Methods of treating acne and rosacea with electrochemically generated zinc ions

Method for treating acne and erythema acne by electrochemically generated zinc ions

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application is a continuation of the co-pending application 10/685, 282 filed on October 14, 2003, which is a part of the co-pending application 10/609, 727 filed on June 30, 2003. Part of the continuation, the full content of these applications are referenced here.

[0003] Background of the invention

[0004] Transdermal devices have been widely used for decades in the treatment of systemic diseases and local conditions. For passive transdermal delivery, the active agent is delivered into the mammal (eg, via passive diffusion through the skin) through a concentration gradient on both sides of the barrier membrane. For example, a patch containing a high concentration of drug is attached to the skin of a patient.

[0005] Electricity can be used to facilitate the transport of drugs through the skin barrier. In electrical assist devices, a potential (voltage) is applied to the membrane to promote drug transport. In transdermal iontophoresis, ionized drugs are driven to migrate into the skin by the applied potential gradient. Anionic drugs are delivered into the skin at the cathode (negatively charged electrode), while cationic drugs are delivered into the skin at the anode (positively charged electrode). Iontophoresis can increase and better control the penetration rate of ionized substances into the skin.

[0006] The most common design of iontophoresis devices includes a power source (such as a battery), an electrical control structure, and two independent conductive electrodes. Each conductive electrode is in contact with a respective electrolyte composition (with or without active agent). The electrolyte or ionic active composition is usually an aqueous solution contained in a liquid chamber or semi-solid. The combination of a conductive electrode and an electrolyte composition is generally referred to as an "electrode assembly" or simply an "electrode". The two electrode assemblies are usually attached to the skin, separated by an electrical insulator between them.

[0007] Alternatively, two electrode assemblies may constitute a single iontophoresis device, and an electrical insulating material is constructed between the two electrode assemblies of the iontophoresis device for electrical insulation to prevent short circuits. An example of such an iontophoresis device is disclosed in U.S. Patent No. 5,387,189.

[0008] In another variation of the commonly used iontophoresis device design, the electrolyte composition of one of the two electrode assemblies is removed, and the conductive electrode is directly placed in contact with the skin to complete the electrical circuit. An example of such an iontophoresis device is disclosed in U.S. Patent 6,385,487.

[0009] In a typical iontophoresis operation (unipolar operation), one of the two electrodes (for example, the active electrode) drives the active agent into the skin. The other electrode (such as a diffusion electrode) is used to close the circuit through the skin. Sometimes, a second active agent of opposite charge may be added to the electrolyte composition in contact with the second electrode, so that the second active agent is delivered into the skin under the second electrode. Alternatively, the electrical polarity of the first and second electrodes can be switched periodically to drive ionic species under both electrodes (bipolar operation). A bipolar iontophoresis device for transdermal drug delivery is disclosed in US Patent 4,406,658.

[0010] The use of galvanic couples as power sources in iontophoresis devices is well known in the art. See, for example, US Patent Nos. 5, 147, 297, 5, 162, 043, 5, 29 & 017, 5, 326, 341, 5, 405, 317, 5, 685, 837, 6, 584, 349, 6, 421, 561 and 6, 653, 014. The typical materials that make up the galvanic couple of galvanic cells include zinc electron-donating electrode and silver chloride counter electrode. This combination produces a potential of about one volt. There is no control method. If body tissues and/or body fluids form a complete circuit with the system, the iontophoresis system driven by the galvanic couple is automatically activated to generate electricity.

[0011] Summary of the invention

[0012] In one aspect, the present invention provides a method of exfoliating the skin, the method comprising applying a device to the

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On a peeled skin, the device includes a housing with a skin contact surface, a first conductive electrode, a second conductive electrode, and a carrier containing a reagent selected from the group consisting of α-phosphoryl acid, β-phosphoryl acid and salts thereof; wherein The first conductive electrode is in electrical communication with the second conductive electrode, the first conductive electrode is in ionic communication with the carrier, the carrier is in communication with the skin contact surface, and the skin contact surface is placed in contact with the skin.

[0013] In another aspect, the present invention provides a method of exfoliating the skin, the method comprising topically applying a composition to the skin, the composition comprising a first conductive electrode in the form of particles and a second conductive electrode in the form of particles 2Vo An electrode and a reagent selected from the group consisting of α-Ignosyl acid, β-Iganoic acid and salts thereof, wherein the standard potential difference between the first conductive electrode and the second conductive electrode is at least 0.2Vo

[0014] In another aspect, the present invention provides a method for promoting a composition comprising a first conductive electrode in the form of particles and a second conductive electrode in the form of particles, wherein the first conductive electrode and the second conductive electrode The standard potential difference of is at least 0.2V, and the method includes promoting the topical application of the composition for treating wounds on the barrier membrane.

[0015] In another aspect, the present invention provides a method of treating skin pores, the method comprising applying a device to the skin in need of such treatment, the device comprising a housing having a skin contact surface, a first conductive electrode , The second conductive electrode and the carrier; wherein the first conductive electrode is electrically connected with the second conductive electrode, the first conductive electrode is in ionic communication with the carrier, the carrier is in communication with the skin contact surface, the skin contact surface is placed in contact with the skin, and the treatment The method of skin pores is selected from: clean skin pores, reduce skin sebum, reduce the appearance of skin blackheads and reduce the appearance of skin pores.

[0016] In another aspect, the present invention provides a method for treating skin pores by topical application of a composition, the composition comprising a first conductive electrode in the form of particles and a second conductive electrode in the form of particles, wherein the first conductive electrode The standard potential difference with the second conductive electrode is at least 0.2Vo

[0017] In another aspect, the present invention provides a method of promoting a composition comprising a first conductive electrode in the form of particles and a second conductive electrode in the form of particles, wherein the first conductive electrode and the second conductive electrode The standard potential difference of is at least 0.2V, and the method includes promoting the topical application of the composition for treating skin pores, wherein the method for treating skin pores is selected from: cleansing skin pores, reducing skin sebum, and reducing the appearance of skin blackheads And reduce the appearance of skin pores.

[0018] In one aspect, the present invention provides a method for treating skin infections, including but not limited to acne or erythema, the method comprising applying electrochemically generated zinc ions to the skin. In one embodiment, the method includes topically applying a device containing a zinc-containing anode. In another embodiment, the device includes a housing having a skin contact surface; a zinc-containing first conductive electrode; a second conductive electrode; and a carrier; wherein the first conductive electrode is in electrical communication with the second conductive electrode, and the first conductive electrode It communicates with the carrier ions, and the carrier communicates with the skin contact surface.

[0019] In another aspect, the present invention provides a device having a barrier film contact surface, the device comprising: a power source; a first conductive electrode; a second conductive electrode; and a carrier; wherein the power source is connected to the first conductive electrode and the second conductive electrode. The conductive electrode is in electrical communication, the first conductive electrode and the second conductive electrode are in ionic communication with the carrier, and the carrier is in communication with the barrier membrane contact surface. In another aspect, the present invention provides a method of administering electricity to a barrier membrane of a human body, the method comprising applying such a device to the membrane. In another aspect, the present invention provides a method of treating skin conditions, the method comprising applying such a device to the skin.

[0020] On the other hand, the present invention provides a device with a barrier film contact surface, the device comprising: a power source; a first conductive electrode; a second conductive electrode; and a carrier containing an active agent; wherein the power source and the first conductive The electrode and the second conductive electrode are in electrical communication, the first conductive electrode and the second conductive electrode are in ionic communication with the carrier, and the carrier is in communication with the contact surface of the barrier membrane. In another aspect, the present invention provides a method of administering electricity to a barrier membrane of a human body, the method comprising applying such a device to the membrane. In another aspect, the present invention provides a method of treating skin conditions, the method comprising applying such a device to the skin.

[0021] In another aspect, the present invention provides a device having a barrier film contact surface, the device comprising: a power source; a first conductive electrode; a second conductive electrode; a first light-emitting diode; and a carrier containing an active agent; wherein, The power supply is in electrical communication with the first conductive electrode, the second conductive electrode and the light emitting diode, and the structure of the device enables the light from the first light emitting diode and the carrier to communicate with the contact surface of the barrier film. In another aspect, the present invention provides a method of administering a barrier membrane active agent to a human body, the method comprising applying such a device to the membrane. In another aspect, the present invention provides a method of treating skin conditions, the method comprising applying such a device to the skin.

[0022] In another aspect, the present invention provides a method of treating skin conditions by applying a device to the skin, the device having a barrier film contact surface that administers an oxidizing agent to the barrier film, wherein the device includes: a power source; A first conductive electrode, wherein the first conductive electrode is an inert anode; a second conductive electrode, wherein the second conductive electrode is a cathode; and an aqueous carrier; wherein the power source is in electrical communication with the first conductive electrode and the second conductive electrode, and the first conductive electrode The electrode is in ionic communication with the carrier, the oxidant is generated by the current passing from the first conductive electrode to the carrier, and the carrier is in communication with the barrier membrane contact surface. In another aspect, the present invention provides a method of administering an oxidizing agent to a barrier film, the method comprising applying such a device to the film.

[0023] In another aspect, the present invention provides a method of treating skin conditions by applying a device to the skin, the device having a barrier film contact surface that administers a barrier film reducing agent, wherein the device includes: a power source : A first conductive electrode, wherein the first conductive electrode is an inert anode; a second conductive electrode, wherein the second conductive electrode is a cathode; and an aqueous carrier; wherein the power source is in electrical communication with the first conductive electrode and the second conductive electrode, the first The conductive electrode is in ionic communication with the carrier, the reducing agent is generated by the current passing from the first conductive electrode to the carrier, and the carrier is in communication with the barrier membrane contact surface. In another aspect, the present invention provides a method of administering a reducing agent to a barrier film, the method comprising applying such a device to the film.

[0024] Other features and advantages of the present invention will be apparent from the detailed description and claims of the present invention.

[0025] Brief Description of the Drawings

[0026] FIG. 1 is a cross-sectional view of an embodiment of a device suitable for implementing the present invention. The conductive electrodes 140 and 240 are connected to the electrically insulated connection line 350 on the back of the device 500 through wires 110 and 210, respectively.

[0027] FIG. 2 is a cross-sectional view of an embodiment of a device suitable for implementing the present invention. The conductive electrodes 140 and 240 are connected to the electrically insulated connecting wire 350 embedded in the carrier layer 120 of the device 500 through wires 110 and 210, respectively.

[0028] FIG. 3 is a cross-sectional view of an embodiment of a device suitable for implementing the present invention. Conductive electrode 140 and

240 is connected to the electrically insulated connecting wire 350 embedded in the carrier layer 120 through wires 110 and 210, respectively.

[0029] FIG. 4 is a cross-sectional view of an embodiment of a device suitable for implementing the present invention. The conductive electrodes 140 and 240 are in electrical communication with each other through a direct connection.

[0030] FIG. 5 is a cross-sectional view of an embodiment of a device suitable for implementing the present invention. The device 800 includes two electrode assemblies 200 and 600.

[0031] FIG. 6 is a top view of an embodiment of the present invention, showing that the conductive electrodes 140 and 240 are connected by an electrically insulated connecting wire 350 embedded in the carrier layer 120. The conductive electrodes 140 and 240 are arranged in a mutually staggered configuration.

[0032] FIG. 7 is a top view of an embodiment of the present invention, showing that the conductive electrodes 140 and 240 are connected by an electrically insulated connecting wire 350 embedded in the carrier layer 120. The conductive electrodes 140 and 240 are arranged in a concentric circle configuration.

[0033] FIG. 8 is a top view of an embodiment of the present invention, showing that multiple sets of conductive electrodes 140 and 240 are connected to each other through a connecting wire 350 to form a plurality of galvanic battery power supplies, and the galvanic cell galvanic power supplies are in contact with the carrier layer 120. The conductive electrodes 140 and 240 are arranged in a parallel configuration.

[0034] FIG. 9 is a top view of an embodiment of the present invention, showing that multiple sets of conductive electrodes 140 and 240 are connected to each other by direct physical contact at the junction 370 to form multiple galvanic battery power supplies, galvanic battery power supplies and a carrier The layer 120 is in contact.

The conductive electrodes 140 and 240 are arranged in a vertical configuration.

[0035] FIG. 10 is a top view of an embodiment of the present invention, showing that the conductive electrodes 140 and 240 are connected by an electrically insulated connecting wire 350 embedded in the carrier layer 120.

[0036] FIG. 11 is a top view of an embodiment of the present invention, showing the conductive electrodes 140 and 240 are embedded in the carrier layer 120.

[0037] Detailed description of the invention

[0038] Based on this, it is believed that those skilled in the art can make full use of the present invention. The following specific embodiments should be understood to be only exemplary, and not to limit the rest of the present disclosure in any way.

[0039] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention belongs. Moreover, all publications, patent applications, patents, and other references mentioned herein are incorporated herein by reference. Unless otherwise specified, percentages refer to weight percentages (ie, weight %).

[0040] "Product" refers to a product in the final packaging form that contains the device. In one embodiment, the product includes instructions instructing the user to apply the device to the barrier film (eg, to treat skin conditions). The instructions can be printed on the device, on the label insert, or on any additional packaging.

[0041] In one aspect, the present invention provides a method of promoting a specific use of the device of the present invention. "Promotion" refers to publicity, advertising or marketing. Examples of promotion include, but are not limited to, words, images, or dictations on products or stores, magazines, newspapers, radio, television, and the Internet.

[0042] "Pharmaceutically acceptable" as used herein refers to the ingredients described by the term are suitable for contact with barrier membranes (such as skin or mucous membranes) without adverse toxicity, incompatibility, instability, irritation , Allergic reactions, etc.

[0043] As used herein, "safe and effective amount" refers to an ingredient or composition in an amount sufficient to provide the desired effect, but low enough to avoid serious side effects. The safe and effective amount of the ingredient or composition will vary with factors such as the site to be treated, the age and skin type of the user, the duration and nature of the treatment, the specific ingredient or composition used, and the specific pharmaceutically acceptable carrier used. .

