Estrogenic compounds, pharmaceutical compositions and formulations comprising the same

• US 8,227,454 B2
• Filed: 06/23/2011
• Issued: 07/24/2012
• Est. Priority Date: 03/10/2000
• Status: Expired due to Fees

• Current Assignee: Duramed Pharmaceuticals Incorporated (Teva Pharmaceutical Industries Limited)
• Original Assignee: Duramed Pharmaceuticals Incorporated (Teva Pharmaceutical Industries Limited)
• Inventors: Hill, Edward N., Sancilio, Frederick D., Whittle, Robert R.
• Primary Examiner(s): Badio, Barbara P
• Application Number:
  US13/167,350
• Publication Number:
  US 20110269725A1
• Time in Patent Office: 397 Days
• Field of Search: 514/170, 514/171, 514/178, 514/182
• US Class Current: 514/178
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: C07J 1/00 Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
• CPC Class Codes: C07J 17/00 Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton cardanolide, bufanolide C07J19/00

Abstract

Novel estrogenic compounds of Formula I are provided.

wherein the bond represented by the wavy line may be a single or double bond such that when the wavy line is a single bond, R₁ is selected from the group consisting of hydrogen, sulfate and glucoronate or other esters, and when the wavy line is a double bond, R₁ does not exist; R₂ is lower alkyl; R₃ may be selected from the group consisting of hydrogen, sulfate, or glucuronide or other esters; and R₄ through R₁₃ may independently be selected from the group consisting of hydrogen, hydroxy, ketone, lower alkyl, lower alkoxy, halogen, and carbonyl groups and R₁₄ is selected from the group consisting of hydrogen, sulfate and glucoronide and other esters. When R₁ is hydroxy, the hydroxy or ester substituent may have either an α or a β orientation. Compositions of matter including compounds of the present invention are also provided as are methods of treating mammals in need of treatment using compounds of the present invention.

Claims

1. A pharmaceutical composition incorporating a compound represented by the following formula:

2. The pharmaceutical composition of claim 1, wherein the compound has the following characteristics:

having a peak located at about 1.2 ppm on a ¹H-NMR; and

having a peak located at about 45 ppm on a ¹³C-NMR.

3. The pharmaceutical composition of claim 1, wherein said compound is greater than 95% pure.

4. The pharmaceutical composition of claim 1, wherein when R₁ is hydrogen, the compound has a β

orientation at the C17 position.

5. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable salt thereof is selected from the group consisting of a sodium salt, a calcium salt, a magnesium salt, a lithium salt and an amine salt.

6. The pharmaceutical composition of claim 1, wherein the composition further comprises at least one additionally pharmaceutically active ingredient.

7. The pharmaceutical composition of claim 6, wherein the at least one additional pharmaceutically active ingredient is selected from the group consisting of estrogenic compounds, androgenic compounds, progestin compounds, vasodilation agents, calcium salts and vitamin D, and mixtures and combinations thereof.

8. The pharmaceutical composition of claim 1, wherein the compound is represented by the following formula:

9. The pharmaceutical composition of claim 8, wherein said compound is greater than 95% pure.

10. The pharmaceutical composition of claim 8, wherein the composition further comprises at least one additionally pharmaceutically active ingredient.

11. The pharmaceutical composition of claim 10, wherein the at least one additional pharmaceutically active ingredient is selected from the group consisting of estrogenic compounds, androgenic compounds, progestin compounds, vasodilation agents, calcium salts and vitamin D, and mixtures and combinations thereof.

12. A topical pharmaceutical formulation comprising:

(a) a compound represented by the following formula;

13. The topical pharmaceutical formulation of claim 12, wherein the formulation is a vaginal cream.

14. The topical pharmaceutical formulation of claim 12, wherein the formulation is a gel.

15. The topical pharmaceutical formulation of claim 12, wherein the formulation is a suppository.

16. The topical pharmaceutical formulation of claim 12, wherein the formulation is a transdermal patch.

17. The topical pharmaceutical formulation of claim 12, wherein the compound is represented by the following formula:

18. The topical pharmaceutical formulation of claim 12, wherein the compound is represented by the following formula: