Claims
- 1. A method for modulating the plasma circulation half-life of an active agent, said method comprising:
(a) providing a liposome having free active agent and precipitated active agent encapsulated therein; and (b) varying the amount of said active agent that is precipitated in said liposome.
- 2. The method of claim 1, wherein step (b) comprises varying said active agent to lipid ratio.
- 3. The method of claim 2, wherein said active agent to lipid ratio is varied by the addition of an empty liposome.
- 4. The method of claim 1, wherein step (b) comprises varying the size of said liposome.
- 5. The method of claim 1, wherein step (b) comprises adding a component that enhances precipitation of said active agent.
- 6. The method of claim 5, wherein said component is a mono-, di-, tri-, or polyvalent anion.
- 7. The method of claim 1, wherein step (b) comprises varying both said active agent to lipid ratio and the size of the liposome.
- 8. The method of claim 1, wherein said active agent is an antineoplastic drug.
- 9. The method of claim 8, wherein said antineoplastic drug is a camptothecin.
- 10. The method of claim 9, wherein said camptothecin is a member selected from the group consisting of irinotecan, topotecan, 9-amino camptothecin, 10,11-methylenedioxy camptothecin, 9-nitro camptothecin, TAS 103, 7-(4-methyl-piperazino-methylene)-10,11-ethylenedioxy-20(S)-camptothecin and 7-(2-N-isopropylamino)ethyl)-20(S)-camptothecin.
- 11. The method of claim 10, wherein said camptothecin is topotecan.
- 12. The method of claim 1, wherein said active antineoplastic drug is a vinca alkaloid.
- 13. The method of claim 12, wherein said vinca alkaloid is a member selected from the group consisting of vincristine, vinblastine, vinorelbine and vindesine.
- 14. The method of claim 1, wherein the precipitated active agent encapsulated in said liposome is at least 50% of said total active agent.
- 15. The method of claim 14, wherein the precipitated active agent encapsulated in said liposome is at least 60% of said total active agent.
- 16. The method of claim 15, wherein the precipitated active agent encapsulated in said liposome is at least 70% of said total active agent.
- 17. The method of claim 1, wherein said liposome comprises sphingomyelin and cholesterol.
- 18. The method of claim 17, wherein said liposome comprises sphingomyelin and cholesterol in a 55:45 ratio.
- 19. The method of claim 1, wherein the plasma circulation half-life of said active agent is modulated for optimum efficacy.
- 20. The method of claim 1, wherein the ratio of said active agent to lipid is about 0.005-1:1 (w/w).
- 21. The method of claim 20, wherein the ratio of said active agent to lipid is about 0.05-0.9:1 (w/w).
- 22. The method of claim 21, wherein the ratio of said active agent to lipid is about 0.1-0.5:1 (w/w).
- 23. A method for modulating the plasma circulation half-life of an active agent, said method comprising:
(a) providing a liposome having free active agent and precipitated active agent encapsulated therein; and (b) adding a liposome with no encapsulated active agent.
- 24. The method of claim 23, wherein the ratio of liposomes containing active agent to liposomes with no encapsulated agent is from about 1:0.5 to 1:1000.
- 25. The method of claim 24, wherein the ratio of liposomes containing active agent to liposomes with no encapsulated agent is from about 1:1 to 1:100.
- 26. The method of claim 25, wherein the ratio of liposomes containing active agent to liposomes with no encapsulated agent is from about 1:2 to 1:10.
- 27. The method of claim 26, wherein the ratio of liposomes containing active agent to liposomes with no encapsulated agent is from about 1:3 to 1:5.
- 28. The method of claim 23, wherein said active agent is an antineoplastic drug.
- 29. The method of claim 28, wherein said antineoplastic drug is a camptothecin.
- 30. The method of claim 29, wherein said camptothecin is a member selected from the group consisting of irinotecan, topotecan, 9-amino camptothecin, 10,11-methylenedioxy camptothecin, 9-nitro camptothecin, TAS 103, 7-(4-methyl-piperazino-methylene)-10,11-ethylenedioxy-20(S)-camptothecin and 7-(2-N-isopropylamino)ethyl)-20(S)-camptothecin.
- 31. The method of claim 30, wherein said camptothecin is topotecan.
- 32. A liposomal formulation, said liposomal formulation comprising:
a) an antineoplastic drug; and b) a liposome having free antineoplastic drug and precipitated antineoplastic drug, wherein the precipitated antineoplastic drug in said liposome is at least 50% of the total antineoplastic drug.
- 33. The liposomal formulation of claim 32, wherein said antineoplastic drug is a camptothecin.
- 34. The liposomal formulation of claim 33, wherein said camptothecin is a member selected from the group consisting of irinotecan, topotecan, 9-amino camptothecin, 10,11-methylenedioxy camptothecin, 9-nitro camptothecin, TAS 103, 7-(4-methyl-piperazino-methylene)-10,11-ethylenedioxy-20(S)-camptothecin and 7-(2-N-isopropylamino)ethyl)-20(S)-camptothecin.