[0044] The term "treatment" or "treatment" as used herein refers to treatment (for example, alleviation or elimination of symptoms and/or cure) and/or prevention or suppression of diseases (for example, skin diseases). "Skin disease" refers to a dermatological disease or condition (including but not limited to acne, erythema or skin infection) or skin characteristics (including but not limited to pigmentation, hair growth regulation, skin texture, skin hardness, skin Elasticity, skin microtubule structure, dark spots, cellulite, cortical regulation and skin luster). Skin infections include but are not limited to those due to susceptible pathogens such as acne, erythema, impetigo, folliculitis, navicular disease, sore ulcers, eczema, psoriasis, atopic dermatitis, herpes, epidermolysis bullosa , Scaly, and infected traumatic injuries (such as ulcers, mild burns, cuts, abrasions, lacerations, wounds, biopsy sites, surgical incisions, and insect bites).

[0045] The present invention relates to a device for delivering electricity (for example, to induce a desired biological response) and/or an active agent into a barrier membrane. In one embodiment, the device of the present invention is a complete device including at least a pair of two different conductive electrodes in electrical communication as a power source. "Electrical communication" refers to the direct passage of electrons between device elements (for example, between the conductive electrodes of the device). In one embodiment, the two conductive electrodes are in electrical communication by directly contacting each other.

[0046] "Ionic communication" refers to the passage of electrons through ion migration as "electron movers" in contact with elements (for example, conductive electrodes, carriers, and/or conductive electrodes and skin) between the elements (for example, through contact with the elements). Conductive electrode and skin contact electrolyte (for example, in the carrier) ion transport, electrons pass between the conductive electrode and the skin).

[0047] In one embodiment, the two conductive electrodes are in ionic communication with an electrolyte-containing carrier (for example, one or more ions in the carrier are in contact with the conductive electrode), and the carrier is in communication with skin ions. This electrode structure is different from the electrode structure of the conventional iontophoresis device. In the conventional iontophoresis device, each conductive electrode is in contact with a separate carrier (for example, each electrode

CN 1829552 Β

Installed in a separate room and attached to the skin, the two electrodes are electrically insulated, so that all electrical connections pass through the skin to complete an electrical loop). The advantages of this embodiment of the present invention include the ability to simultaneously transfer active agents of opposite charges from the same carrier into substantially the same skin area under the conductive electrode. Another advantage is that the device of the present invention is easier to manufacture than conventional iontophoresis devices, and thus can Great cost savings.

[0048] The device includes a barrier film contact surface (such as a skin contact surface) applied to the membrane (such as a user's skin). The structure of the device enables the carrier to communicate with the contact surface of the barrier membrane (for example, enabling the applied current and/or active agent to enter the barrier membrane from the carrier). In one embodiment, the carrier is a barrier membrane contact surface (for example, the carrier is a hydrogel). In one embodiment, the device includes a light-emitting diode that allows light from the light-emitting diode to communicate with the barrier film contact surface (eg, so that light can reach the barrier film).

[0049] In one embodiment, the device of the invention delivers the active agent into the barrier membrane. The active agent to be delivered through the device of the present invention includes the active agent originally contained in the carrier, or the active agent generated electrochemically by the current passing from the conductive electrode to the carrier during use. "Electrochemically generated" means that the chemical substance is produced by the electrochemical reaction caused by the current flowing through the electrode. For example, the chemical substance released from the reactive electrode (such as electrochemically produced zinc ions) is produced in the inert electrode. A chemical substance produced electrochemically on the surface, or a chemical substance that is a subsequent reaction product of the electrochemically produced substance.

[0050] power supply

[0051] In one embodiment, the device of the invention includes a power supply. The power source can be a common direct current (DC) or pulsed DC, for example, as disclosed in US Patent No. 5, 042, 975. In one embodiment, the current density (current intensity per unit area of the barrier film) used by the device of the present invention is generally less than about 0.5 mA/cm², Such as less than about 0.1mA/cm²Or less than about 0.05mA/cm²_oIn one embodiment, the power supply generates a voltage of about 0.1 volts to 9 volts, such as about 1-3 volts, such as about 1.5 volts.

[0052] In one embodiment, the power source is a battery (eg, a rechargeable or disposable battery). In one embodiment, the battery is a small-sized disposable battery suitable for wearing a patch or mask type adhesive device. Examples of suitable batteries include, but are not limited to, button batteries or coin batteries such as silver oxide, lithium, and zinc-air batteries (usually used in small electrical devices). Zinc-air batteries are preferred because of their small size, high energy density, and environmental friendliness. Examples of zinc-air batteries include, but are not limited to, EnergizerTM AC5 and AC10/230 (Eveready Battery Co. Inc., St. Louis, MO). Another preferred battery for this device is a flexible thin-layer open liquid electrochemistry The battery, for example, is disclosed in U.S. Patent No. 5,897,522.

[0053] galvanic couple

[0054] In one embodiment, the device/composition of the present invention has a galvanic couple as a power source, wherein the electrons flowing between the first conductive electrode and the second conductive electrode are generated by the standard potential difference between the electrodes ( That is, electricity is not generated by external batteries or other power sources such as AC power). Examples of such galvanic couples include, but are not limited to: zinc-copper, zinc-copper/copper halide, zinc-copper/copper oxide, magnesium-copper, magnesium-copper/copper halide, zinc-silver, zinc-silver/ Silver oxide, zinc-silver/silver halide, zinc-silver/silver chloride, zinc-silver/silver bromide, zinc-silver/silver iodide, zinc-silver/silver fluoride, zinc-gold, magnesium-gold, aluminum- Gold, magnesium-silver, magnesium-silver/silver oxide, magnesium-silver/silver halide, magnesium-silver/silver chloride, magnesium-silver/silver bromide, magnesium-silver/silver iodide, magnesium-silver/silver fluoride, Magnesium-gold, aluminum-copper, aluminum-silver, aluminum-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-silver/silver bromide, copper-silver/silver iodide, copper-silver/silver fluoride, iron-copper, iron-copper / Copper oxide, iron-copper/copper halide, iron-silver, iron-silver/silver oxide, iron-silver/silver halide, iron-silver/silver chloride, iron-silver/silver bromide, iron-silver/silver iodide , Iron-silver/silver fluoride, iron-gold, iron-conductive carbon, zinc-conductive carbon, copper-conductive carbon,

Magnesium-conductive carbon and aluminum-carbon. The material constituting the galvanic couple can also be used as the conductive electrode of the device, for example, zinc as the conductive anode, silver/silver chloride as the conductive cathode or zinc as the conductive anode and copper as the conductive cathode. Metals that can be used as galvanic couples and conductive electrodes can also be alloys. Non-limiting examples of alloys include zinc, copper, aluminum, and magnesium alloys as anode materials, and silver, copper, and gold alloys as cathode materials.

[0055] In one embodiment, the material constituting the galvanic couple has a standard potential difference equal to or greater than about 0.1 volts, such as greater than about 0.2 volts, such as greater than about 0.5 volts. In one embodiment, the material constituting the galvanic couple has a standard potential difference equal to or less than about 3 volts.

[0056] In one embodiment, the device or composition of the present invention generates and/or is capable of generating a current that enters the barrier film is about InA/cm²-400 μ A/cm', for example about 100A/cm²-50 μ A/cm²_o

[0057] In one embodiment, one of the conductive electrodes is in the form of a metal sheet, a metal wire, or a metal plated on a substrate, and the other conductive electrode is connected to or deposited on the first conductive electrode. In another embodiment, the metal sheet is perforated. In one embodiment, the perforated metal sheet has the form of a mesh, such as a mesh of zinc, magnesium, aluminum, copper, or alloys thereof. In one embodiment, the second conductive electrode is a fabric coated with metal and its oxides, halides, and sulfides, for example, coated with silver, silver/silver oxide, silver/silver halide, zinc, magnesium, copper , Copper/copper halide, copper/copper oxide fabric. In another embodiment, the second conductive electrode is deposited on the first conductive electrode by chemical or electrochemical deposition, such as electroless plating for chemical deposition and electroplating for electrochemical deposition as known in the art. In another embodiment, the second conductive electrode is deposited on the first conductive electrode by physical deposition such as spraying, plasma plating, conductive ink coating, screen printing, dip coating, or vacuum deposition.

[0058] In one embodiment, the device is a single-chamber therapeutic device. "Single-chamber therapeutic device" refers to 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.

[0059] Carrier

[0060] The carrier of the present invention is a liquid (for example, a solution fixed in an absorbent material such as gauze or non-woven mat) that can conduct electricity from a conductive electrode when in use (for example, the carrier contains one or more electrolytes, organic solvents or water) , Suspension or emulsion), semi-solid (for example, gel, cream, lotion, microemulsion or hydrogel), or solid (for example, lyophilized composition containing active agent, added to liquid before use to re-form) . In one embodiment, the carrier (eg, liquid or semi-solid) is added to the device before the user applies the device on the barrier film.

[0061] Examples of electrolytes include, but are not limited to, organic or organic salts of pharmaceutically acceptable carriers and buffers. Examples of salts include, but are not limited to, hydrochlorides (such as sodium chloride, potassium chloride, lithium chloride, calcium chloride, saw chloride, magnesium chloride or other hydrochlorides) and sodium, potassium, lithium, Calcium salt, magnesium salt, saw salt, hydrofluoride, hydroiodide, hydrobromide. Examples of buffers include, but are not limited to, phosphate, citrate, acetate, lactate, and borate.

[0062] In one embodiment, the electrolyte is an active agent, or an active agent that becomes an active agent after being electrically connected through a carrier. Examples of such electrolyte-active agents include, but are not limited to, salicylic acid, salicylate and other weak acid or weak base active agents.

[0063] In one embodiment, the carrier contains water. In another embodiment, the carrier may also contain one or more organic solvents. Examples of organic solvents include, but are not limited to: dimethyl isosorbide; isopropyl myristate; cationic, anionic and nonionic surfactants; vegetable oils; mineral oils; waxes; gums; synthetic and natural gelling agents; Alkanols; diols and polyols.

[0064] Examples of glycols include, but are not limited to, glycerin, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, polyethylene glycol, polypropylene glycol, diethylene glycol, triethylene glycol, glycerol, hexamethylene glycol Alcohol and its copolymers or mixtures. Examples of alkanols include, but are not limited to, alkanols having about 2-12 carbon atoms (for example, about 2-4 carbon atoms), such as isopropanol and ethanol. Example package of polyols

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Including, but not limited to, polyols having about 2-15 carbon atoms (for example, about 2-10 carbon atoms), such as propylene glycol.

[0065] Based on the total weight of the carrier, the amount of organic solvent that may be present in the carrier is about 1% -90% (for example, about 5% -50%). ο Based on the total weight of the carrier, the water present in the carrier (using The amount of front) may be about 5%-95% (for example, about 50%-90%).

[0066] The carrier may also contain: preservatives (such as cresol, chlorocresol, benzyl alcohol, methyl paraben, propyl paraben, phenol, thimerosal, benzalkonium chloride, chlorinated Ethoxyl chloride and phenylmercuric nitrate); stabilizers or antioxidants (such as ascorbic acid, ascorbyl esters, methyl fennel, methyl methyl toluene, cysteine, N-acetyl cysteine, metabisulfite Sodium bisulfite, sodium sulfite, sodium formaldehyde sulfoxylate, acetone sodium bisulfite, tocopherol and nordihydroguaiaretic acid); chelating agents (such as ethylenediaminetetraacetic acid and its salts); buffering agents (such as acetic acid) , Citric acid, phosphoric acid, glutamic acid and its salts); and tonicity modifiers (such as sodium chloride, sodium sulfate, glucose and glycerin).

[0067] In one embodiment, the carrier may also contain suspending materials and/or liquid absorbing materials (for example, components used to physically stabilize the carrier). Examples of suspended materials include, but are not limited to: cotton-based gauze; non-woven mats made of rayon or a mixture of rayon, polyester and/or other polymer fibers; those containing polyurethane, polyester and/or other polymers Open-cell foam and sponge-like materials; and cross-linked and non-cross-linked gel materials, such as polyacrylamide, polyvinyl alcohol, gelatin, methyl cellulose, ethyl cellulose, propyl cellulose, methyl cellulose Base cellulose and methyl cellulose.

[0068] Examples of liquid-absorbing materials include, but are not limited to: cross-linked and non-cross-linked polymers; swellable polymers such as water-swelling cellulose derivatives (eg, methyl cellulose (MC), ethyl methyl Cellulose (ΗΕΜΑ), suspected propyl methyl cellulose (HPMC), ethyl consuming ethyl cellulose (EHEC), suspected ethyl cellulose (HEC), suspected propyl cellulose (HPC), methyl cellulose (CMC) and their salts); polyvinyl alcohol (PVA); polyvinylpyrrolidone (PVP); polyethylene oxide (PE0); from monomers such as ethyl methacrylate (ΗΕΜΑ), Heteroethoxyethyl methacrylate (HΕΕΜΑ), Heterodiethoxyethyl methacrylate (MDEEMA), Methoxyethyl methacrylate (MEMA), Methoxyethoxy methacrylate Ethyl (MΕΕΜΑ), methyldiethoxyethyl methacrylate (MDEEMA), ethylene glycol dimethacrylate (EGDMA), N-vinyl-2-pyrrolidone (NVP), methyl Copolymers made of acrylic acid (MA) and vinyl acetate (VAC); polyacrylamide; gelatin; gums and polysaccharides such as gum arabic, carrageenan, tragacanth, guar gum, benzoin gum, alginic acid and other Salt; polyethylene glycol (PEG); polypropylene glycol (PPG); clay and other swellable mineral materials such as bentonite and montmorillonite. The amount of liquid absorbable material in the carrier is about 0 of that of the carrier. 1%-95% by weight, for example about 1%-20% by weight.

[0069] Another embodiment of the present invention involves pairing one or more inert conductive electrodes to electrochemically generate an oxidizing or reducing agent from an electrochemically reactive substance in situ in a carrier. These oxidizing or reducing agents can be used as active agents to treat barrier membrane diseases.

[0070] Examples of electrochemically reactive substances in the carrier of the present invention include, but are not limited to: water and containing elements selected from the periodic table

Compounds of VIB and VIIB elements (such as oxygen, sulfur, fluorine, chlorine, bromine, and iodine).

