Biocompatible medical article and method

• US 5,782,908 A
• Filed: 11/14/1996
• Issued: 07/21/1998
• Est. Priority Date: 08/22/1995
• Status: Expired due to Fees

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Hendriks, Marc, Verhoeven, Michel, Cahalan, Patrick T., Fouache, Benedicte, Cahalan, Linda L.
• Primary Examiner(s): Weiss, John G.
• Assistant Examiner(s): CUDDIHY, FRANCIS KEVIN
• Application Number:
  US08/748,991
• Time in Patent Office: 614 Days
• Field of Search: 623/1, 623/7, 623/11, 623/12, 623/66, 606/194, 606/195, 424/422, 424/423, 424/424, 427/2.1, 427/2.24, 427/2.25, 525/54.1
• US Class Current: 623/1.13
• CPC Class Codes: A61L 27/28 Materials for coating prostheses
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 33/0029 using an intermediate layer of polymer
• CPC Class Codes: A61L 33/0047 Enzymes, e.g. urokinase, streptokinase
• CPC Class Codes: C08L 33/02 Homopolymers or copolymers of acids; Metal or ammonium salts thereof
• CPC Class Codes: C08L 33/26 Homopolymers or copolymers of acrylamide or methacrylamide
• CPC Class Codes: Y10S 623/924 Material characteristic

Abstract

A medical article having a metal or glass surface with the surface having an adherent coating of improved biocompatibility. The coating is made by first applying to the surface an silane compound having a pendant vinyl functionality such that the silane adheres to the surface and then, in a separate step, forming a graft polymer on the surface with applied vinylsilane such that the pendant vinyl functionality of the vinylsilane is incorporated into the graft polymer by covalent bonding with the polymer. Biomolecules may then be covalently attached to the base layer.

Claims

1. A medical device having a metal or glass surface in contact with body fluids, the surface having a coating thereon comprising:

(a) a silane having a structure

space="preserve" listing-type="equation">C.sub.2 H.sub.3 --R--Si--X.sub.3

wherein X is a halogen, methoxy or ethoxy group and R is an optional short chain alkyl group;

the silane adherent to the surface such that the C₂ H₃ -- functional group is pendant from the surface; and

(b) a graft polymer formed by free radical reaction from an ethylenically unsaturated monomer, the graft polymer formed on the silane adherent to the surface in the presence of an oxidizing chemical free radical initiator such that the pendant C₂ H₃ -- functionality of the silane is activated by the oxidizing chemical free radical initiator and incorporated into the graft polymer.

2. A medical device as in claim 1 also comprising:

(a) a polyalkyleneimine spacer covalently attached to the graft polymer; and

(b) a biomolecule covalently attached to the spacer.

3. A medical device as in claim 1, in which the silane is trichlorovinylsilane.

4. A medical device as in claim 1, in which the monomer is selected from acrylamide and acrylic acid.

5. A medical device as in claim 2, in which the biomolecule is an antithrombotic.

6. A medical device as in claim 5, in which the antithrombotic is selected from the group consisting of heparin and heparin derivatives.

7. In a radially expandable stent comprising a hollow cylindrical shape made of a low-memory level metal such that the metal can controllably deform to effect radial expansion of the stent from a first diameter to a second, expanded diameter, the metal coated with a biologically compatible coating, wherein:

(a) a silane is adherent to the metal; and

(b) a graft polymer is covalently attached to the silane in the presence of an oxidizing chemical free radical initiator such that the silane is activated by the oxidizing chemical free radical initiator and incorporated into the graft polymer and such that the graft polymer is retained on the metal as the stent is expanded.

8. A stent as in claim 7 wherein the silane has a pendant vinyl functionality which is incorporated into the graft polymer.

9. A stent as in claim 8 wherein the biocompatible coating also comprises a biomolecule covalently attached to the graft polymer.

10. A method of providing a medical article having a glass or metal surface with a biocompatible coating on the glass or metal surface comprising the steps of:

(a) providing a medical article with a glass or metal surface;

(b) applying to the surface a silane having a vinyl functionality such that the silane adheres to the surface;

(c) forming a graft polymer on the silane adherent to the surface in the presence of an oxidizing chemical free radical initiator such that the vinyl functionality of the silane is activated by the oxidizing chemical free radical initiator and incorporated into the graft polymer.

11. A method as in claim 10 wherein the silane has a structure

12. A method as in claim 11, in which the silane is trichlorovinylsilane applied to the surface in dilute solution.

13. A method as in claim 10 also comprising the step of covalently attaching a biomolecule to the graft polymer.

14. A method as in claim 13, in which the biomolecule is covalently attached by the steps of:

(a) covalently attaching a spacer molecule to the graft polymer; and

(b) covalently attaching the biomolecule to the spacer molecule.

15. A method of providing a medical article having a glass or metal surface with a bioactive heparin coating on the glass or metal surface comprising the steps of:

(a) applying to the glass or metal surface a silane having a vinyl functionality such that the silane adheres to the surface;

(b) forming a graft polymer on the silane adherent to the surface in the presence of an oxidizing chemical free radical initiator such that the vinyl functionality of the silane is activated by the oxidizing chemical free radical initiator and incorporated into the graft polymer;

(c) covalently attaching a polyamine spacer to the graft polymer;

(d) treating heparin to form aldehyde functional groups on the heparin; and

(e) covalently attaching the heparin to the polyamine spacer.