Anti-neoplastic compositions comprising extracts of black cohosh

• US 20050008717A1
• Filed: 12/23/2003
• Published: 01/13/2005
• Est. Priority Date: 12/27/2002
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Einbond, Linda Saxe, Weinstein, I. Bernard
• Granted Patent: US 7,407,675 B2
• Time in Patent Office: Days
• US Class Current: 424/764
• 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 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 36/71 Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia

Abstract

The present invention provides a composition for use in treating or preventing neoplasia, comprising an effective actein. The present invention also provides a composition for use in treating or preventing neoplasia, comprising an effective anti-neoplastic amount of an ethyl acetate extract of black cohosh. The present invention further provides a combination of anti-neoplastic agents, comprising an effective anti-neoplastic amount of an ethyl acetate extract of black cohosh and an effective anti-neoplastic amount of at least one additional chemopreventive or chemotherapeutic agent. Methods for treating and preventing neoplasia are also provided.

Claims

1. A composition for use in treating or preventing neoplasia, comprising an effective anti-neoplastic amount of an ethyl acetate extract of black cohosh.

2. The composition of claim 1, wherein the ethyl acetate extract comprises at least one triterpene glycoside compound.

3. The composition of claim 2, wherein the triterpene glycoside compound is selected from the group consisting of actein, cimifugoside, cimigenol glycoside, cimiracemoside A, and 23-epi-26-deoxyactein.

4. The composition of claim 3, wherein the triterpene glycoside compound is actein.

5. The composition of claim 4, wherein the effective anti-neoplastic amount of actein is between about 0.5 μ

g/ml and about 40.0 μ

g/ml.

6. The composition of claim 5, wherein the effective anti-neoplastic amount of actein is between about 1.0 μ

g/ml and about 3.0 μ

g/ml.

7. The composition of claim 1, wherein the ethyl acetate extract comprises at least one aglycone.

8. The composition of claim 7, wherein the at least one aglycone is cimigenol.

26. A pharmaceutical composition, comprising the composition of claim 1, 9, 22, or 24 and a pharmaceutically acceptable carrier.

9. A composition of anti-neoplastic agents, comprising an effective anti-neoplastic amount of an ethyl acetate extract of black cohosh and an effective anti-neoplastic amount of at least one additional chemopreventive or chemotherapeutic agent.

10. The composition of claim 9, which is a synergistic combination.

11. The composition of claim 9, wherein the anti-neoplastic agents are combined in a single formulation.

12. The composition of claim 9, wherein a separate, individual formulation of the ethyl acetate extract of black cohosh is combined with a separate, individual formulation of the at least one additional chemopreventive or chemotherapeutic agent.

13. The composition of claim 9, wherein the ethyl acetate extract comprises a triterpene glycoside compound.

14. The composition of claim 13, wherein the triterpene glycoside compound is selected from the group consisting of actein, cimifugoside, cimigenol glycoside, cimiracemoside A, and 23-epi-26-deoxyactein.

15. The composition of claim 14, wherein the triterpene glycoside compound is actein.

16. The composition of claim 9, wherein the ethyl acetate extract comprises at least one aglycone.

17. The composition of claim 16, wherein the at least one aglycone is cimigenol.

18. The composition of claim 9, wherein the at least one additional chemopreventive or chemotherapeutic agent is selected from the group consisting of adriamycin, cisplatin, docetaxel, doxorubicin, 5-fluorouracil, herceptin, paclitaxel, tamoxifen, and vinblastine.

19. The composition of claim 18, wherein the at least one additional chemopreventive or chemotherapeutic agent is paclitaxel.

20. The composition of claim 9, wherein the ethyl acetate extract of black cohosh comprises actein and the at least one additional chemopreventive or chemotherapeutic agent is paclitaxel.

21. The composition of claim 20, wherein the effective anti-neoplastic amount of actein is between about 0.5 μ

g/ml and about 40.0 μ

g/ml, and the effective anti-neoplastic amount of paclitaxel is between about 0.5 nM and about 5.0 nM.

22. A composition for use in treating or preventing neoplasia, comprising an effective anti-neoplastic amount of actein.

23. The composition of claim 22, wherein the neoplasia is a carcinoma, a lymphocytic leukemia, a myeloid leukemia, a malignant lymphoma, a malignant melanoma, a myeloproliferative disease, a sarcoma, a brain tumor, a childhood tumor, or a mixed type of neoplasia.

