Patent EA-003616-B1 (EA)
Title: Skin penetration enhancing components
Inventor: ORMEROD ANTHONY DAVID
IPC: A61K47/12
Filed: 1998-11-05
Abstract: 1. A topical formulation for the treatment of a dermatological condition which comprises: an immunosuppressive macrolide selected from siriolimus, FK506, and SDZ ASM 981 or a pharmacologically active analogue, derivative or pro-drug thereof; a permeation modulator selected from an alkanoic acid and an alkenic acid provided that when the immunosuppressive macrolide is FK506 the permeation modulator is not oleic acid; wherein the permeation modulator and the macrolide or the pharmacologically active analogue, derivative or pro-drug thereof are present in relative amounts such that when a therapeutic amount is applied to the skin a minimal systemic effect is produced. 2. A formulation according to claim 1 comprising up to 10% by weight of the immunosuppressive macrolide or analogue, derivative or prodrug thereof; the permeation modulator being present at 1 to 60% by weight. 3. A formulation according to either claim 1 or 2 wherein the alkanoic acid or alkenic acid is selected from capric acid, octanoic acid, oleic such acid or acids of intermediate chain length. 4. A formulation according to any preceding claim wherein the dermatological condition is selected from psoriasis, alopecia, eczema dermatitis, lichen planus, lupus erthematosus, pyoderma gangrenosum, vitiligo, graft versus host disease, pustular skin infections, bacterial skin infections or acne vulgaris. 5. A formulation according to claim 4 wherein the dermatological condition is eczema dermatitis and the concentration of immunosuppressive macrolide or analogue, derivative or pro-drug thereof is 0.05% to 2% by weight. 6. A formulation according to any preceding claim wherein the permeation modulator is used in conjunction with a solvent system. 7. A formulation according to claim 6 wherein the solvent system comprises an aromatic alcohol or a biologically acceptable benzene derivative, with or without an admixture of monoglycerides and/or a fatty acid ester. 8. A formulation according to either claim 6 or 7 wherein the permeation modulator comprises capric acid and the solvent system comprises benzyl alcohol. 9. A formulation according to any of claims 6 to 8 wherein the concentration of the solvent system is 5% to 90% by weight. 10. A formulation according to any preceding claim further comprising a thickening agent. 11. A formulation according to claim 10 wherein the thickening agent is selected from white soft paraffin, cetostearyl alcohol, yellow soft paraffin, cetyl alcohol, steryl alcohol, divalent carboxylic acid soaps and carnauber wax. 12. A formulation according to any preceding claim wherein the immunosuppressive macrolide is sirolimus. 13. The use of an immunosuppressive macrolide selected from comprising siriolimus, FK506, and SDZ ASM 981 or a pharmacologically active analogue, derivative or pro-drug thereof use in the manufacture of a topical composition for the treatment of a dermatological condition selected from the group comprising an alkanoic acid and an alkenic acid provided that when the immunosuppressive macrolide is FK506 the permeation modulator is not oleic acid. 14. The use of claim 13 wherein the immunosuppressive macrolide is present at up to 10% by weight of the composition. 15. The use of an immunosuppressant macrolide or a pharmacologically active analogue, derivative or pro-drug thereof in the preparation of a topical formulation as claimed in any one of claims 1 to 12. 16. A method for the treatment of a disease of the skin or muccosa which comprises applying thereto a topical composition comprising an immunosuppressive macrolide selected from the group comprising siriolimus, FK506, and SDZ ASM 981 or a pharmacologically active analogue, derivative or pro-drug thereof, wherein the composition further comprises a permeation modulator selected from an alkanoic acid and an alkenic acid provided that when the immunosuppressive macrolide is FK506 the permeation modulator is not oleic acid. 17. A method according to claim 16 wherein the immunosuppressive macrolide is present at up to 10% by weight of the composition.