropamine, Triprolidine done, Cyclopenthiazide, Cyclothiazide, DiaZOxide, Epithiazide, Ethiazide, Fenguizone, Hydrochlorothiaz 0173 Aminoalkyl Ethers such as Bietanautine, Bro ide, Hydroflumethiazide, Indapamide, Methyclothiaz modiphenhydramine, Carbinoxamine, Clemastine, ide, Meticrane, Metolazone, Paraflutizide, Polythiaz Diphenylhydramine, Diphenlypyraline, Doxylamine, ide, Quinethazone, Teclothiazide, Trichlormethiazide Embramine, Medrylamine, Moxastine p-Methyl diphenhydramine, Orphenadrine, Phenyltoloxamine, 0189 N-Carboxyalkyl (peptide/lactam) Derivatives Setasine Such as Alacepril, Benazepril, Captopril, Ceronapril, CilaZapril, Delapril, Enalapril, Enalaprilat, Fosinopril, 0.174 Ethylenediamine Derivatives such as Allocla Imidapril, Lisinopril, Moveltipril, Perindopril, mide, Chloropyramine, Chlorothen, Histapyrrodine, Quinapril, Ramipril Spirapril, Temocarpril, Trandola Methafurylene, Methaphenilene, Methapyrilene, Pyril pril amine, Talastine, Thenyldiamine, Thonzylamine, Tripelennamine, Zolamine 0190. Guanidine Derivatives Bethanidine, Debriso quin, Guanabenz, Guanacline, Guanadrel, GuanaZod 0.175 Piperazines such as Cetirizine, Chlorcyclizine, ine, Guanethidine, Guanfacine, Guanochlor, Guanoxa Cinnarizine, Clocinizine, Hydroxy Zine benz, GuanoXan 0176 Tricyclics 0191 Hydrazines/Phthalazines such as Budralazine, 0177 Phenothiazines such as Ahistan, Etymemazine, Cadralazine, Dihydralazine, Endralazine, Hydracarba Fenethazine, N-Hydroxyethylpromethazine, Iso zine, Hydralazine, Pheniprazine, Pildralazine, Todrala promethazine, Mequitazine, Promethazine, ThiaZina Zine mium Methyl Sulfate 0.192 Imidazole Derivatives such as Clonidine, 0178. Other tricyclics such as AZatadine, Cloben Lofexidine, Monoxidine, Phentolamine, Tiamenidine, Zepam, Cyproheptadine, Deptropine, Isothipendyl, Tolonidine Loratadine 0193 Quaternary Ammonium Compounds Azametho 0179. Others such as Antazoline, Astemizole, Azelas nium, Chlorisondamine, Hexamethonium, Penta tine, Cetoxime, Clemizole, Clobenztropine, Ebastine, cynium Bis(methyl sulfate), Pentamethonium, Pento Emedastine, Epinastine, FeXofenadine, Levocabastine, linium Tartate, Phenactopinium, Trimethidiunum Mebhydroline, Phenindamine, Terfenadine, Tritoqual Methosulfate C 0194 Quinazoline Derivatives such as Alfuzosin, 0180 Antihyperlipoproteinemic BunaZoSin Doxazosin, PraZosin, Terazosin, TrimaZoSin 0.195 Reserpine Derivatives such as Bietaserpine, 0181 Aryloxyalkanoic Acid Derivatives such as DeSerpidine, Rescinnamine, Reserpine, Syrosingopine Beclorbrate, Bazafibrate, Binifibrate, Ciprofibrate, Cli nofibrate, Clofibrate, Clofibric Acid, Etonfibrate, 0196) Sulfonamide Derivatives such as Ambuside, Fenofibrate, Gemfibrozil, Nicofibrate, Pirifibrate, Ron Clopamide, Furosemide, QuinethaZone, Tripamide, ifibrate, Simfibrate, Theofibrate Xipamide 0182 Bile Acid Sequesterants such as Cholestyramine 0.197 Others such as Aimaline, gamma-Aminobutyric Resin, Colestipol, Polidexide Acid, Bufeniode, Carmoxirole, Chlorthalidone, Cicle taine, Ciclosidomine, Clentiazem, Cryptenamine Tan 0183 HMG CoA Reductase Inhibitors such as Atorv nates, Fantofarone, Fenoldopam, FloSequinan, astatin, Fluvastatin, Lovastatin, Pravastatin, Simvasta Indoramin, Ketanserin, Levcromakalim, Metbutamate, tin Mecamylamine, Methyldopa, Methyl 4-Pyridyl Ketone 0.184 Nicotinic Acid Derivatives Acipimox, Alumi Thiosemicarbarzone, Metolazone, Milberfradil, num Nicotinate, Niceritrol, Nicoclonate, Nicomol, Minoxidil, Muzolimine, Naftopidil, Pargyline, Pempi OXiniacic Acid dine, Pinacidil, Piperoxan, Protoveratrines, Raubasine, Rescimetol, Saralasin, Semotiadil, Sodium Nitroprus 0185 Thyroid Hormones/Analogs such as Etiroxate, Side, Ticrynafen, Trimethaphan Camsylate, Tyrosinase, Thyropropic Acid, Thyroxine Urapidil US 2003/0068365A1 Apr. 10, 2003 12

0198 ANTIHYPERTHYROID such as 2-Amino-4- Acid, Amixetrine, BendaZac, BenZydamine, alpha-Bis methylthiazole, 2-Aminothiazole, Carbimazole, 3,5- abolol, Bucolome, Difenpiramide, Ditazol, Emorfa Dibromo-L-tyrosine, 3,5-Diiodotyrosine, Iodine, Zone, Fepradinol, GuaiaZulene, Nabumetone, Nime Methimazole, Methylthiouracil, Propylthiouracil, Sulide, Oxaceprol, Paranyline, Perisoxal, ProquaZone, Sodium Perchlorate, Thibenzazoline, Thiobarbital, Superoxide Dismutase, Tenidap, Zileuton 2-Thiouracil 0212 ANTIMALARIAL Such as Acedapsone, Amo 0199 ANTIHYPOTENSIVE such as Amezinium diacquin, Arteether, Artemether, Artemisinin, ArteSu Methyl Sulfate, Angiotensin Amide, Dimetofrine, nate, Atovaquone, Bebeerine, Berberine, Chirata, Chlo Dopamine, Etifelmin, Etilefrin, Gepefrine, Metarami rguanide, Chloroquine, Chlorproguanil, Cinchona, nol, Methoxamine, Midodrine, Norepinephrine, Cinchonidine, Cinchonine, Cycloguanil, Gentiopicrin, Pholedrine, Synephrine Halofantrine, Hydroxychloroquine, Mefloquine Hydro 0200 ANTIHYPOTHYROID such as Levothyroxine, chloride, 3-Methylarsacetin, Pamaquine, Plasmocid, Liothyronine, Thyroid, Thyroidin, Thyroxine, Tiratri Primaquine, Pyrimethamine, Quinacrine, Quinidine, Quinine, Quinocide, Quinoline, Sodium Arsenate, Dia col, TSH basic 0201 Anti-inflammatory (Nonsteroidal) 0213 ANTIMIGRAINE such as Alpiropride, Dihy 0202 Aminoarylcarboxylic Acid Derivatives such as droergotamine, Dolasetron, Ergocornine, Ergocorni Enfenamic Acid, Etofenamate, Flufenamic Acid, nine, Ergocryptine, Ergot, Ergotamine, FlumedroXone Isonixin, Meclofenamic Acid, Mefanamic Acid, Niflu Acetate, Fonazine, Lisuride, MethySergid(e), Oxetor mic Acid, Talniflumate, Terofenamate, Tolfenamic one, Pizotyline, Sumatriptan Acid 0214) ANTINAUSEANT such as Acetylleucine 0203 Arylacetic Acid Derivatives such as Ace Monoethanolamine, Alizapride, AZasetron, BenZquina clofenac, Acemetacin, Alclofenac, Amfenac, Amtol