Compositions and methods for treating hyperproliferative epidermal diseases

Abstract

The present invention provides compositions and methods for use in the treatment of hyperproliferative dermal diseases. Specifically, the present invention teaches pharmaceutical compositions for topical administration that include a vitamin D metabolite, calcipotriol, and nicotinamide in a combination that is particularly effective in treating and in the maintenance therapy of psoriasis and other related dermal disorders and diseases.

What is claimed is: 
     
         1 . A stable pharmaceutical composition for topical application, comprising calcipotriol at a concentration of about 20 μg/g to about 70 μg/g; nicotinamide in an amount of at least 1 mg/g to help inhibit proliferation of keratinocytes and reduce the symptoms of the hyperproliferative skin disease or disorder; and a polyethylene glycol-based dermatologically acceptable carrier comprising a mixture of PEG-4000, PEG-400 and polyoxyethylated stearyl alcohol (Steareth-20), wherein the PEG-400 comprises about 70% to about 80% (w/w) of the composition and the PEG-4000 comprises about 15% to about 25% (w/w) of the composition. 
     
     
         2 . The composition according to  claim 1 , wherein calcipotriol is present at a concentration of about 50 μg/g. 
     
     
         3 . The composition according to  claim 1 , wherein the nicotinamide is present at a concentration of about 1 to about 50 mg/g. 
     
     
         4 . The composition according to  claim 1 , wherein said composition further comprises vitamin E. 
     
     
         5 . The composition according to  claim 4 , wherein the vitamin E is present at a concentration of about 0.1% to about 1% (w/w). 
     
     
         6 . The composition according to  claim 1 , wherein said polyoxyethylated stearyl alcohol (Steareth-20) is present at a concentration of about 1% to 5% (w/w). 
     
     
         7 . The composition according to  claim 1 , wherein the composition is a topical composition. 
     
     
         8 . The composition according to  claim 7 , wherein the topical composition is in the form of a dermatological ointment. 
     
     
         9 . A method of treating a hyperproliferative skin disease or disorder in a subject in need thereof, the method comprising topically administering to the subject a therapeutically effective amount of a pharmaceutical composition, the composition comprising: calcipotriol at a concentration of about 20 μg/g to about 70 μg/g; nicotinamide in an amount of at least 1 mg/g to help inhibit proliferation of keratinocytes and reduce the symptoms of the hyperproliferative skin disease or disorder; and a polyethylene glycol-based dermatologically acceptable carrier comprising a mixture of PEG-4000, PEG-400 and polyoxyethylated stearyl alcohol (Steareth-20), wherein the PEG-400 comprises about 70% to about 80% (w/w) of the composition and the PEG-4000 comprises about 15% to about 25% (w/w) of the composition; thereby treating the hyperproliferative skin disease or disorder in the subject, wherein the hyperproliferative disease or disorder is selected from the group consisting of: psoriasis, solar keratosis, ichthyosis, Grover's disease, common warts, keratoacanthoma, seborrhoeic keratosis, scleroderma, and seborrhea. 
     
     
         10 . The method according to  claim 9 , wherein the hyperproliferative disease or disorder is psoriasis. 
     
     
         11 . The method according to  claim 9 , wherein calcipotriol is present at a concentration of about 50 μg/g. 
     
     
         12 . The method according to  claim 9 , wherein the nicotinamide is present at a concentration of about 1 to about 50 mg/g. 
     
     
         13 . The method according to  claim 9 , wherein said composition further comprises vitamin E. 
     
     
         14 . The method according to  claim 13 , wherein the vitamin E is present at a concentration of about 0.1% to about 1% (w/w). 
     
     
         15 . The method according to  claim 9 , wherein said polyoxyethylated stearyl alcohol (Steareth-20) is present at a concentration of about 1% to 5% (w/w). 
     
     
         16 . The method according to  claim 9 , wherein less than 5% of the calcipotriol penetrates the skin. 
     
     
         17 . The method according to  claim 9 , wherein the composition is a topical composition. 
     
     
         18 . The method according to  claim 17 , wherein the topical composition is in the form of a dermatological ointment. 
     
     
         19 . The method according to  claim 9 , wherein the subject is a mammal. 
     
     
         20 . The method according to  claim 19 , wherein the subject is a human subject.