IONTOPHORESIS DEVICES AND METHODS OF USE

Michael Nagel, Wendell King

FIELD

[001] The present specification relates to iontophoresis devices, and methods of manufacture and use thereof.

BACKGROUND

[002] Iontophoresis is the introduction of ionizable active agents through tissue by the administration of electrical current into the tissues of the body. It is a physical process in which ions flow diffusively in a medium driven by an applied electric field. The process drives a charged substance, usually a medication or active agent or cosmetic product, transdermal^ by repulsive electromotive force, through the skin.

SUMMARY

[003] Disclosed herein are systems, devices, and methods for use in iontophoretic treatment of subjects. Embodiments disclosed herein can produce a uniform electric current or electric field density throughout/across a given surface area. This uniform current or field density enables delivery of substances through tissue, for example the skin, with a precision unmatched by other methods.

[004] In embodiments the systems comprise devices comprising a multi-array matrix. Such matrices can include a first array comprising a pattern of microcells formed from a first conductive solution or material, the solution or material including a metal species; and a second array comprising a pattern of microcells formed from a second conductive solution or material, the solution or material including a metal species capable of defining at least one voltaic cell for spontaneously generating at least one electrical current with the metal species of the first array when said first and second arrays are introduced to an electrolytic solution and said first and second arrays are not in physical contact with each other.

[005] In embodiments, the systems comprise a pattern of microcells formed from a single conductive solution or material. Certain embodiments can comprise an external power source such as AC or DC power, or pulsed RF or pulsed current, such as high voltage pulsed current. In embodiments, electrical energy can be derived from the dissimilar metals creating a battery at each cell/cell interface, whereas those embodiments with an external power source can comprise conductive electrodes in a spaced apart configuration to predetermine the electric field shape and strength. [006] Systems, devices, and formulations disclosed herein can comprise various concentrations and/or amount of active agent and can be used with different iontophoretic doses (e.g., different current levels and application times). Certain embodiments comprise a solution or formulation comprising an active agent and a solvent or carrier or vehicle. These solutions can, for example:

a. (1) be appropriately buffered to manage initial and terminal pHs,

b. (2) be stabilized to manage shelf-life (chemical stability), and/or

c. (3) include other excipients that modulate solution characteristics, for example osmolarity.

[007] Furthermore, the active agent solutions or formulations can be crafted to minimize the presence of competing ions. These unique dosage forms can address a variety of therapeutic needs. For example, ocular iontophoresis is a novel, non-invasive, out-patient approach for delivering substantial amounts of active agent into many ocular tissues. Disclosed embodiments comprise a method and system for performing ocular iontophoresis.

[008] In embodiments the system or device can comprise bioelectric hydrogels. One embodiment is directed to a hydrogel comprising a hydrophilic polymer base and one or more biocompatible electrodes configured to generate at least one of a low level electric field (LLEF) or low level electric current (LLEC).

[009] Also disclosed is a transcutaneous electrical nerve stimulation ("TENS") device and method of use. TENS devices typically operate by generating low-power electrical impulses that are supplied to the skin of a patient through electrodes. The electrical impulses have been found to diminish or completely relieve pain previously felt by a patient.

BRIEF DESCRIPTION OF THE DRAWINGS

[010] FIG. 1 depicts a detailed plan view of an embodiment disclosed herein;

[011] FIG. 2 depicts a detailed plan view of a pattern of applied electrical conductors according to one or more embodiments;

[012] FIG. 3 depicts an embodiment using the applied pattern of FIG. 2 according to one or more embodiments;

[013] FIG. 4 depicts a cross-section of FIG. 3 through line 3-3 according to one or more embodiments;

[014] FIG. 5 depicts a detailed plan view of an alternate embodiment disclosed herein which includes fine lines of conductive metal solution connecting electrodes;

[015] FIG. 6 depicts a detailed plan view of another alternate embodiment having a line pattern and dot pattern;

[016] FIG. 7 depicts a detailed plan view of another alternate embodiment having two line patterns; [017] FIG. 8 depicts a detailed plan view of yet another alternative embodiment having a random distribution of dots.

[018] FIG. 9 depicts a detailed plan view of a substrate layer electrode pattern disclosed herein.

[019] FIG. 10 depicts a detailed plan view of a substrate layer electrode pattern as disclosed herein.

[020] FIG. 1 1 depicts a detailed plan view of a substrate layer electrode pattern disclosed herein.

DETAILED DESCRIPTION

[021] Embodiments disclosed herein comprise iontophoresis systems and devices that can provide a low level electric field (LLEF) to a tissue or organism or, when brought into contact with an electrically conducting material, can provide a low level electric current (LLEC) to a tissue or organism. Thus, in embodiments an iontophoretic LLEC system is an iontophoretic LLEF system that is in contact with an electrically conducting material, for example a liquid material. In certain embodiments, the micro-current or electric field can be modulated, for example, to alter the duration, size, shape, field depth, duration, current, polarity, or voltage of the system. For example, it can be desirable to employ an electric field of greater strength or depth in an area to achieve optimal treatment. In embodiments the watt-density of the system can be modulated.

[022] Embodiments disclosed herein include methods of treatment. For example, a method of treatment disclosed herein can comprise applying an embodiment disclosed herein to an area to be treated.

[023] Definitions

[024] "Active agent" as used herein means an ingredient in a formulation or solution or drug that is biologically active. Embodiments can contain more than one active agent.

[025] "Affixing" as used herein can mean contacting a patient or tissue with a device or system disclosed herein. In embodiments "affixing" can comprise the use of straps, elastic, adhesive, etc.

[026] "Applied" or "apply" as used herein refers to contacting a surface with a conductive material, for example printing, painting, or spraying a conductive ink on a surface. Alternatively, "applying" can mean contacting a patient or tissue or organism with a device or system disclosed herein.

[027] "Conductive material" as used herein refers to an object or type of material which permits the flow of electric charges in one or more directions. Conductive materials can comprise solids such as metals or carbon, or liquids such as conductive metal solutions and conductive gels. Conductive materials can be applied to form at least one matrix. Conductive liquids can dry, cure, or harden after application to form a solid material. Solid material can also be cast from a polymer solution that contains conductive material and water wherein the water evaporates when the conductive liquids dry, cure, or harden. Solid material can then be activated when soaked in water for use.

[028] "Cosmetic product" as used herein means substances used to enhance the appearance of the body. They are generally mixtures of chemical compounds, some being derived from natural sources, many being synthetic. These products are generally liquids or creams or ointments intended to be applied to the human body for cleansing, beautifying, promoting attractiveness, or altering the appearance. These products can be electrically conductive.

[029] "Discontinuous region" as used herein refers to a "void" in a material such as a hole, slit, slot, or the like. The term can mean any void in the material though typically the void is of a regular shape. A void in the material can be entirely within the perimeter of a material or it can extend to the perimeter of a material. A void in the material can extend through a substrate.

[030] "Dots" as used herein refers to discrete deposits of similar or dissimilar reservoirs or electrodes that can, in certain embodiments, function as at least one battery cell. The term can refer to a deposit of any suitable size or shape, such as squares, circles, triangles, lines, etc. The term can be used synonymously with, microcells, microspheres, etc. "Microspheres" refers to small spherical particles, with diameters in the micrometer range (typically 1 μηι to 1000 μηι (1 mm)). Microspheres are sometimes referred to as microparticles. Microspheres can be manufactured from various natural and synthetic materials. The term can be used synonymously with, microballoons, beads, particles, etc.

[031] "Electrode" refers to similar or dissimilar conductive materials. In embodiments utilizing an external power source the electrodes can comprise similar conductive materials. In embodiments that do not use an external power source, the electrodes can comprise dissimilar conductive materials that can define an anode and a cathode.

[032] "Expandable" as used herein refers to the ability of disclosed devices and systems to stretch while retaining structural integrity and not tearing. The term can refer to solid regions as well as discontinuous or void regions; solid regions as well as void regions can stretch or expand.

[033] "Galvanic cell" as used herein refers to an electrochemical cell with a positive cell potential, which can allow chemical energy to be converted into electrical energy. More particularly, a galvanic cell can comprise a first reservoir serving as an anode and a second, dissimilar reservoir serving as a cathode. Each galvanic cell can store chemical potential energy. When a conductive material is located proximate to a cell such that the material can provide electrical and/or ionic communication between the cell elements the chemical potential energy can be released as electrical energy. Accordingly, each set of adjacent, dissimilar reservoirs can function as a single-cell battery, and the distribution of multiple sets of adjacent, dissimilar reservoirs within the apparatus can function as a field of single-cell batteries, which in the aggregate forms a multiple-cell battery distributed across a surface. In embodiments utilizing an external power source the galvanic cell can comprise electrodes connected to an external power source, for example a battery or other power source. In embodiments that are externally-powered, the electrodes need not comprise dissimilar materials, as the external power source can define the anode and cathode. In certain externally powered embodiments, the power source need not be physically connected to the device.

[034] "Matrix" or "matrices" as used herein refer to a pattern or patterns, such as those formed by electrodes on a surface, such as a fabric or a fiber or microparticle, or the like. Matrices can also comprise a pattern or patterns within a solid or liquid material or a three dimensional object. Matrices can be designed to vary the electric field or electric current or microcurrent generated. For example, the strength and shape of the field or current or microcurrent can be altered, or the matrices can be designed to produce an electric field(s) or current or microcurrent of a desired strength or shape.

[035] "Reduction-oxidation reaction" or "redox reaction" as used herein refers to a reaction involving the transfer of one or more electrons from a reducing agent to an oxidizing agent. The term "reducing agent" can be defined in some embodiments as a reactant in a redox reaction, which donates electrons to a reduced species. A "reducing agent" is thereby oxidized in the reaction. The term "oxidizing agent" can be defined in some embodiments as a reactant in a redox reaction, which accepts electrons from the oxidized species. An "oxidizing agent" is thereby reduced in the reaction. In various embodiments a redox reaction produced between a first and second reservoir provides a current between the dissimilar reservoirs. The redox reactions can occur spontaneously when a conductive material is brought in proximity to first and second dissimilar reservoirs such that the conductive material provides a medium for electrical communication and/or ionic communication between the first and second dissimilar reservoirs. In other words, in an embodiment electrical currents can be produced between first and second dissimilar reservoirs without the use of an external battery or other power source (e.g., a direct current (DC) such as a battery or an alternating current (AC) power source such as a typical electric outlet). Accordingly, in various embodiments a system is provided which is "electrically self contained," and yet the system can be activated to produce electrical currents. The term "electrically self contained" can be defined in some embodiments as being capable of producing electricity (e.g., producing currents) without an external battery or power source. The term "activated" can be defined in some embodiments to refer to the production of electric current through the application of a radio signal of a given frequency or through ultrasound or through electromagnetic induction. In other embodiments, a system can be provided which comprises an external battery or power source. For example, an AC power source can be of any wave form, such as a sine wave, a triangular wave, or a square wave. AC power can also be of any frequency such as for example 50 Hz or 60 HZ, or the like. AC power can also be of any voltage, such as for example 120 volts, or 220 volts, or the like. In embodiments an AC power source can be electronically modified, such as for example having the voltage reduced, prior to use.

[036] "Stretchable" as used herein refers to the ability of embodiments to stretch without losing their structural integrity. That is, embodiments can stretch to accommodate irregular skin surfaces or surfaces wherein one portion of the surface can move relative to another portion.

[037] "Treatment" as used herein can include the use of disclosed embodiments on tissue to prevent, reduce, or repair damage. Treatment can also include the use of disclosed embodiments on the skin, eyes, etc. Treatment can include use on an injury, for example a wound.

[038] "Viscosity" as used herein refers to a measurement of a fluid's resistance to gradual deformation by shear stress or tensile stress.

[039] Iontophoresis Systems, Devices, and Methods of Manufacture

[040] In embodiments, iontophoresis systems and devices disclosed herein comprise patterns of electrodes or micro-batteries that create a field between each dot pair. In embodiments, the unique field is very short, e.g. in the range of physiologic electric fields. In embodiments, the direction of the electric field produced by devices disclosed herein is omnidirectional within a three dimensional material. In embodiments the electrodes are on a substrate.

