WO2000021485A2 - Polyurethanes as topical skin protectants - Google Patents
Polyurethanes as topical skin protectants Download PDFInfo
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- WO2000021485A2 WO2000021485A2 PCT/US1999/023107 US9923107W WO0021485A2 WO 2000021485 A2 WO2000021485 A2 WO 2000021485A2 US 9923107 W US9923107 W US 9923107W WO 0021485 A2 WO0021485 A2 WO 0021485A2
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- polyurethane
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- lower alkyl
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Classifications
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/74—Polyisocyanates or polyisothiocyanates cyclic
- C08G18/75—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic
- C08G18/758—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing two or more cycloaliphatic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/87—Polyurethanes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/48—Polyethers
- C08G18/4825—Polyethers containing two hydroxy groups
Definitions
- This invention relates to the protection of skin from material that is harmful to the skin or substances that are capable of penetrating the skin.
- the invention relates to the use of polyurethanes for such protection.
- the outer skin layer forms a natural barrier to harmful substances from entering the body from the outside world.
- hydrophilic and hydrophobic substances including substances harmful to the body, are capable of penetrating across the stratum corneum layer into the viable skin tissues.
- infectious agents such as viruses or bacteria may more readily enter the body.
- the skin may itself be harmed by commonly used noxious agents, for example toxic chemicals used in the laboratory, in industry, and at home.
- Such a means of protection should guard against toxic substances harmful to the skin itself, and substances capable of penetrating the skin barrier, such as viruses, bacteria, parasites, poisonous gases, toxic agents such as pesticides and herbicides, agents used as chemical weapons, for example mustard gases or neurotoxic agents, chemicals, and the like.
- the skin protectant should be simple and uncomplicated to apply, and not easily removed by water and aqueous environments. Greater skin protection would be provided if the protecting agent not only formed a barrier on the skin surface, but also was absorbed into the outer layer of the skin, i.e. the stratum corneum itself. Its presence in the stratum corneum would enhance efficiency as well as duration of action, in part due to the increased resistance to removal by friction or wiping.
- Polyurethane hydrogels are disclosed for uses including cosmetic, biological and medical applications, such as carrier and delivery systems for pharmacologically active agents in Chvapil, et al., U.S. Patent No. 4,913,897 and Gould, et al., U.S. Patent No. 5,000,955, including the use of hydrogel solutions to form hydrophilic protective films on the skin.
- compositions comprising hydroxy-terminated polyurethanes that are useful for enhancing the cutaneous penetration of topically or transdermally delivered pharmacologically active agents.
- WO 93/21904 assigned to the assignee of the present application, it is disclosed that such polyurethanes are also capable of increasing deposition of retinoic acid and sunscreens on and in the skin.
- One aspect of the present invention relates to a topical composition for protecting the skin of a mammal, comprising: a polyurethane of Formula (I): H-[-(YR) m -OC(O)NH-X-NHC(O)] n —
- X is an alkylene or alkenylene radical containing from 1 to about 20 carbon atoms, or a cycloalkylene or cycloalkenylene radical containing from about 5 to 20 carbon atoms, or a mononuclear or fused ring arylene radical containing from about 6 to about 10 carbon atoms, unsubstituted or substituted with one or more lower alkyl, lower alkoxy, lower alkoxy-substituted lower alkyl, nitro or amino groups or halogen atoms; Y is oxygen, sulfur or -NR'-, where R' is hydrogen or lower alkyl; R is the same or different, and is chosen from alkylene, alkenylene, -SiR R -,
- -Another aspect of the invention relates to a method for protecting the skin of a mammal, comprised of applying an effective amount of a polyurethane of Formula (I), optionally combined with a diluent, to the skin of a m-immal.
- Yet another aspect of the invention pertains to the use of a polyurethane of Formula (I) for the preparation of a topical composition for protecting the skin of a mammal, wherein an effective amount of the topical composition is applied to the skin of a mammal.
- Yet another aspect of the invention relates to an article of manufacture, comprising a topical composition comprising a polyurethane of Formula (I), and optionally, a diluent in combination with labeling instructions for application of said topical composition for the protection of skin.
- Alkyl means a branched or unbranched saturated monovalent hydrocarbon radical containing 1 to 12 carbon atoms, such as methyl, ethyl, propyl, isopropyl, tert-butyl, butyl, n-hexyl, dodecyl, and the like, unless otherwise indicated.
- “Lower alkyl” means a branched or unbranched saturated monovalent hydrocarbon radical containing 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, tert-butyl, butyl, n-hexyl and the like, unless otherwise indicated.
- “Lower alkoxy” means the group -O-(lower alkyl) wherein lower alkyl is as herein defined.
- “Alkylene” means a branched or unbranched saturated divalent hydrocarbon radical containing about 1 to 20 carbon atoms, such as methylene, trimethylene, dimethyltrimethylene, ethylene. 1,2-propylene, 1,4-butylene, 1,3-butylene, 1,5- pentylene, 1,3-pentylene, 1,6-hexylene, 1,12-docecylene, and the like.
- cycloalkylene means a saturated divalent hydrocarbon radical containing from about 5 to 20 carbon atoms, such as cyclopentylene and cyclohexylene.
- Alkenylene means a branched or unbranched unsaturated divalent hydrocarbon radical containing about 1 to 3 double bonds and about 2 to 20 carbon atoms, such as ethene, 1-propene, 1-butene, 3-methylbut-l-ene, 1-pentene, 2- methylpent-1-ene, 1-hexene, 1-docecene, and the like.
- cycloalkenylene means an unsaturated divalent hydrocarbon radical containing from about 5 to 20 carbon atoms such as cyclohexenylene.
- Halo or "halogen” means fluoro, chloro, bromo, or iodo.
- aryl refers to a monovalent unsaturated aromatic carbocyclic radical having a mononuclear or single ring (e.g., phenyl) or two fused rings (e.g., naphthyl, biphenyl, indanyl, 1,2,3,4-tetrahydronaphthyl, benzocycloheptane), containing from about 6 to about 10 carbon atoms , and which can optionally be mono-, di- or tri-substituted, independently, with -OH, -COOH, lower alkyl, lower alkoxy, halo, nitro, amino, alkylamino, dialkylamino, trifluoromethyl and/or cyano.
