Method of wound/burn healing using copper-zinc compositions

Information

  • Patent Grant
  • 7867522
  • Patent Number
    7,867,522
  • Date Filed
    Friday, December 29, 2006
    18 years ago
  • Date Issued
    Tuesday, January 11, 2011
    14 years ago
Abstract
Composition and methods for alleviating or eliminating wounds and/burns by providing an effective amount of one or more copper, zinc and copper-zinc compositions are disclosed. Treatment is accomplished through the use of topical compositions containing one or more copper or zinc salts and/or copper-zinc compounds or complexes, particularly copper-zinc malonate active ingredient.
Description
BACKGROUND

1. Technical Field


This disclosure relates to the use of compositions containing copper and zinc active ingredients for pharmaceutical purposes, and more specifically for healing wounds and/or burns.


2. Background of the Invention


The integumentary system includes the skin and all the structures associated with skin such as hair, nails, sweat glands and oil glands. The functions of the integumentary system include, inter alia, providing a protective barrier for the body to prevent the entry of potentially harmful things. Unfortunately, physical trauma to the protective barrier can result in open wounds such as torn, cut or punctured skin, or closed wounds such as contusions. Furthermore, other factors such as disease make some people prone to developing sores and ulcers. For example, diabetes may make some people prone to developing sores and ulcers on portions of the body that have lost sensitivity. Although there are known treatments for alleviating and healing wounds and/or burns, known treatments are problematic in that results vary from patient to patient. Moreover, no one treatment, if ever, obtains maximum benefit for every patient. As a result, some individuals have an increased risk for complications during healing such as bacterial infection. Accordingly, novel skin treatments are continuously sought after to help minimize burns and/or wounds, and decrease healing times thereof.


Accordingly, there remains room for improvement in skin treatment regimens that enhance burn and/or wound healing. What are needed are new skin care compositions and methods for healing burns and/or wounds.


SUMMARY

Active ingredients such as copper-zinc salts of multifunctional organic acids and formulations containing them may be used to treat wounded and/or burned skin. The copper constituent and zinc constituent, which may be cations, may be combined within a single molecule or used individually in separate molecules during topical application to treat wounds or burns. For example, copper and zinc constituents may be topically applied simultaneously to the skin of the user in order to combine the catalytic properties of each constituent. Moreover, the copper and zinc constituents may be topically applied in the same molecule to combine the catalytic properties of each constituent. Accordingly, the combined application of copper and zinc constituents in the same topical treatment provides enhanced wound and/or burn healing biological activity than the use of either constituent alone.


Skin having one or more wounds and/or burns is treated in accordance with the present disclosure by conditioning skin by the topical application of one or more active ingredients to skin. For example, compositions containing copper-zinc malonates can be directly applied to wounded and/or burned skin in need of treatment. Such conditioning by application of copper, zinc, and/or copper-zinc active ingredients may reduce or eliminate wounds and/or burns and make skin look healthier by stimulating collagen and elastin production in the dermis.


In addition, dermatological treatment regimens in accordance with the present disclosure may improve characteristics of a user's wounded or burned skin. The regimens include the repeated topical application of one or more copper-zinc active ingredients. Suitable corrective compositions include, for example, compositions which help to reduce or eliminate burns and/or wounds. In embodiments, compositions including a single molecule having both copper and zinc constituents are applied to wounds and/or burns to increase levels of collagen, elastin, tropoelastin, and/or elastic fibers in the dermis layer. The resulting increase can improve the wound and/or burn and reduce healing time. Thus, suitable corrective compositions include, for example, compositions which help to reduce or eliminate wounds, close wounds, stimulate collagen and elastin production in the dermis, and/or help to reduce or eliminate burns.


These and other aspects of this disclosure will be evident upon reference to the following detailed description.







DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Active ingredients are used in accordance with the present disclosure to treat wounds and/or burns. During the wound/burn healing process collagen and elastin are laid down by the body in the wound or burn to give the wound/burn strength and support, allow for expansion and contraction of the tissue, and to help necessary chemical reactions in the tissue. As copper and zinc are biologically needed by the body to catalyze the production of collagen, elastin, tropoelastin and/or elastic fibers in the dermis, active ingredients having copper and/or zinc constituents can be topically applied to the wound and/or burn to promote collagen, elastin, tropoelastin and/or elastic fibers production and treat wounds and/or burns. For example, bimetal complexes having copper and/or zinc constituents can be applied to skin to penetrate the dermis to stimulate production of collagen, elastin, tropoelastin and/or elastic fibers resulting in wound or burn healing.


Suitable active ingredients for use in accordance with the present disclosure include non-toxic compounds containing both copper and zinc. Such copper, zinc, and copper-zinc active ingredients include, but are not limited to, water soluble compounds that contain both copper and zinc. The water-soluble copper-zinc compounds include any copper-zinc salts formed from reacting any multifunctional organic or inorganic acid with any zinc or copper metal and/or their metallic bases. The organic acid can be aromatic or aliphatic. Suitable non-limiting examples of the water-soluble copper-zinc compounds include copper-zinc citrate, copper-zinc oxalate, copper-zinc tartarate, copper-zinc malate, copper-zinc succinate, copper-zinc malonate, copper-zinc maleate, copper-zinc aspartate, copper-zinc glutamate, copper-zinc glutarate, copper-zinc fumarate, copper-zinc glucarate, copper-zinc polyacrylic acid, and combinations thereof. Suitable non-water soluble copper-zinc compounds include any copper-zinc salts found from reacting any multifunctional water insoluble organic acid with zinc or copper metal and/or their metallic bases. Accordingly, suitable non-limiting examples of the non-water soluble copper-zinc compounds include copper-zinc adipate, copper-zinc pimelate, copper-zinc suberate, copper-zinc azealate, copper-zinc sebacate, copper-zinc dodecanoate, and combinations thereof. In embodiments, copper-zinc salts of organic multicarboxylic acids are suitable for use in accordance with the present disclosure. Accordingly, it is envisioned that multifunctional organic acids such as carboxylic acids may be reacted with any zinc or copper metal and/or their metallic bases to form the active ingredient of the present disclosure. In embodiments, the molar ratio of copper to zinc in the copper-zinc active ingredient is from about 1:1 to about 3:1. In other embodiments, the molar ratio of copper to zinc in the copper-zinc active ingredient is from about 1:1 to about 2:1.


