Process and composition for therapeutic cisplatin (CDDP)

• US 6,224,883 B1
• Filed: 01/26/1998
• Issued: 05/01/2001
• Est. Priority Date: 10/30/1995
• Status: Expired due to Fees

• Current Assignee: Biomedicines, Inc.
• Original Assignee: Matrix Pharmaceutical, Inc. (Bayer AG)
• Inventors: Roskos, Kathleen V., Maskiewicz, Richard, Jones, Richard E.
• Primary Examiner(s): Kulkosky, Peter F.
• Application Number:
  US09/013,568
• Time in Patent Office: 1,191 Days
• Field of Search: 424/400, 514/492
• US Class Current: 424/400
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• 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

An improved diluent for the preparation of cisplatin suspensions from a lyophilized powder is provided. The diluent contains a pharmaceutically acceptable nonionic surfactant, which improves the accuracy and homogeneity of the therapeutic formulation. The suspension may be used directly, or may be used in preparing gel formulations for direct injection into a neoplastic lesion or surrounding tissue.

Claims

1. A stable, aqueous dispersion of cisplatin useful for delivery of cisplatin to a neoplastic lesion in a patient, comprising:

about 0.05 to 0.75% nonionic surfactant,

about 2 to 8 mg/ml cisplatin;

about 0.5 to 8% collagen; and

about 0.01 to 0.5 mg/ml epinephrine, in an aqueous vehicle.

2. A formulation according to claim 1, further comprising:

about 0.01% to 0.25% carboxymethylcellulose sodium.

3. A formulation according to claim 1, wherein said nonionic surfactant is a polysorbate.

4. A formulation according to claim 3, wherein said polysorbate is polysorbate 80.

5. A formulation according to claim 1, comprising from about 0.02 to 0.2 mg/ml epinephrine.

6. A formulation useful for delivery of cisplatin to a neoplastic lesion in a patient, comprising:

about 0.05 to 0.75% polysorbate 80;

about 0.05 to 0.2 mg/ml epinephrine;

about 1.5 to 6.5 mg/ml cisplatin; and

about 0.5 to 8% collagen;

in an aqueous vehicle.

7. A formulation according to claim 6, further comprising:

about 0.01% to 0.25% carboxymethylcellulose sodium.

8. A method for preparation of a cisplatin dispersion for treatment of a neoplastic lesion in a patient, the method comprising:

resuspending lyophilized cisplatin to form a dispersion of from about 2 to 8 mg/ml cisplatin in an aqueous diluent comprising;

about 0.05 to 0.75% nonionic surfactant and from about 0.01 to 0.5 mg/ml epinephrine.

9. A method according to claim 8, further comprising the step of:

mixing said suspension with a collagen gel to result in an aqueous gel containing about 0.5 to 8.0% collagen.

10. A method according to claim 8, wherein said nonionic surfactant is a polysorbate.

11. A method according to claim 10, wherein said polysorbate is polysorbate 80.

12. A method according to claim 8, wherein said diluent comprises from about 0.02 to 0.2 mg/ml epinephrine.

13. A kit for preparation of a therapeutic cisplatin suspension, comprising:

lyophilized cisplatin; and

an aqueous diluent for resuspension of said cisplatin comprising about 0.05 to 0.75% polysorbate 80 and about 0.01 to 0.5 mg/ml epinephrine.

14. A kit according to claim 13, further comprising:

collagen gel.

15. A kit according to claim 13, where said diluent comprises from about 0.02 to 0.2 mg/ml epinephrine.