Oxaliplatin formulations

• US 6,306,902 B1
• Filed: 02/22/1999
• Issued: 10/23/2001
• Est. Priority Date: 02/25/1998
• Status: Expired due to Term

• Current Assignee: Sanofi-Aventis (Sanofi-Synthélabo SA)
• Original Assignee: Sanofi-Synthelabo Incorporated (Sanofi-Aventis U.S., LLC)
• Inventors: Anderson, Nicholas H., England, David A., Gray, Martin R., Brown, Stephen, Blundell, Ross
• Primary Examiner(s): Goldberg, Jerome D.
• Application Number:
  US09/255,087
• Time in Patent Office: 974 Days
• Field of Search: 514/492
• US Class Current: 514/492
• CPC Class Codes: A61K 31/282 Platinum compounds
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The invention relates to pharmaceutically stable oxaliplatin solution formulations, to the method of use thereof in the treatment of cancer tumors, to processes for the preparation of such formulations, and to a method for stabilizing solutions of oxaliplatin.

Claims

1. A stable oxaliplatin solution formulation comprising a therapeutically effective amount of oxaliplatin, an effective stabilizing amount of a buffering agent and a pharmaceutically acceptable carrier wherein the buffering agent is oxalic acid or an alkali metal salt thereof.

2. A formulation according to claim 1 wherein the pharmaceutically acceptable carrier is water and the buffering agent is oxalic acid or an alkali metal salt thereof.

3. A formulation according to claim 2 wherein the buffering agent is oxalic acid or sodium oxalate.

4. A formulation according to claim 3 wherein the buffering agent is oxalic acid.

5. The formulation according to claim 1 wherein the amount of buffering agent is a molar concentration in the range of from

(a) about 5×

10<sup>−

5</sup> M to about 1×

10<sup>−

2</sup> M,

(b) about 5×

10<sup>−

5</sup> M to about 5×

10<sup>−

3</sup> M,

(c) about 5×

10<sup>−

5</sup> M to about 2×

10<sup>−

3</sup> M,

(d) about 1×

10<sup>−

4</sup> M to about 2×

10<sup>−

3</sup> M, or

(e) about 1×

10<sup>−

4</sup> M to about 5×

10<sup>−

4</sup> M.

6. A formulation according to claim 5 wherein the amount of buffering agent is a molar concentration in the range of from about 1×

10<sup>−

4</sup> M to about 5×

10<sup>−

4</sup> M.

7. A formulation acording to claim 6 wherein the amount of buffering agent is a molar concentration of about 2×

10<sup>−

4</sup> M.

8. A formulation according to claim 6 wherein the amount of buffering agent is a molar concentration of about 4×

10<sup>−

4</sup> M.

9. A formulation according to claim 1 wherein the amount of oxaliplatin is from about 1 to about 7 mg/mL.

10. A formulation according to claim 1 wherein the amount of oxaliplatin is from about 1 to about 5 mg/mL.

11. A formulation according to claim 1 wherein the amount of oxaliplatin is from about 2 to about 5 mg/mL.

12. A formulation according to claim 1 wherein the amount of oxaliplatin is about 5 mg/mL.

13. A formulation according to claim 4 wherein the amount of oxaliplatin is about 5 mg/mL and the amount of buffering agent is a molar concentration of about 2×

10<sup>−

4</sup> M.

14. A formulation according to claim 4 wherein the amount of oxaliplatin is about 5 mg/mL and the amount of buffering agent is a molar concentration of about 4×

10<sup>−

4</sup> M.

15. A method for treating cancer or a solid tumor in a mammal which comprises administering to said mammal an effective amount of a formulation according to any one of claims 1-14.

18. A process for preparing a formulation according to claim 1 which comprises mixing a pharmaceutically acceptable carrier, a buffering agent and oxaliplatin.

19. A process for preparing a formulation according to claim 1 which comprises the steps of:

(a) mixing a pharmaceutically acceptable carrier and a buffering agent;

(b) dissolving oxaliplatin into said mixture;

(c) cooling the mixture resulting from step (b) and making up to final volume with the pharmaceutically acceptable carrier;

(d) filtering the solution resulting from step (c); and

(e) optionally sterilizing the product resulting from step (d).

20. A process according to claim 19 wherein said process is carried out under an inert atmosphere.

21. A process according to claim 19 wherein the product resulting from step (d) is sterilized by exposure to heat.

22. A packaged pharmaceutical product comprising a formulation according to claim 1 in a sealable container.

23. A packaged pharmaceutical product according to claim 22 wherein the container is an ampoule, vial, infusion bag or syringe.

24. A packaged pharmaceutical product according to claim 23 wherein the container is a graduated syringe.

16. A method for stabilizing a solution comprising a therapeutically effective amount of oxaliplatin which comprises adding an effective stabilizing amount of a buffering agent to said solution wherein the buffering agent is oxalic acid or an alkali metal salt thereof.

17. A method according to claim 16 wherein said solution is an aqueous solution and the buffering agent is oxalic acid or an alkali metal salt thereof.