24. The composition of claim 22, further comprising an effective anti-neoplastic amount of at least one additional chemopreventive or chemotherapeutic agent.

25. A composition for use in treating or preventing disorders caused by or related to the abnormality of at least one factor selected from the group consisting of cyclin D1, cdk4, Her2, Iκ

B, Iκ

κ

B, NF-κ

B, p21, p27, PPARγ

, and ppRb, wherein the composition comprises an effective amount of actein.

27. A method for treating or preventing neoplasia in a subject, comprising administering to the subject an amount of an ethyl acetate extract of black cohosh effective to treat or prevent the neoplasia.

28. The method of claim 27, wherein the neoplasia is a carcinoma, a lymphocytic leukemia, a myeloid leukemia, a malignant lymphoma, a malignant melanoma, a myeloproliferative disease, a sarcoma, a brain tumor, a childhood tumor, or a mixed type of neoplasia.

29. The method of claim 28, wherein the carcinoma is breast cancer, colon cancer, lung cancer, ovarian cancer, prostate cancer, bladder cancer, uterine cancer, or skin cancer.

30. The method of claim 27, wherein the ethyl acetate extract comprises at least one triterpene glycoside compound.

31. The method of claim 30, wherein the triterpene glycoside compound is actein.

32. The method of claim 31, wherein the effective amount of actein is between about 0.5 μ

g/ml and about 40.0 μ

g/ml.

33. The method of claim 27, wherein the ethyl acetate extract comprises at least one aglycone.

34. The method of claim 33, wherein the at least one aglycone is cimigenol.

44. The method of claim 33, wherein the effective amount of actein is between about 0.5 μ

g/ml and about 40.0 μ

g/ml, and the effective amount of paclitaxel is between about 0.5 nM and about 5.0 nM.

35. A method for treating or preventing neoplasia in a subject, comprising administering to the subject an amount of an ethyl acetate extract of black cohosh effective to treat or prevent the neoplasia, in combination with an amount of at least one additional chemopreventive or chemotherapeutic agent effective to treat or prevent the neoplasia.

36. The method of claim 35, wherein a synergistic anti-neoplastic effect results.

37. The method of claim 35, wherein administration is concurrent.

38. The method of claim 35, wherein administration is sequential.

39. The method of claim 35, wherein administration is alternate.

40. The method of claim 35, wherein the ethyl acetate extract comprises actein.

41. The method of claim 35, wherein the at least one additional chemopreventive or chemotherapeutic agent is selected from the group consisting of cisplatin, docetaxel, doxorubicin, 5-fluorouracil, herceptin, paclitaxel, tamoxifen, and vinblastine.

42. The method of claim 41, wherein the at least one additional chemopreventive or chemotherapeutic agent is paclitaxel.

43. The method of claim 35, wherein the ethyl acetate extract of black cohosh comprises actein and the at least one additional chemopreventive or chemotherapeutic agent is paclitaxel.

45. A method for treating or preventing neoplasia in a subject, comprising administering to the subject an amount of actein effective to treat or prevent the neoplasia.

46. The method of claim 45, wherein the neoplasia is a carcinoma, a lymphocytic leukemia, a myeloid leukemia, a malignant lymphoma, a malignant melanoma, a myeloproliferative disease, a sarcoma, a brain tumor, a childhood tumor, or a mixed type of neoplasia.

47. The method of claim 46, wherein the carcinoma is breast cancer, colon cancer, lung cancer, ovarian cancer, prostate cancer, bladder cancer, uterine cancer, or skin cancer.

48. The method of claim 45, further comprising administering to the subject an amount of at least one additional chemopreventive or chemotherapeutic agent effective to treat or prevent the neoplasia.

49. The method of claim 48, wherein the at least one additional chemopreventive or chemotherapeutic agent is selected from the group consisting of cisplatin, docetaxel, doxorubicin, 5-fluorouracil, herceptin, paclitaxel, tamoxifen, and vinblastine.

50. A method for treating or preventing disorders in a subject caused by or related to the abnormality of at least one factor selected from the group consisting of cyclin D1, cdk4, Her2, Iκ

B, Iκ

κ

B, NF-κ

B, p21, p27, PPARγ

, and ppRb, comprising administering to the subject an amount of actein effective to treat or prevent the disorder.