Biocompatability of solid surfaces

• US 5,415,938 A
• Filed: 02/09/1994
• Issued: 05/16/1995
• Est. Priority Date: 01/19/1993
• Status: Expired due to Term

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Hendriks, Marc, Verhoeven, Michel, Cahalan, Linda, Cahalan, Patrick T.
• Primary Examiner(s): Seidleck, James J.
• Assistant Examiner(s): Delaney, Patrick R.
• Application Number:
  US08/193,964
• Time in Patent Office: 461 Days
• Field of Search: 428/425.5, 428/409, 428/473.5, 428/525, 435/180, 435/181
• US Class Current: 428/409
• CPC Class Codes: A61L 33/0005 Use of materials characterised by their function or physical properties
• CPC Class Codes: A61L 33/0029 using an intermediate layer of polymer
• CPC Class Codes: A61L 33/0041 characterised by the choice of an antithrombatic agent other than heparin heparinoïd A61L33/08; polypeptides A61L33/12
• CPC Class Codes: A61L 33/0088 by grafting of a monomer onto the substrate
• CPC Class Codes: C08L 33/26 Homopolymers or copolymers of acrylamide or methacrylamide
• CPC Class Codes: C08L 79/02 Polyamines
• CPC Class Codes: Y10T 428/31 Surface property or characteristic of web, sheet or block
• CPC Class Codes: Y10T 428/31504 Composite [nonstructural laminate]
• CPC Class Codes: Y10T 428/31562 Next to polyamide [nylon, etc.]
• CPC Class Codes: Y10T 428/31721 Of polyimide
• CPC Class Codes: Y10T 428/31946 Next to second aldehyde or ketone condensation product

Abstract

An improved spacer material for improving the biocompatibility of a biomaterial and a method for making it in which a polyalkylimine is covalently attached to an aminated substrate and combined with a crosslinking agent which is at least difunctional in aldehyde groups. The polyalkylimine can be, for example, polyethyleneimine and the crosslinking agent can be, for example, glutaraldehyde. Preferably, the crosslinking agent is applied in dilute solution and at a pH suitable to accomplish light crosslinking of the polyalkyaimine and also provide aldehyde linkages at the interface between the biomolecule and the spacer.

Claims

1. A spacer for attaching a biomolecule to a solid surface comprising, in combination:

(a) an aminated substrate including acrylamide graft polymerized onto the substrate anal spaced pendant amine groups extending from the graft polyacrylamide and covalently attached to the graft polyacrylamide;

(b) a polyalkylimine covalently attached to the pendant amine groups of the aminated substrate; and

(c) a crosslinking agent which is at least difunctional in aldehyde groups providing the covalent attachment of the polyalkylimine to the pendant amine groups of the aminated substrate.

2. The spacer according to claim 1 wherein the polyalkylimine is polyethyleneimine.

3. The spacer according to claim 1 wherein the crosslinking agent is selected from the group consisting of glutaraldehyde, glyoxal, malonaldehyde, succinaldehyde, adipaldehyde, and dialdehyde starch.

4. The spacer according to claim 1 wherein the pendant amine groups are provided by amine-functional spacer molecules covalently attached to the grafted acrylamide.

5. The spacer according to claim 1 wherein the polyalkylimine is also crosslinked by a crosslinking agent which is at least difunctional in aldehyde groups.