Topical capecitabine for the treatment of hyperproliferative skin conditions

Abstract

The present invention relates to a novel and unexpected method of using topical Capecitabine composition to obtain therapeutically effective amounts of fluorouracil (FU) within the skin of a subject afflicted with hyperproliferative or inflammatory skin condition. The method comprising topically administering a pharmaceutical composition comprising Capecitabine or a hydrate or solvate thereof to the affected area of the skin of the subject, to form therapeutically effective amounts of FU within the skin.

1 - 16 . (canceled) 
     
     
         17 . A topical pharmaceutical composition comprising an effective amount of a therapeutic agent selected from Capecitabine, 5′-deoxy-5-fluorocytidine (5′DFCR), 5′-deoxy-5-fluorouridine (5′DFUR), or combinations thereof in a pharmaceutically acceptable carrier, wherein the composition is suitable for topical administration and forms a therapeutically effective amounts of FU within the skin. 
     
     
         18 . The composition of  claim 17 , wherein the therapeutic agent is Capecitabine. 
     
     
         19 . The composition of  claim 17 , wherein the therapeutic agent is 5′-deoxy-5-fluorocytidine (5′DFCR). 
     
     
         20 . The composition of  claim 17 , wherein the therapeutic agent is 5′-deoxy-5-fluorouridine (5′DFUR). 
     
     
         21 . The topical composition according to  claim 17 , wherein the composition is a solid topical dosage form, a semisolid topical dosage form or a liquid topical dosage form. 
     
     
         22 . The topical dosage form according to  claim 21 , wherein the dosage form is in the form of dusting powder, paste, solution, ointment, cream, lotion, gel, spray, liniment or foam. 
     
     
         23 . The topical dosage form according to  claim 17 , wherein the pharmaceutically acceptable carrier is one or more of a gelling agent, a solvent, a viscosifier, a penetration enhancer, a preservative, a thickening agent, an antioxidant, a chelating agent, an active ingredient stabilizer, an active ingredient solubilizer and/or a cosmetic ingredient. 
     
     
         24 . The topical composition according to  claim 23 , comprising from about 1% to about 10% of the therapeutic agent by weight. 
     
     
         25 . The topical composition according to  claim 18 , comprising from about 0.1% to about 15% by weight Capecitabine. 
     
     
         26 . The topical composition according to  claim 25 , comprising from about 1% to about 10% Capecitabine by weight. 
     
     
         27 . The topical composition according to  claim 17 , wherein the composition is suitable for application to a subject having a pre-cancerous or cancerous hyperproliferative skin condition. 
     
     
         28 . The topical composition according to  claim 27 , wherein the pre-cancerous skin condition is actinic keratosis. 
     
     
         29 . The topical composition according to  claim 27 , wherein the cancerous skin condition is basal cell carcinoma. 
     
     
         30 . The topical composition according to  claim 17 , further comprising at least one additional pharmaceutical agent useful for treating hyperproliferative skin conditions. 
     
     
         31 . The topical composition according to  claim 30 , wherein the at least one additional pharmaceutical agent is selected from diclofenac, imiquimod, ingenol mebutate or other ingenol derivatives, uracil, 5-chloro-2,4-dihydroxypyridine (CDHP), eniluracil, photosensitizing agents, retinoids, interferons, α-hydroxy acids, and caustic agents. 
     
     
         32 . The topical composition according to  claim 17 , wherein the composition is used in conjunction with at least one therapeutic treatment known to be effective in hyperproliferative or inflammatory skin conditions. 
     
     
         33 . The topical composition according to  claim 32 , wherein the therapeutic treatment is selected from cryosurgery, curettage and desiccation, excision, chemical peeling, dermabrasion, laser surgery and photodynamic therapy. 
     
     
         34 . A method of providing fluorouracil (FU) to a subject in need thereof, the method comprising topically administering a pharmaceutical composition comprising an effective amount of a therapeutic agent selected from Capecitabine, 5′-deoxy-5-fluorocytidine (5′DFCR), 5′-deoxy-5-fluorouridine (5′DFUR), or combinations thereof to the skin of the subject, whereby the therapeutic agent is converted to FU in the skin. 
     
     
         35 . (canceled) 
     
     
         36 . A method of decreasing adverse effects of administration of fluorouracil (FU), the method comprising topically administering a pharmaceutical composition comprising an effective amount of a therapeutic agent selected from Capecitabine, 5′-deoxy-5-fluorocytidine (5′DFCR), 5′-deoxy-5-fluorouridine (5′DFUR), or combinations thereof to the skin of the subject, whereby the therapeutic agent is converted to FU in the skin after administration, whereby adverse effects are decreased by a reduction of exposure to FU during administration. 
     
     
         37 . A method of reducing unintended exposure to fluorouracil (FU) during administration of FU to a subject, the method comprising topically administering a pharmaceutical composition comprising an effective amount of a therapeutic agent selected from Capecitabine, 5′-deoxy-5-fluorocytidine (5′DFCR), 5′-deoxy-5-fluorouridine (5′DFUR), or combinations thereof to the skin of the subject, whereby the therapeutic agent is converted to FU in the skin, whereby unintended exposure does not occur during the administration process. 
     
     
         38 . (canceled)