[041] Embodiments of the iontophoresis systems and devices disclosed herein can comprise electrodes or microcells. Each electrode or microcell can comprise a conductive metal. In embodiments, the electrodes or microcells can comprise any electrically- conductive material, for example, an electrically conductive hydrogel, metals, electrolytes, superconductors, semiconductors, plasmas, and nonmetallic conductors such as graphite and conductive polymers. Electrically conductive metals can comprise silver, copper, gold, aluminum, molybdenum, zinc, lithium, tungsten, brass, carbon, nickel, iron, palladium, platinum, tin, bronze, carbon steel, lead, titanium, stainless steel, mercury, Fe/Cr alloys, and the like. The electrode can be solid, coated or plated with a different metal such as aluminum, gold, platinum or silver.

[042] Dissimilar metals used to make a LLEC or LLEF system disclosed herein can be silver and zinc, and the electrolytic solution can comprise, for example, sodium chloride in water. In certain embodiments the electrodes are applied onto a non-conductive surface to create a pattern, for example an array or multi-array of voltaic cells that do not spontaneously react until they contact an electrolytic solution. Sections of this description use the terms "printing" with "ink," but it is to be understood that the patterns may also be "painted" with "paints." The use of any suitable means for applying a conductive material to a substrate is contemplated. In embodiments "ink" or "paint" can comprise any material such as a solution suitable for forming an electrode on a surface such as a conductive material including a conductive metal solution. In embodiments "printing" or "painted" can comprise any method of applying a solution to a material upon which a matrix is desired.

[043] In certain embodiments dissimilar metals can be used to create an electric field with a desired voltage. In certain embodiments the pattern of reservoirs can control the watt density and shape of the electric field.

[044] In certain embodiments dissimilar metals can be used to create an electric field with a desired voltage within the iontophoresis device or system. In certain embodiments the pattern of reservoirs can control the electric flux and shape of the electric field.

[045] In certain embodiments, reservoir or electrode geometry can comprise circles, polygons, lines, zigzags, ovals, stars, or any suitable variety of shapes. This provides the ability to design/customize surface electric field shapes as well as depth of penetration. For example, in embodiments it can be desirable to employ an electric field of greater strength or depth in an area where skin is thicker to achieve optimal treatment.

[046] Reservoir or electrode or dot sizes and concentrations can vary, as these variations can alter the properties of the electric field created by disclosed embodiments. In embodiments, devices disclosed herein can apply an electric field, an electric current, or both, wherein the field, current, or both can be of varying size, strength, density, shape, or duration in different areas of the embodiment. In embodiments, the shapes of the electric field, electric current, or both can be customized, increasing or decreasing very localized watt densities and allowing for the design of patterns of electrodes or reservoirs wherein the amount of electric field over a tissue can be designed or produced or adjusted based upon feedback from the tissue or upon an algorithm within sensors operably connected to the embodiment and a control module. The electric field, electric current, or both can be stronger in one zone and weaker in another. The electric field, electric current, or both can change with time and be modulated based on treatment goals or feedback from the tissue or patient. The control module can monitor and adjust the size, strength, density, shape, or duration of electric field or electric current based on material parameters or tissue parameters. For example, embodiments disclosed herein can produce and maintain very localized electrical events. For example, embodiments disclosed herein can produce specific values for the electric field duration, electric field size, electric field shape, field depth, current, polarity, and/or voltage of the device or system. [047] A system or device disclosed herein and placed over tissue such as skin can move relative to the tissue. Reducing the amount of motion between tissue and device can be advantageous to treatment. Slotting or placing cuts into the device can result in less friction or tension on the skin. In embodiments, use of an elastic dressing similar to the elasticity of the skin is also possible.

[048] Devices disclosed herein can generate a localized electric field in a pattern determined by the distance and physical orientation of the cells or electrodes. Effective depth of the electric field can be predetermined by the orientation and distance between the cells or electrodes.

[049] In embodiments the electric field can be extended, for example through the use of a hydrogel. A hydrogel is a network of polymer chains that are hydrophilic. Hydrogels are highly absorbent natural or synthetic polymeric networks. Hydrogels can be configured to contain a high percentage of water (e.g. they can contain over 90% water). Hydrogels can possess a degree of flexibility very similar to natural tissue, due to their significant water content. A hydrogel can be configured in a variety of viscosities. Viscosity is a measurement of a fluid or material's resistance to gradual deformation by shear stress or tensile stress. In embodiments the electrical field can be extended through a semi-liquid hydrogel with a low viscosity such an ointment or a cellular culture medium. In other embodiments the electrical field can be extended through a solid hydrogel with a high viscosity such as a Petri dish, clothing, or material used to manufacture a prosthetic. In general, the hydrogel described herein may be configured to a viscosity of between about 0.5 Pa s and greater than about 10 ¹² Pa s. In embodiments the viscosity of a hydrogel can be, for example, between 0.5 and 10 ¹² Pa s, between 1 Pa s and 10 ⁶ Pa s, between 5 and 10 ³ Pa s, between 10 and 100 Pa s, between 15 and 90 Pa s, between 20 and 80 Pa s, between 25 and 70 Pa s, between 30 and 60 Pa s, or the like.

[050] Certain embodiments disclosed herein can comprise a charged active agent. For example, active agents can be positively or negatively charged. In embodiments, positively charged active agents can comprise centbucridine, tetracaine, Novocaine® (procaine), ambucaine, amolanone, amylcaine, benoxinate, betoxycaine, carticaine, chloroprocaine, cocaethylene, cyclomethycaine, butethamine, butoxycaine, carticaine, dibucaine, dimethisoquin, dimethocaine, diperodon, dyclonine, ecogonidine, ecognine, euprocin, fenalcomine, formocaine, hexylcaine, hydroxyteteracaine, leucinocaine, levoxadrol, metabutoxycaine, myrtecaine, butamben, bupivicaine, mepivacaine, beta-adrenoceptor antagonists, opioid analgesics, butanilicaine, ethyl aminobenzoate, fomocine, hydroxyprocaine, isobutyl p-aminobenzoate, naepaine, octacaine, orthocaine, oxethazaine, parenthoxycaine, phenacine, phenol, piperocaine, polidocanol, pramoxine, prilocalne, propanocaine, proparacaine, propipocaine, pseudococaine, pyrrocaine, salicyl alcohol, parethyoxycaine, piridocaine, risocaine, tolycaine, trimecaine, tetracaine, anticonvulsants, antihistamines, articaine, cocaine, procaine, amethocaine, chloroprocaine, marcaine, chloroprocaine, etidocaine, prilocaine, lignocaine, benzocaine, zolamine, ropivacaine, and dibucaine, or combinations thereof.

[051] Embodiments disclosed herein can comprise a cosmetic product. For example, embodiments can comprise a skin care cream wherein the skin care cream is located between the skin and the electrode surface.

[052] In embodiments, the cosmetic product contains an anti-acne and/or anti-rosacea active 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 retinol; salicylic acid; benzoyl peroxide; resorcinol; sulfur; sulfacetamide; urea; antibiotics such as tetracycline, clindamycin, metronidazole, and erythromycin; anti-inflammatory agents such as corticosteroids (e.g., hydrocortisone), ibuprofen, naproxen, and hetprofen; and imidazoles such as ketoconazole and elubiol; and salts and prodrugs thereof. Other examples of anti-acne active agents include essential oils, alpha-bisabolol, dipotassium glycyrrhizinate, camphor, .beta.-glucan, allantoin, feverfew, flavonoids such as soy isoflavones, saw palmetto, chelating agents such as EDTA, lipase inhibitors such as silver and copper ions, hydrolyzed vegetable proteins, inorganic ions of chloride, iodide, fluoride, and their nonionic derivatives chlorine, iodine, fluorine, and synthetic phospholipids and natural phospholipids such as ARLASILK™.

[053] In embodiments, the cosmetic product contains 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 cinnamates; retinoids; dimethylaminoathanol (DMAE), copper containing peptides, vitamins such as vitamin E, vitamin A, vitamin C, and vitamin B and vitamin salts or derivatives such as ascorbic acid di-glucoside and vitamin E acetate or palmitate; alpha hydroxy acids and their precursors such as glycolic acid, citric acid, lactic acid, malic acid, mandelic acid, ascorbic acid, alpha-hydroxybutyric acid, alpha-hydroxyisobutyric acid, alpha-hydroxyisocaproic acid, atrrolactic acid, alpha-hydroxyisovaleric acid, ethyl pyruvate, galacturonic acid, glucoheptonic acid, glucoheptono 1 ,4-lactone, gluconic acid, gluconolactone, glucuronic acid, glucuronolactone, isopropyl pyruvate, methyl pyruvate, mucic acid, pyruvic acid, saccharic acid, saccaric acid 1 ,4-lactone, tartaric acid, and tartronic acid; beta hydroxy acids such as beta-hydroxybutyric acid, beta-phenyl-lactic acid, and beta-phenylpyruvic acid; tetrahydroxypropyl ethylene-diamine, N,N,N',N'-Tetrakis(2-hydroxypropyl)ethylenediamine (THPED); and botanical extracts such as green tea, soy, milk thistle, algae, aloe, angelica, bitter orange, coffee, goldthread, grapefruit, hoellen, honeysuckle, Job's tears, lithospermum, mulberry, peony, puerarua, nice, and safflower; and salts and prodrugs thereof

[054] In embodiments, the cosmetic product contains a depigmentation agent. Examples of suitable depigmentation agents include, but are not limited to: soy extract; soy isoflavones; retinoids such as retinol; kojic acid; kojic dipalmitate; hydroquinone; arbutin; transexamic acid; vitamins such as niacin and vitamin C; azelaic acid; linolenic acid and linoleic acid; placertia; licorice; and extracts such as chamomile and green tea; and salts and prodrugs thereof.

[055] Embodiments can comprise coatings on the surface or within the hydrogel, such as, for example, over or between the electrodes or cells. Such coatings can comprise, for example, silicone, and electrolytic mixture, hypoallergenic agents, drugs, biologies, stem cells, skin substitutes, cosmetic products, combinations, or the like. Drugs suitable for use with embodiments of the invention comprise analgesics, antibiotics, anti-inflammatories, or the like.

[056] In embodiments the material can comprise a port to access the interior of the material, for example to add active agents, carriers, solvents, or some other material. Certain embodiments can comprise a "blister" top that can enclose a material such as an antibacterial. In embodiments the blister top can contain a material that is released into or on to the material when the blister is pressed, for example a liquid or cream. For example, embodiments disclosed herein can comprise a blister top containing an antibacterial or the like.

[057] In embodiments the system comprises a component such as elastic or other such fabric to maintain or help maintain its position. In embodiments the system comprises components such as straps to maintain or help maintain its position. In certain embodiments the system or device comprises a strap on either end of the long axis, or a strap linking on end of the long axis to the other. In embodiments that straps can comprise Velcro or a similar fastening system. In embodiments the straps can comprise elastic materials. In embodiments the hydrogel can be configured into straps as a part of the material. In further embodiments the strap can comprise a conductive material, for example a wire, to electrically link the device with other components, such as monitoring equipment or a power source. In embodiments the device can be wirelessly linked to monitoring or data collection equipment, for example linked via Bluetooth to a cell phone or computer that collects data from the device. In certain embodiments the device can comprise data collection means, such as temperature, pH, pressure, or conductivity data collection means.

[058] In embodiments the system comprises a component such as an adhesive or straps to maintain or help maintain its position. The adhesive component can be covered with a protective layer that is removed to expose the adhesive at the time of use. In embodiments the adhesive can comprise, for example, sealants, such as hypoallergenic sealants, gecko sealants, mussel sealants, waterproof sealants such as epoxies, and the like. Straps can comprise Velcro or similar materials to aid in maintaining the position of the device.

[059] In embodiments the positioning component can comprise an elastic film with an elasticity, for example, similar to that of skin, or greater than that of skin, or less than that of skin. In embodiments, the iontophoresis system can comprise a laminate where layers of the laminate can be of varying elasticities. For example, an outer layer may be highly elastic and an inner layer in-elastic or less elastic. The in-elastic layer can be made to stretch by placing stress relieving discontinuous regions through the thickness of the material so there is a mechanical displacement rather than stress that would break the hydrogel before stretching would occur. In embodiments the stress relieving discontinuous regions can extend completely through a layer or the system or can be placed where expansion is required. In embodiments of the system the stress relieving discontinuous regions do not extend all the way through the system or a portion of the system such as the substrate. In embodiments the discontinuous regions can pass halfway through the long axis of the substrate.

