Patent Application
20050196450
This invention relates to compositions, methods and delivery systems for application on burns and surrounding tissue wherein said composition comprise ammonium hydroxide (or ammonium bicarbonate) and /or 15-70% volatile short chain mono-alcohols
Thermal burn injury induces non-specific inflammatory reaction generating dermal vascular damage, destruction of epidermis, edema and blister formation. These responses lead to progressive ischemic damage to the skin tissue, reduced blood perfusion and tissue necrosis. Since not all the skin tissues are immediately destroyed after thermal burn, depth of burns progresses with time. Cytokines IL6, IL1, TNF alpha, other pro-inflammatory interleukins and globulins are important factors in the development of microvascular injury and wound development in burned skin and tissue. Numerous attempts to favorably alter the burn wound by pharmacologic agent are generally of moderate efficiency. Burned skin could be a result of infliction produced by heat, light, UV rays, X-rays, Laser, Infrared rays, friction, abrasion, cold, liquid nitrogen.
The use of anti-inflammatory agents and local anesthetics to alleviate inflammation and pain resulting from burns is known. Compositions containing steroidal anti-inflammatories, non-steroidal anti-inflammatories, as well as “natural” anti-inflammatories, such as extract of plants such as aloe vera, have been used.
With respect to the care of burns, the main objectives are to relieve pain, help prevent contamination, eliminate the source of heat and stop the burn progress.
In one embodiment, the invention provides a composition and use thereof for treating membrane/organ/ burned, friction inflicted skin comprising ethyl or isopropyl alcohol in a concentration of 1 5-70%w/w.
In another embodiment, the invention provides a composition and use thereof for treating burned skin /membrane/organ comprising ammonium hydroxide.
In another embodiment, the invention provides a delivery system and use thereof for treating burned skin /membrane/organ comprising a polymer matrix and ammonium hydroxide and ethyl or isopropyl alcohol wherein the ethyl or isopropyl alcohol is in a concentration of 20-60%W/W.
In another embodiment, the invention provides a composition comprising ethanol from 20-60% w/w, polyacrylate polymer from 0.05%-10%, ammonium hydroxide from 0.1-10%, water from 30-89% to be applied on burned skin and surrounding area, to treat and/ or impede progression and or impede development of burns.
In another embodiment, the invention provides a Composition comprising ethanol from 25-60% w/w, polyacrylate polymer from 0.05%-10%w/w triethanolamine from 0.1-6%, water from 30-74%, to be applied on burned skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment, the invention provides a composition comprising ethanol from 15-60% w/w, polyacrylate polymer from 0.05%-5%, ammonium hydroxide from 0.1-10%, urea from 0.05 to 5% and water from 30-84%, to be applied on burned skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment, the invention provides a composition comprising ethanol from 15-70% w/w, cellulose derivative (ethyl, methyl, hydroxymethyl, hydroxyethyl, hydroxypropyl or mixtures of) polymer from 0.05%-20%, and water from 30-84%, to be applied on burned skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment, the invention provides a composition comprising ethanol from 15-70% w/w, cellulose derivative (ethyl, methyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, mixtures of) polymer from 0.05%-20%, a hydroxide from 0.1-10%, and water from 30-84%, to be applied on burned skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment, the invention provides a composition comprising ethanol from 15-70% w/w, cellulose derivative (ethyl, methyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, mixtures of) polymer from 0.05%-20%, an alkaline agent from 0.1-10%, and water from 30-84%, to be applied on burned, inflicted skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment, the invention provides a method for treating and/or impeding progression and or impeding development of burns comprising the step of adding to the burned, inflicted area a composition comprising ethyl or isopropyl alcohol in a concentration of 15-70%w/w.
In another embodiment, the invention provides a method for treating and/or impeding progression and or impeding development of burns comprising the step of adding to the burned, inflicted area a composition comprising ethyl or isopropyl alcohol in a concentration of 15-70%w/w being a vehicle for compounds for burn treatments.
In another embodiment, the invention provides a method for treating and/or impeding progression and or impeding development of burns comprising the step of adding a composition to the burned, inflicted area comprising ammonium hydroxide.
In another embodiment, the invention provides a method for treating and/or impede progression and or impede development of burns comprising the step of adding to the burned area a composition comprising ammonium hydroxide and ethyl and/or isopropyl alcohol wherein the ethyl and/or isopropyl alcohol is in a concentration of 20-60%w/w.
In one embodiment, the invention provides a composition for treating burned skin /membrane/organ comprising ethyl or isopropyl alcohol in a concentration of 20-60%w/w.
In another embodiment, the invention provides a composition for treating burned, inflicted skin /membrane/organ comprising ammonium hydroxide.
In another embodiment, the invention provides a delivery system and use thereof for treating burned skin /membrane/organ comprising a polymer matrix and ammonium hydroxide and ethyl or isopropyl alcohol, wherein the ethyl or isopropyl is in a concentration of 15-70%w/w.
In another embodiment, the invention provides a composition comprising ethanol from 20-70% w/w, polyacrylate polymer from 0.05%-5%, ammonium hydroxide from 0.1-10%, water from 30-80% to be applied on burned skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment, the invention provides a composition comprising ethanol from 25-60% w/w, polyacrylate polymer from 0.05%-5%w/w triethanolamine from 0.1-6%, water from 30-74%, to be applied on burned skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment, the invention provides a composition comprising ethanol from 15-70% w/w, polyacrylate polymer from 0.05%-5%, ammonium hydroxide from 0.1-10%, urea from 0.05 to 5% and water from 30-84%, to be applied on burned skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment, the invention provides a method for treating and/or impeding progression and or impeding development of burns comprising the step of adding to the burned area a composition comprising ethyl or isopropyl alcohol in a concentration of 15-70% w/w.
In another embodiment, the invention provides a method for treating and/or impedes progression and or impedes development of burns comprising the step of adding a composition to the burned area comprising ammonium hydroxide.
In another embodiment, the invention provides a method for treating and/or impede progression and or impede development of burns comprising the step of adding to the burned area a composition comprising ammonium hydroxide and ethyl and/or isopropyl alcohol wherein the ethyl and/or isopropyl is in a concentration of 20-70%W/W.
In another embodiment, the invention provides a method for treating and/or impeding progression and or impeding development of burns comprising the step of adding to the burned area a delivery system comprising polymer matrix and ethyl or isopropyl alcohol in a concentration of 20-70% w/w.
In another embodiment, the invention provides a method for treating and/or impedes progression and or impedes development of burns comprising the step of adding a delivery system comprising polymer matrix and ammonium hydroxide.
In another embodiment, the invention provides a method for treating and/or impede progression and/or impede development of burns comprising the step of adding to the burned area a delivery system comprising a polymer matrix ammonium hydroxide and ethyl and/or isopropyl alcohol wherein the ethyl and/or isopropyl is in a concentration of 20-70%w/w.
In another embodiment, the invention provides a method for treating and/or impede progression and/or impede development of burns comprising the step of adding to the burned area a composition comprising ethanol from 10-70% w/w, polyacrylate polymer from 0.05%-5%, ammonium hydroxide from 0.1-10%, water from 30-84% to be applied on burned skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment, the invention provides a method for treating and/or impede progression and/or impede development of burns comprising the step of adding to the burned area a composition comprising ethanol from 25-70% w/w, polyacrylate polymer from 0.05%-5%w/w triethanolamine from 0.1-6%, water from 30-84%, to be applied on burned skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment, the invention provides a method for treating and/or impede progression and or impede development of burns comprising the step of adding to the burned area a composition comprising ethanol from 15-70% w/w, polyacrylate polymer from 0.05%-5%, ammonium hydroxide from 0.1-10%, urea from 0.05 to 5% and water from 30-84%, to be applied on burned skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment of the invention, there is provided a method for inhibiting the rejection of skin implants in a subject in need comprising the step of contact the inflicted area and/or the implant with an effective amount of the composition of the invention.
In another embodiment, the invention provides a method for inhibiting the rejection of skin implants in a subject in need comprising the step of contact the inflicted area and/or the implant with an effective amount of a composition comprising ethyl and/or isopropyl alcohol, wherein the ethyl and/or isopropyl alcohol is in a concentration of 15-70%.
In another embodiment, the invention provides a method for inhibiting the rejection of skin implants in a subject in need comprising the step of contact the inflicted area and/or the implant with an effective amount of a composition comprising ammonium hydroxide.
In another embodiment, the invention provides a method for inhibiting the rejection of skin implants in a subject in need comprising the step of contact the inflicted area and/or the implant with an effective amount of a composition comprising ammonium hydroxide and ethyl or isopropyl alcohol, wherein the ethyl and/or isopropyl alcohol is in a concentration of 15-70%.
