| Title of Invention | TOPICAL COMPOSITION AND METHOD OF MANUFACTURING THE COMPOSITION FOR TREATING ACNE AND ROSACEA WITH GALVANIC GENERATED ELECTRICITY |
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| Abstract | (54) Title: METHODS OF TRATING ACNE AND ROSACEA WITH GALVANIC GENERATED ELECTRICITY (57) Abstract: |
| Full Text | WO2005/004982 PCT/US2004/020271 METHODS OF THEATIHG ACNE AND ROSACKA WITH GALVANIC GEHEEATED ELECTRICITY CROSS REFERENCE TO RELATED APPLICATIONS This is a continuation-in-part of co-pending application Serial Mo. 10/685,282, filed on Oct. 14, 2003, which a continuation-in-part of copending application Serial No. 10/609,727, filed on June 30, 2003, which are hereby incorporated by reference in its entirety. BACKGROUND OF THE INVEHTION Usirtg a galvanic couple as the power source in ionrtophoresis device is well known in the art. See e.g., U.S. Patent Nos. 5,147,297, 5,l62,043, 5,298,017, 5,326,341, 5,405,317, 5,635,037, 6,584,349, 6,421,561 and 6, 653, 014. Typical materials from which a galvanic couple is made includes a zinc donor electrode and a. silver chloride counter electrode. Such a. combination produces an electric potential o* about one volt. Such a galvanic couple powered iont-ophoreais system, absent some COTNtrolling means, activates automatically when body tissue and/or fluids form a complete circuit with the system to generate the electricity. SURFACE OF THE INVENTION In one aspact, the present invention features a method of treating acne, rosaces, and/or wounds and/or reducing the appearance of pigmentation by applying electricity to a barrier membrane in need of such 1 WO2005/004982 PCT/US2004/020271 treatment,wherein the electricity is geneisied by a first conductive electrode in electric communication with a second conductive electrode, wherein both, the first coniuctive electrode and the second conductive electrode are in ionic communication with the barrier membrane, wherein the difference of the standard potentials of the first conductive electrode and the second conductive electrode is at least 0.2 V and wherein the electrons that pass between the first conductive electrode and the second conductive electrode are generated as a result of such difference of the standard potentials, In another aspect, the present invention features a method of promoting a product including a topical carrier, a first conductive electrode in the form of a particulate, and a second composition comprising second conductive electrode in the form of a particulate wherein the differsnce of the standard potentials of the first conductive electrode and the second conductive electrode is at least 0-2 V, such method includinig promoting the topical application of such composition for the treatment of pene, rosaces, and/or wounds, and/or reducing the appearance of pigmentation. In another aspect, the present invention features a method of administering an active agent to a human barrier membrane by applying to the membrane a device including a housing having the barrier membrane contacting surface, a first conductive electrode, a second conductive electrode., and a carrier containing the active agent, wherein the first conductive electrode ia in electric communication with the second conductive electrode, wherein the first conductive electrode and the second conductive electrode are in ionic communication with the carrier, and wherein 2 WO2005/004982 PCT/US2004/020271 the carrier is in communication with the barrier membrane through the barrier membrane contacting surface, wherein the difference of ths standard potentials of the first conductive electrode and the second conductive electrode is at least D.R. v and wherein the electrons that pass between the first conductive electrode and the second conductive electrode are generated as a result of such difference of the standard potentials. In another aspect, the present invention features a method of administering an active agent to a human, barrier membrane by topically applying a composition to such meirbrane, the composition including the active agent, a first conductive electrode in the form of a particulate and a second conductive electrode in the form of a particalate, wherein the difference of the standard potentials of the first conductive electrode and the second conductive electrode is at least 0.2 V. Other features and advantages of the present invention will be apparent from the detailed description of the invention and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS FIG- 1 is a cross-sectional view of one embodiment oF thE galvanic couple powered device suitable for practicing the invention. The conductive alectrodes l20 and 240 are connected respectively by the lead wires 110 and 210 to electrically insulated connecting wire 350 located, at the back of the device 500. FIG. 2 is a cross-sectional view of one embodiment of the galvanic couple powered device suitable for practicing the invention. The conductive electrodes 140 and 240 are 3 WO2005/004982 PCT/US2004/020271 connected respectively by the lead wires 110 and. 210 to electrically insulated connecting wire 350 embedded in the cairier layer 120 of the device 500. FIG. 3 is a Cross-sectional view of one embodiment of end galvanic couple powered device suitable for practicing the invention. The conductive electrodes 140 and 240 are cauiected respectively by Lhe lead wires 110 and 210 to electrically insulated connecting wire 35 0 embedded in the carrier layer 120. FIG. 4 is a cross-sectional view of one embodiment of the galvanic couple powered device suitable lor practicing the invention. The conductive electrodes 140 and 240 are in electric communication with each other by direct cortnection. The two conductive electrodes forms a galvanic couple which is in contact with the carrier layer 120. FIG. 5 is a cross-sectional view of one embodiment in aciordacce with the invention. The device 800 contains two electrode assemblies 200 and 600. FIG. 6 is a top view of one embodiment in accordance with the invention showing the conductive electrodes 140 and 240 connected by electrically insulated connecting wire 350 embedded in the carrier layer 120. The conductive electrodes 14O and 240 are arranged in an inter-digitated configuration. FIG. 7 is a top view ot one embodiment in accordance with the invention showing the conductive electrodes 140 and 240 connected by electrically insulated connecting 4 WO2005/004982 PCT/US2004/020271 wire 350 embedded in the carrier layer 120. The conductive electrodes 140 and 240 are arranged in a concentric configuration . FIG. 3 is a top view of one embodiment in accordance with the invention showing a plurality of sets of conductive; electrodea 140 and 240 connected to each other by connecting wire 350 to form a plurality of galvanic couple power sources, which are in contact with the carrier layer 120. The conductive electrodes 140 and 240 are arranged, in a parallel configuration. FIG. 9 is a top view of one embodiment in accordance with the invention showing a plurality of sees of conductive electrodes 140 and 240 connected no each other by a direct physical contact at intersections 370 to form a plurality of galvanic couple power sources, which are in contact with the carrier layer 120. The conductive electrodes 140 and 240 are arranged in a perpendicular corif iy uration. FIG. 10 ig a top view of one embodiment in accordance with the invention showing the conductive electrodes 140 ana 3A0 eownected by electrically insulated cortnecting wire 340 embadded in the carrier layer 120. FIG, 11 is a top view of one embodiment in accordance witih the invention showing the conductive electrodes 140 and 240 embedded in the carrier layer 120. 5 WO2005/004982 PCT/US2004/020271 DETAILED DESCRIPTION OF THE INVENTION It is believed that, one skilled in the art can, based upon the description herein, utilize the present invention to its fullest extent . The following specific embodiments are to be construed as metely illustrative, and; not limitative of the remainder of the disclosure in any way whatsoever. Unless defined, otherwise, all technical and scientific terms used herein have the same meaning as coramaoly understood by one of ordinary skill in the art to which the invention belongs. Also, all publications, patent applications, patents, and other references mentioned herein are incorporated by reference. Unless otherwise indicated, a percentage refers to a percentage by weight (i.e. (W/W) What is meant by a "product" is a product containing the device in finished packaged form. In one embodiment, the product contains instruct ions directing the user to apply the device to the barrier membrane [e.g., to treat a akin condition) . Such instructions may be printed put the device, label insert, or on any additional packaging. In one aspect, the present invention features promoting a device of the present invention for its intended. use What is meant by "promoting" is promoting, advertising or marketing. Examples of promoting include, but are not limited to, written, visual, or verbal statements made on the product or in stores, magazines, newspaper, radio, television, internet, and the like. As used herein, "pharmaceutically-acceptable" means that the ingredients which the terra describes are suitable for use in contact with the barrier membrane (e.g., the 6 WO2005/004982 PCT/US2004/020271 skin or mucosa) without undue toxicity, incompatibility, instability, irtitation, allergic- response, and the like. As used herein, "safe and effective amount" meanc an amount of the ingredient or of the composition sufficient to provide nhe desired benefit at a desired level, but low enough to avoid serious side effects. The safe and effective amount of the ingredient or composition will vary with the area being treated, the age and skin type of the end user, the duration and nature of the treatment, the specific ingredient or composition employed, the particular pharmaceutically-acceptable carrier utilized, ana like lactors. As used herein. The term "treatment" means the treatment (e.g., alleviation or elimination of symptoms and/or cure) and/or prevention or inhibition of the condition (e.g., a skin condition} . What is meant by a "skin condition" is a derntatological disease or disorder Concluding, but not limited, acne, rosaces, or skin infections} or skin characteristic [including, but not limited to, pigmentation, hair growth regulation, skin teixture, skin tirtmess, skin elasticity, akin vasculature, dark circles, cellulite, sebum regulation, and skin shine) . Examples of skin infections include, but are not limited to, those due to susceptible pathogens such, as acne, rosaces, impetigo, folliculitia, funmculosis, ecthyma, eczema, psoriasis, atopia dermatitis, harper, epldermolysis bulloss, icthyosie, and infected traumatic lesions (e.g., ulcers, minor burns, truts, airafiiona, lacerations, wounds, biopsy sites, surgical incisions and insect bites). The present invention relates to a device for the delivery of electricity (e.g., to induce a desirable 7 WO2005/004982 PCT/US2004/020271 biological response) and/or an active agenx into a barrier membrane. In one embodiment, the device of the present indention is a self-contained device containing at least a pair of two dissimilar conductive electrodes in electric communication as a power source. By "electric communication" is meant that electrons can directly pass between the clements of the device (e.g., between the conductive electrode of the device). In one embodiment, the two conductive electrodes are in electric communication via direct contact with each other. By "ionic communication" it meant that electrons can pass between the elements (e.g., the conductive electrode, the carrier and/or the conductive electrode and the skin) through the migration of ions as "electron inovers" in contact with such elements (e.g., electrons pass between the conductive electrode and the akin via ionic transport of electrolytes (e.g., in the carrier) in contact with the cobductive elect.rode and the akin). In one embodiment, the two conductive electrodes are in ionic communication with the carrier containing an elsctrolyte (e.g., ions of one or more electrolytes in the carrier are in contact with the conductive electrode) and the carrier is in ionic communication with the skin. This electrode configuration differs from those in conventional iontophoresis devices in which each conductive electrode is in contact with a separate carrier (e.g., each electrodc is contained in a separate compartment and affixed to the skin with electric insulation between them in order that all the electric current travels through the skin to complete the electric circuit). An advantage of such an embodiment of the present invention, includes the capability of delivering simultaneously active agents of 8 WO2005/004982 PCT/US2004/020271 opposite charges from the same carrier into substantially the same skin site under the conductive electrodes. Another advantage is that the devices of the present invention are much easier to manufacture than conventional iontophoreais devices, and therefore, are enable substantial cost-savings. The device contains a. barrier membrane contacting surface (e.g., a skin contacting surface) that is applied, to the membrane {e.g., applied by the user to the user's skin) . Ths device ia arranged such that carrier is in communication with the barrier membrane contacting surface {e.g., such that electricity and/or the active agent may be administered