HK1092398A - Methods of treating pores on the skin with electricity - Google Patents

Description

Method for treating skin pores with electricity

Cross Reference to Related Applications

This application is a continuation of co-pending application 10/685,282 filed on day 14/10/2003, which is a continuation of co-pending application 10/609,727 filed on day 30/6/2003, the entire contents of which are incorporated herein by reference.

Background

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 (e.g., via passive diffusion through the skin) through a concentration gradient across the barrier membrane. For example, a patch containing a high concentration of a drug is attached to the skin of a patient.

Transport of the drug across the skin barrier may be facilitated electrically. In an electrically assisted device, an electrical potential (voltage) is applied to the membrane to facilitate drug transport. In transdermal iontophoresis, ionized drugs migrate into the skin driven by an applied potential gradient. Anionic drugs are delivered into the skin at the cathode (negatively charged electrode) and cationic drugs are delivered into the skin at the anode (positively charged electrode). Iontophoresis can increase and better control the rate of penetration of ionized substances into the skin.

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

Alternatively, the two electrode assemblies may constitute a single iontophoresis device, in which an electrically insulating material is constructed to be disposed between the two electrode assemblies for electrical insulation to prevent short circuits. An example of such an iontophoretic device is disclosed in U.S. Pat. No. 5,387,189.

In another variation of the design of a conventional iontophoresis device, the electrolyte composition of one of the two electrode assemblies is removed and the conductive electrode is placed directly in contact with the skin to complete the electrical circuit. An example of such an iontophoretic device is disclosed in U.S. Pat. No. 6,385,487.

In a typical iontophoretic operation (monopolar operation), one of the two electrodes (e.g., the active electrode) drives the active agent into the skin. The other electrode (e.g., a diffusion electrode) is used to close the electrical 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, and thus delivered into the skin under the second electrode. Alternatively, the electrical polarity of the first and second electrodes may be periodically switched to drive ionic species under both electrodes (bipolar operation). A bipolar iontophoretic device for transdermal drug delivery is disclosed in us patent 4,406,658.

The use of galvanic couples as a power source in iontophoresis devices is well known in the art. See, for example, U.S. patents 5,147,297, 5,162,043, 5,298,017, 5,326,341, 5,405,317, 5,685,837, 6,584,349, 6,421,561 and 6,653,014. Typical materials that make up galvanic couples include a zinc donor electrode and a silver chloride counter electrode. This combination produces a potential of about one volt. There is no control means for the galvanic couple driven iontophoretic system to automatically activate and generate electricity if body tissue and/or body fluids form a complete circuit with the system.

Summary of The Invention

In one aspect, the present invention provides a method of exfoliating skin comprising applying to skin in need of such exfoliation a device comprising a housing having a skin contacting surface, a first conductive electrode in electrical communication with the second conductive electrode, a carrier comprising an agent selected from the group consisting of α -hydroxy acids, β -hydroxy acids, and salts thereof, the carrier being in ionic communication with the carrier, the carrier being in communication with the skin contacting surface, and placing the skin contacting surface in contact with the skin.

In another aspect, the present invention provides a method of exfoliating skin comprising topically applying to the skin a composition comprising a first conductive electrode in particulate form, a second conductive electrode in particulate form, and an agent selected from the group consisting of α -hydroxy acids, β -hydroxy acids, and salts thereof, wherein the difference in the standard potentials of the first conductive electrode and the second conductive electrode is at least 0.2V.

In another aspect, the invention provides a method of facilitating a composition comprising a first conductive electrode in particulate form and a second conductive electrode in particulate form, wherein the difference in standard potential between the first conductive electrode and the second conductive electrode is at least 0.2V, the method comprising facilitating topical application of the composition for treating a wound on a barrier membrane.

In another aspect, the present invention provides a method of treating skin pores, the method comprising applying to skin in need of such treatment a device comprising a housing having a skin contacting surface, a first conductive electrode, a second conductive electrode, and a carrier; wherein the first conductive electrode is in electrical communication with the second conductive electrode, the first conductive electrode is in ionic communication with a carrier, the carrier is in communication with the skin contact surface, the skin contact surface is placed in contact with the skin, and the method of treating skin pores is selected from the group consisting of: cleansing skin pores, reducing skin sebum, reducing the appearance of skin blackheads, and reducing the appearance of skin pores.

In another aspect, the present invention provides a method of treating skin pores by topically applying a composition comprising a first conductive electrode in particulate form and a second conductive electrode in particulate form, wherein the difference in the standard potentials of the first conductive electrode and the second conductive electrode is at least 0.2V.

In another aspect, the present invention provides a method of facilitating a composition comprising a first conductive electrode in particulate form and a second conductive electrode in particulate form, wherein the difference in the standard potentials of the first conductive electrode and the second conductive electrode is at least 0.2V, the method comprising facilitating topical application of the composition for treating skin pores, wherein the method of treating skin pores is selected from the group consisting of: cleansing skin pores, reducing skin sebum, reducing the appearance of skin blackheads, and reducing the appearance of skin pores.

In one aspect, the present invention provides a method of treating skin infections, including but not limited to acne or rosacea, the method comprising applying electrochemically generated zinc ions to the skin. In one embodiment, the method includes topically applying a device comprising a zinc-containing anode. In another embodiment, the device includes a housing having a skin-contacting 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, the first conductive electrode is in ionic communication with the carrier, and the carrier is in communication with the skin contact surface.

In another aspect, the present invention provides a device having a barrier membrane contacting surface, the device comprising: a power source; a first conductive electrode; a second conductive electrode; and a carrier; wherein the power source is in electrical communication with the first conductive electrode and the second conductive electrode, 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 invention provides a method of imparting electrical potential to a barrier membrane of a human body, the method comprising applying such a device to the membrane. In another aspect, the invention provides a method of treating a skin condition comprising applying such a device to the skin.

In another aspect, the present invention provides a device having a barrier membrane contacting 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 is in electrical communication with the first conductive electrode and the second conductive electrode, 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 invention provides a method of imparting electrical potential to a barrier membrane of a human body, the method comprising applying such a device to the membrane. In another aspect, the invention provides a method of treating a skin condition comprising applying such a device to the skin.

In another aspect, the present invention provides a device having a barrier membrane contacting 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 source is in electrical communication with the first conductive electrode, the second conductive electrode, and the light emitting diode, and the device is configured to communicate light from the first light emitting diode and the carrier with the barrier film contact surface. In another aspect, the invention provides a method of administering an active agent to a human barrier membrane, the method comprising applying such a device to the membrane. In another aspect, the invention provides a method of treating a skin condition comprising applying such a device to the skin.

In another aspect, the present invention provides a method of treating a skin condition by applying to the skin a device having a barrier membrane contacting surface which administers an oxidizing agent to the barrier membrane, wherein the device comprises: 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 a first conductive electrode and a second conductive electrode, the first conductive electrode is in ionic communication with the carrier, the oxidant is generated by an electrical 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 membrane, the method comprising applying such a device to the membrane.

In another aspect, the present invention provides a method of treating a skin condition by applying to the skin a device having a barrier membrane contacting surface which administers a barrier membrane reducing agent, wherein the device comprises: 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 a first conductive electrode and a second conductive electrode, the first conductive electrode is in ionic communication with the carrier, the reducing agent is generated by an electrical 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 membrane, the method comprising applying such a device to the membrane.

Other features and advantages of the invention will be apparent from the detailed description of the invention and from the claims.

Brief description of the drawings

FIG. 1 is a cross-sectional view of one embodiment of an apparatus suitable for practicing the present invention. The conductive electrodes 140 and 240 are connected to electrically insulated connecting wires 350 on the back side of the device 500 by wires 110 and 210, respectively.

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

Figure 3 is a cross-sectional view of one embodiment of a device suitable for practicing the present invention. The conductive electrodes 140 and 240 are connected to electrically insulated connection wires 350 embedded in the carrier layer 120 by wires 110 and 210, respectively.

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

FIG. 5 is a cross-sectional view of one embodiment of a device suitable for practicing the present invention. The device 800 includes two electrode assemblies 200 and 600.

Fig. 6 is a top view of one embodiment of the present invention showing conductive electrodes 140 and 240 connected by electrically insulating connecting wires 350 embedded in carrier layer 120. The conductive electrodes 140 and 240 are arranged in a staggered configuration with respect to each other.

Fig. 7 is a top view of one embodiment of the present invention showing conductive electrodes 140 and 240 connected by electrically insulating connecting wires 350 embedded in carrier layer 120. The conductive electrodes 140 and 240 are arranged in a concentric circular configuration.

Fig. 8 is a top view of one embodiment of the present invention showing multiple sets of conductive electrodes 140 and 240 interconnected by connecting wires 350 to form multiple galvanic couple power sources in contact with carrier layer 120. Conductive electrodes 140 and 240 are arranged in a parallel configuration.

Fig. 9 is a top view of one embodiment of the present invention showing multiple sets of conductive electrodes 140 and 240 connected to each other by direct physical contact at an interface 370 forming a plurality of galvanic couple power sources in contact with carrier layer 120. The conductive electrodes 140 and 240 are arranged in a vertical configuration.

Fig. 10 is a top view of one embodiment of the present invention showing conductive electrodes 140 and 240 connected by electrically insulating connecting wires 350 embedded in carrier layer 120.

Fig. 11 is a top view of one embodiment of the present invention showing conductive electrodes 140 and 240 embedded in carrier layer 120.

Detailed Description

In light of this description, it is believed that one skilled in the art can, using the present invention. The following detailed description is to be construed as exemplary only and is not intended to limit the remainder of the disclosure in any way.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Moreover, all publications, patent applications, patents, and other references mentioned herein are incorporated by reference. Unless otherwise indicated, percentages refer to weight percent (i.e., wt%).

"product" refers to the product in the final package containing the device. In one embodiment, the product includes instructions directing the user to apply the device to the barrier membrane (e.g., to treat a skin condition). The instructions may be printed on the device, on the label insert or on any additional packaging.

In one aspect, the invention provides a method of promoting a particular use of the device of the invention. "promotion" refers to promotion, advertising, or marketing. Examples of promotions include, but are not limited to, text, graphics or dictation on products or in stores, magazines, newspapers, radio, television, the internet, etc.

As used herein, "pharmaceutically acceptable" means that the ingredients described by the term are suitable for use in contact with a barrier membrane (e.g., skin or mucous membranes) without undesirable toxicity, incompatibility, instability, irritation, allergic response, and the like.

As used herein, "safe and effective amount" means an amount of an ingredient or composition 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 the site being treated, the age and skin type of the user, the duration and nature of the treatment, the particular ingredient or composition used, the particular pharmaceutically acceptable carrier employed, and like factors.

The term "treating" or "treatment" as used herein refers to treating (e.g., alleviating or eliminating symptoms and/or healing) and/or preventing or inhibiting a disease (e.g., a skin disease). "skin disease" refers to a dermatological disease or disorder (including but not limited to acne, rosacea, or skin infections) or a skin characteristic (including but not limited to pigmentation, hair growth regulation, skin texture, skin hardness, skin elasticity, skin microtubule structure, dark spots, cellulite, cortex regulation, and skin radiance). Skin infections include, but are not limited to, those caused by susceptible pathogens such as acne, rosacea, impetigo, folliculitis, furunculosis, ecthyma, eczema, psoriasis, atopic dermatitis, herpes, epidermolysis bullosa, ichthyosis, and infected traumatic injuries (e.g., ulcers, minor burns, cuts, abrasions, lacerations, wounds, biopsy sites, surgical incisions, and insect bites).

The present invention relates to a device for delivering electricity (e.g., to elicit a desired biological response) and/or an active agent into a barrier membrane. In one embodiment, the device of the present invention is a kit comprising at least one pair of two distinct conductive electrodes in electrical communication as a power source. By "in electrical communication" is meant that electrons can pass directly between elements of the device (e.g., between conductive electrodes of the device). In one embodiment, the two conductive electrodes are in electrical communication by being in direct contact with each other.

"ionic communication" refers to the passage of electrons between elements (e.g., by ionic transport of an electrolyte (e.g., in a carrier) in contact with a conductive electrode and the skin, electrons passing between a conductive electrode and the skin) by ionic migration as an "electron mover" in contact with the elements (e.g., the conductive electrode, the carrier, and/or the conductive electrode and the skin).