In another embodiment, the invention provides a method for reducing the level of a cytokine, interleukin, tumor necrosis factor, IL1 or IL6 in an inflicted skin area comprising the step of contact the inflicted or preinflicted area with an effective amount of a composition comprising ethyl and/or isopropyl alcohol, wherein the ethyl and/or isopropyl alcohol is in a concentration of 15-70%.
In another embodiment, the invention provides a method for reducing the level of a cytokine, interleukin, tumor necrosis factor, IL1 or IL6 in an inflicted skin area comprising the step of contact the inflicted or preinflicted area with an effective amount of a composition comprising ammonium hydroxide.
In another embodiment, the invention provides a method for reducing the level of a cytokine, interleukin, tumor necrosis factor, IL 1 or IL6 in an inflicted skin area comprising the step of contact the inflicted or preinflicted area with an effective amount of a composition comprising ammonium hydroxide and ethyl or isopropyl alcohol, wherein the ethyl and/or isopropyl alcohol is in a concentration of 15-70%.
The invention is based on the surprising discovery that compositions as well as delivery systems comprising volatile short chain alcohols such as ethyl or isopropyl alcohol in a concentration of 15-70% w/w alone, or in combination with ammonium hydroxide, applied on burns, skin, surrounding skin, membrane, organ, before or after burn stimulus could impede wound development.
In one embodiment of the invention there is provided a composition for treating burned skin /membrane/organ comprising ethyl or/and isopropyl alcohol in a concentration of 20-70%w/w.
In another embodiment, the invention provides a composition for treating burned skin /membrane/organ comprising ammonium hydroxide.
In another embodiment of the invention the ammonium hydroxide is in concentrations from 0.01% to 10% w/w.
In another embodiment, the invention is directed to a composition for treating burned skin /membrane/organ comprising ammonium hydroxide and ethyl and/or isopropyl alcohol wherein the ethyl and/or isopropyl alcohol is in a concentration of 20-70%.
In one embodiment, the composition may comprise ammonium hydroxide is in concentrations from 0.01% to 10% w/w.
In another embodiment, the composition may comprise ammonium hydroxide is in concentrations from 0.01% to 0.1% w/w.
In another embodiment, the composition may comprise ammonium hydroxide is in concentrations from 0.01% to 0.5% w/w.
In another embodiment, the composition may comprise ammonium hydroxide is in concentrations from 0.01% to 1% w/w.
In another embodiment, the composition may comprise ammonium hydroxide is in concentrations from 0.01% to 0.5% w/w.
In another embodiment, the composition may comprise ammonium hydroxide is in concentrations from 0.01% to 1% w/w.
In another embodiment, the composition may comprise ammonium hydroxide is in concentrations from 1% to 5% w/w.
In another embodiment, the composition may comprise ammonium hydroxide is in concentrations from 5% to 10% w/w.
In an embodiment of the invention the composition may comprise ethyl alcohol or/ and isopropyl alcohol at concentrations of 20-40%w/w.
In an embodiment of the invention the composition may comprise ethyl alcohol or/ and isopropyl alcohol at concentrations of 40-70%w/w.
In another embodiment the concentration of ethyl and/or isopropyl is about 30%.
In another embodiment the concentration of ethyl and/or isopropyl is about 25%.
In another embodiment the concentration of ethyl and/or isopropyl is about 20%.
In another embodiment the concentration of ethyl and/or isopropyl is about 35%.
In another embodiment the concentration of ethyl and/or isopropyl is about 40%.
In another embodiment the concentration of ethyl and/or isopropyl is about 45%.
In another embodiment the concentration of ethyl and/or isopropyl is about 50%.
In another embodiment the composition of the invention further comprises urea in concentrations from 0.05% to 5% w/w.
In another embodiment the composition of the invention further comprises urea in concentrations from 0.05% to 10% w/w.
In another embodiment the composition of the invention further comprises ethanolamine in concentrations from 0.01% to 5% w/w. The ethanol amine may be, for example without limitation, triethanolamine.
In another embodiment of the invention there is provided a delivery system for treating burned skin/membrane/mucosa, organ comprising a polymer matrix and ethyl or/and isopropyl alcohol in a concentration of 20-70%.
In another embodiment, the invention provides a delivery system for treating burned skin /membrane/organ comprising ammonium hydroxide and a polymer matrix.
In another embodiment of the invention the ammonium hydroxide is in concentrations from 0.01% to 10% w/w.
The delivery system may comprise ammonium hydroxide is in concentrations from 0.01% to 0.1% w/w.