- Optional or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances in which it does not.
- “optionally substituted phenyl” or “optionally substituted naphthyl” means that the phenyl or naphthyl may or may not be mono-, di- or tri-substituted, independently, with lower alkyl, lower alkoxy, lower alkoxy-substituted lower alkyl, nitro or amino groups, or halogen atoms, and that the description includes both unsubstituted phenyl and naphthyl and substituted phenyl and naphthyl.
- q.s is used herein to mean adding a quantity sufficient to achieve a stated function., for example to bring a solution to a desired volume (q.s. to 100 ml) or to a desired pH (q.s. to pH 4).
- the polyurethanes of the invention are capable of protecting the skin from material that is harmful to the skin, for example toxic chemicals used in the laboratory, industry, in the home, and substances that are capable of penetrating the skin, for example parasites, viruses, bacteria, poisonous gases, toxic agents such as pesticides, herbicides, agents used as chemical weapons, for example mustard gases or neurotoxic agents, and the like.
- the present invention relates to a topical composition for protecting the skin of a mammal, comprising: a polyurethane of Formula (I): H-[-(YR) m -OC(O)NH-X-NHC(O)]schreib—
- X is an alkylene or alkenylene radical containing from 1 to about 20 carbon atoms, or a cycloalkylene or cycloalkenylene radical containing from about 5 to 20 carbon atoms, or a mononuclear or fused ring arylene radical containing from about 6 to about 10 carbon atoms, unsubstituted or substituted with one or more lower alkyl, lower alkoxy, lower alkoxy-substituted lower alkyl, nitro or amino groups or halogen atoms;
- Y is oxygen, sulfur or -NR'-, where R' is hydrogen or lower alkyl; R is the same or different, and is chosen from alkylene, alkenylene, -SiR R -, and -CR R - NR 4 -CR 2 R 3 -, wherein R 2 , R 3 and R 4 are independently hydrogen or lower alkyl;
- m is an integer selected to provide a (YR) moiety having a molecular
- Preferred X groups include:
- Preferred Y groups include oxygen and -NR'-.
- R is an alkylene radical, it contains about 2 to 6 carbon atoms such as -CH 2 CH 2 -, -CH 2 CH 2 CH 2 -, -CH 2 (CH 3 )-CH 2 - or -CH 2 CH 2 (CH 3 .
- R is an alkenylene radical, it contains about 1 to 2 double bonds.
- m is an integer from about 1 to 60.
- n and n' are integers correlated with m so as to provide a polyurethane compound having a molecular weight of about 220 to 200,000, more preferably from about 1000 to 20,000.
- Polyurethane compounds of Formula (I) where YR is -SiR 2 R 3 - or -CR 2 R 3 - NR 4 -CR 2 R 3 - are well known in the art (See for example U.S. Patent 5,286,787 to Padolo and Majolo; U.S. Patent 4,962,178 to Harisiades; Emmons, et. al., U.S. Patent 4,155,892; and "Polyurethanes Chemistry and Technology" by J. H. Saunders and K. C. Frisch, Interscience Publishers, pp. 65-67.)
- polyurethanes that are hydroxy-terminated polyurethanes, i.e. where Y is oxygen, especially those where R is alkylene or alkenylene, which are disclosed in U.S. Patent Nos. 4,971,800, 5,045,317, and 5,051,260, the complete disclosures of which are hereby incorporated by reference. Also useful are those disclosed in Emmons, et al, U.S. Patent 4,079,028, incorporated herein by reference. These references also describe in detail the synthesis of the polyurethane compounds useful in the compositions of the present invention.
- a particularly suitable hydroxy-terminated polyurethane of Formula (I) is of a class of compounds where Y is oxygen, R is an alkylene radical and X is a cycloalkylene radical.
- X is 4,4'-dicyclohexylmethane
- R is 1 ,2-propylene
- m is 12
- one of n and n' is 0 and the other is from 1-3, i.e., it is a mixture where one of n and n' is 0 and the other one of n and n' is 1, 2 and 3.
- PP-2 polyolprepolymer-2
- PP-2 polyolprepolymer-2
- PP-2 polypropylene glycol and 1 mole of dicyclohexylmethane diisocyanate in the presence of stannous octoate, as detailed in U.S. Patent No. 4,971,800, Examples 1 and 5.
- It has a CAS# 9042-82-4, a CAS name of poly[oxy(methyl-l,2-ethanediyl)], ⁇ -hydro- ⁇ -hydroxy-, polymer with 1, l'-methylene-bis-[4-isocyanatocyclohexane] and a weight average molecular weight of approximately 4000.
- X is 4,4'-dicyclohexylmethane
- R is 1,2- propylene
- m is 51
- n and n' is 0 and the other is from 1-3.
- This polyurethane has a tradename of polyolprepolymer-14 ("PP-14"). It has the same CAS# and name as PP-2, but has higher molecular weight (a weight average molecular weight of 18,000 as opposed to 4000 for PP-2).
- X is 4,4'-dicyclohexylmethane
- R is ethylene
- m is 8
- one of n and n' is 0 and the other is from 1-3.
- This polyurethane has a tradename of polyolprepolymer-15 ("PP-15"). It has a CAS# 39444-87-6, a CAS name of poly(oxy-l,2-ethanediyl), ⁇ hydro- ⁇ -hydroxy-, polymer with l,l'-methylene- bis-[4-isocyanatocyclohexane] and a weight average molecular weight of approximately 1800.
- suitable diluents are known in the art and can be used to formulate the topical composition of the invention. These include, by way of illustration and not limitation, water, and liquid alcohols, glycols, polyethylene glycols, polypropylene glycols, esters, amides, protein hydrolysates, alkylated protein hydrolysates, lanolin, lanolin derivatives, and the like. More typically, suitable diluents are chosen from a mixture of solvents, emollients, humectants, and emulsifiers.