[0071] In one embodiment, the reactive substance reacts with the inert anode to form an oxidizing agent. Examples of such reactive substances include but are not limited to: ions 0H", C", ", Br", S0 and HC0₃\Therefore, the device of the present invention can generate oxidants such as nascent oxygen (ie singlet oxygen), chlorine gas and chlorine dioxide gas, which are difficult to prepare in conventional topical products.

[0072] In one embodiment, the reactive substance reacts with the inert cathode to form a reducing agent. Examples of such reactive substances include, but are not limited to: oxidized or disulfide forms of thio compounds with one or more Ul functional groups, sulfur-containing amino acids and their salts or esters, and sulfides. Examples of such thio compounds include, but are not limited to: eukylacetic acid and its salts, such as calcium, sodium, saw, potassium, saddle, lithium, magnesium and other metal salts of eukylacetic acid; thioglycol; thioglycol; Glycerol; thioethanol; thioacetic acid; and thiosalicylic acid; and their salts. Examples of sulfur-containing amino acids include, but are not limited to, L-cysteine, D-cysteine

Amino acid, DL-cysteine, N-acetyl-L-cysteine, DL-homocysteine, L-cysteine methyl ester, L-cysteine ethyl ester, N- Carbamoylcysteine, glutathione and cysteamine. Examples of sulfides include, but are not limited to, calcium sulfide, sodium sulfide, potassium sulfide, lithium sulfide and saw sulfide and glutathione disulfide. The inert cathode converts the oxidized or disulfide form of the above-mentioned reactive sulfur-containing compound into a sulfur-containing compound, or a compound containing a thiol group. Examples of such conversions are the conversion of cystine to cysteine, and the conversion of the oxidized form of glutathione to glutathione.

[0073] In one embodiment, the concentration of the reactive substance in the carrier may be about 0.01% by weight to 25% by weight of the carrier, for example about 0.1% by weight to about 10% by weight. The pH value of the carrier can be about pH 1.5 to pH 9, preferably pH 2 to pH 7, and most preferably about pH 3 to pH 5.

[0074] In one embodiment, the carrier contains a binder. Adhesive is used to adhere the device to the barrier film. Examples of hydrophobic adhesives include, but are not limited to: siloxane, polyisobutylene and its derivatives, acrylics, natural rubber, and combinations thereof. Examples of silicone adhesives include, but are not limited to: Dow Corning 355 from Dow Corning of Midland, MI; Dow Corningo X7-2920; Dow Corning X7-2960; and GE 6574 from General Electric Company of Waterford, NY. Examples of acrylic adhesives include, but are not limited to, vinyl (D acetate-acrylate) polymers such as Gelva 7371, available from Monsanto Company, St. Louis, MO; Gelvao 7881; Gelva 2943; and 1-780 medical grade adhesive from Avery Dennison of Painesville, OH. Examples of hydrophilic adhesives include, but are not limited to, papaya gum and other natural gums, MC, HEMA, HPMC, EHEC, HEC, HPC, CMC, PVA, PVP, PEO, HEMA, HEEMA, HDEEMA, MEMA, MEEMA, MDEEMA , EGDMA, NVP MA, VAC, polyacrylamide, gelatin, gum arabic, carrageenan, tragacanth, guar gum, benzoin gum, alginic acid and its salts, polyethylene glycol (PEG) and polypropylene glycol ( PPG) ο

[0075] In one embodiment, the concentration of the binder in the carrier may be about 0.1% to 95% by weight of the carrier, for example, about 1% to 20% by weight.

[0076] Electrode

[0077] The conductive electrode of the present invention may be a reactive conductive electrode or an inert conductive electrode. "Reactive conductive electrode" means that during the chemical reaction of the electrode, the chemical composition of the conductive electrode itself changes, and current passes through the electrode in the process. In one embodiment, the reactive conductive electrode is an anode composed of reactive materials such as pure metals or metal alloys, including but not limited to zinc, aluminum, copper, magnesium, manganese, silver, titanium, tin, iron, and alloys thereof. The material constituting the galvanic couple described above can also be used as a reactive conductive electrode. When the electrical connection passes, metal ions such as zinc, copper, magnesium, manganese, and/or aluminum cations are released from the anode into the carrier and transferred to the barrier membrane. These ions may have therapeutic effects, such as antibacterial effects, immunomodulation, enzyme regulation, and/or anti-inflammatory effects.

[0078] In one embodiment, the reactive conductive electrode is composed of a reactive substance such as a metal halide (eg, silver-silver chloride (Ag/AgCl), silver-silver bromide, and silver-silver iodide). In this case, the original electrochemical reaction on the surface of the cathode is the conversion of solid silver halide to metallic silver, and the oxidant produced by the anode does not need to be consumed. The released chloride ions can then be oxidized into oxidants, such as chlorine (Cl?), hypochlorous acid (HC10), hypochlorite (C10"), and iodide ions are converted to iodine.

[0079] "Inert conductive electrode" means that the chemical composition of the conductive electrode itself does not change. In one embodiment, the anode is composed of an inert conductive electrode, so that the electrochemical process on the surface of the anode produces oxidants such as nascent oxygen (for example, by electrolyzing water) and/or chlorine-containing oxidants such as chlorine, hypochlorite, chlorate and Perchlorate, and chlorine dioxide. Neo-Oxygen is an oxidant that inhibits P.acnes, and chlorine-containing oxidant is a powerful antibacterial agent with bactericidal activity.

[0080] In one embodiment, the conductive electrode is composed of an inert material or is plated with an inert material on the surface, for example, noble metal (for example, gold, tongs, or gold-plated conductive metal), conductive carbon (for example, glassy carbon or graphite) , Carbon-inserted polymers (for example,

CN 1829552 Β

Carbon silicone rubber), conductive carbon polymer foam material or sponge, silver halide plated silver (for example, silver chloride plated silver, silver bromide plated silver and silver iodide plated silver), and corrosion-resistant alloys.

[0081] In one embodiment, the anode of the device, used as both a conductive electrode and a part of the galvanic power supply of the galvanic cell, is made of a metal such as zinc, calcium, magnesium, aluminum, iron, tin, which is oxidizable by the above-mentioned reactive conduction. , Copper or its alloys, and also used as a conductive electrode and as part of the galvanic couple power supply cathode is composed of the above-mentioned reactive and reducible conductive materials, such as more chemically stable metals and their metal halides, oxides, Sulfides or other metal salts, such as silver and silver halides (for example, silver chloride, silver bromide, silver iodide, silver fluoride), silver oxide, silver sulfide. In one embodiment, the reducible conductive material is in direct contact with a good conductor, such as a thin layer of silver chloride, silver oxide or sulfide on metallic silver; silver chloride powder containing a binder (for example, silver chloride ink) ; And/or mixing silver or conductive carbon powder and silver chloride powder (for example, silver-silver chloride ink and silver chloride-carbon ink) bonded together by a binder in the matrix.

[0082] In another embodiment, the anode of the device of the present invention is composed of the above-mentioned reactive and oxidizable conductive metal, and the cathode is composed of the above-mentioned more chemically stable electrode material such as conductive carbon, metallic silver, gold or tongs, or conductive carbon. It is composed of a mixture formed by mixing with precious metal powder to form a matrix, as described in US Patent No. 5,162,043.

[0083] In one embodiment, the device of the present invention can target beneficial zinc to the hair follicle sebaceous gland unit (for example, sebaceous glands and related hair follicles) through the hair follicle to treat acne or erythema. Zinc is an essential metal for the human body because it participates in many biological activities of the human body (for example, a 70 kg person contains approximately 2.3 grams of zinc). It is known that the lack of zinc in the human body can cause skin diseases such as acne.

[0084] In another embodiment, using an anode composed of a zinc alloy containing a small amount of other beneficial metals, the device of the present invention can target delivery of other beneficial metals into hair follicles and hair follicle sebaceous glands. These beneficial metals include, but are not limited to, certain essential metals such as iron, copper, magnesium, manganese, calcium, potassium, aluminum and selenium. When the zinc alloy anode is oxidized, it releases zinc ions and other beneficial metals in the zinc alloy into the carrier. Under the action of the electric potential applied on the skin, these components are then transferred into the hair follicle. In one embodiment, the content of the zinc alloy in the anode is greater than about 50% by weight, for example, greater than about 90% by weight. [0085] In one embodiment, (i) the carrier and (ii) the carrier hydrated skin measured between the first conductive electrode and the second conductive electrode conductivity (wherein, the electrodes pass substantially The ratio of all electrical connections through the skin is about 10000: 1-1: 100. That is to say, the current distribution between I carrier and I skin can make the value of I carrier/1 skin about 10,000-0. 01 ο I The carrier is the part of the total current (Itotal) that passes through the device that only passes through the carrier layer between the anode and the cathode and does not pass through the skin. I skin is the most skin-passing part of I total, that is, I total = I carrier + 1 skin.

[0086] Decreasing the ratio of carrier conductance to skin conductance will result in a greater proportion of electrical connections passing through the skin, thereby promoting iontophoresis of any active agent so delivered into the skin. Adding a less conductive substance to the carrier can non-exclusively reduce the conductivity of the carrier. Examples of such less conductive substances include, but are not limited to, oils such as silicone oil or crude oil, air pockets in a semi-solid carrier, or polymers or clays such as air bubbles or air pockets. In an embodiment where the main purpose is to electrochemically produce a substance in a carrier, the value of I carrier/1 skin is about 10,000-1. In an embodiment where the main purpose is to deliver electric current and/or active agent into the skin, 1 The carrier/1 skin value is about 10-0. 01ο For specific purposes, the I carrier/1 skin value can also be adjusted by changing the distance between the first and second electrodes, or the decrease between the second conductive electrode and the skin . For example, as the distance between the two conductive electrodes decreases, the conductance measured between the two electrodes increases, and the I carrier also increases, resulting in an increase in the value of I carrier/1 skin. On the other hand, if the distance between the two conductive electrodes and the skin increases, I skin increases, resulting in a decrease in I carrier/1 skin value.

[0087] Electrochemically Generated Zinc Ions

[0088] In one embodiment, in the topical composition, zinc ions are electrochemically generated by a zinc anode, or zinc ions are added later. The topical composition is then applied to the barrier film of the user to achieve the zinc present in the topical composition

CN 1829552 Β

Specific beneficial effects of ions and other active agents. The active agent in the topical composition may contain anti-acne agents such as salicylic acid or benzoyl peroxide. The method for preparing this electrochemically generated zinc ion is to pack the electrochemical device for the production of zinc into the packaging and/or dispensing container of the topical composition (for example, with a dispensing pump for acne-treatment/skin care Bottle of frost). In one embodiment, an electrochemical device including a zinc anode in electrical communication with each other, a silver/silver chloride cathode, and a power source (such as a battery) are contained in the dispensing pump. As the topical composition (such as cream) flows out of the dispensing pump, it contacts the zinc anode and cathode and completes an electrical loop (that is, current flows from the anode into the cream and returns to the power source through the cathode), and the zinc anode starts Release zinc ions into the cream. Alternatively, the electrochemical device used to produce zinc does not include a battery. Instead, the zinc anode and cathode are connected to form a galvanic cell, and zinc ions are generated when the two electrodes contact the cream.

Active agent

[0090] In one embodiment, the carrier contains one or more active agents. "Active agent" refers to a compound (for example, a synthetic compound or a compound isolated from natural sources) that has a cosmetic or therapeutic effect (for example, a substance that can produce a biological effect on the human body) on the barrier membrane and its surrounding tissues, such as a therapeutic drug , Including but not limited to organic and macromolecular compounds. Examples of such therapeutic drugs include peptides, polypeptides, proteins, nucleotides including DNA and nutrients. Examples of polypeptide and protein active agents include: Thyroid-stimulating hormone-releasing hormone (TRH), vasopressin, gonadotropin-releasing hormone (GnRH or LHRH), melanin-stimulating hormone (MSH), calcitonin, growth hormone-releasing factor (GRF) ), insulin, erythropoietin (EPO), interferon alpha, interferon beta, oxytocin, captopril, bradykinin, atrial peptide, cholecystokinin, endorphins, nerve growth factor, melanocyte inhibition Agent T, gastrin antagonist, somatostatin (somatotatin), cephalin, melatonin, vaccine, botulinum toxin type A (botulinum neurotoxin), cyclosporin and its derivatives (for example, biological Active fragments or analogs). Other active agents include: anesthetics; analgesics (for example, fentanyl and its salts such as fentanyl citrate); drugs to treat psychosis, epilepsy, and migraine; drugs to stop drug addiction and drug abuse; anti- Inflammation medicine; treat high blood pressure, heart Drugs for vascular diseases, stomach acid and ulcers; drugs for hormone replacement therapy and contraception such as estrogen and androgens; antibiotics, antifungals, antivirals and other antimicrobial agents; antitumor drugs, immunosuppressants and immunostimulants ; And drugs that act on the blood and hematopoietic organs, including hematopoietic and anticoagulant drugs, thrombolytics and antiplatelet drugs. Other active agents that can be delivered into the body using the shearing device of the present invention include vaccines for various diseases, such as influenza vaccine, AIDS vaccine, hepatitis vaccine, measles vaccine, mumps vaccine, rubella vaccine, rabies vaccine, rubella vaccine, avercella Vaccines, tetanus vaccine, hypogammaglobulinemia vaccine, Rh disease vaccine, diphtheria vaccine, botulism vaccine, snake bite vaccine, black widow bite and other insect bite/sting vaccine, idiopathic thrombocytopenia ITP vaccine, chronic lymphocytic leukemia vaccine, cytomegalovirus (CMV) infection vaccine, acute renal rejection vaccine, oral polio vaccine, tuberculosis vaccine, pertussis vaccine, Haemophilus type b vaccine , Pneumococcal vaccine and Staphylococcus aureus vaccine.

