Claims for Patent: 10,806,740

Summary for Patent: 10,806,740

Title:	Natural combination hormone replacement formulations and therapies
Abstract:	Pharmaceutical formulations for co-administering estradiol and progesterone are provided herein. In some embodiments, the formulation comprises solubilized estradiol, suspended progesterone, and a medium chain (C6-C12) oil.
Inventor(s):	Peter H. R. Persicaner, Brian A. Bernick, Julia M. Amadio
Assignee:	TherapeuticsMD Inc
Application Number:	US14/512,046
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,806,740
Patent Claims:	1. A pharmaceutical formulation for administering estradiol and progesterone to a female subject in need thereof, comprising: 17β-estradiol, wherein at least about 80% of the estradiol in the formulation is solubilized; suspended progesterone; a solubilizing agent comprising a medium chain oil comprising fatty acid esters of glycerol, polyethylene glycol, or propylene glycol, or mixtures thereof, wherein the fatty acid esters are predominantly esters of C6 to C12 fatty acids; and a surfactant comprising at least one of lauroyl macrogol-32 glycerides, lauroyl polyoxyl-32 glycerides, or lauroyl polyoxylglycerides, wherein the surfactant is present in the formulation in an amount from 0.01 wt % to 10 wt % and the ratio of the medium chain oil to the surfactant is 8:1 or greater; and wherein when administered to a female subject, the formulation produces: (a) one or more progesterone-related pharmacokinetic parameters selected from: (i) an area under the curve (AUC)(0-t) for progesterone that is from 96 ng·hr/mL to 150 ng·hr/mL; (ii) an AUC(0-∞) for progesterone that is from 105 ng·hr/mL to 164 ng·hr/mL; and (iii) a Cmax for progesterone that is from 71 ng/mL to 112 ng/mL; or (b) one or more stradiol-related pharmacokinetic parameters selected from: (i) an AUC(0-t) for estradiol that is from 1123 pg·hr/mL to 1755 pg·hr/mL; (ii) an AUC(0-∞) for estradiol that is from 1968 pg·hr/mL to 3075 pg·hr/mL; and (iii) a Cmax for unconjugated estradiol that is from 52 pg/mL to 81 pg/mL. 2. The pharmaceutical formulation of claim 1, wherein administration of the formulation to the female subject produces both an AUC(0-t) for estradiol that is from 1123 pg·hr/mL to 1755 pg·hr/mL and a Cmax for unconjugated estradiol that is from 52 pg/mL to 81 pg/mL. 3. The pharmaceutical formulation of claim 1, wherein administration of the formulation to the female subject produces both an AUC(0-t) for progesterone that is from 96 ng·hr/mL to 150 ng·hr/mL and a Cmax for progesterone that is from 71 ng/mL to 112 ng/mL. 4. The pharmaceutical formulation of claim 1, wherein when administered to the female subject, the formulation further produces one or more of the following: (i) an AUC(0-t) for estrone sulfate that is from 7277 pg·hr/mL to 11370 pg·hr/mL; (ii) an AUC(0-∞) for estrone sulfate that is from 9596 pg·hr/mL to 14994 pg·hr/mL; or (iii) a Cmax for estrone sulfate that is from 341 pg/mL to 533 pg/mL. 5. The pharmaceutical formulation of claim 4, wherein administration of the formulation to the female subject produces both an AUC(0-t) for estrone sulfate that is from 7277 pg·hr/mL to 11370 pg·hr/mL and a Cmax for estrone sulfate that is from 341 pg/mL to 533 pg/mL. 6. The pharmaceutical formulation of claim 1, wherein when administered to the female subject, the formulation further produces one or more of the following: (i) an AUC(0-t) for total estrone that is from 161 pg·hr/mL to 252 pg·hr/mL; (ii) an AUC(0-∞) for total estrone that is from 171 pg·hr/mL to 267 pg·hr/mL; or (iii) a Cmax for total estrone that is from 28 pg/mL to 44 pg/mL. 7. The pharmaceutical formulation of claim 6, wherein administration of the formulation to the female subject produces both an AUC(0-t) for total estrone that is from 161 pg·hr/mL to 252 pg·hr/mL and a Cmax for total estrone that is from 28 pg/mL to 44 pg/mL. 8. The pharmaceutical formulation of claim 1, wherein at least 50% of the fatty acid esters in the oil have a fatty acid chain length of C6-C12. 9. The pharmaceutical formulation of claim 1, wherein at least 90% of the fatty acid esters in the oil have a fatty acid chain length of C6-C12. 10. The pharmaceutical formulation of claim 1, wherein the medium chain oil is present in the formulation in an amount from 55 wt % to 75 wt %. 11. The pharmaceutical formulation of claim 1, wherein the medium chain oil is a mixture of mono- and diglycerides of capric and caprylic acid. 12. The pharmaceutical formulation of claim 1, wherein the medium chain oil comprises a mixture of mono- and diglycerides of capric and caprylic acid, and the surfactant comprises lauroyl polyoxyl-32 glycerides. 13. The pharmaceutical formulation of claim 1, wherein the formulation comprises progesterone in an amount from 30 wt % to 35 wt %, estradiol in an amount from 0.01 wt % to 0.04 wt %, the medium chain oil in an amount from 55 wt % to 75 wt %, and the surfactant in an amount from 0.01 wt % to 10 wt %. 14. The pharmaceutical formulation of claim 1, wherein the ratio of the medium chain oil to the surfactant is from 60:1 to 70:1. 15. A method of treating a subject having one or more symptoms of estrogen deficiency, the method comprising administering to the subject an effective amount of the pharmaceutical formulation of claim 1. 16. The method of claim 15, wherein the subject is female. 17. The method of claim 15, wherein the subject is a woman having a uterus.