Drug-polymer coated stent with pegylated styrenic block copolymers

• US 6,918,929 B2
• Filed: 01/24/2003
• Issued: 07/19/2005
• Est. Priority Date: 01/24/2003
• Status: Expired due to Term

• Current Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Original Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Inventors: Patel, Kaushik, Udipi, Kishore, Cheng, Peiwen, Sundar, Rangarajan
• Primary Examiner(s): Barrett, Thomas C.
• Application Number:
  US10/351,156
• Publication Number:
  US 20040148003A1
• Time in Patent Office: 907 Days
• Field of Search: 623 142- 146, 427 21- 231
• US Class Current: 623/1.42
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61L 2300/606 Coatings
• 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 51/006 grafted on to block copolymers containing at least one sequence of polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: C08L 53/02 of vinyl-aromatic monomers and conjugated dienes

Abstract

The present invention provides a system for treating a vascular condition, including a catheter, a stent coupled to the catheter, a drug-polymer coating on the stent including a grafted styrenic block copolymer, and at least one bioactive drug dispersed within the drug-polymer coating.

Claims

1. A system for treating a vascular condition, comprising:

a catheter;

a stent coupled to the catheter, the stent including a stent framework;

a drug-polymer coating disposed on the stent framework, wherein the drug-polymer coating comprises a pegylated styrenic block copolymer matrix; and

a bioactive agent dispersed within the pegylated styrenic block copolymer matrix.

2. The system of claim 1 wherein the catheter includes a balloon used to expand the stent.

3. The system of claim 1 wherein the catheter includes a sheath that retracts to allow expansion of the stent.

4. The system of claim 1 wherein the stent framework comprises a metallic base.

5. The system of claim 4 wherein the metallic base is selected from the group consisting of stainless steel, nitinol, tantalum, a nonmagnetic nickel-cobalt-chromium-molybdenum [MP35N] alloy, platinum, titanium, a suitable biocompatible alloy, a suitable biocompatible material, and a combination thereof.

6. The system of claim 1 wherein the stent framework comprises a polymeric base.

7. The system of claim 1 wherein the pegylated styrenic block copolymer matrix comprises a styrenic block copolymer and polymeric grafts of polyethylene glycol.

8. The system of claim 7 wherein the styrenic block copolymer has a molecular weight between 200 Daltons and 200,000 Daltons.

9. The system of claim 7 wherein the polymeric grafts have a molecular weight between 500 Daltons and 500,000 Daltons.

10. The system of claim 1 wherein the pegylated styrenic block copolymer matrix provides a controlled drug-elution characteristic.

11. The system of claim 1 wherein the drug-polymer coating comprises between 0.5 percent and 50 percent of the bioactive agent by weight.

12. The system of claim 1 wherein the drug-polymer coating has a thickness between 0.5 microns and 20 microns.

13. The system of claim 1 wherein the drug-polymer coating has a weight between 50 micrograms and 1500 micrograms.

14. The system of claim 1 wherein the bioactive agent comprises an antirestenotic drug.

15. The system of claim 1 wherein the bioactive agent is selected from a group consisting of an antisense agent, an antineoplastic agent, an antiproliferative agent, an antithrombogenic agent, an anticoagulant, an antiplatelet agent, an antibiotic, an anti-inflammatory agent, a steroid, a gene therapy agent, a therapeutic substance, an organic drug, a pharmaceutical compound, a recombinant DNA product, a recombinant RNA product, a collagen, a collagenic derivative, a protein, a protein analog, a saccharide, and a saccharide derivative.

16. The system of claim 1 wherein the drug-polymer coating comprises a plurality of drugs, each drug having a predetermined elution rate, the pegylated styrenic block copolymer matrix eluting the drugs at the predetermined elution rates.

17. The system of claim 1 wherein the pegylated styrenic block copolymer matrix disposed on the stent framework has a hydrophobic characteristic and a hydrophilic characteristic, the hydrophobic characteristic being more pronounced adjacent the stent framework, and the hydrophilic characteristic being more pronounced adjacent an outer surface of the drug-polymer coating.