In particular embodiments, non-limiting examples of suitable active ingredients include one or more copper-zinc malonates. As used herein “copper-zinc malonate” refers to any salt substances formed from malonic acid having copper and zinc constituents at various mole ratios of copper and zinc in the same molecule. For example, in embodiments, the molar ratio of copper to zinc in the copper-zinc malonate active ingredient is from about 1:1 to about 3:1. In other embodiments, the molar ratio of copper to zinc in the copper-zinc malonate active ingredient is from about 1:1 to about 2:1. In embodiments, copper-zinc malonate includes about 16.5% copper and about 12.4% zinc. In general, the copper-zinc malonate active ingredients used in accordance with the present disclosure include ingredients that are compounds of copper and zinc with malonic acid. Non-limiting examples of suitable ingredients for the formation of suitable copper-zinc malonates include, but are not limited to, malonic acid, zinc base, copper base, and water.


In forming suitable copper-zinc malonates for use in accordance with the present disclosure, malonic acid is present in amounts that will react with metal cations such as copper and zinc in an aqueous solution. Suitable amounts of malonic acid also include excess amounts in relation to the amount of copper and zinc cations to force reactions. In embodiments, malonic acid is present in a 3:1:1 molar ratio in relation to the copper and zinc constituents. Two or more salts containing copper and zinc constituents can be present in amounts that will react with malonic acid in an aqueous solution. Suitable salts that may be employed in making copper-zinc malonate active ingredients in accordance with this disclosure include metal salts containing complex-forming metal ions of copper and/or zinc. Non-limiting examples of suitable metal basic salts are: copper (I) and (II) salts such as copper carbonate, copper oxide, and copper hydroxide; and zinc salts such as zinc carbonate, zinc oxide, zinc hydroxide, metallic copper and metallic zinc. In embodiments, the reaction media includes two metallic salts, such as cupric carbonate (CuCO3.Cu(OH)2), zinc carbonate (3Zn(OH)2.2ZnCO3), or metallic zinc and metallic copper.


In embodiments, any copper salt or zinc salt active ingredient can be topically applied to treat skin. Such conditioning by application of copper or zinc salt active ingredients may reduce or eliminate any wound and/or burn, and stimulate collagen, elastin tropoelastin and/or elastic fiber production in the dermis to facilitate wound closure or burn healing. Suitable non-limiting examples of copper or zinc salts which may be used to treat skin wounds and/or burns include copper (II) malonate and any hydrated form thereof such as copper (II) malonate dihydrate, copper (II) malonate trihydrate, and copper malonate tetrahydrate. Other suitable non-limiting examples of suitable copper or zinc salt active ingredients for treating wounds and/or burns in accordance with the present disclosure include copper or zinc salts of citrate, oxalate, tartarate, malate, succinate, malonate, maleate, aspartate, glutamate, glutarate, fumarate, glucarate, polyacrylic acid, adipate, pimelate, suberate, azealate, sebacate, and/or dodecanoate. Combinations thereof are also possible.


The active ingredient or ingredients may be combined with numerous ingredients to form products to be applied to the skin, or other tissues of humans or other mammals. Such products may include a dermatologically or pharmaceutically acceptable carrier or diluent, vehicle or medium, for example, a carrier, vehicle or medium that is compatible with the tissues to which they will be applied. The term “dermatologically or pharmaceutically acceptable,” as used herein, means that the compositions or components thereof so described are suitable for use in contact with these tissues or for use in patients in general without undue toxicity, incompatibility, instability, allergic response, and the like. In embodiments, compositions in accordance with the present disclosure can contain any ingredient conventionally used in cosmetics and/or dermatology.


As an illustrative example, compositions can be formulated to contain active ingredient in amounts from about 0.001 to about 5% by weight of the total composition. In embodiments, products can be formulated to contain active ingredient in an amount from about 0.05 to about 1% by weight of the total composition. In other embodiments, the amount of active ingredient is from about 0.1 to about 0.5% by weight of the total composition. In such embodiments, the copper or zinc salt and/or copper-zinc present may be in a pharmaceutically acceptable salt form.


In embodiments, products containing active ingredients in accordance with the present disclosure can be in the form of solutions, emulsions (including microemulsions), suspensions, creams, fluid cream, oils, lotions, gels, powders, or other typical solid or liquid compositions used for treatment wounded skin. Such compositions may contain, in addition to the copper and/or zinc salts and/or copper-zinc salts in accordance with this disclosure, other ingredients typically used in such products, such as other active cosmetic substances such as retinol, retinol derivatives, allantoin, tocopherol, tocopherol derivatives, niacinamide, phytosterols, isoflavones, panthenol, panthenol derivatives, bisabolol, farnesol, and combinations thereof, other active drug substances such as corticosteroid, metronidazole, sulfacetamide, sulfur, and combinations thereof, antioxidants, antimicrobials, coloring agents, detergents, dyestuffs, emulsifiers, emollients, fillers, fragrances, gelling agents, hydration agents, moisturizers, odor absorbers, natural or synthetic oils, penetration agents, powders, preservatives, solvents, surfactants, thickeners, viscosity-controlling agents, water, distilled water, waxes, and optionally including anesthetics, anti-itch actives, botanical extracts, conditioning agents, darkening or lightening agents, glitter, humectant, mica, minerals, polyphenols, phytomedicinals, silicones or derivatives thereof, skin protectants, sunblocks, vitamins, and mixtures or combinations thereof. Such compositions may also contain, in addition to the copper or zinc salts and/or copper-zinc salts in accordance with this disclosure, one or more: fatty alcohols, fatty acids, organic bases, inorganic bases, wax esters, steroid alcohols, triglyceride esters, phospholipids, polyhydric alcohol esters, fatty alcohol ethers, hydrophilic lanolin derivatives, hydrophilic beeswax derivatives, cocoa butter waxes, silicon oils, pH balancers, cellulose derivatives, hydrocarbon oils, or mixtures and combinations thereof.


