Natural combination hormone replacement formulations and therapies
View Patent ↗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 method of treating menopause-related symptoms comprising administering once daily an effective amount of a pharmaceutical composition to a subject in need thereof, the pharmaceutical composition comprising:
about 50 mg progesterone;
about 0.25 mg estradiol or about 0.26 mg estradiol hemihydrate;
about 98.24 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 a portion of the progesterone is suspended;
wherein the estradiol or estradiol hemihydrate is about 90% solubilized in the solubilizing agent; and
wherein the estradiol or estradiol hemihydrate and suspended progesterone are uniformly dispersed.
2. The method of claim 1 , wherein the pharmaceutical composition is administered as a continuous-combined therapy regimen.
3. The method of claim 1 , wherein the pharmaceutical composition is administered as a sequentially-combined therapy regimen.
4. A method of treating the symptoms with menopause comprising administering an effective amount of a pharmaceutical composition comprising:
0.25 mg estradiol or about 0.26 mg estradiol hemihydrate, wherein the estradiol or estradiol hemihydrate is about 90% solubilized in the solubilizing agent;
50 mg progesterone; and
a solubilizing agent;
wherein a portion of the progesterone is suspended;
wherein the estradiol or estradiol hemihydrate and suspended progesterone are uniformly dispersed;
wherein the solubilizing agent is selected from at least one of monoglycerides, diglycerides, triglycerides, and combinations thereof;
wherein the monoglycerides, diglycerides, and triglycerides have an effective amount of C6-C12 fatty acid chain lengths; and
wherein the pharmaceutical composition is administered once daily for the treatment of symptoms associated with menopause.
5. The method of claim 4 , wherein the pharmaceutical composition is administered as a continuous-combined therapy regimen.
6. The method of claim 4 , wherein the pharmaceutical composition is administered as a sequentially-combined therapy regimen.
7. The method of claim 4 , wherein more than 50% of the monoglycerides, diglycerides, and triglycerides have C6-C12 fatty acid chain lengths.
8. A method of treating vasomotor symptoms in a woman comprising administering once daily an effective amount of a pharmaceutical composition comprising:
a solubilizing agent;
0.25 mg estradiol or about 0.26 mg estradiol hemihydrate, wherein the estradiol or estradiol hemihydrate is about 90% solubilized in the solubilizing agent; and
50 mg progesterone;
wherein the solubilizing agent comprises an effective amount of a C6-C12 oil;
wherein a portion of the progesterone is suspended; and
wherein the estradiol or estradiol hemihydrate and suspended progesterone are uniformly dispersed.
9. The method of claim 8 , wherein the C6-C12 oil comprises C6-C12 monoglycerides and diglycerides.
10. The method of claim 9 , wherein the monoglycerides and diglycerides contain esters of caprylic acid (C8) and capric acid (C10).
11. A method comprising administering once daily an effective amount of a pharmaceutical composition comprising:
a solubilizing agent;
0.25 mg estradiol or about 0.26 mg estradiol hemihydrate, wherein the estradiol or estradiol hemihydrate is about 90% solubilized in the solubilizing agent; and
50 mg progesterone;
wherein the solubilizing agent comprises an effective amount of a saturated C6-C12 oil;
wherein a portion of the progesterone is suspended; and
wherein the estradiol or estradiol hemihydrate and suspended progesterone are uniformly dispersed.
12. The method of claim 11 , wherein the C6-C12 oil comprises a glyceride of at least one C6-C12 fatty acid.
13. The method of claim 11 , wherein the C6-12 oil substantially contains esters of caprylic acid (C8) and capric acid (C10).