[0091] In one embodiment, the carrier comprises an anti-acne and/or anti-erythema agent. Examples of anti-acne and anti-erythema acne agents include but are not limited to: tretinoin, such as tretinoin, isotretinoin, moretinide, adapalene, tazarotene, azelaic acid and vitamin A; water Salicylic acid; benzoyl peroxide; resorcinol; sulfur; sulfacetamide; urea; antibiotics such as tetracycline, clindamycin, metronidazole and erythromycin; anti-inflammatory drugs such as corticosteroids (for example, hydrogenated Cortisone), ibuprofen, naproxen and hetprofen; imidazoles such as ketoconazole and elubiol; its salts and their prodrugs. Other examples of anti-acne active agents include essential oils, alpha-bisabolol, dipotassium glycyrrhizinate, camphor, beta-glucan, allantoin, wild chamomile, flavonoids such as soy isoflavones, samba palm, Chelating agents such as EDTA, lipase inhibitors such as silver and copper ions, hydrolyzed vegetable protein, inorganic ions chloride, iodide, fluoride and non-ionic derivatives containing chlorine, iodine, fluorine and other valences, synthetic phospholipids and natural phospholipids Such as AriasilkTM Phospholipid CDM, SV, EFA, PLN and GLA (Uniqema, ICI Group of Companies, W Orderton, UK). [0092] In one embodiment, the device of the invention contains an anti-aging agent. Examples of suitable anti-aging agents include but are not limited to

Page Π/27: Inorganic sunscreens such as titanium dioxide and zinc oxide; organic sunscreens such as octyl-methoxy cinnamate; retinoic acids; dimethylaminoethanol (DMAE), copper-containing peptides, vitamins such as vitamin E , Vitamin A, vitamin C, vitamin B and its salts or derivatives such as ascorbyl digluconate and vitamin E acetate or brown thick ester; alpha quaternary acid and its precursors such as glycolic acid, citric acid, lactic acid, malic acid , Mandelic acid, Ascorbic acid, α-Issued butyric acid, α-Issued isobutyric acid, α-Hydroisohexanoic acid, Aldrolactic acid, α-Isovaleric acid, Ethyl pyruvate, Galacturonic acid, Glucoheptonic acid, glucoheptonic acid 1,4-lactone, gluconic acid, gluconolactone, glucuronic acid, glucuronolactone, isopropyl pyruvate, methyl pyruvate, viscose Acid, pyruvic acid, glucaric acid, glucaric acid 1,4-lactone, tartaric acid and serotonin; β serotonic acid such as β-serotonin butyric acid, β -phenyl-lactic acid and β- Phenylpyruvate; zinc and zinc-containing compounds such as zinc oxide; plant extracts such as green tea, soybeans, silymarin, algae, aloe vera, angelica, citrus aurantium, coffee, coptis, grapefruit, hoellen, honeysuckle, Huizhengren, Lithospermum, mulberry, peony, puerarua, nice and safflower; and its salts and prodrugs.

[0093] In one embodiment, the carrier contains a decolorizing agent. Examples of suitable decolorizing agents include, but are not limited to: soybean extract; soy isoflavones; tretinoin such as vitamin A; kojic acid; dibrown thick acyl kojic acid ester; hydrogen glutamate; bear fruit shake; transexamic acid; vitamins such as Niacin and vitamin C; azelaic acid; linolenic acid and linoleic acid; placertia; licorice; extracts such as chamomile and green tea; and its salts and prodrugs.

[0094] In one embodiment, the carrier contains a plant extract. Examples of plant extracts include, but are not limited to: wild chamomile, soybeans, soy glycine, oatmeal, wheat (what), aloe vera, red berries, witch hazel, alder, arnica, cylindrica, Asarum root, white birch, calendula, chamomile, Japanese velvet grass, daisy, fennel, gallnut, hawthorn, Kaicai, hypericum, jujube, kiwi, licorice, magnolia, olive, peppermint , Philodendron taro, Sasa albo-marginata, natural isoflavones, soy isoflavones and natural essential oils.

[0095] In one embodiment, the support contains metals, such as metal ions, metal salts, metal complexes, fine metal powders, metal-coated fine fibers 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. Metal ions provide effects such as antibacterial, anti-inflammatory and/or sebum reduction. This beneficial metal ions can be released by the electrochemical oxidation reaction of the metal anode (for example, zinc ions are electrochemically generated from the zinc anode), which is accompanied by the passage of current at this time.

[0096] In another embodiment, such beneficial ions may indirectly come from electrochemical reactions on the electrode surface, such as hydrogen and hydroxide ions generated at the inert electrode, and then proceed to the process of generating beneficial ions. For example, the device of the present invention may contain a power source, inert electrodes (for example, clamps, clamp-coated conductive electrodes, gold or gold-coated conductive electrodes), reactive cathodes (for example, silver/silver chloride electrodes), and other active electrodes. An aqueous carrier composition containing oxides (such as zinc oxide particles) in the agent. When applied to the skin, the excess hydrogen ions generated by the electrolysis of the inert anode water acidify the carrier to a lower pH value, while the electrochemical reaction at the reactive electrode (such as the conversion of silver chloride to silver ions) does not Affect pH. As the solution becomes more and more acidic, oxides begin to dissolve and release ions (such as zinc ions), which has a beneficial effect on the barrier film.

[0097] Other active agents include those commonly used for topical and cosmetic treatment of skin tissues, such as topical antibiotics for wounds, topical antifungals for the treatment of fungal infections of the skin and nails, treatment of skin psoriasis lesions and psoriatic nails Of antipsoriatic drugs.

[0098] Examples of antifungal drugs include, but are not limited to: miconazole, econazole, ketoconazole, sertacan, itraconazole, fluconazole, voriconazole , Chloriodine, Bifoconazole, Teconazole, Buconazole, Saconazole, Oxyconazole, Thioconazole, Saconazole, Clotrimazole, Undecylenic acid, Halogen Progen, Butenafen, Tonalamate, Nystatin, Cyclopyridone, Terbidafen, Amorolfine, Datifen, ElubioL griseofulvin and its pharmaceutically acceptable salts and Prodrug. In one embodiment, the antifungal agent is pyruvate, allylamine, or a mixture thereof.

CN 1829552 Β

[0099] Examples of antibiotics (or disinfectants) include, but are not limited to: mupirocin, neomycin sulfate, polymyxin B, 1-ofloxacin, tetracyclines (chlortetracycline hydrochloride, hydrochloric acid Oxytetracycline-10 and tetracycline hydrochloride), clindamycin phosphate, gentamycin sulfate, metronidazole, hexaresorcin, methylbenzole, phenol, quaternary saddle compounds, tea tree oil and its pharmacy Acceptable salts and prodrugs.

[0100] Examples of antibacterial agents include, but are not limited to, salts of chlorhexidine, such as lodopropynyl butylaminomethyl, diazolidinyl urea, chlorhexidine digluconate, and chlorhexidine acetate , Chlorhexidine Ethyl Sulfate and Chlorhexidine Hydrochloride. Other cationic antibacterial agents can also be used, such as benzalkonium chloride, benzalkonium chloride, tricarbon, polyhexylidene bimonthly melon, sipyridine chloride, methyl andbenzothonium chloride (methyl andbenzothonium chloride) ο Other antibacterial agents include, but are not limited to: halogenated phenolic compounds, such as 2,4,4,-trichloro-2-methyldiphenyl (triclosan); p-chlorom-xylenol (PCMX); short Chain alcohols, such as ethanol, propanol, etc. In one embodiment, the alcohol is preferably at a low concentration (e.g., less than about 10% of the weight of the carrier, such as less than 5% of the weight of the carrier) so that it does not cause excessive drying of the barrier film.

[0101] Antipsoriatic drugs or drugs used to treat seborrheic dermatitis include, but are not limited to: corticosteroids (for example, betamethasone dipropionate, betamethasone valerate, clobetasol propionate, diacetate difluoro Larson, halbetasol propionate, triamcinolone, dexamethasone, fluocinolone acetate, fluocinolone, hacinonide, triamcinolone acetate, hydrocortisone, hydrocortisone valerate, hydrocortisone butyrate Pine, aclomethasone dipropionate, fludrocortisone, mometasone furoate, prednisone methyl acetate), methotine, cyclosporin A, calcipotriene, scallion, Shale oil and its derivatives, elubiol, ketoconazole, coal tar, salicylic acid, zinc pyrithione, selenium disulfide, hydrocortisone, sulfur, menthol and promorphaine hydrochloride and its salts and precursors medicine.

[0102] Examples of antiviral agents for viral infections such as herpes and hepatitis include, but are not limited to: imiamod and its derivatives, pudafilox, podophyllo resin, interferon alpha, acyclovir, famciclovir , Valacyclovir, reticulos and cidofovir and their salts and prodrugs.

Examples of anti-inflammatory agents include, but are not limited to, suitable anti-inflammatory agents for the body, such as corticosteroids such as hydrocortisone, triamcinolone, α-methyldexamethasone, dexamethasone phosphate, monopropionic acid Beclomethasone, Clobetasol Valerate, Desonide, Deoxymethasone, Deoxycorticosterone Acetate, Dexamethasone, Diclosone, Diflurazone Diacetate, Diflumethasone Valerate, Fluadrenolone, Fluclonacl German, fludrocortisone, diflumethasone pivalate, fluosinolone Acetonide >fluosinolone acetonide, flucortine butylester, fluocorone, fluprednidine acetate, flucortisone, hexonide, Hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodosone, flucetonide, fludrocortisone, difluorosone diacetate, fludrocortisone, formazan Suspected pine, ancifel (amciafel), anxifete, betamethasone, cloprednisone, cloprednisone acetate, clocotrolone, clescinolone, diclosone, difluprednisolone, fluodiclosone, Flunisolide, fluorometholone, fluoroperone, fluoroprednisolone, hydrocortisone valerate, hydrocortisone cyclopentyl propionate, hydrocortate, methylprednisolone, paramethasone, prednisone Songlong, prednisone, beclomethasone dipropionate, betamethasone dipropionate, triamcinolone and its salts and prodrugs. In the present invention The preferred anti-inflammatory agent used is hydrocortisone. The second class of anti-inflammatory agents that can be used in the compositions of the present invention includes non-body anti-inflammatory agents.

[0104] Other active agents include, but are not limited to: wound healing promoters, such as recombinant human platelet-derived growth factor (PDGF) and other growth factors, ketanserin, iloprost, alprostadil E1 and hyaluronic acid; scar Lightening agents such as mannose-6-phosphate, analgesics, anesthetics, hair growth enhancers such as minoxidil; hair growth blockers such as eflornithine hydrochloride; antihypertensive drugs; treatment of coronary artery disease Anticancer drugs; endocrine and metabolic drugs; neuropathic drugs; drugs that block chemical addition and motion sickness; protein and peptide drugs.

[0105] In one embodiment, the carrier contains fragrances that can effectively reduce stress, calm and/or promote sleep, such as smoke

CN 1829552 Β

Cloth and camomile.

[0106] The amount of active agent in the carrier will depend on the specific use of the active agent and/or device. In one embodiment, the carrier contains a safe and effective amount of active agent, for example, about 0.001%-20% of the weight of the carrier, for example about 0.01% -5% of the weight of the carrier.

[0107] Light Emitting Diode

[0108] In one embodiment, the device contains one or more light emitting diodes. The device may include a light-emitting diode (LED) of a certain spectrum in order to emit light onto the barrier membrane (for example, to treat skin conditions such as acne and erythema). The light-emitting diode can also provide a signal to the user that the device is operating normally.

[0109] In one embodiment, the LED emits periodic light (ie, blinking the LED). In another embodiment, the LED also regulates the current passing through the barrier film to form a pulsating DC current. This pulsating DC current can promote the delivery of the active agent into the barrier membrane and stimulate the biological response in the barrier membrane, such as promoting the healing of wounds (such as in acne injuries) and/or strengthening the skin sensation to provide the user with the functioning device signal. Another potential advantage of using blinking LEDs is to provide pulsating DC current without the need for complex circuits.

[0110] The spectrum of the LED of the present invention is about 300nm-1500nm, for example, about 350nm-1000nm_oIn one embodiment, the range of the LED includes violet-blue, green, red and infrared ranges, such as about 400nm-450nm, for example, about 407nm-420nm; about 510nm-550nm; about 600nm-700nm; about 1300nm -1500nm_oIn one embodiment, the device has two LEDs, one emitting light with a wavelength of about 400nm-500nm, and one emitting light with a wavelength of about 700nm-1000nm. The carrier may contain photosensitizers, such as 5-aminolevulinic acid (ALA), hypericin, St. Johns malt powder or extract, or other synthetic or natural photosensitizers as active agents. The device delivers and radiates the active agent. The light radiation from the LED, as well as the photosensitizer and other above-mentioned active agents, electrochemically generated oxidants (such as peroxides, nascent oxygen, chlorine dioxide and chlorine), and/or electrical stimulation of the barrier film can work synergistically to The treatment of membrane diseases such as acne and erythema acne can achieve an improved effect.

[0111] General Purpose

[0112] In one embodiment, the device is used for the treatment of barrier membrane diseases (eg delivery of active agents light and/or electricity into membranes such as skin, eyes (stratum corneum, retina, etc.), mouth, cheek, nose, vagina, stomach The intestinal or rectal mucosal barrier membrane). In one embodiment, the device is used to treat skin diseases. Examples of such treatments include, but are not limited to: treatment of acne, erythema, or other skin microbial infections; reduction of visible features of skin aging (eg, wrinkles, sagging, and age spots); folliculitis and pseudofolliculitis of the hair; Treat wounds and wounds (for example, promote healing and lighten scars); sebum regulation (for example, reduce sebum or inhibit or control the appearance of oily/glossy skin); pigmentation (for example, reduce hyperpigmentation or hyperpigmentation of light-colored skin) ; Hair growth blockers (for example, skin on the legs) or hair irritation (for example, scalp); and treatment of dermatitis (for example, atopic dermatitis, contact dermatitis or seborrheic dermatitis) and/or psoriasis.

[0113] In another embodiment, the device is used to treat mucosal (such as oral mucosa or vaginal mucosa) diseases. Examples of such treatments include, but are not limited to: treatment of vaginal candidiasis and vaginosis, genital and oral herpes, cold sores, mouth sores, oral hygiene, periodontal disease, and other mucosal microbial infections.