In embodiments, product forms can be formulated to contain humectant in amounts from about 1% to about 15% by weight of the total composition. For example glycerine can be added to the composition in amounts from about 1% to about 15% by weight of the total composition. In particular embodiments, glycerine can be added to the composition in amounts from about 1% to about 5% by weight of the total composition.


In embodiments, product forms can be formulated to contain solvent in amounts from about 1% to about 45% by weight of the total composition. For example petroleum derivatives such as propylene glycol can be added to the composition in amounts from about 1% to about 45% by weight of the total composition. In particular embodiments, propylene glycol can be added to the composition in amounts from about 15% to about 30% by weight of the total composition.


In embodiments, product forms can be formulated to contain water in amounts from about 40% to about 99% by weight of the total composition. For example distilled water can be added to the composition in amounts from about 40% to about 99% by weight of the total composition. In particular embodiments, distilled water can be added to the composition in amounts from about 65% to about 80% by weight of the total composition.


The present active ingredients such as copper-zinc active ingredients can be topically applied to skin in need of the reduction or elimination of wounds and/or burns. As used herein the word “treat,” “treating” or “treatment” refers to using the compositions of the present disclosure prophylactically to prevent outbreaks of undesirable wounds and/or burns, or therapeutically to ameliorate an existing wound and/or burn. A number of different treatments are now possible, which reduce and/or eliminate wounds and/or burns.


As used herein “wound” or “wounds” refer to any detectable break in the tissues of the body, such as injury to skin. Such injuries can appear due to a number of factors such as, for example, physical trauma such as those caused by external forces such as motor vehicle accidents, falls and the mishandling of sharp objects, tools, machinery and weapons; environmental damage such as sunburns; and/or other diseased or dysfunctional states of the body such as diabetes. Wounds further refers to cuts and scrapes known as open wounds, as well as others, such as deep bruises, or closed wounds. Non-limiting examples of wounds suitable for treatment in accordance with the present disclosure include abrasions such as those caused by scraping to the outer layer of skin; incisions such as those caused by sharp edges, knives, metal edges, broken glass or other sharp object; lacerations or jagged, irregular cuts or tears of the skin; punctures such as those caused by an object piercing the skin layers and creating a small hole; and/or burns. Additional non-limiting wounds suitable for treatment in accordance with the present disclosure include puncture wounds, gaping wounds, wounds having fatty layers, tissue or muscle exposed, wounds having one or more foreign bodies therein, wounds causing severe pain, wounds having blood flowing there from, or any wound that causes numbness or loss of movement below the wound.


Other non-limiting examples of wounds suitable for treatment in accordance with the present disclosure include animal bites, arterial disease, bee stings, bone infections, compromised skin/muscle grafts, gangrene, insect bites, radiation burns, skin tears or lacerations, surgical incisions, including slow or non-healing surgical wounds, post-operation infections, ulcers, including diabetic foot ulcers, pressure ulcers, traumatic ulcers, and venus stasis ulcers, vascular disease such as peripheral or collagenous. It is understood, that the listed wounds are non-limiting and that only a portion of wounds suitable for treatment in accordance with the present disclosure are listed herein.


As used herein “burn” or “burns” refer to any detectable injury to skin caused by energy applied to the skin. The terms further refer to any burning, or charring of the skin, including thermal burns caused by contact with flames, hot liquids, hot surfaces, and other sources of high heat as well as chemical burns and electrical burns. Burn or burns includes first degree burns which may cause skin manifestations such as reddening, pain, and/or mild swelling. One non-limiting example of first degree burn is a sun burn. Burn or burns further refers to second-degree burns involving the first two layers of skin. Signs of second degree burning include, among other things, deep reddening of the skin, blisters, pain, glossy appearance from leaking fluid, and possible skin loss. Burn or burns further refers to third-degree burns which penetrate the entire thickness of the skin and may destroy tissue. Signs of third degree burning include, among other things, loss of skin, dry skin, leathery skin, charred skin having a mottled appearance, and combinations thereof. In some case, skin with a third degree burn may be painless.


Compositions for use in accordance with the present disclosure contain one or more active ingredients capable of contacting skin with copper and zinc in an effective amount to improve a wound and/or condition. As used herein “effective amount” refers to an amount of a compound or composition having copper and zinc constituents in accordance with the present disclosure that is sufficient to induce a particular positive benefit to tissue having a wound and/or burn. The positive benefit can be health-related, or it may be more cosmetic in nature, or it may be a combination of the two. Here, it is believed that the positive benefit is achieved by contacting tissue such as skin with a combination of copper and zinc which can be in the form of copper and zinc ions, and/or one or more salts having copper and zinc constituents, to improve a wound and/or burn condition.


The particular copper-zinc-containing active ingredient or ingredients employed, and the concentration in the compositions, generally depends on the purpose for which the composition is to be applied. For example, the dosage and frequency of application can vary depending upon the type and severity of the wound and/or burn.


Treatments in accordance with the present disclosure contact wounded or burnt skin with one or more active ingredients such as those containing copper and zinc in an effective amount to increase collagen, elastin (insoluble/soluble), elastic fiber and/or tropoelastin levels therein. As used herein “elastin” refers to a protein in the skin that helps maintain resilience and elasticity. Generally, elastin is a protein in connective tissue that is elastic and allows tissues in the body, including skin, to resume their shape after stretching or contracting. For example, when pressure is applied to skin to change its shape, elastin helps skin to return to its original shape. Elastin may be made by linking multiple tropoelastin protein molecules to make a large insoluble cross-linked aggregate. As used herein “tropoelastin” refers to a water-soluble precursor to the elastin molecule, having a molecular weight of about 70000 Daltons. As used herein, “collagen” refers to a fibrous protein that contributes to the physiological functions of connected tissues in the skin, tendon, bones, and cartilage. Generally, the structural unit is tropocollagen composed of 3-polypeptide chains, designated A1, A2, and A3 that form a triple helical structure stabilized by hydrogen bonds. The term collagen further refers to collagen types, such as type I collagen, type II collagen, and type III collagen.


