Polymeric coating for reducing the rate of release of a therapeutic substance from a stent

• US 8,303,651 B1
• Filed: 09/07/2001
• Issued: 11/06/2012
• Est. Priority Date: 09/07/2001
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Pacetti, Stephen D.
• Primary Examiner(s): Sonnett, Kathleen
• Assistant Examiner(s): Webb, Sarah
• Application Number:
  US09/948,513
• Time in Patent Office: 4,078 Days
• Field of Search: 623 142- 146, 623/1.15, 424/422
• US Class Current: 623/1.46
• 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 2420/08 Coatings comprising two or more layers
• 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

Abstract

A stent for delivery of a therapeutic agent is disclosed. The stent includes a polymer coating for reducing the rate of release of the therapeutic agent. The polymer has a crystalline structure wherein the polymer is capable of significantly maintaining the crystalline lattice structure while the therapeutic agent is released from the stent such that the aqueous environment to which the stent is exposed subsequent to the implantation of the stent does not significantly convert the crystalline lattice structure of the polymer to an amorphous structure.

Claims

1. A stent for delivery of a therapeutic agent, comprising:

a substrate;

a polymer coating on the substrate that substantially reduces the rate of release of the therapeutic agent, the polymer having a crystalline structure with a crystallinity of not less than about 25%, wherein the polymer is capable of significantly maintaining the crystalline structure while the therapeutic agent is released from the stent such that the aqueous environment to which the stent is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the polymer to an amorphous structure such that the crystallinity of the polymer is not less than about 25% when exposed to the aqueous environment subsequent to the implantation of the stent,

wherein the polymer having a crystalline structure is selected from a group consisting of fluoroethylene-alkyl vinyl ether copolymer, low density linear polyethylenes having high molecular weights, ethylene-olefin copolymers, styrene-ethylene-styrene block copolymers, styrene-butylene-styrene block copolymers, styrene-ethylene/butylene-styrene block copolymers, styrene-butadiene-styrene block copolymers, ethylene-anhydride copolymers, styrenic block copolymers, ethylene methacrylic acid copolymers, polyurethanes with a polydimethylsiloxane soft segment, and nylon 6; and

a primer layer ormed on a surface of the substrate, wherein the polymer coating is formed over the primer layer, and wherein the primer layer acts as an adhesive tie between the polymer coating and the surface of the stent.

2. The stent of claim 1, wherein the crystallinity of the polymer is not less than about 50% prior to the implantation of the stent.

3. The stent of claim 1, wherein the melting point of the polymer is greater than or equal to about 135°

C. at ambient pressure.

4. The stent of claim 1, wherein the polymer is a hydrophobic polymer having a solubility parameter of not more than about 10.7 (cal/cm³)^1/2.

5. The stent of claim 1, wherein the coating contains the therapeutic agent for delivery of the therapeutic agent.

6. The stent of claim 1, additionally comprising:

a reservoir layer containing the therapeutic agent formed on the primer layer, wherein the coating is formed on at least a portion of the reservoir layer to reduce the rate of release of the therapeutic agent.

7. The stent of claim 1, wherein the polymer coating comprises a second coating layer over a first coating layer, the first coating layer being a reservoir layer containing a therapeutic agent above the substrate, and the second coating layer being free from therapeutic agents.

8. A method of forming a coating for a stent that substantially reduces the rate of release of a therapeutic agent from the stent, comprising:

forming a primer layer on the stent;

applying a composition including a polymeric material to at least a portion of the stent to form a polymer coating supported by the stent, the polymer having a crystalline structure with a crystallinity of not less than 25%, wherein the aqueous environment to which the coating is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the polymer to an amorphous structure for the duration of time which the agent is released from the coating such that the crystallinity of the polymer is not less than about 25% when exposed to the aqueous environment subsequent to the implantation of the stent,

wherein the polymer having a crystalline structure is selected from a group consisting of fluoroethylene-alkyl vinyl ether copolymer, low density linear polyethylenes having high molecular weights, ethylene-olefin copolymers, styrene-ethylene-styrene block copolymers, styrene-butylene-styrene block copolymers, styrene-ethylene/butylene-styrene block copolymers, styrene-butadiene-styrene block copolymers, ethylene-anhydride copolymers, styrenic block copolymers, ethylene methacrylic acid copolymers, polyurethanes with a polydimethylsiloxane soft segment, and nylon 6.

