Claims
- 1. A pharmaceutical composition comprising a C-21 modified epothilone compound of formula I:
- 2. The composition of claim 1 wherein the epothilone compound is of formula Ia:
- 3. The composition of claim 2 wherein the epothilone compound is of formula Ib:
- 4. The composition of claim 3 wherein the epothilone compound is of formula Ic:
- 5. The composition of claim 1 further comprising a dibasic carboxylic acid and a pharmaceutically acceptable polymer.
- 6. The composition of claim 5 wherein said pharmaceutically acceptable polymer is a dextran polymer.
- 7. The composition of claim 6 prepared by a method comprising lyophilizing an aqueous solution comprising a C-21 modified epothilone compound, a dibasic carboxylic acid, and a dextran polymer.
- 8. The composition of claim 7 wherein said aqueous solution is adjusted to a pH of about 6.
- 9. The composition of claim 6 wherein said dextran polymer is dextran 40.
- 10. The composition of claim 6 wherein said dibasic carboxylic acid is succinic acid.
- 11. The composition of claim 6 wherein said dibasic carboxylic acid is citric acid.
- 12. The composition of claim 6 wherein said dextran polymer is dextran 40 and said dibasic carboxylic acid is succinic acid.
- 13. The composition of claim 6 wherein said dextran polymer is dextran 40 and said dibasic carboxylic acid is citric acid.
- 14. The composition of claim 4 further comprising a dibasic carboxylic acid and a pharmaceutically acceptable polymer.
- 15. The composition of claim 14 wherein said pharmaceutically acceptable polymer is a dextran polymer.
- 16. The composition of claim 15 prepared by a method comprising lyophilizing an aqueous solution comprising a C-21 modified epothilone compound, a dibasic carboxylic acid, and a dextran polymer.
- 17. The composition of claim 16 wherein said aqueous solution is adjusted to a pH of about 6.
- 18. The composition of claim 15 wherein said dextran polymer is dextran 40.
- 19. The composition of claim 15 wherein said dibasic carboxylic acid is succinic acid.
- 20. The composition of claim 15 wherein said dibasic carboxylic acid is citric acid.
- 21. The composition of claim 15 wherein said dextran polymer is dextran 40 and said dibasic carboxylic acid is succinic acid.
- 22. The composition of claim 15 wherein said dextran polymer is dextran 40 and said dibasic carboxylic acid is citric acid.
- 23. A method of preparing the pharmaceutical composition of claim 1 comprising the steps of:
(a) preparing an aqueous solution containing a C-21 modified epothilone derivative of formula Ia, a dibasic carboxylic acid, and a dextran polymer; (b) adjusting the pH of said solution to between about 5 and about 7; (c) lyophilizing said solution of step (b) to form a lyophile; and (d) drying said lyophile of step (c).
- 24. A method of preparing the pharmaceutical composition of claim 2 comprising the steps of:
(a) preparing an aqueous solution containing a C-21 modified epothilone derivative of formula Ia, a dibasic carboxylic acid, and a dextran polymer; (b) adjusting the pH of said solution to between about 5 and about 7; (c) lyophilizing said solution of step (b) to form a lyophile; and (d) drying said lyophile of step (c).
- 25. A method of preparing the pharmaceutical composition of claim 3 comprising the steps of:
(a) preparing an aqueous solution containing a C-21 modified epothilone derivative of formula Ib, a dibasic carboxylic acid, and a dextran polymer; (b) adjusting the pH of said solution to between about 5 and about 7; (c) lyophilizing said solution of step (b) to form a lyophile; and (d) drying said lyophile of step (c).
- 26. A method of preparing the pharmaceutical composition of claim 4 comprising the steps of:
(a) preparing an aqueous solution containing a C-21 modified epothilone derivative of formula Ic, a dibasic carboxylic acid, and a dextran polymer; (b) adjusting the pH of said solution to between about 5 and about 7; (c) lyophilizing said solution of step (b) to form a lyophile; and (d) drying said lyophile of step (c).
- 27. The method of claim 23 wherein said aqueous solution is adjusted to a pH of 6.0.
- 28. The method of claim 23 wherein said dextran polymer is dextran 40.
- 29. The method of claim 23 wherein said dibasic carboxylic acid is succinic acid.
- 30. The method of claim 23 wherein said dibasic carboxylic acid is citric acid.
- 31. The method of claim 23 wherein said dextran polymer is dextran 40 and said dibasic carboxylic acid is succinic acid.
- 32. The method of claim 23 wherein said dextran polymer is dextran 40 and said dibasic carboxylic acid is citric acid.
- 33. The method of claim 26 wherein said aqueous solution is adjusted to a pH of 6.0.
- 34. The method of claim 26 wherein said dextran polymer is dextran 40.
- 35. The method of claim 26 wherein said dibasic carboxylic acid is succinic acid.
- 36. The method of claim 26 wherein said dibasic carboxylic acid is citric acid.
- 37. The method of claim 26 wherein said dextran polymer is dextran 40 and said dibasic carboxylic acid is succinic acid.
- 38. The method of claim 26 wherein said dextran polymer is dextran 40 and said dibasic carboxylic acid is citric acid.