In embodiments, patients are treated by topically applying to a wound/burn in need of collagen, elastin, tropoelastin and/or elastic fibers one or more copper, zinc and/or copper-zinc salts, such as copper-zinc malonate. The active ingredient is applied until the treatment goals are obtained. However, the duration of the treatment can vary depending on the severity of the wound or burn. For example, treatments can last several weeks to months depending on whether the goal of treatment is to promote or repair collagen, elastin, tropoelastin and/or elastic fiber levels in the wounded or burnt skin. In treatment embodiments, 1 to 5 drops of a composition containing 0.1% copper-zinc malonate may be applied to wounded and/or burnt skin twice a day for 4 weeks.


The following non-limiting examples further illustrate methods in accordance with this disclosure.


Example 1

A 65 year old man is suffering from open soars on his feet. A composition containing copper-zinc malonate is applied to the wound twice a day for 10 days. Healing time is reduced.


Example 2

A 25 year old woman is suffering from 6 inch laceration to her right forearm. An emulsion composition suitable for treatment of skin containing an effective amount of copper-zinc malonate active ingredient is applied to her laceration three times a day for 1 week. The application of the copper-zinc malonate active ingredient promotes healing and decreases the time necessary for the wound to close.


Example 3

A 72 year old diabetic woman is suffering from a stage I pressure ulcer characterized by non-blanchable erythema on intact skin. A gel composition suitable for treatment of skin containing an effective amount of copper-zinc malonate active ingredient is routinely applied to the stage I pressure ulcer twice daily. The pressure ulcer is reduced or eliminated.


Example 4

A 72 year old diabetic woman is suffering from a stage II pressure ulcer characterized by partial skin loss involving the epidermis, dermis, or both. The lesion is superficial and presents clinically as a shallow center. A liquid composition suitable for treatment of skin containing an effective amount of copper-zinc malonate active ingredient is applied to the shallow center four times a day for 2 months. The stage II pressure ulcer is reduced or eliminated.


Example 5

A 72 year old diabetic woman is suffering from a stage III pressure ulcer characterized by full thickness skin loss involving damage or necrosis of subcutaneous tissue that extends down to, but not through, underlying fascia. The sore presents clinically as a deep crater. A liquid composition suitable for treatment of skin containing an effective amount of one or more copper-zinc malonate active ingredients is applied to the crater four times a day for 1 month. The stage III pressure ulcer is reduced or eliminated.


Example 6

A 72 year old diabetic woman is suffering from a stage IV pressure ulcer characterized by full thickness skin loss with extensive destruction, and tissue necrosis. A liquid composition suitable for treatment of skin containing an effective amount of copper-zinc malonate active ingredient is applied to the dying tissue four times a day for 1 month. The stage IV pressure ulcer is reduced or eliminated.


Example 7

A 4 year old boy is suffering from a bee sting characterized by pain and swelling. A liquid composition suitable for treatment of skin containing 0.05% copper-zinc malonate active ingredient is applied to the sting four times a day for 2 days. The bee sting is reduced or eliminated.


Example 8

A copper-zinc malonate formulation has the following make-up:
















COMPONENT
% BY WEIGHT



















Copper-zinc malonate*
0.1%



(Active ingredient)



Glycerine
3.0%



Propylene Glycol
25.0%



Distilled Water
71.9%







*Copper-zinc malonate was made by mixing 1 mole Zn/1 mole Cu/3 moles malonic acid.






Example 9

A 9 year old boy is suffering from a wound characterized as a 4 inch lesion on his back. The liquid composition of example 8 suitable for treatment of skin containing 0.1% copper-zinc malonate active ingredient is applied to the lesion 4 times a day for 10 days. The lesion is reduced or eliminated.


Example 10

An 18 year old girl with Fitzpatrick skin type II is suffering from a sun burn characterized by red skin on her back. The liquid composition of example 8 suitable for treatment of skin containing 0.1% copper-zinc malonate active ingredient is applied to the sun burn 4 times a day for 4 days. The sun burn is reduced or eliminated.


Example 11

A 36 year old male truck accident victim is suffering from third degree burns on his left wrist and stomach. A liquid composition suitable for treatment of skin containing an effective amount of copper-zinc malonate active ingredient is applied to the third degree burn four times a day for 1 month. The burnt wrist and stomach improve, and healing time is reduced.


While several embodiments of the disclosure have been described, it is not intended that the disclosure be limited thereto, as it is intended that the disclosure be as broad in scope as the art will allow and that the specification be read likewise. Therefore, the above description should not be construed as limiting, but merely as exemplifications of embodiments. Those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto.