from the carrier into the barrier membrane). In one embodiment, the carrier is the barrier membrane contacting surface (e.g., the carrier is a hydrogel) . In one embodiment, the device contains a light etritting diode such that light from the light emitting diode is in communication with the barrier membrane contacting surface {e.g., such that the light may be administered to the barrier membrane . In one embodiment, the device of the present invention delivers an active agent into the barrier membrane. The active agents to be delivered by the device of the present invention include active agents either initially incorporated in the carrier or electirochemically generated by the elect tic current passing from a conductive electrode through the carrier during use. What is meant by "electrochemically generated" is that the chemical specie is created as a result of an e lectrochemical reaction resulting from electric current flowing through an electrode, such a chemica1 specie released from a reactive electrode (e.g., an 9 WO2005/004982 PCT/US2004/020271 electrochemically generated zinc ion) , a chemical specie electrochemically generated on the surface of an inert electrode, or a chemical specie that is a subsequent reaction product of such eletrochemically generabed spiscie. Galvanic Couple The device/composition of the present invention has a galvanic couple as its power source, wherein the electrons that pass between the first conductive electrode and the second conductive electrode are generated as a result of the difference of the standard potentials between the electrodes (e.g., the ele-ctriclty is not generated by an external battery or other power source such as an AC power source}. Examples of such galvanic couples include, but are not limited to, zinc-copper, zinc-copoer/copcer halide, zinc-copper/copper oxide, magnesium- copper, magnesium-copper/copper ha.lide, zinc- silver, zine-silver/silver oxide, zinc-silver/silvar hal ide, zinc -silver/ silver chloride, zinc -silver/ silver bromide, zinc-silver/silver iodide, zine-sliver/silver fluoride, zine-gold, magnesium-gold, aluminum-gold, magnesium-silver, magnesium-silver/silver oxide, mag nesium-silver/silver halide, magnesium- silver/silver chloride, mignesium-silver/si1ver bromida, magnesium- silver/silver iodide, magnesium-silver/silver fluoride, magnesium-gold, aluminum-copper, aluminum-silver, aluminun-silver/silver oxide, aluminum- silver /silver halide, aluminum-silver/silver chloride, aluminum- silver/silver bromide, aluminum-silver/silver iodide, aluminum-silver/silver fluoride, copper-silver/silver halide, copper-silver/silver chloride, copper- 10 WO2005/004982 PCT/US2004/020271 silvrer/silver bromide, copper-silver/silver iodide, copper-silver/silver fluoride, iron-copper, iron- copper/copper oxide, iron-crupper/ copper halide, iron- silver, iron.-silver/silver oxide , iron-Silver/silver halide, iron-silver/silver chloride, iron-silver/silver bronide, iron-silver/silver iodide, iron-silver/silver flunride, iron-gold, iron-conductive carbon, zinc- coniuctive carbon, copper-conductive carbon, magnesium- coniuctive carbon, and aluminum-carbon. The materials whih serve to make up the galvanic couple may also serve as the conductive electrodes of the device,e.g.zinc as the conductive anode and silver/silver chloride as the conductive cathode or zinc as the conductive anode and copper as the conductive cathode. The metals serve as the galvanic couple and conductive electrodes may also be allays. Non-limiting examples of the alloys include alloys of zinc, copper, a1uminum, magnesium as anode materials, and alloys of silver, copper, gold as cathode materials. In one embodiment, the materials that make up the galvanic couple have a standard potential difference equal to or greater than about 0.1 volts, such as gireater than about 0.2 voltg such as greater than about 0.5 volts. In one embodiment, the materials that make up the galvanic couple have a standard potential difference equal to or less than about 3 volts. In one embodiment, the device or composition of the present invention generates and/or is capable of generating current into the barrier membrane of from about 1 nano-A/cm2 to about 4OO micro-A/cm2 of electricity such as from about 100 A./cm2 to about 50 micro A/cm2 . In one embodiment, one of the conductive electrodes is in the form of a metal sheet, a metal wire, or a metal 11 WO2005/004982 PCT/US2004/020271 coated on a aubscrate, and the other conduceive electrode is attached or deposited to the first conductive electrode. In a further embodiment, the metal sheet is perforated. In one embodiment, such perroraced metal sheet 13 in the form of a mesh such as a mesh of zinc, magnesium, aluminum, copper, or their alloys thereof. In one embodiment, the second conductive electsrode is in the form a fabric coated with a metal, and its oxide, halide, and sulfide, such as a fabric coated with silver, silver/silver oxide, silver/silver halide, zinc, magnesium, copper, copper/copper halide, copper/copper oxide. In another embodiment, the second conductive electrode is deposited to the first conductive electrode by chemical or electrochemical deposition such as electrodes plating for chemical deposition and electroplating for electrochemical deposition a a known in the art, In a further embodiment, the second conductive electrode is deposited to the first conductive electrode by physical deposition, such as spray coating, plasma coating, conductive ink coating, screen printing dip coating or vacuum deposition. In one embodiment, the device is a single compartment treatment device. What is meant by a "single compartment treatment device" is a device in which both conductive electrodes of the device; are in contact with the same carrier, Examples of; such devices are shown in Figures 1- 4 and 6-11- carrier The carrier of the present invention is a liquid (e.fg., a solution, a suspension, or an emulsion which may be immobilized within an absorbent material such ae gauze 12 WO2005/004982 PCT/US2004/020271 or non-wpon pad , a semi -solid (e.g. , a gel, a cream, a lotion, miroeitiiilEion, or hydrogel) , or a solid {e.g., a 3 yapbillzed composition containing active agents, which may be reconstituted by adding s liquid prior to use) that during use is capable of conducting electricity from a conducting electrode {e.g, the carrier contains one or mora electrolytes, organic solvents, and water . In one embodiment, the carriar (e.g, a liquid or semi-solid) is added to the device by the user prior to applying the device to the barrier membrane. Examples of electrolytes include, but are not limited to, pharmaceutically acceptable organic and. organic salts and buffers. Examples of salts include, but are not limited to, chloride salts (such as sodium chloride, potassium chloride, lithium chloride; calcium chloride, strontium chloride, magnesium chloride or other chloride salts), as well as salts of sodium, potassium, lithium, calcium, magnesium, strontium, fluoride, iodide, bromide. Examples of buffers include, but are not limited to, phosphates, citrates, acetates, lactatea, and borates. In one embodiment, the electrolyte is an active agent, or becomes an active agent after the passage of the electric curraat through, the carrier. Examples of such electrolyte-active agents include, but are not limited to, eaicylic acid, salicylates, and other weak acid OR WEAK base active agents. In one embodiment, the carrier contains water. In a further embodiment, the carrier may also contain one or MORE organic solvents. Examples of organic solvents include, but are not limited to, dimethyl isosorbide isopropylrrnristate; surfactants of cat ionic, anionic and non-ionic nature; vegetable oils, mineral oils; waxes; 13 WO2005/004982 PCT/US2004/020271 gums, synthetic and nacutal gelling agents, alkanols; glycols; and polyols. Examples of glycols include, but are not limited to, glycerin, propylene glycol, butylene glycol, penta1ene glycol, hexylene glycol, polyethylene glycol, polypropylene glycol, diethylene glycol, triethylene glycol, glyoerol, and hexaetrol, and copolymers, or mixtures thereof- Examplea of alkanols include, but are not limited Co, those having from about 2 carbon atoms to about 3.2 carbon atoms (e,g. from about 2 carbon atoms to about 4 carbon atoms), such as isopropanol and ethanol. Examples of polyola include, but are not limited, to, those naving from about 2 carbon atoms to about is carbon atoms (e.g., from about 2 carbon atoms to about 10 carlaon atoms) such as prapylsne glycol. The organic solvents may be present in the carrier in an amount, based upon the total weight of the carrier, of from about 1 percent to about 90 percent {e.g., from about 5 percent to about 50 parcent). Water may be present in the carrier (prior to use) in an amount, based upon the total weight of the carrier, of from about 5 percent to about 95 percent (e.g., frotn about 50 percent to about 90 percent). The carrier may also contain preservatives (such as cresol, chloracresal, benzyl alcohol, methyl p- hydroxylbenzoeats, propyl p-hydroxybensoate, phenol, thimerosal, bensalkoniuni chloride, benzethonium chloride, and phenylmer curie nitrate) , stabilizing agents a or antioxidanta (such as ascorbic acid, ascorbic acid estars, butyihydroxy anieole, butylhydroxy toluene, cysteine, N- aretylcysteine, sodium bisulfite, sodium metabiaulfite, sodium formaldehydesulfoxylate, acetone sodium bisulfite, 14 WO2005/004982 PCT/US2004/020271 tocopherols, and nordhydroguaiarecie acid) ; chelatins agents (such as ethyl esiedi ami netietrgacetic acid and its salts}, buffes (such as acetic acid, citric acid, phosphoric acid, glufcamic acid, and salts thereof) and tonicity adjusting agents (such as sodium chloride, sodium sulfate, dextrose and glycerin) . In one embodiment, the carrier may also contain a suspending material and/or- a fluid-absorbing material, [e.g., for physically stabilising the ingredients of the carrier) . Examples of suspending materials include, but are not limited to cotton-based gauze; non-woven pads made of rayon or a mixture of rayon, polyester and/or other polymer fibers, open-cell foam and sponge-like materials contained of polyurethane, polyester and/or other polymers and cross-linked and noncross-linked galling materials, such as polyacrylamide, polyvinyl alcohol, gelatin, hydroxymethylcellulose, hydrcsxyethylcellulose, hydroxypropylcllulose, methyl cellulose, and carboxymethyieellulase . Examples of fluid-absorbing materials include, but are not limited to; cross-linked and (ion-cross-linked polymers; swellable polymers such aa water-swollen cellulose derivatives (e,g., methylcellulose (MC), hydroxyethyl methyl cellulose (HEMA.) , liydroxypropyl methylecellulose (HPMC) , ethylhydroxyethy 1 celluloae CEHEC) , hydi-o-iy ethyl cellulose (KEC) , hydroxypropylcellulose (HPC] and carbonethlcellulose {CMC) and thsir salts); polyvinyl alcohol (PVA); polyvinylpyrrolidone (PVP); polyethylene oxide (PEO); polymers prepared by monomers such as hydroxyethyl methacrylate {HEMA) , hydroxyethoxyethyl emthacrylste (HEEMA) , hydroxydiethoxyethl methscrylate (HDEEMA) , 15 WO2005/004982 PCT/US2004/020271 imethyoxyethyl methacrylate (MEMA) , methoxyethoxyechyl imsth aery late (MEEMA) , methyldiethoxyethyl methacrylate (MDEEMA) , ethylene glycol dimethacrrylate (EGDMA), n-vinyl- 2pyrrolidone (NVF) , methacrylic acid (MA) and vinyl acetace (VAC) ; poly cry 1 amide; gel ah in, gums and polysacchar ides such as gum arable, gum karaya, gum tiragacanth, guar gum, gum benzoin, and algiriic acid and their salts; polyethylene glycol (PEG) , polypropylene giycol (PPG); and clays or other swellable minerals such as bentonite and montmori11onite. The amount of fluid abaorfaable material in the carrier may range from about 0.1% no about 95%, by weight, such as from about 1% to about 20%, by weight, of the carrier. Another embodiment of the present invention is directed to pairing one or more inert conductive electrodes in order to electrochemically generate oxidizing or reducing agents from electiochinically reactive materials in situ in the cairier. such oxidising or reducing agents can be used as active agents to treat barrier membrane conditions. Examples of the electrochemically reactive materials in the carrier according to the present invention include, but are not limited to, water and compounds containing the elements selected from the Periodic Table of the Elements VIB and VIIB (such as oxygen, sulfur, fluorine, chlorine, bromine, and iodine). In one embodiment, the reactive material reacts with the inert anode to form an oxidizing agent. Examples of isuch a reactive material includes, but is not limited to, the ions OH-, Cl-, I-, Br-, so32- and HCO3-, The present device, thus, enables to generation of oxidising agents, such as nascent oxygen (e.g., singlet oxygen), chlorine 16 WO2005/004982 PCT/US2004/020271 and chlorine dioxide gases, which are difficult to formulate in a conventional topical product. In one embodiment; the reactive mecsrial reacts with the inert cathode to form a reducing agent. Examples of such a reactive material includes, but is not limited to, oxidized or bisulfide forms of thio-compounds with one or more aulfhydryl functional groups, thio-containing amino acids and their salts or eaters, and sulfides. Examples of such thio-compounds include, but are not limited to; thioglycolic acid and its salta, such as thioglycolates of calcium, sodium, strontium, pocassium, ammonium, lithium, magnesium, and other metal