In one embodiment, both conductive electrodes are in ionic communication with an electrolyte-containing carrier (e.g., one or more ions in the carrier are in contact with the conductive electrodes), which is in ionic communication with the skin. This electrode configuration differs from that of conventional iontophoresis devices in which each conductive electrode is in contact with a separate carrier (e.g., each electrode is contained in a separate chamber and applied to the skin, with electrical isolation between the two electrodes, allowing all electrical connections to be made through the skin to complete an electrical circuit). Advantages of this embodiment of the invention include the ability to simultaneously deliver active agents of opposite charge from the same carrier into substantially the same skin site beneath the conductive electrode. Another advantage is that the device of the present invention is easier to manufacture than conventional iontophoretic devices, thus enabling significant cost savings.

The device includes a barrier membrane contacting surface (e.g., a skin contacting surface) applied to the membrane (e.g., applied by the user to the user's skin). The device is configured to allow the carrier to communicate with the barrier membrane contacting surface (e.g., to allow an administered electric current and/or active agent to pass from the carrier into the barrier membrane). In one embodiment, the carrier is a barrier membrane contact surface (e.g., the carrier is a hydrogel). In one embodiment, the device includes a light emitting diode, and light from the light emitting diode is communicated with the barrier film contact surface (e.g., such that light can reach the barrier film).

In one embodiment, the device of the present invention delivers an active agent into the barrier membrane. The active agent to be delivered by the device of the present invention includes the active agent originally contained in the carrier or electrochemically generated by passing an electric current through the conductive electrode to the carrier in use. By "electrochemically generated" is meant that the chemical species is generated by an electrochemical reaction caused by an electrical current flowing through the electrode, such as a chemical species released from a reactive electrode (e.g., electrochemically generated zinc ions), a chemical species electrochemically generated on the surface of an inert electrode, or a chemical species that is a product of a subsequent reaction of the electrochemically generated species.

Power supply

In one embodiment, the inventive apparatus includes a power source. The power source may be a conventional Direct Current (DC) or pulsed DC such as disclosed in us patent 5,042,975. In one embodiment, the current density (current intensity per unit area of the barrier membrane) used in the device of the present invention is generally less than about 0.5mA/cm²E.g., less than about 0.1mA/cm²Or less than about 0.05mA/cm². In one embodiment, the power supply generates a voltage of about 0.1 volts to about 9 volts, such as about 1 to about 3 volts, for example about 1.5 volts.

In one embodiment, the power source is a battery (e.g., a rechargeable or disposable battery). In one embodiment, the battery is a small-sized disposable battery suitable for wearable patch or mask-type adhesive devices. Examples of suitable batteries include, but are not limited to, button cells or coin cells such as silver oxide, lithium and zinc air cells (commonly 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, energizer AC5 and AC10/230(Eveready Battery co. Another preferred cell for use in the device is a flexible thin layer open liquid electrochemical cell, such as that disclosed in U.S. patent No. 5,897,522.

Galvanic couple

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 a standard potential difference between the electrodes (i.e., electricity is not generated by an external battery or other power source such as an AC power source). Examples of such galvanic couples include, but are not limited to: zinc-copper, zinc-copper/copper halide, zinc-copper/copper oxide, magnesium-copper/copper halide, 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/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/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/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 a conductive electrode of the device, for example zinc as a conductive anode, silver/silver chloride as a conductive cathode or zinc as a conductive anode and copper as a conductive cathode. The metals that can be used as galvanic couples and conductive electrodes can also be alloys. Non-limiting examples of alloys include alloys of zinc, copper, aluminum, magnesium as the anode material and alloys of silver, copper, gold as the cathode material.

In one embodiment, the galvanic couple is comprised of materials having a standard potential difference equal to or greater than about 0.1 volts, such as greater than about 0.2 volts, for example greater than about 0.5 volts. In one embodiment, the material comprising the galvanic couple has a standard potential difference equal to or less than about 3 volts.

In one embodiment, the device or composition of the invention generates and/or is capable of generating a current into the barrier membrane of about 1nA/cm²-400μA/cm²E.g. about 100A/cm²-50μA/cm²。

In one embodiment, one of the conductive electrodes is in the form of a metal sheet, wire, or metal plated on the 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, such an apertured 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 a metal, and oxides, halides, sulfides thereof, such as a fabric coated with silver, silver/silver oxide, silver/silver halide, zinc, magnesium, copper/copper halide, copper/copper oxide. 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, electroplating for electrochemical deposition as is 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.

In one embodiment, the device is a single-chamber treatment device. By "single-chamber treatment device" is meant a device in which both conductive electrodes of the device are in contact with the same carrier. Examples of such devices are shown in fig. 1-4 and 6-11.

Carrier

The carrier of the present invention is a liquid (e.g., a solution, suspension or emulsion immobilized in an absorbent material such as gauze or a nonwoven pad), a semi-solid (e.g., a gel, cream, lotion, microemulsion or hydrogel), or a solid (e.g., a lyophilized composition containing an active agent to which a liquid is added to reform prior to use) that is capable of conducting electricity from a conductive electrode (e.g., the carrier contains one or more electrolytes, an organic solvent or water) when in use. In one embodiment, a carrier (e.g., liquid or semi-solid) is added to the device before the user applies the device to the barrier membrane.

Examples of electrolytes include, but are not limited to, organic or organic salts and buffers of pharmaceutically acceptable carriers. Examples of salts include, but are not limited to, hydrochlorides (e.g., sodium chloride, potassium chloride, lithium chloride, calcium chloride, strontium chloride, magnesium chloride or other hydrochlorides) and sodium, potassium, lithium, calcium, magnesium, strontium, hydrofluoride, hydroiodide, hydrobromide salts. Examples of buffering agents include, but are not limited to, phosphates, citrates, acetates, lactates, and borates.

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

In one embodiment, the carrier is aqueous. In another embodiment, the carrier may further comprise one or more organic solvents. Examples of organic solvents include, but are not limited to: dimethyl isosorbide ester; isopropyl myristate; cationic, anionic and nonionic surfactants; a vegetable oil; mineral oil; a wax; a gum; synthetic and natural gelling agents; an alkanol; diols and polyols.

Examples of diols include, but are not limited to, glycerol, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, polyethylene glycol, polypropylene glycol, diethylene glycol, triethylene glycol, glycerol, hexanetriol, and copolymers or mixtures thereof. Examples of alkanols include, but are not limited to, alkanols having about 2 to 12 carbon atoms (e.g., about 2 to 4 carbon atoms), such as isopropanol and ethanol. Examples of polyols include, but are not limited to, polyols having from about 2 to about 15 carbon atoms (e.g., from about 2 to about 10 carbon atoms), such as propylene glycol.

The organic solvent may be present in the vehicle in an amount of about 1% to about 90% (e.g., about 5% to about 50%) based on the total weight of the vehicle. The water (prior to use) may be present in the carrier in an amount of about 5% to about 95% (e.g., about 50% to about 90%) based on the total weight of the carrier.

The carrier may further comprise: preservatives (such as cresol, chlorocresol, benzyl alcohol, methyl paraben, propyl paraben, phenol, thimerosal, benzalkonium chloride, benzethonium chloride and phenylmercuric nitrate); stabilizers or antioxidants (e.g., ascorbic acid esters, butylated hydroxyanisole, butylated hydroxytoluene, cysteine, N-acetylcysteine, sodium metabisulfite, sodium sulfite, sodium formaldehyde sulfoxylate, sodium acetone bisulfite, tocopherol, and nordihydroguaiaretic acid); chelating agents (such as ethylenediaminetetraacetic acid and salts thereof); buffering agents (e.g., acetic acid, citric acid, phosphoric acid, glutamic acid and salts thereof); and tonicity adjusting agents (such as sodium chloride, sodium sulfate, glucose and glycerin).

In one embodiment, the carrier may also contain suspending materials and/or liquid absorbing materials (e.g., ingredients to physically stabilize the carrier). Examples of suspending materials include, but are not limited to: cotton-based gauze; non-woven mats made of rayon or blends of rayon, polyester, and/or other polymer fibers; open-cell foams and sponge-like materials comprising polyurethane, polyester and/or other polymers; and crosslinked and non-crosslinked gel materials such as polyacrylamide, polyvinyl alcohol, gelatin, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, and carboxymethyl cellulose.

Examples of liquid-absorbing materials include, but are not limited to: crosslinked and non-crosslinked polymers; swellable polymers such as water-swellable cellulose derivatives (e.g., Methylcellulose (MC), Hydroxyethylmethylcellulose (HEMA), Hydroxypropylmethylcellulose (HPMC), ethylhydroxyethylcellulose (EHEC), Hydroxyethylcellulose (HEC), Hydroxypropylcellulose (HPC), carboxymethylcellulose (CMC), and salts thereof); polyvinyl alcohol (PVA); polyvinylpyrrolidone (PVP); polyethylene oxide (PEO); copolymers made from monomers such as hydroxyethyl methacrylate (HEMA), hydroxyethoxyethyl methacrylate (HEMA), hydroxydiethoxyethyl methacrylate (MDEEMA), methoxyethyl methacrylate (MEMA), methoxyethoxyethyl methacrylate (MEEMA), methyldiethoxyethyl methacrylate (MDEEMA), Ethylene Glycol Dimethacrylate (EGDMA), N-vinyl-2-pyrrolidone (NVP), Methacrylic Acid (MA), and Vinyl Acetate (VAC); polyacrylamide; gelatin; gums and polysaccharides such as acacia, karaya, tragacanth, guar gum, benzoin gum, alginic acid and salts thereof; polyethylene glycol (PEG); polypropylene Glycol (PPG); clays and other swellable mineral materials such as bentonite and montmorillonite. The amount of liquid-absorbable material in the carrier may be from about 0.1% to about 95%, for example from about 1% to about 20% by weight of the carrier.

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

Examples of electrochemically reactive materials in the support of the present invention include, but are not limited to: water and compounds containing elements from groups VIB and VIIB of the periodic table of the elements, such as oxygen, sulfur, fluorine, chlorine, bromine and iodine.

In a fruitIn an embodiment, the reactive species react with the inert anode to form an oxidizing agent. Examples of such reactive species include, but are not limited to: ionic OH^-、Cl^-、I^-、Br^-、SO₃ ^2-And HCO₃ ^-. Thus, the present device is capable of generating oxidants such as nascent oxygen (i.e., singlet oxygen), chlorine, and chlorine dioxide gas, which are difficult to formulate in conventional topical products.

In one embodiment, the reactive species reacts with the inert cathode to form a reducing agent. Examples of such reactive species include, but are not limited to: oxidized or disulfide forms of thio compounds having one or more mercapto functional groups, sulfur-containing amino acids and salts or esters thereof, and sulfides. Examples of such thio compounds include, but are not limited to: thioglycolic acid and its salts, such as calcium, sodium, strontium, potassium, ammonium, lithium, magnesium and other metal salts of thioglycolic acid; a thioethylene glycol; thioglycerol; (ii) a thioalcohol; thioacetic acid; and thiosalicylic acid; and salts thereof. Examples of sulfur-containing amino acids include, but are not limited to, L-cysteine, D-cysteine, 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 strontium sulfide and glutathione disulfide. The inert cathode converts the oxidized or disulfide form of the reactive sulfur compound into a sulfur compound, or a mercapto-containing compound. Examples of such conversions are the conversion of cystine to cysteine and the conversion of the oxidized form of glutathione to glutathione.

In one embodiment, the concentration of the reactive species in the carrier can be from about 0.01 wt% to 25 wt%, for example from about 0.1 wt% to 10 wt% of the carrier. The pH of the carrier may be from about pH 1.5 to pH 9, preferably from pH 2 to pH 7, most preferably from about pH 3 to pH 5.

In one embodiment, the carrier contains a binder. The device is adhered to the barrier membrane using an adhesive. Examples of hydrophobic binders include, but are not limited to: silicones, polyisobutylenes and derivatives thereof, acrylics, natural rubbers, and combinations thereof. Examples of silicone adhesives include, but are not limited to: dow Corning 355 from Dow corninggof Midland, MI; dow Corning 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 Gelva7371 available from Monsanto Company, st.louis, MO; gelvao 7881; gelva 2943; and 1-780 medical grade adhesive available from Avery Dennison of paintesville, OH. Examples of hydrophilic binders include, but are not limited to, papaya and other natural gums, MC, HEMA, HPMC, EHEC, HEC, HPC, CMC, PVA, PVP, PEO, HEMA, hemama, HDEEMA, MEMA, MDEEMA, EGDMA, NVP MA, VAC, polyacrylamide, gelatin, gum arabic, karaya gum, tragacanth gum, guar gum, benzoin gum, alginic acid and salts thereof, polyethylene glycol (PEG), and polypropylene glycol (PPG).

