Pharmaceutical composition comprising a corticosteroid and a specific inhibitor of hedgehog/smoothened signaling

• US 7,629,352 B2
• Filed: 10/18/2007
• Issued: 12/08/2009
• Est. Priority Date: 07/02/2001
• Status: Expired due to Fees

• Current Assignee: Sinan Tas
• Original Assignee: Sinan Tas
• Inventors: Tas, Sinan, Avci, Oktay
• Primary Examiner(s): Marschel; Ardin
• Assistant Examiner(s): Anderson; James D
• Application Number:
  US11/874,653
• Publication Number:
  US 20080090790A1
• Time in Patent Office: 782 Days
• Field of Search: 514/278
• 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 pharmaceutical composition comprising, in combination,

(i) cyclopamine or another compound that specifically inhibits Hedgehog/Smoothened signaling and

(ii) a corticosteroid.

2. A pharmaceutical composition according to claim 1, wherein the corticosteroid is clobetasol 17-propionate or hydrocortisone.

3. A pharmaceutical composition according to claim 1, wherein said composition is a pharmaceutical form enabling controlled release.

4. A pharmaceutical composition according to claim 1, wherein said composition is adsorbed onto a dermal patch.

5. A pharmaceutical composition according to claim 1, wherein said composition is in the form of a cream or ointment or gel or hydrogel or foam.

6. A pharmaceutical composition according to claim 1, wherein said composition is entrapped in liposomes or is in the form of an aqueous solution suitable for systemic administration.

7. A pharmaceutical composition according to claim 1 further comprising a pharmaceutically acceptable carrier.

8. A pharmaceutical composition according to any one of claims 1 to 7, wherein said another compound inhibits Hedgehog/Smoothened signaling by binding to the Smoothened protein.

9. A pharmaceutical composition according to any one of claims 1 to 7 , wherein said cyclopamine or another compound is cyclopamine or a pharmaceutically acceptable salt thereof.