Natural combination hormone replacement formulations and therapies

• US 8,987,237 B2
• Filed: 12/06/2013
• Issued: 03/24/2015
• Est. Priority Date: 11/23/2011
• 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.
• Primary Examiner(s): Parad, Dennis J
• Application Number:
  US14/099,562
• Publication Number:
  US 20140099362A1
• Time in Patent Office: 473 Days
• US Class Current: 514/169
• 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 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 9/16 Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51
• 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: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• 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

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. A pharmaceutical composition comprising:

a solubilizing agent comprising;

mono- and diglycerides of capric and caprylic acid; and

at least one of lauroyl macrogol-32 glycerides EP, lauroyl polyoxyl-32 glycerides NF, or lauroyl polyoxylglycerides;

progesterone; and

estradiol, the estradiol being at least about 90% solubilized in the solubilizing agent;

wherein the estradiol and the progesterone are present in the solubilizing agent, and the estradiol and suspended progesterone are uniformly dispersed.

2. The pharmaceutical composition of claim 1, wherein the ratio of progesterone to estradiol is from about 24:

1 to about 200;

1.

3. The pharmaceutical composition of claim 2, wherein the ratio of progesterone to estradiol comprises one of:

about 24;

1, about 25;

1, about 96;

1, about 100;

1, about 192;

1, and about 200;

1.

4. The pharmaceutical composition of claim 1, wherein the progesterone is between about 7.14% w/w and about 33.33% w/w of the pharmaceutical composition.

5. The pharmaceutical composition of claim 1, wherein the estradiol is between about 0.12% w/w and about 0.35% w/w of the pharmaceutical composition.

6. The pharmaceutical composition of claim 1, wherein the composition is encapsulated in a gelatin capsule;

and

wherein each gelatin capsule comprises from about 25 mg to about 200 mg of progesterone and from about 0.125 mg to about 2.00 mg of estradiol.

7. The pharmaceutical composition of claim 1, wherein the estradiol is at least 90% solubilized in the solubilizing agent.

8. A pharmaceutical composition comprising:

a solubilizing agent comprising;

monoglycerides and diglycerides of caprylic and capric acid; and

a polyethylene glycol glyceride;

progesterone; and

estradiol, the estradiol being at least about 90% solubilized in the solubilizing agent;

wherein the estradiol and the progesterone are present in the solubilizing agent, and the estradiol and progesterone are uniformly dispersed.

9. The pharmaceutical composition of claim 8, wherein the ratio of progesterone to estradiol is from about 24:

1 to about 200;

1.

10. The pharmaceutical composition of claim 9, wherein the ratio of progesterone to estradiol comprises one of:

about 24;

1, about 25;

1, about 96;

1, about 100;

1, about 192;

1 and about 200;

1.

11. The pharmaceutical composition of claim 8, wherein the progesterone is between about 7.14% w/w and about 33.33% w/w of the pharmaceutical composition.

12. The pharmaceutical composition of claim 8, wherein the estradiol is between about 0.12% w/w and about 0.35% w/w of the pharmaceutical composition.

13. The pharmaceutical composition of claim 8, wherein the composition is encapsulated in a gelatin capsule;

and

wherein each gelatin capsule comprises from about 25 mg to about 200 mg of progesterone and from about 0.125 mg to about 2.00 mg of estradiol.

14. The pharmaceutical composition of claim 8, wherein the estradiol is at least 90% solubilized in the solubilizing agent.

15. A pharmaceutical composition comprising:

a solubilizing agent comprising;

mono- and diglycerides of capric and caprylic acid; and

at least one of lauroyl macrogol-32 glycerides, lauroyl polyoxyl-32 glycerides, and lauroyl polyoxylglycerides;

progesterone; and

estradiol, the estradiol being at least about 90% solubilized in the solubilizing agent;

wherein the estradiol and the suspended progesterone are present in the solubilizing agent, and the estradiol and suspended progesterone are uniformly.

16. The pharmaceutical composition of claim 15, wherein the ratio of progesterone to estradiol is from about 24:

1 to about 200;

1.

17. The pharmaceutical composition of claim 15, wherein the ratio of progesterone to estradiol comprises one of:

about 24;

1, about 25;

1, about 96;

1, about 100;

1, about 192;

1 and about 200;

1.

18. The pharmaceutical composition of claim 15, wherein the progesterone is between about 7.14% w/w and about 33.33% w/w of the pharmaceutical composition.

19. The pharmaceutical composition of claim 15, wherein the estradiol is between about 0.12% w/w and about 0.35% w/w of the pharmaceutical composition.

20. The pharmaceutical composition of claim 15, wherein the composition is encapsulated in a gelatin capsule;

and

wherein each gelatin capsule comprises from about 25 mg to about 200 mg of progesterone and from about 0.125 mg to about 2.00 mg of estradiol.