In one embodiment, the concentration of binder in the carrier may be from about 0.1 wt% to about 95 wt%, for example from about 1 wt% to about 20 wt% of the carrier.

Electrode for electrochemical cell

The conductive electrode of the present invention may be a reactive conductive electrode or an inert conductive electrode. By "reactive conductive electrode" is meant that the chemical composition of the conductive electrode itself changes during the course of the electrode chemical reaction, and current passes through the electrode during this process. In one embodiment, the reactive conductive electrode is an anode comprised of a reactive material such as a pure metal or metal alloy, including, but not limited to, zinc, aluminum, copper, magnesium, manganese, silver, titanium, tin, iron, and alloys thereof. The materials that make up the galvanic couples described above can also be used as the reactive conductive electrode. Upon electrical communication, metal ions, such as zinc, copper, magnesium, manganese and/or aluminum cations, are released from the anode into the support and transferred to the barrier membrane. These ions may have a therapeutic effect, such as an antibacterial effect, an immunomodulating effect, an enzyme modulating effect and/or an anti-inflammatory effect.

In one embodiment, the reactive conductive electrode is formed from a reactive material such as a metal halide(e.g., silver-silver chloride (Ag/AgCl), silver-silver bromide, and silver-silver iodide). In this case, the primary electrochemical reaction at the cathode surface is the conversion of solid silver halide to metallic silver, with little unwanted consumption of the oxidant produced at the anode. The liberated chloride ions can then be oxidized to an oxidizing agent, such as chlorine (Cl)₂) Hypochlorous acid (HClO), hypochlorite (ClO)^-) The iodide ions are converted to iodine.

By "inert conductive electrode" is meant that the chemical composition of the conductive electrode itself is not altered. In one embodiment, the anode is comprised of an inert conductive electrode such that electrochemical processes at the surface of the anode produce oxidants such as nascent oxygen (e.g., by electrolysis of water) and/or chlorine-containing oxidants such as chlorine gas, hypochlorite, chlorate, and perchlorate, and chlorine dioxide. Nascent oxygen is an oxidizing agent that inhibits propionibacterium acnes (p.acnes), and chlorine-containing oxidizing agents are potent antibacterial agents with bactericidal activity.

In one embodiment, the conductive electrode is composed of or coated on the surface with an inert material, such as a noble metal (e.g., gold, platinum, or gold-plated conductive metal), a conductive carbon (e.g., glassy carbon or graphite), a carbon-embedded polymer (e.g., carbon silicone rubber), a conductive carbon polymer foam or sponge, silver halide-plated silver (e.g., silver chloride-plated silver, silver bromide-plated silver, and silver iodide-plated silver), and a corrosion resistant alloy.

In one embodiment, the anode of the device, which serves as both the conductive electrode and part of the galvanic couple power source, is comprised of the above-described reactive conductive oxidizable metal, such as zinc, calcium, magnesium, aluminum, iron, tin, copper, or alloys thereof, while the cathode, which also serves as both the conductive electrode and part of the galvanic couple power source, is comprised of the above-described reactive reducible conductive material, such as the more chemically stable metals and their metal halides, oxides, sulfides, or other metal salts, such as silver and silver halides (e.g., silver chloride, silver bromide, silver iodide, silver fluoride), silver oxide, silver sulfide. In one embodiment, the reducible conductive material is in direct contact with the superior conductor, for example: a thin layer of silver chloride, silver oxide or sulfide on metallic silver; a silver chloride powder containing a binder (e.g., silver chloride ink); and/or mixing silver or conductive carbon powder, which is bonded together by a binder, with silver chloride powder (e.g., silver-silver chloride ink and silver chloride-carbon ink) in a matrix.

In another embodiment, the anode of the device of the present invention is comprised of the above-described reactive oxidizable conductive metal, while the cathode is comprised of a mixture of the above-described more chemically stable electrode material, such as conductive carbon, metallic silver, gold or platinum, or a powder mixture of conductive carbon and a noble metal, mixed into a matrix, as described in U.S. Pat. No. 5,162,043.

In one embodiment, the device of the present invention enables the targeted delivery of beneficial zinc to the pilosebaceous unit (e.g., the sebaceous gland and associated hair follicles) through the hair follicles for the treatment of acne or rosacea. Zinc is an essential metal for the human body because it is involved in many biological activities of the human body (for example, a 70 kg person contains about 2.3 g zinc). It is known that zinc deficiency in the human body can lead to skin diseases such as acne.

In another embodiment, the device of the present invention enables targeted delivery of other beneficial metals into hair follicles and pilosebaceous glands using an anode comprised of a zinc alloy containing small amounts of the other beneficial metals. These beneficial metals include, but are not limited to, certain human 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, which are then transferred into the hair follicle under the potential applied to the skin. In one embodiment, the zinc alloy content of the anode is greater than about 50 wt%, such as greater than about 90 wt%.

In one embodiment, the ratio of the electrical conductivity between the first conductive electrode and the second conductive electrode (wherein substantially all electrical connection between the electrodes passes through the skin) as measured by (i) carrier and (ii) hydrated skin of the carrier is from about 10000: 1 to about 1: 100. That is, I_CarrierAnd I_Skin(s)Current distribution between I and I_Carrier/I_Skin(s)Has a value of about 10,000 to about 0.01. I is_CarrierIs the total current (I) through the device_{General assembly}) Only through the carrier layer between the anode and cathode and not through the skinA part of (a) and I_Skin(s)Is I_{Total maximum}The portion of (A) passing through the skin, i.e. I_{General assembly}＝I_Carrier+I_Skin(s)。

Reducing the ratio of carrier conductance to skin conductance will result in a greater proportion of electrical connection through the skin, thereby facilitating iontophoretic delivery of any active agent so delivered into the skin. The addition of less conductive substances to the carrier may non-exclusively reduce the conductivity of the carrier. Examples of such less conductive substances include, but are not limited to, oils such as silicone or hydrocarbon oils, air pockets such as air bubbles or air pockets in a semi-solid carrier, or polymers or clays. In one embodiment, the main objective being the electrochemical generation of substances in the support, I_Carrier/I_Skin(s)The value is about 10,000-1. In one embodiment, where the primary purpose is to deliver an electrical current and/or active agent into the skin, I_Carrier/I_Skin(s)The value is about 10 to 0.01. For certain applications, I can also be adjusted by changing the distance between the first and second electrodes, or a decrease between the second conductive electrode and the skin_Carrier/I_Skin(s)The value is obtained. For example, as the distance between two conducting electrodes decreases, the conductance measured between the two electrodes increases, I_CarrierAlso increases, resulting in I_Carrier/I_Skin(s)The value increases. On the other hand, if the distance between the two conductive electrodes and the skin increases, I_Skin(s)Increase, lead toI_Carrier/I_Skin(s)The value decreases.

Electrochemically generated zinc ions

In one embodiment, the zinc ions are electrochemically generated by the zinc anode in the topical composition, or added later. The topical composition is then applied to the user's barrier membrane to achieve the specific beneficial effects of the zinc ions and other active agents present in the topical composition. The active agent in the topical composition may comprise an anti-acne agent such as salicylic acid or benzoyl peroxide. The method of preparing such electrochemically generated zinc ions is to enclose the electrochemical device for zinc generation in a packaging and/or dispensing container for the topical composition (e.g., a bottle for acne-treatment/skin cream with a dispensing pump). In one embodiment, an electrochemical device comprising a zinc anode, a silver/silver chloride cathode, and a power source (e.g., a battery) in electrical communication with each other is contained within the dispensing pump. As the topical composition (e.g., cream) exits the dispensing pump, it contacts the zinc anode and cathode and completes the electrical circuit (i.e., current flows from the anode into the cream and returns through the cathode to the power source), the zinc anode begins to release zinc ions into the cream. Alternatively, the electrochemical device for producing zinc does not include a battery. Instead, a zinc anode and cathode are connected to form a galvanic cell, and zinc ions are generated when both electrodes are contacted with the cream.

Active agent

In one embodiment, the carrier comprises one or more active agents, "active agent" refers to a compound (e.g., synthetic or isolated from natural sources) having a cosmetic or therapeutic effect (e.g., a substance capable of producing a biological effect on the human body) on the barrier membrane and its surrounding tissues, such as therapeutic drugs, including but not limited to organic and macromolecular compounds.

In one embodiment, the carrier comprises an anti-acne and/or anti-rosacea agent examples of anti-acne and anti-rosacea agents include, but are not limited to, retinoids such as tretinoin, isotretinoin, motretinide, adapalene, tazarotene, azelaic acid and vitamin A, salicylic acid, benzoyl peroxide, resorcinol, sulfur, sulfacetamide, urea, antibiotics such as tetracycline, clindamycin, metronidazole and erythromycin, anti-inflammatories such as corticosteroids (e.g., hydrocortisone), ibuprofen, naproxen and hetrofen, imidazoles such as ketoconazole and elubiol, salts and prodrugs thereof, other examples of anti-acne active agents include essential oil, α -bisabolol, dipotassium glycyrrhizinate, camphor, β -glucan, allantoin, chamomile, isoflavones such as isoflavones, sabal palm fiber, chelators such as EDTA, lipase inhibitors such as silver and copper ions, hydrolyzed vegetable proteins, inorganic chloride, iodide, fluoride and other chloride, fluoride ions, and other synthetic non-ionic derivatives such as synthetic phospholipids and synthetic phospholipids^TMPhospholipids CDM, SV, EFA, PLN and GLA (Uniqema, ICI group Companies, Wilton, UK).

In one embodiment, the device of the present invention comprises an anti-aging agent examples of suitable anti-aging agents include, but are not limited to, inorganic sunscreens such as titanium dioxide and zinc oxide, organic sunscreens such as octyl-methoxy cinnamate, retinoids, Dimethylaminoethanol (DMAE), copper-containing peptides, vitamins such as vitamin E, vitamin A, vitamin C, vitamin B and salts or derivatives thereof such as ascorbic acid diglucoside and vitamin E acetate or palmitate, α hydroxy acids and precursors thereof such as glycolic acid, citric acid, lactic acid, malic acid, mandelic acid, ascorbic acid, α -hydroxybutyric acid, α -hydroxyisobutyric acid, α -hydroxyisocaproic acid, altrolac acid, α -hydroxyisovaleric acid, ethyl pyruvate, galacturonic acid, glucoheptonic acid, 1, 4-lactone, gluconic acid, gluconolactone, glucuronolactone, isopropyl pyruvate, methyl pyruvate, mucic acid, pyruvic acid, glucaric acid 1, 4-lactone, tartaric acid and hydroxylactone, glycolic acid such as 48363-hydroxybutyric acid, β -phenyl-lactic acid, caffeic acid, zinc oxide, and salts or prodrugs of plants such as Glycyrrhiza, Glycyrrhiza glabra, Glycyrrhiza uralensis, and.

In one embodiment, the carrier contains a decolorizing agent. Examples of suitable decolorizing agents include, but are not limited to: a soybean extract; soy isoflavones; retinoids such as vitamin a; kojic acid; dipalmitoyl kojic acid ester; hydroquinone; arbutin; a transexamic acid; vitamins such as niacin and vitamin C; azelaic acid; linolenic acid and linoleic acid; placertia; licorice root; extracts such as chamomile and green tea; and salts and prodrugs thereof.

In one embodiment, the carrier comprises a plant extract. Examples of plant extracts include, but are not limited to: yellowsonia inermis, soybean glycine, oat flour, wheat (what), aloe vera, raspberry, witch hazel, Japanese alder, arnica, oriental wormwood, asiasari radix, white birch, calendula, chamomile, Japanese ligusticum wallichii, daisy, fennel, gallnut, hawthorn, houttuynia, hypericum, date, kiwi (kiwi), licorice, magnolia, olive, peppermint, heliothis, sage, sasa albo-marginata, natural isoflavones, soy isoflavones, and natural essential oils.

