Articles having graft polymer bioactive surfaces

• US 5,476,509 A
• Filed: 06/09/1994
• Issued: 12/19/1995
• Est. Priority Date: 10/30/1992
• Status: Expired due to Term

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Keogh, James R., Hobot, Christopher M., Bergan, Matthew A., Eaton, John W., Jevne, Allan H.
• Primary Examiner(s): Prebilic, Paul B.
• Application Number:
  US08/255,632
• Time in Patent Office: 558 Days
• Field of Search: 623/1, 623/11, 606/76, 604/266
• US Class Current: 623/1.42
• CPC Class Codes: A61L 2300/104 Silver, e.g. silver sulfadiazine
• CPC Class Codes: A61L 2300/206 Biguanides, e.g. chlorohexidine
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/442 Colorants, dyes
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 33/0029 using an intermediate layer of polymer
• 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 623/901 Method of manufacturing prosthetic device
• CPC Class Codes: Y10S 623/921 Blood vessel

Abstract

Articles comprised of bioactive agents coupled to or repelled by a graft polymer (made, for example, from monomers such as N-(3-aminopropyl) methacrylamide hydrochloride (APMA), 2-acrylamido-2-methylpropane sulfonic acid (AMPS), acrylamide (AAm), and acrylic acid (AA)) which is in turn bonded to a polymeric substrate surface. The articles are useful as thromboresistant and/or antimicrobial medical devices.

Claims

1. An article for use in contact with blood or blood products, the article including at least one polymer surface for contacting blood or blood products, the polymeric surface having thereon a graft copolymer and a bioactive agent, the graft copolymer grafted onto the polymeric surface by polymerization of first and second vinyl monomers, the first monomer including pendant groups selected from the group consisting of amine groups and add groups, said pendant groups imparting to the graft polymer a net (-) or (+) ionic charge and a neutral, hydrophilic monomer as the second monomer, the bioactive agent selected from the group consisting of antibiotics, antimicrobials, anticoagulants and albumin-binding dyes having a net (+) or (-) ionic charge, the bioactive agent on the graft polymer such that the bioactive agent retained on or repelled from the graft polymer by ionic attraction or repulsion,

2. The article of claim 1 wherein the graft co-polymer includes as the first monomer a monomer selected from the group consisting of acrylic acid and 2-acrylamido-2-methylpropane sulfonic acid, and the second monomer is acrylamide and the bioactive agent is gentamycin.

3. The article of claim 2 wherein the polymeric surface is polyurethane.

4. The article of claim 1 wherein the bioactive agent has the same net charge as the graft copolymer.

5. The article of claim 1 wherein the graft copolymer has a net (+) charge and the bioactive agent has a net (-) charge.

6. The article of claim 1 wherein the graft copolymer has a net (-) charge and the bioactive agent has a net (+) charge.

7. The article of claim 1 wherein the first monomer is N-(3-aminopropyl) methacrylamide hydrochloride and the second monomer is acrylamide.

8. The article of claim 1 wherein the graft copolymer, includes monomers selected from the group consisting of acrylamide, acrylic acid, 2-acrylamido-2-methylpropane sulfonic acid, 2-hydroxyethyl methacrylate and N-(3-aminopropyl) methacrylamide hydrochloride in predetermined relative amounts to control hydrophilicity and coupling to the polymer.

9. The article of claim 8 wherein the monomers of the copolymer are acrylamide and N-(3-aminopropyl) methacrylamide hydrochloride and heparin is coupled thereto.

10. The article of claim 9 wherein the polymeric surface is polyurethane.