salts; thioethylene glycol; thioglycexol; thioetharasl; thioactic acid; and thioealicylic acid; and. thsir salts. Examples of the thio- containing antino acids include, but are not limited to, L- cysteine, D-cysteine, DL-cyeteine, N-acetyl-L- cyatsijne, DL-horaocysteine, L-cysteine methyl ester, L-cysteine ethyl ester, Pf- cairbamoyi cysneine, glut athione , and cystemine. Examples of aulfides, include but are not limited to, calcium, sodium, potassium, lithium and strontium sulfides and glutathione disulfide. The inert cathode converts the aforementioned reactive oxidized or disulfide form of a sulfur-containing compound to 3 thio-containing compound, or a gulfydryl-containing compound. Examples of such, a conversion is the conversion of cystine to cystsine and the conversion of the oxidized form of glutatnione to glutathdone. In one efntaodiment, the concentration of the reactive material in the carriar may range from about 0.01% to about 25%, by weight, such as from about 0.1% to about 10%, by weight, of the carrier. The pH value of the carrier may range from about pH 1-5 to about pH 9, 17 WO2005/004982 PCT/US2004/020271 preferably from pH 2 to pH 7, and most preferably from about pH 3 to pH 5. In one embodiment, the carrier contains an adhesive. The adesive is used, to affix the device to the barrier membrane. Examples at hydrophobia adhesivea include, but are not limited tO, silicones, polyisobutylenes and derivatives thereof, acrylics, natural rubbsra, and combinations thereof. Examples of silicons adhesives include, but are not limited to, Dow Corning 355 available from Dow coming of Midland, MI; Dow Corringo X7-2920; Dow Corning X7-2960; and GE 6574 available from General Electric Company of WaterCord, NY. Examples of gcrylic adhesives include, but are not limited to, vinyl (D acetate-aerylate) multipolymers auch aa Gelva 7371, available from Monsanto Company of St. Louis, MO; Gelvao 7881; Gelva 2943; and 1-780 medical grade adhesive available from Avery Demison of Painesville, OH. Examples of hydrophilic adhesives include, but are not limited to, gum papaya and other natural gums, MC, HEMA., HPMC, EHEC, HEC, HPG, CMC, PVA, PVP, PBO, HEMA, HEEMA, HDEEMA, MEHR, MBEMA, MDEEMA, EGDMA, NVP MA, VAC, polyerylamide. getatine, gum arabic, gum kargya, gum tragacanth, guar gum, gum benzoin, and alginic acid and their salts, polyethylene glycol [PEG), and polypropylene glycol (PPG), In one emboditnent, the concent ration of the adhesive in the carrier may range from about 0.1% to about 95%, by weight, such as from about 1% to about 20%, by iveigiit, of the carrier. Electrodes The conductive electrodes of the present invention may be a reactive conductive electrodes or inert 18 WO2005/004982 PCT/US2004/020271 conductive electrodes. What is meant by a "reactive conductive electrode" is that the conductive electrode itself goes through a change in its chemical composition during the electrode chemical reactions occurring with the electric current passing through the electrode during the process, In one embodiment, the reactive conductive electrade is an anode made of reaqtivs materials such as a pure metal or a metal alloy including, but not limited to, zinc, aluminum, copper, magnesium, manganese, silver, titanium,, tin, iron, and alloys thereof. The materials which serve to make up the galvanic couple described earlier may also serve as the reactive conductive electrode. Upon passage of an electric current, metal ions such as zinc, copper, magnesium, manganese and/or aluminum cations are released from the anode into the carrier and delivered into the barrier membrane. Such ions may serve therapeutic benefits such as anti-microbial effects, immunologic modulation, enzymatic regulation, and/or anti- inflammatory effects. In one embodiment, the reactive conductive electrode is made of reactive materials such as metal halides (e.g., silver-silver chloride (Ag/AgCl), silver-silver bromide, and silver-silver iodide). In this case, the primary electrochemical reaction at the cathode surface is conversion of solid silver halide to metallic silver with little unwanted consumption of the oxidising agents generated by the anode. The released halide ions may be subsequently oxidised to oxizing agsnts, such as chloride ions to chlorine (Cl2) , hypoctiloroua acid (HC1O), and hypochlorite ions {C1CT} , and iodide ions to iodine. What is meant by an "inert conductive electrode" is that the conductive electrode itself does not go through a 19 WO2005/004982 PCT/US2004/020271 change in its chemical composition. In one embodiment, the anode is made of an inert conductive electrode, so that the electrochemical croceas al the surface of the anode generates oxidizing agents such as rscent oxygen (e.g., by electrolysis of water) and/or chlorine- containing oxidizing agents such as chloride, hypochlorite, chlorate and perchlorate, and chlorine dioxide. Nascent oxygen is an oxidizing agent thau is inhibitive to P. acnes, and chlorine-containing oxidizing agents are patent antimicrobial agent with bacteriocidal activity. In one embodiment.,the conductive electrode is made of, or coated on the surface with, an inert materials such as noble metals {e.g., gold, platinum, or gold-coated conductive metals), conductive carbon (e.g., glassy carbon or graphite), carbon-enibedded polymers (e.g., carbon silicons rubbers) conductive carbon polymree form or sponge, silver halide-coated silver (e.g., silver chloride-coated silver, silver bromide-ceased silver, and silver iodide-coacad silver), and crortosive resistant alloys. In one embodiment, the anode of the device, serving as the conductive electrode as well as a part of the galvanic couple power source, is made of aforementioned reactivs conduotivs oxidisable metala such as sine, calcium, magnesium, aluminium, iron, tin, copper, or alloys thereof, while the cathode, also serving as the conductive Slectrodte as well as a part of the galvanic couple power source, is made of the aforementioned reactive reducible Conductive materials each as a more chemically stable metal and its metal halides, oxidet, sulfide or other metal salts, such as silver and silver halides (e.g., 20 WO2005/004982 PCT/US2004/020271 silver chloride, silver bromide, silver iodide, silver, fluoride) , silver oxide, silver sulfitife. in one embodiment, the reducible conductive material is in direct contact; with a good electric conductor, such as a thin layer of silver chloride, silver oxide, or silver sulfide over metallic silver; silver chloride powder with a binder (e.g., silver cihloxide ink) ; and/or silver chloride powder mixed, with silver or conductive carbon powder held together by a binder in a matrix form (e.g. , silver-silver chloride ink and silver chloride-carbon ink) . In another embodiment, the anode of the device in the present invention is made of aforementioned reactive Conductive oxidizeble metals while the cathode is made of aforementioned more chemically stable electrode materials such as conductive carbon, metallic silver, gold or platinum, or a powder mixture of conductive carbon and the noble metal in a rastrix fount as disclosed in U.S. Patent No. 5,l62,043. In one embodiment, the device of the present invention enables the targeted delivery of beneficial sine through hair follicles to the piloscbacaous unit {i.e. a sebaceous gland and the associated hair follicle} to treat acne or rosacea. Zinc is an essential metal to the human body because it participates in various biological actrities in the body (a.g.,the body of 3. 70-Kg person contains about 2.3 grams of sine). It is known that the lack of zinc in the body may lead to skin diseases such as acne. In another embodiment, the deviee of the present invention enables the targeted delivery of other beneficial metals into the hair follicles and the piloseboaceous glands by using an anode made of sine alloy 21 WO2005/004982 PCT/US2004/020271 containing small quantities of other beneficial metals. Such beneficial metals includes, without limitation, certain metals essential to the human body such asiron, copper, magnesium, manganese, calcium, potatssium, aluminum, and selenium. As the zinc alloy anode oxidizes, it releases into the carrier zine ions and other beneficial metala in the sine alloy, which ingredients subsequently migrate into the hair follicles under the applied electric potential over the skin. In one embodiment, the content of the sine alloy in the anode in greater than about 50% by weight, such, as greater than 90% by weight. In one embodiment, the ratio of the conductance measured between the first conductive and second conductive electrode of (i) the carrier and (ii) the skin hydrated with such carrier (wherein substantially all of the cuurrent passes between the electrodes through the skin) is in a range from about 10 000:1 to about 1:100. In other words, the electric current distribution between Icarrier and Iskin is such that the value of Icarrier/Iskin is between about 10,000 and about 0.01. Icarrier is the portion of the total current going through the device (Itotal) that only passes through the carrier layer between the anode and cathode without traveling through the skin, whereas Iskin is the portion of Itotal that passes through the skin, namely, Itotal = Icarrier + Iskin. Decreasing the ratio of the conductance of the carrier to the conductance of the skin will result in a greater percentage of current passags through the skin, thereby enhancing iontophoretic delivery of any active agents being so delivered into the skin. Decreasing the conductivity of the carrier can nonexclusively be 22 WO2005/004982 PCT/US2004/020271 accomplished by adding less condvctive materials to the carrier. Examples of such less conductive materials include, but are not limited to, oils such as silicons or hydrocarbon oils, air pockets such as air bubbles or air pockets in a serai-solid carrier, or polymer or clay beads. In one embodiment where the primary intention is to electroeheinieally generate species in the carrier, the value of Icarrier / Iskin is between about 10,000 and about 1. in another embodiment where the primary intention is to deliver electricity and/or active agents into the skin, the value of Icarrier/ Iskin is between about 10 and about 1.01. Adjustmnent of the value of Icarrier / Iskin for a particular application can also be achieved by changing the distance between the first and the second electrode, or the distance between the two conductive electrode and the skin. For example, as the distance between the two conductive electrode decreases, the conductance measured between the two electrode increases and so is the Icareer. leading to a increased value of lcarrier / Iskin. On the other hand, if the distance between the two conductive electreaties and the skin increases the Iskin increases, leading to decreased value of Icarrier / Iskin. Active Agents In out embodiment, the carrier contains one or mote active agents. What is meant by an "active agent" is a compound (e.g., a synthetic compound or a compound isolated from a natural source) that has a cosmetic or therapeutic; effect on the barrier membrane and the surrouitdina, tissues (e.g., a material capable of exerting a biological effect on a human body) such as therapeutic drugs, including, but not limited to, organic and 23 WO2005/004982 PCT/US2004/020271 macromolecular compounds. Examples of such therapeutic drugs include peptides, polypeptides, proteins, and nucleic acid, materials comprising DNA; and. nutrients. Examples of polypeptide and protein active agents include thyrotrap in-releasing hormone (TRH), vasopressin, gonadatropin-releasing hormone (GnRH or LHRH) , melimotiropin-stimulating hormone (MSH) , calcitonin, growth horraoae releasing factor (GRF), insulin, erytbropoietin (EPO), Interferon alpha, interferon beta, oxytocin, captopril, bradykinin, atriopeptin, cholecystokinin, endorphins, nerve growth factor, melanocyte inhibitor-I, gastrin antagonist, soxnafcotstia, encephalins, melatonin, vaccines, botox (Botulinutn neurotoxins) , cyclosporin and its derivatives (e.g. biologically active fragments or analogs) , Other active agents include anesthetics; analgesics (e-g., fentanyl and salts thereof such fentanyl citrate); drugs for treating psyctkiacric disorders, epilepsies, and migraine; drugs for stopping drug additione and abuses; anti-inftamiatoiry agents; drugs to treat hypertension, cardiovascular cisaaaee, gastric acidity and ulcers; druge for hormone replacement cherapies and cootraceptives such as estrogens and androgens; antibiotics, antifungal a, antiviral and other ancimiccobial agents, antineoplaatic agents, immunosuppessive acents and imnnotimulants; and drugs acting on blood and the blood forming argans including- heruatopoietic agents and anticoagulants, throtnbolytics, and antiplatslet drugs. Other active agents that can be delivered into the body using the shear device in the present invention include vaccines for various diseases, such as those for iniluensa, AIDS, hepatitis, measles, mutnps, rubella, rabies, rubella, avercella, tetanus, 24 WO2005/004982 PCT/US2004/020271 hypogsmmaglobulinsmia, Rh disease, diphtheria, botulism, snakebite, back yidow bite and other itisect bite/sting, idiopathic throiiibccytopenic purpura (ITP) , chronic lymphocyt i c Jeukp.nia, crtom&galoiirus (CNV) infection, aculie renal rejection, oral polio, tuberculosis, pertussis. Haemophilias b, Pnsumococcus, and. Staphylococcus aureus. In one embodiment, the carrier contains an anti-acne and/or ant±-rosacea