Pharmaceutical Composition

Abstract

A pharmaceutical composition comprising. (A) androgen; (B) a cyclic enhancer of the type used in the compositions and methods claimed by U.S. Pat. No. 5,023,252 to Hsieh; and (C) a thickening agent; including, for example, a composition in which the cyclic enhancer is a macrocyclic ester or a macrocyclic ketone; the use of the composition to treat a condition, for example, male hypogonadism, in a patient by applying the composition to the membrane of the patient; and a method for making the composition.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising: (A) an androgen; (B) a Hsieh enhancer; (C) a thickening agent, and (D) a carrier which is capable of solubilizing one or more of the ingredients of the composition. 
     
     
         2 . A composition according to  claim 1  in the form of a unit dose which is effective in supplying testosterone transdermally to the blood of a male patient such that, following a single application of the unit dose to the patient, the amount of circulating testosterone (AUC.sub.0-24) in the blood serum of the patient achieved in the 24-hour period following the application is about 100 to about 35,000 ng.h/dL greater than the amount of circulating testosterone (AUC.sub.0-24) in the blood serum of the patient that would have been achieved in the same 24-hour period had the dose not been administered, said unit dose comprising up to about 1% by weight testosterone, about 0.01 to about 25% by weight of a Hsieh enhancer, and about 0.1 to about 10% by weight of thickening agent, said testosterone being present in said unit dose in an amount of about 1 to about 300 mg. 
     
     
         3 . A composition according to  claim 1  in the form of a unit dose which is effective in supplying testosterone transdermally to the blood of a female patient such that, following a single application of the unit dose to the patient, the amount of circulating testosterone (AUC.sub.0-24) in the blood serum of the patient achieved in the 24-hour period following the application is about 0.10 to about 11,700 ng.h/dL greater than the amount of circulating testosterone (AUC.sub.0-24) in the blood serum of the patient that would have been achieved in the same 24-hour period had the dose not been administered, said unit dose comprising up to about 1% by weight testosterone, about 0.01 to about 25% by weight of a Hsieh enhancer, and about 0.1 to about 10% by weight of thickening agent, said testosterone being present in said unit dose in an amount of about 0.01 to about 100 mg. 
     
     
         4 . A composition according to  claim 1  in the form of a unit dose which is effective in supplying dihydrotestosterone transdermally to the blood of a male patient such that, following a single application of the unit dose to the patient, the amount of circulating dihydrotestosterone (AUC.sub.0-24) in the blood serum of the patient achieved in the 24-hour period following the application is about 11,625 to about 465,000 pg.h/mL greater than the amount of circulating dihydrotestosterone (AUC.sub.0-24) in the blood serum of the patient that would have been achieved in the same 24-hour period had the dose not been administered, said unit dose comprising up to about 1% by weight dihydrotestosterone, about 0.01 to about 25% by weight of a Hsieh enhancer, and about 0.1 to about 10% by weight of thickening agent, said dihydrotestosterone being present in said unit dose in an amount of about 5 to about 200 mg. 
     
     
         5 . A composition according to  claim 1  in the form of a unit dose which is effective in supplying dihydrotestosterone transdermally to the blood of a female patient such that, following a single application of the unit dose to the patient, the average dihydrotestosterone concentration (AUC.sub.0-24) in the blood serum of the patient achieved in the 24-hour period following the application is about 11.6 about 232,500 pg.h/mL greater than the average dihydrotestosterone concentration (AUC.sub.0-24) in the blood serum of the patient that would have been achieved in the same 24-hour period had the dose not been administered, said unit dose comprising up to about 1% by weight dihydrotestosterone, about 0.01 to about 25% by weight of a Hsieh enhancer, and about 0.1 to about 10% by weight of thickening agent, said dihydrotestosterone being present in said unit dose in an amount of about 0.005 to about 100 mg. 
     
     
         6 . A composition according to  claim 1  comprising: (A) about 0.01 to about 15% by weight of an androgen selected from the group consisting of testosterone, dihydrotestosterone (DHT), and precursors, congeners, salts, complexes, and analogs of testosterone and DHT; (B) about 0.01 to about 15% by weight of a Hsieh enhancer selected from the group consisting of methylcyclopentadecanone (muscone), 9-cycloheptadecen-1-one (civetone), cyclohexadecanone, cyclopentadecanone (normuscone) and oxacyclohexadecan-2one; and (C) about 0.1 to about 10% by weight of thickening agent; and (D) about 40 to about 98% by weight of carrier. 
     
     
         7 . A composition according to  claim 6  comprising: (A) about 0.01 to about 10% by weight of said androgen; and (B) about 0.1 to about 15% by weight of said Hsieh enhancer; (C) about 1 to about 6% by weight of said thickening agent; and (D) about 50 to about 98% by weight of said carrier. 
     
     
         8 . A composition according to  claim 6  comprising: (A) about 0.1 to about 5% by weight of said androgen; (B) about 0.5 to about 15% by weight of said Hsieh enhancer; (C) about 1 to about 6% by weight of said thickening agent; (D) about 50 to about 98% by weight of said carrier. 
     
     
         9 . A composition according to  claim 6  including at least about 40% by weight of a lower alkanol as said carrier. 
     
     
         10 . A composition according to  claim 9  including about 40 to about 80% by weight of the lower alkanol. 
     
     
         11 . A composition according to  claim 9  including about 50 to about 75% by weight of the lower alkanol. 
     
     
         12 . A composition according to  claim 9  including about 60 to about 75% by weight of the lower alkanol. 
     
     
         13 . A composition according to  claim 6  including a carrier comprising a primary solvent and a co-solvent selected from the group consisting of glycerin, propylene glycol, polyethylene, polypropylene, and silicone. 
     
     
         14 . A composition according to  claim 13  including a lower alkanol primary solvent. 
     
     
         15 . A composition according to  claim 14  including ethanol lower alkanol. 
     
     
         16 . A composition according to  claim 14  including isopropanol lower alkanol. 
     
     
         17 . A composition according to  claim 13  including glycerin co-solvent. 
     
     
         18 . A composition according to  claim 13  including about 0.001 to about 5% by weight of a crystallization inhibitor. 
     
     
         19 . A composition according to  claim 18  including polyethylene glycol crystallization inhibitor. 
     
     
         20 . A composition according to  claim 13  including a first fluid which is miscible with or solvates the androgen or the enhancer and a second fluid which is miscible with or partially miscible with the other of said androgen or enhancer, wherein the first fluid evaporates more readily than the second fluid.