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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
A copper-zinc malonate formulation has the following make-up:
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.
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.
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.
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.
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 |
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 |
Number | Date | Country | |
---|---|---|---|
20080081077 A1 | Apr 2008 | US |
Number | Date | Country | |
---|---|---|---|
60848616 | Sep 2006 | US |