- 35. The liposomal formulation of claim 34, wherein said camptothecin is topotecan.
- 36. The liposomal formulation of claim 33, wherein said antineoplastic drug is a vinca alkaloid.
- 37. The liposomal formulation of claim 32, wherein the free antineoplastic drug and the precipitated antineoplastic drug are different.
- 38. The liposomal formulation of claim 36, wherein said vinca alkaloid is a member selected from the group consisting of vincristine, vinblastine, vinorelbine and vindesine.
- 39. The liposomal formulation of claim 32, wherein the ratio of said antineoplastic drug to lipid is about 0.005-1:1 (w/w).
- 40. The liposomal formulation of claim 39, wherein the ratio of said antineoplastic drug:said lipid is about 0.05-0.9:1 (w/w).
- 41. The liposomal formulation of claim 40, wherein the ratio of said antineoplastic drug:said lipid is about 0.1-0.5:1 (w/w).
- 42. The liposomal formulation of claim 32, wherein said liposome comprises sphingomyelin and cholesterol.
- 43. The liposomal formulation of claim 42, wherein said liposome comprises sphingomyelin and cholesterol in a 55:45 ratio.
- 44. The liposomal formulation of claim 32, further comprising a liposome with no encapsulated active agent.
- 45. The liposomal formulation of claim 44, wherein the ratio of liposomes containing active agent to liposomes with no encapsulated agent is from about 1:0.5 to 1:1000.
- 46. The liposomal formulation of claim 45, wherein the ratio of liposomes containing active agent to liposomes with no encapsulated agent is from about 1:1 to 1:100.
- 47. The liposomal formulation of claim 46, wherein the ratio of liposomes containing active agent to liposomes with no encapsulated agent is from about 1:2 to 1:10.
- 48. The liposomal formulation of claim 47, wherein the ratio of liposomes containing active agent to liposomes with no encapsulated agent is from about 1:3 to 1:5.
- 49. A liposomal formulation, said liposomal formulation comprising:
a) an active agent; b) a liposome having free active agent and precipitated active agent encapsulated therein; and c) an empty liposome.
- 50. The liposomal formulation of claim 49, wherein the ratio of liposomes containing said active agent to said empty liposomes is from about 1:0.5 to 1:1000.
- 51. The liposomal formulation of claim 50, wherein the ratio of liposomes containing said active agent to said empty liposomes is from about 1:1 to 1:100.
- 52. The liposomal formulation of claim 51, wherein the ratio of liposomes containing said active agent to said empty liposomes is from about 1:2 to 1:10.
- 53. The liposomal formulation of claim 52, wherein the ratio of liposomes containing said active agent to said empty liposomes is from about 1:3 to 1:5.
- 54. The liposomal formulation of claim 49, wherein said active agent is an antineoplastic drug.
- 55. The liposomal formulation of claim 54, wherein said antineoplastic drug is a camptothecin.
- 56. The liposomal formulation of claim 55, wherein said camptothecin is a member selected from the group consisting of irinotecan, topotecan, 9-amino camptothecin, 10,11-methylenedioxy camptothecin, 9-nitro camptothecin, TAS 103, 7-(4-methyl-piperazino-methylene)-10,11-ethylenedioxy-20(S)-camptothecin and 7-(2-N-isopropylamino)ethyl)-20(S)-camptothecin.
- 57. The liposomal formulation of claim 56, wherein said camptothecin is topotecan.
- 58. The liposomal formulation of claim 57, wherein said antineoplastic drug is a vinca alkaloid.
- 59. The liposomal formulation of claim 58, wherein said vinca alkaloid is a member selected from the group consisting of vincristine, vinblastine, vinorelbine and vindesine.
- 60. The liposomal formulation of claim 49, wherein the ratio of said active agent to lipid is about 0.005-1:1 (w/w).
- 61. The liposomal formulation of claim 60, wherein the ratio of said active agent to lipid is about 0.05-0.9:1 (w/w).
- 62. The liposomal formulation of claim 61, wherein the ratio of said active agent to lipid is about 0.1-0.5:1 (w/w).
- 63. The liposomal formulation of claim 49, wherein said liposome comprises sphingomyelin and cholesterol.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is related to U.S. Provisional Application No. 60/215,556, filed Jun. 30, 2000, entitled “Liposomal Camptothecins and Uses Thereof,” and U.S. Provisional Application No. 60/264,616, filed Jan. 26, 2001, entitled “Liposomal Antineoplastic Drugs and Uses Thereof,” both of which are incorporated herein by reference in their entireties for all purposes. U.S. patent application Ser. No. ______, bearing Attorney Document No. 016303-008020, filed Jun. 29, 2001, entitled “Liposomal Camptothecins and Uses Thereof,” is hereby incorporated by reference for all purposes.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60264616 |
Jan 2001 |
US |
|
60215556 |
Jun 2000 |
US |