Methods for treating congenital epidermal hyperplasia and compositions for same

Abstract

Compositions and methods for treating congenital epidermal or dermal hyperplasia by using topically administered oncokinase inhibitors such as trametinib, pyrrole derivatives, TAK- 733, CH4987655, RDEA119/BAY 869766, cobimetinib, binimetinib, selumetinib, and the like are described herein.

1 . A composition comprising an oncokinase inhibitor, a solubility enhancer, and a base. 
     
     
         2 . The composition of  claim 1 , wherein the oncokinase inhibitor is selected from the group consisting of trametinib (N-(3-{3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d] pyrimidin-1(2H)-yl}phenyl)acetamide), pyrrole derivatives, TAK-733 (one of a series of 8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione derivatives), CH4987655 and RDEA119/BAY 869766, cobimetinib ((S)-[3,4-Difluoro-2-(2-fluoro-4-iodophenylamino)phenyl][3-hydroxy-3-(piperidin-2-yl)azetidin-1-yl]methanone), binimetinib (5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidzole-6-carboxamide), selumetinib (6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyelhoxy)-3-methylbenzimidazole-5-carboxamide), PD-325901, Cl-1040, PD035901, tetrathiomolybtate, TAK-933, and combinations thereof. 
     
     
         3 . The composition of  claim 1 , wherein the solubility enhancer is selected from the group consisting of ethyl acetate, ethanol, methanol, dimethylformamide (DMF), acetone, acetonitrile, tetrahydrofuran (THF), acetic acid, dimethyl sulfoxide (DMSO), chloroform, and combinations thereof. 
     
     
         4 . The composition of  claim 1 , wherein the base is selected from the group consisting of white petrolatum, white petrolatum USP, mineral jelly, petroleum jelly, yellow petrolatum, yellow soft paraffin, white soft paraffin, fats, waxes, sterols, fat-soluble vitamins, monoglycerides, diglycerides, triglycerides, phospholipids, PCCA plasticized base, and combinations thereof. 
     
     
         5 . The composition of  claim 1 , wherein the base is a cream base, an emollient base, or a liposomal base. 
     
     
         6 . The composition of  claim 1 , wherein the composition is in the form of a topical liquids, creams, lotions, foams, or liniments. 
     
     
         7 . A method for making a topical composition comprising:
 dissolving an oncokinase inhibitor in a solubility enhancer or solvent to create a oncokinase inhibitor solution; and   combining the oncokinase inhibitor with a base.   
     
     
         8 . The method of  claim 7 , wherein the oncokinase inhibitor is selected from the group consisting of trametinib (N-(3-{3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d] pyrimidin-1(2H)-yl}phenyl)acetamide), pyrrole derivatives, TAK-733 (one of a series of 8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione derivatives), CH4987655 and RDEA119/BAY 869766, cobimetinib ((S)-[3,4-Difluoro-2-(2-fluoro-4-iodophenylamino)phenyl][3-hydroxy-3-(piperidin-2-yl)azetidin-1-yl]methanone), binimetinib (5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidzole-6-carboxamide), selumetinib (6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyelhoxy)-3-methylbenzimidazole-5-carboxamide), PD-325901, Cl-1040, PD035901, tetrathiomolybtate, TAK-933, and combinations thereof. 
     
     
         9 . The method of  claim 7 , wherein the solubility enhancer is selected from the group consisting of ethyl acetate, ethanol, methanol, dimethylformamide (DMF), acetone, acetonitrile, tetrahydrofuran (THF), acetic acid, dimethyl sulfoxide (DMSO), chloroform, propylene glycol, polyethylene glycol, propane-1,3-diol, and combinations thereof. 
     
     
         10 . The method of  claim 7 , wherein the base is selected from the group consisting of white petrolatum, white petrolatum USP, mineral jelly, petroleum jelly, yellow petrolatum, yellow soft paraffin, white soft paraffin, fats, waxes, sterols, fat-soluble vitamins, monoglycerides, diglycerides, triglycerides, phospholipids, PCCA plasticized base, and combinations thereof. 
     
     
         11 . The method of  claim 7 , wherein the base is a cream base or an emollient base. 
     
     
         12 . A method for treating congenital epidermal, dermal hyperplasia, or vascular anomalies comprising administering to a patient in need of treatment a composition containing an oncokinase inhibitor, a solubility enhancer, and a base. 
     
     
         13 . The method of  claim 12 , wherein administering comprises applying the composition to the skin of the patient. 
     
     
         14 . The method of  claim 12 , further comprising readministering the composition. 
     
     
         15 . The method of  claim 12 , wherein the patient has congenital epidermal hyperplasia, congenital dermal hyperplasia, Costello syndrome, nevus sebaceous syndrome, or combinations thereof. 
     
     
         16 . The method of  claim 12 , wherein the patient has port-wine stains, capillary malformations, Sturge-Weber syndrome, Klippel-Trenaunay syndrome, venous malformation, or lymphatic malformations. 
     
     
         17 . The method of  claim 12 , wherein the oncokinase inhibitor is selected from the group consisting of trametinib (N-(3-{3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d] pyrimidin-1(2H)-yl}phenyl)acetamide), pyrrole derivatives, TAK-733 (one of a series of 8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione derivatives), CH4987655 and RDEA119/BAY 869766, cobimetinib ((S)-[3,4-Difluoro-2-(2-fluoro-4-iodophenylamino)phenyl][3-hydroxy-3-(piperidin-2-yl)azetidin-1-yl]methanone), binimetinib (5-((4-bromo-2-fluorophenyl)amino)-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzo[d]imidzole-6-carboxamide), selumetinib (6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyelhoxy)-3-methylbenzimidazole-5-carboxamide), PD-325901, Cl-1040, PD035901, tetrathiomolybtate, TAK-933, and combinations thereof. 
     
     
         18 . The method of  claim 12 , wherein the solubility enhancer is selected from the group consisting of ethyl acetate, ethanol, methanol, dimethylformamide (DMF), acetone, acetonitrile, tetrahydrofuran (THF), acetic acid, dimethyl sulfoxide (DMSO), chloroform,propylene glycol, polyethylene glycol, propane-1,3-diol, and combinations thereof. 
     
     
         19 . The method of  claim 12 , wherein the base is selected from the group consisting of white petrolatum, white petrolatum USP, mineral jelly, petroleum jelly, yellow petrolatum, yellow soft paraffin, white soft paraffin, fats, waxes, sterols, fat-soluble vitamins, monoglycerides, diglycerides, triglycerides, phospholipids, PCCA plasticized base, and combinations thereof. 
     
     
         20 . The method of  claim 12 , wherein the base is a cream base, an emollient base, or a liposomal base.