- Solvents may be water, liquid alcohols, sulfoxides such as dimethylsulfoxide, pyridines, glycols or polyalkylene glycols, such as propylene glycol, butylene glycol, hexylene glycol, polyethylene glycols, and polypropylene glycols.
- Emollients may be white petrolatum, mineral oil, propylene glycol dicaprylate, lower fatty acid esters and lower alkyl ethers of propylene glycol, cetyl alcohol, cetostearyl alcohol, stearyl alcohol, cetyl esters wax, spermaceti wax, and white wax.
- Humectants may be glycerin and sorbitol; and emulsifiers may be glyceryl monostearate, glyceryl monooleate, polyoxyethylene cetyl ether, polyoxyethylene cetostearyl ether, polyoxyethylene stearyl ether, and polyethylene glycol stearate.
- the pH is adjusted where necessary to a pH of about 3.5-7.0, using an acid e.g. hydrochloric acid, phosphoric acid, or a base e.g. diethanolamine, triethanolamine, sodium hydroxide, or known buffering agents, e.g. phosphates such as monobasic sodium phosphate, and dibasic sodium phosphate, and citrates well known in the art.
- a preservative is generally present, for example benzyl alcohol, sodium benzoate, parabens, and the like.
- the invention also relates to a method for protecting the skin of a mammal, in particular that of a human, comprising the application of an effective amount of a polyurethane of Formula (I), optionally combined with a diluent, to the skin of a mammal.
- a method for protecting the skin of a mammal in particular that of a human, comprising the application of an effective amount of a polyurethane of Formula (I), optionally combined with a diluent, to the skin of a mammal.
- Other mammals for which this method and composition are particularly well suited include domestic pets such as cats and dogs, domestic livestock such as cattle, sheep, and pigs, and other mammals such as horses.
- this invention can be used to protect the skin of a animal from ectoparasites.
- the invention also pertains to the use of a polyurethane of Formula (I) for the preparation of a topical composition for protecting the skin of a mammal, wherein an effective amount of the topical composition is applied to the skin of a mammal.
- the invention further relates to an article of manufacture, comprising a topical composition comprising a polyurethane of Formula (I), and optionally a diluent, in combination with labeling instructions for application of said topical composition for the protection of skin.
- labeling instructions whether stated on the packaging or in the form of a package insert, would include directions on the amount and frequency of application, methods of removal, suggested storage conditions, shelf life expectancy, any precautions or contraindications that may exist, and so forth.
- the amount of polyurethane present in the topical composition of this invention will vary from about 0.1 to about 100 weight percent ("wt%") based upon the total weight of the composition, preferably from about 5 to about 50 wt%.
- the topical composition may be formulated as a cream, ointment, gel, lotion, foam, paste, a liquid such as a solution, or other composition which is applied topically.
- the invention also contemplates compositions in the form of a shampoo that can be applied to the scalp or a soap that can be applied to the hands or other parts of the body, lathered and rinsed to leave a polyurethane coating on the skin.
- Powders and liquid solutions may also be formulated as aerosols or sprays.
- the formulation is a cream, lotion, gel or liquid solution.
- the composition will be of 10wt% polyurethane in an alcoholic solution, such as a 60/40 water/alcohol solution. Examples of such formulations are shown below.
- a cream formulation according to this invention can have the composition shown in Table A, where the polyurethane of Formula (I) is poly [oxy(methyl- 1,2- ethanediyl)], ⁇ -hydro- ⁇ -hydroxy-, polymer with 1, l'-methylene-bis-[4- isocyanatocyclohexane] (PP-2).
- the polyurethane of Formula (I) is poly [oxy(methyl- 1,2- ethanediyl)], ⁇ -hydro- ⁇ -hydroxy-, polymer with 1, l'-methylene-bis-[4- isocyanatocyclohexane] (PP-2).
- An acid such as hydrochloric acid or a base such as diethanolamine, triethanolamine (trolamine), potassium hydroxide or sodium hydroxide is used to adjust the pH to between 3.5 to 7.0.
- a buffering agent such as monobasic or dibasic sodium phosphate with sodium hydroxide or phosphoric acid can be used for pH adjustment.
- White petrolatum is an emollient cream base and can be replaced by mineral oil.
- Propylene glycol is a solvent and can be replaced by butylene glycol, hexylene glycol, polyethylene glycols, or polypropylene glycols.
- Propylene glycol dicaprylate is a solvent/emollient and can be replaced by lower fatty acid esters or lower alkyl ethers of propylene glycol.
- Glycerin is a humectant/emollient and can be replaced by sorbitol.
- Glyceryl monostearate, self emulsifying type is an emulsifier and can be replaced by glyceryl monoleate, self emulsifying type.
- Polyoxyethylene cetyl ether is an emulsifier and can be replaced by polyoxythylene cetostearyl ether, polyoxythylene stearyl ether, or polyethylene glycol stearates.
- Cetyl alcohol is an emollient and a emulsion stabilizer/viscosity increasing agent in the cream and can be replaced by cetostearyl alcohol, stearyl alcohol, cetyl esters wax, spermaceti wax or white wax.
- Sodium benzoate is a preservative and can be replaced by or used in conjunction with benzyl alcohol or parabens, or other commonly used preservatives.
- Stearic acid is present as an emulsifier and a viscosity enhancer.
- Another cream formulation according to this invention can have the composition shown in Table B, where the polyurethane of Formula (I) is PP-2.
- a buffering agent such as monobasic or dibasic sodium phosphate with sodium hydroxide or phosphoric acid is added to achieve a final pH between 3.5 and 7.0.
- White petrolatum is an emollient cream base and can be replaced by mineral oil.
- Propylene glycol is a solvent and can be replaced by butylene glycol or hexylene glycol, polyethylene glycols, polypropylene glycols.
- Ceteareth-30 is an emulsifying agent and can be replaced by ceteareth-20, steareth-20, or steareth-30.
- Another cream formulation according to this invention can have the composition shown in Table C, where the polyurethane of Formula (I) is PP-2.
- An acid such as hydrochloric acid or a base such as diethanolamine, triethanolamine (trolamine), or sodium hydroxide is used to adjust the pH to between 3.5 to 7.0.
