STEROID HORMONE COMPOSITIONS IN MEDIUM CHAIN OILS

• US 20170281776A1
• Filed: 03/30/2017
• Published: 10/05/2017
• Est. Priority Date: 04/01/2016
• Status: Active Grant

• Current Assignee: TherapeuticsMD Inc.
• Original Assignee: TherapeuticsMD Inc.
• Inventors: SHADIACK, Annette, PERSICANER, Peter H.R., INSKEEP, Philip B., THORSTEINSSON, Thorsteinn, SANCILIO, Frederick D., LEGASSIE, Jason D.
• Granted Patent: US 10,286,077 B2
• Time in Patent Office: Days
• 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 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system

Abstract

This disclosure provides a novel pharmaceutical composition capable of forming micelles upon exposure to the gastric environment. The pharmaceutical composition is suitable for delivering steroid hormones, and progesterone in particular, to a subject in need thereof

Claims

1. A pharmaceutical composition for providing enhanced oral bioavailability of progesterone, the pharmaceutical composition comprising:

progesterone, a polysorbate, and a medium chain oil, wherein

the medium chain oil comprises at least about 50 weight percent of a

predominantly medium chain monoglyceride; and

the progesterone is fully solubilized.

2. The pharmaceutical composition of claim 1, wherein the medium chain oil comprises at least about 70 weight percent of a predominantly medium chain monoglyceride.

3. The pharmaceutical composition of claim 2, wherein the polysorbate is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, and polysorbate 80.

4. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition provides an oral bioavailability of at least about 150 percent as measured by an increase in AUC when compared to a reference product.

5. The pharmaceutical composition of claim 1, further comprising at least one of a polyoxyethylene hydrogenated castor oil, a D-α

-Tocopherol polyethylene glycol succinate derivative, or a terpene.

6. The pharmaceutical composition of claim 1, wherein the predominantly medium chain monoglyceride and the progesterone can be present at a weight ratio of about 10:

1 to about 15;

1.

7. The pharmaceutical composition of claim 6, wherein the predominantly medium chain monoglyceride comprises at least about 90 weight percent of the medium chain oil.

8. The pharmaceutical composition of claim 7, wherein the polysorbate is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, and polysorbate 80.

9. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition provides an oral bioavailability of at least about 150 percent as measured by an increase in AUC when compared to a reference product.

10. The pharmaceutical composition of claim 6, further comprising at least one of a polyoxyethylene hydrogenated castor oil, d-α

-tocopherol polyethylene glycol succinate derivative, or a terpene.

15. A method of treating a disease or condition associated with reduced progesterone levels, the method comprising administering to a subject in need thereof a pharmaceutical composition according to claim 1.

17. The method of claim 15, wherein the disease or condition associated with reduced progesterone levels is selected from the group consisting of menopause, endometrial hyperplasia;

secondary amenorrhea;

prevention of preterm birth; and

osteoporosis.

11. An oral, fully-solubilized progesterone pharmaceutical composition comprising:

progesterone and a polysorbate in a weight ratio of from about 1;

2 to about 2;

1; and

a medium chain oil comprising a mixture of medium chain mono- and diglycerides, the medium chain oil not containing more than about 10 weight percent triglycerides.

12. The pharmaceutical composition of claim 11, wherein the polysorbate is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, and polysorbate 80.

13. The pharmaceutical composition of claim 11, wherein the pharmaceutical composition provides an oral bioavailability of at least about 150 percent as measured by an increase in AUC when compared to a reference product.

14. The pharmaceutical composition of claim 11, further comprising at least one of a polyoxyethylene hydrogenated castor oil, a d-α

-tocopherol polyethylene glycol succinate derivative, or a terpene.

16. A method of treating a disease or condition associated with reduced progesterone levels, the method comprising administering to a subject in need thereof a pharmaceutical composition according to claim 11.

18. The method of claim 16, wherein the disease or condition associated with reduced progesterone levels is selected from the group consisting of menopause, endometrial hyperplasia;

secondary amenorrhea;

prevention of preterm birth; and

osteoporosis.

19. A pharmaceutical composition for providing enhanced oral bioavailability of progesterone, the pharmaceutical composition comprising:

progesterone, a polysorbate, and a medium chain oil, wherein

the medium chain oil comprises at least about 50 weight percent of a first medium chain oil component; and

the progesterone is fully solubilized.

20. The pharmaceutical composition of claim 19, wherein the medium chain oil further comprises a second medium chain oil component and wherein the first medium chain oil component is a predominantly medium chain monoglyceride and wherein the second medium chain oil component is a predominantly medium chain diglyceride.

21. The pharmaceutical composition of claim 20, wherein the predominantly medium chain diglyceride is a mixed or complex diglyceride.