Claims
  • 1. A method of treating a wound or burn comprising topically applying to a wound or burn a composition comprising a copper-zinc active ingredient comprising the reaction product of a polyfunctional carboxylic acid with basic salts of copper and zinc, wherein copper, zinc and the polyfunctional carboxylic acid are in the same molecule.
  • 2. The method as in claim 1 wherein the copper-zinc active ingredient is a water soluble copper-zinc compound.
  • 3. The method as in claim 1 wherein the copper-zinc active ingredient comprises copper-zinc citrate, copper-zinc oxalate, copper-zinc tartarate, copper-zinc malate, copper-zinc succinate, copper-zinc malonate, copper-zinc maleate, copper-zinc aspartate, copper-zinc glutamate, copper-zinc glutarate, copper-zinc fumarate, copper-zinc glucarate, copper-zinc polyacrylic acid, copper-zinc adipate, copper-zinc pimelate, copper-zinc suberate, copper-zinc azealate, copper-zinc sebacate, copper-zinc dodecanoate, or combinations thereof.
  • 4. The method as in claim 1 wherein the copper-zinc active ingredient is a copper-zinc malonate.
  • 5. The method as in claim 4 wherein the copper-zinc malonate comprises about 16.5% copper and about 12.4% zinc.
  • 6. The method of claim 1 wherein the molar ratio of copper to zinc in the copper-zinc active ingredient is from about 1:1 to about 3:1.
  • 7. The method of claim 1 wherein the molar ratio of copper to zinc in the copper-zinc active ingredient is from about 1:1 to about 2:1.
  • 8. The method of claim 1 wherein the copper-zinc active ingredient is present in an amount from about 0.001 to about 5% by weight of the composition.
  • 9. The method of claim 1 wherein the copper-zinc active ingredient is present in an amount from about 0.05 to about 1% by weight of the composition.
  • 10. The method of claim 1 wherein the copper-zinc active ingredient is present in an amount from about 0.1 to about 0.5% by weight of the composition.
  • 11. The method according to claim 1 wherein an effective amount of copper-zinc malonate composition is applied to the skin of a user to treat skin afflicted with one or more wounds or burns.
  • 12. The method as in claim 11 wherein the wound comprises a laceration, pressure ulcer, burn or combinations thereof.
  • 13. The method as in claim 1 wherein the composition is a solution, emulsion, microemulsion, suspension, cream, lotion, gel, powder, solid composition, or combinations thereof.
  • 14. The method according to claim 1, wherein the composition comprises a dermatologically acceptable carrier or diluent.
  • 15. A method for forming collagen, elastic fibers, elastin, or tropoelastin in the wound or burn of a patient comprising contacting a wound or burn with an effective amount of a composition wherein the composition comprises one or more copper-zinc active ingredients comprising the reaction product of a polyfunctional carboxylic acid with basic salts of copper and zinc, wherein copper, zinc and polyfunctional carboxylic acid are in the same molecule.
  • 16. The method according to claim 15, wherein the composition comprises a dermatologically acceptable carrier or diluent.
  • 17. The method according to claim 15, wherein the copper-zinc active ingredient is a water soluble copper-zinc compound.
  • 18. The method according to claim 15, wherein the copper-zinc active ingredient is selected from the group consisting of copper-zinc citrate, copper-zinc oxalate, copper-zinc tartarate, copper-zinc malate, copper-zinc succinate, copper-zinc malonate, copper-zinc maleate, copper-zinc aspartate, copper-zinc glutamate, copper-zinc glutarate, copper-zinc fumarate, copper-zinc glucarate, copper-zinc polyacrylic acid, copper-zinc adipate, copper-zinc pimelate, copper-zinc suberate, copper-zinc azealate, copper-zinc sebacate, copper-zinc dodecanoate, and combinations thereof.
  • 19. The method according to claim 15, wherein the copper-zinc active ingredient is a copper-zinc malonate.
  • 20. The method according to claim 19, wherein the copper-zinc malonate comprises about 16.5% copper and about 12.4% zinc.
  • 21. The method according to claim 15, comprising from about 0.001 to about 5 percent by weight of the copper-zinc active ingredient.
  • 22. The method according to claim 15, comprising from about 0.05 to about 1 percent by weight of the copper-zinc active ingredient.
  • 23. The method according to claim 15, comprising from about 0.1 to about 0.5% percent by weight of the copper-zinc active ingredient.
  • 24. The method of claim 15 wherein the composition further comprises a skin lightening agent, a sunscreen agent, a skin conditioning agent, a skin protectant, an emollient, a humectant, or a mixture thereof.
  • 25. A method of treating a wound or burn comprising topically applying to a wound or burn an effective amount of copper-zinc malonate, wherein the molar ratio of copper to zinc in the copper-zinc malonate is from about 1:1 to about 2:1.
  • 26. The method according to claim 25 wherein the copper-zinc malonate was formed in a reaction media including about 1 mole copper from cupric carbonate, about 1 mole of zinc from zinc carbonate and about 3 moles of malonic acid.
CROSS REFERENCE TO RELATED APPLICATION

This Application claims priority benefit of U.S. Provisional Application No. 60/848,616 filed Sep. 28, 2006 the entire disclosure of which is incorporated herein by this reference.