The delivery system may comprise ammonium hydroxide is in concentrations from 0.01% to 0.5% w/w.
The delivery system may comprise ammonium hydroxide is in concentrations from 0.01% to 1% w/w.
The delivery system may comprise ammonium hydroxide is in concentrations from 0.01% to 0.5% w/w.
The delivery system may comprise ammonium hydroxide is in concentrations from 0.01% to 1% w/w.
The delivery system may comprise ammonium hydroxide is in concentrations from 1%-5% w/w.
The delivery system may comprise ammonium hydroxide is in concentrations from 5%-10% w/w.
In another embodiment, the invention provides an aqueous delivery system for treating burned skin /membrane/organ comprising ammonium carbonate and a polymer matrix.
In another embodiment, the invention provides an aqueous delivery system for treating burned skin /membrane/organ comprising ammonium carbonate.
In another embodiment of the invention, the concentration of the ammonium carbonate in the delivery system is from 0.01% to 10% w/w.
In another embodiment of the invention, the delivery system may comprise ammonium hydroxide is in concentrations from 0.01% to 1% w/w.
In another embodiment of the invention, the delivery system may comprise ammonium hydroxide is in concentrations from 0.01% to 0.1% w/w.
In another embodiment of the invention, the delivery system may comprise ammonium hydroxide is in concentrations from 0.01% to 0.5% w/w.
In another embodiment of the invention, the delivery system may comprise ammonium hydroxide is in concentrations from 0.01% to 1% w/w
In another embodiment of the invention, the delivery system may comprise ammonium hydroxide is in concentrations from 0.01% to 0.5% w/w.
In another embodiment of the invention, the delivery system may comprise ammonium hydroxide is in concentrations from 0.01% to 1% w/w.
In another embodiment of the invention, the delivery system may comprise ammonium hydroxide is in concentrations from 1%-5% w/w.
In another embodiment of the invention, the delivery system may comprise ammonium hydroxide is in concentrations from 5%-I0% w/w.
In another embodiment, the invention is directed to a delivery system for treating burned skin /membrane/organ comprising ammonium hydroxide and ethyl and/or isopropyl alcohol, wherein the ethyl and/or isopropyl is in a concentration of 20-60% w/w.
In another embodiment the concentration of the ethyl and/or isopropyl is from 30-50%.
In another embodiment the concentration of ethyl and/or isopropyl is about 30%.
In another embodiment the concentration of ethyl and/or isopropyl is about 25%.
In another embodiment the concentration of ethyl and/or isopropyl is about 20%.
In another embodiment the concentration of ethyl and/or isopropyl is about 35%.
In another embodiment the concentration of ethyl and/or isopropyl is about 40%.
In another embodiment the concentration of ethyl and/or isopropyl is about 45%.
In another embodiment the concentration of ethyl and/or isopropyl is about 50%.
In another embodiment, the ethyl alcohol and/or isopropyl alcohol may be slowly released from the delivery system or the composition.
In another embodiment, each of the composition of the invention may comprise an alkalizing agent.
In another embodiment, the ammonium hydroxide may be slowly released from the delivery system or the composition.
The polymer of the invention is selected from methylcelluose, ethylcellulose, polyacrylate, acrylates, carbomers, chitin, guar, chitozan, PVP, PVA, gums, sylastic, hydroxypropylcellulose and other cellulose derivatives, Eudragits and such, pectines, hyaluronic acid, hyaluronates, gelatin and derivatives, agar, adhesives or mixture thereof.
In another embodiment, the composition or the delivery system further comprising plant extracts/tinctures/oils/macerates such is arnica, plantago, equisetum, lavender, joubarbe, hamamelis, urtica, calendula, daucus, symphytum, sangui sorba, symphytum, aloe vera, roman chamomile, tea tree, witch hazel, mameluca.
The composition or the delivery system of the invention may be in a form of gel, cream, emulsion, lotion, suspension, liposomes, ethosomes, microcapsules, microspheres, bandage, perforated bandage, burn dressing, patch, spray, bath, brushing, douches, aerosols, jet aerosols, foams, used as such or by means of devices.
It is therefore an object of the present invention to provide a method of avoiding or minimizing burn damage to the skin.
In one embodiment, the treatment is a one stage treatment by compositions/devices that stop burn progression and facilitate healing (re-epithelization, re-vascularisation, etc.
In another embodiment, the treatment may comprise two stage treatment: Stage I—treatment for impeding/ stopping wound formation/ burn progression/burn development; Stage II—treatment for healing—re-epithelization.
