Platinum aggregates and process for producing the same

• US 20040101553A1
• Filed: 08/04/2003
• Published: 05/27/2004
• Est. Priority Date: 08/02/2002
• Status: Abandoned Application

• Current Assignee: Transave Inc. (Insmed Incorporated)
• Original Assignee: Transave Inc. (Insmed Incorporated)
• Inventors: Lee, Jin, Boni, Lawrence T., Miller, Brian S., Wu, Fangjun
• Application Number:
  US10/634,144
• Publication Number:
  US 20040101553A1
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1277 Processes for preparing; Proliposomes
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A composition and process for making the composition, the composition comprising a liposome and active platinum compound, the liposome containing one or more lipids, with a high active platinum compound to lipid ratio.

Claims

1. ) A composition comprising a liposome or lipid complex and an entrapped active platinum compound, the liposome or lipid complex containing one or more lipids, wherein the active platinum compound to lipid ratio is from 1:

50 to 1;

2 by weight.

2. ) The composition of claim 1, wherein the active platinum compound to lipid ratio is from 1:

50 to 1;

5 by weight.

3. ) The composition of claim 1, wherein the active platinum compound to lipid ratio is from 1:

50 to 1;

10 by weight.

4. ) The composition of claim 1, wherein the active platinum compound is cisplatin.

5. ) The composition of claim 1, wherein the active platinum compound to lipid ratio is from 1:

25 to 1;

15 by weight.

6. ) The composition of claim 5, wherein the active platinum compound is cisplatin.

7. ) The composition of claim 6, the one or more lipids comprise DPPC.

8. ) The composition of claim 7, the one or more lipids comprise cholesterol.

9. ) The composition of claim 7, the one or more lipids comprise 50-100 [90?] mol % DPPC and 0-50 mol % cholesterol.

10. ) The composition of claim 7, the one or more lipids comprise 50-65 mol % DPPC and 35-50 mol % cholesterol.

29. ) A pharmaceutical formulation comprising the composition of claim 1 and a pharmaceutically acceptable carrier or diluent.

30. ) A pharmaceutical formulation comprising the composition of claim 1, adapted for inhalation by a patient.

31. ) A pharmaceutical formulation comprising the composition of claim 1, adapted for injection into a patient.

11. ) A process for making a platinum aggregate comprising the steps of:

(a) combining an active platinum compound and a hydrophobic matrix carrying system;

(b) establishing the mixture at a first temperature; and

(c) thereafter establishing the mixture at a second temperature, which second temperature is cooler than the first temperature;

wherein the steps (b) and (c) are effective to increase the encapsulation of active platinum compound.

12. ) The process of claim 11, further comprising sequentially repeating the steps (b) and (c) for a total of two or more cycles.

13. ) The process of claim 11, wherein the active platinum compound solution is produced by dissolving active platinum compound in a saline solution to form a platinum solution.

14. ) The process of claim 13, wherein the active platinum compound is cisplatin

15. ) The process of claim 11, wherein the hydrophobic matrix carrying system comprises liposome or lipid complex-forming lipids.

16. ) The process of claim 15, wherein the one or more lipids comprise DPPC.

17. ) The process of claim 15, wherein the one or more lipids further comprise cholesterol.

18. ) The process of claim 11, wherein the hydrophobic matrix carrying system is produced by dissolving one or more lipids in ethanol to form a lipid solution and injecting the lipid solution into an aqueous medium containing active platinum compound.

19. ) The process of claim 11, further comprising sequentially repeating the steps (b) and (c) for a total of three or more cycles.

20. ) The process of claim 19, wherein the step (c) comprises establishing the mixture at a temperature from −

25 degrees Celsius to 25 degrees Celsius.

21. ) The process of claim 19, wherein step (c) comprises establishing the mixture at a temperature from −

5 degree Celsius to 5 degrees Celsius.

22. ) The process of claim 19, wherein the step (b) comprises establishing the mixture at a temperature from 4 degrees Celsius to 75 degrees Celsius.

23. ) The process of claim 19, wherein the step (b) comprises establishing the mixture at a temperature from 45 degrees Celsius to 55 degrees Celsius.

24. ) The process of claim 11, wherein the temperature differential between steps (b) and (c) is 25 degrees Celsius or more.

25. ) The process of claim 24, wherein the temperature established in step (b) is 50 degrees Celsius or more.

26. ) The process of claim 11, wherein the temperature established in step (b) is 50 degrees Celsius or more.

27. ) A platinum aggregate produced by the method of claim 11.

28. ) A platinum aggregate produced by the method of claim 14.

32. ) The process of claim 11, further comprising, after all of steps (b) and steps (c) have been completed:

(d) removing un-entrapped active platinum compound by filtering through a membrane having a molecular weight cut-off selected to retain desired liposomes or lipid complexes and adding a liposome or lipid complex compatible liquid to wash out un-entrapped active platinum compound.