Methods for the treatment of endometriosis

• US 9,532,995 B2
• Filed: 08/27/2004
• Issued: 01/03/2017
• Est. Priority Date: 09/03/2003
• Status: Active Grant

• Current Assignee: Miscon Trading SA
• Original Assignee: Miscon Trading SA
• Inventors: Govindarajan, Mirudhubashini
• Primary Examiner(s): Liu, Sue
• Assistant Examiner(s): Holt, Andriae M
• Application Number:
  US10/927,822
• Publication Number:
  US 20050085453A1
• Time in Patent Office: 4,512 Days
• US Class Current: 1/1
• 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 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/02 for disorders of the vagina
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/34 Gestagens

Abstract

Endometriosis, including endometriosis externa, endometrioma, adenomyosis, adenomyomas, adenomyotic nodules of the uterosacral ligaments, and endometriotic nodules, such as scar endometriosis are effectively treated by the intralesional administration, including transvaginal, endoscopic or open surgical administration including via laparotomy, of a progestogen. Compositions therefor also are provided.

Claims

1. A dosage unit comprising a micronized progestogen in an amount equivalent to 1.0-5.0 g of progesterone in a non-oil based suspension formulated for intralesional injection into an endometriotic lesion or fibroid, wherein the unit dosage is formulated with at least one viscosity increasing/suspending agent for increased retention at the site of injection.

2. The dosage unit according to claim 1, wherein the progestogen is in an amount equivalent to 1-2 g of progesterone.

3. The dosage unit according to claim 1, wherein the progestogen is selected from the group consisting of progesterone, desogestrel, etonogestrel, gestodene, levonorgestrel, medroxyprogesterone, norethisterone, norgestimate, and norgestrel.

4. The dosage unit according to claim 1, wherein the progestogen is progesterone.

5. The dosage unit according to claim 1, wherein the progestogen is micronized to a particle size of less than or equal to 100 μ

m.

6. The dosage unit according to claim 1, wherein the progestogen is micronized to a particle size of greater than 10 μ

m.

7. The dosage unit according to claim 1, wherein the viscosity is 53-60 cP.

8. The dosage unit according to claim 1, wherein the pH is between 4 and 7.5.

9. The dosage unit according to claim 1, wherein the progestogen is 1-50% weight/volume.

10. The dosage unit according to claim 9, wherein the progestogen is 5-20% weight/volume.

11. The dosage unit according to claim 9, wherein the progestogen is 10% weight/volume.

12. The dosage unit of claim 1, wherein 99 wt. % of the progestogen has a particle size less than 10 μ

m and 75 wt. % of the progestogen has a particle size less than 5 μ

m.

13. The dosage unit of claim 12, wherein the viscosity is 53-60 cP.

25. A kit comprising a dosage unit according to claim 1 or a pharmaceutical composition according to claim 14 and a needle.

26. The kit according to claim 25, further comprising instructions for intralesional administration of the dosage unit or pharmaceutical composition.

27. The kit according to claim 25, wherein the dosage unit or pharmaceutical composition comprises a progestogen in an amount equivalent to 1-2 g of progesterone per lesion.

28. The kit according to claim 25, wherein the progestogen in the dosage unit or pharmaceutical composition is selected from the group consisting of progesterone, desogestrel, etonogestrel, gestodene, levonorgestrel, medroxyprogesterone, norethisterone, norgestimate, and norgestrel.

29. The kit according to claim 28, wherein the progestogen in the dosage unit or pharmaceutical composition is progesterone.

30. The kit according to claim 25, wherein the progestogen in the dosage unit or pharmaceutical composition is micronized to a particle size of less than or equal to 100 μ

m.

31. The kit according to claim 25, wherein the progestogen in the dosage unit or pharmaceutical composition is micronized to a particle size of greater than 10 μ

m.

32. The kit according to claim 25, wherein the viscosity of the dosage unit or pharmaceutical composition is 53-60 cP.

33. The kit according to claim 25, wherein the pH of the dosage unit or pharmaceutical composition is between 4 and 7.5.

34. The kit according to claim 25, wherein the progestogen in the dosage unit or pharmaceutical composition is 1-50% weight/volume.

35. The kit according to claim 34, wherein the progestogen in the dosage unit or pharmaceutical composition is 5-20% weight/volume.

36. The kit according to claim 34, wherein the progestogen in the dosage unit or pharmaceutical composition is 10% weight/volume.

14. A pharmaceutical composition formulated for intralesional injection into an endometriotic lesion or fibroid comprising a micronized progestogen in an amount equivalent to 1.0-5.0 g of progesterone per lesion in a non-oil based suspension;

wherein the unit dosage is formulated with at least one viscosity increasing/suspending agent for increased retention at the site of injection and at least one excipient.

15. The pharmaceutical composition according to claim 14, wherein the progestogen is in an amount equivalent to 1-2 g of progesterone per lesion.

16. The pharmaceutical composition according to claim 14, wherein the progestogen is selected from the group consisting of progesterone, desogestrel, etonogestrel, gestodene, levonorgestrel, medroxyprogesterone, norethisterone, norgestimate, and norgestrel.

17. The pharmaceutical composition according to claim 14, wherein the progestogen is progesterone.

18. The pharmaceutical composition according to claim 14, wherein the progestogen is micronized to a particle size of less than or equal to 100 μ

m.

19. The pharmaceutical composition according to claim 14, wherein the progestogen is micronized to a particle size of greater than 10 μ

m.

20. The pharmaceutical composition according to claim 14, wherein the viscosity is 53-60 cP.

21. The pharmaceutical composition according to claim 14, wherein the pH is between 4 and 7.5.

22. The pharmaceutical composition according to claim 14, wherein the progestogen is 1-50% weight/volume.

23. The pharmaceutical composition according to claim 22, wherein the progestogen is 5-20% weight/volume.

24. The pharmaceutical composition according to claim 22, wherein the progestogen is 10% weight/volume.

37. The pharmaceutical composition of claim 14, wherein 99 wt. % of the progestogen has a particle size less than 10 μ

m and 75 wt. % of the progestogen has a particle size less than 5 μ

m.

38. The pharmaceutical composition of claim 37, wherein the viscosity is 53-60 cP.

39. A dosage unit comprising a micronized progestogen in an amount equivalent to 1.0-5.0 g of progesterone in a non-oil based suspension formulated for intralesional injection into an endometriotic lesion or fibroid, wherein the unit dosage is formulated with a hydrophilic colloid to increase retention to the site of injection.

40. The dosage unit of claim 39, wherein 99 wt. % of the progestogen has a particle size less than 10 μ

m and 75 wt % of the progestogen has a particle size less than 5 μ

m.

41. The dosage unit of claim 40, wherein hydrophilic colloid is carboxymethyl cellulose.

42. The dosage unit of claim 41, wherein the viscosity is 53-60 cP.