In one embodiment, the support contains a metal, such as a metal ion, metal salt, metal complex, fine metal powder, 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. The metal ions provide effects such as antibacterial, anti-inflammatory and/or sebum reduction. Such beneficial metal ions can be released by electrochemical oxidation of the metal anode (e.g., zinc ions are electrochemically generated from the zinc anode) with the passage of an electrical current.

In another embodiment, such beneficial ions may be indirectly from electrochemical reactions at the electrode surface, such as hydrogen and hydroxide ions generated at an inert electrode, and then subjected to a process that produces beneficial ions. For example, the device of the present invention may contain a power source, an inert electrode (e.g., platinum coated conductive electrode, gold or gold coated conductive electrode), a reactive cathode (e.g., silver/silver chloride electrode), an aqueous carrier composition containing an oxide (e.g., zinc oxide particles) among other active agents. When applied to the skin, the excess hydrogen ions generated by electrolysis of water at the inert anode acidify the carrier to a lower pH, whereas the electrochemical reaction at the reactive electrode (e.g., conversion of silver chloride to silver ions) does not affect the pH. As the solution becomes more acidic, the oxide begins to dissolve releasing ions (e.g., zinc ions) that have a beneficial effect on the barrier membrane.

Other active agents include those commonly used as topical therapeutic and cosmetic treatments for skin tissue, such as topical antibiotics for wounds, topical antimycotics for treating fungal infections of the skin and nails, and antipsoriatic agents for treating psoriatic lesions of the skin and psoriatic nails.

Examples of antifungal agents include, but are not limited to: miconazole, econazole, ketoconazole, sertaconazole, itraconazole, fluconazole, voriconazole, clioquinol, bifoconazole, terconazole, butoconazole, tioconazole, oxiconazole, sulconazole, clotrimazole, undecylenic acid, haloprogin, butenafine, tolnaftate, nystatin, ciclopirox olamine, terbinafine, amorolfine, naftifine, elubiol, griseofulvin, and pharmaceutically acceptable salts and prodrugs thereof. In one embodiment, the antifungal agent is an azole, an allylamine, or a mixture thereof.

Examples of antibiotics (or disinfectants) include, but are not limited to: mupirocin, neomycin sulfate bacitracin, polymyxin B, 1-ofloxacin, tetracyclines (aureomycin hydrochloride, oxytetracycline hydrochloride-10 and tetracycline hydrochloride), clindamycin phosphate, gentamycin sulfate, metronidazole, hexylresorcinol, benzethonium chloride, phenol, quaternary ammonium compounds, tea tree oil and pharmaceutically acceptable salts and prodrugs thereof.

Examples of antimicrobial agents include, but are not limited to, salts of chlorhexidine, such as thiodipropyl butyl aminomethyl, urea aldehyde (diazolidinyl urea), diglucose chlorhexidine ester, chlorhexidine acetate, chlorhexidine isethionate, and chlorhexidine hydrochloride. Other cationic antibacterial agents may also be used, for example benzalkonium chloride, benzethonium chloride, tricarbazine (tricarban), polyhexamethylene biguanide, cetylpyridinium chloride, methylbenzethonium chloride (chloride). Other antimicrobial agents include, but are not limited to: halogenated phenolic compounds, such as 2, 4, 4' -trichloro-2-hydroxydiphenyl ether (triclosan); p-chloro-m-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% by weight of the carrier, such as less than 5% by weight of the carrier) so that it does not cause excessive drying of the barrier membrane.

Antipsoriatic drugs or drugs used to treat seborrheic dermatitis include, but are not limited to: corticosteroids (e.g., betamethasone dipropionate, betamethasone valerate, clobetasol propionate, diflorasone diacetate, halobetasol propionate, triamcinolone, dexamethasone, fluocinolone acetonide, halcinonide, triamcinolone acetonide acetate, hydrocortisone valerate, hydrocortisone butyrate, alclometasone dipropionate, fluocinolone acetonide, mometasone furoate, methylprednisolone acetate), methotrexate, cyclosporine a, calcipotriene, anthralin, shale oil and its derivatives, elubiol, ketoconazole, coal tar, salicylic acid, zinc pyrithione, selenium disulfide, hydrocortisone, sulfur, menthol, and pramoxine hydrochloride, and salts and prodrugs thereof.

Examples of antiviral agents useful for viral infections such as herpes and hepatitis include, but are not limited to, imiquimod and its derivatives, podofilox, podophyllin, interferon α, acyclovir, famciclovir, valacyclovir, reticros, and cidofovir, as well as salts and prodrugs thereof.

Examples of anti-inflammatory agents include, but are not limited to, suitable steroidal anti-inflammatory agents, for example, corticosteroids such as hydrocortisone, hydroxytriamcinolone, α -methyl dexamethasone, dexamethasone phosphate, beclomethasone dipropionate, clobetasol valerate, desonide, desoximetasone, deoxycorticosterone acetate, dexamethasone, dichloropine, diflorasone diacetate, diflucortolone valerate, fluadronolone, fluocinolone, fludrocortisone, diflucortolone pivalate, fluocinolone Acetonide, fluocinonide, fluocortolone butyrate, fluprednide, fludrocortolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone Acetonide, cortisone, cortolone, flucetonide, fludrocortisone, difluprednide, fludroxyprednisone, amcinolone Acetonide, triamcinolone Acetonide.

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 retardants such as eflornithine hydrochloride; anti-hypertensive agents; drugs for the treatment of coronary artery disease; anti-cancer agents; endocrine and metabolic drugs; a neuroleptic agent; drugs that block chemical adduction, motion sickness; protein and peptide drugs.

In one embodiment, the carrier contains fragrances, such as lavender and chamomile, that are effective in reducing stress, tranquilizing, and/or improving sleep.

The amount of active agent in the carrier will depend on the particular use of the active agent and/or the device. In one embodiment, the carrier contains a safe and effective amount of active agent, for example, from about 0.001% to about 20% by weight of the carrier, such as from about 0.01% to about 5% by weight of the carrier.

Light emitting diode

In one embodiment, the device contains one or more light emitting diodes. A Light Emitting Diode (LED) of some spectral spectrum may be included in the device to emit light onto the barrier membrane (e.g., to treat skin conditions such as acne and rosacea). The light emitting diode may also provide a signal to the user indicating that the device is functioning properly.

In one embodiment, the LEDs emit light periodically (i.e., flash the LEDs). In another embodiment, the LED also regulates the current through the barrier film, creating a pulsating DC current. This pulsating DC current may facilitate the delivery of active agents into the barrier membrane, stimulating a biological response in the barrier membrane, for example, promoting healing of a wound (such as in an acne lesion) and/or enhancing skin feel to provide a signal to the user that the device is functioning. Another potential advantage of using a blinking LED is that a pulsating DC current is provided without the need for complex circuitry.

The LED of the present invention has a spectrum of about 300nm to about 1500nm, for example about 350nm to about 1000 nm. In one embodiment, the range of LEDs includes the violet-blue, green, red and infrared ranges, such as from about 400nm to about 450nm, such as from about 407nm to about 420 nm; about 510nm to about 550 nm; about 600nm to about 700 nm; about 1300nm to about 1500 nm. In one embodiment, the device has two LEDs, one emitting light having a wavelength of about 400nm to about 500nm and one emitting light having a wavelength of about 700nm to about 1000 nm. The carrier may contain a photosensitizer, such as 5-aminolevulinic acid (ALA), hypericin, st john malt flour or extract, or other synthetic or natural photosensitizer as an active agent, which is delivered and irradiated by the LED-bearing device of the present invention. Light radiation from the LED, as well as photosensitizers and other active agents described above, electrochemically generated oxidants (e.g., peroxides, nascent oxygen, chlorine dioxide and chlorine), and/or electrical stimulation of the barrier membrane can act synergistically to achieve improved results in the treatment of membrane disorders such as acne and rosacea.

General purpose

In one embodiment, the present device is used in the treatment of barrier membrane diseases (e.g., delivery of active agents and/or electricity into membranes such as skin, eye (stratum corneum, retina, etc.), oral, buccal, nasal, vaginal, gastrointestinal or rectal mucosal barrier membranes). In one embodiment, the device is used to treat a skin condition. Examples of such treatments include, but are not limited to: treating acne, rosacea, or other microbial infections of the skin; reducing visible features of skin aging (e.g., wrinkles, sagging, and age spots); folliculitis and pseudofolliculitis barbae; treating wounds and wounds (e.g., promoting healing and lightening scars); sebum regulation (e.g., reducing sebum or inhibiting or controlling the appearance of oily/shiny skin); pigment modulation (e.g., reducing hyperpigmentation or pigmentation in light-colored skin); hair growth retardants (e.g., skin on the legs) or hair irritants (e.g., scalp); and treating dermatitis (e.g., atopic dermatitis, contact dermatitis, or seborrheic dermatitis) and/or psoriasis.

In another embodiment, the device is used to treat mucosal (e.g., oral or vaginal mucosa) diseases. Examples of such treatments include, but are not limited to: treating vaginal candidiasis and vaginosis, genital and oral herpes, herpes labialis, aphtha, oral hygiene, periodontal disease and other microbial infections of the mucous membranes.

Another embodiment of the present invention is a device that elicits a desired biological response that facilitates treatment of a barrier membrane condition. This desired biological response may be caused by electrical connection through the barrier membrane, and/or electrochemically generated oxides, which are delivered from the carrier through iontophoresis along with the active agent for the treatment of barrier membrane diseases. Examples of desired reactions of the barrier film include, but are not limited to: sebum regulation (e.g., reduced sebaceous gland activity), inhibition of growth of anaerobic microorganisms and establishment of a healthier membrane microflora or (e.g., reduced growth of propionibacterium acnes and reduced production of irritating fatty acids), vasoconstriction (thus promoting local accumulation of active agents or removal of dark eye circles due to deoxyhemoglobin), enhanced tissue immune activity (e.g., increased clearance of pathogenic microorganisms on the tissue's own defense system), improved tissue repair (e.g., enhanced healing and lightening of damaged scars such as acne scars), and improved stratum corneum-separating activity of the carrier (e.g., softening and promoting clearance of acne keratotic plugs in acne miliaria and blackhead acne).

In another aspect, the invention also provides a method for converting an active agent from a less active form to a more active form (e.g., cystine to cysteine, acetyl-cysteine disulfide to acetyl-cysteine, and vitamin a to vitamin a) by oxidation or reduction of an inert electrode. Thus, labile agents can be stored in a more stable form and converted to their active form prior to administration. In yet another aspect, the reducing agent produced by the device of the present invention can be used to stabilize an oxygen-sensitive active agent. Examples of such oxygen-sensitive active agents include, but are not limited to, retinoids, ascorbic acid, and benzoyl peroxide.

In one embodiment, the present invention also provides a method for converting an active agent from a less active form to a more active form by oxidation with a reactive anode, such as an anode comprised of zinc, magnesium, copper, aluminum, alloys or mixtures of these metals. For example, an anode made of zinc releases zinc ions as electrical connections are made through the electrodes. The zinc ions generated by this electrochemical reaction are then transported into the barrier membrane by positively charged repulsion. In one embodiment, such ions are deposited on hair follicles and/or sebaceous glands, thereby inhibiting the growth of propionibacterium acnes and/or inhibiting skin tissue infections due to overgrowth of propionibacterium acnes prior to 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, respectively, into the hair follicles and sebaceous glands for the treatment and prevention of acne.

Skin diseases

In one embodiment, the device of the present invention is used to treat skin disorders such as: acne and acne (e.g., blackheads and whiteheads) and acne-related skin disorders such as rosacea and nodular-cysts; hyperpigmentation such as freckles, dark spots, actinic and senile lentigo, age spots, post-inflammatory hyperpigmentation, Becker nevi, dark circles under the eyes, facial melanosis; stress marks; skin aging effects on the skin (e.g., due to photodamage) include wrinkles, roughness, pigmentation, pallor, fine lines, and laxity, delivered to the skin tissue by passing a pre-formulated active agent and an electrochemically generated active agent (e.g., beneficial metal ions) contained in a carrier through the electrodes, and/or by providing electrical stimulation.

In one embodiment, the device of the present invention provides multiple mechanisms of action to treat the above-mentioned disorders: that is, (a) targeted delivery of a pre-formulated active agent into the pilosebaceous unit by iontophoresis and electroosmosis; (b) electrochemically generating new active agents (e.g., beneficial metal ions from a reactive anode) and targeting the freshly generated active agents to the pilosebaceous unit (e.g., beneficial ions such as zinc and copper are known to enhance the skin's autoimmune system); and/or (c) providing electrical stimulation of the pilosebaceous unit and its surrounding skin tissue to increase blood circulation and treat skin disorders by reducing inflammation, promoting wound healing and/or increasing skin exfoliation.