mide, Bietanautine, Bromopride, Buclizine, Chlorpro metin Guacil, Bromfenac, BufeXamac, Cinmetacin, mazine, Clebopride, Cyclizine, Dimenhydrinate, Clopirac, Diclofenac, Etodolac, Felbinac, Fenclozic Dipheniodol, Dolasetron, Domperidone, Granisetron, Acid, Fentiazac, Glucametacin, Ibufenac, Indometha Meclizine, Methalltal, Metoclopramide, Metopi cin, IsofeZolac, ISOXepac, Lonazolac, Metiazinic Acid, mazine, Nabilone, Ondansteron, Oxypendyl, Pipam MofeZolac, Oxametacine, PiraZolac, Proglumetacin, azine, Prochlorperazine, Scopolamine, Sulpiride, Tet Sulindac, Tiaramide, Tolimetin, Tropesin, Zomepirac rahydrocannabinols, Thiethylperazine, 0204 Arylbutyric Acid Derivatives such as Bumadi Thioproperazine, Trimethobenzamide, Tropisetron Zon, Butibufen, Fenbufen, Xenbucin 0215 Antineoplastic 0205 Arylcarboxylic Acids such as Clidanac, Ketoro 0216 Alkylating agents lac, Tinoridine 0217 Alkyl Sulfonates such as Busulfan, Improsulfan, 0206 Arylpropionic Acid Derivatives such as Almi Piposulfan noprofen, Benoxaprofen, Bermoprofen, Bucloxic Acid, Carprofen, Fenoprofen, Flunoxaprofen, Flurbiprofen, 0218 Aziridines such as Benzodepa, Carboquone, Ibuprofen, Ibuproxam, Indoprofen, Ketoprofen, LOXO Meturedepa, Uredepa profen, Naproxen, Oxaprozin, Piketoprofen, Pirprofen, 0219 Ethylenimines and Methylmelamines such as Pranoprofen, Protizinic Acid, Suprofen, Tiaprofenic Altretamine, Triethylenemelamine, TriethylenephoS Acid, Ximoprofen, Zaltoprofen phoramide, Triethylenethiophosphoramide 0207 Pyrazoles such as Difenamizole, Epirizole 0220 Nitrogen Mustards such as Chlorambucil, Chlo 0208 Pyrazolones such as Apazone, BenZpiperylon, rnaphazine, Cyclophosphamide, Estramustine, Ifosfa Feprazone, Mofebutazone, Morazone, Oxyphenbuta mide, Mechlorethamine, Mechlorethamine Oxide Zone, PhenylbutaZone, PipebuZone, PropyphenaZone, Hydrochloride, Melphalan, Novembichin, Perfosfa RamifenaZone, SuxibuZone, ThiazolinobutaZone mide, Phenesterine, Prednimustine, Trofosfamide, 0209 Salicylic Acid Derivatives such as Acetaminos Uracil Mustard alol, Aspirin, Benorylate, Bromosaligenin, Calcium 0221) Nitrosoureas Carmustine, Chlorozotocin, Fote Acetylsalicylate, Diflunisal, EterSalate, Fendosal, Gen mustine, Lomustine, Nimustine, Ranimustine tisic Acid, Glycol Salicylate, Imidazole Salicylate, Lysine Acetylsalicylate, MeSalamine, Morpholine Sali 0222. Others such as Dacarbazine, Mannomustine, cylate, 1-Naphthyl Salicylate, Olsalazine, Parsalmide, Mitobronitol, Mitolactol, Pipobroman, Temozolomide Phenyl Acetylsalicylate, Phenyl Salicylate, Salaceta 0223 Antibiotics Such as Aclacinomycins, Actinomy mide, Salacetamide O-Acetic Acid, Salicylsulfuric cin F, Anthramycin, AZaSerine, Bleomycins, Cactino Acid, Salsalate, SulfaSalazine mycin, Carubicin, CarZinophilin, Chromomycins, Dac tinomycin, Daunorubicin, 6-Diazo-5-oxo-L- 0210. Thiazinecarboxamides such as Ampiroxicam, norleucine, Doxorubicin, Epirubicin, Idarubicin, DroXicam, ISOXicam, Lornoxicam, PiroXicam, Tenoxi Menogaril, Mitomycins, Mycophenolic Acid, Nogala Ca mycin, Olivomycins, Peplomycin, Pirarubicin, Plica 0211. OtherS Such as epsilon-Acetamidocaproic Acid, mycin, Porfiromycin, Puromycin, Streptonigrin, Strep S-Adenosylmethionine, 3-Amino-4-hydroxybutyric toZocin, Tubercidin, Zinostatin, Zorubicin US 2003/0068365A1 Apr. 10, 2003

0224) Antimetabolites Mepartricin, Metronidazole, Nifuratel, Nifuroxime, 0225. Folic Acid Analogs such as Denopterin, Edatr Nimorazole, Secnidazole, Silver Picrate, Tenonitro exate, Methotrexate, Piritrexim, Pteropterin, Tomu Zole, Tinidazole dex(E), Trimetrexate 0243 ANTIPROTOZOAL (TRYPANOSOMA) such 0226 Purine Analogs such as Cladribine, Fludarabine, as Benznidazole, Eflornithine, Melarsoprol, Nifur 6-Mercaptopurine, Thiamiprine, Thioguanaine timox, OXophenarsine, Pentamidine, Propamidine, Puromycin, Quinapyramine, Stilbamidine, Suramin 0227 Pyrimidine Analogs such as Ancitabine, AZac Sodium, Trypan Red, Tryparasmide itidine, 6-AZauridine, Carmofur, Cytarabine, DOXiflu ridine, Emitefur, Enocitabine, Floxuridine, Fluororacil, 0244 ANTIPRURITIC such as Camphor, Cyprohep Gemcitabine, Tegafur tadine, Dichlorisone, Glycine, Halometasone, 3-Hy 0228 Enzymes Such as L-Asparaginase droxycamphor, Menthol, Mesulphen, Methdilazine, Phenol, Polidocanol, Spirit of Camphor, Thenaldine, 0229. Others such as Aceglatone, Amsacrine, Bisant Tolpropamine, Trimeprazine rene, Defofamide, Demecolcine, Diaziquone, Elforni thine, Elliptinium Acetate, Etoglucid, Fenretinide, Gal 0245 ANTIPSORIATIC such as Acitretin, Ammo lium Nitrate, Hydroxyurea, Lonidamine, Miltefosine, nium Salicylate, Anthralin, 6-AZauridine, Ber MitoguaZone, Mitoxantrone, Mopidamol, Nitracrine, gapten(e), Calcipotriene, Chrysarobin, Etretinate, Pentostatin, Phenamet, Podophyllinicc Acid, Lonapalene, Pyrogallol, Tacalcitol, Tazaroteine 2-Ethythydrazide, Procarbazine, Razoxane, Sobuzox ane, Spirogermanium, TenuaZonic Acid, Triaziquone, 0246 Antipsychotic 2,2',2"-Trichlorotriethylamine, Urethan 0247 Butyrophenones such as Benperidol, Bromperi dol, Droperidol, Fluanisone, Haloperidol, Melperone, 0230 Antineoplastic (Hormonal) Moperone, Pipamperone, Sniperone, Timiperone, Tri 0231 Androgens such as Calusterone, Dromo fluperidol Stanolone, EpitioStanol, MepitioStane, Testolactone 0248 Phenothiazines such as Acetophenazine, 0232 Antiadrenals such as Aminoglutethimide, Mito Butaperazine, Carphenazine, Chlorproethazine, Chlor tane, TriloStane promazine, Clospirazine, Cyamemazine, Dixyrazine, Fluphenazine, Imiclopazine, Mepazine, Mesoridazine, 0233 Antiandrogens such as Bicalutamide, Flutamide, Methoxypromazine, Metofenazate, Oxaflumazine, Nilutamide Perazine, Pericyazine, Perimethazine, Perphenazine, 0234 Antiestrogens such as Droloxifene, Tamoxifen, Piperacetazine, Pipotiazine, Prochlorperazine, Pro