Method of modifying the surface of a medical device

• US 5,811,151 A
• Filed: 05/31/1996
• Issued: 09/22/1998
• Est. Priority Date: 05/31/1996
• Status: Expired due to Term

• 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): PIANALTO, BERNARD D
• Application Number:
  US08/656,614
• Time in Patent Office: 844 Days
• Field of Search: 427/2.24, 427/2.3, 427/333, 427/340, 427/399, 427/407.1
• US Class Current: 427/2.24
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 27/22 Polypeptides or derivatives thereof , e.g. degradation products
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/044 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 29/045 Collagen
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/043 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 31/044 Collagen
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• 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 33/0076 Chemical modification of the substrate
• CPC Class Codes: A61L 33/0088 by grafting of a monomer onto the substrate
• CPC Class Codes: A61L 33/128 Other specific proteins or polypeptides not covered by A61L33/122 - A61L33/126
• CPC Class Codes: C08L 51/00 Compositions of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds for ABS polymers C08L55/02; Compositions of derivatives of such polymers
• CPC Class Codes: Y10S 530/815 Carrier is a synthetic polymer
• CPC Class Codes: Y10S 530/816 : Attached to the carrier via a bridging agent

Abstract

A medical device having a surface graft matrix comprising carboxyl-functional groups located on the device, the surface graft matrix comprising an outer portion; and one or more biomolecules covalently coupled to the surface graft matrix, wherein a majority of the biomolecules are located in the outer portion of the surface graft matrix. The surface graft matrix can also be loaded with a pharmaceutical agent.

Claims

1. A method of modifying the surface of a medical device comprising:

(a) forming a surface graft matrix comprising carboxyl-functional groups on the surface of a medical device;

(b) treating the surface graft matrix with an aqueous solution having a pH that is less than the pKa of the surface graft matrix; and

(c) covalently coupling one or more biomolecules to the surface graft matrix in an aqueous solution having a pH that is less than the pKa of the surface graft matrix, wherein a majority of the biomolecules are located in the outer portion of the surface graft matrix.

2. A method according to claim 1, wherein the pH of the solutions in steps b and c is no greater than about 5.5.

3. A method according to claim 1, wherein the step of forming a surface graft matrix further comprises forming the surface graft matrix in a solution having a pH less than the pKa of the surface graft matrix.

4. A method according to claim 3, further comprising rinsing the formed surface graft matrix in an aqueous solution having a pH greater than the pKa of the surface graft matrix.

5. A method according to claim 1, wherein the biomolecule is selected from the group consisting of antithrombotic agents, antibacterial agents, anti-inflammatory agents, growth factors, cytokines, naturally occurring or synthetically prepared proteins, peptides, and amino acids, and mixtures thereof.

6. A method according to claim 1, wherein the surface graft matrix is formed from carboxyl-functional monomers selected from the group consisting of acrylic acid, methacrylic acid, itaconic acid, trans-cinnamic acid, crotonic acid, linoleic acid, linolenic acid, maleic acid, sorbic acid, and mixtures thereof.

7. A method according to claim 1, wherein the surface graft matrix is formed from carboxyl-functional monomers and vinyl monomers having no carboxyl functionality.

8. A method of modifying the surface of a medical device comprising:

(a) forming a surface graft matrix comprising carboxyl-functional groups on the surface of a medical device;

(b) treating the surface graft matrix with an aqueous solution having a pH that is less than the pKa of the surface graft matrix;

(c) covalently coupling one or more linker molecules to the surface graft matrix in an aqueous solution having a pH that is less than the pKa of the surface graft matrix, wherein a majority of the linker molecules are located in the outer portion of the surface graft matrix; and

(d) covalently coupling one or more biomolecules to the linker molecules.

9. A method according to claim 8, wherein the pH of the solutions in steps b and c is no greater than about 5.5.

10. A method according to claim 8, wherein the step of forming a surface graft matrix further comprises forming the surface graft matrix in a solution having a pH less than the pKa of the surface graft matrix.

11. A method according to claim 10, further comprising rinsing the formed surface graft matrix in an aqueous solution having a pH greater than the pKa of the surface graft matrix.

12. A method according to claim 8, wherein thee biomolecule is selected from the group consisting of antithrombotic agents, antibacterial agents, anti-inflammatory agents, growth factors, cytokines, naturally occurring or synthetically prepared proteins, peptides, and amino acids, and mixtures thereof.

13. A method according to claim 8, wherein the surface graft matrix is formed from carboxyl-functional monomers selected from the group consisting of acrylic acid, methacrylic acid, itaconic acid, trans-cinnamic acid, crotonic acid, linoleic acid, linolenic acid, maleic acid, sorbic acid, and mixtures thereof.

14. A method according to claim 8, wherein the surface graft matrix is formed from carboxyl-functional monomers and vinyl monomers having no carboxyl functionality.

15. A method of delivering a pharmaceutical agent comprising contacting a body with a medical device comprising a surface graft matrix comprising carboxyl-functional groups located on the device, the surface graft matrix comprising an outer portion in which a majority of one or more biomolecules are coupled, wherein the pharmaceutical agent is located within the surface graft matrix when the device is initially contacted with the body.