Progesterone formulations

• US 10,639,375 B2
• Filed: 07/17/2018
• Issued: 05/05/2020
• Est. Priority Date: 06/18/2012
• Status: Active Grant

• Current Assignee: TherapeuticsMD Inc.
• Original Assignee: TherapeuticsMD Inc.
• Inventors: Bernick, Brian A., Amadio, Julia M., Persicaner, Peter H. R., Cacace, Janice Louise, Thorsteinsson, Thorsteinn, Sancilio, Frederick D., Irani, Neda
• Primary Examiner(s): Jean-Louis, Samira J
• Application Number:
  US16/037,452
• Publication Number:
  US 20190008968A1
• Time in Patent Office: 658 Days
• 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 31/566 having an oxo group in position 17, e.g. estrone
• 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 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• 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 9/4825 Proteins, e.g. gelatin gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/06 Antiabortive agents; Labour repressants
• 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
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: A61P 5/34 Gestagens

Abstract

Various pharmaceutical formulations are disclosed herein. For example, a pharmaceutical formulation is disclosed comprising ultra-micronized progesterone.

Claims

1. A pharmaceutical composition comprising:

progesterone and an effective amount of estradiol not exceeding 2 mg, wherein the estradiol and progesterone are present in a weight ratio of 1;

100;

a medium chain oil; and

a non-ionic surfactant;

further wherein the progesterone is present from about 20 to about 50 weight percent of the composition.

2. The pharmaceutical composition of claim 1, wherein a portion of the progesterone is solubilized and a portion of the progesterone is suspended.

3. The pharmaceutical composition of claim 1, wherein the non-ionic surfactant is selected from the group consisting of lauroyl macrogol-32 glycerides EP, lauroyl polyoxyl-32 glycerides, and caprylocaproyl macrogol-8 glycerides EP.

4. The pharmaceutical composition of claim 1, wherein the composition is provided in a gelatin capsule.

5. The pharmaceutical composition of claim 1, wherein the composition provides increased progesterone bioavailability compared to a micronized progesterone suspended in peanut oil.

6. The pharmaceutical composition of claim 1, wherein the medium chain oil comprises at least one C6-C14 fatty acid mono-, di-, or tri-ester of glycerol or mono- or di-ester of a glycol.

7. The pharmaceutical composition of claim 6, wherein the at least one C6-C14 fatty acid mono-, di-, or tri-ester of glycerol is a C8 fatty acid mono-, di-, or tri-ester of glycerol.

8. The pharmaceutical composition of claim 6, further comprising a second C6-C14 fatty acid mono-, di-, or tri-ester of glycerol.

9. The pharmaceutical composition of claim 8, wherein the second C6-C14 fatty acid mono-, di-, or tri-ester of glycerol is a C10 fatty acid mono-, di-, or tri-ester of glycerol.

10. The pharmaceutical composition of claim 9, wherein the medium chain oil is CAPMUL MCM.

11. The pharmaceutical composition of claim 1, comprising 50 mg of progesterone.

12. The pharmaceutical composition of claim 1, comprising 100 mg of progesterone.

13. The pharmaceutical composition of claim 12, wherein the progesterone is ultra-micronized and has an X50 less than or equal to 15 microns.

14. The pharmaceutical composition of claim 13, wherein the ultra-micronized progesterone has an X90 of less than about 25 microns.

15. The pharmaceutical composition of claim 12, wherein a portion of the progesterone is solubilized and a portion of the progesterone is suspended.

16. The pharmaceutical composition of claim 15, wherein the non-ionic surfactant is selected from the group consisting of lauroyl macrogol-32 glycerides EP, lauroyl polyoxyl-32 glycerides, and caprylocaproyl macrogol-8 glycerides EP.

17. The pharmaceutical composition of claim 16, wherein the composition is provided in a gelatin capsule.

18. The pharmaceutical composition of claim 16, wherein the composition provides increased progesterone bioavailability compared to a micronized progesterone suspended in peanut oil.

19. The pharmaceutical composition of claim 18, wherein the medium chain oil comprises at least one C6-C14 fatty acid mono-, di-, or tri-ester of glycerol or mono- or di-ester of a glycol.

20. The pharmaceutical composition of claim 19, wherein the at least one C6-C14 fatty acid mono-, di-, or tri-ester of glycerol is a C8 fatty acid mono-, di-, or tri-ester of glycerol.

21. The pharmaceutical composition of claim 20, further comprising a second C6-C14 fatty acid mono-, di-, or tri-ester of glycerol.

22. The pharmaceutical composition of claim 21, wherein the second C6-C14 fatty acid mono-, di-, or tri-ester of glycerol is a C10 fatty acid mono-, di-, or tri-ester of glycerol.

23. The pharmaceutical composition of claim 22, wherein the medium chain oil is CAPMUL MCM.