Toremifene mazine, Sulforidazine, Thiopropazate, Thioridazine, 0235 Antineoplastic Adjunct Trifluoperazine, Triflupromazine 0249. Thioxanthenes such as Chlorprothixene, Clo 0236. Folic Acid Replenisher such as Folinic Acid penthixol, Flupentixol, Thiothixene 0237 ANTIPARKINSONIAN such as Amantadine, Benserazide, Bietanautine, Biperiden, Bromocriptine, 0250 Other Tricyclics such as Benzquinamide, Budipine, Carbidopa, Dexetimide, Diethazine, Droxi Carpipramine, Clocapramine, Clomacran, Clothiapine, dopa, Ethopropazine, Ethylbenzhydramine, LaZabe Clozapine, Mosapramine, Olanzapine, Opipramol, Pro mide, Levodopa, Mofegiline, Pergolide, Piroheptine, thipendyl, Serocquel E), Tetrabenazine, Zotepine Pramipexole, Pridinol, Prodipine, Ropinirole, Sel 0251. Others such as Buramate, Fluspirilene, Molin egiline, Talipexole, Terguride, Trihexyphenidyl Hydro done, Penfluridol, Pimozide, Ziprasidone chloride 0252 ANTIPYRETIC such as Acetominophen, 0238 ANTIPHEOCHROMOCYTOMA such as AcetaminoSalol, Acetanilide, Alclofenac, Aluminum Metyrosine, Phenoxybenzamine, Phentolamine Bis(ascetylsalicylate), Aminochlorhenoxazin, Ami 0239). ANTIPNEUMOCYSTIS such as Atovaquone, nopyrine, Aspirin, Benorylate, BenZydamine, Ber Effornithine, Pentamidine, Sulfamethoxazole berine, Bermoprofen, para-Bromoacetanilide, BufeX amac, Bumadizon, Calcium Acetylsalicylate, 0240 ANTIPROSTATIC HYPERTROPHY such as Chlorthenoxazin(e), Choline Salicylate, Clidanac, Epristeride, Finasteride, Gestonorone Caproate, Dihydroxyaluminum Acetylsalicylate, Dipyrocetyl, Mepartricin, OSaterone, Oxendolone, Tamsulosin, Dipyrone, Epirizole, EterSalate, Imidazole Salicylate, Terazosin Indomethacin, ISOfeZolac, para-Lactophenetide, Lysine 0241 ANTIPROTOZOAL (LEISHMANIA) such as Acetylsalicylate, Magnesium Acetylsalicylate, Ethylstibamine, HydroxyStilbamidine, N-Methylglu Meclofenamic Acid, Morazone, Morpholine Salicylate, Naproxen, Mifenazone, 5'-Nitro-2'-propoxyacetanilide, camine, Pentamidine, Stilbamidine, Sodium Stiboglu Phenacetin, Phenicarbazide, Phenocoll, Phenopyra conate, Urea Stibamine Zone, PhenylAcetylsalicyliate, Phenyl Salicylate, Pipe 0242 ANTIPROTOZOAL (TRICHOMONAS) such buZone, Propacetamol, PropyphenaZone, Ramifena as AcetarSone, Aminitrozole, Anisomycin, AZanida Zone, Salacetamide, SSalicylamide-O-Acetic Acid, Zole, Furazolidone, Hachimycin, Lauroguadine, Sodium Salicylate, Tetrandrine, Tinoridine US 2003/0068365A1 Apr. 10, 2003

0253) ANTIRICKETTSIAL such as p-Aminobenzoic 0264. ANTITHROMBOTIC such as Argatroban, Cil Acid, Chloramphenicol, Tetracycline OStaZol, Clopidrgrel, Cloricromen, Dalteparin, Dal troban, Defibrotide, Enoxaparin, Indobufen, Iloprost, 0254 ANTISEBORRHEIC such as Chloroxine, 3-O- Integrelin, Isbogrel, Lamifiban, Lamoparan, Nadro Lauroylpyridoxol Diacetate, Piroctone, Pyrithione, parin, OZagrel, Picotamide, Plafibride, Reviparin Resorcinol, Selenium Sulfides, Tioxolone Sodium, Ridogrel, Sulfinpyrazone, Taprostene, Ticlo 0255 Antiseptic pidine, Tinzaparin, Tirofiban, Triflusal 0256 Guanidines such as Alexidine, Ambazone, Chlo 0265 ANTITUSSIVE such as Allocamide, Amici rhexidine, Picloxydine bone, Benproperine, BenZonatate, Bibenzonium, Bro moform, Butamirate, Butethamate, Caramiphen 0257 Halogens/Halogen Compounds such as Bismuth Ethanedisulfonate, Carbetapentane, Chlophedianol, Iodide Oxide, Bismuth Iodosubgallate, Bismuth Tri Clobutinol, Cloperastine, Codeine, Codeine Methyl bromophenate, Bornyl Chloride, Calcium Iodate, Chlo Bromide, Codeine N-Oxide, Codeine Phosphate, rinated Lime, Cloflucarban, Iodic Acid, Iodine, Iodine Codeine Sulfate, Cyclexanone, Dextromethorphan, Monochloride, Iodine Trichloride, Iodoform, Meth Dihydrocodeine, Dihydrocodeinone Enol Acetate, enamine Tetraiodine, Oxychlorosene, PoVidone-Iodine, Dimemorfan, Dimethoxanate, Dropropizine, Drote Sodium Hypochlorite, Sodium Iodate, Symclosene, banol, Eprazinone, Ethyl Dibunate, Ethylmorphine, Triclocarban, Triclosan, Troclosene Potassium Fominoben, Guiaiapate, Hydrocodone, Isoaminile, 0258 Nitrofurans such as Furazolidone, 2-(Meth Levopropoxyphene, Morclofone, Narceline, Normetha oxymethyl)-5-Nitrofuran, Nidroxy Zone, Nifuroxime, done, NoScapine, Oxeladin, OXolamine, Pholcodine, Nifurzide, Nitrofurazone Picoperine, Pipazethate, Piperidione, Prenoxdiazine, Racemethorphan, Sodium Dibunate, Tipepidine, 0259 Phenols such as Acetomeroctol, Bithionol, Cad Zipeprol mium Salicylate, Carvacrol, Chloroxylenol, Clo rophene, Creosote, CreSol, Fenticlor, Hexachlo 0266 ANTIULCERATIVE such as Aceglutamide rophene, 1-Napthyl Salicylate, 2-Napthyl Salicylate, Aluminum Complex, epsilon-Acetamidocaproic Acid 2,4,6-Tribromo-m-cresol, 3',4',5-Trichlorosalicylanil Zinc Salt, Acetoxolone, Aldioxa, Arbaprostil, Benexate ide Hydrochloride, Carbenoxolone, Cetraxate, Cimetidine, Colloidal Bismuth Subcitrate, Ebrotidine, Ecabet, 0260 Quinolines such as Aminoquinuride, Benzox EnproStil, Esaprazole, Famotidine, Gefarnate, Guaia iquine, Broxyquinoline, Chloroxine, Chlorquinaldol, Zulene, IrSogladine, Lansoprazole, Misoprostol, Niza Cloxyquin, Ethylhydrocupreine, Euprocin, Halquinol, tidine, Omeprazole, Ornoprostil, gamma-Oryzanol, Hydrastine, 8-Hydroxquinoline Sulfate, Iodochlorhy Pantoprazole, Pifarnine, Pirenzepine, Plaunotol, Pola droxyquin preZinc, Rabeprazole, Ranitidine, Rebamipide, Rio 0261). Others such as Aluminum Acetate Solution, Alu prostil, Rosaprostol, Rotraxate, Roxatidine Acetate, minum Subacetate Solution, Aluminum Sulfate, Sofalicone, Spizofurone, Sucralfate, Telenzepine, 3-Amino-4-hydroxybutyric Acid, Boric Acid, Chlo Teprenone, Trimoprostil, Thrithiozine, Troxipide, Zoli rhexidine, ChloroaZodin, m-Cresyl Acetate, Cupric midine Sulfate, Dibromopropamidine, Ichthammol, Negatol, 