Natural combination hormone replacement formulations and therapies

• US 8,993,548 B2
• Filed: 09/03/2014
• Issued: 03/31/2015
• 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:
  US14/475,814
• Publication Number:
  US 20140371182A1
• Time in Patent Office: 209 Days
• Field of Search: 514/169, 424/452
• 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 formulation comprising solubilized estradiol, suspended progesterone, and a medium chain solubilizing agent;

wherein each of the estradiol and the suspended progesterone are present in the solubilizing agent and the estradiol and the suspended progesterone are uniformly dispersed;

wherein at least about 90% of the estradiol is solubilized in the solubilizing agent; and

wherein the solubilizing agent comprises an effective amount of a C6-C12 oil.

2. The pharmaceutical formulation of claim 1, further comprising partially solubilized progesterone.

3. The pharmaceutical formulation of claim 1, wherein the formulation is contained within a gelatin capsule.

4. The pharmaceutical formulation of claim 1, wherein the medium chain solubilizing agent is selected from at least one of mono-, di-, and triglycerides and combinations thereof.

6. The pharmaceutical formulation of claim 1, wherein the ratio of progesterone to estradiol is at least 95:

1.

5. The pharmaceutical formulation of claim , wherein said estradiol has a dosage strength at least about 0.125 mg and wherein said progesterone has a dosage strength at least about 25 mg.