University of California

Cellegy Pharmaceuticals Inc.

Other

Novartis Ag

American Cyanamid Company

Peter Michael Elias

Kenneth R Feingold

Carl R Thornfeldt

Karen Hanley

Stephen Grayson

Walter Martin Holleran

Nathan N Bass

Walter M Holleran

John R Schiltz

An effective barrier function for the lips is restored and maintained by the topical administration of various formulations, including mixtures of ceramides and essential and nonessential free fatty acids, and mixtures of a &bgr;-glucocerebrosidase and a phospholipase A .

Compositions for metabolic protection and repair of lips

A method for disrupting epithelial barrier function in a host in need of the topical administration of a physiologically active substance which comprises applying to the epithelium of the host, barrier-disrupting amount of at least one agent selected from the group consisting of an inhibitor of ceramide synthesis, inhibitor of acylceramide synthesis, inhibitor of glucosylceramide synthesis, and inhibitor of sphingomyelin synthesis, an inhibitor of fatty acid synthesis, an inhibitor of cholesterol synthesis, a degradation enzyme of ceramides, acylceramide, glucosylceramides, sphingomyelin, an inhibitor of phospholipid, glycosphingolipid, including glucosylceramide, acylceramide or sphingomyelin degradation, and both inhibitors and stimulators of metabolic enzymes of free fatty acids, ceramide, and cholesterol, as well as a topical composition useful therefor are disclosed.

Methods and compositions for disrupting the epithelial barrier function

The invention herein encompasses methods effective to stimulate epithelial cell proliferation and/or enhance epithelial moisturization and lubrication in a mammalian subject utilizing a composition comprising one or more inhibitors of &bgr;-glucosidase activity or &bgr;-glucocerebrosidase activity. The composition of the method may alternatively comprise a glycosphingolipid, particularly glucocerebroside, or a combination of the above inhibitor(s) and a glycosphingolipid. The method is effective to enhance the cosmetic appearance of skin and promote healing of skin and mucous membranes damaged or deficient from aging, traumatic wounds, photo-aging and a variety of atrophic conditions. The method may be applied to cells in culture. Also included in the invention is a composition comprising one or more inhibitors of &bgr;-glucosidase and a glycosphingolipid useful to stimulate cell proliferation and enhance tissue moisturization and lubrication.

Methods and compositions for stimulating tissue growth and epithelial moisturization

A method for disrupting epithelial barrier function in a host in need of the topical administration of a physiologically active substance which comprises applying to the epithelium of the host, barrier-disrupting amount of at least one agent selected from the group consisting of an inhibitor of ceramide synthesis, inhibitor of acylceramide synthesis, inhibitor of glucosylceramide synthesis, and inhibitor of sphingomyelin synthesis, an inhibitor of fatty acid synthesis, an inhibitor of cholesterol synthesis, a degradation enzyme of ceramides, acylceramide, glucosylceramides, sphingomyelin, an inhibitor of phospholipid, glycosphingolipid, including glucosylceramide, acylceramide or sphingomyelin degradation, and both inhibitors and stimulators of metabolic enzymes of free fatty acids, ceramide, and cholesterol, as well as a topical composition useful therefore are disclosed.

Method and compositions for disrupting the epithelial barrier function

Disorders of the skin and mucous membranes that have a disrupted or dysfunctional epidermal barrier are treated or prevented by topical application of compounds that are either activators of the farnesoid X receptor, activators of the peroxisome proliferator-activated receptor &agr;, and oxysterol activators of the LXR&agr; receptor. The same compounds are also effective in treating disorders of epidermal differentiation and proliferation.

Treatment of skin conditions with FXR activators

Treatment of skin conditions with oxysterol activators of LXR&agr;

Acne vulgaris and acneiform skin conditions are treated by the application of compounds that is juvenile hormone III, 7-methyl-9-(3,3-dimethyloxiranyl)-3-methyl-2,6-nonadienoic acid methyl ester.

FXR, PPARA and LXRA activators to treat acne/acneiform conditions

Disorders of the skin and mucous membrane that have a disrupted or dysfunctional epidermal barrier are treated or prevented by topical application of compounds that are either activators of the farnesoid X receptor, activators of the peroxisome proliferator-activated receptor .alpha., and oxysterol activators of the LXR.alpha. receptor. The same compounds are also effective in treating disorders of epidermal differentiation and proliferation.

Treatment of skin conditions by use of PPAR.alpha. activators

The invention herein encompasses methods effective to stimulate epithelial cell proliferation and/or enhance epithelial moisturization and lubrication in a mammalian subject utilizing a composition comprising one or more inhibitors of .beta.-glucosidase activity or .beta.-glucocerebrosidase activity. The composition of the method may alternatively comprise a glycosphingolipid, particularly glucocerebroside, or a combination of the above inhibitor(s) and a glycosphingolipid. The method is effective to enhance the cosmetic appearance of skin and promote healing of skin and mucous membranes damaged or deficient from aging, traumatic wounds, photo-aging and a variety of atrophic conditions. The method may be applied to cells in culture. Also included in the invention is a composition comprising one or more inhibitors of .beta.-glucosidase and a glycosphingolipid useful to stimulate cell proliferation and enhance tissue moisturization and lubrication.

Methods and compositions for stimulating tissue growth and epithelial

The permeation of a therapeutic agent through the epithelium by topical administration is enhanced by the further topical administration of a stearylamine, transvaccenic acid or a combination of a stearylamine and transvaccenic acid.

Methods for enhancing permeation of a topically administered

A method for enhancing penetration of a therapeutic or prophylactic agent in a host in need of the topical administration thereof which comprises applying to the epithelium of the host, an effective amount of one or more penetration enhancing epithelial sterols and the therapeutic or prophylactic agent.

Methods for inducing phase separation of epithelial lipid bilayers

Pharmaceutical compositions comprising a cyclosoporin, e.g. Ciclosporin, and a mono- or poly-unsaturated fatty acid or alcohol, e.g. oleic acid or oleyl alcohol. The compositions are suitable for dermal application, e.g. in the treatment of autoimmune disease of the skin or for the promotion of hair growth.

Cyclosporin compositions for topical application

The epidermal permeability barrier to systemically and/or topically active agents or compositions designed for topical administration is enhanced to an unexpected degree by certain combinations of known penetration enhancing excipients. One group of combinations comprise a glycol and an alcohol at a weight ratio within the range of 1:0.1 to 1:10 with one or more further additives, selected from the excipient groups of branched-chain esters of fatty acids, surfactants, and membrane fluidizers. Another group of combinations comprise an alcohol of four or more carbon atoms and one or more further additives selected from the excipient groups of glycols and surfactants.

Growing community of inventors

Mill Valley, CA, United States of America

Peter Michael Elias