IP Library Granted Patent US 7,235,540
Granted Patent B2
US 7,235,540 · App. 11/235,574 · Granted Jun 26, 2007

Methods of using 2-methoxyestradiol of high purity

Assignee: EntreMed, Inc.
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Quick Facts
Patent No.
US 7,235,540
App. No.
11/235,574
Granted
Jun 26, 2007
Kind
B2
Abstract

2-methoxyestradiol having greater than 98% purity is obtained by synthetic or purification methods. This highly pure 2-methoxy estradiol, lacking estrogenic components, is particularly suitable for clinical use in humans. The purification methods of the invention involve the use of liquid-solid chromatography (LSC) to separate 2-ME2 from other compounds. The chromatographic media is preferably silica. The solvent system comprises a non-polar solvent, such as chloroform, and a polar solvent, such as methanol.

Claims (35)

1. A method of treating a disease or condition in a human or an animal selected from atherosclerosis, tumor growth, proliferation of solid tumors, tumor angiogenesis, vascular malfunctions, endometriosis, retinopathies, arthropathies, inflammatory response or immune response comprising administering to the human or animal an effective disease or condition treating amount of a composition substantially free of steroid contaminants having estrogenic or carcinogenic effects comprising 2-methoxyestradiol having a purity greater than 99.5% as determined by HPLC.

2. The method of claim 1 , wherein said composition comprises less than 0.03% estradiol and less than 0.02% estrone.

3. The method of claim 1 , wherein said composition comprises less than 0.01% estradiol and less than 0.01% estrone.

4. The method of claim 1 , wherein said composition comprises less than 0.02% 2-hydroxyestradiol.

5. The method of claim 1 , wherein said composition comprises less than 0.02% 4-hydroxyestradiol.

6. The method of claim 1 , wherein said composition comprises less than 0.02% 4-methoxyestradiol.

7. The method of claim 1 , wherein said composition comprises 0.01% or less estradiol, 0.02% or less 2-hydroxyestradiol, 0.01% or less 4-hydroxyestradiol, 0.01% or less 4-methoxyestradiol and 0.01% or less estrone.

8. The method of claim 1 , wherein said disease or condition is atherosclerosis.

9. The method of claim 1 , wherein said disease or condition is tumor growth.

10. The method of claim 1 , wherein said disease or condition is proliferation of solid tumors.

11. The method of claim 1 , wherein said disease or condition is tumor angiogenesis.

12. The method of claim 1 , wherein said disease or condition is vascular malfunctions.

13. The method of claim 1 , wherein said disease or condition is endometriosis.

14. The method of claim 1 , wherein said disease or condition is retinopathy.

15. The method of claim 1 , wherein said disease or condition is arthropathy.

16. The method of claim 1 , wherein said disease or condition is inflammatory response.

17. The method of claim 1 , wherein said disease or condition is immune response.

18. A method of treating a disease or condition in a human or an animal selected from atherosclerosis, tumor growth, proliferation of solid tumors, tumor angiogenesis, vascular malfunctions, endometriosis, retinopathies, arthropathies, inflammatory response or immune response comprising administering to the human or animal an effective disease or condition treating amount of a composition substantially free of steroid.contaminants having estrogenic or carcinogenic effects comprising 2-methoxyestradiol having a purity greater than 98.0% and containing less than 0.03% estradiol and less than 0.02% estrone.

19. The method of claim 18 , wherein said composition comprises less than 0.01% estradiol and less than 0.01% estrone.

20. The method of claim 18 , wherein said composition comprises 0.01% or less estradiol, 0.02% or less 2-hydroxyestradiol, 0.01% or less 4-hydroxyestradiol, 0.01% or less 4-methoxyestradiol and 0.01% or less estrone.

21. The method of claim 18 , wherein said 2-methoxyestradiol has a purity greater than 99.0%.

22. The method of claim 21 , wherein said composition comprises less than 0.01% estradiol and less than 0.01% estrone.

23. The method of claim 21 , wherein said composition comprises 0.01% or less estradiol, 0.02% or less 2-hydroxyestradiol, 0.01% or less 4-hydroxyestradiol, 0.01% or less 4-methoxyestradiol and 0.01% or less estrone.

24. The method of claim 21 , wherein said disease or condition is a atherosclerosis.

25. The method of claim 21 , wherein said disease or condition is tumor growth.

26. The method of claim 21 , wherein said disease or condition is proliferation of solid tumors.

27. The method of claim 21 , wherein said disease or condition is tumor angiogenesis.

28. The method of claim 21 , wherein said disease or condition is vascular malfunctions.

29. The method of claim 21 , wherein said disease or condition is endometriosis.

30. The method of claim 21 , wherein said disease or condition is retinopathy.

31. The method of claim 21 , wherein said disease or condition is arthropathy.

32. The method of claim 21 , wherein said disease or condition is inflammatory response.

33. The method of claim 21 , wherein said disease or condition is immune response.

34. A method of treating tumor growth, proliferation of solid tumors or tumor angiogenesis in a human or an animal comprising administering to the human or animal an effective tumor treating amount of a composition substantially free of steroid contaminants having estrogenic or carcinogenic effects comprising 2-methoxyestradiol having a purity greater than 99.0% and containing 0.01% or less estradiol, 0.02% or less 2-hydroxyestradiol, 0.01% or less 4-hydroxyestradiol, 0.01% or less 4-methoxyestradiol and 0.01% or less estrone.

35. A method of treating arthropathy in a human or an animal comprising administering to the human or animal an effective arthropathy treating amount of a composition substantially free of steroid contaminants having estrogenic or carcinogenic effects comprising 2-methoxyestradiol having a purity greater than 99.0% and containing 0.01% or less estradiol, 0.02% or less 2-hydroxyestradiol, 0.01% or less 4-hydroxyestradiol, 0.01% or less 4-methoxyestradiol and 0.01% or less estrone.

Assignments (2)
CHANGE OF NAME Recorded Aug 7, 2014
From: ENTREMED, INC.
To: CASI PHARMACEUTICALS, INC.
Reel/Frame 033497/0728 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 27, 2005
From: SHAH, JAMSHED; AGOSTON, GREGORY; TRESTON, ANTHONY
To: ENTREMED, INC.
Reel/Frame 016692/0941 →
Continuity (3)
Continuation 0964438700 · Aug 23, 2000
Provisional Application 6015029300 · Aug 23, 1999
Related Publication 20060025619A1 · Feb 2, 2006