Claims for Patent: 11,529,360

Summary for Patent: 11,529,360

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:	US16/520,167
Patent Claims:	1. A pharmaceutical composition comprising: (a) a solubilizing agent, the solubilizing agent comprising an effective amount of a C6-C12 oil; (b) about 1 mg of 17β-estradiol or estradiol hemihydrate, the 17β-estradiol or the estradiol hemihydrate being at least about 90% solubilized in the solubilizing agent; and (c) about 100 mg of progesterone, wherein a first portion of the progesterone is solubilized and a second portion of the progesterone is micronized; wherein the 17β-estradiol or the estradiol hemihydrate, and the progesterone are present in the solubilizing agent; wherein the second portion of the progesterone is uniformly dispersed in the solubilizing agent; and wherein the 17β-estradiol or the estradiol hemihydrate has a solubility in the solubilizing agent of at least about 10 mg/g, and the progesterone has a solubility in the solubilizing agent of at least about 73 mg/g. 2. The pharmaceutical composition of claim 1, wherein the solubilizing agent is selected from at least one of monoglycerides, diglycerides, and triglycerides, and wherein the at least one of monoglycerides, diglycerides, and triglycerides is predominantly of C6-C12 fatty acid chain lengths. 3. A pharmaceutical composition comprising: (a) about 100 mg of progesterone, wherein a first portion of the progesterone is solubilized and a second portion of the progesterone is micronized; (b) about 1 mg of 17β-estradiol or estradiol hemihydrate, the 17β-estradiol or the estradiol hemihydrate being at least about 90% solubilized; (c) a solubilizing agent comprising about 196 mg of monoglycerides and diglycerides of caprylic acid and capric acid; and about 3 mg of at least one of lauroyl macrogol-32 glycerides or lauroyl polyoxyl-32 glycerides; wherein the 17β-estradiol or the estradiol hemihydrate, and the progesterone are present in the solubilizing agent; wherein the second portion of the progesterone is uniformly dispersed in the solubilizing agent; and wherein the 17β-estradiol or the estradiol hemihydrate has a solubility in the solubilizing agent of at least about 10 mg/g, and the progesterone has a solubility in the solubilizing agent of at least about 73 mg/g. 4. A pharmaceutical composition comprising: (a) about 100 mg of progesterone, wherein a first portion of the progesterone is solubilized and a second portion of the progesterone is micronized; (b) about 1 mg of 17β-estradiol or estradiol hemihydrate, the 17β-estradiol or the estradiol hemihydrate being at least about 90% solubilized; (c) a solubilizing agent comprising about 55 to about 75 weight percent of monoglycerides and diglycerides of caprylic acid and capric acid; and about 0.5 to about 10 weight percent of at least one of lauroyl macrogol-32 glycerides or lauroyl polyoxyl-32 glycerides; wherein the 17β-estradiol or the estradiol hemihydrate, and the progesterone are present in the solubilizing agent; wherein the second portion of the progesterone is uniformly dispersed in the solubilizing agent; and wherein the 17β-estradiol or the estradiol hemihydrate has a solubility in the solubilizing agent of at least about 10 mg/g, and the progesterone has a solubility in the solubilizing agent of at least about 73 mg/g. 5. The pharmaceutical composition according to claim 4, wherein the monoglycerides and diglycerides of caprylic acid and capric acid are present at about 65 weight percent. 6. The pharmaceutical composition according to claim 4, wherein the at least one of lauroyl macrogol-32 glycerides or lauroyl polyoxyl-32 glycerides is present at about 1 weight percent. 7. A pharmaceutical composition comprising: (a) about 100 mg of progesterone, wherein a first portion of the progesterone is solubilized and a second portion of the progesterone is micronized; (b) about 1 mg of 17β-estradiol or estradiol hemihydrate, the 17β-estradiol or the estradiol hemihydrate being at least about 90% solubilized; (c) a solubilizing agent comprising about 55 to about 75 weight percent of monoglycerides and diglycerides of caprylic acid and capric acid; and about 0.5 to about 10 weight percent of a surfactant; wherein the 17β-estradiol or the estradiol hemihydrate, and the progesterone are present in the solubilizing agent; wherein the second portion of the progesterone is uniformly dispersed in the solubilizing agent; and wherein the 17β-estradiol or the estradiol hemihydrate has a solubility in the solubilizing agent of at least about 10 mg/g, and the progesterone has a solubility in the solubilizing agent of at least about 73 mg/g. 8. The pharmaceutical composition according to claim 7, wherein the monoglycerides and diglycerides of caprylic acid and capric acid are present at about 65 weight percent. 9. The pharmaceutical composition according to claim 7, wherein the surfactant comprises fatty acid mono- and di-esters of polyethylene glycol. 10. The pharmaceutical composition according to claim 9, wherein the fatty acid mono- and di-esters of polyethylene glycol are present at about 1 weight percent of the pharmaceutical composition. 11. The pharmaceutical composition of claim 1, wherein the 17β-estradiol or the estradiol hemihydrate is fully solubilized in the solubilizing agent. 12. The pharmaceutical composition of claim 3, wherein the 17β-estradiol or the estradiol hemihydrate is fully solubilized in the solubilizing agent. 13. The pharmaceutical composition of claim 4, wherein the 17β-estradiol or the estradiol hemihydrate is fully solubilized in the solubilizing agent. 14. The pharmaceutical composition of claim 7, wherein the 17β-estradiol or the estradiol hemihydrate is fully solubilized in the solubilizing agent. 15. The pharmaceutical composition of claim 1, wherein the 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 3, wherein the micronized progesterone has an X50 particle size value below about 15 microns, an X90 particle size value below about 25 microns, or both. 17. The pharmaceutical composition of claim 4, wherein the 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 7, wherein the micronized progesterone has an X50 particle size value below about 15 microns, an X90 particle size value below about 25 microns, or both. 19. The pharmaceutical composition of claim 1, wherein up to about 14% by weight of the progesterone is solubilized in the solubilizing agent. 20. The pharmaceutical composition of claim 3, wherein up to about 14% by weight of the progesterone is solubilized in the solubilizing agent. 21. The pharmaceutical composition of claim 4, wherein up to about 14% by weight of the progesterone is solubilized in the solubilizing agent. 22. The pharmaceutical composition of claim 7, wherein up to about 14% by weight of the progesterone is solubilized in the solubilizing agent.