Treatment of psoriasis and of other skin disorders associated with inhibition of differentiation of epidermal cells

• US 20090286822A1
• Filed: 07/22/2009
• Published: 11/19/2009
• Est. Priority Date: 07/02/2001
• Status: Active Grant

• Current Assignee: Sinan Tas
• Original Assignee: Sinan Tas
• Inventors: Tas, Sinan, Avci, Oktay
• Granted Patent: US 9,757,361 B2
• Time in Patent Office: Days
• US Class Current: 514/278
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4355 the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 8/63 Steroids; Derivatives thereof
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61Q 19/02 for chemically bleaching or whitening the skin

Abstract

This invention concerns the use of cyclopamine, a naturally occurring steroidal alkaloid known for over thirty years, for the treatment of psoriasis and achievement of rapid clearance of the psoriatic skin lesions together with the reversion of the histopathological signs of disease to normalcy with no detectable side effects. The cyclopamine-induced clearance of psoriatic lesions from the skin of patients is associated with the causation of cellular differentiation in lesional epidermis and with the rapid disappearance of CD4(+) lymphocytes and other inflammatory cells from lesional skin. Therapeutic compositions comprising of cyclopamine and a corticosteroid and/or the pre-treatment of lesions with a corticosteroid provide significantly further increased therapeutic effectiveness over the use of cyclopamine alone or a corticosteroid alone.

Claims

1. A method of treating a human subject having a skin disorder presenting non-tumoral skin lesions comprising:

identifying the skin disorder in said subject as a skin disorder that is associated with inhibition of differentiation of epidermal cells in the skin lesions; and

administering to the subject a medicament comprising cyclopamine or another pharmaceutically acceptable compound that selectively inhibits Hedgehog/Smoothened signaling, wherein

administration of cyclopamine or of said another compound in a sufficient dose induces differentiation of epidermal cells in lesional skin and causes regression or disappearance of the skin lesions.

3. A method as in any of claims 1 or 2, wherein said another compound binds to the Smoothened protein to inhibit Hedgehog/Smoothened signaling.

4. A method as in any of claims 1 or 2, wherein said medicament comprises a pharmaceutically acceptable salt of cyclopamine.

5. A method as in any of claims 1 or 2, wherein combining said another compound with a corticosteroid in said medicament or pre-treating the skin lesions with a corticosteroid provides increased therapeutic effectiveness and causes faster regression or disappearance of the skin lesions.

6. A method as in any of claims 1 or 2, wherein said medicament is in the form of a cream or ointment or gel or hydrogel or foam or another form formulated for topical administration.

7. A method as in any of claims 1 or 2, wherein cyclopamine or said another compound is entrapped in liposomes or is in an aqueous solution for systemic administration.

8. A method as in any of claims 1 or 2, wherein said medicament is a pharmaceutical form enabling controlled release.

9. A method as in any of claims 1 or 2, wherein cyclopamine or said another compound is adsorbed onto a dermal patch.

2. A method of treating psoriasis comprising:

administering to a psoriasis patient a medicament comprising cyclopamine or another pharmaceutically acceptable compound that selectively inhibits Hedgehog/Smoothened signaling, wherein

administration of cyclopamine or of said compound in a sufficient dose induces differentiation of epidermal cells in lesional skin and causes regression or disappearance of psoriatic skin lesions.

10. A method of treating psoriasis, comprising administration of a medicament comprising cyclopamine or another pharmaceutically acceptable compound that inhibits Hedgehog/Smoothened signaling to a psoriasis patient in a sufficient dose to provide, within eight days of administration, an average of 80% or greater decrease in the severity of psoriatic lesions, taking into account the elevation from skin surface, erythema and scaling of lesions.

11. A method as in claim 10, wherein said another compound binds to the Smoothened protein to inhibit Hedgehog/Smoothened signaling.

12. A method as in any of claims 10 or 11, wherein said medicament comprises a pharmaceutically acceptable salt of cyclopamine.

13. A method as in any of claims 10 or 11, wherein said medicament is in the form of a cream or ointment or gel or hydrogel or foam or another form formulated for topical administration.

14. A method as in any of claims 10 or 11, wherein cyclopamine or said another compound is entrapped in liposomes or is in an aqueous solution for systemic administration.

15. A method as in any of claims 10 or 11, wherein said medicament is a pharmaceutical form enabling controlled release.

16. A method as in any of claims 10 or 11, wherein cyclopamine or said another compound is adsorbed onto a dermal patch.

17. A medicament comprising cyclopamine or another compound that selectively inhibits Hedgehog/Smoothened signaling with instructions for effective administration to treat a non-tumoral skin disorder associated with inhibition of differentiation of epidermal cells in skin lesions, wherein said administration induces differentiation of the epidermal cells in lesional skin and causes regression or disappearance of the skin lesions.

19. A medicament as in any of claims 17 or 18, wherein said another compound binds to the Smoothened protein to inhibit Hedgehog/Smoothened signaling.

20. A method as in any of claims 17 or 18, comprising a pharmaceutically acceptable salt of cyclopamine.

18. A medicament comprising cyclopamine or another compound that selectively inhibits Hedgehog/Smoothened signaling with instructions for effective administration to treat psoriasis, wherein said administration induces differentiation of the epidermal cells in lesional skin and causes regression or disappearance of psoriatic skin lesions.