[0114] Another embodiment of the present invention is a device that can cause a certain desired biological response, which can facilitate the treatment of barrier membrane conditions. This desired biological response can be caused by electrical connection through the barrier membrane, and/or electrochemically generated oxides, which together with the active agent can be transferred from the carrier through self-osmosis, and are used to treat barrier membrane diseases. Examples of desired responses of barrier membranes include, but are not limited to: sebum regulation (e.g., reduction of sebaceous gland activity), inhibition of the growth of anaerobic microorganisms and establishment of a healthier membrane microbiota or (e.g., reduction of the growth and reduction of P. acnes Stimulating fatty acid production), blood vessels

CN 1829552 Β

Contraction (thereby promoting the local accumulation of active agents or removing dark circles due to deoxyhemoglobin), enhanced tissue immune activity (for example, increased clearance of pathogenic microorganisms from the tissues own defense system), and improved tissue repair (for example, enhanced healing and diminished Injury scars such as spasm scars), as well as the improvement of the stratum corneum separation activity of the carrier (for example, softening the acne cutin plugs in acne miliaria and blackheads and promoting their removal).

[0115] On the other hand, the present invention also provides the oxidation or reduction of an inert electrode to convert the active agent from a less active form to a more active form (for example, the conversion of cystine to cysteine, acetyl disulfide -The method of converting cysteine into acetyl-cysteine and converting vitamin A into tretinoin). Therefore, unstable reagents can be stored in a more stable form and converted to their active form before administration. In another aspect, the reducing agent produced by the device of the present invention can be used to stabilize the oxygen-sensitive active agent. Examples of such oxygen-sensitive active agents include, but are not limited to, tretinoin, ascorbic acid, and benzoyl peroxide.

[0116] In one embodiment, the present invention also provides a reactive anode, such as an anode composed of zinc, magnesium, copper, aluminum, alloys or mixtures of these metals, to perform oxidation to convert the active agent from a less active form It is a more active form of method. For example, as the electrical connection passes through the electrode, the anode made of zinc releases zinc ions. Then, the zinc ions generated by this electrochemical reaction are transferred into the barrier membrane by positive charge electric repulsion. In one embodiment, such ions are deposited in hair follicles and/or sebaceous glands, thereby inhibiting the growth of P. acnes and/or inhibiting skin tissue infections due to overgrowth of P. acnes before treatment. Similarly, a zinc-copper alloy anode or another zinc-beneficial metal alloy releases zinc ions and copper ions or zinc ions and another beneficial ion into hair follicles and sebaceous glands, respectively, for the treatment and prevention of acne.

[0117] Skin diseases

[0118] In one embodiment, the device of the present invention is used to treat skin diseases, such as: acne and acne (for example, blackhead and milia) and acne-related skin diseases such as erythema and nodule-cyst; Excessive pigmentation such as freckles, dark spots, actinic and age spots, age spots, excessive melanosis after inflammation, Becker's nevi, dark circles, facial melanosis; stress marks; skin aging effects on the skin (for example, due to Photodamage) including wrinkles, roughness, pigment changes, paleness, fine lines and relaxation, by passing the pre-formulated active agent contained in the carrier and the electrochemically generated active agent (such as beneficial metal ions) through the electrode, and/ Or by providing electrical stimulation to the skin tissue.

[0119] In one embodiment, the device of the present invention provides multiple mechanisms of action to treat the above-mentioned diseases: (a) through iontophoresis and electroosmosis, the pre-formulated active agent is targeted to deliver into the hair follicle sebaceous gland unit; (b) ) Electrochemically generate new active agents (for example, beneficial metal ions from reactive anodes) and target the freshly generated active agents to the hair follicle sebaceous gland unit (for example, beneficial ions such as zinc and copper are known to enhance skin autoimmunity System); and/or (c) provide electrical stimulation of the hair follicle sebaceous gland unit and surrounding skin tissue to increase blood circulation, and treat skin diseases by reducing inflammation, promoting wound healing and/or increasing skin exfoliation.

[0120] Wounds and scars

[0121] In one embodiment, the device of the present invention may be included in wound dressings and wound dressings to provide electrotherapy for enhancing healing and preventing scars. In one embodiment, wound exudate and/or wound lotion is used to activate the electrical wound dressing/dressing, and the active agent and/or electrochemically generated beneficial metal ions pre-contained in the wound dressing/dressing are transferred Into the wound. The device can also use therapeutic current to treat wounds. The therapeutic current can increase blood circulation, stimulate tissue immune response and/or inhibit tissue inflammation, thereby accelerating healing and scarring.

[0122] Enhanced chemical peeling

[0123] Chemical peeling treatment is a method in use in which chemical agents are applied to the skin to cause controlled destruction or exfoliation of old skin and stimulate the growth of new epidermis with a more uniform distribution of melanin. When the peeling reagent reaches the dermis

At the same time, it produces important wound healing activity, leading to skin remodeling and skin smoothing, both of which have anti-aging effects. In many skin diseases, including but not limited to acne, hyperpigmentation after inflammation, dark spots, scars, light damage, age spots, wrinkles, stress marks, birthmarks, uneven texture and tone, warts and pseudofolliculitis of the hair In the treatment, a chemical peeling agent contained in the electrogenerating device/composition can be delivered. The device/composition also has the added advantage of reducing skin irritation and reducing the risk of pre-cancerous and early cancer damage to the photo-aged skin on the face, because iontophoresis gives chemical peeling agents and standard chemical peeling methods that do not use such devices In comparison, much lower chemical peeling agent concentrations can be used. The reduction of the chemical peeling agent required can also minimize the risk of erythema, inflammation and scars after continuous peeling from chemical peeling while achieving the desired effect.

[0124] Examples of chemical peeling agents include, but are not limited to: doubt acid such as α- doubt acid, such as lactic acid, malic acid, glycolic acid, glycolic arginine, glycolic acid saddle and sodium glycolate; 3-doubt acid Acids such as salicylic acid; doubtful acids (PHA) such as gluconolactone; and non-doubtful acids such as acetic acid, trichloroacetic acid (TCA), pyruvic acid and α-keto-acids, phenol and their derivatives or mixtures . They can also be combined with sulfur, resorcinol, retinoic acid or other active agents such as Jessner solution peeling agent (which contains lactic acid, salicylic acid, resorcinol and ethanol). The chemical peeling agent of the present invention may also include, but is not limited to: protease reagents or derivatives thereof, such as apoprotease, holoenzyme, idoenzyme, or acid protease in the form of zymogen. Examples include pepsin, bromelain, papain and cathepsin. Examples also include naturally-derived chemical peeling agents such as fruit extracts, mushroom extracts and other plant extracts.

[0125] In one embodiment, the application time of the device on the skin is about 2-10 minutes, depending on the individual's skin condition. In one embodiment, the carrier contains about 0.1% to 70% by weight of a chemical peeling agent, for example, about 0.5% to 20%, for example, about 2% to 10%.

[0126] Shape

[0127] The device includes a housing, which can be configured in various shapes and sizes to match the contours of various tissue surfaces of the barrier membrane. For example, the outer shell may be a kind of substrate, shaped as the entire mask with openings/holes to expose the eyes, eyebrows, nose and mouth; only cover part of the upper or lower part of the face; or cover only the forehead, or Patches under the eyes, chin and mandibular areas, neck, back, wounds, acne injuries or pustules or other specific barrier membrane areas that require treatment.

[0128] In one embodiment of the present invention, the housing is a water-insoluble substrate, which contains galvanic couples such as fine zinc wires or zinc-coated fine fibers (for example, zinc-coated polymer fibers) connected to the fine Copper wires or copper-coated fine fibers (for example, copper-coated polymer fibers). The substrate may contain one or more of such fine galvanic wires or fibers to produce a device that can generate an electric current when in contact with a carrier (for example, tap water or a liquid or semi-liquid composition containing an active agent). In one embodiment, the substrate containing the galvanic couple may be composed of multiple layers, for example, a layer of zinc-containing substrate (for example, fine zinc threads or zinc-coated fine fibers in a woven or non-woven fabric). A layer of copper-containing substrate (for example, thin copper wires or copper-coated thin fibers in woven or non-woven fabrics). When in use, the layers contact each other to form a galvanic couple. In another embodiment, the device releases beneficial ions (e.g., zinc ions or aluminum ions) when the user applies the substrate (e.g., as a wipe to clean the skin or as a face patch or mask to treat the skin) , These beneficial ions are delivered to the barrier membrane (such as the skin). The active agent can also be added to the substrate during the production process, or applied to the substrate before being applied to the barrier film (for example, the substrate is wetted in the form of an electrolyte or a liquid spray containing the active agent). In one embodiment, the fabric is used as a dry wipe or all or part of a dry mask, which is moistened just before use. At this time, water is added to the dry wipe or Mask to pre-moisturize the skin (for example, by washing with tap water).

[0129] "Water-insoluble" means that the substrate is not easily dissolved or decomposed when the substrate is immersed in distilled water at 25°C. However, the water-insoluble substrate may disintegrate or slowly dissolve, for example, in a period of several hours to several days. Many materials can be used as water-insoluble substrates. Examples of suitable substrates include, but are not limited to: non-woven substrates, woven substrates, hydro-entangled substrates, air-entangled substrates

Materials, natural sponges, synthetic sponges and polymer screens.

[0130] The water-insoluble substrate can be washed away. As used herein, "flushable" means that in two toilet flushes, the substrate can pass through at least 10 feet of sewage pipe. The material can also be biodegradable.

[0131] In one embodiment, the substrate contains a non-woven material. "Non-woven" means that the substrate or a layer of substrate is composed of fibers that are not woven into a fabric but form a sheet, felt, or cushion. The fibers can be random (that is, randomly arranged) or combed (that is, the machine is combed to be mainly oriented in one direction. Moreover, the non-woven substrate can be composed of a combination of a random fiber layer and a combed fiber layer). [0132] The non-woven substrate can be composed of a variety of natural and/or synthetic materials. "Natural" refers to materials derived from plants, animals and insects or by-products of plants, animals and insects. "Synthetic" means that materials are mainly obtained from various artificial materials or further processed from natural materials. Non-limiting examples of natural materials used in the present invention are silk cellulose, keratin fibers (such as wool fibers, camel hair fibers) and cellulose fibers (such as wood pulp fibers, cotton fibers, hemp fibers, jute fibers, and flax fibers) ).

[0133] Examples of synthetic materials include, but are not limited to: acetate fiber, acrylic fiber, cellulose ester fiber, cotton fiber, modified polyacrylic fiber, polyamide fiber, polyester fiber, polyene fiber, polyvinyl alcohol fiber , Rayon fibers, polyurethane foam materials and their mixtures.

[0134] Substrates composed of one or more natural and synthetic materials that can be used in the present invention can be obtained from a variety of commercial sources¹J, such as Freudenberg & Co. (Durham, NC USA), BBA Nonwovens (Nashville, TN USA), PG I Nonwovens (North Charleston, SC USA)> BuckeyeTechnologies/Walkisoft (Memphis, TN USA) and Fort James Corporation (Deerfield, IL USA) ).

[0135] Methods for preparing non-woven substrates are also well known in the art. These methods include, but are not limited to: air-laid, water-laid, meltblown, spunbond, or carding methods. Then, regardless of the preparation method or composition, the resulting substrate is subjected to at least one of several bonding methods to fix the fibers together to form a self-supporting net. Non-woven substrates can be prepared by a variety of methods, including hydroentanglement, thermal bonding, and a combination of these methods. Furthermore, the substrate may have a single layer or multiple layers. In addition, the multilayer substrate may include film layers (e.g., porous or non-porous film layers) and other non-fibrous materials.

[0136] The strength and firmness of the nonwoven material may be desirable characteristics. This can be achieved, for example, by adding bonding materials such as wet strength resins, or by polymer bonding coatings, such as materials based on stable fibers such as cotton, wool, and flax. Wet strength resins include but are not limited to: ethyl acetate-ethylene (VAE) and ethylene-vinyl chloride (EVCL) Airflex emulsion (Air Products, Lehigh, PA), Flexbond acrylic polymer (Air Products, Lehigh, PA), Rhoplex ST -954 Acrylic adhesive (Rohm and Haas, Philadelphia, PA) and ethylene-vinyl acetate (EVA) emulsion (DUR-O-SET ®, National Starch Chemicals, Bridgewater, Town). The amount of binding material in the substrate may be about 5%-20% of the weight of the substrate.

[0137] The so-called spunlace or hydroentanglement technique can also be used to obtain strength to increase the strength of the non-woven material. In this technique, the fibers are kinked together to obtain acceptable strength and firmness without the use of adhesive materials. The advantage of the latter technique lies in the excellent flexibility of the non-woven material.

[0138] In one embodiment, the nonwoven material is composed of a superabsorbent polymer. For the present invention, the term "superabsorbent polymer" refers to a material that can absorb and retain at least about 10 times its weight in body fluids under a pressure of 0.5 psi. The superabsorbent polymer particles of the present invention may be inorganic or organic cross-linked hydrophilic polymers, such as polyvinyl alcohol, polyethylene oxide, cross-linked starch, guar gum, xanthan gum, and others known in the field of absorbent product manufacturing material.

[0139] Additives can also be added to increase the flexibility of the substrate. Examples of such additives include but are not limited to: polyols such as glycerol, propylene glycol and polyethylene glycol, phthalate derivatives, citrate esters, surfactants such as polyoxyethylene

(20) Sorbitan esters and acetylated monoglycerides.

[0140] Sensory characteristics may also be included in the insoluble nonwoven substrate. Examples of such sensory characteristics include, but are not limited to: color, texture, style, and embossing.

[0141] In one embodiment, the device of the present invention is used as wipes and towels (for example, having a surface area of about 20 cm²-10, 000cm²). In another embodiment, the device of the present invention is used as a therapeutic patch or mask, applied to a part or substantially all of the face (for example, having a surface area of about 1 cm²-600cm²） _o

[0142] In one embodiment, prior to use, the carrier is present at least about 50% of the total weight of the water-insoluble substrate, such as at least about 75%. In another embodiment, (i) the liquid carrier present is at least about 10% of the total weight of the water-insoluble substrate, such as less than about 1% (for example, the device may not contain a carrier before use). In another embodiment, the product contains instructions for use that instruct the user to (i) wet the substrate or (ii) wet the barrier film (eg, skin) with water and/or another liquid before application.

