Natural combination hormone replacement formulations and therapies

Abstract

Estrogen and progesterone replacement therapies are provided herein. Among others, the following formulations are provided herein: solubilized estradiol without progesterone; micronized progesterone without estradiol; micronized progesterone with partially solubilized progesterone; solubilized estradiol with micronized progesterone; solubilized estradiol with micronized progesterone in combination with partially solubilized progesterone; and solubilized estradiol with solubilized progesterone.

What is claimed is: 
     
         1 . A pharmaceutical composition
 a solubilizing agent;   0.50 mg estradiol or about 0.52 mg estradiol hemihydrate, wherein at least about 90% of the estradiol or estradiol hemihydrate is solubilized; and   50 mg progesterone;   wherein the solubilizing agent comprises predominantly a C6-C12 oil; and   wherein the estradiol or estradiol hemihydrate and the progesterone are uniformly dispersed in the solubilizing agent.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the C6-C12 oil comprises C6-C12 monoglycerides and diglycerides. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the monoglycerides and diglycerides contain esters of caprylic acid (C8) and capric acid (C10). 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein the C6-C12 oil comprises >50% C6-C12 fatty acid chain lengths. 
     
     
         5 . A pharmaceutical composition comprising:
 a solubilizing agent;   0.50 mg estradiol or about 0.52 mg estradiol hemihydrate, wherein at least about 90% of the estradiol or estradiol hemihydrate is solubilized; and   50 mg progesterone;   wherein the solubilizing agent comprises an oil that is predominantly a saturated C6-C12 oil; and   wherein the estradiol or estradiol hemihydrate, and the progesterone are uniformly dispersed in the solubilizing agent.   
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the saturated C6-C12 oil comprises a glyceride of at least one C6-C12 fatty acid. 
     
     
         7 . The pharmaceutical composition of  claim 6 , wherein the saturated C6-12 oil predominantly contains an ester of caprylic acid (C8) and capric acid (C10). 
     
     
         8 . The pharmaceutical composition of  claim 5 , wherein the saturated C6-C12 oil comprises >50% C6-C12 fatty acid chain lengths. 
     
     
         9 . A pharmaceutical composition comprising:
 0.50 mg estradiol or about 0.52 mg estradiol hemihydrate, wherein at least about 90% of the estradiol or estradiol hemihydrate is solubilized; and   50 mg progesterone; and   a solubilizing agent;   wherein the estradiol or estradiol hemihydrate, and the progesterone are uniformly dispersed.   
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein the solubilizing agent is selected from at least one of monoglycerides, diglycerides, triglycerides, and combinations thereof; and wherein the monoglycerides, diglycerides, and triglycerides are predominantly of C6-C12 fatty acid chain lengths. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein more than 50% of the monoglycerides, diglycerides, and triglycerides are C6-C12 fatty acid chain lengths. 
     
     
         12 . A pharmaceutical composition comprising:
 about 50 mg progesterone;   about 0.50 mg estradiol or about 0.52 mg estradiol hemihydrate, wherein at least about 90% of the estradiol or estradiol hemihydrate is solubilized;   about 97.98 mg of a solubilizing agent comprising monoglycerides and diglycerides containing esters of caprylic acid and capric acid (CAPMUL MCM); and   about 1.50 mg of at least one of lauroyl macrogol-32 glycerides EP, lauroyl polyoxyl-32 glycerides NF, or lauroyl polyoxylglycerides (GELUCIRE 44/14);   wherein the estradiol or estradiol hemihydrate, and the suspended progesterone are uniformly dispersed.