Method of treating cancerous tumors with a dendritic-platinate drug delivery system

• US 6,790,437 B2
• Filed: 06/14/2001
• Issued: 09/14/2004
• Est. Priority Date: 07/07/1997
• Status: Expired due to Term

• Current Assignee: Dendritic NanoTechnologies, Inc. (Loveland Products, Inc.)
• Original Assignee: The Dow Chemical Company (Dow, Inc.)
• Inventors: Malik, Navid, Duncan, Ruth
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US09/881,126
• Publication Number:
  US 20020054863A1
• Time in Patent Office: 1,188 Days
• Field of Search: 424/78.17, 424/78.27, 424/78.37, 424/DIG.16
• US Class Current: 424/78.17
• CPC Class Codes: A61K 47/6949 inclusion complexes, e.g. clathrates, cavitates or fullerenes
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C08G 69/00 Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule products obtained from isocyanates or isothiocyanates C08G18/00; polyamide-imides C08G73/14
• CPC Class Codes: C08G 69/02 Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
• CPC Class Codes: C08G 83/003 Dendrimers
• CPC Class Codes: Y10S 424/16 Dendrimers and dendritic polymers

Abstract

Dendritic polymer conjugates which are useful drug delivery systems for carrying platinum containing anti-tumor agents to malignant tumors are prepared by obtaining a dendritic polymer having functional groups which are accessible to a platinum containing compound capable of interacting with the functional groups, contacting the dendritic polymer with the platinum containing compound, and reacting the dendritic polymer with the platinum containing compound. The dendritic polymer platinates may be administered intravenously, orally, parentally, subcutaneously or topically to an animal having a malignant tumor in an amount which is effective to inhibit growth of the malignant tumor. The dendritic polymer platinates exhibit high drug efficiency, high drug carrying capacity, good water solubility, good stability on storage, reduced toxicity, and improved anti-tumor activity in vivo.

Claims

1. A method for treatment of cancerous tumors in mammals, comprising administering a therapeutically effective quantity of a dendritic polymer-platinate compound to a mammal having a cancerous tumor.

2. The method of claim 1, wherein the dendritic polymer is a dendrimer.

3. The method of claim 1, wherein the dendritic polymer has anionic functional groups.

4. The method of claim 3, wherein the anionic groups are carboxylate groups.

5. The method of claim 1, wherein the dendritic polymer is a polyamidoamine dendrimer.

6. The method of claim 1, wherein the dendritic polymer is polypropylamine.

7. The method of claim 1, wherein the platinum containing compound is a compound comprising a central tetravalent platinum atom bonded to the nitrogen atom of two amine ligands, which may b the same or different, the amine ligands being in cis confirmation with respect to each other and at least one of the remaining ligand sites is coupled to the dendritic polymer.

8. The method of claim 1, wherein the platinum containing compound is cisplatin.

9. The method claim 1, wherein the dendritic polymer-platinate compound is administered parentally.

10. The method of claim 1, wherein the dendritic polymer-platinate compound is administered intravenously or intraperitoneally.

11. The method of claim 1, wherein the dendritic polymer-platinate compound is administered orally.

12. The method of claim 1, wherein the dendritic polymer-platinate compound is administered topically.

13. The method of claim 1, wherein the dendritic polymer-platinate compound is administered intraperitoneally.

14. The method of claim 1, wherein the molar ratio of cisplatin to dendritic polymer in the conjugate is from about 100:

1 to about 1;

1.

15. The method of claim 1, wherein the molar ratio of cisplatin to dendritic polymer in the conjugate is about 35:

1.