Multifunctional organic polymers

• US 5,462,990 A
• Filed: 10/05/1993
• Issued: 10/31/1995
• Est. Priority Date: 10/15/1990
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Drumheller, Paul D., Hubbell, Jeffrey A., Elbert, Donald, Sawhney, Amarpreet, Hill-West, Jennifer L., Chowdhury, Sanghamitra
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US08/132,507
• Time in Patent Office: 756 Days
• Field of Search: 525/54.1, 525/54.2, 525/54.3, 528/354
• US Class Current: 525/54.1
• CPC Class Codes: A61K 47/62 the modifying agent being a protein, peptide or polyamino acid
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: C08G 81/00 Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers involving only carbon-to-carbon unsaturated bond reactions C08F299/00 ; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42

Abstract

Described herein is a multi-functional polymeric material for use in inhibiting adhesion and immune recognition between cells and cells, cells and tissues, and tissues and tissues. One component of the polymeric material adsorbs well to cells or tissue, and the other component of the polymeric material does not adsorb well to tissues. A water-soluble polymer that does not bear charge (polynonion) is used as the non-binding component, and a water soluble polymer that is positively charged at physiological pH (polycation) is used as the tissue binding component. When the bi-functional polymeric material contacts a tissue, the tissue-binding component binds and thus immobilizes the attached non-binding component, which will then extend generally away from the tissue surface and sterically block the attachment of other tissues. The method and compositions are useful in inhibiting formation of post-surgical adhesions, protecting damaged blood vessels from thrombosis and restenosis, and decreasing the extent of metastasis of attachment-dependent tumor cells.

Claims

1. A biocompatible polymeric material selected from the group consisting of block copolymers having the formulas (A)x-(B)y where the polymer is a brush copolymer having bristles of poly(A), (A)x(B)y, (A)x(B)y(A)z, and (B)x(A)y(B)z wherein

(A)x, (A)y and (A)z are biocompatible synthetic polymers and mixtures of polymers that form a region which is polynonionic at a pH of between 6.5 and 8.5 and does not bind tissue, and

(B)y, (B)x, and (B)z are biocompatible, water-soluble synthetic polymers or mixture of polymers that form a region which is polycationic at a pH of between 6.5 and 8.5 and binds to tissue;

and wherein

x is an integer of greater than or equal to 5, y is an integer of greater than or equal to 3 and z is an integer of greater than or equal to 0,

wherein the polymer has a molecular weight of at least 300 g/mole,

in combination with a pharmaceutically acceptable carrier for administration to a patient.

2. The biocompatible polymeric material of claim 1 wherein the polymer has the formula (A)x-(B)y wherein

x is an integer of greater than or equal to 5, y is an integer of greater than or equal to 3 and z is an integer of greater than or equal to 0.

3. The polymeric material of claim 1 wherein (A)x and (A)z are selected from the group consisting of poly(oxyalkylene oxides), poly(ethyloxazoline), poly(N-vinyl pyrrolidone), poly(vinyl alcohol), neutral poly(amino acids) and copolymers of monomers selected from the group consisting of oxyalkylene oxides, ethyloxazoline, N-vinyl pyrrolidone, vinyl alcohol, and amino acids.

4. The polymeric material of claim 1 wherein (B)y is selected from the group consisting of poly(ethyleneimine), quaternary amines, and polyamines having amine groups on either the polymer backbone or the polymer sidechains.

5. The polymeric material of claim 1 further comprising a region C that is subject to degradation in vivo by hydrolysis, enzymatic degradation, or oxidation.

6. The polymeric material of claim 5 wherein C is selected from the group consisting of peptide sequences and saccharide sequences cleaved by an enzyme present in vivo.

7. The polymeric material of claim 5 wherein C is selected from the group of chemical compounds which hydrolyze in the presence of water.

8. The polymeric material of claim 5 wherein C is selected from the group of chemical compounds which oxidize in vivo.

9. The polymeric material of claim 5 wherein the C region or regions is between the tissue binding regions (B)y and the non-tissue binding regions (A)x.

10. The polymeric material of claim 5 wherein the C region is located within the tissue binding region (B)y between the points of attachment of the non-tissue binding regions (A)x.

11. The polymeric material of claim 1 wherein the tissue binding region (B)y converts to a non-tissue binding region when exposed to water, oxidation or to enzymatic attack.

12. The polymeric material of claim 11 wherein the tissue binding region (B)y is formed by polymerization of amides or esters.

13. The polymeric material of claim 1 wherein the non-tissue binding region (A)x converts to a tissue binding region when exposed to water, oxidation or to enzymatic attack.

14. The polymeric material of claim 1 further comprising an agent which is biologically active in a patient.

15. The polymer of claim 14 wherein the polymeric material is biodegradable, and the biologically active agent is a component which is released as the polymer degrades.

16. The polymeric material of claim 14 wherein the biologically active agent is chemically coupled to the polymer.

17. The polymeric material of claim 1 wherein the pharmaceutically acceptable carrier for administration to a patient in need of treatment thereof is selected from the group consisting of water and buffered aqueous solutions.

18. The polymeric material of claim 17 where the non-tissue binding region (A)x is polyanionic and soluble in water.