Wounds and scars

In one embodiment, the present device may be incorporated into wound dressings and wound dressings to provide electrotherapy for enhanced healing and scar prevention. In one embodiment, wound exudate and/or wound lotion is used to activate an electric wound dressing/dressing to deliver active agents and/or electrochemically generated beneficial metal ions pre-contained in the wound dressing/dressing into the wound. The device may also treat wounds with therapeutic currents that increase blood circulation, stimulate tissue immune response, and/or inhibit tissue inflammation, thereby accelerating healing and scar reduction.

Enhanced chemical peeling

Chemical peel treatment is an ongoing method of applying chemical agents to the skin to cause controlled destruction or exfoliation of the old skin and to stimulate new epidermal growth with a more uniform distribution of melanin. When the desquamating agent reaches the dermis layer, important wound healing activities are produced, resulting in skin remodeling and skin smoothing, both of which have anti-aging effects. Delivery of chemical exfoliants for inclusion in electrical generating devices/compositions can be used in the treatment of a number of skin conditions, including but not limited to acne, post-inflammatory hyperpigmentation, dark spots, scars, photodamage, age spots, wrinkles, stress marks, birthmarks, uneven texture and tone, warts, and pseudofolliculitis barbae. The device/composition also has the added advantage of reducing skin irritation and reducing the risk of pre-cancerous and early cancerous lesions of photo-aged skin on the face, since iontophoretic administration of chemical peels enables the use of much lower concentrations of chemical peels than standard chemical peeling methods that do not use such devices. The reduction in the need for chemical exfoliants also minimizes the risk of erythema, inflammation, and scarring from chemical exfoliations following continued desquamation while achieving the desired effect.

Examples of chemical exfoliants include, but are not limited to, hydroxy acids such as α -hydroxy acids, e.g., lactic acid, malic acid, glycolic acid arginine, ammonium glycolate, and sodium glycolate, β -hydroxy acids such as salicylic acid, polyhydroxy acids (PHAs) such as gluconolactone, and non-hydroxy acids such as acetic acid, trichloroacetic acid (TCA), pyruvic acid, and α -keto-acid, phenol, and derivatives or mixtures thereof, which may also be combined with sulfur, resorcinol, retinoids, or other active agents such as Jessner's solution exfoliants (which contain lactic acid, salicylic acid, resorcinol, and ethanol).

In one embodiment, the device is applied to the skin for a period of time ranging from about 2 minutes to about 10 minutes, depending on the skin condition of the individual. In one embodiment, the carrier contains about 0.1% to 70% by weight of the chemical exfoliant, such as about 0.5% to 20%, such as about 2% to 10%.

Shape of

The device includes a housing that can be configured in a variety of shapes and sizes to match the contours of a variety of tissue surfaces of the barrier membrane. For example, the housing may be a substrate shaped as a mask with openings/holes to expose the entire face of the eye, eyebrow, nose and mouth; a partial mask covering only the upper or lower half of the face; or a patch that covers only the forehead, or under the eye area, chin and jaw area, neck, back, wound, acne lesion or pustule or other specific barrier membrane area in need of treatment.

In one embodiment of the invention, the housing is a water insoluble substrate containing galvanic couples such as fine zinc wires or zinc coated fine fibers (e.g., zinc coated polymeric fibers) connected to fine copper wires or copper coated fine fibers (e.g., copper coated polymeric fibers). One or more such fine galvanic couple wires or fibers may be included in the substrate to create a device that generates an electric current when contacted with a carrier, such as tap water or a liquid or semi-liquid composition containing an active agent. In one embodiment, the galvanic couple-containing substrate can be comprised of multiple layers, such as a layer of a zinc-containing substrate (e.g., fine zinc wires or zinc-coated fine fibers in a woven or nonwoven fabric) on top of a layer of a copper-containing substrate (e.g., fine copper wires or copper-coated fine fibers in a woven or nonwoven fabric). When in use, the layers are contacted with each other to form a galvanic couple. In another embodiment, the device releases beneficial ions (e.g., zinc ions or aluminum ions) that are transferred to the barrier membrane (e.g., skin) when the substrate is applied by the user (e.g., used as a wipe to clean the skin or as a mask or mask to treat the skin). The active agent may also be added to the substrate during manufacture or applied to the substrate prior to application to the barrier film (e.g., wetting the substrate with an electrolyte or a liquid spray containing the active agent). In one embodiment, the fabric is used as a dry wipe or a dry full or partial mask that is moistened just prior to use, in which case water is first added to the dry wipe or mask to pre-moisten the skin (e.g., by washing with tap water).

By "water insoluble" is meant that the substrate is not readily soluble or decomposable by immersion in distilled water at 25 ℃. However, the water-insoluble substrate may disintegrate or dissolve slowly, for example over a period of hours to days. A number of materials can be used as the water insoluble substrate. Examples of suitable substrates include, but are not limited to: nonwoven substrates, woven substrates, hydroentangled substrates, air-entangled substrates, natural sponges, synthetic sponges, and polymeric screens.

The water insoluble substrate may be rinsed away. As used herein, "flushable" means that the substrate can pass through at least 10 feet of a waste pipe in two toilet flushes. The material may also be biodegradable.

In one embodiment, the substrate comprises a nonwoven material. By "nonwoven" is meant that the substrate or a layer of substrate is comprised of fibers that are not woven into a fabric, but rather are formed into a sheet, mat, or blanket. The fibers may be random (i.e., randomly aligned) or carded (i.e., carded to be primarily oriented in one direction. furthermore, the nonwoven substrate may be comprised of a combination of layers of random fibers and layers of carded fibers).

The nonwoven substrate can be constructed from a variety of natural and/or synthetic materials. By "natural" is meant that the material is derived from plants, animals, and insects or by-products of plants, animals, and insects. By "synthetic" is meant that the material is obtained primarily from various artificial materials or from further processing of natural materials. Non-limiting examples of natural materials for use in the present invention are silk cellulose, keratin fibers (e.g., wool fibers, camel hair fibers) and cellulosic fibers (e.g., wood pulp fibers, cotton fibers, hemp fibers, jute fibers, and flax fibers).

Examples of synthetic materials include, but are not limited to: acetate fibers, acrylic fibers, cellulose ester fibers, cotton fibers, modacrylic fibers, polyamide fibers, polyester fibers, polyolefin fibers, polyvinyl alcohol fibers, rayon fibers, polyurethane foams, and mixtures thereof.

Substrates composed of one or more natural and synthetic materials useful in the present invention are available from a variety of commercial sources, such as Freudenberg & Co. (Durham, NC USA), BBA Nonwovens (Nashville, TN USA), PGI Nonwovens (North Charleston, SC USA), Buckey technologies/Walksofft (Memphis, TN USA), and Fort James Corporation (Deerfield, IL USA).

Methods of making nonwoven substrates are also well known in the art. These methods include, but are not limited to: air laying, water laying, melt blowing, spunbond or carding processes. The resulting substrate is then subjected to at least one of several bonding methods, regardless of the method of preparation or composition, to secure the individual fibers together to form a self-supporting web. Nonwoven substrates can be prepared by a variety of methods including hydroentanglement, thermal bonding, and combinations of these methods. Also, the substrate may have a single layer or multiple layers. In addition, the multilayer substrate may include a film layer (e.g., a porous or non-porous film layer) and other non-fibrous materials.

The strength and consistency of the nonwoven material may be a desired characteristic. This can be achieved, for example, by adding binding materials, such as wet strength resins, or by materials consisting of polymeric adhesive coatings, such as stable fibers based on cotton, wool, linen and the like. Wet strength resins include, but are not limited to: ethyl acetate-ethylene (VAE) and Ethylene Vinyl Chloride (EVCL) Airflex emulsions (Air Products, Lehigh, PA), Flexbond acrylic polymers (Air Products, Lehigh, PA), Rhoplex ST-954 acrylic adhesives (Rohm and Haas, Philadelphia, PA), and Ethylene Vinyl Acetate (EVA) emulsions (DUR-O-SET, National starch chemicals, Bridgewater, NJ). The amount of bonding material in the substrate may be from about 5% to about 20% by weight of the substrate.

Strength can also be obtained using so-called spunlace or hydroentanglement techniques to increase the strength of the nonwoven material. In this technique, the individual fibers are kinked together, resulting in acceptable strength and consistency without the use of a bonding material. The latter technique has the advantage of excellent softness of the nonwoven material.

In one embodiment, the nonwoven material is composed of superabsorbent polymers. For purposes of the present invention, the term "superabsorbent polymer" refers to a material that is capable of absorbing and retaining at least about 10 times its weight in body fluids under a pressure of 0.5 psi. The superabsorbent polymer particles of the invention may be inorganic or organic crosslinked hydrophilic polymers, such as polyvinyl alcohol, polyethylene oxide, crosslinked starch, guar gum, xanthan gum, and other materials known in the art of absorbent article manufacture.

Additives may also be added to increase the softness of the substrate. Examples of such additives include, but are not limited to: polyols such as glycerol, propylene glycol and polyethylene glycol, phthalate derivatives, citric acid esters, surfactants such as polyoxyethylene (20) sorbitan esters and acetylated monoglycerides.

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.

In one embodiment, the device of the present invention is used as a wipe and towel (e.g., having a surface area of about 20 cm)²-10,000cm²). In another embodiment, the device of the present invention is used as a therapeutic patch or mask to be applied to a portion or substantially all of the face (e.g., having a surface area of about 1 cm)²-600cm²)。

In one embodiment, the carrier is present prior to use in an amount of at least about 50%, for example at least about 75%, of the total weight of the water-insoluble substrate. In another embodiment, (i) the liquid carrier is present in an amount of at least about 10%, for example less than about 1% by weight of the total weight of the water-insoluble substrate (e.g., the device may not contain a carrier prior to use). In another embodiment, the product comprises instructions directing the user to (i) wet the substrate or (ii) wet the barrier membrane (e.g., skin) with water and/or another liquid prior to application.

Device for measuring the position of a moving object

One embodiment of the present invention is schematically represented as figure 1. The apparatus 500 comprises: a removable release liner (release liner)100, a carrier layer 120, a first conductive electrode 140, a second conductive electrode 240, electrical leads 110 and 210 connecting two ends of an electrically insulating connecting wire 350 to two different conductive electrodes, an optional power switch 330 located on the leads 210, a backing layer 160, and a cover layer 340.

The spacing "b" represents the distance between the two conductive electrodes 140 and 240 and the release liner (or film after application of the device), and the spacing "a" represents the distance between the two oppositely charged conductive electrodes. In one embodiment, the spacing "a" is about 0-20 centimeters and the spacing "b" is about 0-1 centimeter. In another embodiment, the ratio of interval "a" to interval "b" is about 0-20.

In a device containing a battery as a power source, the electrically insulated connection wire 350 may be replaced with a battery (not shown) in the figure. The cell may be provided with an electrically insulating, water-impermeable polymer layer (not shown in the figures). Optionally, circuitry (not shown) may be present 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.

When a zinc-air battery is used as the power source for the device 500, the battery (not shown) is constructed such that the holes in the stainless steel cover face the opposite side of the carrier layer 120. The cell cover layer is perforated to expose the pores of the zinc air cell covered by a removable oxygen impermeable cover. In this case, the power switch 330 is replaced by a removable oxygen impermeable cover. The removable oxygen impermeable cover can be used to initiate (by removing it) or terminate (by re-covering the pores) the electrotransport process of the device.

The backing layer 160 is impermeable to the active agent contained in the carrier layer 120, and, preferably, is 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 impermeable to water and electrically insulating, for example, a polymer such as polyethylene, polypropylene, polyvinyl acetate, polyurethane, silicone rubber, or polyvinyl chloride.

In another embodiment, the backing layer 160 is permeable to electrochemically generated gases (e.g., oxygen, chlorine, and hydrogen) to limit excessive accumulation of gases in the carrier, as such excessive accumulation of gases can cause irritation to human tissue and/or undesirable device deformation. Examples of such "breathable backing" materials include, but are not limited to, cotton or synthetic woven and nonwoven layers, such as the textile materials commonly used in bandages and athletic bandages.

