# US 5,700,483 A · Retinoic acid-containing compositions > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,700,483 A - Document ID: US5700483A - Status: Granted - Kind: A - Application number: 08/708,181 - Filed: 1996-09-06 - Granted: 1997-12-23 - Earliest claimed: 1992-04-29 - Assignees: Penederm, Inc. - Inventors: John W. Quigley, Jr.; Harris Goodman - Web page: https://patentgrep.com/patent/US5700483A ## CPC - A61K 8/671: {Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal} - A61K 8/87: Polyurethanes - A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)} - A61K 31/20: having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids - A61K 31/203: Retinoic acids {; Salts thereof} - A61K 31/785: Polymers containing nitrogen - A61K 47/18: Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids - A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) - A61Q 19/00: Preparations for care of the skin - A61Q 19/08: Anti-ageing preparations - A61K 2800/75: Anti-irritant - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS ## Abstract Novel retinoic acid-containing topical compositions in the form of creams, lotions, gels, and the like, are disclosed. These compositions contain a urethane compound having a molecular weight of up to about 200,000, prepared by reacting approximately two moles of a hydroxy-terminated linear alkylene or polyalkylene glycol with approximately one mole of a monomeric organic diisocyanate. The presence of the urethane compound leads to decreased percutaneous transmission of the retinoic acid, resulting in reduced skin irritation but undiminished therapeutic effectiveness of the retinoic acid when compared to retinoic acid-containing topical formulations otherwise identical except for the absence of a urethane compound. The compositions of this invention can be used to treat acne vulgaris and ameliorate photoaging of the skin, to retard and reverse the effects of senile keratosis, and to treat a variety of other skin conditions, such as hyperpigmentation and psoriasis, hitherto considered unsuitable for treatment with retinoic acid. ## Claims ### Claim 1 A topical composition comprising: (a) retinoic acid in an amount effective to treat acne vulgaris or the effects of senile keratosis or photoageing of the skin; (b) an urethane compound in an amount of about one percent by weight to about twenty percent by weight, wherein said urethane compound exhibits a molecular weight up to about 200,000, is prepared by reacting approximately two moles of a hydroxy-terminated linear alkylene or polyalkylene glycol or polyether with approximately one mole of a monomeric organic diisocyanate, and is sufficient to permit the topical composition to exhibit reduced skin irritation but undiminished effectiveness as compared to a composition otherwise identical except for the absence of the urethane compound; and (c) a topical carrier in an amount sufficient to provide said topical composition in the form of a liquid, a cream or a gel. ### Claim 2 (depends on 1) The topical composition of claim 1 wherein the molecular weight of the urethane compound is up to 60,000. ### Claim 3 (depends on 2) The topical composition of claim 2 wherein the urethane compound is represented by the general formula: ##STR3## wherein R represents an alkylene or alkenylene radical, a cycloalkylene or cycloalkenylene radical, or a mononuclear or fused ring arylene radical, all of which can be unsubstituted or substituted, R.sup.1 represents the same or different alkylene or alkenylene radicals, m is an integer selected so as to provide an .paren open-st.O--R.sup.1 .paren close-st. moiety having a molecular weight of from about 40 to about 6,000, and each of n and n' is the same or a different integer of from 0 to 30, inclusive, correlated with m so as to provide a urethane compound having a molecular weight of up to about 60,000. ### Claim 4 (depends on 3) The topical composition of claim 3 wherein the urethane compound has a molecular weight of from about 1,000 to about 15,000. ### Claim 5 (depends on 3) The topical composition of claim 3 wherein the urethane compound is (a) prepared by reacting about one mole of dicyclohexylmethanediisocyanate with about two moles of propylene glycol 725 and (b) has a molecular weight of about 4,000. ### Claim 6 (depends on 1) The topical composition of claim 1 in the form of a liquid. ### Claim 7 (depends on 1) The topical composition of claim 1 in the form of a gel. ### Claim 8 (depends on 1) The topical composition of claim 1 in the form of a cream. ### Claim 9 (depends on 1) The topical composition of claim 1, wherein the amount of retinoic acid is about 0.001% to about 3.0% by weight. ### Claim 10 A method of treating acne vulgaris or the effects of senile keratosis or photoageing of the skin, which method comprises topically applying to a human a topical composition comprising (a) retinoic acid in an amount effective to treat the acne vulgaris or the effects of senile keratosis or photoageing of the skin; (b) an urethane compound in an amount of about one percent by weight to about twenty percent by weight, wherein said urethane compound exhibits a molecular weight of up to about 200,000, is prepared by reacting approximately two moles of a hydroxyterminated