Medical devices to treat or inhibit restenosis

• US 20060062822A1
• Filed: 09/14/2005
• Published: 03/23/2006
• Est. Priority Date: 09/21/2004
• Status: Abandoned Application

• Current Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Original Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Inventors: Hezi-Yamit, Ayala
• Application Number:
  US11/227,729
• Publication Number:
  US 20060062822A1
• Time in Patent Office: Days
• US Class Current: 424/422
• CPC Class Codes: A61K 31/4188 condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• 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 2300/434 of enzymes
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• 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

Abstract

Implantable medical devices having anti-restenotic coatings are disclosed. Specifically, implantable medical devices having coatings of aldose reductase (AR) inhibitors are disclosed. Preferred AR inhibitors are enumerated. The anti-restenotic medical devices include stents, catheters, micro-particles, probes and vascular grafts. Intravascular stents are preferred medical devices. The medical devices can be coated using any method known in the art including compounding the AR inhibitor with a biocompatible polymer prior to applying the coating. Moreover, medical devices composed entirely of biocompatible polymer-AR inhibitor blends are disclosed. Additionally, medical devices having a coating comprising at least one AR inhibitor in combination with at least one additional therapeutic agent are also disclosed. Furthermore, related methods of using and making the anti-restenotic implantable devices are also disclosed.

Claims

1. An implantable medical device for the treatment or inhibition of restenosis, said device coated with an aldose reductase inhibitor.

2. The medical device according to claim 1 wherein the aldose reductase inhibitor is selected from the group consisting of sorbinil, epalrestat, ponalrestat, methosorbinil, risarestat, imirestat, ALO-1567, quercetin, zopolrestat, AD-5467, NZ-314, M-16209, minalrestat, AS-3201, WP-921, luteolin, tolrestat, EBPC, fidarestat, and the pharmaceutically acceptable derivatives thereof.

3. The medical device according to claim 1 selected from the group consisting of stents, catheters, micro-particles, probes and vascular grafts.

4. The medical device according to claim 3 wherein said stent is an intravascular stent, esophageal stent, urethral stent or biliary stent.

5. The medical device according to claim 4 coated with a biocompatible polymer.

6. An intravascular stent having a coating comprising a biocompatible polymer and an aldose reductase inhibitor.

7. The intravascular stent of claim 6 wherein the aldose reductase inhibitor is selected from the group consisting of sorbinil, epalrestat, ponalrestat, methosorbinil, risarestat, imirestat, ALO-1567, quercetin, zopolrestat, AD-5467, NZ-314, M-16209, minalrestat, AS-3201, WP-921, luteolin, tolrestat, EBPC, fidarestat, and the pharmaceutically acceptable derivatives thereof.

8. The intravascular stent according to claim 6 wherein said coating comprises:

between about 10 μ

g and 1.0 mg of an aldose reductase inhibitor, and

a biocompatible polymer,

wherein said aldose reductase inhibitor and said biocompatible polymer are in a ratio relative to each other of between about 1;

1 to about 1;

10 (w/w).

9. The intravascular stent according to claim 6 wherein said stent has a metallic body.

10. The intravascular stent according to claim 6 wherein said coating comprises at least one additional therapeutic agent.

11. A method of treating or inhibiting restenosis comprising:

providing an intravascular stent having a coating comprising an aldose reductase inhibitor; and

implanting said intravascular stent into a blood vessel lumen at risk for restenosis,

wherein said aldose reductase inhibitor is released into tissue adjacent said blood vessel lumen.

12. The method according to claim 11 wherein said coating comprises:

between about 10 μ

g and 1.0 mg of aldose reductase inhibitor, and

a biocompatible polymer,

wherein said aldose reductase inhibitor and said biocompatible polymer are in a ratio relative to each other of between about 1;

1 to about 1;

10 (w/w).

13. The method according to claim 11 wherein said aldose reductase inhibitor is selected from the group consisting of sorbinil, epalrestat, ponalrestat, methosorbinil, risarestat, imirestat, ALO-1567, quercetin, zopolrestat, AD-5467, NZ-314, M-16209, minalrestat, AS-3201, WP-921, luteolin, tolrestat, EBPC, fidarestat, and the pharmaceutically acceptable derivatives thereof

14. A method for producing a medical device comprising:

providing medical device to be coated;

compounding an aldose reductase inhibitor with a carrier compound; and

coating said medical device with said aldose reductase inhibitor compounded with said carrier compound.

15. The method according to claim 14 wherein said medical device is an intravascular stent.

16. The method according to claim 14 wherein said carrier compound is a biocompatible polymer.

17. The method according to claim 14 wherein said coating is performed in multiple steps.

18. The method according to claim 14 wherein said aldose reductase inhibitor is selected from the group consisting of sorbinil, epalrestat, ponalrestat, methosorbinil, risarestat, imirestat, ALO-1567, quercetin, zopolrestat, AD-5467, NZ-314, M-16209, minalrestat, AS-3201, WP-921, luteolin, tolrestat, EBPC, fidarestat, and the pharmaceutically acceptable derivatives thereof.