agent. Examples of anti-acne and anti-roaacea agents include, but are not limited to: retinoids such as tretinoin, isotretinoin, motretinide, adapalene, tazarotene, azelaic acid, and retinol, salicylic acid; benzoyl peroxide; resorcinol; sulfur; salfacetamide; urea; antibiotics such as tetracyclirue, clindamycin, metronidasole, and erythroraycin anti- inflarntnatory agents such as corticosteroids (e.g., hyictrocortisone) , ibuprofen, naproxen, and hetprofen; and imidazoles such as ketoconazole and elubiol; and salts and prodrugg thereof. Other examples of anti-acne active agents include essential oils, alpha-bisabolol, dipotassium glycvrrhisinate, camphor, b-glucan, allantoin, feverfew, flavonoida such as soy isoflavones, saw palmetto, chelating agents such as EDTA, lipase inhibitors such as silver and copper iong, hydrolyzed vegetable proteins, inorganic ions of chloride iocliole, fluoride, and their nonionic derivatives chlorine, iodine, fluorine, and other valences, synthetic phospholipida and natural phospholipids such as Arlasilk™ phospholipida CDM, SV, EFA, PLH, and QUA. (Oniqema, ICI Group of Companies, Wilcon, UK). In one embodiment, the device of the present invention contains an anti-aging agent. Examples of 25 WO2005/004982 PCT/US2004/020271 suitable anti-aging agents include, but are not limited co. inorganic sunscreens such as titanium dioxide and zinc oxide, organic sunscreens such as octyl-methoxy cinnatflates; retinoids; dimethylaminoathana1 (DMAE), copper containiny peptides, vitamins such as vitamin E, vitamin A, vitamin C, and vitamin B and vitamin salts or derivatives such as ascorbic acid di-glucoside and vitamin E acetate or parmitate; alpha hydrcocy acids and their precursors such as glycolic acid, citric acid, lactic acid, malic acid, mandelic acid, ascorbic acid, alpha- hydroxybutyrie acid, alpha- hydroxyisobunyric acid, alpha- hydroxyisoeaproic acid, atrrolactic acid, alpha- hydroxyisovaleiric acid, ethyl pyruvate, galacturonic acid glticoheptonic acid, glucoireptona 1.4-lactons , gluconie acid, gluconolactone, glucuronic acid, glacuronolactone, isapropyl pymvate, methyl pyiuvace, mucic acid, pyruvic acid, saccharic acid, saccaric acid 1,4-lactone, tartoric acid, and tartronic acid; beta hydroxy acids such as beta- hydroxybutyric acid, beta-phcnyl-lactic acid, and beta- phenylpyruvic acid; zinc and zinc containing compounds such as sine oxides; and botanical extracts such as green tea, soy, milk: thistle, algae, aloe, angelica, bitter orange, coffee, goldthread, grapefruit, hoellen, honeysuckle, Job's tears, lithospermum, mulberry, peony, pueiarua, nice, and safflower and salts and prodrugs thereof. In. one embodiment, the carrier contains a depigmerrtaticm agent. Examples of suitable depigmentgition agents include, but are not limited to: soy extract; soy isoflsvones; retinoids such as retinol; kojic acid; kojic dipalmi tate; hydroquinone; arhucin, transexatnic acid; vitamins such as niacin and vitpmin. C; aeelaic acid; 26 WO2005/004982 PCT/US2004/020271 linoletic acid and linoleic acid; placertia; licorice, and extracts such, as chamopiile and green tea; and galte and prodrugs chereof. In one embodiment, the carrier contains, a plant extract. Rxamples of plant extracts include, but are not limited to, feverfew, soy, glycine soja, oatmeal, what, aloe Vera, cranberry, hasel witch, alnus, arnica, artemisia capillaris, aeiasarum root, birch, calendula, chacnornile, cnidium, cornEiiey, fennel, galla rhois, hawthorn, houttuynia, hypericum, jujube, kiwi, licorice, magnolia, olive, peppermint, philodendron, sal via, sasa albo- marginata, natuiral isoflavonoids, soy isoflavones, and natural easential oils. in one embodiment, the carrier contains metals such as metal ions, metal salts, metal complexes, fine metal pawdexs, fine metal coated fibera and fabrics of synthetic or natural origin, or fine metal fibers. Examples of such metals include, but are not limited to, zinc, copper, aluminum, gold, silver, titanium. The metal ions provide benefits such as antimicrobial, anti-inflammatory, and/or sebum-reduction effects. The beneficial metal ions may be released from the metal anode as the result of an electrochemical oxidation reaction concurrent with electric current passage (e.g., zinc ions electrochsmieally- generated from a zine anode). In another embodiment, the beneficial ions may be generated indirectly from the electrochemical reactions at the electrode surface, sucn as the generation of hydrogen or hydroxyl ions at an inert electrode, which subsequently leads to a process to generate beneficial ions. For example, a device of the present invention may contain a power source, an inert anode (e.g., platinum, platinum 27 WO2005/004982 PCT/US2004/020271 coated conductive electrode, gold, or gold-coated conductive electrods) , a reactive cathode (e,g., silver/silver chloride electrode) , and an aqueous carrier composition containing an oxide (e.g., zinc oxide particles) among other active agents. During application to the skin, the electrolysis of water at the inert anode produces excess hydrogen ions which acidify the carrier toward a lower pH value, while the electrochemical reaction at the reactive cathode (e.g., the conversion of silver chloride to silver ions) does not affectthe pH. As the solution becomes more acidic, the oxide starts to dissolve to release ions (e.g., zinc ions) for their beneficial effects to the barrier membrane. Other active agent a include those commonly used as for topical treatment and in cosmetic treatment of skin tissues, such, as topical antibiotics for wounds, topical antifungal drugs to treat fungal infections of the skin and nails, and antipsorianic drugs to treat psoriatic lesions of the skin and paoriatic nails. Examples of antifunctal drugs include but are not limited to miconazole, econazole, ketoconazole, sertacontisole, itraconaaole, fluconasole, voriconazole, clioquinol, bifoconaaale, terconazole, butoconazole, tioconazole, oxiconazole, sulconazole, saperconasole, clotrimazole, undecylenic acid, halopieogin, butenafine, tolnaftate, nystatin, ciclopirox olemine, terbinafirte, amorolfine, naftifine, elubiol, griseofulvin, and their pharmaceutically acceptable salts and prodrugs. In one embodiment, the antifunga1 drugs are an azole, an allylamine, or a mixture thereof. Examples of antibiotics (or antiseptics} include but are not limited to raupirocin, neomycin sulfate bacitracin, 28 WO2005/004982 PCT/US2004/020271 as from about 0.01 percent to about 5 percent, by weight, of the carrier. Light Emitting Diode In one embodiment, the device contains one or more light emitting diodes. "Light emitting diodes (LEDS) of certain spectrum may be incorporated into the device to emit light to the-barrier membrane (e.g., to treat skin conditions such as acne and rosacea) , The light emitting diode may also provide a signal to the user indicating that the device is operating properly. In one embodiment,the LED is one that emits light periodically (i.e., a blinking LED) , In a further embodiment, such LED also modulates the current passing chrough the barrier membrane to form a pulsatile DC current. Such pulsatile DC current can enhance delivery of active agents into the barrier membrane, stimulate biological responses in the barrier membrane such a.s enhancing wound healing (e.g,, in acne lesions), and/or enhanced skin in sensation which serves a signal to a user chat the device is working. Another potential advantage of using a blinking LED is to produce pulsatile DC current without the nsed of a complex electric circuit. The spectrum of the LED's according to the current invention may range front about 300 nm to about 150 um, such as from about 350 nm to about 1000 mn. In one embodiment, the range of the LED includes violet-blue, green, red and infrared ranges, e.g., from about 400 nm to about 450 nm such as from about 407 ran to about 420 nm from about 510 nm to about 55 0 nm; from about 600 nm to about 700 nm; and from about 1300 nm to about 1500 nm. In one embodiment, the device contains two LEDB, one that 32 WO2005/004982 PCT/US2004/020271 emits light, having a wavelength of from about 400 nu to about 500 nm and one "which emits light from about. 700 nm to about 1000 nm.Photoseneitizer agents, such as 5- aminolaevulinic acid (ALA) , hypericin, Se John's wort powder or extract, or other synthetic or natural photosnsitisier agents, may toe incorporated into the carrier as active agents to be delivered and irradiated by the device with LED's of the present invention. The light irradiation from the LED's, together with the photoeenaitiaer agent(s) and other aforementioned active agents, electrochemically generated oxidizing agents (e.g., peroxides, nascent oxygen, chlorine dioxide, and chlorine) , and/or electric stimulation of the barrier membrane may work synergistically to achieve an improved efficacy in treating membrane disorders such as acne and rosacea. Genera1 Use In one embodiment, the device is used for the treatment of a barrier membrane condition (e.g., the delivery of an active agent light, and/or electricity into the membrane such as the skin, eye [cornea, retina, etc.), oral, buccal, nasal, vaginal, gastrointestinal, or rectal rnucosa barrier membrane, of a human). In one embodiment, the device is used for the treatment of skin conditions. Examples of such treatments include, but are not limited to treatment of acne, rosscea,, or other microbial infections of the skin, reduction the visible signs of akin aging (e.g., wrinkles, sagging, and age-spots) folliculitis and pseudo-folliculitis barbae, treatment of wounds and lesions (e.g., enhancing healing and soar reduction); sebum regulations {e.g., sebrum reduction or 33 WO2005/004982 PCT/US2004/020271 oily/shining skin appearance inhibition or control) ; pigmentation regulation (e.g., reduction of hyperpigmentation or pigmentation of light skin) ; hair growth retardation (e.g., skin on the leg) or hair- stimulation (e.g., scalp); and treatment of dermatitis (e.g., atopic, contact, or seborrheic dermatitis} and/or paoriesis. In another embodiment, the device is used for the treatment of micosal conditions (e.g., mucosa in the oral or vaginal cavities). Examples of such treatments include, but are not limited to treatinent of vaginal candidiaeis and vaginosis, genital and oral herpes, cold sore, canker sore, oral hygiene, periodontal disease, and other nticrabisl infections of the ntucosa. Another embodiment of the present invention is the device induces certain desirable biological responses that facilitate the treatment of the barrier membrane conditions. These desirable biological responses may be induced by the electric current passage through the barrier membrane, and/or the electrochemically generated oxidising materials, together with the active agents delivered by iontophoresis from the carrier, in treating the barrier conditions. Examplea of the desirable responses of the barrier membrane may include, but are not limited to, xxx regulation (e.g., reduction of sebaceous gland activity), inhibition of anaerobotic microbial growth, and establishment of a healthier membrane microflora or (e.g, reduction of p. acne growth and of production of irritating fatty acids), blood vasoconstriction (thus promoting local accumulation of active agents or removal of dark circle under the eye due to deoxyhernoglobina) , enhanced tissue nnmunological 34 WO2005/004982 PCT/US2004/020271 activity (e.g, increased elimination of pathogenic microbes on tissue's own defense ayatetns) , iinproved tissue repairing (e.g., enhanced healing and reduced scarring of lesions such as acne lesions}, and improved keratolytic activity or the carrier (e.g., softening of keratin plugs of comedos in whiteheada and blackheads of acne, and Facilitating their removal). In another aspect, the invention also features the method of converting an active agent from a less active form to a more active form via oxidation or reduction, via an inert eleccrade (e.g., cystine to cyeteine, diaulfide acetyl-Cygteine to acetyl-cysteine, and retinol to retinoic acid). Thue, an unstable agent can be stored in a more stable form and converted to its active form prior to administration. In a further aspect, the generation of reducing agents by the device of the present invention can be used to stabilise oxygen-labile active agents. Examples of such oxygen-labile active agents include, but are not limited to, retinoids, ascorbic acid, and oenzoyl peroxide. In one embodiment, the invention also features the method of converting an active agent from a leas active form to a more active form via. oxidation at an reactive anode, such as an anode made of zinc, magnesium, copper, aluminum, slloy or mixture of these metals for example, an anode made of sine releases zinc ions with the passage of an electric current through the electroda. The zinc ions generated by such an electrochemical reactions are then subsequently delivered by the electric repulsion of the positively charged anode into the barrier membrane. In one embodiment, such ions are deposited into the hair follicles and/or sebaceous glands to inhibit p. acnes 35 WO2005/004982 PCT/US2004/020271 growth arid/or suppress skin tissue inflamnation resulted from p. acnes ovsr growth before the treatment Similarly, a sine-copper alloy anode or another zinc-beneficial metal alloy releases both zinc ions and copper ions or the other beneficial ions, respecytively, into the hair follicles and sebaceous glands for acne treatment and prevention. Skin Conditions In one embodiment, the device of the present invention is used to treat skin conditions such as: acne and acne (e,g. , blscklieads and whiteheads} and acne- related skin conditions such as roeacea and nodule-cystic; hypeirpigmentation such as freckles, tnelasttta, actinic and senile lentigines, age-spcts, post-inflammatory hypetmnelanoaia, Becker's naevus, datk circles under the eye, ersd facial melanoais; stretch marks; and skin aging effects on the skin (such as those caused by photodamage) including wrinkling, roughness, pigmentary alterations, sallovnesa, fine lines, and laxity, by delivering active agents that including pra-formulated active agentig in the carrier and electrochemically generated active agents (e.g., beneficial metal ions) by the electrodes, and/or by providing electric stimulation to the skin tissues. In one embodiment, the device of the present invention provide multiple mechanism of actions to treat such conditions: namely, (a) target- delivering pre- foxraulated. active agents into the piloaebaceous unit by iontcsphoresia and electro-oamosis; {b) electro chemically generating new active agents (e.g, the beneficial metal ions from a reactive anode) and targeted delivery of the freshly generated active agents to the pilosebaceous unit (e.g., beneficial iona such as sine and copper have known. 