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 liquid droplets such as creams, lotions, emulsions, multiple emulsions, microemulsions and/or liposome compositions. The support layer 120 may also contain a solid support matrix (e.g., gauze, nonwoven material, or sponge-like material).

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 polymer coated fabric that has weak adhesion to the adhesive hydrogel layer 120, thus allowing it to be easily removed from the carrier layer 120 before use without damaging the carrier layer 120. Examples of polymers commonly used as release liners 100 are silicone and polyethylene. Alternatively, the release liner 100 may be coated with wax instead of polymer.

In addition to or instead of using an adhesive in the carrier layer 120, the devices 500 may be secured to the barrier membrane with tape, elastic tape, a band of buckles (similar to a watchband), or Velcro @'s bands.

In use of the device 500, the removable release liner layer 100 is peeled away, securing the carrier hydrogel layer of the device 500 to a barrier membrane of a user, for example, a skin or mucosal membrane such as a vaginal, oral, buccal, nasal, gastrointestinal or rectal mucosal barrier membrane. If the carrier layer 120 contains an adhesive hydrogel, the device can be secured directly to the barrier film. Turning on power switch 330 applies a potential difference between conductive electrodes 140 and 240.

Another embodiment of the invention is schematically represented in fig. 2. Electrically insulated connecting wires 350 are located within the carrier layer 120. The advantages of this structure are reduced bulk, enhanced aesthetics and comfort of use.

The light emitting portion of the LED 122 is preferably located within the carrier layer 120 next to the skin. Placing the light source in a carrier layer 120 secured to the barrier film has the advantage of minimizing loss of light energy due to reflection from the skin surface. In addition, the use of a light reflective layer (e.g., a metallized polymer film) as the backing layer 160 can further enhance the effectiveness of phototherapy and achieve more uniform illumination. The backing layer 160 may optionally be perforated as some point that makes the light visible to the user as an indication that the device is functioning properly.

Another embodiment of the invention is schematically represented in fig. 3. The backing layer 160 (e.g., housing) includes an adhesive layer 130 coated on the outer edge of the backing layer 160 for securing the device to the barrier membrane in 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: silicones, polyisobutylenes and derivatives thereof, acrylics, natural rubbers, and combinations thereof. Suitable silicone adhesives include, but are not limited to, Dow Corning 355 (available from Dow Corning of Midland, Mich.); dow Corning X7-2920; dow Corning 0X 7-2960; GE 6574 (available from General Electric Company of Waterford, NY); a 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 adhesives.

One embodiment of the invention is a two-pack system in which the electrical device and the carrier (or a portion of the carrier) are packaged separately. A portion of the carrier layer 120 may be a matrix that holds an anhydrous liquid, such as a dry woven or nonwoven fabric, a sponge, or a dehydrated hydrogel layer (e.g., a lyophilized hydrogel), while the liquid portion of the carrier, such as a solution, gel, or cream containing the active agent, is packaged in a separate liquid-containing compartment (not shown), such as a unit dose pouch, gas-permeable container, or vial. Prior to use, the liquid-containing chamber is opened and the liquid or semi-solid portion of the carrier is applied to a liquid-immobilized substrate to activate the generation of an electrical current for dermal application. The active agent is contained in a matrix that immobilizes the liquid or in a liquid/semisolid composition.

One embodiment of the present invention is schematically represented as figure 4. The conductive electrodes 140 and 240 are in electrical communication with each other through a direct connection, i.e., the separation "a" (the distance between two oppositely charged conductive electrodes) is equal to zero. The two conductive electrodes form a galvanic couple that contacts the carrier layer 120, the carrier layer 120 is encapsulated in the backing layer 160, and the opening is secured to the release liner 100 with an adhesive layer 130. One of the main advantages of this construction is the simplicity and ease of manufacture.

Another embodiment of the invention is schematically represented in fig. 5. The electrotransport device 800 comprises two electrode assemblies 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, an electrically insulated connecting wire 350 and an optional electrical switch 330. Similar to the typical iontophoresis device described above, the two electrode assemblies 200 and 600 are fixed to the barrier membrane, respectively, after the release liner 100 is removed before use.

In one embodiment, the carrier layer 120 comprises at least two oppositely charged active agents. An example of such a composition is one containing about 0.5-2% salicylic acid and about 0.01-0.2% cationic quaternary ammonium antimicrobial agents (e.g., benzalkonium chloride, benzethonium chloride, methylbenzethonium chloride, and cetylpyridinium chloride), phenol, and/or chlorhexidine gluconate. The device 500 of the present invention can simultaneously deliver active agents of opposite charge into the barrier membrane.

Fig. 6 and 7 show two different configurations of examples of different conductive electrodes 140 (double line representation) and 240 (single line representation) in carrier layer 120 connected by electrically insulated wires 350 (three line representation) to form a galvanic couple power source. Fig. 6 shows that the conductive electrodes 140 and 240 are arranged in a staggered configuration with respect to each other. Fig. 7 shows the conductive electrodes as concentric circular configurations.

Fig. 8 and 9 show two different configuration examples of different conductive electrodes 140 and 240 in carrier layer 120, interconnected by connecting wires 350 as shown in fig. 8 or by direct physical contact at interface 370 as shown in fig. 9, forming a plurality of galvanic couple power sources in contact with carrier layer 120. The conductive electrodes 140 and 240 in fig. 8 and 9 are in a parallel configuration and a perpendicular configuration, respectively.

In fig. 8, the alternating parallel arrangement of the conductive electrodes 140 and 240 results in a more uniform current distribution throughout the carrier layer 120 and underlying dermal tissue, thereby facilitating more uniform delivery of the active agent into the skin. One exemplary manufacturing method of forming a galvanic cell device, shown in fig. 8, is to knit a silver-coated polymer fabric and a zinc-coated polymer fabric (or zinc wire) into a liquid-absorbing fabric layer according to a parallel electrode pattern, and then connect a zinc electrode and a silver electrode by printing with a conductive ink (e.g., a conductive silver ink or a carbon ink) on the silver and zinc regions. Another layer of electrically insulating ink is overlaid on the conductive ink, creating electrically insulating connection lines 350.

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 polymeric substrate layer (e.g., a polymeric material comprised of backing layer 160) to produce a first conductive electrode; a second conductive electrode was printed with conductive zinc ink. Then, two different conductive electrodes are connected by printing through them with a conductive silver ink or zinc ink (or different conductive inks such as carbon ink). Then, a covering ink is optionally printed on the connection lines to produce an electrically insulating polymer layer on the connection lines. If a device is made that is not insulated with an electrically insulating cover, the resulting device is a variation of the device shown in FIG. 9.

Fig. 9 is a top view of one embodiment of the present invention showing conductive electrodes 140 and 240 interconnected by direct physical contact at interface 370 to form a plurality of galvanic couple power sources in contact with carrier layer 120. The conductive electrodes 140 and 240 are arranged in a vertical configuration. The method of manufacturing the device of fig. 8 described above is also applicable to the manufacture of such a device.

Fig. 10 is a top view of one embodiment of the present invention showing a device constructed of a zinc mesh with conductive electrodes 140 (shown in bold lines) and conductive electrodes 240 (shown in double lines) connected by electrically insulated connecting wires 350 (shown in single lines) embedded in a carrier layer 120. The conductive electrode 140 is an uncoated area of 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 portion of the zinc mesh with an electrically insulating paint, ink or polymer solution.

Fig. 11 is a top view of one embodiment of the present invention showing conductive electrodes 140 and 240 embedded in carrier layer 120. The conductive electrode 140 is made of a sheet of zinc mesh. Conductive electrode 240 is prepared by coating the designated portions of the zinc mesh with silver-silver chloride ink or silver ink, or other silver deposition methods such as electroless deposition (chemical reduction deposition), electroplating, plasma spraying, or vacuum deposition. Eliminating electrically insulated connecting wires 350 in this configuration simplifies the manufacturing process. The location, pattern, shape and size of the metallic silver, silver-silver chloride or silver-silver oxide electrodes may vary according to the needs of a particular product.

Zinc mesh (or "reticulated zinc" as commonly known in the battery and corrosion resistance arts) can be prepared from thin layers of zinc foil by mechanical perforation and then expanded into a reticulated pattern. The main advantage of the zinc mesh anode in the galvanic cell device of the present invention is the ability of the user to create and retain the desired mask/patch shape, the ability of the user to stretch in any direction to create a mask/patch of the desired size; and is air permeable.

It should be noted that although one embodiment of using zinc mesh as an electrode pattern is described herein, other above-described materials suitable for galvanic couple formation and for conductive electrodes can also be made in mesh or porous form to provide the same function.

The zinc mesh is pressed gently and is also able to conform to and maintain the shape of the surface of the film (e.g., the shape of an individual's face). This ability makes it uniquely suited for use as a mask or certain skin patches to better match certain anatomical features contours of the face (e.g., nasal patches) or body regions. This unique property also facilitates better electrical contact and also reduces reliance on the use of adhesives to secure the device to the skin.

It would be very convenient and desirable for the consumer if the mask or patch could be extended to different sizes to cover a particular area of skin without compromising its electrical performance. Zinc mesh anodes (or other mesh conductive electrodes) are uniquely able to meet this consumer need. In another embodiment, the mesh does not expand prior to use, making the device smaller and more compact for convenient storage and carrying. But rather is spread open to the desired size by the consumer during use.

Good breathability is important for larger size masks or patches, especially when the device is designed to be worn by the user for a longer period of time (e.g., more than half an hour, such as overnight). In order for the device to be extensible and/or breathable, the carrier layer 120 and backing layer 160 should also be extensible and breathable, such as extensible woven and nonwoven materials.

In another embodiment, for mask and patch devices, the backing layer 160 in fig. 3-5 can be perforated or completely removed, particularly for short-time applications, such as about 5-30 minutes. As the water in the carrier composition evaporates, the electrical conductance and current decrease. Ultimately, the current will be significantly reduced, essentially providing a self-terminating device as a safety measure for the user to prevent any inadvertent over-action of the current on the skin and potential eventual skin damage.

One example of such a self-terminating device is a galvanic fabric face mask consisting in part of a zinc mesh coated with silver-silver chloride ink, placed between a backing film/casing (e.g., a perforated or non-perforated polyethylene film) and a nonwoven fabric ((e.g., polyester and/or rayon nonwoven) using an adhesive method based on heat, ultrasound, or other mechanism A powder or a solution that is first dissolved in an organic solvent (e.g., polyethylene glycol, propylene glycol, glycerol and/or alcohol) to form a non-conductive or very low conductive layer, which is then absorbed into the nonwoven fabric layer.

The zinc anode material can be produced by a number of manufacturing methods including, but not limited to, metal working, electroless deposition, electroplating, plasma spraying, vacuum deposition, printing methods such as screen printing using a zinc conductive ink, woven or non-woven techniques. Similarly, other conductive metal materials, such as silver-silver chloride, silver-silver oxide, copper, magnesium of zinc, copper, aluminum alloys, and aluminum, can be manufactured into the above-described electrode forms using the above-described manufacturing methods.

Topical compositions containing galvanic pairs

In one embodiment, the present invention provides a topical composition containing a first electrically conductive metal particle (e.g., a flake, a wire/fiber, or a metal-coated fiber) selected from zinc, aluminum, copper, and alloys thereof; and second conductive metal particles (e.g., flakes, wires/fibers or metal coated fibers) selected from silver, copper, gold, and alloys thereof. The first and second metal particles may be selected from the electrode materials described above, forming a galvanic couple. Upon contact, the first conductive metal and the second conductive metal form a galvanic cell pair, generating an electric current and electrochemically generating ions. In yet another embodiment, the difference in the standard potentials of the first conductive metal and the second conductive metal is at least about 0.1V, such as at least about 0.5V. For example, the composition generates an electric current and zinc ions in the topical composition by contact with a first conductive metal containing zinc (e.g., fine zinc wires, zinc flakes, or zinc coated polymeric fibers) and a second conductive metal containing silver (e.g., fine silver wires/fibers, silver flakes, or silver coated polymeric fibers).