- Isopropyl myristate is a solvent/emollient and isopropyl palmitate may be used in its place.
- Cetyl palmitate is an emollient and an emulsion stabilizer/ viscosity increasing agent and can be replaced by cetyl esters wax or its various ester components, spermaceti wax, or a white wax.
- Polysorbate 60 is a hydrophilic nonionic surfactant and is used as an emulsifier.
- Polysorbate 80 or other suitable polysorbates may be used in its place.
- Sorbitan monostearate is a lipophilic nonionic surfactant and is used as an emulsifier.
- Sorbitan palmitate or other sorbitan fatty acid esters may be used in its place.
- the cream formulations of Tables A-C are prepared using standard techniques for preparing creams of the oil-in- water emulsion type.
- a gel formulation according to this invention can have the composition shown in Table D, where the polyurethane of Formula (I) is poly [oxy (methyl- 1,2- ethanediyl)], ⁇ -hydro- ⁇ -hydroxy-, polymer with 1, l'-methylene-bis-[4- isocyanatocyclohexane] (PP-2).
- An acid such as hydrochloric acid or a base such as diethanolamine, triethanolamine (trolamine), or sodium hydroxide is used to adjust the pH to between 3.5 to 7.0.
- buffering agents such as monobasic or dibasic sodium phosphate with sodium hydroxide or phosphoric acid or citric acid in combination with dibasic sodium phosphate can be used to adjust the pH.
- Isopropyl alcohol can be used in place of ethanol.
- Propylene glycol is a solvent and can be replaced by butylene glycol, hexylene glycol, polyethylene glycols, or polypropylene glycols.
- Glycerin is a humectant/emollient and can be replaced by sorbitol.
- PP-2 can be replaced by polyolprepolymer-14, or polyolprepolymer-15.
- Gels are prepared by the addition of the polyurethanes of the invention to the non-aqueous solvents. If necessary, the base or the buffer (in solution) is added to the above solution with mixing to achieve the desired pH. The hydroxypropyl cellulose is then dispersed into the solution.
- An ointment formulation according to this invention can have the composition shown in Table E, where the polyurethane of Formula (I) is PP-2. TABLE E
- Propylene glycol is a solvent and can be replaced by butylene glycol or hexylene glycol, polyethylene glycols, or polypropylene glycols.
- Propylene glycol stearate or glyceryl oleate may be used in place of glyceryl stearate as an emulsifier.
- the ointment is prepared by mixing the solvents, which are then added to the melted petrolatum and emulsifier with mixing. The preparation is then allowed to cool with continued mixing. Further mixing with a homogenizer may be done.
- a lotion formulation according to this invention can have the composition shown in Table F, where the polyurethane of Formula (I) is poly [oxy (methyl- 1,2- ethanediyl)], ⁇ -hydro- ⁇ -hydroxy-, polymer with 1, l'-methylene-bis-[4- isocyanatocyclohexane] (PP-2).
- the polyurethane of Formula (I) is poly [oxy (methyl- 1,2- ethanediyl)], ⁇ -hydro- ⁇ -hydroxy-, polymer with 1, l'-methylene-bis-[4- isocyanatocyclohexane] (PP-2).
- An acid such as hydrochloric acid or a base such as diethanolamine, triethanolamine (trolamine), or sodium hydroxide is used to adjust the pH to between 3.5 to 7.0.
- a buffering agent such as monobasic or dibasic sodium phosphate with sodium hydroxide or phosphoric acid can be used for pH adjustment.
- the materials may be substituted as shown in the cream formulation of Table A.
- These lotions are prepared using standard techniques for formulating a lotion of oil-in- water emulsion type.
- the melted oil phase is added to the aqueous phase in which the thickeners, magnesium aluminum silicate and xanthan gum, are already dispersed.
- the mixture is then homogenized.
- a liquid solution formulation according to this invention can have the composition shown in Table G, where the polyurethane of Formula (I) is PP-2.
- An acid such as hydrochloric acid or a base such as diethanolamine, triethanolamine (trolamine), or sodium hydroxide can be used to adjust the pH to between 3.5 to 7.0.
- buffering agents such as monobasic or dibasic sodium phosphate with sodium hydroxide or phosphoric acid or a combination of citric acid with dibasic sodium phosphate can be used to adjust the pH.
- Isopropyl alcohol can be used in place of ethanol.
- Sorbitol can be used in place of glycerin.
- PP- 2 can be replaced by any polyurethane of the invention, such as polyolprepolymer-14, or polyolprepolymer-15.
- liquid solutions are prepared by addition of the polyolprepolymer to the non-aqueous solvents followed by mixing. If necessary, the base or the buffer (in solution) is added to the above solution with mixing to achieve the desired pH.
- the liquid solution formulation can be used as a spray as is or as an aerosol with the addition of suitable propellants, for example hydrocarbon gases or low boiling liquids, or standard compressed gases, for example carbon dioxide.
- EXAMPLE 1 A cream having the following composition and containing a polyurethane of Formula (I), e.g., poly[oxy(methyl-l,2-ethanediyl)], ⁇ -hydro- ⁇ - hydroxy-, polymer with 1, l'-methylene-bis-[4-isocyanatocyclohexane] (PP-2):
- a polyurethane of Formula (I) e.g., poly[oxy(methyl-l,2-ethanediyl)], ⁇ -hydro- ⁇ - hydroxy-, polymer with 1, l'-methylene-bis-[4-isocyanatocyclohexane] (PP-2):
- a suitable vessel for holding the water phase Into a suitable vessel for holding the water phase, the water is added, followed by the glycerin, triethanolamine, and sodium benzoate with mixing while heating to about 80°C.
- a mixture of the white petrolatum, cetyl alcohol, stearic acid, polyoxyethylene (23) cetyl ether, glyceryl monostearate SE, propylene glycol dicaprylate, propylene glycol, and polyolprepolymer-2 are heated to about 80°C to melt while mixing continuously until uniform. While maintaining the temperature, the oil phase is added to the water phase while mixing. The mixture is cooled to about 50°C with mixing, then benzyl alcohol is added and mixing continued until uniform.