36 WO2005/004982 PCT/US2004/020271 to enhance skin's own immune system) ; and/or (c) providing electric stimulation to the pilosebaceous unit and its surrounding skin tissues to increase blood circulation, and to treat the skin by reducing inflammation, enhancing wound healing, and/or increasing skin exfoliation. Mounds and Sears In one embodiment, the device of the present invention can be incorporated into wound dressings and bandages to provide electric therapy for healing enhancement and scar prenvetion. In one embodiment, the wound exudation fluid and/or wound cleansing solution serves tts activate a galvanic wound dressing /bandage to deliver active agents pre-incorporated in the wound dress ing/bandage and/or to generate clectrochemically beneficial metal ions followed with delivery of the beneficial metal ions into the wound. The device also treats the wound with therapeutic electric current which may increase blood circulation, stimulate tissue immune response, and/or suppress tissue inflammation, which may lead, to accelerated healing and reduced scarring. Enhanced Chemical Peel chemical peel treatments are an in-office procedure that involves the application of a chemical agent to the skin to induce controlled destruction or exfoliation of old skin and stimulation of new epidermal growth with more evenly distributed melanin. When peel agents reach the dermal layer, important wound-healing activities occur that cause skin remodeling and skin smoothing, both are anti-agins benefits. Delivery of chemical peel agents 37 WO2005/004982 PCT/US2004/020271 idoensyma, or zymogen form. Examples include pepsin, Bromelain, papaya, and cathepain- Further examples include natural extract chemical peeling agents such as fruit extracts, muattrooni extract, and other plant esnrarts. In one embodiment, the duration of the application of the device to the skin is froin about 2 to about 10 minutes depending on the individual skin, conditions. In one embodimerit, the carrier contains from about 0.1% to about 70% by weight of such chemical peel agent, such as from about 0.5% to about 20% such as from about 3% to about 103. Shape The device includes a housing that may be fabricated into various shapes and sizes to fit the contoura of various anatomical surfaces of the barrier membranes. For examples, the housing may be a substrate made in the shape of a whole facial mask with openings/holes to expose the eyes, eye bows, nose, and mouth; a partial facial mask covering only the upper or lower half of the face; or a patch coveting only the forehead, or the under eye region, the chin and jaw region, the neck, the back, wound, acne lesion or pimple, or other specific area of a barrier membrane in need of treatment. In one embodiment of the present invention, the housing is a water-insoluble substtate containing a galvanic couple, for example, a tine sine wire or a fine zinc-coated fiber {e.g., zine-coated polymer fiber) connected to a fine copper wire or a fine copper-coated fiber (e.g., copper-coated polymer fiber). One or more such fine galvanic couple wire(s) or fiber (a) may be 39 WO2005/004982 PCT/US2004/020271 incorporated into the substrate to create a dsvics which, when, in contact with the carrier (such as tap water or a liquid or semi-liquid composition including active agents) generates an electric current. In one embodiment, a galvanic couple-containing suistiate may be made of multiple layer, for exampla, a layer of the zinc containing subscracs (e.g., a fine zinc wire- or a fine zine-coated fiber in a woven or non-woven fabric) over a layer of copper-containing substrate (e.g., a fins copper wire- or a fine copper-coated fiber in a woven, or non- woven fabric). During use, the layers contact each other to form the galvanic couple. In a further embodiment, the device releases beneficial ions (e.g., zinc ions or aluminum ions) that are delivered to the barrier membrane (e.g., the skin) when such a substrate is applied by the user (e.g., used as a wipe for cleaning the skin or a facial patch or mask to treat the skin) . Active agents may also be incorporated into the substrate during manufacturing processes or be subsequently applied to the substarts prior to the application to the barrier membrane (e,g. , in the fornt of an electrolyte or active agent containing liquid, apray to wet the substrate}. In one embodiment the fabric is used as a dry wipe or a dry full or partial facial mask, to be wetted immediately before use, by applying water to the dry wipe or facial mask to pre-moisturised skin {e.g, by washing with tap water). By "water insoluble" is meant that the substrate, upon immersion in distilled water at 25oC, does not readily diasolve in or readily break apart. The water- insoluble substrate may, however, be disintegrated and/or dissolved slowly, i.e., over a period of several hours up to several days. A wide variety of materials can be used 40 WO2005/004982 PCT/US2004/020271 as the water-insoluble subserve. Examples of suitable substrates include, but are not limited, to, non-woven substarates, woven substrates, hydno-entarigleid substrates, air entangled substrates, natural sponges, synthetic aponges, and polymeric netted meshes. The Water insoluble substrates may be fluehable. As used bereia, by "flutshable" is meant that the substrate will pass through at least l0 foat of waste pipe in two toilet flushes. The material may also be biodegradable. In one enibodiment, the substrates contain a non-woven material. By "non-woven" is meant that the substrate, or a layer of the substrate, is comprised of fibers that are not woven into a fabric but rather are formed into a sheet, mat, or pad layer. The fibers can either be random i.e., randomly aligned) or they can be carded (i.e., combed to be oriented in primarily one direction. Purthermore, the non-woven substrate can be composed of a combination of layers of random and carded fibers). Non-woven substrates may be comprised of a variety of natural and/or synthetic materials. By "natural" is meant that the materials are derived from plants, animals, insects, or byproducts of plants, animals, and insects. By "synthetic" is meant that the materiala are obtained primarily from various man-made materials or from natural materials, which havs been further altered. Nan-limiting exemples of natural materials useful in the present invention are silk fibers, Keratin fibers (such as wool fibers, camel hair fibers) and cellulesic fibers (such as wool pulp fibers, cotton fibers, hemp fibers, jute fibers, and flax fibers}. Examples of synthetic materials include, but are not limited to, those selected from the group containing 41 WO2005/004982 PCT/US2004/020271 attetace fibers, acrylic fibers, cellulose eater fibers, ctrtton fibers, raodacryl ic fibers, polyaniide fibers, pclyoster fibers, polyolefixi fibers, polyvinyl alcohol fibers, rayon fibers, polyurethane foam, and mixtures thereol . Substrates made from one ore more of the natural and synthetic naterials useful in the present invention can be obtained from a wide variety of connnercial sources such as Freudenberg & Co. (Durham, NC USA), BBA Nonwovens (Nashville, TN USA) , PGI Nonwovena (North Charleston, SC USA), Buckeye Technologies/Walkisoft (Mamphis, TN USA), and Fort James Corporation (Deerfield, IL USA} . Methods of making non-woven substrates are also well known in the art. Such, methods include, but are not limited to, air-laying, water-laying, melt-blowing, spin- bonding, or carding processes, The resulting substrate, regardless of its method of production or composition, is then subjected to at least one of several types of bonding operations to anchor the individual fibers together to from a self-sustaining web. The non-woven substrate can be prepared by a variety of processes including hydro- entanglement, thermally boudirtig, and combinations of these processes. Moreover, the substrates can have a single layer or multiple layers. In addition, a multi-layered substrate can include film layer (s) (e.g., aperture or non-aperture film laysrs) and other non-fibrous materials. Strength or firmness of the non-woven material may be a desirable attribute. This can be achieved, for example, by the addition of binding materials, such as wet strength reiains, or the material may be made of polymer binder coatings, stable fibres, e.g. based on cotton, wool, linen and the like. Examples of wet strength resins include, but 42 WO2005/004982 PCT/US2004/020271 are not limited to, vinyl acretate-ethylene (VAE) and athylene-vinyl. chloride (EVCL) Airflex emulsions (Air Products, Lehigh, PA), Flextaond. acrylic polymers (Air Ptoducrs, Lehigh, PA) , Rhoplex ST-954 acrylic binder (Rohm and Haas. Philadelphia, PA) , and Ethylene-vinyl acetate (EVA) emulsion (DUR-O-SET* by National Starch Chemicals, Bridgewater, NJ} . The amount of binding material in the substrate may range from about 5% to about 20%, by weight, of the substrate. Non-woven materials Of increased strength can also be obtained by using the so-called spunlace or hydxro- sntanglement technique. In this technique, the indivictual fibers are twisted together so that an acceptable strength if firmness is obtained without the need to use binding naterials. The advantage of the latter technique is the lesteclient softness of the non-woven material. In one embodiment, the non-woven material is made of a super absorbent polymer. For the purposes of the present invention, the term " superabsorbant polymer" refers to materials which are capable of absorbing and retaining" at least about 10 times their weight in body fluids under a 0.5 pai pressure. The superabsorbent polymer particles of the invention may be inorganic or organic crosslinked hydrophilic polymers, such as polyvinyl alcohols, polyethylene oxides, cross linked starches, guar gum, xanthan gum, and other material known to the art of absorbent article manufacture, Additives may also be added in order to increase the softness of the substrates. Examples of such additives include, but are not limited to, polyols such as glycerol, propylene glyeol and polyethylene glycol, phthalate 43 WO2005/004982 PCT/US2004/020271 contains a removable release liner 100, a carrier layer 120, a First conductive electrode 140, a second conductive clectrude 240, electric lead wires 110 and 210 connecting the two ends of an elecirrically insulated connecting wire 350 to the two dissimilar conductive electrodes, an optional electric powsr switch 330 located on the lead wire 210, a backing layer 160, and a cover layer 340. The gap "b" depicts the distance between two conductive electrodes 140 and 240 to the release liner (or the membrane following application of the device) , and the gap "a" represents the distance between two oppositely charged conductive electrodes. In one embodiment, gap "a" is between 0 to about 20 centimeter. and gap "b" is between 0 and to about 1 centimeters. In another embodiment, the ratio of gap "a" to gap "b" is from about 0 to about 20. The backing layer 160 may be impermeable to the active agent contained within the carrier layer 120, and is preferably not permeable to water or other solvents in the carrier layer 120. The backing layer 160 and cover layer 340 may be made of flexible material that is impermeable to water and electrically insulating, e.g., polymers suah as polyethylene, polypropylene, polyvinyl acetate, polyurethane, silicone rubber, or polyvinyl ahloride. In a further embodiment the backing layer 160 is permeable to electrocherically generated gases (e.g., oxygen, chlorine, and hyirogen) in order to limit excess accumulation of the gases in the carrier which can cause tissue irritation and/or undesirable deformation of the device. Examples of such "breathabl backing" material include, but are not lited to, a cotton or synthetic 45 WO2005/004982 PCT/US2004/020271 woven and nonwoven fabric Iayer, such as those fabric materials commonly used for bandages and sports bandages. The carrier layer 120 is an adhesive hydrogel containing the active agent. The active agent may be incorporated into the carrier layer 120 as dissolved molecules and ions, dispersed solid particles, or liquid droplets such as