Bioactive agent release coating

• US 7,008,667 B2
• Filed: 10/10/2002
• Issued: 03/07/2006
• 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): Page, Thurman K
• Assistant Examiner(s): Sheikh, Humera N.
• Application Number:
  US10/268,163
• Publication Number:
  US 20030031780A1
• Time in Patent Office: 1,244 Days
• Field of Search: 424/489, 427/2.1
• US Class Current: 427/2.1
• 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 composition for coating the surface of a medical device with one or more bioactive agents in a manner that permits the coated surface to release the bioactive agent(s) over time when implanted in vivo, the composition comprising one or more bioactive agents in combination with a first polymer component comprising at least one poly(alkyl)(meth)acrylate and a second polymer component comprising poly(ethylene-co-vinyl acetate), wherein the device is one that undergoes flexion and/or expansion in the course of implantation or use in vivo.

4. A composition according to claim 1, 2 or 3 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.

5. A composition according to claim 1, 2, or 3 wherein the first and second polymer components are adapted to be mixed to provide a mixture that exhibits an optimal combination of physical characteristics and bioactive release characteristics as compared to the polymers when used alone.

6. A composition according to claim 1, 2, or 3 wherein the amount and rate of release of agent(s) from the medical device can be controlled by adjusting the relative types and/or concentrations of the first polymer component and the second polymer component.

2. A composition for coating the surface of a medical device with one or more bioactive agents in a manner that permits the coated surface to release the bioactive agent(s) over time when implanted in vivo, the composition comprising one or more bioactive agents in combination with a first polymer component comprising at least one poly(alkyl)(meth)acrylate and a second polymer component comprising poly(ethylene-co-vinyl acetate), 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.

3. A composition for coating the surface of a medical device with one or more bioactive agent(s) in a manner that permits the coated surface to release the bioactive agent(s) over time when implanted in vivo, the composition comprising one or more bioactive agent(s) in combination with a first polymer component comprising at least one poly(alkyl)(meth)acrylate and a second polymer component comprising poly(ethylene-co-vinyl acetate), wherein the device is selected from the group consisting of catheters and stents.

7. A polymeric coating composition comprising a first polymer component comprising at least one poly(alkyl)(meth)acrylate and a second polymer component comprising poly(ethylene-co-vinyl acetate) and one or more bioactive agents and positioned upon the surface of a medical device in a manner that permits the coated surface to release the bioactive agent(s) over time when implanted in vivo, wherein the composition provides sufficient durability and flexibility to be used upon a device is one that undergoes flexion and/or expansion in the course of implantation or use in vivo.

8. A composition according to claim 7 wherein the bioactive release rate from a coated medical device can be manipulated by adjusting the relative concentrations of the first and second polymers.

9. A polymeric coating composition according to claim 7 wherein the coating comprises multiple polymeric layers.

10. A method for providing an implantable medical device with a therapeutic effect, the method comprising the step of providing a medical device having a surface coated with a composition comprising one or more bioactive agents in a manner that permits the coated surface to release the bioactive agent(s) over time when implanted in vivo, the composition comprising one or more bioactive agents in combination with a first polymer component comprising at least one poly(alkyl)(meth)acrylate and a second polymer component comprising poly(ethylene-co-vinyl acetate), wherein the device is one that undergoes flexion and/or expansion in the course of implantation or use in vivo.

13. A method according to claim 10, 11 or 12 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.

14. A method according to claim 10, 11, or 12 wherein the first and second polymer components are adapted to be mixed to provide a mixture that exhibits an optimal combination of physical characteristics and bioactive release characteristics as compared to the polymers when used alone.

15. A method according to claim 10, 11, or 12 wherein the amount and rate of release of agent(s) from the medical device can be controlled by adjusting the relative types and/or concentrations of the first and second polymers.

11. A method for providing an implantable medical device with a therapeutic effect, the method comprising the step of providing a medical device having a surface of the medical device with a composition comprising one or more bioactive agents in a manner that permits the coated surface to release the bioactive agent(s) over time when implanted in vivo, the composition comprising one or more bioactive agents in combination with a first polymer component comprising at least one poly(alkyl)(meth)acrylate and a second polymer component comprising poly(ethylene-co-vinyl acetate), 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.

12. A method for providing an implantable medical device with a therapeutic effect, the method comprising the step of providing a medical device having a coated with a composition comprising one or more bioactive agent(s) in a manner that permits the coated surface to release the bioactive agent(s) over time when implanted in vivo, the composition comprising one or more bioactive agent(s) in combination with a first polymer component comprising at least one poly(alkyl)(meth)acrylate and a second polymer component comprising poly(ethylene-co-vinyl acetate), wherein the device is selected from the group consisting of catheters and stents.

16. A composition for coating the surface of a medical device with a bioactive agent in a manner that permits the coated surface to release the bioactive agent over time when implanted in vivo, the composition comprising a bioactive agent in combination with a plurality of polymers, including a first polymer component comprising at least one poly(alkyl)(meth)acrylate and a second polymer component comprising poly(ethylene-co-vinyl acetate).

17. A composition according to claim 7 or 16 wherein the bioactive agent comprises an antithrombogenic agent.

18. A composition according to claim 7 or 16 wherein the bioactive agent comprises an anti-inflammatory agent.

19. A composition according to claim 7 or 16 wherein the bioactive agent comprises a remodeling inhibitor.

20. A composition according to claim 7 or 16 wherein the bioactive agent comprises an antiproliferative.

21. A combination comprising a medical device coated with a composition according to claim 7 or 16.

22. A combination according to claim 21 wherein the medical device comprises a stent.

23. A combination according to claim 21 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 combination according to claim 21 or 22 wherein the bioactive agent comprises an antithrombogenic agent.

25. A combination according to claim 21 or 22 wherein the bioactive agent comprises an anti-inflammatory agent.

26. A composition according to claim 21 or 22 wherein the bioactive agent comprises a remodeling inhibitor.

27. A composition according to claim 21 or 22 wherein the bioactive agent comprises an antiproliferative.