NATURAL COMBINATION HORMONE REPLACEMENT FORMULATIONS AND THERAPIES

• US 20130338123A1
• Filed: 03/15/2013
• Published: 12/19/2013
• 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 9,301,920 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. A pharmaceutical formulation for administering estradiol, progesterone, or estradiol and progesterone to a mammal in need thereof, comprising

(i) solubilized estradiol,

(ii) fully solubilized progesterone,

(iii) partially solubilized/partially micronized progesterone,

(iv) solubilized estradiol and fully solubilized progesterone, or

(v) solubilized estradiol and partially solubilized/partially micronized progesterone,

in an oil wherein the oil comprises a medium chain fatty acid ester or mixtures thereof.

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

C6 to C12 fatty acids,

C6 to C10 fatty acids,

C8 to C12 fatty acids, or

C8 to C10 fatty acids.

3. The pharmaceutical formulation of claim 2 wherein the oil is predominantly mono- and diglycerides.

4. The pharmaceutical formulation of claim 1 that comprises estradiol and partially solubilized/partially micronized progesterone wherein at least 80% of the total progesterone is solubilized.

5. The pharmaceutical formulation of claim 2 that comprises estradiol and partially solubilized/partially micronized progesterone wherein at least 80% of the total progesterone is solubilized.

6. The pharmaceutical formulation of claim 3 that comprises estradiol and partially solubilized/partially micronized progesterone wherein at least 80% of the total progesterone is solubilized and that further comprises a surfactant.

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

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

9. The pharmaceutical formulation of claim 1 in a hard capsule, a soft capsule, or a tablet for oral administration.

10. The pharmaceutical formulation of claim 9 comprising:

30 to 35 wt % progesterone,

0.1 to 0.4 wt % estradiol

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

0.5 to 10 wt % non-ionic surfactant.

11. The pharmaceutical formulation of claim 10 further comprising gelatin, glycerol, and coloring agents.

12. The pharmaceutical formulation of claim 1 that comprises

(i) fully solubilized progesterone,

(ii) partially solubilized/partially micronized progesterone,

(iii) solubilized estradiol and fully solubilized progesterone, or

(iv) solubilized estradiol and partially solubilized/partially micronized progesterone,

and in which the progesterone is released more rapidly than progesterone in peanut oil.

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 claims 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 claims 1.