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1. WO2001072319 - FORMULATIONS DE CATECHINES DU THE ET PROCEDES DE FABRICATION ASSOCIES

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]

WHAT IS CLAIMED IS:

1. A method of producing a tea catechin formulation which has reduced levels of

EGCg comprising the steps of:
a) incubating a mixture comprising green tea extract and tannase where said green tea extract comprises tea catechins with a gallate moiety for a time sufficient for the tannase to cleave the gallate moiety; and
b) extracting the incubated mixture with an organic solvent.

2. The method according to claim 1 further comprising the step of:
c) removing impurities from the extracted mixture.

3. The method according to claim 1 or 2 further comprising the step:
d) adding pure EGCg to the extracted mixture.

4. The method of claim 1 wherein the incubation step is carried out at about 38-40°C for about 30 minutes.

5. The method of claim 1 wherein the incubation step is carried out in a buffered solution having a pH between 5 and 7.

6. The method of claim 5 wherein the buffered solution has a pH between 6.0 and 6.2.

7. The method of claim 5 wherein the buffered solution is combination of

NaH2PO4 and K2HPO4.

8. The method of claim 1 wherein the tannase has an activity of about 500 units/g.

9. The method of claim 1 wherein the organic solvent is ethyl acetate.

10. A method of preparing a catechin composition with a reduced level of EGCg comprising the steps of:
a) incubating a mixture of green tea extract and tannase in a buffered solution having a pH between about 6 and about 6.5 at about 38-40°C for where said green tea extract comprises tea catechins with a gallate moiety for about 30 minutes; and b) extracting the incubated mixture having reduced levels of EGCg with
ethyl acetate; and
c) removing impurities from the extracted mixture.

11. The method of claim 2 wherein the tannase is immobilized on a resin prior to incubation.

12. The method of claim 2 or 11 wherein the removal of impurities utilizes liquid chromatography and a solvent of 90% ethanol.

13. The method of claim 2 or 11 wherein the primary impurity removed is gallic acid.

14. A pharmaceutical composition for use in a mammal comprising tea catechins, wherein the EGCg content is less than 0.01% of the total catechins and a pharmaceutically acceptable carrier.

15. The pharmaceutical composition of claim 14 wherein gallic acid has been removed.

16. A pharmaceutical composition for use in a mammal comprising tea catechins, wherein the EGCg content is less than 0.1 % of the total catechins and a pharmaceutically acceptable carrier.

17. The pharmaceutical composition of claim 16 wherein gallic acid has been removed.

18. A pharmaceutical composition for use in a mammal comprising tea catechins, wherein the EGCg content is less than 1.0% of the total catechins and a pharmaceutically acceptable carrier.

19. The pharmaceutical composition of claim 18 wherein gallic acid has been removed.

20. A pharmaceutical composition for use in a mammal comprising tea catechins, wherein the EGCg content is less than 5% of the total catechins and a pharmaceutically acceptable carrier.

21. The pharmaceutical composition of claim 20 wherein gallic acid has been removed.

22. A pharmaceutical composition for use in a mammal comprising tea catechins, wherein the ratio of EC to EGCg concentration is about 10:1, and a pharmaceutically acceptable carrier.

23. The pharmaceutical composition of claim 22 wherein gallic acid has been removed.

24. A pharmaceutical composition for use in a mammal comprising tea catechins, wherein the ratio of EC to EGCg concentration is about 100:1, and a pharmaceutically acceptable carrier.

25. The pharmaceutical composition of claim 24 wherein gallic acid has been removed.

26. A pharmaceutical composition for use in a mammal comprising tea catechins, wherein the ratio of EC to EGCg concentration is about 1000:1, and a pharmaceutically acceptable carrier.

27. The pharmaceutical composition of claim 26 wherein gallic acid has been removed.

28. A dietary or nutritional supplement for use in a mammal comprising a composition of tea catechins effective to prevent cancer, wherein the content of EGCg is less than 0.01%) of the total catechins, and an ingestable carrier.

29. The supplement of claim 28 wherein gallic acid has been removed.

30. A dietary or nutritional supplement for use in a mammal comprising a composition of tea catechins effective to prevent cancer, wherein the content of EGCg is less than 0.1 %> of the total catechins, and an ingestable carrier.

31. The supplement of claim 30 wherein gallic acid has been removed.

32. A dietary or nutritional supplement for use in a mammal comprising a composition of tea catechins effective to prevent cancer, wherein the content of EGCg is less than 1.0% of the total catechins, and an ingestable carrier.

33. The supplement of claim 32 wherein gallic acid has been removed.

34. A dietary or nutritional supplement for use in a mammal comprising a composition of tea catechins effective to prevent cancer, wherein the content of EGCg is less than 5% of the total catechins, and an ingestable carrier.

35. The supplement of claim 34 wherein gallic acid has been removed.

36. A dietary or nutritional or nutritional supplement for use in a mammal comprising a composition of tea catechins effective to prevent cancer, wherein the ratio of EC to EGCg concentration is about 10:1, and an ingestable carrier.