[060] Embodiments disclosed herein comprise biocompatible electrodes or reservoirs or dots on a surface or substrate, for example a fabric, a fiber, or the like. In embodiments the surface or substrate can be pliable, for example to better follow the contours of an area to be treated, such as the face or back. In embodiments the surface or substrate can comprise a gauze or mesh or plastic. Suitable types of pliable surfaces or substrates for use in embodiments disclosed herein can be absorbent or non-absorbent textiles, low-adhesives, vapor permeable films, hydrocolloids, hydrogels, alginates, foams, foam-based materials, cellulose-based materials including Kettenbach fibers, hollow tubes, fibrous materials, such as those impregnated with anhydrous / hygroscopic materials, beads and the like, or any suitable material as known in the art. In embodiments the pliable material can form, for example, a mask, such as that worn on the body, pants, shorts, gloves, socks, shirts or a portion thereof, for example an elastic or compression shirt, or a portion thereof such as a sleeve, wrappings, towels, cloths, fabrics, or the like. Multi layer embodiments can include, for example, a skin-contacting layer, a hydration layer, and a hydration containment layer.

[061] An iontophoresis system disclosed herein can comprise "anchor" regions or "arms" or straps to affix the system securely. The anchor regions or arms can anchor the iontophoresis system. For example, an iontophoresis system can be secured to an area proximal to a joint or irregular skin surface, and anchor regions of the system can extend to areas of minimal stress or movement to securely affix the system. Further, the iontophoresis system can reduce stress on an area, for example by "countering" the physical stress caused by movement. [062] In embodiments the iontophoresis system can comprise additional materials to aid in treatment.

[063] In embodiments, the system can comprise instructions or directions on how to place the system to maximize its performance. Embodiments include a kit comprising a disclosed system and directions for its use. Embodiments can include software to integrate the system or device with, for example, a computer, or cellular telephone, or the like.

[064] Certain embodiments can utilize a power source, for example a battery. The power source can be any energy source capable of generating a current in the LLEC system and can include, for example, AC power, DC power, radio frequencies (RF) such as pulsed RF, induction, ultrasound, and the like. For example, an AC power source can be of any wave form, such as a sine wave, a triangular wave, or a square wave. AC power can also be of any frequency such as for example 50 Hz, or 60 HZ, or the like. AC power can also be of any voltage, such as for example 120 volts, or 220 volts, or the like. In embodiments an AC power source can be electronically modified, such as for example having the voltage reduced, prior to use.

[065] Dissimilar metals used to make an iontophoresis system or device disclosed herein can be coupled with a non-conductive material to create a random dot pattern or a uniform dot pattern, most preferably an array or multi-array of voltaic cells that do not spontaneously react until they contact an electrolytic solution. Sections of this description use the terms "coated," "plated," or "printed" with "ink," but it is to be understood that a dot in a hydrogel may also be a solid microsphere of conductive material. The use of any suitable means for applying a conductive material is contemplated. In embodiments "coated," "plated," or "printed" can comprise any material such as a solution suitable for forming an electrode on a surface of a microsphere such as a conductive material comprising a conductive metal solution.

[066] In another embodiment, "coated," "plated," or "printed" can comprise electroplating microspheres. Electroplating is a process that uses electric current to reduce dissolved metal cations so that they form a coherent metal coating on an electrode. Electroplating can be used to change the surface properties of microspheres or to build up thickness of a microsphere. Building thickness by electroplating microspheres can allow the microspheres to be formed with a specific conductive material and at a specific gravity determined by the user.

[067] In embodiments, printing devices can be used to produce iontophoresis systems disclosed herein. For example, inkjet or "3D" printers can be used to produce embodiments. In certain embodiments the binders or inks used to produce iontophoresis systems disclosed herein can comprise, for example, poly cellulose inks, poly acrylic inks, poly urethane inks, silicone inks, and the like. In embodiments the type of ink used can determine the release rate of electrons from the reservoirs. In embodiments various materials can be added to the ink or binder such as, for example, conductive or resistive materials can be added to alter the shape or strength of the electric field. Other materials, such as silicon, can be added, for example to enhance scar reduction. Such materials can also be added to the spaces between reservoirs.

[068] Turning to the figures, in FIG. 1 , the dissimilar first electrode 6 and second electrode 10 are applied onto a desired primary surface 2 of an article or substrate 4. In one embodiment a primary surface is a surface of an iontophoresis system that comes into direct contact with an area to be treated such as a skin surface.

[069] In various embodiments the difference of the standard potentials of the electrodes or dots or reservoirs can be in a range from about 0.05 V to approximately about 5.0 V. For example, the standard potential can be about 0.05 V, about 0.06 V, about 0.07 V, about 0.08 V, about 0.09 V, about 0.1 V, about 0.2 V, about 0.3 V, about 0.4 V, about 0.5 V, about 0.6 V, about 0.7 V, about 0.8 V, about 0.9 V, about 1 .0 V, about 1 .1 V, about 1 .2 V, about 1 .3 V, about 1 .4 V, about 1 .5 V, about 1 .6 V, about 1 .7 V, about 1 .8 V, about 1 .9 V, about 2.0 V, about 2.1 V, about 2.2 V, about 2.3 V, about 2.4 V, about 2.5 V, about 2.6 V, about 2.7 V, about 2.8 V, about 2.9 V, about 3.0 V, about 3.1 V, about 3.2 V, about 3.3 V, about 3.4 V, about 3.5 V, about 3.6 V, about 3.7 V, about 3.8 V, about 3.9 V, about 4.0 V, about 4.1 V, about 4.2 V, about 4.3 V, about 4.4 V, about 4.5 V, about 4.6 V, about 4.7 V, about 4.8 V, about 4.9 V, about 5.0 V, about 5.1 V, about 5.2 V, about 5.3 V, about 5.4 V, about 5.5 V, about 5.6 V, about 5.7 V, about 5.8 V, about 5.9 V, about 6.0 V, about 6.1 V, about 6.2 V, about 6.3 V, about 6.4 V, about 6.5 V, about 6.6 V, about 6.7 V, about 6.8 V, about 6.9 V, about 7.0 V, about 7.1 V, about 7.2 V, about 7.3 V, about 7.4 V, about 7.5 V, about 7.6 V, about 7.7 V, about 7.8 V, about 7.9 V, about 8.0 V, about 8.1 V, about 8.2 V, about 8.3 V, about 8.4 V, about 8.5 V, about 8.6 V, about 8.7 V, about 8.8 V, about 8.9 V, about 9.0 V, or the like.

[070] In embodiments, systems and devices disclosed herein can produce a low level electric current of between for example about 1 and about 200 micro-amperes, between about 10 and about 190 micro-amperes, between about 20 and about 180 micro-amperes, between about 30 and about 170 micro-amperes, between about 40 and about 160 microamperes, between about 50 and about 150 micro-amperes, between about 60 and about 140 micro-amperes, between about 70 and about 130 micro-amperes, between about 80 and about 120 micro-amperes, between about 90 and about 100 micro-amperes, between about 100 and about 150 micro-amperes, between about 150 and about 200 micro-amperes, between about 200 and about 250 micro-amperes, between about 250 and about 300 microamperes, between about 300 and about 350 micro-amperes, between about 350 and about 400 micro-amperes, between about 400 and about 450 micro-amperes, between about 450 and about 500 micro-amperes, between about 500 and about 550 micro-amperes, between about 550 and about 600 micro-amperes, between about 600 and about 650 micro-amperes, between about 650 and about 700 micro-amperes, between about 700 and about 750 microamperes, between about 750 and about 800 micro-amperes, between about 800 and about 850 micro-amperes, between about 850 and about 900 micro-amperes, between about 900 and about 950 micro-amperes, between about 950 and about 1000 micro-amperes (1 milli- amp [mA]), between about 1 .0 and about 1 .1 mA, between about 1 .1 and about 1 .2mA, between about 1 .2 and about 1 .3mA, between about 1 .3 and about 1 .4mA, between about

1.4 and about 1 .5mA, between about 1 .5 and about 1 .6mA, between about 1 .6 and about 1.7mA, between about 1.7 and about 1 .8mA, between about 1 .8 and about 1 .9mA, between about 1 .9 and about 2.0mA, between about 2.0 and about 2.1 mA, between about 2.1 and about 2.2mA, between about 2.2 and about 2.3mA, between about 2.3 and about 2.4mA, between about 2.4 and about 2.5mA, between about 2.5 and about 2.6mA, between about 2.6 and about 2.7mA, between about 2.7 and about 2.8mA, between about 2.8 and about 2.9mA, between about 2.9 and about 3.0mA, between about 3.0 and about 3.1 mA, between about 3.1 and about 3.2mA, between about 3.2 and about 3.3mA, between about 3.3 and about 3.4mA, between about 3.4 and about 3.5mA, between about 3.5 and about 3.6mA, between about 3.6 and about 3.7mA, between about 3.7 and about 3.8mA, between about 3.8 and about 3.9mA, between about 3.9 and about 4.0mA, between about 4.0 and about 4.1 mA, between about 4.1 and about 4.2mA, between about 4.2 and about 4.3mA, between about 4.3 and about 4.4mA, between about 4.4 and about 4.5mA, between about 4.5 and about 5.0mA, between about 5.0 and about 5.5mA, between about 5.5 and about 6.0mA, between about 6.0 and about 6.5mA, between about 6.5 and about 7.0mA, between about

7.5 and about 8.0mA, between about 8.0 and about 8.5mA, between about 8.5 and about 9.0mA, between about 9.0 and about 9.5mA, between about 9.5 and about 10.0mA, between about 10.0 and about 10.5mA, between about 10.5 and about 1 1 .0mA, between about 1 1 .0 and about 1 1 .5mA, between about 1 1 .5 and about 12.0mA, between about 12.0 and about 12.5mA, between about 12.5 and about 13.0mA, between about 13.0 and about 13.5mA, between about 13.5 and about 14.0mA, between about 14.0 and about 14.5mA, between about 14.5 and about 15.0mA, or the like.

[071] In embodiments, systems and devices disclosed herein can produce a low level electric current of between, for example, about 1 and about 400 micro-amperes, between about 20 and about 380 micro-amperes, between about 40 and about 360 micro-amperes, between about 60 and about 340 micro-amperes, between about 80 and about 320 microamperes, between about 100 and about 300 micro-amperes, between about 120 and about 280 micro-amperes, between about 140 and about 260 micro-amperes, between about 160 and about 240 micro-amperes, between about 180 and about 220 micro-amperes, or the like.

[072] In embodiments, systems and devices disclosed herein can produce a low level electric current of between for example about 1 micro-ampere and about 1 milli-ampere, between about 50 and about 800 micro-amperes, between about 200 and about 600 microamperes, between about 400 and about 500 micro-amperes, or the like.

