NATURAL COMBINATION HORMONE REPLACEMENT FORMULATIONS AND THERAPIES

• US 20140100205A1
• Filed: 12/06/2013
• Published: 04/10/2014
• Est. Priority Date: 06/18/2012
• Status: Active Grant

• Current Assignee: TherapeuticsMD Inc.
• Original Assignee: TherapeuticsMD Inc.
• Inventors: Bernick, Brian A., Cacace, Janice Louise, Persicaner, Peter H.R., Irani, Neda, Amadio, Julia M.
• Granted Patent: US 8,933,059 B2
• Time in Patent Office: Days
• US Class Current: 514/170
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/02 Suppositories; Bougies; Bases therefor; Ovulesapparatus for making A61J3/08; devices for introducing into the body A61M31/00
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/24 of the sex hormones

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.

Claims

1-14. -14. (canceled)

15. A pharmaceutical composition comprising:

a solubilizing agent;

0.5 mg estradiol, the estradiol being substantially solubilized in the solubilizing agent; and

100 mg progesterone.

16. The pharmaceutical composition of claim 15, wherein the 0.5 mg estradiol comprises about 0.52 mg estradiol hemihydrate.

17. The pharmaceutical composition of claim 15, wherein the solubilizing agent comprises a C6-C12 oil.

18. The pharmaceutical composition of claim 15, wherein the solubilizing agent is selected from at least one of mono-, di-, triglycerides, and combinations thereof, wherein the at least one mono-, di-, and triglycerides are predominantly C6-C12 fatty acid chain lengths.

19. The pharmaceutical composition of claim 18, wherein the at least one mono-, di-, and triglycerides are predominantly about >

50 wt % C6-C12 fatty acid chain lengths.

20. A pharmaceutical composition comprising:

about 100 mg progesterone;

about 0.5 mg estradiol;

about 196.48 mg CAPMUL MCM, NF; and

about 3.0 mg GELUCIRE 44/14 NF.

21. The pharmaceutical composition of claim 20, wherein the 0.5 mg estradiol comprises about 0.52 mg estradiol hemihydrate.

22. A method comprising administering an effective amount of the pharmaceutical composition to a subject in need thereof, the pharmaceutical composition comprising:

about 100 mg progesterone;

about 0.5 mg estradiol;

about 196.48 mg CAPMUL MCM, NF; and

about 3.0 mg GELUCIRE 44/14 NF.

23. The method of claim 22, wherein the pharmaceutical composition is administered as a continuous-combined therapy regimen.

24. The method of claim 22, wherein the pharmaceutical composition is administered as a sequentially-combined therapy regimen.

25. The method of claim 22, wherein the 0.25 mg estradiol comprises about 0.26 mg estradiol hemihydrate.

26. A method comprising administering an effective amount of a pharmaceutical composition comprising:

0.5 mg estradiol, the estradiol being substantially solubilized in the solubilizing agent;

100 mg progesterone; and

a solubilizing agent;

wherein the pharmaceutical composition is administered once daily for the treatment of symptoms associated with menopause.

27. The method of claim 26, wherein the pharmaceutical composition is administered as a continuous-combined therapy regimen.

28. The method of claim 26. wherein the pharmaceutical composition is administered as a sequentially-combined therapy regimen.

29. The method of claim 26, wherein the 0.5 mg estradiol comprises about 0.52 mg estradiol hemihydrate.

30. The method of claim 26, wherein the solubilizing agent is selected from at least one of mono-, di-, triglycerides, and combinations thereof, wherein the at least one mono-, di-, and triglycerides are predominantly C6-C12 fatty acid chain lengths.

31. The method of claim 30, wherein the at least one mono-, di-, and triglycerides are predominantly about >

50 wt % C6-C12 fatty acid chain lengths.