[0143] Device

[0144] An embodiment of the present invention is schematically represented as FIG. 1. The device 500 includes: a removable release liner (release liner) 100, a carrier layer 120, a first conductive electrode 140, a second conductive electrode 240, and two ends of the electrically insulated connection line 350 are connected to two different conductive electrodes. Electrical wires 110 and 210, an optional power switch 330 on the wire 210, a backing layer 160, and a cover layer 340.

[0145] The interval "b" indicates the distance between the two conductive electrodes 140 and 240 and the release liner (or the film after the device is applied), and the interval "a" indicates the distance between two conductive electrodes with opposite charges. In one embodiment, the interval "a" is about 0-20 cm, and the interval "b" is about 0-1 cm. In another embodiment, the ratio of the interval "a" to the interval "b" is about 0-20 ο

[0146] In a device including a battery as a power source, in the figure, a battery (not shown) may be used in place of the electrically insulated connecting wire 350. The battery can be mounted on an electrically insulating, water-impermeable polymer layer (not shown in the figure). Optionally, there may be a circuit (not shown) in the device 500 to provide a constant current between the battery (not shown) and the conductive electrode 140 and/or the conductive electrode 240.

[0147] When a zinc-air battery is used as the power source of the device 500, the configuration of the battery (not shown) enables the holes in the stainless steel cover to face the opposite side of the carrier layer 120. Holes are punched in the battery cover to expose the holes on the zinc-air battery covered by the removable oxygen impermeable cover. In this case, the power switch 330 is replaced by a removable oxygen impermeable cover. This removable oxygen impermeable cover can be used to initiate (by removing it) or stop (by re-covering holes) the electrotransport process of the device.

[0148] The backing layer 160 is impermeable to the active agent contained in the carrier layer 120, and is preferably impermeable to water and other solvents in the carrier layer 120. The backing layer 160 and the cover layer 340 may be composed of a flexible material that is water-impermeable and electrically insulating, such as a polymer, such as polyethylene, polypropylene, polyvinyl acetate, polyurethane, silicone rubber, or polyvinyl chloride.

[0149] In another embodiment, the backing layer 160 is permeable to electrochemically generated gases (such as oxygen, chlorine, and hydrogen) to limit the excessive accumulation of gas in the carrier, because such excessive accumulation of gas can lead to Irritating to human tissues and/or undesirable deformation of the device. Examples of such "breathable backing" materials include, but are not limited to, cotton or synthetic woven fabrics and non-woven fabric layers, such as fabric materials commonly used in bandages and sports bandages.

[0150] The carrier layer 120 is an adhesive hydrogel containing an active agent. The active agent contained in the carrier layer 120 may be dissolved molecules or ions, dispersed solid particles, or droplets such as cream, lotion, emulsion, multiphase emulsion, microemulsion and/or liposome composition . The carrier layer 120 may also contain a solid support matrix (for example, gauze, non-woven material, or sponge-like material).

[0151] The removable liner layer 100 covers the carrier layer 120. The choice of the removable release liner 100 depends on the type of adhesive hydrogel used in the carrier layer 120. The release liner layer 100 is typically a polymer layer or paper or a fabric coated with a polymer, which has weak adhesiveness to the adhesive hydrogel layer 120 so that it can be easily removed from the carrier layer before use. 120 is removed without damaging the carrier layer 120. Examples of polymers commonly used as release liner 100 are silicone and polyethylene. Alternatively, wax can be used instead of polymer to coat the release liner 100.

[0152] In addition to the adhesive used in the carrier layer 120, or instead of the adhesive used in the carrier layer 120, tapes, elastic bands, belts with buckles (similar to leather straps) or Velcro ® belts can be used. The device 500 is fixed on the barrier film.

[0153] When using the device 500, peel off the removable release liner layer 100, and fix the carrier hydrogel layer of the device 500 on the barrier membrane of the user, such as skin or mucous membranes such as vagina, mouth, cheek, nose, and stomach On the mucosal barrier membrane of the intestine or rectum. If the carrier layer 120 contains an adhesive hydrogel, the device can be directly fixed to the barrier film. The power switch 330 is turned on to apply a potential difference between the conductive electrodes 140 and 240.

[0154] Another embodiment of the present invention is schematically represented as FIG. 2. The electrically insulated connecting wire 350 is located in the carrier layer 120. The advantages of this structure are reduced volume, increased aesthetics and comfortable use.

[0155] The light-emitting part of the LED 122 is preferably located in the carrier layer 120 close to the skin. Placing the light source in the carrier layer 120 fixed to the barrier film has the advantage of minimizing the loss of light energy due to reflection on the skin surface. In addition, using a light reflective layer (for example, a metalized polymer film) as the backing layer 160 can further improve the light curative effect and achieve more uniform irradiation. Optionally, the backing layer 160 may be perforated as some points that make the light visible to the user, and serve as an indication that the device is functioning normally.

[0156] Another embodiment of the present invention is schematically represented as FIG. 3. The backing layer 160 (for example, a shell) includes an adhesive layer 130 coated on the outer edge of the backing layer 160 to fix the device on the barrier film during use. The adhesive in the adhesive layer 130 may be polymeric, pressure sensitive, and/or non-conductive. Suitable adhesive materials include, but are not limited to: silicone, polyisobutylene and its derivatives, acrylic resin, natural rubber, and combinations thereof. Suitable silicone adhesives include, but are not limited to, Dow Corning 355 (available from Dow Corning of Midland, MI); Dow Corning X7-2920; Dow Corning 0X7-2960; GE6574 (available from General Electric Company of Waterford, NY) ); Silicone pressure sensitive adhesive. Suitable acrylic adhesives include, but are not limited to, vinyl acetate-acrylate polymers, including, for example, Gelva-7371 (available from Monsanto Company of St. Louis, MO); Gelva T7881; Gelvac 2943; 1-780 medical grade adhesive, available from Avery Dennison of Painesville, OH; and acrylic pressure sensitive adhesive.

[0157] One embodiment of the present invention is a dual packaging system, in which the electrical device and the carrier (or part of the carrier) are separately packaged. A part of the carrier layer 120 may be a substrate for immobilizing anhydrous liquid, such as a dry woven fabric or non-woven fabric, a sponge or a dehydrated hydrogel layer (for example, a freeze-dried hydrogel), and the liquid part of the carrier, such as containing The active agent solution, gel, or cream is packaged in a separate liquid-containing chamber (not shown in the figure), such as a unit-dose pouch, gas-permeable container or vial. Before use, the liquid-containing chamber is opened, and the liquid or semi-solid part of the carrier is applied to the liquid-fixed matrix to activate the generation of electric current for skin application. The active agent is contained in a liquid-fixed matrix or liquid/semi-solid composition.

[0158] An embodiment of the present invention is schematically represented as FIG. 4o conductive electrodes 140 and 240 are electrically connected to each other through a direct connection, that is, the interval "a" (the distance between two oppositely charged conductive electrodes) is equal to zero. The two conductive electrodes form a galvanic couple, the galvanic couple is in contact with the carrier layer 120, the carrier layer 120 is encapsulated in the backing layer 160, and the opening is fixed to the release liner 100 with an adhesive layer 130. One of the main advantages of this structure is It is simple and easy to manufacture.

[0159] Another embodiment of the present invention is schematically represented as FIG. 5. The electrotransport device 800 includes two electrode groups

CN 1829552 Β

Pieces 200 and 600, respective adhesive layers 230 and 630, respective carrier layers 220 and 620, respective conductive electrodes 240 and 640, respective backing layers 270 and 670, respective electrical leads 210 and 610, electrically insulating connection Line 350 and optional electrical switch 330. Similar to the above-mentioned typical iontophoresis device, after the release liner 100 is removed before use, the two electrode assemblies 200 and 600 are respectively fixed on the barrier film.

[0160] In one embodiment, the carrier layer 120 includes at least two oppositely charged active agents. An example of such a composition is containing about 0.5-2% salicylic acid and about 0.01-0. 2% cationic quaternary antimicrobial agent (for example, benzalkonium chloride, benzalkonium chloride, methyl knot A combination of soclosan and xipiclosan), phenol and/or chlorhexidine gluconate. The device 500 of the present invention can simultaneously transfer the oppositely charged active agents into the barrier film.

[0161] FIGS. 6 and 7 show two different configuration embodiments of different conductive electrodes 140 (represented by a double line) and 240 (represented by a single line) in the carrier layer 120, the two conductive electrodes passing through an electrically insulated wire 350 (Indicated by three lines) connected to form a galvanic battery power supply. FIG. 6 shows that the conductive electrodes 140 and 240 are arranged in a mutually staggered configuration. Figure 7 shows that the conductive electrodes are in a concentric configuration.

[0162] FIGS. 8 and 9 show two different configuration examples of different conductive electrodes 140 and 240 in the carrier layer 120, through the connecting line 350 as shown in FIG. 8 or through the junction as shown in FIG. 9 370 are in direct physical contact and are connected to each other to form a plurality of galvanic battery power supplies, and these galvanic battery power supplies are in contact with the carrier layer 120. The conductive electrodes 140 and 240 in FIGS. 8 and 9 are in a parallel configuration and a vertical configuration, respectively.

[0163] In FIG. 8, the alternate parallel arrangement of the conductive electrodes 140 and 240 makes the current distribution of the entire carrier layer 120 and the underlying skin tissue more uniform, thereby helping to more uniformly deliver the active agent into the skin. An exemplary manufacturing method for forming the galvanic cell device shown in FIG. 8 is to knit the silver-coated polymer fabric and the zinc-coated polymer fabric (or zinc wire) into a liquid-absorbing fabric layer according to the pattern of parallel electrodes. Then, by printing with conductive ink (for example, conductive silver ink or carbon ink) on the silver area and the zinc area, the zinc electrode and the silver electrode are connected. Another layer of electrically insulating ink is covered on the conductive ink to produce an electrically insulating connection line 350.

[0164] Another manufacturing method of the device of FIG. 8 is by printing: printing with conductive silver or silver-silver chloride ink on a non-conductive polymer substrate layer (for example, a polymer material composed of a backing layer 160) , Produce the first conductive electrode; Use conductive zinc ink to print out the second conductive electrode. Then, use conductive silver ink or zinc ink (or different conductive ink such as carbon ink) to print through two different conductive electrodes to connect them. Then, an overlay ink is optionally printed on the connecting wires to create an electrically insulating polymer layer on the connecting wires. If a device is manufactured that does not use an electrically insulating cover layer for insulation, the resulting device is a variant of the device shown in FIG.

[0165] FIG. 9 is a top view of an embodiment of the present invention, showing that the conductive electrodes 140 and 240 are connected to each other by direct physical contact at the junction 370 to form a plurality of galvanic battery power supplies. It is in contact with the carrier layer 120. The conductive electrodes 140 and 240 are arranged in a vertical configuration. The manufacturing method of the device of Fig. 8 described above is also suitable for manufacturing such a device.

[0166] FIG. 10 is a top view of an embodiment of the present invention, showing a device made of zinc mesh with conductive electrodes 140 (represented by thick lines) and conductive electrodes 240 (represented by double lines), the two conductive electrodes are embedded in the carrier The electrically insulated connecting wires 350 (indicated by a single line) in the layer 120 are connected. The conductive electrode 140 is an uncoated area of the zinc mesh. The conductive electrode 240 is prepared by coating a designated portion of the zinc mesh with silver-silver chloride ink. The electrically insulated connecting wire 350 is prepared by coating a designated part of the zinc mesh with an electrically insulating paint, ink, or polymer solution.

[0167] FIG. 11 is a top view of an embodiment of the present invention, showing that the conductive electrodes 140 and 240 are embedded in the carrier layer 120. The conductive electrode 140 is composed of a piece of zinc mesh. The conductive electrode 240 is deposited by using silver-silver chloride ink or silver ink, or other silver

CN 1829552 Β

Methods such as electroless deposition (chemical reduction deposition), electroplating, plasma spraying, or vacuum deposition, coating the designated part of the zinc mesh preparation. Eliminating the electrically insulated connecting wire 350 in this structure can simplify the production process. The position, style, shape and size of metallic silver, silver-silver chloride or silver-silver oxide electrodes can be changed according to the needs of specific products.

[0168] A zinc mesh can be prepared from a thin layer of zinc foil by mechanical perforation and then expanded into a mesh pattern (or commonly referred to as "mesh zinc" in the battery and anti-corrosion field). The main advantage of the zinc mesh anode in the galvanic cell device of the present invention is the user's ability to form and retain the desired shape of the mask/patch, and the user can stretch in any direction to form the desired size of the mask/patch ; And breathable.

[0169] It should be noted that although an example of using zinc mesh as the electrode pattern is described herein, other above-mentioned materials suitable for galvanic cell formation and for conductive electrodes can also be made into mesh or porous form to provide The same function.

[0170] Lightly press the zinc mesh, it can also fit the shape of the film surface (for example, the shape of an individual's face) and maintain the shape. This ability makes it uniquely suitable for use as a facial mask or certain skin patches to better match certain anatomical features of the face (such as nasal patches) or body regions. This unique property also contributes to better electrical contact and also reduces reliance on the use of adhesives to secure the device to the skin.

[0171] If the mask or patch can be expanded into different sizes to cover a specific skin area without compromising its electrical properties, it will be very convenient and desirable for consumers. Zinc mesh anodes (or other mesh conductive electrodes) are uniquely able to meet this consumer need. In another embodiment, the net is not expanded before use to make the device smaller and denser to facilitate storage and portability. Instead, it is stretched to the required size by the consumer during use.

[0172] Good air permeability is important for larger-sized masks or patches, especially when the device is designed to be worn by the user for a longer period of time (for example, more than half an hour, such as overnight). In order to make the aforementioned device extensible and/or breathable, the carrier layer 120 and the backing layer 160 should also be extensible and breathable, such as extensible woven fabrics and non-woven materials.

