Bioactive agent release coating

• US 6,890,583 B2
• Filed: 11/21/2001
• Issued: 05/10/2005
• Est. Priority Date: 04/27/1998
• Status: Expired due to Term

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Chappa, Ralph A., Anderson, Aron B., Chudzik, Stephen J., Kloke, Timothy M.
• Primary Examiner(s): CHEN, BRET P
• Application Number:
  US09/989,033
• Publication Number:
  US 20020032434A1
• Time in Patent Office: 1,266 Days
• Field of Search: 427/2.1, 427/2.24, 427/2.25, 427/2.28, 427/2.3, 427/421, 427/430.1
• US Class Current: 427/2.24
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• 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 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08L 33/06 of esters containing only carbon, hydrogen and oxygen, which oxygen atoms are present only as part of the carboxyl radical

Abstract

A coating composition for use in coating implantable medical devices to improve their ability to release bioactive agents in vivo. The coating composition is particularly adapted for use with devices that undergo significant flexion and/or expansion in the course of their delivery and/or use, such as stents and catheters. The composition includes the bioactive agent in combination with a mixture of a first polymer component such as poly(butyl methacrylate) and a second polymer component such as poly(ethylene-co-vinyl acetate).

Claims

1. A method of preparing a medical device coated with a composition, the method comprising the steps of providing a composition comprising a bioactive agent in combination with a plurality of hydrophobic polymers, including a first polymer component comprising at least one poly(alkyl)(meth)acrylate having alkyl chain lengths from 2 to 8 carbons and a second polymer component comprising poly(ethylene-vo-vinyl acetate) having vinyl acetate concentrations of between about 10% and about 50% by weight, in a manner that permits the coated surface to release the bioactive agent over time when implanted in vivo, and applying the composition to the medical device.

2. A method according to claim 1 wherein the coating is provided by dipping or spraying the device with the composition.

3. A method according to claim 2 wherein the coating composition includes a solvent and the coating upon the device is cured by evaporation of the solvent.

4. A method according to claim 1 wherein the device is one that undergoes flexion and/or expansion in the course of implantation or use in vivo.

5. A method according to claim 1 wherein the composition comprises a mixture of poly(n-butylmethacrylate) and poly(ethylene-co-vinyl acetate).

6. A method according to claim 1 wherein the total combined concentrations of both polymers in the coating composition is between about 0.25% and about 70% by weight.

7. A method according to claim 6 wherein the bioactive agent is dissolved or suspended in the coating mixture at a concentration of 0.01% to 90% by weight.

8. A method according to claim 1 wherein the weight of the coating attributable to the bioactive agent is in the range of about 0.05 mg to about 10 mg of bioactive agent per cm² of the gross surface area of the device.

9. A method according to claim 8 wherein the weight of the coating attributable to the bioactive agent is between about 1 mg and about 5 mg of bioactive agent per cm² of the gross surface area of the device, and the coating thickness of the composition is in the range of about 5 micrometers to about 100 micrometers.

10. A method according to claim 1 wherein the medical device comprises an implantable medical device fabricated from metal or polymeric materials.

11. A method according to claim 10 wherein the device is selected from catheters and stents.

12. A method according to claim 11 wherein the device comprises a stent selected from the group consisting of self-expanding stents and balloon expandable stents.

13. A method according to claim 12 wherein the stent comprises a material selected from the group consisting of stainless steel and tantalum.

14. A method according to claim 10 wherein the medical device comprises a catheter selected from the group consisting of urinary catheters and intravenous catheters.

15. A method according to claim 14 wherein the catheter comprises a urinary catheter and the bioactive agent comprises an antimicrobial agent.

16. A method according to claim 14 wherein the catheter comprises an intravenous catheter and the bioactive agent comprises an antimicrobial or antithrombotic agent.

17. A method according to claim 14 wherein the catheter is fabricated from a group comprising silicone rubber, polyurethane, latex and polyvinyichloride.

18. A method according to claim 1 wherein the composition permits the amount and rate of release of agent(s) from the medical device to be controlled by adjusting the relative types and/or concentrations of polymers in the mixture.

19. A method according to claim 1 wherein the vinyl acetate concentrations are between about 24% and about 36% by weight.

20. A method according to claim 19 wherein the vinyl acetate concentrations are between about 30% and about 34% by weight.

21. A method according to claim 1 wherein the composition further comprises a solvent in which the polymers form a true solution.

22. A method according to claim 1 wherein the bioactive agent is dissolved or suspended in the coating mixture at a concentration of 0.01% to 90% by weight.

23. A method according to claim 22 wherein the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives, anticancer chemotherapeutic agents, anti-inflammatory steroid or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents.

24. A method according to claim 23 wherein the vinyl acetate concentrations are between about 24% and about 36% by weight and the total combined concentrations of both polymers in the coating composition is between about 0.25% and about 70% by weight.

25. A method according to claim 24 wherein the medical device comprises an implantable medical device fabricated from metal or polymeric materials.

26. A method according to claim 25 wherein the device is selected from catheters and stents.

27. A method according to claim 26 wherein the medical device comprises a catheter selected from the group consisting of urinary catheters and intravenous catheters.

28. A method according to claim 27 wherein the catheter comprises a urinary catheter and the bioactive agent comprises an antimicrobial agent.

29. A method according to claim 27 wherein the catheter comprises an intravenous catheter and the bioactive agent comprises an antimicrobial or antithrombotic agent.

30. A method according to claim 27 wherein the catheter is fabricated from a group comprising silicone rubber, polyurethane, latex and polyvinylchloride.

31. A method according to claim 26 wherein the device comprises a stent selected from the group consisting of self-expanding stents and balloon expandable stents.

32. A method according to claim 31 wherein the stent comprises a material selected from the group consisting of stainless steel and tantalum.