US Referenced Citations (435)
Number Name Date Kind
46494 Pike Feb 1865 A
51868 Schuster Jan 1866 A
55889 Noll Jun 1866 A
81008 Roemheld Aug 1868 A
81711 Van Wagenen Sep 1868 A
87343 Johnson Mar 1869 A
88973 McDowell Apr 1869 A
92065 Lighthall Jun 1869 A
93300 Hall et al. Aug 1869 A
116875 Shannon Jul 1871 A
124751 Lauer Mar 1872 A
127925 Roskopf Jun 1872 A
128385 Goffinet Jun 1872 A
140768 Fisher Jul 1873 A
143133 Fehr Sep 1873 A
145749 Pawlewski et al. Dec 1873 A
149857 Halpen Apr 1874 A
171875 Sievers Jan 1876 A
173607 Fehr Feb 1876 A
209331 Littleton Oct 1878 A
229014 Sharetts Jun 1880 A
232807 Dennett Oct 1880 A
238015 Yater Feb 1881 A
264783 Squier Sep 1882 A
277221 Buse May 1883 A
284335 Scott Sep 1883 A
318468 Haley May 1885 A
320836 Bisaillon Jun 1885 A
411657 Grosbety Sep 1889 A
415208 Johson Nov 1889 A
430048 Wainwright Jun 1890 A
432611 Hall Jul 1890 A
627296 Camnitzer Jun 1899 A
928539 Pucciarelli Jul 1909 A
944738 Loose Dec 1909 A
992937 Brodbeck et al. May 1911 A
1059841 Crookes Apr 1913 A
1086900 David Feb 1914 A
1332190 Hull Feb 1920 A
1411577 Mullins et al. Apr 1922 A
1488097 Creger Mar 1924 A
1584173 Holzapfel May 1926 A
1593485 Crosnier Jul 1926 A
1627963 Fuller May 1927 A
1809082 Urkov et al. Jun 1931 A
1908176 Osterberg May 1933 A
1947568 Noonan Feb 1934 A
1949797 Kaufmann Mar 1934 A
1982148 Zimbron, Jr. Nov 1934 A
2002829 Osterberg May 1935 A
2054989 Moore Sep 1936 A
2087162 Moore Jul 1937 A
2095092 Barton Oct 1937 A
2114490 Harris Apr 1938 A
2129836 Goodman Sep 1938 A
2153653 Stux Apr 1939 A
2194218 Thurstan Mar 1940 A
2223142 Weirich Nov 1940 A
2241331 Shelton May 1941 A
2254636 Vangunten Sep 1941 A
2267739 Kemppe Dec 1941 A
2289125 Keil Jul 1942 A
2299604 Weirich Oct 1942 A
2344830 Mohs Mar 1944 A
2361161 Anderson Oct 1944 A
2370561 Mecca Feb 1945 A
2372807 Brown Apr 1945 A
2420271 Travis et al. May 1947 A
2420389 Travis et al. May 1947 A
2469228 Gertler May 1949 A
2527686 Sandberg Oct 1950 A
2556567 Wright Jun 1951 A
2602039 Wershaw Jul 1952 A
2649398 Wright et al. Aug 1953 A
2652355 Ercoli et al. Sep 1953 A
2673364 Diveley Mar 1954 A
2703777 Feinstein et al. Mar 1955 A
2736681 Tishler Feb 1956 A
2748781 Collat Jun 1956 A
2838440 Thurmon Jun 1958 A
2843522 Mahon Jul 1958 A
2846322 Buchalter Aug 1958 A
2870150 Wright et al. Jan 1959 A
2870151 Wright et al. Jan 1959 A
2872372 Hull Feb 1959 A
2991224 Bell Jul 1961 A
3013883 Welcker et al. Dec 1961 A
3033755 Jacobi May 1962 A
3035988 Cohen May 1962 A
3084105 Slodki Apr 1963 A
3137622 Mueller et al. Jun 1964 A
3146168 Battista Aug 1964 A
3164523 Fox et al. Jan 1965 A
3184376 Degoli May 1965 A
3210248 Feldmann et al. Oct 1965 A
3215599 Thau et al. Nov 1965 A
3255079 Schroeder et al. Jun 1966 A
3290218 de Jong Dec 1966 A
3317372 Hart May 1967 A
3366114 Kanter Jan 1968 A
3590123 Melloh et al. Jun 1971 A
3749772 Cardarelli et al. Jul 1973 A
3821370 Tenta Jun 1974 A
3821371 Battista Jun 1974 A
3826845 Suyama et al. Jul 1974 A
3856941 Turner Dec 1974 A
3896238 Smith Jul 1975 A
3903268 Balassa Sep 1975 A
3949072 Tenta Apr 1976 A
4048300 Tomlinson et al. Sep 1977 A
4100269 Pader Jul 1978 A
4138477 Gaffar Feb 1979 A
4146607 Ritchey Mar 1979 A
4160821 Sipos Jul 1979 A
4161526 Gorman Jul 1979 A
4166108 Brown et al. Aug 1979 A
4226851 Sompayrac Oct 1980 A
4226889 Yuhas Oct 1980 A
4229430 Fahim et al. Oct 1980 A
4229437 Likens et al. Oct 1980 A
4255418 Bailey Mar 1981 A
4273763 Horrobin Jun 1981 A
4285967 Gubernick et al. Aug 1981 A
4291025 Pellico Sep 1981 A
4298601 Howard Nov 1981 A
4302447 Horrobin Nov 1981 A
4309989 Fahim Jan 1982 A
4310516 Chang et al. Jan 1982 A
4315916 Likens et al. Feb 1982 A
4322400 Yuhas Mar 1982 A
4330527 Arima et al. May 1982 A
4331653 Brown et al. May 1982 A
4335110 Collins Jun 1982 A
4349536 Hausler Sep 1982 A
4372296 Fahim Feb 1983 A
4375968 Manhart Mar 1983 A
4376115 McCrorey Mar 1983 A
4395398 Yamamoto Jul 1983 A
4406881 Ladanyi Sep 1983 A
4428933 King Jan 1984 A
4430324 Viccaro Feb 1984 A
4444755 Horrobin Apr 1984 A
4465666 Lukas et al. Aug 1984 A
4469684 Huggins et al. Sep 1984 A
4477439 D'Alelio Oct 1984 A
4486488 Pietsch et al. Dec 1984 A
4503037 Szijjarto et al. Mar 1985 A
4512978 Inwood Apr 1985 A
4515779 Elliott May 1985 A
4522806 Muhlemann et al. Jun 1985 A
4568540 Asano et al. Feb 1986 A
4604234 Fujii et al. Aug 1986 A
4606920 Walter Aug 1986 A
4647452 Ritchey et al. Mar 1987 A
4654213 Ramirez et al. Mar 1987 A
4661354 Finnerty Apr 1987 A
4665054 Pickart May 1987 A
4678664 Schmolka Jul 1987 A
4683133 Southard Jul 1987 A
4713242 Trenzeluk Dec 1987 A