0267 ANTIUROLITHIC such as Acetohydroxamic Noxythiolin, Octenidine, Ornidazole, beta-Propriolac Acid, Allopurinol, Potassium Citrate, Succinimide tone, alpha-Terpineol 0268 ANTIVENIN such as Lyovac Antivenin 0262 ANTISPASMODIC such as Alibendol, Ambuc etamide, Aminopromazine, Apoatropine, Bevonium 0269. Antiviral Methyl Sulfate, Bietamiverine, Butaverine, Butropium, 0270 Purines/Pyrimidinones such as Acyclovir, Cido N-Butylscopolammonium fovir, Cytarabine, Dideoxyadenosine, Didanosine, 0263 Bromide, Caroverine, Cimetropium, Cinnamed Edoxudine, Famciclovir, Floxuridine, Ganciclovir, rine, Clebopride, Cyclonium Iodide, Difemerine, Idoxuridine, Inosine Pranobex, Lamivudine, MADU, Diisopromine, Dioxaphetyl Butyrate, Diponium Bro Penciclovir, Sorivudine, Stavudine, Trifluridine, Vala mide, Drofenine, Emepronium Bromide, Ethaverine, cyclovir, Vidrarbine, Zalcitabine, Zidovudine Etomidoline, Feclemine, Fenalamide, Fenoverine, Fen 0271 Others such as Acemannan Acetylleucine Mono piprane, Fenpiverinium Bromide, Fentonium Bromide, ethanolamine, Amantadine, Amidinomycin, Delaviri Flavoxate, Flopropione, Gluconic Acid, Hydramitra dine, Foscarnet Sodium, Indinavir, Interferon (alpha, Zine, Hymecromone, Leiopyrrole, Mebeverine, Mox beta, gamma), Kethoxal, Lysozyme, Methisazone, averine, Nafiverine, Octamylamine, Octaverine, Pen Moroxydine, Nevirapine, Podophyllotoxin, Ribavirin, tapiperide, Phenamacide, Phloroglucinol, Pinaverium, Rimantadine, Ritonavir, Saquinavir, Stallimycin, Sta Piperilate, Pipoxolan Hydrochloride, Pramiverin, Pri tolon, Tromantadine, Xenazoic Acid finium Bromide, Propyromazine, Prozapine, Racefem ine, Rociverine, Sintropium Bromide, Spasmolytol, 0272 Anxiolytic Sultroponium, Tiemonium Iodide, Tigloidine, Tiqui 0273 Arylpiperazines Such as Buspirone, Enciprazine, Zium Bromide, Tiropramide, Trepibutone, Tricromyl, Flesinoxan, Ipsapirone, Lesopitron, TandoSpirone Trifolium, Trimebutine, N,N-1Trimethyl-3,3-diphenyl propylamine, Tropenzile, TroSpium Chloride, Xenotro 0274 Benzodiazepine Derivatives Alprazolam, Bro pium Bromide mazepam, Camazepam, Chlordiazepoxide, Clobazam, US 2003/0068365A1 Apr. 10, 2003 15

CloraZepate, Chotiazepam, Cloxazolam, Diazepam, talin, Digitalis, Digitoxin, Digoxin, Dobutamine, Ethyl Loflazepate, Etizolam, Fluidazepam, Flutazolam, Docarpamine, Dopamine, Dopexamine, Enoximone, Flutoprazepam, Halazepam, Ketazolam, Lorazepam, Erythrophleine, Fenalcomine, Gitalin, Gitoxin, Glyco Loxapine, Medazepam, Metaclazepam, Mexazolam, cyamine, Heptaminol, Hydrastinine, Ibopamine, Lano Nordazepam, Oxazepam, Oxazolam, Pinazepam, todises, Loprinone, Milrinone, Neriifolin, Oleandrin, Prazepam, Tofisopam Ouabain, Oxyfedrine, Pimobendan, Prenalterol, 0275 Carbamates such as Cyclarbamate, Emylcamate, Proscillaridin, Resibufogenin, Scillaren, Scillarenin, Hydroxyphenamate, Meprobamate, Phenprobamate, Strophanthin, Sulmazole, Theobromine, Vesnarinone, Tybamate Xamoterol 0276. Others Abecarnil, Alpidem, Benzoctamine, Cap 0290 CHELATING AGENT such as Deferoxazmine, todiamine, ChlormeZanone, Etifoxine, Fluoresone, Ditiocarb Sodium, Edetate Calcium Disodium, Edetate Glutamic Acid, Hydroxyzine, Mecloralurea, Mephe Disodium, Edeate Sodium, Edetate Trisodium, Penicil noxalone, Oxanamide, PaZinaclone, Suriclone lamine, Pentetate Calcium Trisodium, Pentectic Acid, Succimer, Trientine 0277 BENZODIAZEPINE ANTAGONIST such as Flumazenil 0291 Cholecystokinin Antagonist (CCK Antagonist) 0278 Bronchodilator 0292 CHOLELITHOLYTICAGENT such as Cheno diol, Methyl tert-Butyl Ether, Monooctanoin, Ursodiol 0279 Ephedrine Derivatives such as Albuterol, Bam buterol, Bitolterol, Carbuterol, Clenbuterol, Clorprena 0293 CHOLERETIC such as Alibendol, Anethole line, Dioxethedrine, Ephedrine, Epinephrine, Trithion, AZintamide, Cholic Acid, Cicrotoic Acid, EproZinol, Etafedrine, Ethylnorepinephrine, Fenoterol, Clanobutin, Cyclobutyrol, Cyclovalone, Cynarin(e), Formoterol, HeXoprenaline, Isoetharine, Isoproterenol, Dehydrocholic Acid, Deoxycholic Acid, Dimecrotic Mabuterol, Metaproterenol, N-Methylephedrine, Pir Acid, alpha-Ethylbenzyl Alcohol, Exiproben, Febu buterol, Procaterol, Protokylol, Reproterol, Rimiterol, prol, Fencibutirol, Fenipentol, Florantyrone, Hymec Salmeterol, Soterenol, Terbutaline, Tulobuterol romone, Menbutone, 3-(o-Methoxyphenyl)-2-pheny lacrylic Acid, Metochalcone, Moquizone, OSalmid, OX 0280 Quaternary Ammonium Compounds such as Bile Extract, 4,4'-Oxydi-2-butanol, Piprozolin, 4-Sali Bevonium Methyl Sulfate, Flutropium Bromide, Ipra cyloylmorpholine, Sincalide, Taurocholic Acid, tropium Bromide, Oxitropium Bromide, Tiotropium Tocamphyl, Trepibutone, Vanitiolide Bromide 0281 Xanthine Derivatives such as Acefylline, Ace 0294 CHOLINERGIC such as Aceclidine, Acetylcho fylline Piperazine, Ambuphylline, Aminophylline, line, Acetylcholide, Aclatonium Napadisilate, BenZpy rinium Bromide, Bethanechol, Carbachol, Carpronium, Bamifylline, Choline Theophyllinate, Doxofylline, Demecarium, Dexpanthenol, Diisopropyl Paraoxon, Dyphylline, Etamiphyllin, Etofylline, Guaithylline, Echothiophate, Edrophomium, Eptastigmine, Eseri Proxyphylline, Theobromine, 1-Theobromineacetic dine, Furtrethonium, Isoflurophate, Methacholine Acid, Theophylline Chloride, Muscarine, NeoStigmine, Oxapropanium, 0282. Others such as Fenspiride, Medibazine, Meth PhySoStigmine, Pyridostigmine, Xanomeline Oxyphenanime, Tretoquinol 0295). CHOLINESTERASE INHIBITOR such as 0283 Calcium Channel Blocker Ambenonium, Distigmine, Eptastigmine, Galan 0284 Arylalkylamines such as Bepridil, Clentiazen, thamine Diltiazem, Fendiline, Gallopamil, Mibefradil, Preny 0296 CHOLINESTERASE REACTIVATOR such as lamine, Semotiadil, Terodiline, Verapamil ASOXime, Obidoximine, Pralidoxime 0285 Dihydropyridine