9. A stent comprising a polymeric coating, wherein the coating is produced using the method of claim 8.

10. The method of claim 8, wherein the crystallinity of the polymeric material is not less than about 25% during the release of the therapeutic agent from the stent.

11. The method of claim 8, wherein the polymeric material has a solubility parameter not more than about 10.7 (cal/cm³)^1/2.

12. The method of claim 8, wherein the polymeric material has a melting point greater than or equal to about 135°

C. at ambient pressure.

13. The method of claim 8, wherein the polymer coating comprises a second coating layer over a first coating layer, the first coating layer being a reservoir layer containing a therapeutic agent above the substrate, and the second coating layer being free from therapeutic agents.

14. A stent for delivering a therapeutic agent to an implanted site, comprising:

a radially expandable body structure;

a primer on a surface of the radially expandable body structure; and

a polymeric coating supported by the body structure that substantially increases the residence time of the therapeutic agent at the implanted site, wherein the polymeric coating is made from a hydrophobic polymer having a degree of crystallinity that remains at or above about 10% at least until a significant amount of the therapeutic substance has been released from the stent,

wherein the polymer having a degree of crystallinity that remains at or above about 10% is selected from a group consisting of fluoroethylene-alkyl vinyl ether copolymer, low density linear polyethylenes having high molecular weights, ethylene-olefin copolymers, styrene-ethylene-styrene block copolymers, styrene-butylene-styrene block copolymers, styrene-ethylene/butylene-styrene block copolymers, styrene-butadiene-styrene block copolymers, ethylene-anhydride copolymers, ethylene-acrylic acid copolymers, styrenic block copolymers, ethylene methacrylic acid copolymers, polyurethanes with a polydimethylsiloxane soft segment, and nylon 6.

15. The stent of claim 14, wherein the polymer coating comprises a second coating layer over a first coating layer, the first coating layer being a reservoir layer containing a therapeutic agent above the substrate, and the second coating layer being free from therapeutic agents.

16. A stent for delivery of a therapeutic agent, comprising:

a substrate; and

a polymer coating on the substrate that substantially reduces the rate of release of the therapeutic agent, the polymer having a crystalline structure with a degree of crystallinity of not less than about 10%, wherein the polymer is capable of significantly maintaining the crystalline structure while the therapeutic agent is released from the stent such that the aqueous environment to which the stent is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the polymer to an amorphous structure, and

wherein the polymer is an ethylene-acrylic acid copolymer.

17. A method of forming a coating for a stent that substantially reduces the rate of release of a therapeutic agent from the stent, comprising:

applying a composition including a polymeric material to at least a portion of the stent to form a polymer coating supported by the stent, the polymer having a crystalline structure with a degree of crystallinity of not less than about 10%, wherein the aqueous environment to which the coating is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the polymer to an amorphous structure for the duration of time which the agent is released from the coating, and

wherein the polymer is an ethylene-acrylic acid copolymer.

18. A stent for delivery of a therapeutic agent, comprising:

a substrate; and

a polymer coating on the substrate that substantially reduces the rate of release of the therapeutic agent, the polymer having a crystalline structure with a crystallinity of not less than about 25%, wherein the polymer is capable of significantly maintaining the crystalline structure while the therapeutic agent is released from the stent such that the aqueous environment to which the stent is exposed subsequent to the implantation of the stent does not significantly convert the crystalline structure of the polymer to an amorphous structure such that the crystallinity of the polymer is not less than about 25% when exposed to the aqueous environment subsequent to the implantation of the stent,

with the proviso of (1) a primer layer being under the coating, a barrier layer being over the coating, or both;

or (2) wherein the polymer coating is a barrier layer disposed over a reservoir layer.