creats, lotion, emulsion, multi-emuision, microemulsion, and/or liposome compositions. The carrier layer 320 may also contain a, solid supporting matrix (e.g., a gauze, non-woven or sponoe-like material) . A removable liner sheet 100 covers the carrier layer 120, The selection of the removable release-liner 100 is dependent on the type of the adhesive hydxogel used in carrier layer 120. The release liner sheet 10 0 is typicslly a polymer sheet or a paper or fabric coated with a polymer, which has weak adhesion toward the adhesive hydrogel layer 120, thereby allowing it to be easily removed from the carrier layer 120 prior to use without damaging the carrier layer 120. Examples of the polymere typically used for the release liner 100 are silicones and polyethylenes. Alternatively a wax may be used in the place of the polyrner to coat the release liner 100. In addition to, or in lieu of, the use of an adhesive in the carrier layer 120, the device 500 may be .fastened to the barrier membrane with an adhesive tape, an elastic band, a band with a buckle (similar to a leather watch band) or a velcro hand. In order to use device 500, the renovahle release liner sheet 100 is peoled off, and the carrier hydrogel layer 120 of the device 500 is affixed, to a barrier membrane, such, as the skin of mucosal membranes each as vaginal, oral, buccal, nasal, gastrointestinal or rectal 46 WO2005/004982 PCT/US2004/020271 each other through direct connect ion, naraely, the gap "a" (the distance between, two oppositely charged conductive electrodes) is equal to zero. Two conductive electrodes forms a galvanic couple which is contact the carrier layer 120 enclosed in backing layer 160 with an opening affixed to the release liner 100 with an adhesive layer 130. One major advantage of this configuration is its simplicity and easiness to manufacture. Another embodiment of the present invention is represented achematically in FIG. 5. The electrotransport device 800 containes two electrode assemblies 200 and 600, reeptccive adhesive layers 230 and 630, respective carrier layete 220 and 620, respective conductive electrodes 240 and 640, respective backing layers 270 and 670, respective eiectric leads 210 and 610, electrically insulated connecting wire 350 and optional electric switch 330. Similar to the aforementioned typical iontophoresis device, the two electrode assemblies 200 and 600 are to be affixed to the barrier membrane apart from each other, after the release liner 100 is removed prior to use. In one embodiment, the carrier layer 120 contains at least two active agents carrying opposite electric charges. One example of such a composition is a composition containing from about 0.5 to about 2% of salicylic acid. and from about 0.01 to about 0,2% of a cationic quaternary ammonium antimicrobial agents (such as benzalKonium chloride, benzechoium chloride, methyl benzetlionium chloride, and cetylpyridirsium chloride), phenol, and/or chloarhexidine gluconate. The device 500 of the present invention can simultaneously deliver both active agents of opposite charges into the membrane. 49 WO2005/004982 PCT/US2004/020271 Fig’s 5 and 7 show two examples of different configurations of dissimilar conductive electrodes 140 (shown by a double line) and 240 (shown by a single line) in carrier layer 120, connected by electrically insulated wires 350 (shown by a triple line) to form a galvanic couple power source. FIG. 6 shows that the conductive electrodes 140 and 240 are arranged in an inter-digitated configuration. FIG, 7 shows the conductive electrodes in a concentric configuration. FIG's 8 and 9 show two examples of other configurations of dissimilar conductive electrodes 140 and 240 in carrier layer 120, connected to each other either; connective wire 350 as in FIG 8 or by a direct physical contact at each intersection 370 as in FIG 9 to form a plural of galvanic; couple power sources, which are in contact with the carrier layer 120. The conductive electrodes 140 and 240 in FIG'a 8 and 9 are arranged in parallel and perpendicular configurations, respectively. The alternating parallel arrangement of the conductive electrodes 140 and 240 in FIG. 8 provides a more uniform electric current distribution throughout the carrier layer 120 and the underlying skin tissue, and consequently, assist in enabling a more uniform delivery of active agents into the skin. One exemplifying fabrication method for the galvanic device shown in FIG. 8 is by weaving a silver-coated polymer fabric and zinc- coated polymer Cabrie (or zinc wire} into a liquid- absorbant fabric layer according to the parallel electrode pattern, then connecting zinc and silver electrodes by printing over the silver and sine regions with an electric conductive ink (e.g., conductive silver or carbon ink). Covering another layer of an electric insulating ink over 50 WO2005/004982 PCT/US2004/020271 the electric; conductive ink will produce the electrically insulaLed connecting wire 350. Another fabrication method for the device of FIG 8 is via printing; to prinL onto a non-conductivs polymeric substrate layer (e.g. the polymer material made of the bicking layer 160) using a conductive silver or silver- silvear chloride ink to produce the first conductive electrode; and to print the second conductive electrode using a conductive sine ink. The two dissimilar conductive electrodes are then connected by printing cross them with either the conductive Silver or zinc ink (or a different conductive ink such as carbon ink). A covering ink may then optionally be printed over the connecting wire to produce an electric insulating polymer layer over it. If the device is made without insulating with an electrically insulating coverying layer, the resulting device is a variation of that depicted in FIG. 9. FIG 9 is a top view of one embodiment in accordance with the invention showing the conductive electrodes 140 and 240 connected to each other by direct physical contact at the intersections 370 to form a galvanic couple power source, which is in contact with the carrier layer 120. The conductive electrodes 140 and 240 are arranged in a Perpendicular configuration. The aforementioned fabrication methods for the device in FIG. 8 is also suitable to produce this device. FIG. 10 is a top view of one embodiment in accordance with the invention showing a device made of a zinc meth having conductive electrodes 140 (shown in bold lines) and electrodes 240 (shown in double lines) connected by ilcctrically insulated connecting wires 350 (shown in single lines') embedded in the carrier layer 120. The 51 WO2005/004982 PCT/US2004/020271 sbrsductive electrodes 140 are uncoated regions of the zinc mesh. The conductive elefctrodis 240 is prepared by coating the designated portion of the zinc mesh with a silver- silver chloride ink. The electrically insulated coiinecting wire 350 is prepared by coating th^ designated portion of the zinc mesh with an electrically insulating paint, ink., or polymer solution. FIG, 11 is a top view of one embodiment in accordance with the invent ion showing the conductive electrodes 140 and 240 embedded in the carriex layer 120. The conductive electrodes 140 are made of a piece of zinc mesh. The conductive electrodes 240 are prepared by costing the designated portion of the zinc mesh with a silver-silver chloride or silver ink, or by other silver seposifcing methods such as electroless deposition (chemical reduction ieposition), electroplating, plasma spray, or vacuum deposition. Elimination of the electrically insulated connecting wire 350 in this design would simplify the manufacturing process. The location, pattern, shape, and size of the electrode of metallic silver, silver-silver chloride or silver-silver oxide may vary depending on the need, of a particular products. zine mesh, (or expended zinc" as common called in battery and anti-corrosion fields) may be prepared from a thin zinc fol] with mechanical perforation and subsequent expansion into net-like patterns. The major advantages of a zine mesh enode in the galvanic device of the present invention are its ability of forming and retaining the desirable mask/patch shape by a uaer,stretching by a user toward any directions to form mask/patch of desirable size, and being breathable. 52 WO2005/004982 PCT/US2004/020271 It should be noted although the use of zinc mesh is described here as an example of electrode designs, other aforement ioned materials suitable for galvanic couple formulation and for conductive electrodes can also be made into a mesh or an expanded form to provide the same function. Zinc mesh also has the ability to conform to the shape of the membrans surface (e.g. the shape of an individual's face} by gently pressuring it, and to retain this shape. This capability makes it uniquely suitable for a facial mask, or certain skin patches to better fit the contours of certain anatomic features of the face (e.g., a NOse patch) or body areas. This unique feature also ansists in better electric contact and may also reduce dependence on using adhesives to affix the device to the skin. It is also highly convenient and desirable to a consumer if a facial mask or patch can be stretched to different sizes in order to cover a particular skin area without compromising its electric performance. A zinc mesh aiode tor other mesh conductive electrode) is uniquely Cipable to fulfill this consumer need. In another e nbodiment the mesh is not expanded before use so that the device is smaller and more compact for easy storage and jsnymg. Rather it is stretched open to a desired size during application by a consumer. Good breatliability is important for a facial mask or a patch ox relatively large sise, especially if the device is designed to be worn by a user for an extended period of time (e.g., longer than one half hour such as overnight). In order Co make aforementioned device etretchable and/or breathable, the carrier layer 120 and backing layer 160 53 WO2005/004982 PCT/US2004/020271 should also be stretchable and breathable, such as stretchable woven and nonwaven fabric teaheriala. In anothe embodiment, the baking layer 160 in FIG'S 3-5, can be pert orated or eliminatetd entirely for a mask or patch device, which is especially suitable for the application of short duration, e.g., from about 5 to about 30 minutes. As water in the carrier composition evaporates, the electric conductance and the electric current decrease. Eventually, the electric current will significantly diminish, providing in essence a self- terminating device to serve as a safety measure for the user to prevent any unintentional over-exposure of the skin to the electric current and potential resulting skin damage. One example of such a self-terminating device is a galvanic cloth facial mask made with a sine mesh partially coated with silver-silver chloride ink, which is placed in between a backing film/housing (e.g., a perforated or nonperforated polyethylene film) and a nonwoven fabric (e.g., a polyester and/or rayon nonwoven sheet) using a binding process based on heating, ultrasound or other mechanism Prior to application, a liquid or semisolid earner composition containing ionic and non-ionc active agents and other optional electrolytes is applied to the non-woven AND OF the device to activate the galvanic power source. The galvanic device is then pressed onto the light's face with the nonwoven side in direct contact with the skin. Alternatively, the active agents and other optional electrolyte may be incorporated in nonwovan layer during manufacturing process in an anhydrous stats. In use, the device can be applied to water-wetted face, and the water will dissolve the active agents and electrolytes 54 WO2005/004982 PCT/US2004/020271 to activate the galvanic current. The anhydrous active agenta may be in the form of dry powder immobilized onto the inhers or the nonwoen, or dissolved firgt in an organic solvent (e.g., polyethylene glycol, propylcne glycol, glycerin, and/or alcohol) to form a non-conductive or very law conductive solution, which is absorbed in the ion woven layer . The zinc anode materials may be manufactured with a wide variety of manufacturing process, including, but not limited to, metal processing, electroless deposition, electroplating, plasma spray, vacuum deposition, print processes such as screen, printing using a zinc conductive ink, textile or nonwoven technologies. Similarly, other conductive metal materials, such as silver-silver chloride, silver-silver oxide, copper, magnesium, aluminum alloys Of sine, magnesium, copper and aluminum, may be manufactured into the aforementioned electrode forms uaing the manufacturing processes disclosed above. Topical Compositions Containing Galvanic Pairs In one embodiment, the present invention features a topical composition containing a first conductive metal particulates such as fine flakes, wires/fibers or metal- coated fibers) selected from zinc, aluminum, copper, and their alloys; and a second conductive metal particulates (such as fine flakes, wires/fibers or metal-coated fibers) selected from silver, copper, gold, and their alloys. The first and second metal particulates can be selected from aforementioned electrode materials to form galvanic couples. Upon contact, the first conductive metal and the second conductive metal form a galvanic pair, generates electric current, and electrochemicaliy generates ions. 55 WO2005/004982 PCT/US2004/020271 In a further embodiment, the difisrence of the standard potentials ef the first conductive metal end