In another embodiment, the invention provides delivery systems that could impede wound development, which comprise short chain volatile alcohols such as ethanol and isopropyl alcohol with or without additional agents, applied on burned skin, surrounding skin, membrane or organ, before or after burn stimulus.
The composition or the delivery system may further include other agents, such as for example without limitation, a antibiotic, a plant extract, a local anesthetic.
The composition can also contain antimicrobials, including antibiotics, sulpha derivatives, silver sulphadiazine and mafenide, antifungal, iodine anti-viral compounds and other which may complement or supplement the activity of the basic composition. Suitable antibiotics include tetracycline, polymyxin, erythromycin, bacitracin, gentamycin, vincomycin, or other antibiotics used in or systemic administration, including over-the-counter formulations. Examples of useful antifungal include tolnaftate, nystatin, micatin.
Examples of antivirals include interferon, either natural or recombinant, as well as nucleoside analogs, e.g., acyclovir. Counter-irritants such as camphor and menthol, drying agents such as benzyl alcohol, resorcinol and phenol, and astringents such as zinc sulfate and tannic acid can also be added to the composition as can other types of agents such as sunscreens, emollients, preservatives, fragrances, antioxidants, color additives, lubricants, moisturizers or drying agents. For example, a sunscreen, e.g., PABA, can be added to the formula since it is known that burns can be caused by ultraviolet radiation.
Examples of antibiotics include: chloramphenicol, chlortetracycline, clyndamycin, clioquinol, erythromycin, framycetin, gramicidin, fusidic acid, gentamicin, mafenide, mupiroicin, neomycin, polymyxin B, bacitracin, silver sulfadiazine, tetracycline and chlortetracycline, steroidal antibiotics, peptide antibiotics. Those of ordinary skill in the art will appreciate that there are other appropriate antibiotics such as those listed in the pharmaceutical formularies or new antibiotic molecules.
In another embodiment, the composition or the delivery system may include Tea Tree Blend. Tea Tree Blend is a mixture of terpenes and terpinols that are generally naturally occurring, but can be synthetically prepared. The terpene and terpinol compounds can be obtained either as pure compounds derived from the natural oils or as mixtures of components derived from plants of Melaleuca alternifolia, Melaleuca lineariifolia, Melaleuca leucadendron, Eucalyptus longirostris and closely related species.
In another embodiment, a local anesthetic may be added. The anesthetic is preferably selected from the group consisting of esters, amides, ethers, and combinations thereof and, in particular, anesthetics and other anesthetics which may be formulated in accordance with the preferred embodiments of the present invention and applied, including procaine, chloroprocaine, tetracaine, propoxycaine, benzocaine, cocaine, proparacaine, bupivacaine, dibucaine, etidocaine, lidocaine, mepivacaine, prilocaine, dyclonine, promazine and combinations thereof.
Antiinflammatory actives useful in accordance with the present invention include steroidal actives such as hydrocortisone as well as non-steroidal actives including propionic derivatives; acetic acid derivatives; biphenylcarboxylic acid derivatives; fenamic acid derivatives; and oxicams. Examples of antiinflammatory actives include without limitation acetominaphen, diclofenac, ibuprofen, acetaminophen, indomethacin, oxaprozin, pranoprofen, benoxaprofen, bucloxic acid, elocon; and mixtures thereof.
Vitamin actives which may be used in accordance with the present invention include vitamin A and derivatives, including retinoic acid, retinyl aldehyde, retin A, retinyl palmitate, adapalene, and beta-carotene; vitamin B (panthenol, provitamin B5, panthenic acid, vitamin B complex factor); vitamin C (ascorbic acid and salts thereof) and derivatives such as ascorbyl palmitate; vitamin D including calcipotriene (a vitamin D3 analog) vitamin E including its individual constituents alpha-, beta-, gamma-, delta-tocopherol and cotrienols and mixtures thereof and vitamin E derivatives including vitamin E palmitate, vitamin E linolate and vitamin E acetate; vitamin K and derivatives; vitamin Q (ubiquinone) and mixtures thereof
The composition may also contain one or more additional agents, including, buffering agents, surfactants, antioxidants, permeation enhancing agents, preservatives, parabens, coloring agents, fragrances, lubricants, moisturizers, sunscreens, drying agents and the like and, more specifically, may include ingredients such as stearic acid, borax, eucalyptus oil, beeswax..
