Biocompatible microcapsules

• US 5,232,984 A
• Filed: 08/05/1991
• Issued: 08/03/1993
• 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: Sawhney, Amarpreet S., Hubbell, Jeffrey A.
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US07/740,632
• Time in Patent Office: 729 Days
• Field of Search: 525/54.1, 525/54.2, 525/54.3
• US Class Current: 525/54.1
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• 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 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• 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

Abstract

Biocompatible microcapsules useful for transplanting foreign material into an animal body, and the method of their production, are described, wherein the microcapsules contain an outermost layer of water soluble non-ionic polymers such as PEO to create resistance to cell adhesion on the surface of the microcapsules.

Claims

1. A method for grafting water soluble non-ionic polymers to polyamine or polyimine polycationic polymers comprising:

a) activating the reactive groups capable of being covalently linked to a coupling agent on the water soluble non-ionic polymers by using an activation agent selected from the group consisting of carbodiimidazole, sulfonyl chlorides and chlorocarbonates, and

b) coupling the activated water soluble non-ionic polymers to the polycationic polypeptides.

2. The method of claim 1 wherein the reactive groups are selected from the group consisting of hydroxyls, carboxyls, diols, aldehydes, amines, and thiols.

3. The method of claim 1 wherein the non-ionic water soluble polymers are selected from the group consisting of poly(ethylene oxide), poly(vinyl pyrrolidone), poly(ethyl oxazoline), poly(vinyl alcohol) and polysaccharides.

4. The method of claim 1 wherein the polycationic polymers are selected from the group consisting of polylysine, polyornithine, polyethyleneimine, and polyallylamine.

5. The method of claim 1 wherein the sulfonyl chloride is trifyl chloride.

6. The method of claim 1 wherein the sulfonyl chloride is tresyl chloride.

7. The method of claim 1 wherein the sulfonyl chloride is tosyl chloride.

8. The method of claim 1 wherein the sulfonyl chloride is pentafluorobenzenesulfonyl chloride.

9. The method of claim 1 wherein the chlorocarbonate is p-nitrophenyl chlorocarbonate.

10. The method of claim 1 wherein the chlorocarbonate is 2,4,5 trichlorophenyl chlorocarbonate.

11. The method of claim 1 wherein the chlorocarbonate is N-hydroxysuccinamide chlorocarbonate.