37. The supplement of claim 36 wherein gallic acid has been removed.

38. A dietary or nutritional supplement for use in a mammal comprising a composition of tea catechins effective to prevent cancer, wherein the ratio of EC to EGCg concentration is about 100:1, and an ingestable carrier.

39. The supplement of claim 38 wherein gallic acid has been removed.

40. A dietary or nutritional supplement for use in a mammal comprising a composition of tea catechins effective to prevent cancer, wherein the ratio of EC to EGCg concentration is about 1000:1, and an ingestable carrier.

41. The supplement of claim 40 wherein gallic acid has been removed.

42. A method for treating cancer in a mammal which comprises administering to a mammal in need of cancer treatment, wherein the cancer is a type having cancer cells which express tNOX, a therapeutically effective amount of a composition comprising tea catechins with a reduced level of EGCg.

43. A method for treating a solid tumor in a mammal which comprises
administering to a mammal with a solid tumor, wherein the solid tumor comprises cancer cells which express tNOX, a therapeutically effective amount of a composition comprising tea catechins with a reduced level of EGCg.

44. The method of claim 42 wherein the mammal is a human.

45. The method of claim 43 wherein the mammal is a human.

46. The method of claim 44 wherein the cancer is selected from a group comprising rectal carcinoma, colon carcinoma, breast carcinoma, ovarian carcinoma, small cell lung carcinoma, colon carcinoma, chronic lymphocytic carcinoma, hairy cell leukemia, osophogeal carcinoma, prostate carcinoma, breast cancer, myeloma, and lymphoma.

47. The method of claim 45 wherein the tumor is a tumor of epithelial tissue, lymphoid tissue, connective tissue, bone, or central nervous system.

48. The method of claim 44 wherein the human is immunosuppressed by reason of having undergone anti-cancer therapy prior to administration of said composition comprising tea catechins with a reduced level of EGCg.

49. A method for treating metastases in a human which comprises administering to a human having a primary cancer, wherein the cancer is a type having cancer cells which express tNOX, a therapeutically effective amount of a composition comprising tea catechins with a reduced level of EGCg.

50. A method for treating cancer in a mammal which comprises administering to a mammal in need of therapy a therapeutically effective amount of a catechin composition with a reduced level of EGCg, or a pharmaceutically acceptable salt thereof, in combination with an effective amount of at least one other chemotherapeutic agent.

51. The method of claim 50 wherein said other anti-cancer agent is selected from the group consisting of adriamycin and adriamycin conjugates, mechlorethamine,
cyclophosphamide, ifosfamide, melphalan, chlorambucil, hexamethylmelamine, thiotepa, busulfan, carmustine, lomustine, semustine, streptozocin, dacarbazine, methotrexate, fluorouacil, floxuridie, cytarabine, mercaptopurine, thioguanine, pentostatin, vinblastine, vincristine, etoposide, teniposide, actinomycin D, daunorubicin, doxorubicin, bleomycin, plicamycin, mitomycin, L-asparaginase, interferon-alpha, cisplatin, carboplatin, mitoxantrone, hydroxyurea, procarbazine, mitotane, aminoglutethimide,, prednisone, hydroxyprogesterone caproate, medroxyprogesterone acetate, megestrol acetate, diethylstilbestrol, ethinyl estradiol, tamoxifen, testosterone propionate, fluoxymesterone, flutamide, leuprolide, acetogenins, e.g., bullatacin, and quassanoids, e.g. simalikalactone D and glaucarubolone, and pharmaceutically acceptable derivatives thereof.

o 52. The method of claim 42, 43, 49 or 50 wherein said administration is made parenterally, orally, or directly into the tumor.

53. The method of claim 42, 43, 49 or 50 wherein said administration is made via an implantation device.
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54. The method of claim 42, 43, 49 or 50 wherein said administration is made with a sustained release formulation.

55. The method of claim 42, 43, 49 or 50 wherein the EGCg content is less than 0 0.01 % of the total catechins.

56. The method of claim 55 wherein gallic acid has been removed.

57. The method of claim 42, 43, 49 or 50 wherein the EGCg content is less than 5 0.1 %> of the total catechins.

58. The method of claim 57 wherein gallic acid has been removed.

59. The method of claim 42, 43, 49 or 50 wherein the EGCg content is less than 0 1.0% of the total catechins.

60. The method of claim 59 wherein gallic acid has been removed.

61. The method of claim 42, 43, 49 or 50 wherein the ratio of EC to EGCg 5 concentration is about 10:1.

62. The method of claim 61 wherein gallic acid has been removed.

63. The method of claim 42, 43, 49 or 50 wherein the ratio of EC to EGCg concentration is about 100: 1.

64. The method of claim 63 wherein gallic acid has been removed.

65. The method of claim 42, 43, 49 or 50 wherein the ratio of EC to EGCg concentration is about 1000:1.

66. The method of claim 65 wherein gallic acid has been removed.