the second conductivs metal is at least about 0.lv, such as at least abput 0.5 V. For example., upon contact with a first conductive metal that contains sine (such as fine zinc wires, sine flakes or polymer fibers coated with sine) and a second conductive metal that contains silver (such as a fine silver wires/fibers, silver flakes, or polymer fibers coated with silver), the cortpositien. generates electric current and zinc ions within the topical composition. The composition may additionally contain an active agent, such as an anti-acne agent (such as ealicylic acid, benzoyl peroxide, retinoic acid and/or retinol). The topical composition containing the first mecal and the second metal is preferably a semi-solid dosage form (such as a gel, a hydragel, a water-in-oil emulsion, an oil-in- water emulsion, a cream, a lotion, an ointment, a multi- emiilsion, a liposome, and/or a microcapsule formulation), and may contain the aforementioned fluid suspending or fluid absorbing materials. The topical composition may be prepaired as such that one of the conductive metal is formulated in a. separate phase from other conductive metal, for example, the first conductive metal (e.g., zinc flakes) is formulated in the discontinuous oil phase of an oil-in-water emilsian (e.g., a creem), while the secornd conductive metal (e.g, silver flakes) is formulated in the continuous aqueous phase of the emulsion. The topical composition of the present invention may also further contain a humectant (such as glycerin, propylene glycol, polyethylene glycol, aotbitol and/or urea) and aforementioned electrolytes to maintain certain moisture level and conductivity of the skin. 56 WO2005/004982 PCT/US2004/020271 In one embodiment, during storage of such a topical composition, the first conductive metal and the second conduct metal are suspended substantially apart, in a semi— solid composition (e.g., are not in contact with each other) . Upon application to the membrane (such as the skin or mucose) and partial drying of the liquid carrier, the contact of the first conductive metal and the second conductive metals results in galvanic couple fonraatioin and generation of electric current and metal ions of the first conductive metal, which provides benefits to the membrane such as antimicrobial, antiinflammation, wound healing, iontophoretic delivery of active agents, tissue stimulation, and/or sebum reduction. In one embodiment, the wires/fibers, flakea of conductive metals, or polymer fibers coated With the conductive metals are fine enough that they can be isuspended in the semi-aolid composations during storage. In a further embodiment, they are in elongated shapes. The advantages of elongrated shapes of the conductive metals (e.g., fine wires/fibets, flakes and polymer fibers coated with the conductive metals) include a lovrer apparent density and, therefore, a better floating/snapending capability in the topical composition; a higher probability at connected with each other when low concentrations of the conductive metals are used; and a wider and deeper range of the membrane tissue (e.g, the skin) that the galvanic current travels through and provides the benefits to. In one embodiment, the first and second conductive metal particles are formulated into different compositions and are stored in separate compartments of a, dual chamber dispensing package. For example, the less chemically 57 WO2005/004982 PCT/US2004/020271 stable (e.g., more oxidizable)zinc or its alloy particulates may be formulated in an anhydrous, essentially non-conductive composition with organic solvents; such as polyethylene giycols, gropyletie glycol, glycerin, liquid siliane and/or alcohol, or other pharmaceutically-acceptable organic solvents. The more chemically Stable (e.g., less oxidxzable) silver and silver chloride; particulates may be formulated in an aqueous compositon. The active agents may be formulated into either composition depending on their chemical stability and solubility. In use, the compositions are dispensed from dual chamber package (e.g., dual chamber pump, tube, pouch, bottle, etc.) and mixed prior or during application to the skin to form galvanic couples in situ to generate galvanic current and to treat the skin conditions. In another embodiment, the aforementioned, galvanic couples are manufactured as particuIatee to be incorporated into topical compositions. The particulates may be of any shape, including but not limited to, Spherical or non-spherical particles or elongeted or flattened shapea (e.g., metal or metal-coated spheres, hollow metal or metal-coated epheres, short metal-coated fibere or fabrics, and flakes), regular shapes (e.g., metal crystals), and irregular shapes (e.g., aggtegsued Spheres). In one embodiment, the parciculates have an average particle size of from about 1 micrometer to about 5 centimeters. What is meant by the particle size the maximum dimension in at least one direction. In one embodiment, the particulates have an average particle size of from about 1 micrometer to about 2 millimsters for non- elongated shapes. In another embodiment, the particulates 58 WO2005/004982 PCT/US2004/020271 with elongated shapes have an average particle size from about 10 micrometers to about 2 centimeters such as from about 100 micrometerg to about 50 millimeters. For example, a polymer fiber of about 100 micrometers to about 10 millimeters in length may be coated partially with silver or silver-silver chloride on one end (or only on certain portions of the fiber),and zinc on the other end (or on the remaining portions). In another example, the polymer fiber is coated completely with the first conductive metal (e.g., silver-silver oxide or silver- silver chloride), and one end {or certain portions of the fiber) is coated with the second conductive metal (e.g., zinc or magnesium) . In practice, silver-coated, polymer fibers mnufactured by Noble Fiber Technologies, Inc. [Clarks Summit, PA.) may be coated with zinc using methods such as conductive sine ink printing, electroplating, electroless depositior, vacum deposition, and spray coating. Alternatively, a metallic sine or magnesium particulate (e.g., bead or thin wire) may be coated at one end or at certain portions) with silver-silver oxide or silver- silver chloride. Spherical or non-spherical particles with an average particle size ranging from about one micrometer to about 5 millimeters may be partially covered with the first and second conductive metal coatings in a similar fashion. The coating methods for such first and second conductive metals in preparing the galvanic couples may be electroless deposition, electric plating, vacuum vapor deposition, arc spray, conductive metal ink, and other known metal coating methods commonly used in electronic and medical device manufacturing processes. The galvanic 59 WO2005/004982 PCT/US2004/020271 couple particulates ate preferably stored in aforementioned anhydrous forms, e.g., as a dry powder or immobilized in a fabric with binding agents, or as at essentially anhydrous non-conducting origanic solvent composition (e.g., dissolved in polyethylene ctlycols, prupylene glycol, glycerin., liquid gilicone, and/or alcohol) . The galvanic particulstas have great versatility in applications, and can be used in many consumer and medical products such as patches, bandages, masks, garments, cloths, socks, bed sheets (e.g., by immobilized into the carrier or fabric) , spread -on facial mask composition (such as a paste, cream or gel), creams, lotions, gels, shampoos, cleansers, powders, or incorporated into personal and medical products such as toothbrushes, dental flosses, wound dressings, diapers, sanitary napkins, dry wipes, pre-moistured wipes (with aforementioned anhydrous solvents), tampons, and rclal and vaginal suppositories. The galvanic particulares may also be incorporated into transdermal drug delivery patches to enhance drug penetration into the skin by iontophoresis and to reduce skin irritation by electrie stimulation and electrically generated beneficial ions such as zinc ions. Example 1: Carriers Examples of several carriers, including the weight percentage range of the ingredients of such, carriers, are set forth in Table 1. 61 WO2005/004982 PCT/US2004/020271 WO2005/004982 PCT/US2004/020271 In order to evaluate the proposed mechanism of action for the electrochemically generated beneficial agents, an in vitro inicrobiologic study was conducted to investigabe effect of electrolysis on p. acne inhibition in certain electrochemical systems; and an in vivo study was conducted in human volunteers using e commercial iontophoresis device, EXAMPLE 2. In. vitro Inhibition of P. acnes by Electrolysis A BacT/ALERT system (BioMerieux, Inc., Durham, Nc) was used in the P. acnes inhibition experiment. Briefly, 40 ml of an anaerobic casein and soy based broth culture medium in a bottle (BacT/ALERT SN, Organon Tekniks Corp., Durham, NC) was inoculated with P. acnes. The fully automated BacT/ALERT system was used to detect P. acnes growth over a 14-day study at 35°C by continuous monitoring of CO2 production using an optical colorimetric sensory system. A selected pair of the electrodes (Table 2, Columns 2 and 3) was disinfected with 70% isopropyl alcohol, and inserted through the rubber stopper into the culture medium in a nitrogen glove box. Some electrodes were connected to the poles of a battery (either 1.5 or 3v as indicated in Table 2, Column 3) for 30 minutes. The electrodes more then immediately removed from the BacT/ALERT bottle, which was then placed into the automated incubation and monitoring system for two weeks. Other elscrodes (i.e., Nos. 3 & 5 in Table 2), were not connected to an external battery, but rather were directly connected, to each other at their ends outside the BacT/ALERT bottle to form galvanic couple. The electrodes of these galvanic couples (i.e., NON. 3 & 5) remained in 62 WO2005/004982 PCT/US2004/020271 contact with the culture medium in the bottle during the 14-day study. Zinc as the positive electrode (anode), with various materials as the negative electrode (cathode) , was evaluated through the test conditions 1 to 7 (No.l-7 in Column 1). Column 4 shows the voltage applied to the conductive electrode by the external battery. However, by simply connecting two conductive electrode materials, a voltage was also generated just from the galvanic pair. For example, zinc-silver/silver chloride galvanic couple has a voltage of 0.9849V or about IV (zn2+ + 2e- = Zn, standard potential: -0.7626V, and AgCl + e- = Ag + Cl-, standard potential: 0.2223V} and zinc-copper- galvanic couple has a voltage of about 1.1-1.3V (Cu2 +2e- = Cu, standard potential: 0.340V, and Cu+ + e- = Cu, standard potential: 0.520V} Reference; Electrochemistry Handbook, 1995, Table 14.1, McGraw-Hill, Inc. New York, NY). In the test condition No. 7, the electrodes {i.e., zinc-silver/silver chloride galvanic couple) were taken from a commercial iontophoresis device (lontoPatch, Sp, Birch Point Medical, Inc., Oakdale, MN) . The lontoPatch is an iontophoresis device powered by a galvanic couple battery strip made of zinc and silver/silver chloride in a bandage-like device. In this experiment, the "battery strip" in the Iontopatch was taken out of the bandage-like device, and placed into the BacT/ALERT bottle. The electrodes of the commercial zinc-silver/silver chloride galvanic couple (NO- 7) remained in the BacT/ALERT bottle through out the entire two-week experiments. Test conditions of Noa. 15-27 were positive controls (i.e., without electrodes) : Test condition No.15 used a concentrated P. acne culture that was used to inoculate 63 WO2005/004982 PCT/US2004/020271 the rast of the culture medium in each EaeT/ALERT bottle to P. acmes counts of 106 per ml and Test conditions No. 16 and No.17 used, the inoculated culture mediura of P. acnes counts or 105 per ml (with the rubbed stoppers of No.16 additionally being punctured in a way similar to the rest of electrode-tested conditions in order to eliminate any false p.acnes inhibition results due to potential enviromental oxygen entry into the test bottle and affecting anaerobic P. acnes growth). 