[073] In embodiments, systems and devices disclosed herein can produce a low level electric current of about 10 micro-amperes, about 20 micro-amperes, about 30 microamperes, about 40 micro-amperes, about 50 micro-amperes, about 60 micro-amperes, about 70 micro-amperes, about 80 micro-amperes, about 90 micro-amperes, about 100 micro-amperes, about 1 10 micro-amperes, about 120 micro-amperes, about 130 microamperes, about 140 micro-amperes, about 150 micro-amperes, about 160 micro-amperes, about 170 micro-amperes, about 180 micro-amperes, about 190 micro-amperes, about 200 micro-amperes, about 210 micro-amperes, about 220 micro-amperes, about 240 microamperes, about 260 micro-amperes, about 280 micro-amperes, about 300 micro-amperes, about 320 micro-amperes, about 340 micro-amperes, about 360 micro-amperes, about 380 micro-amperes, about 400 micro-amperes, about 450 micro-amperes, about 500 microamperes, about 550 micro-amperes, about 600 micro-amperes, about 650 micro-amperes, about 700 micro-amperes, about 750 micro-amperes, about 800 micro-amperes, about 850 micro-amperes, about 900 micro-amperes, about 950 micro-amperes, about 1 milli-ampere (mA), about 1 .1 mA, about 1 .2mA, about 1 .3mA, about 1 .4mA, about 1 .5mA, about 1.6mA, about 1 .7mA, about 1 .8mA, about 1 .9mA, about 2.0mA, about 2.1 mA, about 2.2mA, about 2.3mA, about 2.4mA, about 2.5mA, about 2.6mA, about 2.7mA, about 2.8mA, about 2.9mA, about 3.0mA, about 3.1 mA, about 3.2mA, about 3.3mA, about 3.4mA, about 3.5mA, about 3.6mA, about 3.7mA, about 3.8mA, about 3.9mA, about 4.0mA, about 4.1 mA, about 4.2mA, about 4.3mA, about 4.4mA, about 4.5mA, about 4.6mA, about 4.7mA, about 4.8mA, about 4.9mA, about 5.0mA, about 5.1 mA, about 5.2mA, about 5.3mA, about 5.4mA, about 5.5mA, about 5.6mA, about 5.7mA, about 5.8mA, about 5.9mA, about 6.0mA, about 6.1 mA, about 4.2mA, about 6.3mA, about 6.4mA, about 6.5mA, about 6.6mA, about 6.7mA, about 6.8mA, about 6.9mA, about 7.0mA, about 7.1 mA, about 7.2mA, about 7.3mA, about 7.4mA, about 7.5mA, about 7.6mA, about 7.7mA, about 7.8mA, about 7.9mA, about 8.0mA, about 8.1 mA, about 8.2mA, about 8.3mA, about 8.4mA, about 8.5mA, about 8.6mA, about 8.7mA, about 8.8mA, about 8.9mA, about 9.0mA, about 9.1 mA, about 9.2mA, about 9.3mA, about 9.4mA, about 9.5mA, about 9.6mA, about 9.7mA, about 9.8mA, about 9.9mA, about 10.0mA, about 10.1 mA, about 10.2mA, about 10.3mA, about 10.4mA, about 10.5mA, about 10.6mA, about 10.7mA, about 10.8mA, about 10.9mA, about 1 1 .0mA, about 1 1 .1 mA, about 1 1.2mA, about 1 1 .3mA, about 1 1 .4mA, about 1 1 .5mA, about 1 1 .6mA, about 1 1 .7mA, about 1 1.8mA, about 1 1 .9mA, about 12.0mA, about 12.1 mA, about 12.2mA, about 12.3mA, about 12.4mA, about 12.5mA, about 12.6mA, about 12.7mA, about 12.8mA, about 12.9mA, about 13.0mA, about 13.1 mA, about 13.2mA, about 13.3mA, about 13.4mA, about 13.5mA, about 13.6mA, about 13.7mA, about 13.8mA, about 13.9mA, about 14.0mA, about 14.1 mA, about 14.2mA, about 14.3mA, about 14.4mA, about 14.5mA, about 14.6mA, about 14.7mA, about 14.8mA, about 14.9mA, about 15.0mA, about 15.1 mA, about 15.2mA, about 15.3mA, about 15.4mA, about 15.5mA, about 15.6mA, about 15.7mA, about 15.8mA, or the like.

[074] In embodiments, the disclosed systems and devices can produce a low level electric current of not more than 10 micro-amperes, or not more than about 20 micro-amperes, not more than about 30 micro-amperes, not more than about 40 micro-amperes, not more than about 50 micro-amperes, not more than about 60 micro-amperes, not more than about 70 micro-amperes, not more than about 80 micro-amperes, not more than about 90 microamperes, not more than about 100 micro-amperes, not more than about 1 10 micro-amperes, not more than about 120 micro-amperes, not more than about 130 micro-amperes, not more than about 140 micro-amperes, not more than about 150 micro-amperes, not more than about 160 micro-amperes, not more than about 170 micro-amperes, not more than about 180 micro-amperes, not more than about 190 micro-amperes, not more than about 200 micro-amperes, not more than about 210 micro-amperes, not more than about 220 microamperes, not more than about 230 micro-amperes, not more than about 240 micro-amperes, not more than about 250 micro-amperes, not more than about 260 micro-amperes, not more than about 270 micro-amperes, not more than about 280 micro-amperes, not more than about 290 micro-amperes, not more than about 300 micro-amperes, not more than about 310 micro-amperes, not more than about 320 micro-amperes, not more than about 340 micro-amperes, not more than about 360 micro-amperes, not more than about 380 microamperes, not more than about 400 micro-amperes, not more than about 420 micro-amperes, not more than about 440 micro-amperes, not more than about 460 micro-amperes, not more than about 480 micro-amperes, not more than about 500 micro-amperes, not more than about 520 micro-amperes, not more than about 540 micro-amperes, not more than about 560 micro-amperes, not more than about 580 micro-amperes, not more than about 600 micro-amperes, not more than about 620 micro-amperes, not more than about 640 microamperes, not more than about 660 micro-amperes, not more than about 680 micro-amperes, not more than about 700 micro-amperes, not more than about 720 micro-amperes, not more than about 740 micro-amperes, not more than about 760 micro-amperes, not more than about 780 micro-amperes, not more than about 800 micro-amperes, not more than about 820 micro-amperes, not more than about 840 micro-amperes, not more than about 860 micro-amperes, not more than about 880 micro-amperes, not more than about 900 microamperes, not more than about 920 micro-amperes, not more than about 940 micro-amperes, not more than about 960 micro-amperes, not more than about 980 micro-amperes, not more than about 1 milli-ampere (mA), not more than about 1 .1 mA, not more than about 1 .2mA, not more than about 1 .3mA, not more than about 1 .4mA, not more than about 1 .5mA, not more than about 1 .6mA, not more than about 1 .7mA, not more than about 1 .8mA, not more than about 1 .9mA, not more than about 2.0mA, not mo re than about 2.1 mA, not more than about

2.2mA, not more than about 2.3mA, not more than about 2.4mA, not more than about

2.5mA, not more than about 2.6mA, not more than about 2.7mA, not more than about

2.8mA, not more than about 2.9mA, not more than about 3.0mA, not more than about

3.1 mA, not more than about 3.2mA, not more than about 3.3mA, not more than about

3.4mA, not more than about 3.5mA, not more than about 3.6mA, not more than about

3.7mA, not more than about 3.8mA, not more than about 3.9mA, not more than about

4.0mA, not more than about 4.1 mA, not more than about 4.2mA, not more than about

4.3mA, not more than about 4.4mA, not more than about 4.5mA, not more than about

4.6mA, not more than about 4.7mA, not more than about 4.8mA, not more than about

4.9mA, not more than about 5.0mA, not more than about 5.1 mA, not more than about

5.2mA, not more than about 5.3mA, not more than about 5.4mA, not more than about

5.5mA, not more than about 5.6mA, not more than about 5.7mA, not more than about

5.8mA, not more than about 5.9mA, not more than about 6.0mA, not more than about

6.1 mA, not more than about 6.2mA, not more than about 6.3mA, not more than about

6.4mA, not more than about 6.5mA, not more than about 6.6mA, not more than about

6.7mA, not more than about 6.8mA, not more than about 6.9mA, not more than about

7.0mA, not more than about 7.1 mA, not more than about 7.2mA, not more than about

7.3mA, not more than about 7.4mA, not more than about 7.5mA, not more than about

7.6mA, not more than about 7.7mA, not more than about 7.8mA, not more than about

7.9mA, not more than about 8.0mA, not more than about 8.1 mA, not more than about

8.2mA, not more than about 8.3mA, not more than about 8.4mA, not more than about

8.5mA, not more than about 8.6mA, not more than about 8.7mA, not more than about

8.8mA, not more than about 8.9mA, not more than about 9.0mA, not more than about

9.1 mA, not more than about 9.2mA, not more than about 9.3mA, not more than about

9.4mA, not more than about 9.5mA, not more than about 9.6mA, not more than about

9.7mA, not more than about 9.8mA, not more than about 9.9mA, not more than about

10.0mA, not more than about 10.1 mA, not more than about 10.2mA, not more than about

10.3mA, not more than about 10.4mA, not more than about 10.5mA, not more than about

10.6mA, not more than about 10.7mA, not more than about 10.8mA, not more than about

10.9mA, not more than about 1 1 .0mA, not more than about 1 1 .1 mA, not more than about

1 1 .2mA, not more than about 1 1 .3mA, not more than about 1 1 .4mA, not more than about

1 1 .5mA, not more than about 1 1 .6mA, not more than about 1 1 .7mA, not more than about 1 1 .8mA, not more than about 1 1 .9mA, not more than about 12.0mA, not more than about

12.1 mA, not more than about 12 .2mA, not more than about 12 .3mA, not more than about

12.4mA, not more than about 12 .5mA, not more than about 12 .6mA, not more than about

12.7mA, not more than about 12 .8mA, not more than about 12 .9mA, not more than about

13.0mA, not more than about 13 .1 mA, not more than about 13 .2mA, not more than about

13.3mA, not more than about 13 .4mA, not more than about 13 .5mA, not more than about

13.6mA, not more than about 13 .7mA, not more than about 13 .8mA, not more than about

13.9mA, not more than about 14 .0mA, not more than about 14 .1 mA, not more than about

14.2mA, not more than about 14 .3mA, not more than about 14 .4mA, not more than about

14.5mA, not more than about 14 .6mA, not more than about 14 .7mA, not more than about

14.8mA, not more than about 14 .9mA, not more than about 15 .0mA, not more than about

15.1 mA, not more than about 15 .2mA, not more than about 15 .3mA, not more than about

15.4mA, not more than about 15 .5mA, not more than about 15 .6mA, not more than about

15.7mA, not more than about 15.8mA, and the like.

[075] In embodiments, systems and devices disclosed herein can produce a low level electric current of not less than 10 micro-amperes, not less than 20 micro-amperes, not less than 30 micro-amperes, not less than 40 micro-amperes, not less than 50 micro-amperes, not less than 60 micro-amperes, not less than 70 micro-amperes, not less than 80 microamperes, not less than 90 micro-amperes, not less than 100 micro-amperes, not less than 1 10 micro-amperes, not less than 120 micro-amperes, not less than 130 micro-amperes, not less than 140 micro-amperes, not less than 150 micro-amperes, not less than 160 microamperes, not less than 170 micro-amperes, not less than 180 micro-amperes, not less than 190 micro-amperes, not less than 200 micro-amperes, not less than 210 micro-amperes, not less than 220 micro-amperes, not less than 230 micro-amperes, not less than 240 microamperes, not less than 250 micro-amperes, not less than 260 micro-amperes, not less than 270 micro-amperes, not less than 280 micro-amperes, not less than 290 micro-amperes, not less than 300 micro-amperes, not less than 310 micro-amperes, not less than 320 microamperes, not less than 330 micro-amperes, not less than 340 micro-amperes, not less than 350 micro-amperes, not less than 360 micro-amperes, not less than 370 micro-amperes, not less than 380 micro-amperes, not less than 390 micro-amperes, not less than 400 microamperes, not less than about 420 micro-amperes, not less than about 440 micro-amperes, not less than about 460 micro-amperes, not less than about 480 micro-amperes, not less than about 500 micro-amperes, not less than about 520 micro-amperes, not less than about 540 micro-amperes, not less than about 560 micro-amperes, not less than about 580 microamperes, not less than about 600 micro-amperes, not less than about 620 micro-amperes, not less than about 640 micro-amperes, not less than about 660 micro-amperes, not less than about 680 micro-amperes, not less than about 700 micro-amperes, not less than about 720 micro-amperes, not less than about 740 micro-amperes, not less than about 760 microamperes, not less than about 780 micro-amperes, not less than about 800 micro-amperes, not less than about 820 micro-amperes, not less than about 840 micro-amperes, not less than about 860 micro-amperes, not less than about 880 micro-amperes, not less than about 900 micro-amperes, not less than about 920 micro-amperes, not less than about 940 microamperes, not less than about 960 micro-amperes, not less than about 980 micro-amperes, not less than about 1 milli-ampere (mA), not less than about 1.1 mA, not less than about 1.2mA, not less than about 1.3mA, not less than about 1.4mA, not less than about 1.5mA, not less than about 1.6mA, not less than about 1.7mA, not less than about 1.8mA, not less than about 1.9mA, not less than about 2.0mA, not less than about 2.1 mA, not less than about 2.2mA, not less than about 2.3mA, not less than about 2.4mA, not less than about 2.5mA, not less than about 2.6mA, not less than about 2.7mA, not less than about 2.8mA, not less than about 2.9mA, not less than about 3.0mA, not less than about 3.1 mA, not less than about 3.2mA, not less than about 3.3mA, not less than about 3.4mA, not less than about 3.5mA, not less than about 3.6mA, not less than about 3.7mA, not less than about 3.8mA, not less than about 3.9mA, not less than about 4.0mA, not less than about 4.1 mA, not less than about 4.2mA, not less than about 4.3mA, not less than about 4.4mA, not less than about 4.5mA, not less than about 4.6mA, not less than about 4.7mA, not less than about 4.8mA, not less than about 4.9mA, not less than about 5.0mA, not less than about 5.1 mA, not less than about 5.2mA, not less than about 5.3mA, not less than about 5.4mA, not less than about 5.5mA, not less than about 5.6mA, not less than about 5.7mA, not less than about 5.8mA, not less than about 5.9mA, not less than about 6.0mA, not less than about 6.1 mA, not less than about 6.2mA, not less than about 6.3mA, not less than about 6.4mA, not less than about 6.5mA, not less than about 6.6mA, not less than about 6.7mA, not less than about 6.8mA, not less than about 6.9mA, not less than about 7.0mA, not less than about 7.1 mA, not less than about 7.2mA, not less than about 7.3mA, not less than about 7.4mA, not less than about 7.5mA, not less than about 7.6mA, not less than about 7.7mA, not less than about 7.8mA, not less than about 7.9mA, not less than about 8.0mA, not less than about 8.1 mA, not less than about 8.2mA, not less than about 8.3mA, not less than about 8.4mA, not less than about 8.5mA, not less than about 8.6mA, not less than about 8.7mA, not less than about 8.8mA, not less than about 8.9mA, not less than about 9.0mA, not less than about 9.1 mA, not less than about 9.2mA, not less than about 9.3mA, not less than about 9.4mA, not less than about 9.5mA, not less than about 9.6mA, not less than about 9.7mA, not less than about 9.8mA, not less than about 9.9mA, not less than about 10.0mA, not less than about 10.1 mA, not less than about 10.2mA, not less than about 10.3mA, not less than about 10.4mA, not less than about 10.5mA, not less than about 10.6mA, not less than about 10.7mA, not less than about 10.8mA, not less than about 10.9mA, not less than about 1 1 .0mA, not less than about 1 1 .1 mA, not less than about

