Stents with hybrid coating for medical devices

• US 6,231,600 B1
• Filed: 05/26/1999
• Issued: 05/15/2001
• Est. Priority Date: 02/22/1995
• Status: Expired due to Fees

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Inventors: Zhong, Sheng-ping
• Primary Examiner(s): Isabella, David J.
• Assistant Examiner(s): Koh, Choon P.
• Application Number:
  US09/320,340
• Time in Patent Office: 720 Days
• Field of Search: 623/1.42, 623/1.43, 623/1.46, 427/2.24, 427/402, 428/423.1, 428/424.4
• US Class Current: 623/1.42
• CPC Class Codes: A61L 2300/21 Acids
• CPC Class Codes: A61L 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2300/61 containing two or more active agents in different layers
• 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 75/04 Polyurethanes
• CPC Class Codes: Y10T 428/31551 Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]
• CPC Class Codes: Y10T 428/31576 Ester monomer type [polyvinylacetate, etc.]

Abstract

A device such as a stent is provided with a hybrid coating including a time released, restenosis inhibiting coating and a non-thrombogenic coating to prevent clotting on the device. One first coat or layer includes a polymer, a crosslinking agent, and pacitaxel, analogues, or derivatives thereof. The first coat preferably includes a polymer having Taxol admixed therein so as to be releasable over time. The first coat preferably includes a polyfunctional aziridine as the crosslinking agent. The second coat preferably includes heparin to inhibit clot formation on the device. The crosslinking agent can covalently bond to both the first coat polymer and the second coat heparin. A stent can be provided with a first coat including an aqueous dispersion or emulsion of a polymer and an excess of crosslinking agent. The first coating can be dried, leaving a water insoluble polymer coating. A second aqueous coating including a solution or dispersion of heparin can be applied over the first coating, the heparin becoming covalently bound to the crosslinking agent on the first coating surface. The resulting stent can inhibit restenosis while preventing blood clot formation on the stent.

Claims

1. A stent comprising:

a substantially tubular body;

a first coating disposed over said body, said first coating including a polymeric material, a first therapeutic agent admixed in said polymeric material, and a crosslinking agent; and

a second coating disposed over said first coating including a second therapeutic agent, wherein said crosslinking agent binds said second therapeutic agent to said polymeric material.

2. A stent as recited in claim 1, wherein said second therapeutic agent has non-thrombogenic properties.

3. A stent as recited in claim 1, wherein said second therapeutic agent is covalently bound to said crosslinking agent.

4. A stent as recited in claim 1, said first therapeutic is selected from the group consisting of paclitaxel, paclitaxel analogues, paclitaxel derivatives, and combinations thereof, and said second therapeutic agent includes heparin.

5. A stent as recited in claim 1, wherein said crosslinking agent includes polyfunctional aziridine.

6. A stent comprising:

a substantially tubular body;

means for inhibiting restenosis;

means for adhering said restenosis inhibiting means to said stent body and releasing said restenosis inhibiting means from said stent body over time; and

means for rendering said stent body non-thrombogenic.

7. A stent comprising:

a substantially tubular body;

a polymer having organic acid functional groups;

a first coating layer including a first therapeutic agent admixed with said polymer and a polyfunctional crosslinking agent covalently bonded to said polymer organic acid functional groups; and

a second coating layer disposed over said first coating layer including a second therapeutic agent covalently bonded to said polyfunctional crosslinking agent.

8. A stent as recited in claim 7, wherein said first therapeutic agent is capable of diffusing out of said first layer.

9. A stent as recited in claim 7, wherein said second therapeutic agent is biocompatible with a human blood stream.

10. A stent as recited in claim 7, wherein said first therapeutic agent includes taxol, analogues, or derivatives thereof and said second therapeutic agent has non-thrombogenic properties.

11. A stent as recited in claim 7, wherein said first therapeutic agent includes pacitaxel, analogues, or derivatives thereof, said polymer includes polyurethane, said crosslinking agent includes a polyfunctional aziridine, and said second therapeutic agent includes heparin, wherein said polyfunctional aziridine is covalently bonded to said polyurethane and to said heparin.

12. A method for providing a substrate with a biocompatible and restenosis inhibiting coating comprising the steps of:

coating said substrate with a first aqueous coating composition including a polymer having organic acid functional groups, a first therapeutic agent, an excess of a polyfunctional crosslinking agent having functional groups capable of reacting with organic acid groups;

drying said first coating composition to obtain a substantially water insoluble coating layer still including functional groups being reactive with organic acid groups;

forming a non-thrombogenic surface over said first coating composition by contacting said dried first coating composition with a second aqueous coating composition including heparin; and

drying said second coating, to bond said heparin to said excess crosslinking agent.

13. A method according to claim 12, wherein said organic acid functional groups are selected from the group consisting of free carboxylic and sulfonic acid groups, metal salts of said acid groups, alkali metal salts of said acid groups, and quaternary amine salts of said acid groups.

14. A method according to claim 12, wherein said polyfunctional crosslinking agent is selected from polyfunctional aziridines, polyfunctional carboimides, and combinations thereof.

15. A method according to claim 12, wherein said polymer in said first coating composition is selected from the group consisting of polyurethanes, polyacrylates, polymethacrylates, polyisocrotonates, epoxy resins, acrylate-urethane co-polymers, and combinations thereof.

16. A method according to claim 15, wherein said polymer in the first coating composition selected from the group consisting of acrylate-urethane co-polymers, polyurethane, and mixtures thereof.