64 65 WO2005/004982 PCT/US2004/020271 65 WO2005/004982 PCT/US2004/020271 positive P. acnes growth probably due bacterial centamination, see Note C of Table 2) . The copper anode was also found to significantly inhibit P acnes growth (Nos, 8-9) . Under Lhese experimental conditions, the platinum anode shewed little P. acne inhibition affect and the silver or silver/silver chloride anodes provided only a weak P, acne inhibition. Since all the positive control (renditions (N0s. 15-17) showed positive P. acnes growth less than two days after the beginning of the study, the negative F. acnes growth can be attributed, to the inhibition effect of the electracheraically generated species or electric current passage through, the culture medium. Because electric current passage in NOS. 10-14 failed to show strong P. acnes inhibition as those in Nos. 1-9, the observed bacterial inhibition in Nos. 1-9 were likely due to certain electrochemical reactions occurred at the anode, namely, when zinc and copper were used as the anode. It was also unexpected that the silver ions released; from silver or silver/silver chloride anode under these expearimental conditions failed to show the same P, acnes inhibition (Nos. 12-14) , since silver ion is well- known anti-microbial agent. See. e.g., Spacciapoli et al. ("Antimicrobia) activity of silver nitrate againts periodontal pathogens.", J Periodontal RSE 36: 2, 103-13, Apr, 2001) . It was surprising that, in the absence or external battery {Nos. 3, 5 and 7), a pair of electrodes of galvanic couple with sine as anode were sufficient to inhibit P-acnes growth during the entire two week Study • EXAMPLE 3- In vitro Electrode-salicyljc acid compatibility The following experiment was conducted to determine the compatibility of electrodes with salicylic acid. A 66 WO2005/004982 PCT/US2004/020271 pair of test electrodes was immersed in 5 ml oE 1.5% salicylic acid solution (solvent 50% ethanol/ 50% water). A pre-determined voltage was applied to the electrodes (by connecting the electrodes to a battery or batteries) for certain length of time as indicated in Table 3. Observations were made on color change of the test solution. The solution with the sine anode showed no discoloration, indicating good compatibility with salicylic acid during the passage of electric current. Use of the platinum anode unexpectedly resulted in discoloration, indicating incompatibility with salicylic acid under this experimental condition. EXAMPLE 4: In vivo human iontophoresis stuudy An in vivo study was conducted in human volunteers using a commercial iontophoresis device (IontoPatch*, Model: SP, Birch Point Medical Inc., North Oakdale, MN). The study recruilted the healthy female volunteers with 67 WO2005/004982 PCT/US2004/020271 oily skin, aged from 20-45 years. The sebumeter reading from each subject's forehead was at least greater than 150 mg/cm2/hr . The study was blind and controlled. Briefly, an iontoPatch® with a voltage of 1 volt , an operating current of 0.06 mA; and an active treatment area of 1.25 in2, was applied to the treatment site of the human subject (e.g. fotehead}. The positive electrode and negative consisted of zinc and silver/silver chloride (Ag/AgCl) material, respectively. Both, electrodes were filled with saline (0.9% NaCl). As soon as the saline solution was added into the different electrodes, the electric patch begin to function. The patch was left on the treatment area overnight {e.g., approximately 8 hours). The following evaluations were conducted: (i) the effects of electrolysis on the skin condition were monitored using a normal photography and (ii) The change in p. acnes counts was determined through analyzing the cup wash solution for the treatment site before and after wearing the patch overnight.The cup wash micro sampling procedure was performed as follows; a cylindrical cup (2.1 cm diameter and 2.5 cm height) having two open ends was fastened onto the treatment area. The treatment area inside the cylinder was then washed with 3 ml of cleansing buffer (eterile 0.075M Phosphate Buffer containing 0.1% Triton X-ioo) while the same area with a sterile polished glass. The wash solution was then collected. This washing procedure was then repeated. The two collected samples were pooled and used in the P-acnes aanalysis The p. acnes counts were determined by Spiral Plating the scrub samples anaerohically in Actinomyces Agar for 5 days, and the predominant contaminants on the spiral 68 WO2005/004982 PCT/US2004/020271 plates were Gram stained and identified using the VITEK system Using an automated colnny counter, the P-acne count per mL of each sample Durtsr was determined. After only one overnight patch application, P. acne quantification measurment an the treatment area shows a 45% p, acne reduction relative to the baseline under the sine anode and 30% under the Ag/AgCl cathode. After four consecutive overnight patch applications, photo images displayed the clear evidences of significant reduction in the color and size of post-acne hyperpigmentation apot under the zinc electrode. This test subject had a post- ache hypeipigmentation spot at the test akin site. The sppeaiance of the hypexpigmented spot was improved from a very dark color to a lighter color. Also, after four consecutive overnight patch applications, photo images also displayed the evidence of significant reduction in the color and size of an acne pimple under the Ag/AgCl electrode. This test subject had an acne pimple at the test skin site. The redness of the pimple was rapidly reduced from very red color to became almost invisible while the pimples at the non-treated skin area remained largely unchanged. EXAMPLE 5:In vivo human iontophoresis study using histamine hidrochloride as marker An in vivo study was conducted in three human volunteers using a galvanic sine-silver/silver oxide device to deliver histamine hydrocholoride as a marker into the skin. Histamine-induced skin erythema and itchinees were recorded during and after- the study. The study recruited two healthy male and one female volunteers with ages ranging 41 to 49 years. The galvanic devices were 69 WO2005/004982 PCT/US2004/020271 prepared by cutting a thin Zinc foil (0.25mm thick, Alfa Aesar, word Hill, MA) into rectangular piece (2.5cm wide & 3cm long) - A silver ink {Silver Print, M.G- Chemicals, Toronto, Ontario, Canada) was painted onto one side of the sine foil as a 0.5cm wide stripe along the long-axis at the center. The ink Was air-dried to produce the silver eletyode stripe on the zinc foil. Two rectangular adhesive Scotch® tape stripes of 0.5cm wide and 3cm long were placed on the both sides of the silver electrode stripe creating an electric insulating gap on the surface (electrode gap = 0.5cm). A rectangular piece of nonwoven fabric (50% Rayon/50% PET, 75 gsm, PGI Polymer Group Inc. , Landisville, NJ) of 3cm wide and 3.5cm long was placed over the zinc-silver electrode side of the zinc foil. A rectangular adhesive backing film of 4cm wide and 5cm long was affixed to the opposite side of the zinc foil to complete the zinc-silver galvanic device. A second type of the zinc-silver galvanic device without and electric insulating gap on the surface (electrode gap = 0cm) was prepared by simply omitting the addition of the adhesive Scotch® tape. A third type (control) patch was prepared by using only the zinc foil, the nonwoven pad, and the adhesive backing film to construct the device. To begin histamine iontohorasis, o.8ml aquepua solution of 0.1% histamine hydrochloride (sigma-Aldrich, St. Louis, Mo) was added to each device, which was then affixed to the forearm skin of each volunteer for 30 minutes. At the end of the study, red spots (histamine induced erythema) appeared under both zinc-silver galvanic patch devices, which disappeared within about one half hour. A 70 WO2005/004982 PCT/US2004/020271 close examination showed the red spots around the hair follicles. There was also itchiness reported at the galvanic patch sites reported during the patch application. In contrast, there were no change in skin color under, nor any itchiness reported with, the control patch devices. EXAMPLE 6: In vivo human iontophoresis study using histamine_hydrochloride with a galvanic nose patch comprising zinc mesh As a continuation of the human in vivo study in the previotis example, a galvanic patch device (designated here as "Test Device D" ) comprising a zinc mesh (diamond openings of lcm long & 0.4cm wide, Exmet Corporation, Naug attick, CT) instead of sine foil was prepared with the same dimension and procedure as the galvanic device (gap electrode = 0) in EXAMPLE 5. The device thus prepared Resembled to the design shown in FIG. 11 with three parallel electrodes the silver electrode in the center and sine electrodes on both sides. Two male volunteers participated this study using a similar test conditions as in EXAMPE 5. One Test Device containing 0.8 ml of 0.1% histamine hydrochloride was applied to the nose of each volmitee for 30 minutes. It chiness was reported within 5 minutes of the nose patch application, indicating rapid delivery of histamine into the relatively larger skin pores on the nose. For both test subjects, pronounced erythema was observed at the akin site under the nose patch after patch removal at the end of the study, in comparison to the study conducted on the forearm skin. 71 WO2005/004982 PCT/US2004/020271 It is "understood that while the invention has been described in conjunction with the detailed description thereof, that the foregoing description is intended to illustrate and not limit the scope of the invent ion, which is defined by the scope of the appended. claims. Other aspects, advantages, and modifications are within the claims. What is claimed is: 72 WO2005/004982 PCT/US2004/020271 1. A method of treating acne or rosacea on the skin said method comprising applying electricitiy no skin in need of such treatment wherein said electricity is generated by a first conductive electrode in electric communication with a second conductive electrode, wherein both said first conductive electrode and said second conductive electrode are in ionic communication with said skin wherein the difference of the standard potentials of said first conductive electrode and said second conductive electrode is at least 0,2 V and wherein the elections that pa.se between said first conductive electrode and said second conductive electrode are generated as a result of said difference of the standard potentials . 2. A method of claim 1, wherein said, first Conductive electrode comprises zinc. 3. A method of claim a, said method comprising applying to said skin a device, said device comprising: a housing having a skin contacting surface, a first conductive electrode; a second conductive electrode; and a carrier, Wherein said first conductivs electrode is in ionic communication with said carrier and wherein said carrier is in communication with said skin through said skin contacting surface. 4. A method of claim 3, wherein said first conductive electrode comprises zinc. 73 WO2005/004982 PCT/US2004/020271 5. A method of claim 3, wherein said second conductive electrode is also an iconic communication with said carrier. 6. A method of claim 4, wherein said second conductive electrode is also in iotiic communication with said carrier. 7. A method of claim 3, wherein said housing is a non-woven subatrats. 8. A method of claim 3, wherein carrier is added to said device by the user prior to application to said skin. 9. A method of claim 5, wherein carrier is added to said device by the user prior to application to said skin. 10. A method of claim 3, wherein said carrier further canr-priseE an anti-acne agent selected from the group comprising tretimoin, isotratiuoin, motretinicte, adapalene, casarotena, aaelaic acid, retinol, salicylic acid, benzoyl peroxide, rsaorcinsl, sulfur, sulfacetamide, tfetrsycline, clinciaxnycin, metrcriirfazole, erythromycin, and salts thereof. 11. A method of claim 1, wherein said method comprises topically applying a composition to said skin said composition comprising said first conductive electrode in the form of a, particulate and a second conductive electrode an the form of a particulate. 74 WO2005/004982 PCT/US2004/020271 application, said mrsu conctuttive eieccroae is storea separately from said composition. 14. A method, of claim 11, wherein said firsc conductive electrode and said second conductive electrode on the same partictilate. 15. A method of claim 11, wherein said composition further corapriaes an anti-acne agent selected from the group comprising tretinoin, isotretinoin, raotretinide, adapalene, tazarotene, azelaic acid, retinol, salicylic acid, benzayl peroxide, resorcinol, sulfur, sulfacetamide, tetracycline, clindaniycin, metronidaaole, erythxoraycin, and salts thereof. 16. A method of promoting a product comprising a topical carrier, a first conductive electrode in the form of a particulars, and a second composition comprising second conductive electrode in the form of a participate whenein. the difference of the stsndard potentials of said firgt conductive electrode and said second conductive electrode is at least 0.2 V, said method comprising promot±ng the topical application of such composition, for the treatment of acne or roaacea. 75 WO2005/004982 PCT/US2004/020271 conductive electrode is suspended in said carrier and said second conductive electrode is contained separate front said carrier. 20. A method of claim 11, wherein said composition further comprisea an anti-acne agent selected from the group comprising tretinoin, iaotretinoin, motretinide, adapslsne, taafotene, azelaic acid, recinol, salicylic acid, benzoyl peroxide, resoreifiol, sulfur, gulfacetamide, tetracycline, cliadamycin, mettonidazole, erythromycin, and salta thereof. 76 (54) Title: METHODS OF TRATING ACNE AND ROSACEA WITH GALVANIC GENERATED ELECTRICITY (57) Abstract: |
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| Patent Number | 270588 | ||||||||||||||||||
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| Indian Patent Application Number | 714/KOLNP/2006 | ||||||||||||||||||
| PG Journal Number | 02/2016 | ||||||||||||||||||
| Publication Date | 08-Jan-2016 | ||||||||||||||||||
| Grant Date | 31-Dec-2015 | ||||||||||||||||||
| Date of Filing | 24-Mar-2006 | ||||||||||||||||||
| Name of Patentee | JOHNSON & JOHNSON CONSUMER COMPANIES, INC | ||||||||||||||||||
| Applicant Address | 199 GRANDVIEW ROAD, SKILLMAN NEW JERSEY 08558, U.S.A | ||||||||||||||||||
Inventors:
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| PCT International Classification Number | A61N 1/30 | ||||||||||||||||||
| PCT International Application Number | PCT/US2004/020271 | ||||||||||||||||||
| PCT International Filing date | 2004-06-24 | ||||||||||||||||||
PCT Conventions:
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