The composition may also contain active agents, such as anti-acne agents (e.g., salicylic acid, benzoyl peroxide, tretinoin, and/or vitamin a). The topical compositions containing the first metal and the second metal are preferably in the form of a semisolid dosage form (e.g., a gel, hydrogel, water-in-oil emulsion, oil-in-water emulsion, cream, lotion, ointment, multiphase emulsion, liposome, and/or microcapsule formulation) that may contain a liquid suspending material or a liquid absorbing material as described above. Topical compositions are prepared by formulating one conductive metal in a separate phase from the other conductive metal, for example, a first conductive metal (e.g., zinc flakes) in a discontinuous oil phase of an oil-in-water emulsion (e.g., a cream) and a second conductive metal (e.g., silver flakes) in a continuous aqueous phase of the emulsion. The topical compositions of the present invention may also contain a humectant (e.g., glycerin, propylene glycol, polyethylene glycol, sorbitol, and/or urea) and the above-mentioned electrolytes to maintain a certain degree of moisturization and conductivity of the skin.

In one embodiment, the first conductive metal and the second conductive metal are substantially independently suspended in the semi-solid composition (i.e., not in contact with each other) during storage of such a topical composition. When applied to a barrier membrane (e.g., skin or mucous membrane) and the liquid carrier is partially dried, the second conductive metal of the first conductive metal comes into contact, causing galvanic couples to form and generate an electric current and metal ions of the first conductive metal, resulting in beneficial effects on the membrane, such as antimicrobial, anti-inflammatory, wound healing, iontophoretic delivery of active agents, tissue stimulation, and/or sebum reduction.

In one embodiment, the wires/fibers, sheets or conductive metal coated polymer fibers of the conductive metal are sufficiently fine or thin to be suspended in the semi-solid composition during storage. In another embodiment, they are elongate in shape. Advantages of the elongated shape of conductive metals (e.g., pure metal wires/fibers, flakes, and conductive metal coated polymer fibers) include: less apparent density and thus better ability to float/suspend in topical compositions; when a low concentration of conductive metal is used, the possibility of mutual contact is high; and a wide and deep range of barrier membrane (e.g., skin) tissues through which the current penetrates and provides a beneficial effect.

In one embodiment, the first and second conductive metal particles are formulated in two different compositions and stored in separate compartments of a dual compartment component package. For example, the less chemically stable (i.e., more oxidizing) zinc or zinc alloy particles can be formulated in an anhydrous, substantially non-conductive composition containing an organic solvent such as polyethylene glycol, propylene glycol, glycerol, liquid siloxanes, and/or alcohols or other pharmaceutically acceptable organic solvents. Silver and silver chloride particles that are chemically more stable (i.e., less oxidizing) are formulated in an aqueous composition. The active agent may be formulated in any composition, depending on its chemical stability and solubility. In use, the two compositions are dispensed from a dual chamber package (e.g., a dual chamber pump, tube, pouch, bottle, etc.) and mixed prior to or during application to the skin to form a galvanic couple in situ to generate an electric current to treat the skin condition.

In another embodiment, the galvanic couple described above is produced in a topical composition in particulate form. The particles can be any shape including, but not limited to, spherical or non-spherical particles or elongated or flat shapes (e.g., metal or metal coated spheres, hollow metal or metal coated spheres, short metal coated staple fibers or fabrics and flakes), regular shapes (e.g., metal crystals) and irregular shapes (e.g., aggregated spheres). In one embodiment, the particles have an average particle size of about 1 micron to about 2 centimeters. Particle size refers to the largest dimension in at least one direction. In one embodiment, for non-elongated shapes, the particles have an average particle size of about 1 micron to about 2 millimeters. In another embodiment, the elongated particles have an average particle size of about 10 microns to about 2 cm, such as about 100 microns to about 50 mm. For example, a polymer fiber that is about 100 microns to 10 millimeters long can be partially coated with silver or silver-silver chloride on one end (or only on certain portions of the fiber) and zinc on the other end (or the remaining portion). In another embodiment, the polymer fiber is completely coated with a first conductive metal (e.g., silver-silver oxide or silver-silver chloride) and one end (or some portion of the fiber) is coated with a second conductive metal (e.g., zinc or magnesium).

In practice, silver coated polymer fibers produced by Noble Fiber Technologies, inc. (Clarks Summit, PA) may be coated with zinc using methods such as conductive zinc ink printing, electroplating, electroless deposition, vacuum deposition, and spray metallization. Alternatively, metallic zinc or magnesium particles (e.g., beads or wires) may be coated at one end or some portion with silver-silver oxide or silver-silver chloride. Spherical or non-spherical particles having an average particle size of about 1 micron to 5 millimeters can be partially coated with the first and second conductive metallic coatings in a similar manner.

In making galvanic couples, the coating methods for the first and second conductive metals can be electroless deposition, electroplating, vacuum vapor deposition, arc spraying, conductive metal inks, and other known metal coating methods commonly used in the manufacture of electronic and medical devices. Galvanic couple particles are preferably stored in the above-described anhydrous form, e.g., as a dry powder or fixed in a fabric with a binder, or as a substantially anhydrous non-conductive organic solvent composition (e.g., dissolved in polyethylene glycol, propylene glycol, glycerol, liquid silicones and/or alcohols). The galvanic cell particles have great application versatility and can be used in many consumer and medical products such as patches, bandages, masks, garments, cloths, socks, bed sheets (e.g., by being immobilized in a carrier or fabric), overlying mask compositions (e.g., creams, and gels), creams, lotions, gels, shampoos, cleansers, powders, or incorporated into personal and medical products such as toothbrushes, dental floss, wound dressings, diapers, sanitary napkins, dry wipes, pre-moistened wipes (containing the above anhydrous solvents), tampons, and rectal and vaginal suppositories. Electrochemical particles may also be included in transdermal drug delivery patches to facilitate iontophoretic penetration of the drug into the skin and to reduce skin irritation caused by electrical stimulation and the electrically generated beneficial ions, such as zinc ions.

Example 1: carrier

Some examples of carriers, including ranges of weight percentages of the components of these carriers, are shown in table 1.

TABLE 1

Composition (I)	Weight percent of carrier
								Number 1	Number 2	Number 3	Number 4	Number 5	Number 6
Salicylic acid	0.1-10	2	2	0	0	0.1-10
							Benzyl peroxide	0	0	0	0.5-10	0	0
Sulfur	0	0	0	0	3	3
							Resorcinol	0	0	0	1	1	1
Benzalkonium chloride	0-2	0.1	0.1	0-2	0-2	0-2
							Benzethonium chloride or benzethonium Ammonium chloride	0-2	0	0	0-2	0-2	0-2
Cetylpyridinium chloride	0-2	0.1	0.1	0-2	0-2	0-2
							Phospholipid CDM	0-40	5	5	0-40	0-40	0-40
Hydrogen peroxide	0-30	0	3	0-30	0-30	0-30
							Buffers (sodium, potassium or lithium) Citrate and lactic acid of Salts or phosphates of	0-10	2	2	0-10	0-10	0-10
Gelling agents (e.g. polypropylene) Acid salt, cellulose Or synthetic gums, or Polyacrylamide	0-20	5	5	0-20	0-20	0-20
							Chelating agents (e.g. EDTA)	0-2	0.1	0.1	0-2	0-2	0-2
Propylene glycol	0-30	20	15	0-30	0-30	0-30
							Polyethylene glycol	0-50	0	0	0-50	0-50	0-50
Polypropylene glycol	0-40	0	0	0-40	0-40	0-40
							Ethanol	0-50	0	15	0-50	0-50	0-50
Isopropanol (I-propanol)	0-50	0	0	0-50	0-50	0-50
							Dimethyl isosorbide ester	0-20	2	0	0-20	0-20	0-20
Myristic acid isopropyl ester	0-30	1	1	0-30	0-30	0-30
							Pure water	Is quantified to 100	Is quantified to 100	Is quantified to 100	Is quantified to 100	Is quantified to 100	Is quantified to 100

In order to evaluate the possible mechanism of action of the electrochemically generated beneficial agent, in vitro microbiological tests were performed in certain electrochemical systems to study the inhibition of electrolysis on propionibacterium acnes; and in vivo experiments were performed in volunteers using a commercially available ion permeation device.

Example 2: in vitro inhibition of Propionibacterium acnes by electrolysis

The BacT/ALERT system (BioMerieux, Inc., Durham, NC) was used in the Propionibacterium acnes inhibition assay. Briefly, 40ml of anaerobic casein and soy based broth was inoculated with acne in a culture flask (BacT/ALERT SN, organic Tekniks Corp., Durham, NC)Propionibacterium. Continuous CO monitoring at 35 deg.C by using a light colorimetric sensing system₂The growth of propionibacterium acnes was monitored in a 14-day trial using a fully automated BacT/ALERT system. A pair of selected electrodes (table 2, columns 2 and 3) were sterilized with 70% isopropyl alcohol and inserted through a rubber stopper into the culture medium of a nitrogen glove box. Some electrodes are connected to the battery (1.5 or 3V, e.g.)Table 2, column 3) for 30 minutes. The electrodes were then immediately removed from the BacT/ALERT bottles and the bottles were placed in an automated culture and monitoring system for two weeks. The other electrodes (i.e., numbers 3 and 5 in table 2) were not connected to an external battery, but were directly connected to each other at the ends of the electrodes outside the BacT/ALERT bottle to form galvanic couples. The electrodes of these galvanic couples (i.e. numbers 3 and 5) remained in contact with the culture medium in the flask during the 14 day test.

From test conditions 1 to 7 (numbers 1 to 7 in column 1), zinc was evaluated as a positive electrode (anode) and various materials as negative electrodes (cathode). Column 4 shows the voltage applied to the conductive electrode by the external battery. However, by simply connecting the two conductive electrode materials, a voltage can also be generated from a galvanic pair. For example, the voltage of a zinc-silver/silver chloride galvanic couple is 0.9849V or about 1V: (The standard potential: -0.7626V of the air-conditioner,the standard potential: 0.2223V), the voltage of the galvanic couple of the zinc-copper primary battery is about 1.1-1.3V (The standard potential: the voltage of the liquid crystal is 0.340V,the standard potential: 0.520V) reference: electrochemical Handbook (Electrochemistry Handbook), 1995, table 14.1, McGraw-Hill, inc.

In test condition 7, two electrodes (i.e., zinc-silver/silver chloride galvanic couples) were taken from a commercially available ion permeation device (IontoPatch, SP, Birch Point Medical, Inc., Oakdale, MN). IontoPatch is an ion permeation device that is powered by a galvanic couple "battery strip" of zinc and silver/silver chloride in a bandage-like device. In this test, the "battery strip" in IontoPatch was removed from the bandage-like device and placed in a BacT/ALERT vial. A commercial zinc-silver/silver chloride galvanic couple electrode (No. 7) was maintained in a BacT/ALERT vial throughout the two week experiment. Test conditions 15-17 are positive controls (i.e., no electrodes): experimental conditions 15 use concentrated Propionibacterium acnes culture for growing the remaining medium in each BacT/ALERT flask toPropionibacterium acnes count 10⁶Per ml; test conditions 16 and 17 using a Propionibacterium acnes count of 10⁶One/ml of incubation medium (the rubber stopper number 16 was also punctured in a manner similar to the rest of the electrode test conditions to eliminate any false propionibacterium acnes inhibition results due to potential ambient oxygen entering the test vial and affecting growth of anaerobic propionibacterium acnes).

TABLE 2

Numbering	Positive electrode	Negative electrode	By connecting to Battery or cell Applied in groups Voltage of	Positive acne Propionibacterium sp Growth of the plant Time of average	Number of positives- Number of trials
						1	Zinc	Silver/silver chloride	3V	-	0/3
2	Zinc	Zinc	3V	-	0/1
						3	Zinc	Copper (Cu)	No a	-	0/2
4	Zinc	Copper (Cu)	1.5V	-	0/1
						5	Zinc	Silver/silver chloride	No a	-	0/2
6	Zinc	Silver/silver chloride	1.5V	-	0/2
						7	Zinc	Silver/silver chloride	No a	-b	2/6
8	Copper (Cu)	Silver/silver chloride	3V	-	0/3
						9	Copper (Cu)	Copper (Cu)	3V	-	0/2
10	Platinum (II)	Silver/silver chloride	3V	1.6	2/2
						11	Platinum (II)	Platinum (II)	3V	1.1	1/1
12	Silver (Ag)	Silver/silver chloride	3V	5.7c	2/3
						13	Silver (Ag)	Silver (Ag)	3V	2.8d	2/2
14	Silver/silver chloride	Silver/silver chloride	3V	3.0	2/2
						15	Is free of	Is free of	Is free of	0.8	2/2
16	Is free of	Is free of	Is free of	1.4	2/2
						17	Is free of	Is free of	Is free of	1.3	2/2

a. The conductive metal electrodes are not connected to any cell, but to each other. Thus, there is a voltage on both electrodes controlled by the galvanic cell pair.

b. A total of 6 samples were tested; 4 negative and 2 positive (0.6d, 0.8 d); positive results are likely due to bacterial contamination and were omitted because they were determined faster than the positive control samples (nos. 16 and 17).