linear alkylene or polyalkylene glycol or polyether with approximately one mole of a monomeric organic diisocyanate, and is sufficient to permit the topical composition to exhibit reduced skin irritation but undiminished effectiveness as compared to a composition otherwise identical except for the absence of the urethane compound; and (c) a topical carrier in an amount sufficient to provide said topical composition in the form of a liquid, a cream or a gel. ### Claim 11 (depends on 10) The topical composition of claim 10 wherein the molecular weight of the urethane compound is up to 60,000. ### Claim 12 (depends on 10) The method of claim 10 wherein the urethane compound is represented by the general formula: ##STR4## wherein R represents an alkylene or alkenylene radical, a cycloalkylene or cycloalkylene radical, or a mononuclear or fused ring arylene radical, all of which can be unsubstituted or substituted, R.sup.1 represents the same or different alkylene or alkenylene radicals, m is an integer selected so as to provide an .paren open-st.O--R.sup.1 .paren close-st. moiety having a molecular weight of from about 40 to about 6,000, and each of n and n' is the same or a different integer of from 0 to 30, inclusive, correlated with m so as to provide a urethane compound having a molecular weight of up to about 60,000. ### Claim 13 (depends on 12) The method of claim 12 wherein the urethane compound has a molecular weight of from about 1,000 to about 15,000. ### Claim 14 (depends on 13) The method of claim 13 wherein the urethane compound is prepared by reacting about one mole of dicyclohexylmethanediisocyanate with about two moles of propylene glycol 725, and has a molecular weight of about 4,000. ### Claim 15 (depends on 10) The method of claim 10 in the form of a liquid. ### Claim 16 (depends on 10) The method of claim 10 in the form of a gel. ### Claim 17 (depends on 10) The method of claim 10 in the form of a cream. ### Claim 18 (depends on 10) The method of claim 10 wherein the amount of retinoic acid is about 0.001 percent by weight to about 3.0 percent by weight. ### Claim 19 A topical composition comprising: (a) retinoic acid in an amount of about 0.025 percent by weight to about 0.5 percent by weight; (b) urethane compound in an amount of about two percent by weight to about fifteen percent by weight, wherein said urethane compound (i) exhibits a molecular weight up to about 200,000, (ii) is represented by the general formula: ##STR5## wherein R represents an alkylene or alkenylene radical, a cycloalkylene or cycloalkenylene radical, or a mononuclear or fused ring arylene radical, all of which can be unsubstituted or substituted R.sup.1 represents the same or different alkylene or alkenylene radicals, m is an integer and each of n and n' is the same or a different integer of from 0 to 30, inclusive, correlated with m so as to provide a urethane compound having a molecular weight of up to about 200,000, and (iii) is sufficient to permit the topical composition to exhibit reduced skin irritation but undiminished effectiveness as compared to a composition otherwise identical except for the absence of a urethane compound; and (c) a topical carrier in an amount sufficient to provide said topical composition in the form of a liquid, a cream or a gel. ### Claim 20 (depends on 19) The composition of claim 19, wherein the urethane compound exhibits a molecular weight of about 4,000 and is prepared by reacting about one mole of dicyclohexylmethanediisocyanate with about two moles of propylene glycol 725. ### Claim 21 A method of treating acne vulgaris or the effects of senile keratosis or photoageing of the skin, which method comprises topically applying to a human a topical composition comprising (a) retinoic acid in an amount of about 0.025 percent by weight to about 0.5 percent by weight; (b) urethane compound in an amount of about two percent by weight to about fifteen percent by weight, wherein said urethane compound (i) exhibits a molecular weight up to about 60,000, (ii) is represented by the general formula: ##STR6## wherein R represents an alkylene or alkenylene radical, a cycloalkylene or cycloalkenylene radical, or a mononuclear or fused ring arylene radical, all of which can be unsubstituted or substituted, R' represents the same or different alkylene or alkenylene radicals, m is an integer selected so as to provide an .paren open-st.O--R'.paren close-st. moiety having a molecular weight of from about 40 to about 6,000, and n and n' are the same or a different integer of from 0 to 30, inclusive, correlated with m so as to provide a urethane compound having a molecular weight of up to about 60,000, and (iii) is sufficient to permit the topical composition to exhibit reduced skin irritation but undiminished effectiveness as compared to a composition otherwise identical except for the absence of a urethane compound; and (c) a topical carrier in an amount sufficient to provide said topical composition in the form of a liquid, a cream or a gel. ### Claim 22 (depends on 21) The method of claim 21, wherein the urethane compound exhibits a molecular weight of about 4,000 and is prepared by reacting about one mole of dicyclohexylmethanediisocyanate with about two moles of propylene glycol 725.