- polyurethanes of Formula (I) can be used in the preparation of the topical formulations of this example.
- EXAMPLE 2 A cream having the following composition and containing a polyurethane of Formula (I), e.g., poly[oxy(methyl-l,2-ethanediyl)], ⁇ -hydro- ⁇ - hydroxy-, polymer with 1, l'-methylene-bis-[4-isocyanatocyclohexane] (PP-2): is prepared as shown in Example 1.
- a polyurethane of Formula (I) e.g., poly[oxy(methyl-l,2-ethanediyl)], ⁇ -hydro- ⁇ - hydroxy-, polymer with 1, l'-methylene-bis-[4-isocyanatocyclohexane] (PP-2): is prepared as shown in Example 1.
- polyurethanes of Formula (I) can be used in the preparation of the topical formulations of this example.
- a polyurethane of Formula (I) e.g., poly[oxy(methyl-l,2-ethanediyl)], ⁇ -hydro- ⁇ - hydroxy-, polymer with 1, l'-methylene-bis-[4-isocyanatocyclohexane] (PP-2):
- a cream having the following composition is prepared containing a polyurethane of Formula (I), e.g., poly[oxy(methyl-l,2-ethanediyl)], ⁇ -hydro- ⁇ - hydroxy-, polymer with 1, -methylene-bis-[4-isocyanatocyclohexane] (PP-2).
- a polyurethane of Formula (I) e.g., poly[oxy(methyl-l,2-ethanediyl)], ⁇ -hydro- ⁇ - hydroxy-, polymer with 1, -methylene-bis-[4-isocyanatocyclohexane] (PP-2).
- the dibasic sodium phosphate is dissolved in the water and phosphoric acid is added.
- the white petrolatum, cetearyl alcohol, stearic acid, ceteareth-30, mineral oil, polyolrepolymer-2, and propylene glycol are heated to melt with mixing until uniform.
- the oil phase is then added to the water phase with mixing.
- the batch is allowed to cool to about 50°C and benzyl alcohol is added.
- the batch is homogemzed until smooth and uniform and allowed to cool to room temperature with mixing.
- polyurethanes of Formula (I) can be used in the preparation of the topical formulations of this example.
- a gel having the following composition containing a polyurethane of Formula (I), e.g., poly[oxy(methyl-l,2-ethanediyl)], ⁇ -hydro- ⁇ -hydroxy-, polymer with 1, 1'- methylene-bis-[4-isocyanatocyclohexane] (PP-2) is prepared.
- the polyethylene glycol 400, propylene glycol, glycerin, and polyolprepolymer-2 are added to the ethanol and mixed until uniform. Water is then added and mixed until uniform. If necessary, the base or the buffer (in solution) is added to the above solution with mixing to achieve the desired pH. The hydroxypropyl cellulose is then dispersed into the solution.
- polyurethanes of Formula (I) can be used in the preparation of the topical formulations of this example.
- a lotion having the following composition and containing a polyurethane of Formula (I), e.g., poly[oxy(methyl-l,2-ethanediyl)], ⁇ -hydro- ⁇ -hydroxy-, polymer with 1, l'-methylene-bis-[4-isocyanatocyclohexane] (PP-2) is prepared.
- EXAMPLE 7 A liquid solution containing a polyurethane of Formula (I), e.g., poly [oxy (methyl- 1,2-ethanediyl)], ⁇ -hydro- ⁇ -hydroxy-, polymer with 1, 1'- methylene-bis-[4-isocyanatocyclohexane] (PP-2) and having the following composition is prepared.
- a polyurethane of Formula (I) e.g., poly [oxy (methyl- 1,2-ethanediyl)], ⁇ -hydro- ⁇ -hydroxy-, polymer with 1, 1'- methylene-bis-[4-isocyanatocyclohexane] (PP-2) and having the following composition is prepared.
- the polyethylene glycol 400, propylene glycol, glycerin, and polyolprepolymer-2 are added to the ethanol and mixed until dissolved and uniform. Water is added, and mixed until uniform.
- the pH of the solution is 4.4.
- Triethanolamine (TEA) can be added to further increase the pH if necessary. For example, 0.05 g of TEA in 100 g of solution would bring the pH to 5.1 whereas 0.1 g of TEA would give a pH of 5.6.
- polyurethanes of Formula (I) can be used in the preparation of the topical formulations of this example.
- the hair relaxer was tested alone ("control") or in combination with 10% (v/v) poly [oxy(methyl- 1,2-ethanediyl)], ⁇ -hydro- ⁇ -hydroxy-, polymer with 1, 1'- methylene-bis-[4-isocyanatocyclohexane] ("PP-2") or 10% (v/v) poly(oxy-l,2- ethanediyl), ⁇ hydro- ⁇ -hydroxy-, polymer with l,l'-methylene-bis-[4- isocyanatocyclohexane] (“PP-15").
- Three 1 cm 2 dose areas of the skin were demarcated on the previously non- exposed ventral forearm skin of each of three human volunteers (Subjects 1, 2 and 3, respectively).
- Each site was labeled as A, B or C, and 5 ⁇ L of the respective formulation was applied to the site using a positive displacement syringe. After about 5 minutes (“exposure time”), each site was washed with cold water with liquid soap and then rinsed with cold running tap water. Changes in skin irritation were recorded over a 24 hour period using a scale of 0-7, with 0 being no evidence of irritation and 7 indicating a strong reaction spreading beyond the test site. The experiment was subsequently repeated with a 10 minute exposure time and a 15 minute exposure time.
- a hair relaxer (regular strength) + 10% (v/v) PP-15
- the topical formulations were first prepared as inhibitor in a 50% dimethylsulfoxide (“DMSO”)/water (v/v) stock solutions, followed by the addition of 10% (v/v) polyolprepolymer.