Derivatives such as Amlo 0297 CNS STIMULANT/AGENT such as Aminept dipine, Aranidipine, Barnidipine, Benidipine, Cilnid ine, Amphetimine, Amphetaminil, Bemegride, Benz ipine, Efonidipine, Elgodipine, Felodipine, Isradipine, phetamine, Brucine, Caffeine, Chlorphentermine, Clo Lacidipine, Lercanidipine, Manidipine, Nicardipine, rtermine, Coca, Deanol, Demanyl Phosphate, Nifedipine, Nilvadipine, Nimodipine, Nisoldipine, Dexoxadrol, Dextroamphetamine Sulfate, Diethylpro Nitrendipine pion, N-Ethylamphetamine, Ethamivan, Etifelmin, 0286 Piperazine Derivatives such as Cinnarizine, Flu Etryptamine, Fencamfamine, Fenethylline, FenoZo narizine, Lidoflazine, Lomerizine lone, Flurothyl, Hexacyclonate Sodium, Homocamfin, Mazindol, Mefexamide, Methamphetamine, Meth 0287. Others such as Bencyclane, Etafenone, Fanto ylphenidate, Modafinil, Nikethamide, Pemoline, Pen farone, Perhexiline tylenetetrazole, Phenidimetrazine, Phenmetrazine, 0288 CALCIUM REGULATOR such as Calcifediol, Phentermine, Picrotoxin, Pipradrol, Prolintane, Pyrov Calcitonin, Calcitriol, Dihydrotachysterol, Elcatonin, alerone, Tetrahydrobenzothienopyridines Ipriflavone, Parathyroid Hormone, Teriparatide Acetate 0298 DECONGESTANT such as Amidephrine, Caf 0289 CARDIOTONIC such as Acetfylline, Acetyldig aminol, Cyclopentamine, Ephedrine, Epinephrine, ititoxins, 2-Amino-4-picoline, Amrinone, Benfurodil Fenoxazoline, Indanazoline, Metizoline, Naphazoline, Hemisuccinate, Buclasdesine, Camphotamide, Conva Nordefrin, Octodrine, Oxymetazoline, Phenylephrine, latoxin, Cymarin, Denopamine, Deslanoside, Digi Phenylpropanolamine, Phenylpropylmethylamine, US 2003/0068365A1 Apr. 10, 2003

Propyhexedrine, Pseudoephredrine, Tetrahydrolzoline, Estrone, Ethinyl Estradiol, Mestranol, Moxestrol, TramaZoline, Tuaminoheptane, TymaZoline, Xylometa Mytatrienediol, Quinestradiol, Quinestrol Zoline 0318 GASTRIC SECRETION INHIBITOR such as 0299. DENTAL CARRIES PROPHYLACTIC such as Enterogastrone, Octreotide, Telenzepine Sodium Fluoride 03.19 GLUCOCORTICOID such as 21-Acetox 0300 DEPIGMENTOR such as Hydroquinine, Hyd yprefnenolone, AlclometaSone, AlgeStone, Amcinon roquinone, Monobenzone ide, Beclomethasone, Betamethasone, BudeSonide, Chloroprednisone, Clobetasol, ClobetaSone, Clocor 0301 Diuretic tolone, Cloprednol, Corticosterone, Cortisone, Cortiva 0302 Organomercurials such as Chlormerodrin, Mer Zol, Deflazacort, DeSonide, DeSoximetasone, Dexam alluride, Mercamphamide, Mercaptomerin Sodium, ethasone, Diflorasone, Diflucortolone, Difluprednate, Mercumallylic Acid, Mercumatilin Sodium, Mercurous Enoxolone, Fluazacort, Flucloronide, Flumethasone, Chloride, Mersalyl Flunisolide, Fluocinolone Acetonide, Fluocinonide, Fluocortin Butyl, Fluocortolone, Fluorometholone, 0303 Purines such as Acefylline, 7-Morpholinometh Fluperolone Acetate, Fluprednidene Acetate, Flupred yltheophylline, Pamabrom, Protheobromine, Theobro nisolone, Flurandrenolide, Fluticasone Propionate, For mine mocortal, Halcinonide, Halobetasol Propionate, 0304 Steroids such as Canrenone, Oleandrin, Spirono Halometasone, Halopredone Acetate, Hydrocortamate, lactone Hydrocortisone, Loteprednol Etabonate, MaZipredone, Medrysone, Meprednisone, Methyolprednisolone, 0305 Sulfonamide Derivatives such as Acetazolmide, Mometasone Furcate, Paramethasone, Prednicarbate, AmbuSide, AZOSemide, Bumetanide, Butazolamide, Prednisolone, Prednisolone 25-Diethylaminoacetate, Chloraminophenamide, Clofenamide, Clopamide, Clo Prednisone Sodium Phosphate, Prednisone, Prednival, reXolene, Disulfamide, EthoXZolamide, Furosemide, Prednylidene, Rimexolone, Tixocortol, Triamcinolone, Mefruside, Methazolamide, Piretanide, Torasemide Triamcinolone Acetonide, Triamcinolone Benetonide, Tripamide, Xipamide Triamcinolone Hexacetonide 0306 Uracils such as Aminometradine, Amisometra 0320 GONAD-STIMULATING PRINCIPLE such as dine BuSerelin, Chorionic Gonadotropin, Clomiphene, 0307. Others such as Amanozine, Amiloride, Arbutin, Cyclofenil, Epimestrol, FSH, LH, LH-RH Chlorazanil, Ethacrynic Acid, EtoZolin, Hydracarba 0321) GONADOTROPIC HORMONE such as LH, Zine, Isosorbide, Mannitol, Metochalcone, PMSG Muzolimine, Perhexiline, Triamterene, Urea 0322 GROWTH HORMONE INHIBITOR such as 0308) DOPAMINE RECEPTOR AGONIST such as Bromocriptine, Cabergoline, Carmoxirole, DopeXam Octreotide, Somatostatin ine, Fenoldopam, Ibopamine, Lisuride, Pergolide, 0323 GROWTH HORMONE RELEASING FAC Pramipexole, Quinagolide, Ropinirole, ROXindole, Tal TOR Such as Semorelin ipexole 0324 GROWTH STIMULANT such as Somatotropin 0309 ECTOPARASITICIDE such as Amitraz, Benzyl Benzoate, Carbaryl, Crotamiton, DDT, Dixanthogen, 0325 HEMOLYTIC such as Phenylhydrazine Lime Sulfurated Solution, Lindane, Malathion, Mercu 0326 HEPARIN ANTAGONIST such as Hexa ric Oleate, Mesulfen, Sulfiram, Sulphur (Pharmaceuti dimethrine cal) 0327) HEPATOPROTECTANT such as S-Adenosul 0310 Enzyme methionine, Betaine, Catechin, Citolone, Malotilate, 0311 Digestive Such as Amylase, Lipase, Pancreli Methionine, Orazamide, Phosphorylcholine, Protopor 9. y p phyrin IX, Silymarin-Group, Thiotic Acid, Timonacic, pase, Pepsin, Rennin Tiopronin 0312 Penicillin Inactivating such as Penicillinase 0328 IMMUNOMODULATOR such as Acemannan, 0313 Proteolytic such as Collagenase, Chymopapain, Amiprilose, Bucillamine, Ditiocarb Sodium, Imiqui Chymotrypsins, Papain, Trypsin mod, Inosine Pranobex, Interferon (alpha, beta, gamma), Lentinan, Levamisole, Macrophage Colony 0314) ENZYME INDUCER (HEPATIC) such as Flu Stimulating Factor, Pidotimod, Platonin, Procodazole, mecinol Propagermanium, Romurtide, Thymomodulin, Thymo 0315 Estrogen pentin, Ubenimex 0316 Nonsteroidal such as Benzestrol, Broparoestrol, 0329 IMMUNOSUPPRESSANT such as Azathio Chlorotrianisene, Dienestrol, Diethylstilbestrol, prine, Brequinar, CycloSporins, Gusperimus, 6-Mer Dimestrol, Fosfestrol, Hexestrol, Methallenestril, captopurine, Mizoribine, Rapamycin Methestrol 0330) ION EXCHANGE RESIN such as Carbacrylic 0317 Steroidal such as Colpormon, Conjugated Estro Resins, Cholestyramine Resin, Colestipol, Polidexide, genic Hormones, Equilenin, Equilin, Estradiol, Estriol, Resodec, Sodium Polystyrene Sulfonate US 2003/0068365A1 Apr. 10, 2003 17