18. The system of claim 17 wherein a first bioactive drug having a hydrophobic characteristic is concentrated adjacent the stent framework, and a second bioactive drug having a hydrophilic characteristic is concentrated adjacent the outer surface of the drug-polymer coating.

19. The system of claim 18 wherein the first bioactive drug comprises an antirestenotic drug and the second bioactive drug comprises an anti-inflammatory drug.

20. The system of claim 1 further comprising:

a primer coating disposed on the stent framework between the stent framework and the drug-polymer coating.

21. The system of claim 20 wherein the primer coating is selected from the group consisting of parylene, polyurethane, phenoxy, epoxy, polyimide, polysulfone, pellathane, and a suitable polymeric primer material.

22. A method of manufacturing a drug-polymer coated stent, comprising:

forming a polymeric solution including a styrenic block copolymer and a pegylated styrenic block copolymer solvent;

adding polyethylene glycol to the polymeric solution to form polymeric grafts of polyethylene glycol along the styrenic block copolymer;

mixing at least one bioactive agent with the polymeric solution to form a drug-polymer solution;

applying the drug-polymer solution onto a stent framework; and

drying the drug-polymer solution.

23. The method of claim 22 wherein the pegylated styrenic block copolymer solvent is selected from the group consisting of chloroform, tetrahydrofuran, methyl chloride, toluene, ethyl acetate, dioxane, and a organic solvent.

24. The method of claim 22 further comprising:

adding an aliquot of maleic anhydride to the polymeric solution to initiate formation of the polymeric grafts.

25. The method of claim 22 wherein the drug-polymer solution is applied using an application technique selected from the group consisting of dipping, spraying, painting, and brushing.

26. The method of claim 22 wherein the drug-polymer solution is dried in a vacuum environment.

27. The method of claim 22 wherein the drug-polymer solution is dried at a temperature between 25 degrees centigrade and 45 degrees centigrade.

28. A drug-polymer coated stent, comprising:

a stent framework; and

a drug-polymer coating disposed on the stent framework, wherein the drug-polymer coating comprises a styrenic block copolymer grafted with polyethylene glycol; and

a bioactive drug dispersed within the drug-polymer coating.

29. The system of claim 28 wherein the stent framework comprises one of a metallic base or a polymeric base.

30. The system of claim 28 wherein the grafted styrenic block copolymer comprises a chain length of the styrenic block copolymer, a chain length of the polyethylene glycol grafts, and a polyethylene glycol based on a predetermined elution rate of the bioactive drug.

31. The system of claim 28 wherein the bioactive drug comprises a bioactive agent selected from the group consisting of an antirestenotic agent, an antisense agent, an antineoplastic agent, an antiproliferative agent, an antithrombogenic agent, an anticoagulant, an antiplatelet agent, an antibiotic, an anti-inflammatory agent, a steroid, a gene therapy agent, a therapeutic substance, an organic drug, a pharmaceutical compound, a recombinant DNA product, a recombinant RNA product, a collagen, a collagenic derivative, a protein, a protein analog, a saccharide, and a saccharide derivative.

32. The system of claim 28 further comprising:

a primer coating disposed on the stent framework between the stent framework and the drug-polymer coating.

33. The system of claim 32 wherein the primer coating is selected from the group consisting of parylene, polyurethane, phenoxy, epoxy, polyimide, polysulfone, pellathane, and a suitable polymeric primer material.

34. A method of treating a vascular condition, comprising:

inserting a drug-polymer coated stent within a vessel of a body, the drug-polymer coated stent including at least one bioactive agent and a block copolymer grafted with polyethylene glycol; and

eluting the bioactive agents from the drug-polymer coated stent into the body.

35. The method of claim 34 wherein the grafted styrenic block copolymer controls an elution rate of each bioactive agent.

36. The method of claim 34 further comprising:

selecting the grafted styrenic block copolymer based on a predetermined elution rate of each bioactive agent.