1 1 .2mA, not less than about 1 1 .3mA, not less than about 1 1 .4mA, not less than about

1 1 .5mA, not less than about 1 1 .6mA, not less than about 1 1 .7mA, not less than about

1 1 .8mA, not less than about 1 1 .9mA, not less than about 12.0mA, not less than about

12.1 mA, not less than about 12.2mA, not less than about 12.3mA, not less than about

12.4mA, not less than about 12.5mA, not less than about 12.6mA, not less than about

12.7mA, not less than about 12.8mA, not less than about 12.9mA, not less than about

13.0mA, not less than about 13.1 mA, not less than about 13.2mA, not less than about

13.3mA, not less than about 13.4mA, not less than about 13.5mA, not less than about

13.6mA, not less than about 13.7mA, not less than about 13.8mA, not less than about

13.9mA, not less than about 14.0mA, not less than about 14.1 mA, not less than about

14.2mA, not less than about 14.3mA, not less than about 14.4mA, not less than about

14.5mA, not less than about 14.6mA, not less than about 14.7mA, not less than about

14.8mA, not less than about 14.9mA, not less than about 15.0mA, not less than about

15.1 mA, not less than about 15.2mA, not less than about 15.3mA, not less than about

15.4mA, not less than about 15.5mA, not less than about 15.6mA, not less than about

15.7mA, not less than about 15.8mA, and the like.

[076] In embodiments comprising a hydrogel, the reservoirs or dots can be configured to be same specific gravity as the hydrophilic polymer base of the hydrogel. This embodiment, allows the reservoirs or dots to be suspended in the hydrogel for a desired used without the reservoirs or dots being pulled to the bottom of the hydrogels due to other factors such as gravity. In particular, the reservoirs or dots will not settle and the hydrogel can be manufactured and stored for extended periods of times without altering the hydrogels intended purpose.

[077] In certain embodiments that utilize a poly-cellulose binder, the binder itself can have a beneficial effect such as reducing the local concentration of matrix metallo-proteases through an iontophoretic process that drives the cellulose into the surrounding tissue. This process can be used to electronically drive other components such as drugs into the surrounding tissue. The binder can comprise any biocompatible liquid material that can be mixed with a conductive element (preferably metallic crystals of silver or zinc) to create a conductive solution which can be applied as a thin coating to a microsphere. One suitable binder is a solvent reducible polymer, such as the polyacrylic non-toxic silk-screen ink manufactured by COLORCON ^® Inc., a division of Berwind Pharmaceutical Services, Inc. (see COLORCON ^® NO-TOX ^® product line, part number NT28). In an embodiment the binder is mixed with high purity metallic silver crystals to make the silver conductive solution. The silver crystals, which can be made by grinding silver into a powder, are preferably smaller than 100 microns in size or about as fine as flour. In an embodiment, the size of the crystals is about 325 mesh, which is typically about 40 microns in size or a little smaller. The binder is separately mixed with high purity (at least 99.99%, in an embodiment) metallic zinc powder which has also preferably been sifted through standard 325 mesh screen, to make the zinc conductive solution. For better quality control and more consistent results, most of the crystals used should be larger than 325 mesh and smaller than 200 mesh. For example the crystals used should be between 200 mesh and 325 mesh, or between 210 mesh and 310 mesh, between 220 mesh and 300 mesh, between 230 mesh and 290 mesh, between 240 mesh and 280 mesh, between 250 mesh and 270 mesh, between 255 mesh and 265 mesh, or the like.

[078] Other powders of metal can be used to make other conductive metal solutions in the same way as described in other embodiments.

[079] The size of the metal crystals, the availability of the surface to the conductive fluid and the ratio of metal to binder affects the release rate of the metal from the mixture. When COLORCON ^® polyacrylic ink is used as the binder, about 10 to 40 percent of the mixture should be metal for a long term bandage (for example, one that stays on for about 10 days). For example, for a longer term LLEC or LLEF system the percent of the mixture that should be metal can be 8 percent, or 10 percent, 12 percent, 14 percent, 16 percent, 18 percent, 20 percent, 22 percent, 24 percent, 26 percent, 28 percent, 30 percent, 32 percent, 34 percent, 36 percent, 38 percent, 40 percent, 42 percent, 44 percent, 46 percent, 48 percent, 50 percent, or the like.

[080] If the same binder is used, but the percentage of the mixture that is metal is increased to 60 percent or higher, a disclosed system or device can be effective for longer. For example, for a longer term device, the percent of the mixture that should be metal can be 40 percent, or 42 percent, 44 percent, 46 percent, 48 percent, 50 percent, 52 percent, 54 percent, 56 percent, 58 percent, 60 percent, 62 percent, 64 percent, 66 percent, 68 percent, 70 percent, 72 percent, 74 percent, 76 percent, 78 percent, 80 percent, 82 percent, 84 percent, 86 percent, 88 percent, 90 percent, or the like.

[081] For LLEC or LLEF systems comprising a pliable substrate it can be desired to decrease the percentage of metal down to 5 percent or less, or to use a binder that causes the crystals to be more deeply embedded, so that the primary surface will be antimicrobial for a very long period of time and will not wear prematurely. Other binders can dissolve or otherwise break down faster or slower than a polyacrylic ink, so adjustments can be made to achieve the desired rate of spontaneous reactions from the voltaic cells.

[082] To maximize the number of voltaic cells, in various embodiments, a pattern of alternating silver masses (e.g., 6 as shown in FIG. 1) or electrodes or reservoirs and zinc masses (e.g., 10 as shown in FIG.1) or electrodes or reservoirs can create an array of electrical currents across the hydrogel. A basic embodiment, shown in FIG. 1 , has each mass of silver randomly spaced from masses of zinc, and has each mass of zinc randomly spaced from masses of silver, according to an embodiment. In another embodiment, mass of silver can be equally spaced from masses of zinc, and has each mass of zinc equally spaced from masses of silver. That is, the electrodes or reservoirs or dots can either be a uniform pattern, a random pattern, or a combination of the like. The first electrode 6 is separated from the second electrode 10 by a hydrophilic polymer base 2. The designs of first electrode 6 and second electrode 10 are simply round dots, and in an embodiment, are repeated throughout the hydrogel. For an exemplary device comprising silver and zinc, each silver design preferably has about twice as much mass as each zinc design, in an embodiment. For the embodiment in FIG. 1 , the silver designs are most preferably about a millimeter from each of the closest four zinc designs, and vice-versa. The resulting pattern of dissimilar metal masses defines an array of voltaic cells when introduced to an electrolytic solution. To maximize the density of electrical current over a primary surface the pattern of FIG. 2 can be used. The first electrode 6 in FIG. 2 is a large hexagonally shaped dot, and the second electrode 10 is a pair of smaller hexagonally shaped dots that are spaced from each other. The spacing 8 that is between the first electrode 6 and the second electrode 10 maintains a relatively consistent distance between adjacent sides of the designs. Numerous repetitions 12 of the designs result in a pattern 14 that can be described as at least one of the first design being surrounded by six hexagonally shaped dots of the second design.

[083] FIGS. 3 and 4 show how the pattern of FIG. 2 can be used to make an embodiment disclosed herein. The pattern shown in detail in FIG. 2 is applied to the primary surface 2 of an embodiment. The back 20 of the printed material is fixed to a substrate layer 22. This layer is adhesively fixed to a pliable layer 16.

[084] FIG. 5 shows an additional feature, which can be added between designs, that can initiate the flow of current in a poor electrolytic solution. A fine line 24 is printed using one of the conductive metal solutions along a current path of each voltaic cell. The fine line will initially have a direct reaction but will be depleted until the distance between the electrodes increases to where maximum voltage is realized. The initial current produced is intended to help control edema so that the iontophoresis system will be effective. If the electrolytic solution is highly conductive when the system is initially applied the fine line can be quickly depleted and the device will function as though the fine line had never existed.

[085] FIGS. 6 and 7 show alternative patterns that use at least one line design. The first electrode 6 of FIG. 6 is a round dot similar to the first design used in FIG. 1 . The second electrode 10 of FIG. 6 is a line. When the designs are repeated, they define a pattern of parallel lines that are separated by numerous spaced dots. FIG. 7 uses only line designs. The first electrode 6 can be thicker or wider than the second electrode 10 if the oxidation- reduction reaction requires more metal from the first conductive element (mixed into the first design's conductive metal solution) than the second conductive element (mixed into the second design's conductive metal solution). The lines can be dashed. Another pattern can be silver grid lines that have zinc masses in the center of each of the cells of the grid. The pattern can be letters printed from alternating conductive materials so that a message can be printed onto the primary surface-perhaps a brand name or identifying information such as patient blood type.

[086] FIG. 8 depicts a detailed plan view of yet another alternative embodiment having a random distribution of dots. In FIG. 8, the dissimilar first electrode 801 and second electrode 802 are on a desired substrate 803 of a device 800, for example a bandage, eye patch, or the like. In one embodiment a device 800 is a material of an iontophoresis system that comes into direct contact with an area to be treated such as a skin. Device 800 can also be configured or shaped into a three dimensional object or material wherein the first electrode 801 and second electrode 802 are randomly distributed within substrate 803 of object or material such as a orthopedic cast, pacemaker, ankle brace, or the like.

[087] FIG. 9 shows an embodiment utilizing two electrodes (one positive and one negative). Upper arms 140 and 145 can be, for example, 1 , 2, 3, or 4 mm in width. Lower arm 147 and serpentine 149 can be, for example, 1 , 2, 3, or 4 mm in width. The electrodes can be, for example, 1 , 2, or 3 mm in depth.

[088] FIG. 10 shows an embodiment utilizing two electrodes (one positive and one negative). Upper arms 150 and 155 can be, for example, 1 , 2, 3, or 4 mm in width. The extensions protruding from the lower arm 156 can be, for example, 1 , 1 .5, 2, 2.5, 3, 3.5, or 4 mm in width. The extensions protruding from the comb 158 can be, for example, 1 , 2, 3, 4, 5, 6, or 7 mm in width. The electrodes can be, for example, 1 , 2, or 3 mm in depth.

[089] FIG. 1 1 shows an embodiment utilizing two electrodes (one positive and one negative). Upper arms 160 and 165 can be, for example, 1 , 2, 3, or 4 mm in width. Lower block 167 can be, for example, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, or 54 mm along its shorter axis. Lower block 167 can be, for example, 60, 65, 70, 75, 80, 85, 90, 95, or 100 mm along its longer axis. The electrodes can be, for example, 1 , 2, or 3 mm in depth.