0331) LACTATION STIMULATING HORMONE 0343 OPHTHALMIC AGENT such as 15-ketopros Such as Prolactin taglandins 0332 LH-RH AGONIST such as Buserelin, Deslore 0344) OVARIAN HORMONE such as Relaxin lin, Goserelin, Histrelin, Leuprolide, Nafarelin, Trip 0345 OXYTOCIC such as Carboprost, Cargutocin, torelin Deaminooxytocin, Ergonovine, Gemeprost, Methyler gonovine, Oxytocin, Pituitary (Posterior), Prostaglan 0333) LIPOTROPIC such as N-Acetylmethionine, din E, ProStaglandin F, Sparteine Choline Chloride, Choline Dehydrocholate, Choline 0346 PEPSIN INIBITOR such as Sodium Amylosul Dihydrogen Citrate, Inositol, Lecithin, Methionine fate 0334) LUPUS ERYTHEMATOSUS SUPPRESSANT 0347 PERISTALTIC STIMULANT such as Cinitap Such as Bismuth Sodium Triglycollamate, Bismuth ride, Cisapride, Fedotozine, Loxiglumide Subsalicylate, Chloroquine, Hydroxychloroquine 0348 PROGESTOGEN such as Allylestrenol, Anage 0335) MINERALOCORTICOID such as Aldosterone, Stone, Chlormadinone Acetate, Delmadinone Acetate, Deoxycorticosterone, Fludrocortisone Demegestone, DeSogeStrel, Dimethisterone, Dro spirenone, Dydrogesterone, Ethisterone, Ethynodiol, 0336 MIOTIC such as Carbachol, Neostigmine, Phy Flurogestone Acetate, Gestodene, Gestonorone SoStigmine, Pilocarpine Caproate, 17-Hydroxy-16-methylene-progesterone, 17 alpha-Hydroxyprogesterone, LyneStrenol, Medroge 0337 MONOAMINE OXIDASE INHIBITOR such as Stone, Medroxyprogesterone, Megestrol Acetate, Iproclozide, Iproniazid, Isocarboxazid, LaZabemide, Melengestrol, Norethindrone, Norethynodrel, Norges Mefegiline, Meclobemide, Octamoxin, Pargyline, terone, Norgestimate, Norgestrel, Norgestrienone, Nor Phenelzine, Phenoxypropazine, Pivalylbenzhydrazine, Vinisterone, Pentagestrone, Progesterone, Promege Prodipine, Selegiline, Toloxatone, Tranylcypromine Stone, Trengestone 0338 MUCOLYTIC such as Acetylcysteine, Brom 0349 PROLACTIN INHIBITOR such as Bromocrip hexine, Carbocysteine, Domiodol, Erdosteine, Leto tine, Cabergoline, LiSuride, Metergoline, Quinagolide, Steine, Lysozyme, Mecysteine, Mesna, Sobrerol, Terguride Stepronin, Tiopronin, Tyloxapol 0350 PROSTAGLANDIN/PROSTAGLANDIN ANALOG such as Arbaprostil, Bemeprost, Carboprost, 0339) MUSCLE RELAXANT (SKELETAL) such as EnproStil, Gemeprost, Latanoprost, Limaprost, Miso Afloqualone, Alcuronium, Atracurium BeSylate, prostol, Ornoprostil, ProStacyclin, ProStaglandin E, Baclofen, BenZOctamine, Benzoquinonium, C-Cale Prostaglandin E, PrSotaglandin F, Rioprostil, bassine, Carisoprodol, ChlormeZanone, Chlorphenesin ROSaprostol, Sulprostone, Trimoprostil, Unoprostone Carbamate, Chlorphenesin, Chlorproethazine, ChloZ Oxazone, Curare, Cyclobamate, Cyclobenzaprine, Dan 0351 PROTEASE INHIBITOR such as Aprotinin, trolene, Decamethonium, Diazepam, Doxacurium CamoStat, Gabexate, NafamoStat, Urinastatin Chloride, Eperisone, Fazadinium, Flumetramide, Gal 0352) RESPIRATORY STIMULANT such as Almi lamine Triethiodide, Hexacarbacholine, Hexafluore trine, Bemegride, Cropropamide, Crotethamide, Dime nium, Idrocilamide, Inaperisone, Lauexium Methyl fline, Dimorpholamine, Doxapram, Ethamivan, Formi Sulfate, Leptodactyline, Memantine, Mephenesin, noben, Lobeline, Mepixanox, Nikethamide, Picotoxin, Mephenoxalone, Metaxalone, Methocarbamol, Meto Pimeclone, Pyridofylline, Sodium Succinate, Tacrine curine Iodide, Mivacurium Chloride, Nimetazepam, 0353 SCLEROSINGAGENT such as Ethanolamine, Orphenadrine, Pancuronium, Phenprobamate, Ethylamine, 2-Hexyldecanoic Acid, Polidocanol, Phenyramidol, Pipecurium, Promoxolane, Quinine, Sodium Ricinoleate, Sodium Tetradecyl Sulfate, Rocuronium, Styramate, Succinylcholine, Suxetho Tribenoside nium Bromide, Tetrazepam, Thiocolchicoside, Tizani dine, Tolperisone, Tubocurarine, Vecuronium, Zoxola 0354 Sedative/hypnotic C 0355 Acyclic Ureides such as Acecarbromal, Apronalide, BomisoValum, Capuride, Carbromal, 0340) NARCOTIC ANTAGONIST such as Ami Ectylurea phenazole, Cyclazocine, Levallorphan, Nalmafene, 0356 Alcohols such as Chlorhexadol, Ethchlorvynol, Nalorphine, Naloxone, Naltrexone Meparfynol, 4-Methyl-5-thiazoleethanol, tert-Pentyl 0341, NEUROPROTECTIVE such as Riluzole Alcohol, 2.2.2-Trichloroethanol 0342) NOOTROPIC such as Aceglutamide, Acetylcar 0357 Amides such as Butoctamide, Diethylbromoac nitine, Aniracetam, Besipridine, Bifemalane, Choline etamide, Isovaleryl Diethylamide, Niaprazine, Trime AlfoScerate, Exifone, Fipexide, Idebenone, Indeloxa toZine, Zolpidem, Zopiclone Zune, Nebracetam, Nefiracetam, Nizofenone, OXirac 0358 Barbituric Acid Derivatives such as Allobarbital, etam, Piracetam, Pramiracetam, Propentofylline, Amobarbital, Aprobarbital, Barbital, Brallabarbital, Pyritinol Sabeluzole, Tacrine, Velnacrine, Vinconate, Butabarbital Sodium, Butalbital, Butallylonal, Xanomeline Butethal, Carbubarb, Cyclobarbital, Cyclopentobar US 2003/0068365A1 Apr. 10, 2003 18

