Transdermal hormone replacement therapies

• US 9,248,136 B2
• Filed: 01/25/2013
• Issued: 02/02/2016
• Est. Priority Date: 11/23/2011
• Status: Expired due to Fees

• Current Assignee: TherapeuticsMD Inc.
• Original Assignee: TherapeuticsMD Inc.
• Inventors: Bernick, Brian A., Amadio, Julia M., Persicaner, Peter H. R., Cacace, Janice Louise, Irani, Neda, Sancilio, Frederick D.
• Primary Examiner(s): TRAN, MY CHAU T
• Application Number:
  US14/125,554
• Publication Number:
  US 20140329783A1
• Time in Patent Office: 1,103 Days
• Field of Search: 514/170, 514/177, 514/182
• US Class Current: 1/1
• 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

Hormone replacement therapies are provided comprising solubilized progesterone alone and optionally with an estrogen, cyclic/sequential and continuous-combined dosing, and administered via transdermal HRT delivery systems.

Claims

1. A transdermal pharmaceutical formulation comprising progesterone and a solubilizing agent, wherein the solubilizing agent comprises an oil containing a C6-C12 fatty acid, wherein the progesterone is solubilized in the solubilizing agent and wherein the solubilized progesterone is present in a transdermal patch.

2. The transdermal pharmaceutical formulation of claim 1, wherein the oil is a monoglyceride, a diglyceride, or a triglyceride containing a C6—

C12 fatty acid, and combinations thereof.

3. The transdermal pharmaceutical formulation of claim 1, wherein the solubilizing agent is selected from the group consisting of Transcutol and Miglyol;

Transcutol, Miglyol and Capmul PG8;

Transcutol, Miglyol and Capmul PG10;

Campul MCM; and

Capmul MCM and Gelucire.

4. The transdermal pharmaceutical formulation of claim 1, wherein the solubilizing agent is Capmul MCM and a non-ionic surfactant.

5. The transdermal pharmaceutical formulation of claim 4, wherein the solubilizing agent is Capmul MCM and Gelucire.

6. The transdermal pharmaceutical formulation of claim 1, wherein the daily dose of progesterone is from about 10 mg to about 100 mg per patch.

7. The transdermal pharmaceutical formulation of claim 1, wherein the daily dose of progesterone is from about 20 mg to about 80 mg per patch.

8. The transdermal pharmaceutical formulation of claim 1, wherein the daily dose of progesterone is from about 20 mg to about 30 mg per patch.

9. The transdermal pharmaceutical formulation of claim 1, wherein the transdermal patch is from about 9 cm² to about 16 cm² in surface area.

10. The transdermal pharmaceutical formulation of claim 1, further comprising 17β

-estradiol.

11. The transdermal pharmaceutical formulation of claims 10, wherein the 17β

-estradiol is solubilized.

12. The transdermal pharmaceutical formulation of claim 10, wherein the daily dose of 17β

-estradiol is from about 0.01 mg to about 0.1 mg per patch.

13. A method of treating at least one progesterone-deficient state in a mammal in need of treatment comprising administering an effective amount of a transdermal pharmaceutical formulation of claim 1.

14. A method of treating at least one progesterone-deficient state and at least one estrogen-deficient state in a mammal in need of treatment comprising administering an effective amount of a transdermal pharmaceutical formulation of claim 10.

15. The method of claim 14, wherein the progesterone and the 17β

-estradiol drug substance are administered in a cyclic-sequential method.

16. The method of claim 14, wherein the progesterone and the 17β

-estradiol drug substance are administered in a continuous-combined method.

17. A method of treating at least one progesterone-deficient state and at least one estrogen-deficient state in a mammal in need of treatment comprising administering an effective amount of a transdermal pharmaceutical formulation of claim 1, and an effective amount of at least one estrogen drug substance wherein the estrogen drug substance is administered via a method independent of the administration of progesterone in the transdermal pharmaceutical formulation.

18. The method of claim 17, wherein the progesterone and the estrogen drug substance are administered in a cyclic-sequential method.

19. The method of claim 17, wherein the progesterone and the estrogen drug substance are administered in a continuous combined method.

20. The method of claim 17, wherein the estrogen drug substance is estradiol administered via oral administration.