Natural Combination Hormone Replacement Formulations and Therapies
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.
1 . A pharmaceutical composition comprising:
a solubilizing agent, the solubilizing agent comprising an effective amount of a C6-C12 oil;
1.0 mg estradiol or 1.03 mg estradiol hemihydrate, the estradiol or estradiol hemihydrate being at least about 90% solubilized in the solubilizing agent; and
100 mg progesterone;
wherein the estradiol or the estradiol hemihydrate, and the progesterone are uniformly distributed in the solubilizing agent.
2 . The pharmaceutical composition of claim 1 , wherein the solubilizing agent is selected from at least one of monoglycerides, diglycerides, triglycerides, and combinations thereof, wherein the monoglycerides, diglycerides, and triglycerides are predominantly of C6-C12 fatty acid chain lengths.
3 . The pharmaceutical composition of claim 2 , wherein the monoglycerides, diglycerides, and triglycerides are >50% C6-C12 fatty acid chain lengths.
4 . A pharmaceutical composition comprising:
about 100 mg progesterone;
about 1.0 mg estradiol or 1.03 mg estradiol hemihydrate, the estradiol or estradiol hemihydrate being at least about 90% solubilized;
about 195.97 mg of monoglycerides and diglycerides of caprylic acid and capric acid (CAPMUL MCM); and
about 3.0 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 the estradiol hemihydrate, and the progesterone are uniformly distributed in the solubilizing agent.
5 . A method of treating a menopause-related symptom in a woman in need thereof, the method comprising administering an effective amount of a pharmaceutical composition to the woman, the pharmaceutical composition comprising:
about 100 mg progesterone;
about 1.0 mg estradiol or 1.03 mg estradiol hemihydrate, the estradiol or estradiol hemihydrate being at least about 90% solubilized;
about 195.97 mg of monoglycerides and diglycerides of caprylic acid and capric acid (CAPMUL MCM); and
about 3.0 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 the estradiol hemihydrate, and the progesterone are uniformly distributed in the solubilizing agent.
6 . The method of claim 5 , wherein the pharmaceutical composition is administered as a continuous-combined therapy regimen.
7 . The method of claim 5 , wherein the pharmaceutical composition is administered a sequentially-combined therapy regimen.
8 . A pharmaceutical composition comprising:
about 100 mg progesterone;
about 1.0 mg estradiol or 1.03 mg estradiol hemihydrate, the estradiol or estradiol hemihydrate being at least about 90% solubilized;
about 55 to about 75 weight percent of monoglycerides and diglycerides of caprylic acid and capric acid (CAPMUL MCM); and
about 0.5 to about 10 weight percent 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 the estradiol hemihydrate, and the progesterone are uniformly distributed in the solubilizing agent.
9 . The pharmaceutical composition according to claim 8 , wherein the monoglycerides and diglycerides of caprylic acid and capric acid (CAPMUL MCM) are present at about 65 weight percent.
10 . The pharmaceutical composition according to claim 8 , wherein the lauroyl macrogol-32 glycerides EP, lauroyl polyoxyl-32 glycerides NF, or lauroyl polyoxylglycerides (GELUCIRE 44/14) is present at about 1 weight percent.
11 . A method of treating a menopause-related symptom in a woman in need thereof, the method comprising administering an effective amount of a pharmaceutical composition to the woman, the pharmaceutical composition comprising:
about 100 mg progesterone;
about 1.0 mg estradiol or 1.03 mg estradiol hemihydrate, the estradiol or estradiol hemihydrate being at least about 90% solubilized;
about 55 to about 75 weight percent of monoglycerides and diglycerides of caprylic acid and capric acid (CAPMUL MCM); and
about 0.5 to about 10 weight percent 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 the estradiol hemihydrate, and the progesterone are uniformly distributed in the solubilizing agent.
12 . The method of claim 11 , wherein the pharmaceutical composition is administered as a continuous-combined therapy regimen.
13 . The method of claim 11 , wherein the pharmaceutical composition is administered a sequentially-combined therapy regimen.
14 . The method of claim 11 , wherein the monoglycerides and diglycerides of caprylic acid and capric acid (CAPMUL MCM) are present at about 65 weight percent.
15 . The method of claim 11 , wherein the lauroyl macrogol-32 glycerides EP, lauroyl polyoxyl-32 glycerides NF, or lauroyl polyoxylglycerides (GELUCIRE 44/14) is present at about 1 weight percent.
16 . A pharmaceutical composition comprising:
about 100 mg progesterone;
about 1.0 mg estradiol or 1.03 mg estradiol hemihydrate, the estradiol or estradiol hemihydrate being at least about 90% solubilized;
about 55 to about 75 weight percent of monoglycerides and diglycerides of caprylic acid and capric acid (CAPMUL MCM); and
about 0.5 to about 10 weight percent of a surfactant;
wherein the estradiol or the estradiol hemihydrate, and the progesterone are uniformly distributed in the solubilizing agent.
17 . The pharmaceutical composition according to claim 16 , wherein the monoglycerides and diglycerides of caprylic acid and capric acid (CAPMUL MCM) are present at about 65 weight percent.
18 . The pharmaceutical composition according to claim 16 , wherein surfactant comprises fatty acid mono- and di-esters of polyethylene glycol.
19 . The pharmaceutical composition according to claim 18 , wherein the fatty acid mono- and di-esters of polyethylene glycol are present at about 1 weight percent of the pharmaceutical composition.
20 . A method of treating a menopause-related symptom in a woman in need thereof, the method comprising administering an effective amount of a pharmaceutical composition to the woman, the pharmaceutical composition comprising:
about 100 mg progesterone;
about 1.0 mg estradiol or 1.03 mg estradiol hemihydrate, the estradiol or estradiol hemihydrate being at least about 90% solubilized;
about 55 to about 75 weight percent of monoglycerides and diglycerides of caprylic acid and capric acid (CAPMUL MCM); and
about 0.5 to about 10 weight percent of fatty acid mono- and di-esters of polyethylene glycol;
wherein the estradiol or the estradiol hemihydrate, and the progesterone are uniformly distributed in the solubilizing agent.
21 . The method of claim 20 , wherein the pharmaceutical composition is administered as a continuous-combined therapy regimen.
22 . The method of claim 20 , wherein the pharmaceutical composition is administered a sequentially-combined therapy regimen.
23 . The method of claim 20 , wherein the monoglycerides and diglycerides of caprylic acid and capric acid (CAPMUL MCM) are present at about 65 weight percent.
24 . The method of claim 20 , wherein the fatty acid mono- and di-esters of polyethylene glycol are present at about 1 weight percent.