[0173] In another embodiment, for facial masks and patch devices, the backing layer 160 in FIGS. 3-5 can be perforated or completely removed, which is particularly suitable for short-term applications, such as about 5-30 minutes. As the water in the carrier composition evaporates, the conductance and current decrease. Eventually, the current will be significantly reduced, essentially providing a self-terminating device as a safety measure for the user to prevent any unintentional over-effect of the skin by the current and potential ultimate skin damage.

[0174] An example of such a self-terminating device is a galvanic fabric mask composed of zinc mesh partially coated with silver-silver chloride ink, which is placed on the back using a bonding method based on heating, ultrasound or other mechanisms. Between the lining film/shell (for example, perforated or non-perforated polyethylene film) and non-woven fabric (for example, polyester and/or rayon non-woven fabric). Before use, it will contain ionic and non-ionic active agents and other An optional electrolyte liquid or semi-liquid carrier composition is applied on the non-woven fabric surface of the device to activate the galvanic battery power source. Then the galvanic battery device is pressed on the face of the user, and the non-woven surface directly contacts the skin. Alternatively, the active agent Or other optional electrolytes can be included in the non-woven layer in an anhydrous state during the production process. When in use, the device can be applied to the face wetted with water, and the water will dissolve the active agent and electrolyte to activate the galvanic current. No water The active agent can be a dry powder fixed on a non-woven fiber, or it can be dissolved in an organic solvent (for example, polyethylene glycol, propylene glycol, glycerol and/or alcohol) to form a non-conductive or very low-conductivity solution. , And then absorbed in the non-woven fabric layer.

[0175] Many manufacturing methods can be used to produce zinc anode materials, including, but not limited to, metal processing, electroless deposition, electroplating, plasma spraying, vacuum deposition, printing methods such as screen printing using zinc conductive ink, textile or non-woven technology. Similarly, other conductive metal materials such as silver-silver chloride, silver-silver oxide, copper, magnesium, zinc magnesium, copper, aluminum alloy, and aluminum can be manufactured into the above-mentioned electrode form using the above-mentioned manufacturing method.

[0176] Topical composition containing galvanic pair

CN 1829552 Β

[0177] In one embodiment, the present invention provides a topical composition containing a first conductive metal particle selected from zinc, aluminum, copper and alloys thereof (for example, flakes, threads/fibers or metal coatings). Coated fibers); and second conductive metal particles selected from silver, copper, gold and alloys thereof (for example, flakes, threads/fibers or metal-coated fibers). The first and second metal particles can be selected from the above-mentioned electrode materials to form a galvanic couple. After contacting, the first conductive metal and the second conductive metal form a galvanic pair, generate current, and electrochemically generate ions. In yet another embodiment, the standard potential difference between the first conductive metal and the second conductive metal is at least about 0.1V, for example, at least about 0.5V. For example, by combining with a first conductive metal containing zinc (such as fine zinc wires, zinc flakes or zinc-coated polymer fibers) and silver (such as fine silver wires/fibers, silver flakes or silver-coated polymer fibers) The second conductive metal contacts, the composition generates current and zinc ions in the topical composition.

[0178] The composition may also contain active agents, such as anti-acne agents (such as salicylic acid, benzoyl peroxide, tretinoin and/or vitamin A). The topical composition containing the first metal and the second metal is preferably a semisolid dosage form (e.g., gel, hydrogel, water-in-oil emulsion, oil-in-water emulsion, cream, lotion, ointment, multiphase emulsion, Liposomes and/or microcapsule preparations) may contain the above-mentioned liquid suspending materials or liquid absorbing materials. A conductive metal is formulated in a phase separate from other conductive metals to prepare a topical composition, for example, the first conductive metal (such as zinc flake) is formulated in the discontinuous oil phase of an oil-in-water emulsion (such as a cream) , And the second conductive metal (such as silver flakes) is formulated in the continuous aqueous phase of the emulsion. The topical composition of the present invention may also contain a wetting agent (for example, glycerol, propylene glycol, polyethylene glycol, sorbitol and/or urea) and the above-mentioned electrolytes to maintain a certain degree of moisture and conductivity of the skin.

[0179] In one embodiment, during the storage of this topical composition, the first conductive metal and the second conductive metal are substantially independently suspended in the semi-solid composition (ie, do not contact each other). When applied to a barrier film (such as skin or mucous membrane) and the liquid carrier is partially dried, the first conductive metal and the second conductive metal contact, so that a galvanic couple is formed and a current is generated and the metal ions of the first conductive metal are opposed to the film. Produce beneficial effects such as anti-microbial, anti-inflammatory, wound healing, ion-osmotic delivery of active agents, tissue irritation and/or sebum reduction.

[0180] In one embodiment, the wires/fibers, sheets, or conductive metal-coated polymer fibers of conductive metal are sufficiently thin or thin to be suspended in the semi-solid composition during storage. In another embodiment, they are elongated in shape. The advantages of the elongated shape of conductive metals (for example, pure metal wires/fibers, flakes and conductive metal-coated polymer fibers) include: The apparent density is lower, and therefore the floating/suspension ability is better in the local composition; when used At low concentrations of conductive metals, the possibility of mutual contact is higher; and the barrier membrane (such as skin) through which the current penetrates and provides beneficial effects has a wider and deeper tissue.

[0181] In one embodiment, the first and second conductive metal particles are formulated in two different compositions and stored in a separate compartment of a two-compartment package. For example, zinc or its alloy particles with lower chemical stability (that is, higher oxidation) can be formulated in anhydrous, substantially non-conductive organic solvents such as polyethylene glycol, propylene glycol, glycerol, and liquid siloxane. , And/or alcohol or other pharmaceutically acceptable organic solvents. Silver and silver chloride particles with higher chemical stability (ie lower oxidation) are formulated in an aqueous composition. Depending on the chemical stability and solubility of the active agent, it can be formulated in any composition. When used, these two compositions diffuse from the dual-chamber packaging (for example, dual-chamber pumps, tubes, bags, bottles, etc.), and are mixed before or during application to form a galvanic couple in situ to produce Electric current to deal with skin conditions.

[0182] In another embodiment, included in the topical composition in the form of particles, resulting in the galvanic couple described above. The particles can be of any shape, including, but not limited to, spherical or non-spherical particles or elongated or flat shapes (for example, metal or metal-coated spheres, hollow metal or metal-coated spheres, short metal-coated short fibers Or fabrics and flakes), regular shapes (for example, metal crystals) and irregular shapes (for example, aggregated spheres). In one embodiment, the average particle size of the particles

CN 1829552 Β

The diameter is about 1 micron-2 cm. The particle size refers to the largest dimension in at least one direction. In one embodiment, for non-elongated shapes, the average particle size of the particles is about 1 micron to 2 millimeters. In another embodiment, the average particle size of the elongated particles is about 10 microns to 2 cm, for example, about 100 microns to 50 mm. For example, a polymer fiber with a length of about 100 microns to 10 mm can be partially coated with silver or silver-silver chloride on one end (or only on certain parts of the fiber), and the other end (or the remaining part) is coated with silver or silver-silver chloride. Zinc coated. In another embodiment, the polymer fiber is completely coated with the first conductive metal (for example, silver-silver oxide or silver-silver chloride), and one end (or some part of the fiber) is coated with the second conductive metal ( Such as zinc or magnesium).

[0183] In the implementation, methods such as conductive zinc ink printing, electroplating, electroless deposition, vacuum deposition and metal spraying are used, and silver coating produced by Noble Fiber Technologies, Inc. (Clarks Summit, PA) can be coated with zinc. Of polymer fibers. Alternatively, metallic zinc or magnesium particles (for example, beads or fine wires) can be coated with silver-silver oxide or silver-silver chloride on one end or some parts. In a similar manner, the first and second conductive metal coatings can be partially coated with spherical or non-spherical particles with an average particle size of about 1 micron to 5 mm.

[0184] In the preparation of galvanic couples, the coating methods of the first and second conductive metals can be electroless deposition, electroplating, vacuum vapor deposition, arc spraying, conductive metal ink, and in the manufacture of electronic and medical devices. Other known metal coating methods commonly used in the process. The galvanic couple particles are preferably stored in the above-mentioned anhydrous form, for example, as a dry powder or fixed in a fabric with an adhesive, or as a substantially anhydrous non-conductive organic solvent composition (for example, dissolved in polyethylene glycol, Propylene glycol, glycerol, liquid silicone and/or alcohol). The galvanic battery particles have a huge application universality, and can be used in many consumer and medical products such as patches, bandages, masks, clothes, cloth, socks, bed sheets (for example, by fixing in a carrier or fabric), and laying on them Mask composition (such as ointments, creams and gels), creams, lotions, gels, shampoos, cleansers, powders, or included in personal and medical products such as toothbrushes, dental floss, wound dressings, diapers, hygiene Wipes, dry wipes, pre-moistened wipes (containing the above-mentioned anhydrous solvents), tampons, and rectal and vaginal suppositories. Electrochemical particles can also be included in a transdermal drug delivery patch to promote the penetration of drugs into the skin through iontophoresis and reduce skin irritation caused by electrical stimulation and beneficial ions such as zinc ions generated by electricity.

Example 1: Vector

[0186] Some examples of carriers, including the weight percentage ranges of the components of these carriers, are shown in Table 1.

[0187] Table 1

[0188]

<td>ingredient</td><td colspan="6">Carrier weight percentage</td>

<td></td><td>Number 1</td><td>Number 2</td><td>Number 3</td><td>Number 4</td><td>Number 5</td><td>Number 6</td>

<td>Salicylic acid</td><td>0.1-10</td><td>2</td><td>2</td><td>0</td><td>0</td><td>0. 1-10</td>

<td>Benzyl peroxide</td><td>0</td><td>0</td><td>0</td><td>0. 5-10</td><td>0</td><td>0</td>

<td>sulfur</td><td>0</td><td>0</td><td>0</td><td>0</td><td>3</td><td>3</td>

<td>Resorcinol</td><td>0</td><td>0</td><td>0</td><td>1</td><td>1</td><td>1</td>

<td>Benzalkonium chloride</td><td>0-2</td><td>0. 1</td><td>0. 1</td><td>0-2</td><td>0-2</td><td>0-2</td>

CN 1829552 Β

<td>Knots or A Knots</td><td>0-2</td><td>0</td><td>0</td><td>0-2</td><td>0-2</td><td>0-2</td>

<td>Sipiclosan</td><td>0-2</td><td>0. 1</td><td>0. 1</td><td>0-2</td><td>0-2</td><td>0-2</td>

<td>Phospholipid CDM</td><td>0-40</td><td>5</td><td>5</td><td>0-40</td><td>0-40</td><td>0-40</td>

<td>hydrogen peroxide</td><td>0-30</td><td>0</td><td>3</td><td>0-30</td><td>0-30</td><td>0-30</td>

<td>Buffer (citrate, lactate or phosphate of sodium, potassium or lithium</td><td>0-10</td><td>2</td><td>2</td><td>0-10</td><td>0-10</td><td>0-10</td>

<td>Gelling agent (such as polyacrylate, cellulose, natural or synthetic gum, or polyacrylamide</td><td>0-20</td><td>5</td><td>5</td><td>0-20</td><td>0-20</td><td>0-20</td>

<td>Chelating agent (such as EDTA)</td><td>0-2</td><td>0. 1</td><td>0. 1</td><td>0-2</td><td>0-2</td><td>0-2</td>

<td>Propylene Glycol</td><td>0-30</td><td>20</td><td>15</td><td>0-30</td><td>0-30</td><td>0-30</td>

<td>Polyethylene glycol</td><td>0-50</td><td>0</td><td>0</td><td>0-50</td><td>0-50</td><td>0-50</td>

<td>Polypropylene glycol</td><td>0-40</td><td>0</td><td>0</td><td>0-40</td><td>0-40</td><td>0-40</td>

<td>Ethanol</td><td>0-50</td><td>0</td><td>15</td><td>0-50</td><td>0-50</td><td>0-50</td>

<td>Isopropanol</td><td>0-50</td><td>0</td><td>0</td><td>0-50</td><td>0-50</td><td>0-50</td>

<td>Dimethyl isosorbide</td><td>0-20</td><td>2</td><td>0</td><td>0-20</td><td>0-20</td><td>0-20</td>

<td>Isopropyl myristate</td><td>0-30</td><td>1</td><td>1</td><td>0-30</td><td>0-30</td><td>0-30</td>

<td>Pure water</td><td>Quantitative to 100</td><td>Quantitative to 100</td><td>Quantitative to 100</td><td>Quantitative to 100</td><td>Quantitative to 100</td><td>Quantitative to 100</td>

[0189] In order to evaluate the possible mechanism of action of beneficial reagents produced by electrochemistry, in vitro microbiological tests were carried out in a certain electrochemical system to study the inhibitory effect of electrolysis on P. acnes; and commercial ions were used in volunteers The infiltration device was tested in vivo.

Example 2: In vitro inhibitory effect of electrolysis on P. acnes

[0191] The BacT/ALERT system (BioMerieux, Inc., Durham, NC) was used in the P. acnes inhibition test. Simply put, in a culture flask (BacT/ALERT SN, Organon Tekniks Corp., Durham, NC) , Inoculate Propionibacterium acnes with 40ml anaerobic broth based on casein and soybeans. At 35°C, C0 is continuously monitored by using a light colorimetric sensor system₂The production, monitored using a fully automated BacT/ALERT system in a 14-day trial

The growth of Propionibacterium acnes. Sterilize a pair of selected electrodes (Table 2, columns 2 and 3) with 70% isopropanol, and insert them into the culture medium of the nitrogen glove box through the rubber plug. Some electrodes are connected to the poles of the battery (1.5 or 3V, as shown in Table 2, column 3) for 30 minutes. Then, immediately remove the electrode from the BacT/ALERT bottle and place the bottle in the automatic culture and monitoring system for two weeks. The other electrodes (numbers 3 and 5 in Table 2) are not connected to the external battery, but are directly connected to each other at the ends of the external electrodes of the BacT/ALERT bottle to form a galvanic couple. During the 14-day test, the electrodes of these galvanic couples (namely numbers 3 and 5) were kept in contact with the culture medium in the bottle.

