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, the pharmaceutical composition comprising:
a solubilizing agent comprising:
mono- and diglycerides of capric and caprylic acid; and
at least one of lauroyl macrogol-32 glycerides EP, lauroyl polyoxyl-32 glycerides NF, or lauroyl polyoxylglycerides;
progesterone; and
estradiol, the estradiol being at least about 90% solubilized in the solubilizing agent;
wherein the estradiol and the progesterone are present in the solubilizing agent, and the estradiol and suspended progesterone are uniformly dispersed.
2 . The composition of claim 1 , wherein the ratio of progesterone to estradiol is from about 24:1 to about 200:1.
3 . The composition of claim 2 , wherein the ratio of progesterone to estradiol comprises one of: about 24:1, about 25:1, about 96:1, about 100:1, about 192:1, and about 200:1.
4 . The composition of claim 1 , wherein the progesterone is between about 7.14% w/w and about 33.33% w/w of the pharmaceutical composition.
5 . The composition of claim 1 , wherein the estradiol is between about 0.12% w/w and about 0.35% w/w of the pharmaceutical composition.
6 . The composition of claim 1 , wherein the composition is encapsulated in a gelatin capsule; and
wherein each gelatin capsule comprises from about 25 mg to about 200 mg of progesterone and from about 0.125 mg to about 2.00 mg of estradiol.
7 . The composition of claim 1 , wherein the estradiol is at least 95% solubilized in the solubilizing agent.
8 . A method of treating a menopause symptom in a woman with a uterus comprising: administering an effective amount of a pharmaceutical composition, the pharmaceutical composition comprising:
a solubilizing agent comprising:
monoglycerides and diglycerides of caprylic and capric acid; and
a polyethylene glycol glyceride;
progesterone; and
estradiol, the estradiol being at least about 90% solubilized in the solubilizing agent;
wherein the estradiol and the progesterone are present in the solubilizing agent, and the estradiol and progesterone are uniformly dispersed.
9 . The method of claim 8 , wherein the ratio of progesterone to estradiol is from about 24:1 to about 200:1.
10 . The method of claim 9 , wherein the ratio of progesterone to estradiol comprises one of: about 24:1, about 25:1, about 96:1, about 100:1, about 192:1 and about 200:1.
11 . The method of claim 8 , wherein the progesterone is between about 7.14% w/w and about 33.33% w/w of the pharmaceutical composition.
12 . The method of claim 8 , wherein the estradiol is between about 0.12% w/w and about 0.35% w/w of the pharmaceutical composition.
13 . The method of claim 8 , wherein the composition is encapsulated in a gelatin capsule; and
wherein each gelatin capsule comprises from about 25 mg to about 200 mg of progesterone and from about 0.125 mg to about 2.00 mg of estradiol.
14 . The method of claim 8 , wherein the estradiol is at least 95% solubilized in the solubilizing agent.
15 . A method of treating a menopause symptom in a woman with a uterus comprising: administering an effective amount of a pharmaceutical composition, the pharmaceutical composition comprising:
a solubilizing agent comprising:
mono- and diglycerides of capric and caprylic acid; and
at least one of lauroyl macrogol-32 gylcerides, lauroyl polyoxyl-32 glycerides, and lauroyl polyoxylglycerides;
progesterone; and
estradiol, the estradiol being at least about 90% solubilized in the solubilizing agent;
wherein the estradiol and the suspended progesterone are present in the solubilizing agent, and the estradiol and suspended progesterone are uniformly dispersed.
16 . The method of claim 15 , wherein the ratio of progesterone to estradiol is from about 24:1 to about 200:1.
17 . The method of claim 16 , wherein the ratio of progesterone to estradiol comprises one of: about 24:1, about 25:1, about 96:1, about 100:1, about 192:1 and about 200:1.
18 . The method of claim 15 , wherein the progesterone is between about 7.14% w/w and about 33.33% w/w of the pharmaceutical composition.
19 . The method of claim 15 , wherein the estradiol is between about 0.12% w/w and about 0.35% w/w of the pharmaceutical composition.
20 . The method of claim 15 , wherein the composition is encapsulated in a gelatin capsule; and
wherein each gelatin capsule comprises from about 25 mg to about 200 mg of progesterone and from about 0.125 mg to about 2.00 mg of estradiol.
21 . A method of treating a menopause symptom in a woman with a uterus comprising: administering an effective amount of a pharmaceutical composition that comprises progesterone, estradiol and a solubilizing agent;
wherein the solubilizing agent comprises mono- and diglycerides of capric and caprylic acid, and at least one of lauroyl macrogol-32 gylcerides, lauroyl polyoxyl-32 glycerides, and lauroyl polyoxylglycerides;
wherein the estradiol is at least about 90% solubilized in the solubilizing agent; and
wherein the estradiol and the suspended progesterone are present in the solubilizing agent, and the estradiol and suspended progesterone are uniformly dispersed.