- DMSO dimethylsulfoxide
- v/v v/v
- Lower extremity or abdominal human skin samples were harvested from autopsy or surgical pathology specimens. After removal of subcutaneous fat, the skin was placed between two plastic chambers or in strips over wells of a 24- well tissue culture dish. Tissue culture media (RPMI-1640) was added to the wells beneath the skin and warmed to 37°C to crate a thermal gradient. Three thousand cercariae in water were introduced into the upper chamber. Formulations to be evaluated were placed on the skin surface. The DMSO solvent was allowed to evaporate for 30 min. before application of cercariae.
- Tissue culture media RPMI-1640
- the plates were incubated for 2 hrs., the cercariae removed, and the skin cut into 1 mm strips and fixed in 10% phosphate buffered formalin. Following routine paraffin embedding, the histologic sections were prepared and stained with hematoxylin and eosin to identify organisms that had penetrated the skin.
- mice were then exposed to 120 cercariae by tail immersion for 30 min. Seven weeks later, the mice were euthanized and worm burden and egg burden determined as described by Amiri, et al., Nature 356:604-607 (1992).
- Adult worms were perfused from the liver and counted, and the liver tissue was digested with 0.7% trypsin phosphate buffered saline to release eggs, which were counted in a hemocytometer. Egg burden was calculated per gram of liver tissue. Table 4
- FTIR-ATR Fourier Transform Infrared spectrometers equipped with the attenuated total reflectance
- the FTIR-ATR technique was used to assess the presence and amount of polyolprepolymer-2 ("PP-2") in the stratum corneum of two human subjects, in vivo.
- PP-2 polyolprepolymer-2
- the feasibility of FTIR-ATR in quantifying the amount of PP-2 in stratum corneum was confirmed by the results from in vitro uptake studies and in vivo occlusive and non-occlusive studies performed with radiolabeled PP-2.
- FTIR-ATR in vivo
- test solution contained 10 wt% PP-2 dissolved in ethanol/water (60:40 v/v).
- control solution consisted only of ethanol/water (60:40 v/v).
- WebtrilTM pads (12cm x 2.5cm) were saturated either with test or control solution and were applied to the left and right forearms of two subjects, respectively. The pads were secured in place with Tegaderm 1626TM occlusive transparent dressing during the entire 3 hour exposure period. The skin surface of the dosing sites was lightly wiped with two cotton-tipped swabs following the exposure period. A total of 8 tape shippings were performed: 6 were done immediately and 2 were done 2 hours later.
- FTIR spectra of the dosing sites were obtained prior to tape stripping and subsequently after each tape strip using the FTIR-ATR (Nicolet 520) equipped with a 7.2 cm 2 ZnSe crystal.
- FTIR spectrum of PP-2 at a known surface concentration was obtained with 30 ⁇ L of test solution (specific gravity of 0.902 g/mL).
- FTIR spectra of the stratum corneum was measured from the dosing site and compared with the FTIR spectra of PP-2.
- the ratio of PP-2 absorption at 1095 cm “1 to stratum corneum absorption at 675 cm “1 (R 1095/675) was determined to account for potential differences in degree of contact between the sample (forearm) and the ATR crystal.
- the difference in the ratios between the treated and control sites was obtained to determine the skin surface concentration of PP-2.
- the absorbance ratio, R 1095/675, of PP-2 was determined.
- the skin surface concentration of PP-2 was estimated using R 1095/675 and ⁇ b values.
- PP-2 was found to be in the range of 13-17 ⁇ g/cm of stratum corneum.
- the test solution contained ⁇ 0.1 ⁇ Ci 3 H-polyurethane oligomers/mg PP-2. Approximately 15 mg of the test solution was applied to the left ventral forearms of two subjects. Thereafter, the occlusive (absent the WebtrilTM pad) or non-occlusive (Bucks, et al., Pharm. Res. 5:313-315 (1988)) chamber was placed over the site of the application for the entire 24 hour exposure period. Radiolabel dose accountability was assessed from the chamber wash, skin wash, tape strips, and urine samples by liquid scintillation counting (Packard 1900CA).
- the mean radiolabel ( 3 H-polyurefhane oligomers) recovered was 95% from the occlusive study and 93% from the non-occlusive study.
- 3-7 and 4-7 ⁇ g polyurethane oligomers/cm 2 of stratum corneum was recovered from the occlusive and non-occlusive studies, respectively.
- test solution contained -0.9 ⁇ Ci 3 H-PP-2/mg PP-2 dissolved in 2.5 n L of 40% ethanol in water for the measurement of uptake of 3 H-PP-2 from a solution of 1 % PP-2 in 40% ethanol in water as well as the measurement of uptake of unlabeled PP-2 by weight.
- Human stratum corneum sheets (-0.3 mg for labeled and -50 mg for unlabeled) were prepared as described in Golden, et al., Jour, of Investigative
- the uptake of PP-2 was determined to range from 30-48 and 10-26 ⁇ g/cm 2 of stratum corneum, respectively.
- PP-2 is perhaps localized in stratum corneum by a mechanism similar to that for the localization of sebaceous lipids.
- EXAMPLE 11 Determination of Skin Barrier Properties Against Herbicides
- the barrier properties of two different polyurethanes were studied for their ability to inhibit penetration of the commercial herbicide AAtrex 4L (Novartis), which contains 41% atrazine.
- the hydrophilic polyurethane, poly(oxy-l,2-ethanediyl), ⁇ -hydro- ⁇ -hydroxy-, polymer with 1,1'- methylene-bis-[4-isocyanatocyclohexane] or polyolprepolymer-15 (“PP-15”) were chosen for evaluation.
- Excised hairless mouse skin (CRL:SKH1) was placed in a flow-through cell diffusion system.
- the polyurethanes were diluted to 10, 20 and 30% (v/v) strength with ethanol.
- Ten microliters of each polyurethane solution was then placed on the epidermis and equilibrated for one hour.
- AAtrex 4L was diluted 1 :40 (v/v) with water giving a concentration similar to that typically used in the agricultural industry.
- One hundred microliters of this solution, spiked with I4 C labeled atrazine were then placed on pretreated skin. Atrazine penetration (unoccluded) was determined in 90-minute increments over a 24-hour exposure period.