[090] In embodiments such as those depicted in FIG.s 9-1 1 , the width and depth of the various areas of the electrode can be designed to produce a particular electric field, or, when both electrodes are in contact with a conductive material, a particular electric current. For example, the width of the various areas of the electrode can be, for example, 0.1 mm, or 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1 .1 mm, 1 .2 mm,

1.3 mm, 1 .4 mm, 1 .5 mm, 1 .6 mm, 1 .7 mm, 1 .8 mm, 1 .9 mm, 2 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3 mm, 3.1 mm, 3.2 mm, 3.3 mm,

3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9 mm, 4 mm, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm, 5 mm, 5.1 mm, 5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6 mm, 5.7 mm, 5.8 mm, 5.9 mm, 6 mm, or 7 mm, or 8 mm, or 9 mm, or 10 mm, or 11 mm, or the like.

[091] In embodiments, the depth or thickness of the various areas of the electrode can be, for example, 0.1 mm, or 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1 .1 mm, 1 .2 mm, 1 .3 mm, 1 .4 mm, 1 .5 mm, 1.6 mm, 1 .7 mm, 1 .8 mm, 1 .9 mm, 2 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3 mm,

3.1 mm, 3.2 mm, 3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9 mm, 4 mm, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm, 5 mm, 5.1 mm,

5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6 mm, 5.7 mm, 5.8 mm, 5.9 mm, 6 mm, or the like.

[092] The shortest distance between the two electrodes in an embodiment can be, for example, 0.1 mm, or 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1 .1 mm, 1 .2 mm, 1 .3 mm, 1.4 mm, 1 .5 mm, 1 .6 mm, 1 .7 mm, 1 .8 mm, 1 .9 mm, 2 mm,

2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3 mm, 3.1 mm, 3.2 mm, 3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9 mm, 4 mm, 4.1 mm,

4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm, 5 mm, 5.1 mm, 5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6 mm, 5.7 mm, 5.8 mm, 5.9 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm, 24 mm, 25 mm, 26 mm, 27 mm, 28 mm, 29 mm, 30 mm, 31 mm, 32 mm, 33 mm, 34 mm, or the like.

[093] In embodiments, the length of the long axis of the electrode can be, for example, 2 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3 mm,

3.1 mm, 3.2 mm, 3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9 mm, 4 mm, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm, 5 mm, 5.1 mm,

5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6 mm, 5.7 mm, 5.8 mm, 5.9 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm, 24 mm, 25 mm, 26 mm, 27 mm, 28 mm, 29 mm, 30 mm, 31 mm, 32 mm, 33 mm, 34 mm, 35 mm, 36 mm, 37 mm, 38 mm, 39 mm, 40 mm, 41 mm, 42 mm, 43 mm, 44 mm, 45 mm, 46 mm, 47 mm, 48 mm, 49 mm, 50 mm, 75 mm, 100 mm, 150 mm, 200 mm, 250 mm, 300 mm, 350 mm, 400 mm, 450 mm, 500 mm, 600 mm, 700 mm, 800 mm, 900 mm, 1000 mm, or more, or the like.

[094] In embodiments, the length of the short axis of the electrode can be, for example, 2 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3 mm,

3.1 mm, 3.2 mm, 3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9 mm, 4 mm, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm, 5 mm, 5.1 mm,

5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6 mm, 5.7 mm, 5.8 mm, 5.9 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm, 24 mm, 25 mm, 26 mm, 27 mm, 28 mm, 29 mm, 30 mm, 31 mm, 32 mm, 33 mm, 34 mm, 35 mm, 36 mm, 37 mm, 38 mm, 39 mm, 40 mm, 41 mm, 42 mm, 43 mm, 44 mm, 45 mm, 46 mm, 47 mm, 48 mm, 49 mm, 50 mm, 75 mm, 100 mm, or more, or the like.

[095] Because the spontaneous oxidation-reduction reaction of silver and zinc uses a ratio of approximately two silver to one zinc, the silver design can contain about twice as much mass as the zinc design in an embodiment. At a spacing of about 1 mm between the closest dissimilar metals (closest edge to closest edge) each voltaic cell that contacts a conductive fluid such as a cosmetic cream can create approximately 1 volt of potential that will penetrate substantially through a hydrogel and its surrounding surfaces. Closer spacing of the dots can decrease the resistance, providing less potential, and the current will not penetrate as deeply. If the spacing falls below about one tenth of a millimeter, a benefit of the spontaneous reaction is that which is also present with a direct reaction; silver can be electrically driven into the skin. Therefore, spacing between the closest conductive materials can be, for example, 1 μηι, 2 μηι, 3 μηι, 4 μηι, 5 μηι, 6 μηι, 7 μηι, 8 μηι, 9 μηι, 10 μηι, 11 μηι, 12 μηι, 13 μηι, 14 μηι, 15 μηι, 16 μηι, 17 μηι, 18 μηι, 19 μηι, 20 μηι, 21 μηι, 22 μηι, 23 μηι, 24 μηι, 25 μηι, 26 μηι, 27 μηι, 28 μηι, 29 μηι, 30 μηι, 31 μηι, 32 μηι, 33 μηι, 34 μηι, 35 μηι, 36 μηι, 37 μηι, 38 μηι, 39 μηι, 40 μηι, 41 μηι, 42 μηι, 43 μηι, 44 μηι, 45 μηι, 46 μηι, 47 μηι, 48 μηι, 49 μηι, 50 μηι, 51 μηι, 52 μηι, 53 μηι, 54 μηι, 55 μηι, 56 μηι, 57 μηι, 58 μηι, 59 μηι, 60 μηι, 61 μηι, 62 μηι, 63 μηι, 64 μηι, 65 μηι, 66 μηι, 67 μηι, 68 μηι, 69 μηι, 70 μηι, 71 μm, 72 μm, 73 μηι, 74 μm, 75 μηι, 76 μm, 77 μm, 78 μηι, 79 μm, 80 μηι, 81 μm, 82 μm, 83 μηι, 84 μm, 85 μηι, 86 μm, 87 μm, 88 μηι, 89 μm, 90 μηι, 91 μm, 92 μm, 93 μηι, 94 μm, 95 μηι, 96 μm, 97 μm, 98 μηι, 99 μm, 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1 .1 mm, 1 .2 mm, 1 .3 mm, 1 .4 mm, 1.5 mm, 1 .6 mm, 1 .7 mm,

1.8 mm, 1 .9 mm, 2 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm, 2.5 mm, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3 mm, 3.1 mm, 3.2 mm, 3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm,

3.9 mm, 4 mm, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm, 4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm, 5 mm, 5.1 mm, 5.2 mm, 5.3 mm, 5.4 mm, 5.5 mm, 5.6 mm, 5.7 mm, 5.8 mm, 5.9 mm, 6 mm, or the like.

[096] In certain embodiments the spacing between the closest conductive materials can be not more than 1 μηι, or not more than 2 μηι, or not more than 3 μηι, or not more than 4 μηι, or not more than 5, or not more than 6 μηι, or not more than 7 μηι, or not more than 8 μηι, or not more than 9 μηι, or not more than 10 μηι, or not more than 11 μηι, or not more than 12 μηι, or not more than 13 μηι, or not more than 14 μηι, or not more than 15 μηι, or not more than 16, or μηι not more than 17 or μηι, or not more than 18 μηι, or not more than 19, or μηι not more than 20, or μηι not more than 21 , or μηι not more than 22 μηι, or not more than 23 or μηι, or not more than 24 μηι, or not more than 25 μηι, or not more than 26 μηι, or not more than 27 μηι, or not more than 28 μηι, or not more than 29 μηι, or not more than 30 μηι, or not more than 31 μηι, or not more than 32 μηι, or not more than 33 μηι, or not more than 34 μηι, or not more than 35 μηι, or not more than 36 μηι, or not more than 37 μηι, or not more than 38 μηι, or not more than 39 μηι, or not more than 40 μηι, or not more than 41 μηι, or not more than 42 μηι, or not more than 43 μηι, or not more than 44 μηι, or not more than 45 μηι, or not more than 46 μηι, or not more than 47 μηι, or not more than 48 μηι, or not more than 49 μηι, or not more than 50 μηι, or not more than 51 μηι, or not more than 52 μηι, or not more than 53 μηι, or not more than 54 μηι, or not more than 55 μηι, or not more than 56 μηι, or not more than 57 μηι, or not more than 58 μηι, or not more than 59 μηι, or not more than 60 μηι, or not more than 61 μηι, or not more than 62 μηι, or not more than 63 μηι, or not more than 64 μηι, or not more than 65 μηι, or not more than 66 μηι, or not more than 67 μηι not more than 68 μηι not more than 69 μηι, or not more than 70 μηι, or not more than 71 μηι, or not more than 72 μηι, or not more than 72 μηι, or not more than 74 μηι, or not more than 75 μηι, or not more than 76 μηι, or not more than 77 μηι, or not more than 78 μηι, or not more than 79 μηι, or not more than 80 μηι, or not more than 81 μηι, or not more than 82 μηι, or not more than 83 μηι, or not more than 84 μηι, or not more than 85 μηι, or not more than 86 μηι, or not more than 87 μηι, or not more than 88 μηι not more than 89 μηι, or not more than 90 μηι, or not more than 91 μηι, or not more than 92 μηι, or not more than 93 μηι, or not more than 94 μηι, or not more than 95 μηι, or not more than 96 μηι, or not more than 97 μηι, or not more than 98 μηι, or not more than 99 μηι, or not more than not more than 0.1 mm, not more than 0.2 mm, not more than 0.3 mm, not more than 0.4 mm, not more than 0.5 mm, not more than 0.6 mm, not more than 0.7 mm, not more than 0.8 mm, not more than 0.9 mm, not more than 1 mm, not more than 1 .1 mm, not more than 1 .2 mm, not more than 1 .3 mm, not more than 1 .4 mm, not more than 1 .5 mm, not more than 1 .6 mm, not more than 1 .7 mm, not more than 1 .8 mm, not more than 1 .9 mm, not more than 2 mm, not more than 2.1 mm, not more than 2.2 mm, not more than 2.3 mm, not more than

2.4 mm, not more than 2.5 mm, not more than 2.6 mm, not more than 2.7 mm, not more than 2.8 mm, not more than 2.9 mm, not more than 3 mm, not more than 3.1 mm, not more than 3.2 mm, not more than 3.3 mm, not more than 3.4 mm, not more than 3.5 mm, not more than 3.6 mm, not more than 3.7 mm, not more than 3.8 mm, not more than 3.9 mm, not more than 4 mm, not more than 4.1 mm, not more than 4.2 mm, not more than 4.3 mm, not more than 4.4 mm, not more than 4.5 mm, not more than 4.6 mm, not more than 4.7 mm, not more than 4.8 mm, not more than 4.9 mm, not more than 5 mm, not more than 5.1 mm, not more than 5.2 mm, not more than 5.3 mm, not more than 5.4 mm, not more than

5.5 mm, not more than 5.6 mm, not more than 5.7 mm, not more than 5.8 mm, not more than 5.9 mm, not more than 6 mm, or the like.

