Medical device with biomolecule-coated surface graft matrix

• US 5,866,113 A
• Filed: 03/07/1997
• Issued: 02/02/1999
• 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, Cahalan, Patrick T., Fouache, Benedicte, Cahalan, Linda L., Verhoeven, Michel
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US08/813,470
• Time in Patent Office: 697 Days
• Field of Search: 424/484, 424/78.17, 424/78.18, 424/486-487, 530/815-816, 525/64, 525/78, 525/937, 427/2.24, 427/2.25, 427/2.28, 427/2.3
• US Class Current: 424/78.17
• 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 medical device comprising:

a) a polymerized surface graft matrix comprising carboxyl-functional groups located on the device, the polymerized surface graft matrix comprising an outer portion; and

b) one or more biomolecules covalently coupled to the polymerized surface graft matrix, wherein a majority of the biomolecules are located in the outer portion of the polymerized surface graft matrix.

2. A device according to claim 1, wherein a majority of the biomolecules are located within about 10 nm of the outer surface of the polymerized surface graft matrix.

3. A device 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, amino acids, and mixtures thereof.

4. A device according to claim 3, wherein the biomolecule is selected from the group consisting of collagen, albumin, fibrinogen, laminin, vitronectin, fibronectin, RGD-containing peptides, heparin, heparin sulfate, fibroblast growth factors (FGF), insulin-like growth factor, nerve growth factor, interferons (IFN), tumor necrosis factors (TNF), interleukins, gelatin, elastin, fibrin, von Willebrand factor, dermatan sulfate, hyaluronic acid, dextran sulfate, and mixtures thereof.

5. A device according to claim 1, wherein the polymerized surface graft matrix is prepared 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.

6. A device according to claim 1, wherein the polymerized surface graft matrix is prepared from carboxyl-functional monomers and vinyl monomers having no carboxyl functionality.

7. A device according to claim 6, wherein the polymerized surface graft matrix is prepared from acrylic acid monomers and acrylamide monomers.

8. A device according to claim 1, further including a pharmaceutical agent in the polymerized surface graft matrix.

9. A device according to claim 8, wherein the pharmaceutical agent is selected from the group consisting of antimicrobial agents, antibacterial agents, anticoagulant agents, antithrombotic agents, platelet agents, anti-inflammatory agents, dyes which act as biological ligands, steroids, enzymes, catalysts, hormones, growth factors, drugs, vitamins, antibodies, antigens, nucleic acids, peptides, DNA &

RNA segments, and mixtures thereof.

10. A medical device comprising:

a) a polymerized surface graft matrix comprising carboxyl-functional groups located on the device, the polymerized surface graft matrix comprising an outer portion;

b) one or more linker molecules covalently coupled to the polymerized surface graft matrix, wherein a majority of the linker molecules are located in the outer portion of the polymerized surface graft matrix; and

c) one or more biomolecules covalently coupled to the linker molecules.

11. A device according to claim 10, wherein a majority of the linker molecules are located within about 10 nm of the outer surface of the polymerized surface graft matrix.

12. A device according to claim 10, wherein the linker molecules, prior to coupling, are amine-functional compounds.

13. A device according to claim 12, wherein the amine-functional compounds are selected from the group consisting of polyethyleneimine, polyallylamine, and mixtures thereof.

14. A device according to claim 10, 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.

15. A device according to claim 14, wherein the biomolecule is selected from the group consisting of collagen, albumin, fibrinogen, laminin, vitronectin, fibronectin, RGD-containing peptides, heparin, heparin sulfate, fibroblast growth factors (FGF), insulin-like growth factor, nerve growth factor, interferons (IFN), tumor necrosis factors (TNF), interleukins, gelatin, elastin, fibrin, von Willebrand factor, dermatan sulfate, hyaluronic acid, dextran sulfate, and mixtures thereof.

16. A device according to claim 10, wherein the polymerized surface graft matrix is prepared 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.

17. A device according to claim 10, wherein the polymerized surface graft matrix is prepared from carboxyl-functional monomers and vinyl monomers having no carboxyl functionality.

18. A device according to claim 17, wherein the polymerized surface graft matrix is prepared from acrylic acid monomers and acrylamide monomers.

19. A device according to claim 10, further including a pharmaceutical agent in the polymerized surface graft matrix.

20. A device according to claim 19, wherein the pharmaceutical agent is selected from the group consisting of antimicrobial agents, antibacterial agents, anticoagulant agents, antithrombotic agents, platelet agents, anti-inflammatory agents, dyes which act as biological ligands, steroids, enzymes, catalysts, hormones, growth factors, drugs, vitamins, antibodies, antigens, nucleic acids, peptides, DNA &

RNA segments, and mixtures thereof.