Bioactive agent release coating

• US 7,442,402 B2
• Filed: 11/17/2005
• Issued: 10/28/2008
• Est. Priority Date: 04/27/1998
• Status: Expired due to Fees

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Chappa, Ralph A., Anderson, Aron B., Chudzik, Stephen J., Kloke, Timothy M.
• Primary Examiner(s): Sheikh; Humera N
• Application Number:
  US11/281,845
• Publication Number:
  US 20060067968A1
• Time in Patent Office: 1,076 Days
• Field of Search: 427/2.1, 424/489
• 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 method of adjusting the rate of release of one or more bioactive agents from a medical device comprising;

providing a medical device having one or more surfaces;

applying a mixture to the one or more surfaces, the mixture comprising hydrophobic polymers in combination with one or more bioactive agents;

wherein the hydrophobic polymers comprise at least one poly(alkyl)(meth)acrylate and at least one poly(ethylene-co-vinyl acetate); and

adjusting the relative concentrations of hydrophobic polymers in the mixture to control the rate of release of the bioactive agent.

2. The method of claim 1 wherein individual hydrophobic polymer concentrations in the mixture are between about 0.05 and about 70 weight percent.

3. The method of claim 1, wherein the hydrophobic polymers are complementary.

4. A combination comprising:

a medical device having one or more surfaces;

a mixture carried on the one or more surfaces, the mixture comprising complementary hydrophobic polymers in combination with one or more bioactive agents, wherein individual hydrophobic polymer concentrations in the mixture are between about 0.05 and about 70 weight percent;

wherein the complementary hydrophobic polymers comprise at least one poly(alkyl)(meth)acrylate and at least one poly(ethylene-co-vinyl acetate).

5. The combination of claim 4 wherein the device is one that undergoes flexion and/or expansion in the course of implantation or use in vivo.

6. The combination of claim 4 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.

7. A combination comprising:

a stent having one or more surfaces;

a mixture carried on the one or more surfaces, the mixture comprising a plurality of polymers, including a first polymer component comprising a poly(alkyl)(meth)acrylate and a second polymer component comprising a poly(ethylene-co-vinyl acetate) in combination with one or more bioactive agents, wherein the first polymer and the second polymer concentrations in the mixture are each between about 0.05 and about 70 weight percent.

8. The combination of claim 7 wherein the first polymer component is selected from the group consisting of poly(alkyl)(meth)acrylates with alkyl chain lengths from 2 to 8 carbons.

9. The combination of claim 8 wherein the first polymer component has a molecular weight of from 50 kilodaltons to 900 kilodaltons.

10. The combination of claim 8 wherein the first polymer component comprises poly n-butylmethacrylate.

11. The combination of claim 7 wherein the second polymer component is selected from the group consisting of poly(ethylene-co-vinyl acetate) polymers having vinyl acetate concentrations of between about 10% and about 50% by weight.

12. The combination of claim 11 wherein the vinyl acetate concentrations are between about 24% and about 36% by weight.

13. The combination of claim 12 wherein the vinyl acetate concentrations are between about 30% and about 34% by weight.

14. A combination comprising:

a medical device having one or more surfaces;

a mixture carried on the one or more surfaces, the mixture consisting essentially of a first hydrophobic polymer and a second hydrophobic polymer and a bioactive agent, wherein the first hydrophobic polymer and the second hydrophobic polymer each have a concentration in the mixture between about 0.05 and about 70 weight percent;

wherein the first hydrophobic polymer is a poly(alkyl)(meth)acrylate and the second hydrophobic polymer is a poly(ethylene-co-vinyl acetate).

15. A combination according to claim 14 wherein the device is one that undergoes flexion and/or expansion in the course of implantation or use in vivo.

16. A combination according to claim 14 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.

17. A method of adjusting the rate of release of one or more bioactive agents from a medical device comprising;

providing a medical device having one or more surfaces;

applying a mixture to the one or more surfaces, the mixture comprising a first hydrophobic polymer and a second hydrophobic polymer in combination with one or more bioactive agents; and

adjusting the relative concentrations of the first and second hydrophobic polymers in the mixture to either increase or decrease the release rate of the bioactive agent as desired;

wherein the hydrophobic polymers comprise at least one poly(alkyl)(meth)acrylate and at least one poly(ethylene-co-vinyl acetate).

18. The method of claim 17, wherein the rate of release is increased by increasing the concentration of poly(ethylene-co-vinyl acetate).

19. The method of claim 17, wherein the rate of release is decreased by increasing the concentration of poly(ethylene-co-vinyl acetate) relative to the concentration of poly(alkyl)(meth)acrylate.