Of the c.3 samples, two positive results (4.1d, 7.3d) were averaged.

It was surprisingly found that under all test voltage conditions (nos. 1-7; 7, two of six commercially available galvanic couples showed positive propionibacterium acnes growth, most likely due to bacterial contamination, see note c of table 2), the zinc anode almost completely inhibited the growth of propionibacterium acnes in the 14-day incubation test. It was found that the copper anode also significantly inhibited the growth of propionibacterium acnes (nos. 8-9). Under this experimental condition, the platinum anode had little propionibacterium acnes inhibition, and the silver or silver/silver chloride anode had only weak propionibacterium acnes inhibition. Since all positive control conditions (nos. 15-17) had less than two days of positive propionibacterium acnes growth after the start of the experiment, negative propionibacterium acnes growth was due to the inhibition of the electrochemically produced species or the electrical connection through the culture medium. Since the electric currents passed in nos. 10 to 14 did not have a strong acne-suppressing effect as in nos. 1 to 9, the bacterial suppression observed in nos. 1 to 9 was probably due to some kind of electrochemical reaction occurring at the anode, i.e., when zinc and copper were used as the anode. It was also surprisingly found that under these experimental conditions the silver ions released from the silver or silver/silver chloride anode did not have the same propionibacterium acnes inhibitory effect (nos. 12-14) as silver ions are a well known antimicrobial substance. See, for example, Spaccaripoli et al, "antimicrobial activity of silver nitrate against Periodontal pathogens" ("antimicrobial activity of silver nitrate acquired dental pathogen"), J dental Res 36: 2, 108-13, Apr, 2001). Surprisingly, throughout the two week experiment, a pair of electrodes of a galvanic couple with zinc as anode was sufficient to inhibit the growth of propionibacterium acnes in the absence of an external battery (nos. 3, 5 and 7).

Example 3: electrode-salicylic acid in vitro compatibility test

The following test was performed to determine the compatibility of the electrode with salicylic acid. A pair of test electrodes were immersed in 5ml of a 1.5% salicylic acid solution (solvent 50% ethanol/50% water). A predetermined voltage is applied to the electrodes (connecting the electrodes to an external battery or battery) for a period of time, as shown in table 3. The test solution was observed for color change.

The solution with zinc as anode did not discolor, indicating its good compatibility with salicylic acid during the passage of the electrical connection. The use of platinum anodes unexpectedly resulted in discoloration, indicating incompatibility with salicylic acid under this experimental condition.

TABLE 3

Electrode material		Voltage (V)	Duration of the test Interval (min)	Observation of
					Anode (+)	Cathode (-)	Color change of solution Transforming
Platinum (II)	Platinum (II)			3				10	Colorless → yellow
		Platinum (II)	Platinum (II)		9	10	Colorless → brown
Zinc	Platinum (II)			1.5				10	No color change
		Zinc	Platinum (II)		3	10	No color change
Zinc	Platinum (II)			9				30	No color change

Example 4: human iontophoresis in vivo test

Commercially available iontophoresis devices (IontoPatch @, model: SP, Birch Point medical Inc., North Oakdale, MN) were used in volunteers. Healthy female volunteers aged 20-45 years with oily skin were recruited for the trial. The sebum reading per subject is at least greater than 150mg/cm per forehead²And/hr. Double blind and control experiments were performed. Briefly, the voltage is 1V, the operating current is 0.06mA, and the active treatment area is 1.25cm²Applied at the treatment site (e.g. forehead) of human subjects. Positive and negative electrodesThe poles are constructed of zinc and silver/silver chloride (Ag/AgCl) materials, respectively. Both electrodes were filled with saline (0.9% NaCl). The electrical patch starts to function while saline solution is added to the different electrodes. Leave the patchOver the treated area overnight (e.g., about 8 hours).

The following evaluations were carried out: (i) monitoring the effect of electrolysis on skin condition using conventional photography, and (ii) determining the change in the number of propionibacterium acnes by analyzing the cup wash solution at the treatment site before wearing the patch and after overnight wear. The cup wash microsampling process was as follows: a cylindrical cup (2.1 cm diameter and 2.5cm height) with two open ends was mounted on the treatment area. The treated area inside the cylindrical cup was then washed with 2ml of clean buffer (sterile 0.075M phosphate buffer containing 0.1% TritonX-100). The same area was used for sterile polishing of the glass. The wash solution is then collected. The washing process is then repeated. The two collected samples were combined for propionibacterium acnes analysis.

The number of propionibacterium acnes was determined by spin plating anaerobically washed samples in actinomycete agar for 5 days, gram staining and determination of the major contaminants on the spin plates using the VITEK system. The propionibacterium acnes count per ml of each sample buffer was determined using an automated colony counter.

After only one overnight patch application, quantitative measurements of propionibacterium acnes on the treated site showed a 45% reduction in propionibacterium acnes under the zinc anode and a 30% reduction under the Ag/AgCl cathode relative to baseline. After four consecutive overnight patch applications, the photographs clearly show a significant reduction in both the color and size of the hyperpigmented spot after acne under the zinc electrode. The subject has post-acne hyperpigmented spots at the skin site of the subject. The appearance of the hyperpigmented spot improves from a very dark color to a lighter color.

Also, the photographs showed a significant reduction in the color and size of the acne pustules under the Ag/AgCl electrode after four consecutive overnight patch applications. The subject had acne pustules at the site of the skin tested. The redness of the pustules quickly diminished from a very red color to almost invisible, while the pustules in the untreated skin areas were not much changed.

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

In three volunteers, the marker histamine hydrochloride was delivered into the skin using a galvanic zinc-silver/silver oxide device and an in vivo study was performed. Erythema and itching of the skin by histamine was recorded during and after the test. Two healthy male volunteers and one female volunteer aged 41-49 years were recruited for the trial. The thin zinc foil was cut into rectangular pieces (width 2.5cm, length 3cm) with a thickness of 0.25mm (Alfa Aesar, Word Hill, MA) to prepare galvanic devices. Silver ink (Silver Print, m.g. chemicals, Toronto, Ontario, Canada) was brushed on one side of the zinc foil in 0.5cm wide strips along the long axis at the center. The silver ink was air dried to form silver electrode strips on the zinc foil. Two rectangular Scotch tape strips 0.5cm wide and 3cm long were placed on both sides of the silver electrode strips to produce electrically insulating spaces on the surface (electrode spacing 0.5 cm). A rectangular sheet of non-woven fabric (50% rayon/50% PET, 75gsm, PGI Polymer Group inc., Landisville, NJ) 3cm wide and 3.5cm long was placed on the zinc-silver electrode side of the zinc foil. A rectangular adhesive backing film 4cm wide by 5cm long was affixed to the back of the zinc foil to complete the zinc-silver galvanic cell device.

A second zinc-silver galvanic cell device without electrically insulating spacers on the surface (electrode spacing 0cm) was prepared by omitting only the step of adding Scotch tape. A third (control) patch was prepared by using only zinc foil, nonwoven liner and adhesive backing film to construct the device.

0.8ml of 0.1% aqueous histamine hydrochloride (Sigma-Aldrich, St. Louis, Mo.) was added to each device and then fixed to the forearm skin of each volunteer for 30 minutes to initiate the histamine ion permeation test.

At the end of the test, red spots (histamine-induced erythema) appeared under the zinc-silver electric patch device and the spots disappeared within about half an hour. Close examination revealed red spots around the follicles. Itching also occurs at the site of the electrical patch during patch application. In contrast, there was no skin color change or any itching phenomenon with the control patch device.

Example 6: in vivo study of human iontophoresis of histamine dihydrochloride Using Primary cell nasal Patches containing Zinc mesh

As a continuation of the in vivo study in humans of the foregoing example, an electrical patch device (herein referred to as "test device D") containing zinc mesh (diamond-shaped openings 1cm long by 0.4cm wide, Exmet Corporation, Naugatuck, CT) instead of zinc foil was prepared in the same dimensions and method as the galvanic cell device (spacer electrode 0) in example 5. The device thus prepared was similar to the structure shown in fig. 11, with three parallel electrodes: a silver electrode in the center and zinc electrodes on both sides. Two male volunteers were studied using experimental conditions similar to those of example 5. A test device containing 0.8ml 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 rapidly transferred into the larger skin pores on the nose. For both subjects, a distinct erythema was observed on the skin site under the nose patch after removal of the nose patch at the end of the trial compared to the trial on the forearm skin.

While the invention has been described in conjunction with the detailed description, it is to be understood that the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and improvements are within the claims.

Claims (20)

1. A method of treating skin pores, the method comprising applying to skin in need of such treatment a device comprising:

a housing having a skin contacting surface;

a first conductive electrode;

a second conductive electrode; and

a carrier;

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, the skin contact surface is placed in contact with the skin, and the method of treating skin pores is selected from the group consisting of: cleansing skin pores, reducing skin sebum, reducing the appearance of skin blackheads, and reducing the appearance of skin pores.

2. The method of claim 1, wherein the housing contains the first conductive electrode and the second conductive electrode.

3. The method of claim 1, wherein the carrier further comprises salicylic acid or a salt thereof.

4. The method of claim 2, wherein the carrier further comprises salicylic acid or a salt thereof.

5. The method of claim 1, wherein the device further comprises a power source in electrical communication with the first conductive electrode and the second conductive electrode.

6. The method of claim 1, wherein the first conductive electrode and the second conductive electrode have a standard potential difference of at least 0.2V, and wherein electrons passing between the first conductive electrode and the second conductive electrode are generated by the standard potential difference.

7. The method of claim 1, wherein the second conductive electrode is also in ionic communication with the carrier.

8. The method of claim 1, wherein the shell is a nonwoven substrate.

9. The method of claim 1, wherein the housing contains the first conductive electrode and the second conductive electrode.

10. The method of claim 1, wherein a carrier is added to the device by the user and then applied to the skin.

11. A method of treating skin pores, the method comprising topically applying to the skin a composition comprising a first conductive electrode in particulate form and a second conductive electrode in particulate form, wherein the difference in the standard potentials of the first conductive electrode and the second conductive electrode is at least 0.2V, the method of treating skin pores being selected from the group consisting of: cleansing skin pores, reducing skin sebum, reducing the appearance of skin blackheads, and reducing the appearance of skin pores.

12. The method of claim 11, wherein the first conductive electrode comprises zinc and the second conductive electrode comprises silver.

13. The method of claim 11, wherein the first conductive electrode is stored separately from the composition prior to application.

14. The method of claim 11, wherein the first conductive electrode and the second conductive electrode are on the same particle.

15. The method of claim 11, wherein the composition further comprises salicylic acid or a salt thereof.

16. A method of exfoliating skin comprising applying a device to skin in need of such exfoliation, said device comprising:

a housing having a skin contacting surface;

a first conductive electrode;

a second conductive electrode; and

a carrier comprising an agent selected from the group consisting of α -hydroxy acids, β -hydroxy acids, 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.

17. The method of claim 16, wherein the agent is selected from the group consisting of: glycolic acid, lactic acid, citric acid, malic acid, maleic acid, salicylic acid, and salts thereof.

18. The method of claim 16, wherein the device further comprises a power source in electrical communication with the first conductive electrode and the second conductive electrode.

19. The method of claim 16, wherein the first conductive electrode is at least 0.2V different from the second conductive electrode by a standard potential difference, and wherein electrons passing between the first conductive electrode and the second conductive electrode are generated by the standard potential difference.

20. A method of exfoliating skin comprising topically applying to said skin a composition comprising a first conductive electrode in particulate form, a second conductive electrode in particulate form, and an agent selected from the group consisting of α -hydroxy acids, β -hydroxy acids, and salts thereof, wherein the difference in the standard potentials of said first conductive electrode and said second conductive electrode is at least 0.2V.