- the amount of atrazine penetrating through the skin was reduced by 70, 64 and 40 percent for the 30, 20 and 10 percent PP-2 (v/v) formulations, respectively.
- PP-15 although less effective, still significantly reduced atrazine penetration, exhibiting 53, 39 and 21 percent reduction for the 30, 20 and 10 percent (v/v) formulations, respectively.
- This work showed that the polyurethanes of the invention are effective at reducing the quantity of the atrazine-containing herbicide AAtrex 4L that is able to penetrate the skin.
- the barrier properties of two different polyurethanes were studied for their ability to inhibit penetration of 5-fluorouracil ("5-FU").
- the hydrophobic polyurethane, PP-2, and the hydrophilic polyurethane, PP-15 were chosen for the study.
- the dermis was perfused overnight (approximately 20 hours) with phosphate-buffered saline at pH 7.4 containing 0.1% sodium azide and 1.5% oleth 20 at 1 mL/hour at 37°C.
- the skin was double wiped consecutively with wash solution (1% sodium laurel sulfate, 1% aluminum laurel sulfate in water) soaked swabs, followed by two repetitive water swabs, and wiped dry with a single swab. The swabs were discarded.
- the skin was then dosed with 150 ⁇ L of saturated aqueous 5-FU (10.2 mg/mL at 32 ⁇ 1°C) at a concentration sufficient to achieve an approximately 2.0 ⁇ Ci 3 H 5-FU dose.
- the receptor phase was then collected every 6 hours for 24 hours.
- EXAMPLE 13 Determination of Skin Barrier Properties Against Toxic Chemicals
- the barrier properties of three different polyurethanes were studied for their ability to inhibit penetration of two highly toxic chemical warfare agents, radiolabeled for purposes of evaluation.
- [1,3- 14 C] diisopropylfluorophosphate (“DFP") specific activity of 160 mCi/mmole and a reported radiochemical purity of 99% was obtained from DuPont-NEN (Wilmington, DE), and was diluted with diisopropylfluorophosphate (Sigma Chemical Company, St. Louis, MO) to a specific activity of approximately 0.07 ⁇ Ci/ ⁇ L.
- DFP diisopropylfluorophosphate
- NBCS n-butyl-2- chloroethylsulfide
- PP-2, PP-14 and PP-15 were chosen for the study.
- the formulations were all q.s. to 5.0 ml with 75% (w/w) ethanol.
- the control formulation was an ethanol, propylene glycol, water mixture.
- Silastic membrane (0.1 mm thick) was cut into circles and mounted on diffusion cells. The cells were maintained at 37°C. Each membrane was dosed with 10 ⁇ L of test or control formulation, spread onto the membrane with a glass rod or placed as a droplet on the membrane surface. The treatments were challenged with 1 ⁇ L (0.00573 mmole) of C 14 -labeled DFP or C 14 -labeled NBCS). The donor chamber was closed and a peristaltic pump caused tissue culture medium (Roswell Park Memorial Institute formula 1640, Sigma) to flow underneath the silastic membranes for 4 hours at 1 ml/hr. The flow was fractionated into hourly samples, which were weighed and the radioactivity counted. After the four hour period, the diffusion cell was disassembled and the silastic membrane removed and placed in a vial and its radioactivity measured.
- tissue culture medium Roswell Park Memorial Institute formula 1640, Sigma
- PP-15 Penetration of DFP was slightly inhibited by PP-15.
- PP-2, PP-14 and PP-14 were all able to inhibit penetration of NBCS.
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- Veterinary Medicine (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99956517.9A EP1119374B1 (en) | 1998-10-09 | 1999-10-05 | Polyurethanes as topical skin protectants |
ES99956517.9T ES2470974T3 (en) | 1998-10-09 | 1999-10-05 | Polyurethanes as typical skin protectors |
AU13114/00A AU1311400A (en) | 1998-10-09 | 1999-10-05 | Polyurethanes as topical skin protectants |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/169,208 US6277364B1 (en) | 1998-10-09 | 1998-10-09 | Polyurethanes as topical skin protectants |
US09/169,208 | 1998-10-09 |
Publications (3)
Publication Number | Publication Date |
---|---|
WO2000021485A2 true WO2000021485A2 (en) | 2000-04-20 |
WO2000021485A3 WO2000021485A3 (en) | 2000-07-20 |
WO2000021485B1 WO2000021485B1 (en) | 2000-11-09 |
Family
ID=22614638
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1999/023107 WO2000021485A2 (en) | 1998-10-09 | 1999-10-05 | Polyurethanes as topical skin protectants |
Country Status (6)
Country | Link |
---|---|
US (1) | US6277364B1 (en) |
EP (1) | EP1119374B1 (en) |
AU (1) | AU1311400A (en) |
ES (1) | ES2470974T3 (en) |
PT (1) | PT1119374E (en) |
WO (1) | WO2000021485A2 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1463633A1 (en) * | 2001-12-07 | 2004-10-06 | Regenesis, Llc | Cleaning article containing hydrophilic polymers |
Families Citing this family (9)
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US6984404B1 (en) * | 1998-11-18 | 2006-01-10 | University Of Florida Research Foundation, Inc. | Methods for preparing coated drug particles and pharmaceutical formulations thereof |
FR2811993B1 (en) * | 2000-07-21 | 2006-08-04 | Oreal | NOVEL CATIONIC ASSOCIATIVE POLYMERS AND THEIR USE AS THICKENERS |
FR2823118B1 (en) * | 2001-04-04 | 2004-03-19 | Lavipharm Lab Inc | NOVEL FILM-FORMING COMPOSITION FOR TOPICAL USE AND ITS USE FOR THE DELIVERY OF ACTIVE AGENTS |
US7294342B2 (en) * | 2002-07-11 | 2007-11-13 | Summers Laboratories, Inc. | Ectoparasite asphyxiator compositions and methods for their application |
US8258191B2 (en) | 2005-10-31 | 2012-09-04 | Coloplast A/S | Topical skin barriers and methods of evaluation thereof |
