Pharmaceutical composition and method for treating hypogonadism

Abstract

A pharmaceutical composition useful for treating hypogonadism is disclosed. The composition comprises an androgenic or anabolic steroid, a C1-C4 alcohol, a penetration enhancer such as isopropyl myristate, and water. Also disclosed is a method for treating hypogonadism utilizing the composition.

1 . A method of testosterone replacement in a male subject in need thereof, comprising applying a hydroalcoholic gel pharmaceutical composition directly onto an area of skin of the male subject, wherein the composition comprises:
 a. from about 0.5% to about 10% testosterone;   b. from about 30% to about 98% alcohol selected from the group consisting of ethanol and isopropanol;   c. from about 0.1% to about 5% of a thickening agent; and   d. from about 0.25% to about 2.5% of at least one penetration enhancer selected from the group consisting of isostearic acid, octanoic acid, lauryl alcohol, isopropyl myristate, butyl stearate, methyl laurate, diisopropyl adipate, glyceryl monolaurate, tetrahydrofurfuryl alcohol polyethylene glycol ether, polyethylene glycol, propylene glycol, 2-(2-ethoxyethoxy)ethanol, diethylene glycol monomethyl ether, dimethyl sulfoxide, glycerol, ethyl acetate, acetoacetic ester, N-alkylpyrrolidone, derivatives thereof, and combinations thereof;   e water in an amount sufficient to make the composition 100%;   wherein the percentages are weight by weight of the composition; and   wherein the testosterone is absorbed by the skin and released into a blood stream of the subject such that a serum testosterone concentration of greater than about 300 ng/dl is achieved.   
     
     
         2 . The method of  claim 1 , wherein the testosterone is present in a concentration of from about 0.5% to about 5% (w/w) of the composition. 
     
     
         3 . The method of  claim 1 , wherein the alcohol is ethanol. 
     
     
         4 . The method of  claim 1 , wherein the thickening agent is an anionic polymer. 
     
     
         5 . The method of  claim 4 , wherein the anionic polymer is selected from the group consisting of polyacrylic acid, carboxymethyl cellulose, and combinations thereof. 
     
     
         6 . The method of  claim 1 , wherein the composition further comprises 0.1 N sodium hydroxide. 
     
     
         7 . The method of  claim 1 , wherein the penetration enhancer comprises isostearic acid. 
     
     
         8 . The method of  claim 1 , wherein the penetration enhancer comprises octanoic acid. 
     
     
         9 . The method of  claim 1 , wherein the penetration enhancer comprises lauryl alcohol. 
     
     
         10 . The method of  claim 1 , wherein the penetration enhancer comprises isopropyl myristate. 
     
     
         11 . The method of  claim 1 , wherein the penetration enhancer comprises butyl stearate. 
     
     
         12 . The method of  claim 1 , wherein the penetration enhancer comprises methyl laurate. 
     
     
         13 . The method of  claim 1 , wherein the penetration enhancer comprises diisopropyl adipate. 
     
     
         14 . The method of  claim 1 , wherein the penetration enhancer comprises glyceryl monolaurate. 
     
     
         15 . The method of  claim 1 , wherein the penetration enhancer comprises tetrahydrofurfuryl alcohol polyethylene glycol ether. 
     
     
         16 . The method of  claim 1 , wherein the penetration enhancer comprises polyethylene glycol. 
     
     
         17 . The method of  claim 1 , wherein the penetration enhancer comprises propylene glycol. 
     
     
         18 . The method of  claim 1 , wherein the penetration enhancer comprises 2-(2-ethoxyethoxy)ethanol. 
     
     
         19 . The method of  claim 1 , wherein the penetration enhancer comprises diethylene glycol monomethyl ether. 
     
     
         20 . The method of  claim 1 , wherein the penetration enhancer comprises dimethyl sulfoxide. 
     
     
         21 . The method of  claim 1 , wherein the penetration enhancer comprises glycerol. 
     
     
         22 . The method of  claim 1 , wherein the penetration enhancer comprises ethyl acetate. 
     
     
         23 . The method of  claim 1 , wherein the penetration enhancer comprises acetoacetic ester. 
     
     
         24 . The method of  claim 1 , wherein the penetration enhancer comprises N-alkylpyrrolidone. 
     
     
         25 . The method of  claim 1 , wherein the serum testosterone concentration of greater than about 300 ng/dl is achieved during a time period between about 2 hours and 24 hours after application. 
     
     
         26 . The method of  claim 1 , wherein the composition is applied daily to the subject for at least about 7 days. 
     
     
         27 . The method of  claim 1 , wherein the composition is applied daily to the subject for at least about 30 days. 
     
     
         28 . The method of  claim 1 , wherein the composition is applied daily to the subject for at least about 180 days. 
     
     
         29 . The method of  claim 1 , wherein the serum testosterone concentration is maintained between about 300 ng/dl and about 1050 ng/dl. 
     
     
         30 . The method of  claim 1 , wherein the serum testosterone concentration is maintained between about 400 ng/dl and about 1050 ng/dl. 
     
     
         31 . The method of  claim 1 , wherein the subject has primary hypogonadism prior to administration application. 
     
     
         32 . The method of  claim 1 , wherein the composition is provided to the subject for daily application in a dose of from about 0.1 g to about 10 g.