- 39. A unit dose of a pharmaceutical composition according to claim 22 comprising a sealed vial containing between about 10 mg and about 25 mg of citric acid, between about 50 mg and about 150 mg of dextran 40, and between about 5 mg and about 20 mg of [1S-[1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-3-[2-[2-(aminomethyl)-4-thiazolyl]-1-methylethenyl]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxabicyclo[14.1.0] heptadecane-5,9-dione.
- 40. A unit dose of a pharmaceutical composition according to claim 39 comprising a sealed vial containing between about 12.5 mg and about 16.7 mg of citric acid, between about 99 mg and about 132 mg of dextran 40, and between about 9 mg and about 12 mg of [1S-[1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-3-[2-[2-(aminomethyl)-4-thiazolyl]-1-methylethenyl]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxabicyclo[14.1.0] heptadecane-5,9-dione.
- 41. A unit dose according to claim 40 containing about 13.9 mg of citric acid, about 110 mg of dextran 40, and about 11 mg of [1S-[1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-3-[2-[2-(aminomethyl)-4-thiazolyl]-1-methylethenyl]-7,11-dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxabicyclo[14.1.0] heptadecane-5,9-dione.
- 42. A method for treating a patient in need of treatment with an epothilone compound of formula I:
- 43. A method for treating a patient in need of treatment with an epothilone compound of formula Ia:
- 44. A method for treating a patient in need of treatment with an epothilone compound of formula Ib:
- 45. A method for treating a patient in need of treatment with an epothilone compound of formula Ic:
- 46. The method of claim 42 wherein said epothilone compound is administered orally in a dose of about 0.05 mg/kg to 200 mg/kg.
- 47. The method of claim 42 wherein said epothilone compound is administered intravenously at a dose of about 1 mg/m2 to 100 mg/m2.
- 48. The method of claim 42 wherein said epothilone compound is administered daily or weekly.
- 49. The method of claim 42 wherein said epothilone compound is administered once every week.
- 50. The method of claim 42 wherein said epothilone compound is administered once every three weeks.
- 51. The method of claim 42 wherein said epothilone compound is administered at least once a day for 3 days with a period of at least 4 days where there is no treatment.
- 52. The method of claim 42 wherein said epothilone compound is administered at least once a day for 5 days with a period of at least 2 days where there is no treatment.
- 53. The method of claim 42 wherein said epothilone compound is administered intravenously over a period of 15 minutes to 90 minutes.
- 54. The method of claim 42 for the treatment of cancer.
- 55. The method of claim 54 wherein said patient has not previously been treated for cancer.
- 56. The method of claim 54 wherein said patient has previously been treated for cancer.
- 57. The method of claim 42 further comprising administering to said patient one or more additional agents to prevent nausea, vomiting, hypersensitivity, or gastric irritation.
- 58. The method of claim 45 wherein said epothilone compound is administered orally in a dose of about 0.05 mg/kg to 200 mg/kg.
- 59. The method of claim 58 wherein said epothilone compound is administered orally in a dose of about 0.05 mg/kg to 50 mg/kg.
- 60. The method of claim 45 wherein said epothilone compound is administered intravenously at a dose of about 1 mg/m2 to 100 mg/m2.
- 61. The method of claim 60 wherein said epothilone compound is administered intravenously at a dose of about 1 mg/m2 to 70 mg/m2.
- 62. The method of claim 61 wherein said epothilone compound is administered intravenously at a dose of about 10 mg/m2 to 70 mg/m2.
- 63. The method of claim 62 wherein said epothilone compound is administered intravenously at a dose of about 10 mg/m2 to 65 mg/m2.
- 64. The method of claim 63 wherein said epothilone compound is administered intravenously at a dose of about 50 mg/m2.
- 65. The method of claim 63 wherein said epothilone compound is administered intravenously at a dose of about 30 mg/m2.
- 66. The method of claim 45 wherein said epothilone compound is administered daily or weekly.
- 67. The method of claim 45 wherein said epothilone compound is administered once every week.
- 68. The method of claim 45 wherein said epothilone compound is administered once every three weeks.
- 69. The method of claim 45 wherein said epothilone compound is administered at least once a day for 3 days with a period of at least 4 days where there is no treatment.
- 70. The method of claim 45 wherein said epothilone compound is administered at least once a day for 5 days with a period of at least 2 days where there is no treatment.
- 71. The method of claim 45 wherein said epothilone compound is administered intravenously over a period of 15 minutes to 90 minutes.
- 72. The method of claim 45 for the treatment of cancer.
- 73. The method of claim 72 wherein said patient has not previously been treated for cancer.
- 74. The method of claim 72 wherein said patient has previously been treated for cancer.
- 75. The method of claim 72 wherein said cancer is refractory to radiation therapy.
- 76. The method of claim 72 wherein said cancer is refractory to anticancer chemotherapy.
- 77. The method of claim 72 wherein said cancer is a solid tumor.
- 78. The method of claim 45 further comprising administering to said patient one or more additional agents to prevent nausea, vomiting, hypersensitivity, or gastric irritation.
- 79. The method of claim 78 wherein said agent is an H1 or H2 antihistamine.
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of U.S. Provisional Application No. 60/380,634, filed May 15, 2002, incorporated herein by reference in its entirety.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60380634 |
May 2002 |
US |