Claims for Patent: 10,206,932

Summary for Patent: 10,206,932

Title:	Natural combination hormone replacement formulations and therapies
Abstract:	Pharmaceutical compositions for co-administering estradiol and progesterone to a human subject in need thereof are provided. In some embodiments, the pharmaceutical composition comprises solubilized estradiol, suspended progesterone, and a solubilizing agent comprising a medium chain (C6-C12) oil.
Inventor(s):	Bernick; Brian A. (Boca Raton, FL), Persicaner; Peter H. R. (Boca Raton, FL), Amadio; Julia M. (Boca Raton, FL)
Assignee:	TherapeuticsMD, Inc. (Boca Raton, FL)
Application Number:	14/719,933
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,206,932
Patent Claims:	1. A method of treating a subject having vasomotor symptoms associated with estrogen deficiency, the method comprising administering to the subject an effective amount of a pharmaceutical composition comprising: about 0.25 mg estradiol, wherein at least 80% of the estradiol in the composition is solubilized estradiol; progesterone, wherein the progesterone comprises suspended progesterone; and a medium-chain oil comprising medium chain fatty acid esters of glycerol, polyethylene glycol, or propylene glycol, or mixtures thereof, wherein the medium chain fatty acid esters are predominantly esters of C6 to C12 fatty acids, and wherein the entire amount of the estradiol and the progesterone in the composition is present in the oil; wherein administration of the composition to the subject produces, in a plasma sample from the subject, one or more parameters selected from: (i) an area under the curve (AUC).sub.(0-t) for estradiol that is from 140.3733 pghr/ml to 219.3333 pghr/ml; and (ii) a C.sub.max for estradiol that is from 6.4790 pg/ml to 10.1235 pg/ml. 2. The method of claim 1, wherein the subject is female. 3. The method of claim 1, wherein the subject is a woman having a uterus. 4. The method of claim 1, wherein administration of the composition to the subject produces both an AUC.sub.(0-t) for estradiol that is from 140.3733 pghr/ml to 219.3333 pghr/ml and a C.sub.max for estradiol that is from 6.4790 pg/ml to 10.1235 pg/ml. 5. The method of claim 1, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from: (i) an AUC.sub.(0-t) for progesterone that is from 24.0174 nghr/ml to 37.5272 nghr/ml; and (ii) a C.sub.max for progesterone that is from 17.8444 ng/ml to 27.8819 ng/ml. 6. The method of claim 1, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from: (i) an AUC.sub.(0-t) for estrone that is from 909.6091 pghr/ml to 1421.2642 pghr/ml; and (ii) a C.sub.max for estrone that is from 42.6549 pg/ml to 66.6483 pg/ml. 7. The method of claim 1, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from: (i) an AUC.sub.(0-t) for total estrone that is from 20.1752 nghr/ml to 31.5238 nghr/ml; and (ii) a C.sub.max for total estrone that is from 3.5429 ng/ml to 5.5358 ng/ml. 8. A method of treating a subject having vasomotor symptoms associated with estrogen deficiency, the method comprising administering to the subject an effective amount of a pharmaceutical composition comprising: about 0.5 mg estradiol, wherein at least 80% of the estradiol in the composition is solubilized estradiol; progesterone, wherein the progesterone comprises suspended progesterone; and a medium-chain oil comprising medium chain fatty acid esters of glycerol, polyethylene glycol, or propylene glycol, or mixtures thereof, wherein the medium chain fatty acid esters are predominantly esters of C6 to C12 fatty acids, and wherein the entire amount of the estradiol and the progesterone in the composition is present in the oil; wherein administration of the composition to the subject produces, in a plasma sample from the subject, one or more parameters selected from: (i) an area under the curve (AUC).sub.(0-t) for estradiol that is from 280.7467 pghr/ml to 438.6667 pghr/ml; and (ii) a C.sub.max for estradiol that is from 12.9580 pg/ml to 20.2469 pg/ml. 9. The method of claim 8, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from: (i) an AUC.sub.(0-t) for estrone that is from 1819.2181 pghr/ml to 2842.5283 pghr/ml; and (ii) a C.sub.max for estrone that is from 85.3098 pg/ml to 133.2966 pg/ml. 10. The method of claim 8, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from: (i) an AUC.sub.(0-t) for total estrone that is from 40.3505 nghr/ml to 63.0476 nghr/ml; and (ii) a C.sub.max for total estrone that is from 7.0858 ng/ml to 11.0715 ng/ml. 11. The method of claim 8, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or more parameters selected from: (i) an AUC.sub.(0-t) for progesterone that is from 48.0348 nghr/ml to 75.0543 nghr/ml; and (ii) a C.sub.max for progesterone that is from 35.6889 ng/ml to 55.7639 ng/ml. 12. A method of treating a subject having vasomotor symptoms associated with estrogen deficiency, the method comprising administering to the subject an effective amount of a pharmaceutical composition comprising: about 1 mg estradiol, wherein at least 80% of the estradiol in the composition is solubilized estradiol; progesterone, wherein the progesterone comprises suspended progesterone; and a medium-chain (C6-C12) oil comprising medium chain fatty acid esters of glycerol, polyethylene glycol, or propylene glycol, or mixtures thereof, wherein the medium chain fatty acid esters are predominantly esters of C6 to C12 fatty acids, and wherein the entire amount of the estradiol and the progesterone in the composition is present in the oil; wherein administration of the composition to the subject produces, in a plasma sample from the subject, one or more parameters selected from: (i) an area under the curve (AUC).sub.(0-t) for estradiol that is from 561.4933 pghr/ml to 877.3333 pghr/ml; and (ii) a C.sub.max for estradiol that is from 25.9161 pg/ml to 40.4939 pg/ml. 13. The method of claim 12, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from: (i) an AUC.sub.(0-t) for estrone that is from 3638.4363 pghr/ml to 5685.0567 pghr/ml; and (i) a C.sub.max for estrone that is from 170.6197 pg/ml to 266.5933 pg/ml. 14. The method of claim 12, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from: (i) an AUC.sub.(0-t) for total estrone that is from 80.7010 nghr/ml to 126.0953 nghr/ml; and (ii) a C.sub.max for total estrone that is from 14.1716 ng/ml to 22.1431 ng/ml. 15. The method of claim 8, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from: (i) an AUC.sub.(0-t) for progesterone that is from 24.0174 nghr/ml to 37.5272 nghr/ml; and (ii) a C.sub.max for progesterone that is from 17.8444 ng/ml to 27.8819 ng/ml. 16. The method of claim 12, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from: (i) an AUC.sub.(0-t) for progesterone that is from 48.0348 nghr/ml to 75.0543 nghr/ml; and (ii) a C.sub.max for progesterone that is from 35.6889 ng/ml to 55.7639 ng/ml. 17. The method of claim 1, wherein the composition comprises about 0.25 mg estradiol and about 50 mg progesterone. 18. The method of claim 8, wherein the composition comprises about 0.5 mg estradiol and about 50 mg progesterone. 19. The method of claim 8, wherein the composition comprises about 0.5 mg estradiol and about 100 mg progesterone. 20. The method of claim 12, wherein the composition comprises about 1 mg estradiol and about 100 mg progesterone.