The surfactant may be selected from the group consisting of anionic, nonionic, and cationic surfactants and combinations thereof. Suitable ionic surfactants include anionic surfactants such as monovalent salts, e.g., sodium and potassium salts of alkyl, aryl and alkyl-aryl sulfates and sulfonates, particularly those with from about 8 to 22 carbon atoms, and cationic surfactants, such as quaternary ammonium salts. Suitable non-ionic surfactants include polyethylene oxide adducts of fatty alcohols, e.g., alkylated polyoxyethylenes, alkylated polyoxyethylene-polyoxypropylene copolymers, and the surfactant nonoxynol, lauramide DEA.
In addition, cationic surfactants may be used, alone. An example is trimethyldodecylammonium chloride, a positively charged quaternary ammonium complex that has antimicrobial characteristics. Other quaternary salts, with and without long chain moieties to provide surface activity.
Nonionic surfactants such as polysorbates, nonoxynol, polyoxyethylene alkyl ethers, polyoxyethylene alkyl ethers, sorbitan esters. Other common nonionic surfactants include polyoxyethylenes amines and polyoxyethylenes amides, polyoxyethylene-polyoxypropylene copolymers, alkyl sorbitols.
The composition of the invention can be prepared in almost any relatively inert carrier. Generally, the formulation could take several forms, e.g., cream, gel, spray, ointment, “Chapstick” and solution forms. Each of these formulations may contain the two active ingredients as well as microorganism growth inhibitors (preservatives). Many such carriers are routinely used and can be obtained by reference to pharmaceutical texts. Examples include polyethylene glycols (PEG), polypropylene copolymers (Pluronics), and some water soluble gels.
Thickeners could include natural and synthetic types. The thickeners used can include but are not limited to xanthan, karaya, guar gum, clay tragacanth various polyssacharide materials such as starches. The thickeners can be present in an amount of about 0 parts to about 5 parts.
Preservative or preservatives are selected from the group consisting of phenoxyethanol, methylparaben, propylparaben, benzyl alcohol, benzoic acid, sodium benzoate, potassium benzoate, sorbic acid, sodium sorbate, potassium sorbate and phenylethyl alcohol.
Another ingredient, which may be formulated with the compositions of the present invention, is a moisturizer. As used herein a “moisturizer” is an ingredient, which promotes the retention of water to the surface area of the human body skin. The term moisturizer as used herein includes both components that deliver water to the skin, also commonly referred to in the art as “humectant”. Moisturizers that may used in accordance with the present invention include without limitation polyhydroxy alcohols, including glycerol, butylene glycol, hexylene glycol, propylene glycol, tetraglycol, sorbitol and the like; lactic acid and lactate salts, such as sodium or ammonium salts; C.sub.3 and C.sub.6 diols and triols including hexylene glycol, 1,4 dihydroxyhexane, 1,2,6-hexane triol; aloe vera in any of its forms, for example aloe vera gel; sugars and starches; sugar and starch derivatives, for example alkoxylated glucose; hyaluronic acid; lactamide monoethanolamine; acetamide monoethanolamine; glycolic acid; alpha and beta hydroxy acids (e.g. lactic, glycolic salicylic acid); glycerin; panthenol; urea; vaselin; natural oils; oils and waxes (see: the emollients section herein) and mixtures thereof.
A further ingredient, which may be formulated with the compositions of the present invention, is an emollient. Emollients are used to add or replace lipids and natural oils to the surface area of the human body. The term emollient as used herein is intended to include conventional lipids (for example, oils, waxes, lipids and other water insoluble components) and polar lipids (lipids which have been modified in order to increase water solubility typically through esterfication of a lipid to a hydrophilic moiety for example hydroxy groups, carbonyl groups and the like). Emollients which may be used in the present invention may be selected from the group consisting of natural oils and plant-derived and essential oils, esters, silicone oils, polyunsaturated fatty acids, lanoline and its derivatives and petrochemicals.
Natural oils which may be used in accordance with the present invention may be obtained from sesame; soybean; apricot kernel; palm; peanut; safflower; coconut; olive; cocoa butter; palm kernel; shea butter; sunflower; almond; avocado; borage; carnauba; hazel nut; castor; cotton seed; evening primrose; orange roughly; rapeseed; rice bran; walnut; wheat germ; peach kernel; babassu; mango seed; black current seed; jojoba; macadamia nut; sea buckthorn; sasquana; tsubaki; mallow; meadow foam seed; coffee; emu; mink; grape seed; thistle; tea tree; pumpkin seed; kukui nut; and mixtures thereof.