[097] In certain embodiments spacing between the closest conductive materials can be not less than 1 μηι, or not less than 2 μηι, or not less than 3 μηι, or not less than 4 μηι, or not less than 5 μηι, or not less than 6 μηι, or not less than 7 μηι, or not less than 8 μηι, or not less than 9 μηι, or not less than 10 μηι, or not less than 11 μηι, or not less than 12 μηι, or not less than 13 μηι, or not less than 14 μηι, or not less than 15 μηι, or not less than 16 μηι, or not less than 17 μηι, or not less than 18 μηι, or not less than 19 μηι, or not less than 20 μηι, or not less than 21 μηι, or not less than 22 μηι, or not less than 23 μηι, or not less than 24 μηι, or not less than 25 μηι, or not less than 26 μηι, or not less than 27 μηι, or not less than 28 μηι, or not less than 29 μηι, or not less than 30 μηι, or not less than 31 μηι, or not less than 32 μηι, or not less than 33 μηι, or not less than 34 μηι, or not less than 35 μηι, or not less than 36 μηι, or not less than 37 μηι, or not less than 38 μηι, or not less than 39 μηι, or not less than 40 μηι, or not less than 41 μηι, or not less than 42 μηι, or not less than 43 μηι, or not less than 44 μηι, or not less than 45 μηι, or not less than 46 μηι, or not less than 47 μηι, or not less than 48 μηι, or not less than 49 μηι, or not less than 50 μηι, or not less than 51 μηι, or not less than 52 μηι, or not less than 53 μηι, or not less than 54 μηι, or not less than 55 μηι, or not less than 56 μηι, or not less than 57 μηι, or not less than 58 μηι, or not less than 59 μηι, or not less than 60 μηι, or not less than 61 μηι, or not less than 62 μηι, or not less than 63 μηι, or not less than 64 μηι, or not less than 65 μηι, or not less than 66 μηι, or not less than 67 μηι, or not less than 68 μηι, or not less than 69 μηι, or not less than 70 μηι, or not less than 71 μηι, or not less than 72 μηι, or not less than 73 μηι, or not less than 74 μηι, or not less than 75 μηι, or not less than 76 μηι, or not less than 77 μηι, or not less than 78 μηι, or not less than 79 μηι, or not less than 80 μηι, or not less than 81 μηι, or not less than 82 μηι, or not less than 83 μηι, or not less than 84 μηι, or not less than 85 μηι, or not less than 86 μηι, or not less than 87 μηι, or not less than 88 μηι, or not less than 89 μηι, or not less than 90 μηι, or not less than 91 μηι, or not less than 92 μηι, or not less than 93 μηι, or not less than 94 μηι, or not less than 95 μηι, or not less than 96 μηι, or not less than 97 μηι, or not less than 98 μηι, or not less than 99 μηι, or not less than 0.1 mm, not less than 0.2 mm, not less than 0.3 mm, not less than 0.4 mm, not less than 0.5 mm, not less than 0.6 mm, not less than 0.7 mm, not less than 0.8 mm, not less than 0.9 mm, not less than 1 mm, not less than 1 .1 mm, not less than 1 .2 mm, not less than 1 .3 mm, not less than 1 .4 mm, not less than 1 .5 mm, not less than 1 .6 mm, not less than 1 .7 mm, not less than 1 .8 mm, not less than 1 .9 mm, not less than 2 mm, not less than 2.1 mm, not less than 2.2 mm, not less than 2.3 mm, not less than 2.4 mm, not less than 2.5 mm, not less than 2.6 mm, not less than 2.7 mm, not less than 2.8 mm, not less than 2.9 mm, not less than 3mm, not less than 3.1 mm, not less than 3.2 mm, not less than 3.3 mm, not less than 3.4 mm, not less than 3.5 mm, not less than 3.6 mm, not less than 3.7 mm, not less than 3.8 mm, not less than 3.9 mm, not less than 4 mm, not less than 4.1 mm, not less than 4.2 mm, not less than 4.3 mm, not less than 4.4 mm, not less than 4.5 mm, not less than 4.6 mm, not less than 4.7 mm, not less than 4.8 mm, not less than 4.9 mm, not less than 5 mm, not less than 5.1 mm, not less than 5.2 mm, not less than 5.3 mm, not less than 5.4 mm, not less than 5.5 mm, not less than 5.6 mm, not less than 5.7 mm, not less than 5.8 mm, not less than 5.9 mm, not less than 6 mm, or the like.

[098] Disclosures of the present specification comprise iontophoresis systems comprising a hydrophilic polymer base and a first electrode design formed from a first conductive liquid that comprises a mixture of a polymer and a first element, the first conductive liquid being applied into a position of contact with the primary surface, the first element comprising a metal species, and the first electrode design comprising at least one dot or reservoir, wherein selective ones of the at least one dot or reservoir have approximately a 1 .5 μηι +/- 1 μηι mean diameter; a second electrode design formed from a second conductive liquid that comprises a mixture of a polymer and a second element, the second element comprising a different metal species than the first element, the second conductive liquid being printed into a position of contact with the primary surface, and the second electrode design comprising at least one other dot or reservoir, wherein selective ones of the at least one other dot or reservoir have approximately a 2 μιτι +/- 2 μηι mean diameter; a spacing on the primary surface that is between the first electrode design and the second electrode design such that the first electrode design does not physically contact the second electrode design, wherein the spacing is approximately 1 .5 μηι +/- 1 μηι, and at least one repetition of the first electrode design and the second electrode design, the at least one repetition of the first electrode design being substantially adjacent the second electrode design, wherein the at least one repetition of the first electrode design and the second electrode design, in conjunction with the spacing between the first electrode design and the second electrode design, defines at least one pattern of at least one voltaic cell for spontaneously generating at least one electrical current when introduced to an electrolytic solution. Therefore, electrodes, dots or reservoirs can have a mean diameter of, for example, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 .0 mm, 1 .1 mm, 1 .2 mm, 1 .3 mm, 1 .4 mm, 1 .5 mm, 1 .6 mm, 1 .7 mm, 1 .8 mm, 1 .9 mm, 2.0 mm, 2.1 mm, 2.2 mm, 2.3 mm, 2.4 mm,

2.5 mm,, 2.6 mm, 2.7 mm, 2.8 mm, 2.9 mm, 3.0 mm, 3.1 mm, 3.2 mm, 3.3 mm, 3.4 mm, 3.5 mm, 3.6 mm, 3.7 mm, 3.8 mm, 3.9 mm, 4.0 mm, 4.1 mm, 4.2 mm, 4.3 mm, 4.4 mm, 4.5 mm,

4.6 mm, 4.7 mm, 4.8 mm, 4.9 mm, 5.0 mm, or the like.

[099] In further embodiments, electrodes, dots or reservoirs can have a mean diameter of not less than 0.2 mm, or not less than 0.3 mm, not less than 0.4 mm, not less than 0.5 mm, not less than 0.6 mm, not less than 0.7 mm, not less than 0.8 mm, not less than 0.9 mm, not less than 1 .0 mm, not less than 1 .1 mm, not less than 1 .2 mm, not less than 1 .3 mm, not less than 1 .4 mm, not less than 1 .5 mm, not less than 1 .6 mm, not less than 1 .7 mm, not less than 1 .8 mm, not less than 1 .9 mm, not less than 2.0 mm, not less than 2.1 mm, not less than 2.2 mm, not less than 2.3 mm, not less than 2.4 mm, not less than 2.5 mm, not less than 2.6 mm, not less than 2.7 mm, not less than 2.8 mm, not less than 2.9 mm, not less than 3.0 mm, not less than 3.1 mm, not less than 3.2 mm, not less than 3.3 mm, not less than 3.4 mm, not less than 3.5 mm, not less than 3.6 mm, not less than 3.7 mm, not less than 3.8 mm, not less than 3.9 mm, not less than 4.0 mm, not less than 4.1 mm, not less than 4.2 mm, not less than 4.3 mm, not less than 4.4 mm, not less than 4.5 mm, not less than 4.6 mm, not less than 4.7 mm, not less than 4.8 mm, not less than 4.9 mm, not less than 5.0 mm, or the like.

[0100] In further embodiments, electrodes, dots or reservoirs can have a mean diameter of, for example, not more than 0.2 mm, or not more than 0.3 mm, not more than 0.4 mm, not more than 0.5 mm, not more than 0.6 mm, not more than 0.7 mm, not more than 0.8 mm, not more than 0.9 mm, not more than 1 .0 mm, not more than 1 .1 mm, not more than 1 .2 mm, not more than 1 .3 mm, not more than 1 .4 mm, not more than 1 .5 mm, not more than 1.6 mm, not more than 1 .7 mm, not more than 1 .8 mm, not more than 1 .9 mm, not more than 2.0 mm, not more than 2.1 mm, not more than 2.2 mm, not more than 2.3 mm, not more than 2.4 mm, not more than 2.5 mm, not more than 2.6 mm, not more than 2.7 mm, not more than 2.8 mm, not more than 2.9 mm, not more than 3.0 mm, not more than 3.1 mm, not more than 3.2 mm, not more than 3.3 mm, not more than 3.4 mm, not more than 3.5 mm, not more than 3.6 mm, not more than 3.7 mm, not more than 3.8 mm, not more than 3.9 mm, not more than 4.0 mm, not more than 4.1 mm, not more than 4.2 mm, not more than 4.3 mm, not more than 4.4 mm, not more than 4.5 mm, not more than 4.6 mm, not more than 4.7 mm, not more than 4.8 mm, not more than 4.9 mm, not more than 5.0 mm, or the like.

[0101] The material concentrations or quantities within and/or the relative sizes (e.g., dimensions or surface area) of the first and second reservoirs can be selected deliberately to achieve various characteristics of the iontophoresis systems' behavior. For example, the quantities of material within a first and second reservoir can be selected to provide an apparatus having an operational behavior that depletes at approximately a desired rate and/or that "dies" after an approximate period of time after activation. In an embodiment the one or more first reservoirs and the one or more second reservoirs are configured to sustain one or more currents for an approximate pre-determined period of time, after activation. It is to be understood that the amount of time that currents are sustained can depend on external conditions and factors (e.g., the quantity and type of activation material), and currents can occur intermittently depending on the presence or absence of activation material.

[0102] In various embodiments the difference of the standard potentials of the first and second reservoirs can be in a range from 0.05 V to approximately 5.0 V. For example, the standard potential can be 0.05 V, or 0.06 V, 0.07 V, 0.08 V, 0.09 V, 0.1 V, 0.2 V, 0.3 V, 0.4 V, 0.5 V, 0.6 V, 0.7 V, 0.8 V, 0.9 V, 1 .0 V, 1 .1 V, 1 .2 V, 1 .3 V, 1 .4 V, 1 .5 V, 1 .6 V, 1 .7 V, 1 .8 V, 1 .9 V, 2.0 V, 2.1 V, 2.2 V, 2.3 V, 2.4 V, 2.5 V, 2.6 V, 2.7 V, 2.8 V, 2.9 V, 3.0 V, 3.1 V, 3.2 V, 3.3 V, 3.4 V, 3.5 V, 3.6 V, 3.7 V, 3.8 V, 3.9 V, 4.0 V, 4.1 V, 4.2 V, 4.3 V, 4.4 V, 4.5 V, 4.6 V, 4.7 V, 4.8 V, 4.9 V, 5.0 V, or the like.

[0103] In a particular embodiment the difference of the standard potentials of the first and second reservoirs can be, for example, at least 0.05 V, or at least 0.06 V, at least 0.07 V, at least 0.08 V, at least 0.09 V, at least 0.1 V, at least 0.2 V, at least 0.3 V, at least 0.4 V, at least 0.5 V, at least 0.6 V, at least 0.7 V, at least 0.8 V, at least 0.9 V, at least 1 .0 V, at least 1.1 V, at least 1 .2 V, at least 1 .3 V, at least 1.4 V, at least 1 .5 V, at least 1 .6 V, at least 1 .7 V, at least 1 .8 V, at least 1 .9 V, at least 2.0 V, at least 2.1 V, at least 2.2 V, at least 2.3 V, at least 2.4 V, at least 2.5 V, at least 2.6 V, at least 2.7 V, at least 2.8 V, at least 2.9 V, at least 3.0 V, at least 3.1 V, at least 3.2 V, at least 3.3 V, at least 3.4 V, at least 3.5 V, at least 3.6 V, at least 3.7 V, at least 3.8 V, at least 3.9 V, at least 4.0 V, at least 4.1 V, at least 4.2 V, at least 4.3 V, at least 4.4 V, at least 4.5 V, at least 4.6 V, at least 4.7 V, at least 4.8 V, at least 4.9 V, at least 5.0 V, or the like.

