Natural combination hormone replacement formulations and therapies

• US 9,301,920 B2
• Filed: 03/15/2013
• Issued: 04/05/2016
• 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.
• Primary Examiner(s): Parad, Dennis J
• Application Number:
  US13/843,428
• Publication Number:
  US 20130338123A1
• Time in Patent Office: 1,117 Days
• Field of Search: 514/170, 514/899
• 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 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. A pharmaceutical formulation for administering estradiol and progesterone to a mammal in need thereof, comprising

solubilized estradiol,

solubilized progesterone,

suspended progesterone, and

an oil,

wherein each of the solubilized estradiol, the solubilized progesterone, and the suspended progesterone is present in the oil, and

wherein the oil comprises 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.

2. The pharmaceutical formulation of claim 1 wherein the oil comprises medium chain fatty acid esters of glycerol, polyethylene glycol, or propylene glycol, or mixtures thereof, and wherein the medium chain fatty acid esters are predominantly esters of

C6 to C10 fatty acids.

3. The pharmaceutical formulation of claim 1 wherein the oil is predominantly mono- and diglycerides.

4. The pharmaceutical formulation of claim 1 wherein at least 90% of the total estradiol is solubilized.

5. The pharmaceutical formulation of claim 1 further comprising a surfactant.

6. The pharmaceutical formulation of claim 5 wherein the surfactant is a non-ionic surfactant.

7. The pharmaceutical formulation of claim 6 wherein the surfactant is lauroyl polyoxyl-32-glycerides.

8. The pharmaceutical formulation of claim 1 comprising:

30 to 35 wt % progesterone,

0.1 to 0.4 wt % estradiol

55 to 75 wt % of the oil, wherein the oil is predominantly medium chain fatty acid mono- and diglycerides, and

0.5 to 10wt % non-ionic surfactant.

9. The pharmaceutical formulation of claim 8 further comprising gelatin, glycerol, and coloring agents.

10. The pharmaceutical formulation of claim 1 wherein the progesterone is released more rapidly than progesterone in peanut oil.

11. The pharmaceutical formulation of claim 1 wherein the oil comprises medium chain fatty acid esters of glycerol, polyethylene glycol, or propylene glycol, or mixtures thereof, and wherein the medium chain fatty acid esters are predominantly esters of C8 to C12 fatty acids.

12. The pharmaceutical formulation of claim 1 wherein the oil comprises medium chain fatty acid esters of glycerol, polyethylene glycol, or propylene glycol, or mixtures thereof, and wherein the medium chain fatty acid esters are predominantly esters of C8 to C10 fatty acids.

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 pharmaceutical formulation of claim 1.

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