Claims for Patent: 11,166,963

Summary for Patent: 11,166,963

Title:	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.
Inventor(s):	Brian A. Bernick, Janice Louise Cacace, Peter H. R. Persicaner, Neda Irani, Julia M. Amadio, Frederick D. Sancilio
Assignee:	TherapeuticsMD Inc
Application Number:	US15/999,040
Patent Claims:	1. A pharmaceutical composition comprising: a fill material comprising a solubilizing agent; 0.50 mg 17β-estradiol or about 0.52 mg estradiol hemihydrate, wherein the 17β-estradiol or estradiol hemihydrate is greater than 90% solubilized in the solubilizing agent; and 100 mg progesterone, wherein the 100 mg progesterone comprises suspended micronized progesterone and solubilized progesterone; wherein the solubilizing agent comprises predominantly a C6-C12 oil; wherein the 17β-estradiol or estradiol hemihydrate has a solubility of at least 10 mg/g in the solubilizing agent; wherein the progesterone has a solubility of at least 73.3 mg/g in the solubilizing agent; wherein the 17β-estradiol or estradiol hemihydrate is about 0.1% to about 0.4% by weight of the fill material; wherein the progesterone is about 30% to about 35% by weight of the fill material; and wherein the 17β-estradiol or estradiol hemihydrate, and the progesterone are present in the solubilizing agent, and the 17β-estradiol or estradiol hemihydrate, and the progesterone are uniformly dispersed. 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 wherein the C6-C12 oil is >50% C6-C12 fatty acid chain lengths. 5. A pharmaceutical composition comprising: a fill material comprising a solubilizing agent; 0.50 mg 17β-estradiol or about 0.52 mg estradiol hemihydrate, wherein the 17β-estradiol or estradiol hemihydrate is greater than 90% solubilized in the solubilizing agent; and 100 mg progesterone, wherein the 100 mg progesterone comprises suspended micronized progesterone and solubilized progesterone; wherein the solubilizing agent comprises an oil that is predominantly a saturated C6-C12 oil; wherein the 17β-estradiol or estradiol hemihydrate has a solubility of at least 10 mg/g in the solubilizing agent; wherein the progesterone has a solubility of at least 73.3 mg/g in the solubilizing agent; wherein the 17β-estradiol or estradiol hemihydrate is about 0.1% to about 0.4% by weight of the fill material; wherein the progesterone is about 30% to about 35% by weight of the fill material; and wherein the 17β-estradiol or estradiol hemihydrate, and the progesterone are present in the solubilizing agent, and the 17β-estradiol or estradiol hemihydrate, and the progesterone are uniformly dispersed. 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 contains predominantly esters of caprylic acid (C8) and capric acid (C10). 8. The pharmaceutical composition of claim 5, wherein the wherein the saturated C6-C12 oil comprises >50% C6-C12 fatty acid chain lengths. 9. A pharmaceutical composition comprising: a fill material comprising a solubilizing agent; 0.50 mg 17β-estradiol or about 0.52 mg estradiol hemihydrate, wherein the 17β-estradiol or estradiol hemihydrate is greater than 90% solubilized in the solubilizing agent; and 100 mg progesterone, wherein the 100 mg progesterone comprises suspended micronized progesterone and solubilized progesterone; wherein the 17β-estradiol or estradiol hemihydrate has a solubility of at least 10 mg/g in the solubilizing agent; wherein the progesterone has a solubility of at least 73.3 mg/g in the solubilizing agent; wherein the 17β-estradiol or estradiol hemihydrate is about 0.1% to about 0.4% by weight of the fill material; wherein the progesterone is about 30% to about 35% by weight of the fill material; and wherein the 17β-estradiol or estradiol hemihydrate, and the progesterone are present in the solubilizing agent, and the 17β-estradiol or estradiol hemihydrate, and the progesterone are uniformly dispersed. 10. The pharmaceutical composition of claim 9, wherein the solubilizing agent is selected from monoglycerides, diglycerides, triglycerides, and combinations thereof; and wherein the monoglycerides, diglycerides, and triglycerides have an effective amount of C6-C12 fatty acid chain lengths. 11. The pharmaceutical composition of claim 10, wherein more than 50% of the monoglycerides, diglycerides, and triglycerides have C6-C12 fatty acid chain lengths. 12. A pharmaceutical composition comprising: a fill material comprising a solubilizing agent; about 100 mg progesterone, wherein the about 100 mg progesterone comprises suspended micronized progesterone and solubilized progesterone; about 0.50 mg 17β-estradiol or about 0.52 mg estradiol hemihydrate; about 196.5 mg of the solubilizing agent, wherein the solubilizing agent comprises monoglycerides and diglycerides containing esters of caprylic acid and capric acid; and about 3.0 mg of at least one of lauroyl macrogol-32 glycerides EP, lauroyl polyoxyl-32 glycerides NF, or lauroyl polyoxylglycerides; wherein the 17β-estradiol or estradiol hemihydrate has a solubility of at least 10 mg/g in the solubilizing agent; wherein the progesterone has a solubility of at least 73.3 mg/g in the solubilizing agent; wherein the 17β-estradiol or estradiol hemihydrate is about 0.1% to about 0.4% by weight of the fill material; wherein the progesterone is about 30% to about 35% by weight of the fill material; and wherein the 17β-estradiol or estradiol hemihydrate, and the progesterone are present in the solubilizing agent, and the 17β-estradiol or estradiol hemihydrate, and the progesterone are uniformly dispersed. 13. The pharmaceutical composition of claim 1, wherein the suspended micronized progesterone has an X50 particle size value below about 15 microns, an X90 particle size value below about 25 microns, or both. 14. The pharmaceutical composition of claim 1, wherein the 17β-estradiol does not precipitate for at least 14 days. 15. The pharmaceutical composition of claim 5, wherein the suspended micronized progesterone has an X50 particle size value below about 15 microns, an X90 particle size value below about 25 microns, or both. 16. The pharmaceutical composition of claim 5, wherein the 17β-estradiol does not precipitate for at least 14 days. 17. The pharmaceutical composition of claim 9, wherein the suspended micronized progesterone has an X50 particle size value below about 15 microns, an X90 particle size value below about 25 microns, or both. 18. The pharmaceutical composition of claim 9, wherein the 17β-estradiol does not precipitate for at least 14 days. 19. The pharmaceutical composition of claim 12, wherein the suspended micronized progesterone has an X50 particle size value below about 15 microns, an X90 particle size value below about 25 microns, or both. 20. The pharmaceutical composition of claim 12, wherein the 17β-estradiol does not precipitate for at least 14 days. 21. The pharmaceutical composition of claim 1, wherein the 17β-estradiol or estradiol hemihydrate is about 93%, 95%, 97%, 99%, or 100% solubilized in the solubilizing agent. 22. The pharmaceutical composition of claim 5, wherein the 17β-estradiol or estradiol hemihydrate is about 93%, 95%, 97%, 99%, or 100% solubilized in the solubilizing agent. 23. The pharmaceutical composition of claim 9, wherein the 17β-estradiol or estradiol hemihydrate is about 93%, 95%, 97%, 99%, or 100% solubilized in the solubilizing agent.