[0192] From the test conditions 1-7 (numbers 1-7 in column 1), zinc was evaluated as the positive electrode (anode) and various materials were used as the negative electrode (cathode). Column 4 shows the voltage applied to the conductive electrode by the external battery. However, by simply connecting two conductive electrode materials, voltage can also be generated from a pair of galvanic cells. For example, the voltage of zinc-silver/silver chloride galvanic couple is 0.9849V or about 1V (Zn+2e = Zn, standard potential: -0.7626V, AgCl+e = Ag+CF, standard potential: 0. 2223V), the voltage of the zinc-copper galvanic couple is about 1. 1-1. 3V (Ci?++2e "= Cu, standard potential: 0. 340V, Cu*+e "= Cu, standard potential :0. 520V) Reference: Electrochemistry Handbook, 1995, Table 14. 1, McGraw-Η Order 1, Inc. New York, NY).

[0193] In test condition 7, two electrodes (ie zinc-silver/silver chloride galvanic couple) were taken from a commercially available ion permeation device (IontoPatch, SP, Birch Point Medical, Inc., Oakdale, MN). IontoPatch is an ion penetration device that is powered by a galvanic couple of zinc and silver/silver chloride in a bandage-like device. In this test, the "battery strap" in the IontoPatch was taken out of the bandage-like device and placed in a BacT/ALERT bottle. Throughout the two-week experiment, the commercially available zinc-silver/silver chloride galvanic battery electrode (No. 7) was kept in a BacT/ALERT bottle. Test condition 15-17 is a positive control (ie no electrode): Test condition 15 uses a concentrated P. acnes culture to cultivate the remaining medium in each BacT/ALERT bottle to count P. acnes 10°/ml; test conditions 16 and 17 use P. acnes count as 10⁶A/ml incubation medium (also pierce the rubber stopper No. 16 in a manner similar to the remaining electrode test conditions to eliminate any potential environmental oxygen entering the test bottle and affecting the growth of anaerobic Propionibacterium acnes False Propionibacterium acnes inhibition results).

[0194] Table 2

[0195]

<td>Numbering</td><td>positive electrode</td><td>negative electrode</td><td>The voltage applied by connecting to a battery or battery pack</td><td>Average time for positive P. crampi growth</td><td>Number of positives / number of trials</td>

<td>1</td><td>Zinc</td><td>Silver/Silver Chloride</td><td>3V</td><td></td><td>0/3</td>

<td>2</td><td>Zinc</td><td>Zinc</td><td>3V</td><td></td><td>0/1</td>

<td>3</td><td>Zinc</td><td>copper</td><td>No a</td><td></td><td>0/2</td>

<td>4</td><td>Zinc</td><td>copper</td><td>1. 5V</td><td></td><td>0/1</td>

<td>5</td><td>Zinc</td><td>Silver/Silver Chloride</td><td>No a</td><td></td><td>0/2</td>

<td>6</td><td>Zinc</td><td>Silver/Silver Chloride</td><td>1. 5V</td><td></td><td>0/2</td>

<td>7</td><td>Zinc</td><td>Silver/Silver Chloride</td><td>No a</td><td>-b</td><td>2/6</td>

<td>8</td><td>copper</td><td>Silver/Silver Chloride</td><td>3V</td><td></td><td>0/3</td>

<td>9</td><td>copper</td><td>copper</td><td>3V</td><td></td><td>0/2</td>

<td>10</td><td>clamp</td><td>Silver/Silver Chloride</td><td>3V</td><td>1. 6</td><td>2/2</td>

<td>11</td><td>clamp</td><td>clamp</td><td>3V</td><td>1. 1</td><td>1/1</td>

<td>12</td><td>silver</td><td>Silver/Silver Chloride</td><td>3V</td><td>5. 7c</td><td>2/3</td>

<td>13</td><td>silver</td><td>silver</td><td>3V</td><td>2. 8d</td><td>2/2</td>

<td>14</td><td>Silver/Silver Chloride</td><td>Silver/Silver Chloride</td><td>3V</td><td>3. 0</td><td>2/2</td>

<td>15</td><td>no</td><td>no</td><td>no</td><td>0. 8</td><td>2/2</td>

<td>16</td><td>no</td><td>no</td><td>no</td><td>1. 4</td><td>2/2</td>

<td>17</td><td>no</td><td>no</td><td>no</td><td>1. 3</td><td>2/2</td>

[0196] a. The conductive metal electrodes are not connected to any batteries, but to each other. Therefore, there is a voltage on the two electrodes controlled by a pair of galvanic cells.

[0197] b. A total of 6 samples were tested; 4 negative and 2 positive (0.6d, 0.8d); the positive result is probably due to bacterial contamination, because they are determined to be better than the positive control samples (No. 16 and 17) It's faster, so save it.

[0198] c. Among 3 samples, two positive results (4.1d, 7.3d) were averaged.

[0199] It was unexpectedly found that under all test voltage conditions (No. 1-7; No. 7, two of the six commercially available galvanic couples showed positive growth of P. convulsions, most likely due to bacterial contamination See note c) in Table 2. In the 14-day incubation test, the zinc anode can almost completely inhibit the growth of P. acnes. It was found that copper anodes can also significantly inhibit the growth of P. acnes (No. 8-9). Under this experimental condition, the clamp anode has very little P. acnes inhibition, and silver or silver/silver chloride anodes only have Weak inhibitory effect on P. acnes. After the experiment started, the growth of P. acnes positive for all the positive control conditions (No. 15-17) was less than two days, and the growth of P. acnes negative was due to the inhibition of electrochemically produced substances or electrical connections through the medium. Caused. Because the current passed in numbers 10-14 does not have the strong acne-inhibiting effect as in numbers 1-9, the bacterial inhibition observed in numbers 1-9 may be due to the anode, that is, when zinc and copper are used as anodes Caused by some kind of electrochemical reaction. It was also unexpectedly found that under these experimental conditions, the silver ions released from silver or silver/silver chloride anodes did not have the same inhibitory effect on P. acnes (No. 12-14), because silver ions are well-known antimicrobial substance. For example, see Spacciapoli et al., "Antimicrobial activity of silver nitrate against periodontal disease pathogens" Antimicrobialactivity of silver nitrate against periodontai pathogens. ), J Periodontal Res36 :2,108-13, Apr, 2001) Unexpectedly, in the entire two-week experiment, in the absence of external batteries (numbers 3, 5 and 7) Next, a pair of electrodes of a galvanic couple with zinc as the anode is sufficient to inhibit the growth of P. acnes.

Example 3: In vitro compatibility test of electrode-salicylic acid

CN 1829552 Β

[0201] The following test was performed to determine the compatibility of the electrode with salicylic acid. Immerse a pair of test electrodes in 5ml.5% salicylic acid solution (solvent is 50% ethanol/50% water). Apply a predetermined voltage to the electrode (connect the electrode to an external battery or battery pack) for a period of time, as shown in Table 3. Observe the color change of the test solution.

[0202] The solution of zinc as an anode does not change color, indicating that it has good compatibility with salicylic acid during the electrical connection. The use of a clamp anode accidentally caused discoloration, indicating incompatibility with salicylic acid under this experimental condition.

[0203] Table 3

[0204]

<td colspan="2">Electrode material</td><td rowspan="2">Voltage (V)</td><td rowspan="2">Test duration (min)</td><td>Observed</td>

<td>Anode (+)</td><td>cathode(-)</td><td>Solution color change</td>

<td>clamp</td><td>clamp</td><td>3</td><td>10</td><td>Colorless-yellow</td>

<td>clamp</td><td>clamp</td><td>9</td><td>10</td><td>Colorless and brown</td>

<td>Zinc</td><td>clamp</td><td>1. 5</td><td>10</td><td>No color change</td>

<td>Zinc</td><td>clamp</td><td>3</td><td>10</td><td>No color change</td>

<td>Zinc</td><td>clamp</td><td>9</td><td>30</td><td>No color change</td>

[0205] Example 4: Human Iontophoresis In-Vivo Test

[0206] A commercially available iontophoresis device (IontoPatch@, model: SP, Birch Point Medical Inc., North Oakdale, MN) was used in volunteers. The trial recruited healthy female volunteers with oily skin and aged 20-45. The sebum reading of each subjects forehead is at least greater than 150 mg/cm²/hro for double-blind trials and controlled trials. Simply put, the voltage is 1 volt, the operating current is 0. 06mA, and the active treatment area is 1. 25cm²The IontoPatch ® is applied to the treatment part of the human subject (such as the forehead). The positive and negative electrodes are respectively composed of zinc and silver/silver chloride (Ag/AgCl) materials. Both electrodes are filled with salt water (0.9% NaCl). At the same time that the saline solution was added to the different electrodes, the electrical patch began to work. Leave the patch on the treatment area overnight (for example, about 8 hours).

[0207] The following evaluations were performed: (i) using conventional photography to monitor the effect of electrolysis on skin conditions, and (ii) determining acne propionic acid by analyzing the cup wash solution of the treated area before and after wearing the patch overnight Changes in the number of bacilli. The cup washing micro-sampling process is as follows: a cylindrical cup (diameter 2.1 cm, height 2.5 cm) with two open ends is fixed on the treatment area. Then use 2ml of cleaning buffer (sterile 0.075M phosphate buffer containing 0.1% TritonX-100) to wash the treatment area in the cylindrical cup. The same area is used for aseptic polished glass. Then the washing solution is collected. Then repeat the washing process. The two collected samples were combined and used for the analysis of P. acnes.

[0208] The anaerobic washing sample was inoculated in Actinomycetes agar on a rotating plate for 5 days to determine the number of P. acnes, Gram staining and using the VITEK system to determine the main contaminants on the rotating plate. Use an automated colony counter to determine the P. acnes count per milliliter of each sample buffer.

[0209] After only one application of the overnight patch, the quantitative measurement results of P. acnes on the treatment site showed that relative to

CN 1829552 Β

At baseline, P. acnes decreased by 45% under the zinc anode and 30% under the Ag/AgCl cathode. After four consecutive overnight patch applications, the photo clearly showed that the color and size of hyperpigmented spots after the acne under the zinc electrode were significantly reduced. The subject had hyperpigmentation spots after acne on the tested skin site. The appearance of hyperpigmented spots improves from a very dark color to a lighter color.

[0210] Moreover, after four consecutive overnight patch applications, the photos also showed that the color and size of the acne pustules under the Ag/AgCl electrode were significantly reduced. The test subject has acne pustules at the test skin site. The redness of the pustules quickly decreased from a very red color to almost invisible, while the pustules in the untreated skin area did not change much.

Example 5: In vivo study of human iontophoresis using histamine hydrochloride as a marker

[0212] In three volunteers, a galvanic zinc-silver/silver oxide device was used to deliver the marker histamine hydrochloride into the skin for in vivo studies. The skin erythema and itching caused by histamine were recorded during and after the test. The trial recruited two healthy male volunteers and one female volunteer aged 41-49 years old. The thin zinc foil was cut into (thickness 0.25 mm, Alfa Aesar, Word Hill, MA) rectangular pieces (width 2.5 cm, length 3 cm) to prepare a galvanic cell device. In the center, silver ink (S Book Ver Print, MG Chemicals, Toronto, Ontario, Canada) was brushed on one side of the zinc foil with a 0.5 cm wide strip along the long axis. Air-dry the silver ink to form a silver electrode strip on the zinc foil. Two rectangular Scotch ® tapes with a width of 0.5 cm and a length of 3 cm were placed on both sides of the silver electrode strip to create an electrical insulation gap on the surface (electrode gap = 0.5 em). A rectangular sheet of non-woven fabric (50% rayon/50% PET, 75gsm, PGI Polymer Group Inc., Landisvädle, Town) with a width of 3cm and a length of 3.5cm was placed on the zinc-silver electrode surface of the zinc foil. A rectangular adhesive backing film with a width of 4 cm and a length of 5 cm was fixed on the back of the zinc foil to complete the zinc-silver galvanic cell device.

[0213] By simply omitting the step of adding Scotch ® tape, a zinc-silver galvanic cell device with no electrical insulation interval (electrode interval = 0 cm) on the second surface was prepared. A third (control) patch was prepared by using only zinc foil, a non-woven pad and an adhesive backing film to construct the device.

[0214] 0.8 ml of 0.1% histamine hydrochloride (Sigma-Aldrich, St. Louis, MO) aqueous solution was added to each device, and then fixed on the forearm skin of each volunteer for 30 minutes to start histamine ion Penetration test.

[0215] At the end of the test, red spots (erythema caused by histamine) appeared under the zinc-silver patch device, and the spots disappeared within about half an hour. Close inspection reveals that red spots are around the hair follicles. During the application of the patch, there is also itching at the electrical patch site. In contrast, under the control patch device, there was no skin color change or any itching.

[0216] Example 6: In vivo study of human iontophoresis of histamine hydrochloride using galvanic cell nasal patch containing zinc mesh

[0217] As a continuation of the in vivo human body study of the foregoing example, the same size and method as the galvanic cell device (spacer electrode = 0) in Example 5 was used to prepare a zinc mesh (long lem, 0.4 cm wide diamond-shaped opening). , Exmet Corporation, Naugatuck, CT) instead of zinc foil electric patch device (here called test device D). The device prepared in this way is similar to the structure shown in Figure 11, with three parallel electrodes: a silver electrode in the center and a zinc electrode on both sides. Using test conditions similar to Example 5, a study was conducted on two male volunteers. A test device containing 0.8 ml of 0.1% histamine hydrochloride was applied to the nose of each volunteer for 30 minutes. Itching occurred within 5 minutes of application of the nasal patch, suggesting that histamine was quickly passed into the larger skin pores on the nose. For the two subjects, compared with the test performed on the forearm skin, after the nasal patch was removed at the end of the test, obvious erythema was observed in the skin area under the nasal patch.

[0218] Although the present invention has been described in conjunction with the detailed description, it should be understood that the foregoing description is to clarify the present invention and not to limit the scope of the present invention, which is defined by the scope of the appended claims. Other aspects, advantages and improvements are in the claims.

CN 1829552 Β