US8211871B2 (en) * | 2005-10-31 | 2012-07-03 | Coloplast A/S | Topical skin barriers and methods of evaluation thereof |
WO2015138926A1 (en) | 2014-03-14 | 2015-09-17 | Gojo Industries, Inc. | Hand sanitizers with improved aesthetics and skin-conditioning to encourage compliance with hand hygiene guidelines |
US10078207B2 (en) | 2015-03-18 | 2018-09-18 | Endochoice, Inc. | Systems and methods for image magnification using relative movement between an image sensor and a lens assembly |
US11452685B2 (en) * | 2017-10-30 | 2022-09-27 | L'oreal | Cosmetic compositions providing for a transformative texture |
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US3888995A (en) | 1968-07-19 | 1975-06-10 | Syntex Corp | Fatty alcohol-propylene glycol vehicle |
US4155892A (en) | 1975-10-03 | 1979-05-22 | Rohm And Haas Company | Polyurethane thickeners for aqueous compositions |
US4079028A (en) | 1975-10-03 | 1978-03-14 | Rohm And Haas Company | Polyurethane thickeners in latex compositions |
US4255550A (en) | 1978-12-22 | 1981-03-10 | Tyndale Plains - Hunter Ltd. | Polyurethane polymers characterized by carboxylate groups and hydroxyl groups in the polymer backbone |
US5045317A (en) | 1987-07-16 | 1991-09-03 | The Regents Of The University Of California | Enhancing the cutaneous penetration of pharmacologically active agents |
US4971800A (en) | 1988-07-08 | 1990-11-20 | The Regents Of The University Of California | Method and compositions for enhancing the cutaneous penetration of pharmacologically active agents |
US5051260A (en) | 1987-07-16 | 1991-09-24 | The Regents Of The University Of California | Method and composition for enhancing the cutaneous penetration of pharmacologically active agents |
US4913897A (en) | 1987-12-28 | 1990-04-03 | Bio-Products, Inc. | Use of hydrogel solutions to form a hydrophilic protective film on the skin against toxic substances, pollutants, infections and skin secretions |
US5000955A (en) | 1988-07-29 | 1991-03-19 | Tyndale Plains-Hunter Ltd. | Thermally reversible polyurethane hydrogels and cosmetic, biological and medical uses |
US5126136A (en) | 1988-08-05 | 1992-06-30 | Merat Pierre H | Skin protection lotion |
US4962178A (en) | 1988-11-03 | 1990-10-09 | Ciba-Geigy Corporation | Novel polysiloxane-polyurethanes and contact lens thereof |
US5019604A (en) | 1989-04-26 | 1991-05-28 | Lemole Gerald M | Protective gel composition |
DE3943090A1 (en) | 1989-12-27 | 1991-07-04 | Henkel Kgaa | MOISTURIZING POLYURETHANEAS MASSES WITH IMPROVED PROPERTIES |
US5192536A (en) | 1990-10-26 | 1993-03-09 | Huprich Carl A | Method and composition for coating a wound with polyether polyurethane |
US5686065A (en) | 1991-03-27 | 1997-11-11 | Special Advanced Biomaterials, Inc. | Topical siloxane sunscreen compositions having enhanced performance and safety |
US5650171A (en) | 1992-04-29 | 1997-07-22 | Penederm, Inc. | Retinoic acid-containing polyether-polyurethane compositions |
JPH05339124A (en) * | 1992-06-02 | 1993-12-21 | Peenidam Inc | Foundation composition for makeup |
US5370876A (en) | 1993-01-08 | 1994-12-06 | Microbarriers | Antimicrobial protective skin composition and method for protecting skin from body fluids |
US5707612A (en) * | 1996-04-08 | 1998-01-13 | Alzo, Inc. | Use urethane polymers of castor oil skin and personal care product compositiions |
US5942239A (en) | 1996-05-09 | 1999-08-24 | Iowa State University Research Foundation, Inc. | Method and composition for coating wound or protecting animal skin |
US5688498A (en) | 1996-05-09 | 1997-11-18 | Iowa State University Research Foundation, Inc. | Method and composition for coating wound or protecting animal skin |
EP0920467A4 (en) * | 1996-08-26 | 1999-10-13 | Tyndale Plains Hunter Ltd | Hydrophilic and hydrophobic polyether polyurethanes and uses therefor |
US5837274A (en) * | 1996-10-22 | 1998-11-17 | Kimberly Clark Corporation | Aqueous, antimicrobial liquid cleaning formulation |
US5807957A (en) * | 1996-12-23 | 1998-09-15 | Macrochem Corporation | Cationic film-forming polymer compositions, and use thereof in topical agents delivery system and method of delivering agents to the skin |
-
1998
- 1998-10-09 US US09/169,208 patent/US6277364B1/en not_active Expired - Lifetime
-
1999
- 1999-10-05 EP EP99956517.9A patent/EP1119374B1/en not_active Expired - Lifetime
- 1999-10-05 PT PT99956517T patent/PT1119374E/en unknown
- 1999-10-05 WO PCT/US1999/023107 patent/WO2000021485A2/en active Application Filing
- 1999-10-05 ES ES99956517.9T patent/ES2470974T3/en not_active Expired - Lifetime
- 1999-10-05 AU AU13114/00A patent/AU1311400A/en not_active Abandoned
Non-Patent Citations (2)
Title |
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None |
See also references of EP1119374A4 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1463633A1 (en) * | 2001-12-07 | 2004-10-06 | Regenesis, Llc | Cleaning article containing hydrophilic polymers |
EP1463633A4 (en) * | 2001-12-07 | 2006-06-07 | Regenesis Llc | Cleaning article containing hydrophilic polymers |
Also Published As
Publication number | Publication date |
---|---|
WO2000021485B1 (en) | 2000-11-09 |
PT1119374E (en) | 2014-06-24 |
WO2000021485A3 (en) | 2000-07-20 |
ES2470974T3 (en) | 2014-06-24 |
US6277364B1 (en) | 2001-08-21 |
EP1119374B1 (en) | 2014-03-12 |
EP1119374A4 (en) | 2007-08-01 |
AU1311400A (en) | 2000-05-01 |
EP1119374A2 (en) | 2001-08-01 |
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