4760051 Pickart Jul 1988 A
4762715 Lukas et al. Aug 1988 A
4767753 Pickart Aug 1988 A
4810693 Pickart Mar 1989 A
4816254 Moss Mar 1989 A
4847083 Clark Jul 1989 A
4849211 Schrauzer Jul 1989 A
4855138 Trenzeluk Aug 1989 A
4863897 Dede et al. Sep 1989 A
4863987 Hoshino et al. Sep 1989 A
4874361 Obagi Oct 1989 A
4877770 Pickart Oct 1989 A
4895727 Allen Jan 1990 A
4911932 Clum et al. Mar 1990 A
4937230 Pickart Jun 1990 A
4938969 Schinitsky et al. Jul 1990 A
4956354 Gutierrez Sep 1990 A
RE33512 Ramirez et al. Jan 1991 E
4992259 Schiraldi et al. Feb 1991 A
5000944 Prencipe et al. Mar 1991 A
5023237 Pickart Jun 1991 A
5059588 Pickart Oct 1991 A
5075469 Chevion Dec 1991 A
5079010 Natterer Jan 1992 A
5091171 Yu et al. Feb 1992 A
5091193 Enjolras et al. Feb 1992 A
5093099 Haishi et al. Mar 1992 A
5104644 Douglas Apr 1992 A
5118665 Pickart Jun 1992 A
5120831 Pickart Jun 1992 A
5135913 Pickart Aug 1992 A
5145838 Pickart Sep 1992 A
5154932 Burba, III et al. Oct 1992 A
5164367 Pickart Nov 1992 A
5165914 Vlock Nov 1992 A
5166176 Obagi et al. Nov 1992 A
5174990 Douglas Dec 1992 A
5177061 Pickart Jan 1993 A
5209932 Nichols May 1993 A
5214032 Pickart May 1993 A
5227156 Wiese Jul 1993 A
5232691 Lemole Aug 1993 A
5240696 Van Der Ouderaa et al. Aug 1993 A
5244651 Kayane et al. Sep 1993 A
5258183 Grimberg Nov 1993 A
5310546 Douglas May 1994 A
5330748 Winston et al. Jul 1994 A
5330749 Giacin et al. Jul 1994 A
5348943 Pickart Sep 1994 A
5382431 Pickart Jan 1995 A
5385727 Winston et al. Jan 1995 A
5401730 Sauvage et al. Mar 1995 A
5424077 Lajoie Jun 1995 A
5439863 Bottcher et al. Aug 1995 A
5455023 Giacin et al. Oct 1995 A
5466470 Lajoie Nov 1995 A
5480975 Goldberg et al. Jan 1996 A
5482720 Murphy et al. Jan 1996 A
5500448 Cummins et al. Mar 1996 A
5547676 Rocher et al. Aug 1996 A
5550183 Pickart Aug 1996 A
5552147 Znaiden et al. Sep 1996 A
5554375 Pickart Sep 1996 A
5554647 Perricone Sep 1996 A
5582817 Otsu et al. Dec 1996 A
5597550 Mo Jan 1997 A
5597552 Herms et al. Jan 1997 A
5616313 Williams et al. Apr 1997 A
5622724 Bryce-Smith Apr 1997 A
5624675 Kelly Apr 1997 A
5631013 Bergmann et al. May 1997 A
5632972 Williams et al. May 1997 A
5645840 Lajoie et al. Jul 1997 A
5663213 Jones et al. Sep 1997 A
5686083 Chamness Nov 1997 A
5688492 Galley et al. Nov 1997 A
5690967 Yu et al. Nov 1997 A
5696169 Otsu et al. Dec 1997 A
5698184 Pickart Dec 1997 A
5707609 Mo Jan 1998 A
5708023 Modak et al. Jan 1998 A
5728404 Von Rheinbaben et al. Mar 1998 A
5747005 Barels et al. May 1998 A
5753637 Fried May 1998 A
5762945 Ashley et al. Jun 1998 A
5780020 Peterson et al. Jul 1998 A
5795574 Breton et al. Aug 1998 A
5798121 Cauwet et al. Aug 1998 A
5827884 Obagi et al. Oct 1998 A
5837270 Burgess Nov 1998 A
5855873 Yam Jan 1999 A
5858335 Lucas et al. Jan 1999 A
5858371 Singh et al. Jan 1999 A
5858993 Pickart Jan 1999 A
5861143 Peterson et al. Jan 1999 A
5861144 Peterson et al. Jan 1999 A
5861145 Lucas et al. Jan 1999 A
5861146 Peterson et al. Jan 1999 A
5861147 Dodd et al. Jan 1999 A
5871718 Lucas et al. Feb 1999 A
5871719 Lucas et al. Feb 1999 A
5874067 Lucas et al. Feb 1999 A
5874070 Trinh et al. Feb 1999 A
5879666 Lucas et al. Mar 1999 A
5882638 Dodd et al. Mar 1999 A
5886184 Dolling et al. Mar 1999 A
5888515 Albert et al. Mar 1999 A
5888522 Pickart Mar 1999 A
5897854 Lucas et al. Apr 1999 A
5897855 Trinh et al. Apr 1999 A
5897856 Trinh et al. Apr 1999 A
5911976 Trinh et al. Jun 1999 A
5928631 Lucas et al. Jul 1999 A
5928658 Kishida et al. Jul 1999 A
5928659 Moy Jul 1999 A
5935608 Fujikawa et al. Aug 1999 A
5942214 Lucas et al. Aug 1999 A
5948390 Nelson et al. Sep 1999 A
5951990 Ptchelintsev Sep 1999 A
5955067 Oge et al. Sep 1999 A
5961993 Boussouira et al. Oct 1999 A
5965137 Petrus Oct 1999 A
5965610 Modak et al. Oct 1999 A
5972999 Murad Oct 1999 A
5994403 Donatiello Nov 1999 A
6019976 Bryant Feb 2000 A
6022565 Albert et al. Feb 2000 A
6030605 D'Ameila et al. Feb 2000 A
6037386 Modak et al. Mar 2000 A
6046178 Silvetti, Sr. Apr 2000 A
6060079 Freeman et al. May 2000 A
6071543 Thornfeldt Jun 2000 A
6083490 Ellis et al. Jul 2000 A
6086666 Noguchi et al. Jul 2000 A
6103247 Boussouira et al. Aug 2000 A
6103273 Antoun Aug 2000 A
6113636 Ogle Sep 2000 A
6121254 Saint-Leger Sep 2000 A
6123925 Barry et al. Sep 2000 A
6132743 Kuroda et al. Oct 2000 A
6143318 Gilchrist et al. Nov 2000 A
6149947 Hon et al. Nov 2000 A
6183785 Westfall Feb 2001 B1
6190407 Ogle et al. Feb 2001 B1
6191167 Yu et al. Feb 2001 B1
6200580 Horino et al. Mar 2001 B1
6200680 Takeda et al. Mar 2001 B1
6217914 Meisner Apr 2001 B1
6221403 Nesbit Apr 2001 B1