Esters, which may be used. Examples of these materials include isopropyl palmitate; isopropyl myristate; isopropyl isononate; C12/C14 benzoate ester (also known as Finesolve); sorbitan palmitate, sorbitan oleate; sucrose palmitate; sucrose oleate; isostearyl lactate; sorbitan laurate; lauryl pyrrolidone carboxylic acid; panthenyl triacetate; and mixtures thereof
Further useful emollients include silicone oils, including non-volatile and volatile silicones. Examples of silicone oils that may be used in the compositions of the present invention are dimethicone; cyclomethycone; dimethycone-copolyol; aminofunctional silicones; phenyl modified silicones; alkyl modified silicones; dimethyl and diethyl polysiloxane; mixed C1-C30 alkyl polysiloxane; and mixtures thereof. A yet further useful group of emollients, which may be formulated in accordance with the present invention, are lanolin and lanolin derivatives for example lanolin esters.
It is noted that although the ingredients mentioned herein are generally defined as emollients they may also possess other properties such as moisturization or other conditioning properties (see under: Moisturizers, hereinbefore mentioned).
In an embodiment of the invention the composition may comprise ethanol from 20-60% w/w, polyacrylate polymer from 0.05%-5%, ammonium hydroxide from 0.1-10%, water from 30-79% to be applied on burned skin and surrounding area, to treat/impede progression/ impede development of burns (produced by heat, cold, light, u v rays, x rays, Laser, Infrared Rays, liquid nitrogen).
In another embodiment of the invention, the composition may comprise ethanol from 25-60% w/w, polyacrylate polymer from 0.05%-5%w/w triethanolamine from 0.1-6%, water from 30-75%, to treat/impede progression/impede development of burns (produced by heat, cold, light, UV rays, X-Rays, Laser, Infrared Rays, friction, abrasion, liquid nitrogen).
In another embodiment the composition may comprise ethanol from 15-60% w/w, polyacrylate polymer from 0.05%-5%, ammonium hydroxide from 0.1-10%, urea from 0.05 to 5% and water from 30-84%, to treat/impede progression/impede development of burns (produced by heat, cold, light, UV rays, X-Rays, Laser, Infrared Rays, liquid nitrogen).
It is therefore an object of the present invention to provide a method of avoiding or minimizing burn damage to the skin by applying to the burned area the composition of the invention, as described hereinabove. Accordingly, the invention provides use of the composition described hereinabove for treating and/or impedes progression and/or impedes development of burns.
In another embodiment, the invention provides a method for treating and/or impede progression and/or impede development of burns comprising the step of adding to the burned area a composition comprising ethyl or isopropyl alcohol in a concentration of 20-60% w/w.
In another embodiment, the invention provides a method for treating and/or impedes progression and/or impedes development of burns comprising the step of adding a composition to the burned area comprising ammonium hydroxide.
In another embodiment, the invention provides a method for treating and/or impede progression and/or impede development of burns comprising the step of adding to the burned area a composition comprising ammonium hydroxide and ethyl and/or isopropyl alcohol wherein the ethyl and/or isopropyl is in a concentration of 20-60% w/w.
In another embodiment, the invention provides a method for treating and/or impede progression and/or impede development of burns comprising the step of adding to the burned area a delivery system comprising polymer matrix and ethyl or isopropyl alcohol in a concentration of 20-60%w/w.
In another embodiment, the invention provides a method for treating and/or impedes progression and/or impedes development of burns comprising the step of adding a delivery system comprising polymer matrix and ammonium hydroxide.
In another embodiment, the invention provides a method for treating and/or impede progression and/or impede development of burns comprising the step of adding to the burned area a delivery system comprising a polymer matrix ammonium hydroxide and ethyl and/or isopropyl alcohol wherein the ethyl and/or isopropyl is in a concentration of 20-60%w/w.
In another embodiment, the invention provides a method for treating and/or impede progression and/or impede development of burns comprising the step of adding to the burned area a composition comprising ethanol from 20-60% w/w, polyacrylate polymer from 0.05%-5%, ammonium hydroxide from 0.1-10%, water from 30-80% to be applied on burned skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment, the invention provides a method for treating and/or impede progression and or impede development of burns comprising the step of adding to the burned area a composition comprising ethanol from 25-60% w/w, polyacrylate polymer from 0.05%-5%w/w triethanolamine from 0.1-6%, water from 30-74%, to be applied on burned skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment, the invention provides a method for treating and/or impeding progression and/or impeding development of burns comprising the step of adding to the burned area a composition comprising ethanol from 15-60% w/w, polyacrylate polymer from 0.05%-5%, ammonium hydroxide from 0.1-10%, urea from 0.05 to 5% and water from 30-84%, to be applied on burned skin and surrounding area, to treat an or impede progression and or impede development of burns.