bital, Enallylpropymal, 5-Furfuryl-5-isopropylbarbitu 0371 VASODILATOR (PERIPHERAL) such as Alu ric Acid, Heptabarbital, Hexethal Sodium, Hexobar minum Nicotinate, Bamethan, Bencyclane, Betahis bital, Mephobarbital, Methitural, Narcobarbital, tine, Bradykinin, Brovincamine, Bufeniode, Buflom Nealbarbital, Pentobarbital Sodium, Phenallymal, Phe edil, Butalamine, Cetiedil, Ciclonicate, Cinepazide, nobarbital, Phenylmethylbarbituric Acid, Propally Cinnarizine, Cyclandelate, Diisopropylamine Dichlo lonal, ProXibarbal, Reposal, Secobarbital Sodium, roacetate, Eledoisin, Fenoxedil, Hepronicate, Iloprost, Inositol Niacinate, ISOXSuprine, Kallidin, Kallikrein, Talbutal, Tetrabarbital, Vinbarbital Sodium, Vinylbital Moxisylyte, Nafronyl, Nicergoline, Nicofuranose, Nic 0359 Benzodiazepine Derivatives such as Brotizolam, otinyl Alcohol, Nylidrin, Pentifylline, Pentoxifylline, Cinolazepam, Doxefazepam, Estazolam, Fluni Prostaglandin E, Piribedil, Suloctidil, Tolazoline, trazepam, Flurazepam, Haloxazolam, Loprazolam, Xanthinal Niacinate Lormetazepam, Nitrazepam, Quazepam, Temazepam, Triazolam 0372 VASOPROTECTANT such as Benzarone, Bioflavonoids, Chromocarb, Clobeoside, Diosmin, 0360 Bromides such as Ammonium Bromide, Cal Dobesilate Calcium, Escin, Folescutol, Leucocyanidin, cium Bromide, Calcium Bromolactobionate, Lithium Metescufylline, Quercetin, Rutin, Troxerutin Bromide, Magnesium Bromide, Potassium Bromide, Sodium Bromide 0373) VITAMIN/VITAMIN SOURCE/EXTRACTS Such as Vitamins A, B, C, D, E, and K and derivatives 0361 Carbamates such as Carfimate, Ethinamate, thereof Hexapropymate, Novonal, Tricholorourethan 0374 VULNERARY such as Acetylcysteine, Allan 0362 Chloral Derivatives such as Carbocloral, Chloral toin, Asiaticoside, CadeXomer Iodine, Chitin, Dextra Betaine, Chloral Formamide, Chloral Hydrate, Dichlo nomer, Oxaceprol, Tocoretinate ralphenazone, Pentaerythritol Chloral, Triclofos 0375. The above list of pharmaceutical agents is based 0363 Piperidinediones such as Glutethimide, Meth upon the list provided in The Merk Index, 21th Edition, yprylon, Piperidione, Pyrithyldione, Thalidomide Merck & Co. Rahway, N.J. (1996). Moreover, the above 0364 Quinazolone Derivatives such as Etaqualone, drugs may be used either in the free form or, if capable of Mecloqualone, Methaqualone forming Salts, in the form of a Salt with a Suitable acid or base; if the drug has a carboxyl group, its esters may also be 0365 Others such as Acetal, Acetophenone, Aldol, employed. Ammonium Valerate, Amphenidone, d-Bornyl alpha Bromoisovalerate, d-Bornyl ISOValerate, Bromoform, 0376 The preferred embodiments described herein are Calcium 2-Ethylbutanoate, alpha-Chlorolose, Clom illustrative only, and although the examples given include ethiazole, Cypripedium, Doxylamine, Etodroxizine, much specificity, they are intended as illustrative of only a Etomidate, Fenadiazole, Homofenazine, Hydrobromic few possible embodiments of the invention. Other embodi Acid, Mecloxamine, Menthyl Valerate, Opium, Paral ments and modifications will, no doubt, occur to those dehyde, Perlapine, Propiomazine, Rilmazafone, skilled in the art. The examples given should only be Sodium Oxybate, Sulfonethylmethane, Sulfonmethane interpreted as illustrations of Some of the preferred embodi ments of the invention. 0366 THROMBOLYTIC such as Anistreplase, Plas min, Pro-Urokinase, Streptokinase, Tissue Plasmino What is claimed is: gen Activator, Urokinase 1. An active agent composition using liposome beads for 0367 Thyrotropic Hormone such as TRH, TSH topical application comprising: 0368 URICOSURIC such as Benzbromarone, Ethe a. preparing a liposomal Suspension of multilamellar benecid, Orotic Acid, Oxycinchophen, Probenecid, Sulfin Vesicles wherein the liposomal Suspension of multila pyrazone, Zoxazolamine mellar vesicles encapsulate at least one active agent, 0369) VASODILATOR (CEREBRAL) such as Bency ... mixing the liposomal Suspension of multilamellar clane, Cinnarizine, Citicoline, Cyclandelate, Cicloni Vesicles into a bonding Solution resulting in a liposomal cate, Diisopropylamine Dichloractetate, Eburnamo first Solution, nine, Fasudil, Fenoxedil, Flunarizine, Ibudilast, Ifenprodil, Lomerizine, Nafronyl, Nicametate, Nicer ... introducing an aliquot of the liposomal first Solution goline, Nimodipine, Papaverine, Pentifylline, into a Second Solution, the Second Solution containing Tinofedrine, Vincamine, Vinpocetine, Vicquidil at least one inorganic Salt, wherein the aliquot of the 0370 VASODILATOR (CORONARY) such as Amot liposomal first Solution develops a hardened Surface riphene, Bendazol, Benfurodil Hemisuccinate, Benzi upon contact with the Second Solution to form a lipo odcarone, Chloacizine, Chromonar, Clobenfurol, Some bead, the hardened Surface having a yield Clonitrate, DilaZep, Dipyridamole, Droprenilamine, Strength of 1 to 4 grams per cubic millimeter, Efloxate, Erythrityl Tetranitrate, Etafenone, Fendiline, d. repeating Step C to form a plurality of lipoSome beads, Floredil, Ganglefene, Heart Muscle Extract, Hexestrol Bis(..beta-diethylaminoethyl ether), Hexobendine, Itra C. aggregating the plurality of liposome beads, and min Tosylate, Khellin, Lidoflazine, Mannitol Hexani trate, Medibazine, Nitroglycerin, Pentaerythritol Tet f. Washing the plurality of liposome beads with a chemi ranitrate, Pentrinitrol, Perhexiline, Pimefylline, cally inert Solution. Prenylamine, Propatyl Nitrate, Pyridofylline, Trapidil, 2. The composition of claim 1, wherein the liposomal Tricromyl, Trimetazidine, Trolnitrate Phosphate, Vis Suspension of multilamellar vesicles is derived from a nadine phospholipid. US 2003/0068365A1 Apr. 10, 2003