6224896 Redmond May 2001 B1
6248370 Harris Jun 2001 B1
6261574 Costello Jul 2001 B1
6267782 Ogle et al. Jul 2001 B1
6287541 Creeth et al. Sep 2001 B1
6303651 Hersh Oct 2001 B1
6322588 Ogle et al. Nov 2001 B1
6322820 Simoneau Nov 2001 B1
6331567 Watson et al. Dec 2001 B1
6361800 Cooper et al. Mar 2002 B1
6375942 Rico Apr 2002 B1
6395301 Cantin May 2002 B1
6416744 Robinson et al. Jul 2002 B1
6444699 Meisner Sep 2002 B2
6451294 Simon Sep 2002 B1
6471972 Bonte et al. Oct 2002 B1
6475526 Smith Nov 2002 B1
6517849 Seger et al. Feb 2003 B1
6521265 Patterson Feb 2003 B1
6558710 Godfrey May 2003 B1
6579541 Antelman Jun 2003 B2
6582684 Abrahamson Jun 2003 B1
6582710 Deckers et al. Jun 2003 B2
6592852 Ryles et al. Jul 2003 B1
6599513 Deckers et al. Jul 2003 B2
6607716 Smith et al. Aug 2003 B1
6627178 Cawthon Sep 2003 B1
6660306 Peshoff Dec 2003 B2
6663852 Simon Dec 2003 B2
6680073 Tarbet Jan 2004 B1
6682720 Ryles et al. Jan 2004 B2
6696071 Kelly Feb 2004 B2
6726919 Pace et al. Apr 2004 B2
6730309 Horino May 2004 B2
6730329 Smith May 2004 B1
6743416 Riedl Jun 2004 B2
6750209 Hudson et al. Jun 2004 B1
6773698 Melinte et al. Aug 2004 B1
6780439 Wilk Aug 2004 B2
6800301 Smith Oct 2004 B2
6833362 Bowen, Jr. et al. Dec 2004 B2
6844012 Forceville et al. Jan 2005 B1
6849277 Roig Feb 2005 B2
6855341 Smith Feb 2005 B2
6858201 Pickart Feb 2005 B2
6929800 Salman Aug 2005 B2
6932976 Brooks Aug 2005 B2
6939568 Burrell et al. Sep 2005 B2
6942878 Ishii et al. Sep 2005 B2
6949248 Nishihama Sep 2005 B2
6949249 Healy et al. Sep 2005 B2
6964782 Smith et al. Nov 2005 B1
6989156 Gillis Jan 2006 B2
7008647 Burrell et al. Mar 2006 B2
7014870 Hon et al. Mar 2006 B1
7049339 Thomson May 2006 B2
20010014356 Yoshida et al. Aug 2001 A1
20010041193 Meisner Nov 2001 A1
20020001629 Voellmy Jan 2002 A1
20020031557 Meisner Mar 2002 A1
20020114847 Peshoff Aug 2002 A1
20020182244 Jackson Dec 2002 A1
20030004564 Elkins et al. Jan 2003 A1
20030026848 Joshi Feb 2003 A1
20030035825 Shiau et al. Feb 2003 A1
20030059484 Bonte et al. Mar 2003 A1
20030068351 Roig Apr 2003 A1
20030069369 Belenkaya et al. Apr 2003 A1
20030072819 Tao Apr 2003 A1
20030077304 McCadden Apr 2003 A1
20030077332 Godfrey Apr 2003 A1
20030082219 Warren et al. May 2003 A1
20030082223 Healy et al. May 2003 A1
20030099721 Yoshida et al. May 2003 A1
20030118623 De Paoli Ambrosi Jun 2003 A1
20030133991 Monroe et al. Jul 2003 A1
20030138497 Sakuma et al. Jul 2003 A1
20030161892 McFarland Aug 2003 A1
20030190371 Graaf et al. Oct 2003 A1
20030194446 Akes et al. Oct 2003 A1
20030199488 Trotta Oct 2003 A1
20030215412 Waugh et al. Nov 2003 A1
20030215522 Johnson et al. Nov 2003 A1
20030224023 Faryniarz et al. Dec 2003 A1
20030224027 Faryniarz et al. Dec 2003 A1
20040022863 Hamtini Feb 2004 A1
20040028708 Brooks Feb 2004 A1
20040033270 Kropf et al. Feb 2004 A1
20040037910 Hon et al. Feb 2004 A1
20040058011 Petersson Mar 2004 A1
20040058015 Tao Mar 2004 A1
20040062730 Kurosawa et al. Apr 2004 A1
20040062817 Peshoff Apr 2004 A1
20040076686 Riesinger Apr 2004 A1
20040091551 Damji May 2004 A1
20040101541 Heffernan et al. May 2004 A1
20040109902 McDonagh et al. Jun 2004 A1
20040131700 Cifra et al. Jul 2004 A1
20040156875 Fabre et al. Aug 2004 A1
20040157921 Cifra et al. Aug 2004 A1
20040170701 Carter Sep 2004 A1
20040170703 Hoekstra et al. Sep 2004 A1
20040170712 Sadek El Mogy Sep 2004 A1
20040175433 Thomson Sep 2004 A1
20040185015 Zhang et al. Sep 2004 A1
20040185074 Faryniarz et al. Sep 2004 A1
20040202689 Subramanyan et al. Oct 2004 A1
20040220100 Waugh et al. Nov 2004 A1
20040253321 Fechner et al. Dec 2004 A1
20040258769 Barker et al. Dec 2004 A1
20050032751 Wang et al. Feb 2005 A1
20050048010 Klis et al. Mar 2005 A1
20050069506 Katusic et al. Mar 2005 A1
20050069588 Taal Mar 2005 A1
20050074425 Waugh et al. Apr 2005 A1
20050079229 Cawthon Apr 2005 A1
20050100571 Keyes May 2005 A1
20050123620 Chiou Jun 2005 A1
20050136129 Verheul-Koot et al. Jun 2005 A1
20050175719 Sun et al. Aug 2005 A1
20050202054 Faryniarz et al. Sep 2005 A1
20050234239 Taillefer et al. Oct 2005 A1
20050238730 Le Fur et al. Oct 2005 A1
20060029682 Monroe et al. Feb 2006 A1
20060036007 Hsieh et al. Feb 2006 A1
20070163465 Anderson et al. Jul 2007 A1
Foreign Referenced Citations (6)
Number Date Country
2001039809 Feb 2001 JP
WO 0210 0383 Dec 2002 WO
WO 2004039238 May 2004 WO
WO 2004039238 May 2004 WO
WO 200605 5526 May 2006 WO
WO 200708 9267 Aug 2007 WO
Related Publications (1)
Number Date Country
20080081077 A1 Apr 2008 US
Provisional Applications (1)
Number Date Country
60848616 Sep 2006 US