Polymer-bound paclitaxel derivatives

Patent 5362831 Issued on November 8, 1994. Estimated Expiration Date:

June 16, 2013. Estimated Expiration Date is calculated based on simple USPTO term provisions. It does not account for terminal disclaimers, term adjustments, failure to pay maintenance fees, or other factors which might affect the term of a patent.

Abstract Claims Description Full Text

Patent References

Preparation of biogically active substances bearing -NH₂ groups in a form releasable by enzymatic cleavage
Patent #: 4097470
Issued on: 06/27/1978
Inventor: Drobnik , et al.

Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof Patent #: 4960790
Issued on: 10/02/1990
Inventor: Stella, et al.

Inventors

Assignee

Farmitalia Carlo Erba Spa

Application

No. 077065 filed on 06/16/1993

US Classes:

526/304, Contains oxygen atom other than in amide form bonded to a carbon atom424/78.08, SOLID SYNTHETIC ORGANIC POLYMER AS DESIGNATED ORGANIC ACTIVE INGREDIENT (DOAI)424/78.32, Heterocyclic monomer526/307.3, With monomer containing nitrogen other than (meth)-acrylonitrile526/307.4With monomer containing oxygen

Examiners

Primary: Page, Thurman K.
Assistant: Kulkosky, Peter F.

Attorney, Agent or Firm

Oblon, Spivak, McClelland, Maier & Neustadt

Foreign Patent References

0187547 EP. 07/13/1986
0393575 EP. 10/13/1990
0537905 EP. 04/13/1993

International Classes

A61K 031/765
C80F 222/38

Foreign Application Priority Data

1992-06-19 GB

Abstract

A polymer conjugate consisting essentially of: from 90 to 99.9 mol % of units represented by the formula ##STR1## from 0.1 to 5 mol % of units represented by the formula ##STR2## wherein one of R1 and R2 is a copolymer residue of the formula ##STR3## and the other one is hydrogen atom; from 0 to 9.9 mol % of units represented by the formula ##STR4## wherein R is a phenyl or t-butoxy group, R3 is H or an acetyl group, A and A1 which may be the same or different, represent a chemical single bond, an amino acid residue or peptide spacer selected from ଲ Ala, Gly, Phe-Gly, Phe-Phe-, Leu-Gly, Val-Ala, Phe-Ala, Leu-Phe, Leu-Ala, Phe-Leu-Gly, Phe-Phe-Leu, Leu-Leu-Gly, Phe-Tyr-Ala, Phe-Gly-Phe, Phe-Phe-Gly, Phe-Leu-Gly-Phe, Gly-Phe-Leu-Gly-Phe,-댪la, Phe-Gly-댪la, Phe-Phe-댪la, Leu-Gly-댪la, Val-Ala-댪la, Phe-Ala-댪la, Leu-Phe-댪la, Leu-Gly-댪la, Phe-Leu-Gly-댪la, Phe-Phe-Leu 댪la, Leu-Leu-Gly-댪la, Phe-Tyr-Ala-댪la, Phe-Gly-Phe-ଲ, Phe-Phe-Gly 댪la, Phe-Leu-Gly-Phe-댪la or Gly-Phe-Leu-Gly-Phe-댪la. The compounds are endowed with antitumor activity and show improved water solubility and decreased toxicity in comparison with paclitaxel or its known analogs. A method for their preparation and pharmaceutical compositions containing them are also described.

Other References

Journal of Controlled Release, vol. 16, 1991, pp. 121-136, R. Duncan, et al., "Macromolecular Prodrugs for Use in Targeted Cancer Chemotherapy: Melphalan Covalently Coupled to HMPA Copolymers"
J. Med. Chem., vol. 35, 1992, pp. 145-151, A. E. Mathew, et al., "Synthesis and Evaluation of Some Water-Soluble Prodrugs and Derivatives of Taxol with Antitumor Activity"
Journal of Controlled Release, vol. 18, No. 2, Feb. 1992, pp. 123-132, V. Subr, et al., "Polymers Containing Enzymatically Degradable Bonds, XII. Effect of Spacer Structure on the Rate of Release of Daunomycin and Adriamycin from HMPA Copolymer Drug Carriers in Vitro and Antitumor Measured in Vivo