Polymer coatings grafted with polyethylene oxide chains containing covalently bonded bio-active agents

• US 6,107,416 A
• Filed: 02/01/1999
• Issued: 08/22/2000
• Est. Priority Date: 11/25/1996
• Status: Expired due to Term

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Inventors: Zdrahala, Richard J., Patnaik, Birendra K.
• Primary Examiner(s): GORR, RACHEL F
• Application Number:
  US09/243,378
• Time in Patent Office: 568 Days
• Field of Search: 525/453, 525/460, 528/76, 427/2.1, 523/112
• US Class Current: 525/453
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/28 Materials for coating prostheses
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/08 Materials for coatings
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: A61L 33/0029 using an intermediate layer of polymer
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: C08L 75/04 Polyurethanes
• CPC Class Codes: Y10S 623/90 Stent for heart valve
• CPC Class Codes: Y10T 428/31551 Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]

Abstract

Disclosed are bio-active coating compositions for polymeric substrates. In particular, a bio-active coating is described which is the reaction product formed by providing a polymer backbone with at least one free isocyanate group, wherein the isocyanate group is pendant from the polymer backbone. There is further provided a hydrophilic, amine-terminated spacer which has at least one amine group at its first and second ends. One of the amine groups of the spacer is reacted with one or more of the isocyanate groups on the polymer backbone in the presence of an optional catalyst agent. A bio-active agent is then covalently bonded onto an unreacted end of the spacer in the presence of a catalyst. Also disclosed are coating compositions for a substrate and methods of preparing same.

Claims

1. A biocompatible composition useful as a coating for medical devices, said composition comprising;

a hydrophobic polymer backbone having at least one free reactive functionality independent of any urethane linkages; and

a pendant hydrophilic spacer group having a first and second end, said first end bonded to said backbone through said free reactive functionality;

wherein the hydrophilic property of said spacer group and the hydrophobic property of said backbone repel said spacer group away from said backbone to tether said second end of said spacer group at a bio-effective distance from said backbone.

2. The composition of claim 1 wherein said polymer backbone is a polyurethane selected from the group consisting of a segmented poly(esterurethane)urea, a poly(carbonateurethane)urea, a poly(etherurethane)urea, and combinations thereof.

3. The composition of claim 1, wherein said spacer group is selected from the group consisting of aliphatic hydrocarbons, poly(oxy olefins), hydrophilic polyethers, hydrophilic polyethylenes, hydrophilic polyolefins, aliphatic polyesters, polyamines, polysiloxanes, polysilazanes, hydrophilic acrylates, hydrophilic methacrylates, polyamino acids, and linear polysaccharides.

4. The composition of claim 1 further including a bio-active agent covalently bonded to said second end of said spacer group.

5. The composition of claim 4, wherein said bio-active agent is selected from the group consisting of antithrombogenic agents, antibiotics, antibacterial agents, antiviral agents, their pharmaceutical salts and combinations thereof.

6. The composition of claim 4 wherein said bio-active agent is selected from the group of heparin, aldehyde-terminated heparin and pharmaceutical salts thereof.

7. The composition of claim 1, wherein said reactive functionality is selected from the group consisting of isocyanates, carboxyls, amines, and combinations thereof.

8. The composition of claim 1, wherein said spacer group is all amino-terminated poly(ethylene oxide) having a molecular weight of about 100 daltons to about 200,000 daltons.

9. The composition of claim 1, wherein said spacer group is an amino-terminated poly(ethylene oxide) having a molecular weight of about 200 daltons to about 50,000 daltons.

10. The composition of claim 1, wherein said spacer group is an amino-terminated poly(ethylene oxide) having a molecular weight of about 1,000 daltons to about 4,000 daltons.

11. The composition of claim 1, wherein said spacer group has a molecular weight of about 100 daltons to about 200,000 daltons to further define said bio-effective distance.