3. The composition of claim 1, wherein the at least one cium carbonate, magnesium chloride, magnesium Sulfate, active agent is from a class of compounds Selected from the barium chloride, and barium Sulfate. group consisting of antifungal drugs, anti-inflammatory 15. The liposome encapsulated bead composition of claim drugs, anti-arthritic drugs, corticosteroids, Vitamins, whit 13, wherein the at least one inorganic Salt is in an amount ening agents, nitrous oxide, moisturizers, anabolic drugs, from about 1 to 2 weight percent of the Second Solution. analgesic drugs, anesthetic drugs, anti-asthmatic drugs, anti 16. The liposome encapsulated composition of claim 12, bacterial drugs, antihistaminic drugs, anti-neoplastic drugs, wherein the hardened bead shell has a yield strength of 1 to anti-parasitic drugs, vasodilator drugs, vasoconstrictor 4 grams per cubic millimeter. drugs, anti-tumor drugs, anti-Viral drugs, anti-Seborrheic 17. The liposome encapsulated composition of claim 12, drugs, anti-vertigo drugs, deliverance of toxins, deliverance wherein the at least one active agent is in Solid form at of hormones, delivery of nicotine, compounds for anti-cold, ambient temperatures and preSSures. compounds for release of heat, compounds for prevention of 18. The liposome encapsulated composition of claim 12, contact dermatitis, compounds for prevention of irritants, wherein the at least one active agent is in liquid form at minerals, amino acids, lipids, herbs and metabolite Supple ambient temperatures and preSSures. mentS. 19. The liposome encapsulated composition of claim 12, 4. The composition of claim 1, wherein the at least one wherein the at least one active agent is from a class of active agent is in an amount from about 0.01 to about 5 compounds Selected from the group consisting of antifungal weight percent based on a total weight of the liposomal drugs, anti-inflammatory drugs, anti-arthritic drugs, corti Suspension of multilamellar vesicles. costeroids, Vitamins, whitening agents, nitrous oxide, mois 5. The composition of claim 1, wherein the bonding turizers, anabolic drugs, analgesic drugs, anesthetic drugs, Solution is a physical bonding Solution anti-asthmatic drugs, antibacterial drugs, antihistaminic 6. The composition of claim 1, wherein the bonding drugs, anti-neoplastic drugs, antiparasitic drugs, vasodilator Solution is a physiochemical bonding Solution. drugs, vasoconstrictor drugs, anti-tumor drugs, anti-viral 7. The composition of claim 1, wherein the bonding drugs, anti-Seborrheic drugs, anti-vertigo drugs, deliverance Solution is Selected from the group consisting of aragrose, of toxins, deliverance of hormones, delivery of nicotine, cellulose, Sodium alginate, chitosans, and polymeric Sub compounds for anti-cold, compounds for release of heat, StanceS. compounds for prevention of contact dermatitis, compounds 8. The composition of claim 1, wherein the step of for prevention of irritants, minerals, amino acids, lipids, introducing the aliquot of the liposomal first Solution into the herbs and metabolite Supplements. Second Solution is performed by regulating a flow of the 20. The liposome encapsulated composition of claim 12, liposomal first Solution through an orifice. wherein the bonding Solution is a physical bonding Solution. 9. The composition of claim 1, wherein the at least one 21. The liposome encapsulated composition of claim 12, inorganic Salt is Selected from the group consisting of wherein the bonding Solution is a physiochemical bonding calcium chloride, calcium Sulfate, calcium carbonate, mag Solution. nesium chloride, magnesium Sulfate, barium chloride, 22. The liposome encapsulated bead composition of claim barium Sulfate and Sodium hydroxide. 12, wherein the bonding Solution is Selected from the group 10. The composition of claim 1, wherein the at least one consisting of aragrose, cellulose, Sodium alginate, chitosans inorganic Salt is in an amount from about 1 to 2 weight and polymeric Substances. percent of the Second Solution. 23. A method of administering at least one active agent to 11. The composition of claim 1, wherein the step of a Subject comprising the Steps of: aggregating the plurality of lipoSome beads is performed by physical Separation. providing the lipoSome encapsulated composition Set 12. A liposome encapsulated composition for topical forth in claim 12; and application comprising: contacting an area of skin or mucous membrane with the a therapeutically effective amount of at least one active liposome encapsulated composition to administer the agent encapsulated in a lipoSome Suspension of multi active agent. 24. The method of claim 23, wherein the at least one lamellar vesicles in an amount from about 0.01 to about active agent is from a class of compounds Selected from the 5 weight percent based on a total weight of the lipo group consisting of antifungal drugs, anti-inflammatory Somal Suspension of multilamellar vesicles in admix drugs, anti-arthritic drugs, corticosteroids, Vitamins, whit ture with a bonding Solution, ening agents, nitrous oxide, moisturizers, anabolic drugs, wherein the liposomal Suspension of multilamellar analgesic drugs, anesthetic drugs, anti-asthmatic drugs, anti vesicles in admixture with the bonding Solution is bacterial drugs, antihistaminic drugs, anti-neoplastic drugs, encapsulated within a hardened bead Shell. anti-parasitic drugs, vasodilator drugs, vasoconstrictor 13. The liposome encapsulated composition of claim 12, drugs, anti-tumor drugs, anti-Viral drugs, anti-Seborrheic wherein the hardened bead shell is formed by introducing an drugs, anti-vertigo drugs, deliverance of toxins, deliverance aliquot of the liposomal Suspension of multilamellar vesicles of hormones, delivery of nicotine, compounds for anti-cold, in admixture with the bonding Solution into a Second Solu compounds for release of heat, compounds for prevention of tion, the Second Solution containing at least one inorganic contact dermatitis, compounds for prevention of irritants, Salt. minerals, amino acids, lipids, herbs and metabolite Supple 14. The liposome encapsulated composition of claim 13, mentS. wherein the at least one inorganic Salt is Selected from the group consisting of calcium chloride, calcium Sulfate, cal