In another embodiment of the invention, there is provided a method for inhibiting the rejection of skin implants in a subject in need, comprising the step of contact the inflicted area, the surrounding area and/or the implant with an effective amount of the composition of the invention.
In another embodiment of the invention, there is provided a method for interfering at the infliction site with production of cytokines, interleukins, tumor necrosis factors, IL1, IL6, TNF, comprising the step of contact of the inflicted area, the surrounding area and/or the implant with an effective amount of the composition of the invention.
In another embodiment of the invention, the composition and the delivery system described above are refrigerated before or during use.
Composition 1: a Carbomer Gelled Matrix Containing Ethanol 35% w/w.
Composition 1 was applied to a second degree burn (as a result of short contact with 175° C. hot oven) on the skin of left hand of a 30 years aged female and remained for about one hour. This treatment completely impeded the development of the burn.
Ethanolic plant extracts in
Alcohol containing Gel base
Where the concentration of ethanol is 60% w/w
The preparation was applied and remained on the injury for 20 minutes, on a very thick layer, on the a surface of about 5 centimeters square of the arm of a man aged 35, injured by boiling water. The pain was completely relived after application of the composition in example 7. No vesicles or wound developed after this treatment.
The aim of the experiment was to measure the effect of the treatment on wound histology and burn depth after heat burn:
Standardized partial thickness burns were inflicted on the back shaved (24 hours before the experiment) of Sprauge Dawly rats by using a copper cylinder, (R=1 cm, H=1 cm, W=100 g), heated to 75 ° C. in a water bath.
The composition of Example 5 was applied, to an area larger than the injury, immediately after the burn or one hour after. Following the treatment, the rats were sacrificed and the wound as well as adjacent normal tissues were sampled, fixed, processed by routine technique and stained with hematoxylin & eosin. The progress of the wound was assessed at various times and compared with untreated control groups. The effect of the treatment on preventing the burn progress was evaluated by measuring the burn depth by using a program for evaluation of the vascular network damage and by histological analysis of skin anatomic elements. The data were analyzed by ANOVA test. Animal experiments complied with animal care regulations.
The progress of the burn damage was prevented or reduced significantly in rats treated with the composition described in Example 5 stored previous to the experiment at +5° C.
Compositions were applied to the burn skin inflicted as previously described (example 11):
The following compositions were used:
Burn progress was assessed by measuring the burn depth by using a program—Galay CUE 2—for evaluation of vascular network damage.
The histological burn depth was calculated by measuring the level of blocked and patent vessels within the burn specimens. Histological tissue sections were taken from burn area. The depth of the deepest blocked vessel and that of the most superficial undamaged vessel were measured microscopically from the surface of the burn, using Galay CUE2 advanced software. The resulting values were expressed as a percentage of the total skin thickness, the mean of which was considered to be the percentage depth of the burn. These assessments were made at 3, 6 and 24 hours after the burn. These measurements were expressed as a percentage (%) of the total skin thickness.
Histological Analysis of Skin Anatomic Elements:
After the treatment, the animals were sacrificed and the wound as well as adjacent normal tissues were sampled, fixed, processed by routine techniques and stained with hematoxylin & eosin. The parameters investigated included edema formation, inflammation cells migration and preservation of skin structures (epidermis, basal layer, collagen, muscles and appendages). Every histological parameter has been scored using a scale from 0 to 4. Numbers express the balance between the damaged and preserved parameters. A normal parameter is has a score of “0”. With increasing damage, the parameter is represented by higher numbers. Number “4” represents total damage. The sums of all scored parameters express the preservation or destruction of the skin after thermal burn for every treatment. The scored number representing total damage is “28”. These assessments were made at 3, 6 and 24 hours after burn infliction.
In these experiments preparations and delivery systems containing ethanol between 20 to 50% were the most effective in stopping burn progression.
In this experiment heat burns were inflicted as previously described in 14 rats Two rats served as control and the other animals (4 groups of 3 rats each.) were immediately treated as follows:
Mean value histological parameters assessed
The results of this experiment indicate that compositions containing ethanol and ammonium hydroxide were efficient in impeding the burn development as compared to controls—untreated or aqueous gels treated animals.