[0104] In a particular embodiment, the difference of the standard potentials of the first and second reservoirs can be not more than 0.05 V, or not more than 0.06 V, not more than 0.07 V, not more than 0.08 V, not more than 0.09 V, not more than 0.1 V, not more than 0.2 V, not more than 0.3 V, not more than 0.4 V, not more than 0.5 V, not more than 0.6 V, not more than 0.7 V, not more than 0.8 V, not more than 0.9 V, not more than 1 .0 V, not more than 1 .1 V, not more than 1 .2 V, not more than 1 .3 V, not more than 1 .4 V, not more than 1 .5 V, not more than 1 .6 V, not more than 1 .7 V, not more than 1 .8 V, not more than 1 .9 V, not more than 2.0 V, not more than 2.1 V, not more than 2.2 V, not more than 2.3 V, not more than 2.4 V, not more than 2.5 V, not more than 2.6 V, not more than 2.7 V, not more than 2.8 V, not more than 2.9 V, not more than 3.0 V, not more than 3.1 V, not more than 3.2 V, not more than 3.3 V, not more than 3.4 V, not more than 3.5 V, not more than 3.6 V, not more than 3.7 V, not more than 3.8 V, not more than 3.9 V, not more than 4.0 V, not more than 4.1 V, not more than 4.2 V, not more than 4.3 V, not more than 4.4 V, not more than 4.5 V, not more than 4.6 V, not more than 4.7 V, not more than 4.8 V, not more than 4.9 V, not more than 5.0 V, or the like. In embodiments that include very small reservoirs (e.g., on the nanometer scale), the difference of the standard potentials can be substantially less or more. The electrons that pass between the first reservoir and the second reservoir can be generated as a result of the difference of the standard potentials.

[0105] The voltage present at the site of use of the iontophoresis system is typically in the range of millivolts but disclosed embodiments can introduce a much higher voltage, for example near 1 volt when using the 1 mm spacing of dissimilar metals already described. The higher voltage is believed to drive the current deeper into the treatment area. In this way the current not only can drive silver and zinc into the treatment if desired for treatment, but the current can also provide a stimulatory current so that the entire surface area can be treated. The electric field can also have beneficial effects on cell migration, ATP production, and angiogenesis.

[0106] While various embodiments have been shown and described, it will be realized that alterations and modifications can be made thereto without departing from the scope of the following claims. It is expected that other methods of applying the conductive material can be substituted as appropriate. Also, there are numerous shapes, sizes and patterns of voltaic cells that have not been described but it is expected that this disclosure will enable those skilled in the art to incorporate their own designs which will then become active when brought into contact with an electrolytic solution.

[0107] Certain embodiments comprise iontophoresis LLEC or LLEF systems comprising embodiments designed to be used on irregular, non-planar, or "stretching" surfaces. Embodiments disclosed herein can be used with numerous irregular surfaces of the body, comprising the face, the shoulder, the elbow, the wrist, the finger joints, the hip, the knee, the ankle, the toe joints, decubitus wound, diabetic ulcer etc. Additional embodiments disclosed herein can be used in areas where tissue is prone to movement, for example the eyelid, the ear, the lips, the nose, the shoulders, the back, etc.

[0108] In certain embodiments, the iontophoresis system or device can be shaped to fit a particular region of the body such as an arm, leg, ankle, chest, decubitus wound, or diabetic ulcer. Additionally, an iontophoresis system or device can be shaped to form objects such as clothing.

[0109] Certain embodiments disclosed herein comprise a method of manufacturing an iontophoresis LLEC or LLEF system, the method comprising coupling a substrate with one or more biocompatible electrodes configured to generate at least one of a low level electric field (LLEF) or low level electric current (LLEC). In another embodiment, the method comprises joining a substrate with one or more biocompatible electrodes comprising a first bioelectric element comprising a first microparticle formed from a first conductive material, and a second bioelectric element comprising a second microparticle formed from a second conductive material. For example, the first microparticle formed from a first conductive material can be a reducing agent. The second microparticle formed from a second conductive material can be an oxidizing agent.

[0110] Embodiments disclosed herein comprise iontophoresis systems that can produce an electrical stimulus and/or can electromotivate, electroconduct, electroinduct, electrotransport, and/or electrophorese one or more therapeutic materials in areas of target tissue (e.g., iontophoresis), and/or can cause one or more biologic or other materials in proximity to, on or within target tissue to be rejuvenated. [0111] Aspects disclosed herein include systems, devices, and methods for data collection and/or data transmission, for example using bioelectric devices that comprise a substrate with one or more sensing elements, multi-array matrix of biocompatible microcells which can generate a LLEF or LLEC, and wherein a data element is collected from the sensing element and transmitted by a control module to an external device. Embodiments can include, for example, data collection equipment so as to track and/or quantify a user's movements or performance. Embodiments can include, for example, an accelerometer, so as to measure a user's speed, or impact forces on a user. Embodiments can include optical data collection devices, for example a camera.

[0112] In embodiments the device can be mechanically or wirelessly linked to monitoring or data collection equipment, for example linked via Bluetooth to a cell phone or computer that collects data from the device. In certain embodiments, disclosed devices and systems can comprise data collection means, such as location, temperature, pH, pressure, or conductivity data collection means. Embodiments can comprise a display, for example to visually present, for example, the location, temperature, pH, pressure, or conductivity data to a user.

[0113] In embodiments, the visual display can indicate when a data reading is outside a desired or approved range. For example, in an embodiment the device can provide a visual or audible warning or alarm when an accelerometer reading indicates an impact greater than the desired range, or a visual or audible warning or alarm when a temperature, pulse, or respiration reading is outside a desired range.

[0114] In certain embodiments, a substrate comprising the multi-array matrix can comprise one layer of a composite dressing, for example a composite garment or fabric comprising the substrate, an adhesive layer, an expandable absorbent layer, and a stretchable, expandable film layer. The expandable absorbent layer can absorb excess fluid such as perspiration from the substrate and expand away from the treatment area, thus preventing oversaturation of the treatment area with resultant maceration and increased infection risk.

[0115] The stretchable, expandable film layer can stretch to accommodate a larger foam volume as the foam absorbs liquid. This aspect reduces shear forces on the skin.

Additionally, the vertically-expanding foam and film allows the dressing to absorb more volume of fluid in a smaller contact area.

[0116] Iontophoresis Systems, Devices, and Methods of Use

[0117] Yet other aspects of the present specification disclose methods for applying a disclosed device over an area to be treated wherein the device is expandable along at least one axis, and/or the device comprises at least one discontinuous region wherein a long axis of the discontinuous region is perpendicular to the axis upon which the device is expandable, and further wherein the pliable dressing material comprises on its surface a multi-array matrix of biocompatible microcells, wherein such matrix comprises a first array comprising a pattern of microcells formed from a first conductive solution, such solution including at least one metal species and a second array comprising a pattern of microcells formed from a second conductive solution, such solution including at least one metal species capable of defining at least one voltaic cell for generating at least one electrical current with the metal species of the first array when said first and second arrays are introduced to an electrolytic solution and said first and second arrays are not in physical contact with each other.

[0118] In embodiments the device can be shaped to fit an area of desired use, for example the human face, or around a subject's eyes, or around a subject's forehead, a subject's cheeks, a subject's chin, a subject's back, a subject's chest, a subject's legs, a subject's ankle, a subject's arms, a subject's wound or any area where treatment is desired.

[0119] Methods disclosed herein can comprise applying a disclosed embodiment to an area to be treated. Embodiments can comprise selecting or identifying a patient in need of treatment. In embodiments, methods disclosed herein can comprise formation and application of an iontophoresis system or device disclosed herein to an area to be treated.

[0120] In embodiments, disclosed methods comprise application to the treatment area or the device of an iontophoresis system disclosed herein comprising an active agent.

[0121] Embodiments disclosed herein can comprise a cosmetic procedure. For example, embodiments can be employed before, after, or during a cosmetic procedure, such as before, after, or during a dermal filler injection. Certain embodiments can comprise use of a device disclosed herein before, after, or during a BOTOX ^® injection. Certain embodiments can comprise use of a device disclosed herein before, after, or during a rhinoplasty procedure. Certain embodiments can comprise use of a device disclosed herein before, after, or during a resurfacing procedure.

[0122] In an exemplary embodiment, a method disclosed herein comprises applying a conductive cosmetic product to an area where treatment is desired, then applying over the cosmetic product an iontophoresis device as disclosed herein comprising a multi-array matrix of biocompatible microcells.

[0123] In certain embodiments, for example treatment methods, it can be preferable to utilize AC or DC current. For example, embodiments disclosed herein can employ phased array, pulsed, square wave, sinusoidal, or other wave forms, combinations, or the like. Certain embodiments utilize a controller to produce and control power production and/or distribution to the device.

[0124] Embodiments disclosed herein relating to iontophoresis treatment can also comprise selecting a patient or tissue in need of, or that could benefit by, using a disclosed system.

EXAMPLES [0125] The following non-limiting examples are provided for illustrative purposes only in order to facilitate a more complete understanding of representative embodiments. These examples should not be construed to limit any of the embodiments described in the present specification.

Example 1

[0126] An iontophoresis system as described herein is used to iontophoretically deliver a charged active agent to an area where treatment is desired. The iontophoresis system provides a uniform electric micro current across the treatment area, thus providing consistent delivery of the charged active agent.

Example 2

[0127] An iontophoresis system as described herein is used to iontophoretically deliver a charged active agent to an area where treatment is desired. The iontophoresis system provides a uniform electric field across the treatment area, thus providing consistent delivery of the charged active agent.

Example 3

[0128] A 44 year old male seeks treatment for headaches. An iontophoresis system as described herein is used to deliver a pulsed micro current to the patient's forehead. The patient reports reduced pain.

Example 4

[0129] A 24 year old female seeks treatment for knee pain. An iontophoresis system as described herein is used to deliver a pulsed micro current to the patient's knee. The patient reports reduced pain.

Example 5

[0130] A 66 year old male seeks treatment for back pain. An iontophoresis system as described herein is used to deliver a pulsed micro current to the patient's back. The system also iontophoretically delivers a pain reducing agent to the area. The patient reports reduced pain.

Example 6

[0131] A 32 year old male has a rhinoplasty performed. Following the surgery, the patient applies an iontophoresis system as described herein to deliver an anti-inflammatory to the area surrounding his nose. The patient reports reduced swelling.

Example 7

[0132] A 44 year old female suffers from arthritis pain in her hands. The patient applies an iontophoresis system as described herein to deliver an anti-inflammatory to her hands. The device also delivers a pain medication. The patient reports reduced pain.

[0133] In closing, it is to be understood that although aspects of the present specification are highlighted by referring to specific embodiments, one skilled in the art will readily appreciate that these disclosed embodiments are only illustrative of the principles of the subject matter disclosed herein. Therefore, it should be understood that the disclosed subject matter is in no way limited to a particular methodology, protocol, and/or reagent, etc., described herein. As such, various modifications or changes to or alternative configurations of the disclosed subject matter can be made in accordance with the teachings herein without departing from the spirit of the present specification. Lastly, the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present disclosure, which is defined solely by the claims. Accordingly, embodiments of the present disclosure are not limited to those precisely as shown and described.

[0134] Certain embodiments are described herein, comprising the best mode known to the inventor for carrying out the methods and devices described herein. Of course, variations on these described embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. Accordingly, this disclosure comprises all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described embodiments in all possible variations thereof is encompassed by the disclosure unless otherwise indicated herein or otherwise clearly contradicted by context.

[0135] Groupings of alternative embodiments, elements, or steps of the present disclosure are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other group members disclosed herein. It is anticipated that one or more members of a group may be comprised in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.

[0136] Unless otherwise indicated, all numbers expressing a characteristic, item, quantity, parameter, property, term, and so forth used in the present specification and claims are to be understood as being modified in all instances by the term "about." As used herein, the term "about" means that the characteristic, item, quantity, parameter, property, or term so qualified encompasses a range of plus or minus ten percent above and below the value of the stated characteristic, item, quantity, parameter, property, or term. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical indication should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and values setting forth the broad scope of the disclosure are approximations, the numerical ranges and values set forth in the specific examples are reported as precisely as possible. Any numerical range or value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Recitation of numerical ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate numerical value falling within the range. Unless otherwise indicated herein, each individual value of a numerical range is incorporated into the present specification as if it were individually recited herein.

[0137] The terms "a," "an," "the" and similar referents used in the context of describing the disclosure (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein is intended merely to better illuminate the disclosure and does not pose a limitation on the scope otherwise claimed. No language in the present specification should be construed as indicating any non-claimed element essential to the practice of embodiments disclosed herein.

[0138] Specific embodiments disclosed herein may be further limited in the claims using consisting of or consisting essentially of language. When used in the claims, whether as filed or added per amendment, the transition term "consisting of excludes any element, step, or ingredient not specified in the claims. The transition term "consisting essentially of limits the scope of a claim to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s). Embodiments of the present disclosure so claimed are inherently or expressly described and enabled herein.