Implantable Drug Delivery Devices Having Alternating Hyrdrophilic And Amphiphilic Polymer Layers

• US 20090297575A1
• Filed: 05/30/2008
• Published: 12/03/2009
• Est. Priority Date: 05/30/2008
• Status: Active Grant

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Inventors: Hossainy, Syed F.A., Kleiner, Lothar W., Trollsas, Mikael O.
• Granted Patent: US 8,202,529 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: Y10T 428/31551 Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]
• CPC Class Codes: Y10T 428/31562 Next to polyamide [nylon, etc.]
• CPC Class Codes: Y10T 428/31591 Next to cellulosic
• CPC Class Codes: Y10T 428/31736 Next to polyester
• CPC Class Codes: Y10T 428/3175 Next to addition polymer from unsaturated monomer[s]
• CPC Class Codes: Y10T 428/31786 Of polyester [e.g., alkyd, etc.]
• CPC Class Codes: Y10T 428/3179 Next to cellulosic
• CPC Class Codes: Y10T 428/31855 Of addition polymer from unsaturated monomers
• CPC Class Codes: Y10T 428/31891 Where addition polymer is an ester or halide

Abstract

An implantable drug delivery medical device with alternating hydrophilic and amphiphilic polymer layers and methods of using for the treatment of vascular disease are disclosed.

Claims

1. An implantable medical device comprising:

a device body; and

a soluble coating comprising,

a primer layer disposed over the device body, wherein the primer layer comprises either a hydrophilic polymer or an amphiphilic polymer;

a reservoir layer disposed over the primer layer, wherein if the primer layer comprises a hydrophilic polymer the reservoir layer comprises an amphiphilic polymer or alternatively if the primer layer comprises an amphiphilic polymer the reservoir layer comprises a hydrophilic polymer; and

a topcoat layer disposed over the reservoir layer, wherein if the reservoir layer comprises a hydrophilic polymer the topcoat layer comprises an amphiphilic polymer or alternatively if the reservoir layer comprises an amphiphilic polymer the topcoat layer comprises a hydrophilic polymer,

wherein the soluble coating solvates completely within about 30 days after deployment of the implantable medical device.

2. The implantable medical device according to claim 1, wherein the device body comprises a soluble stent, a metal stent or a bare polymer stent.

3. The implantable medical device according to claim 2, wherein the metal stent material is selected from the group consisting of stainless steel, nitinol, tantalum, tantalum alloy, titanium, titanium alloy, cobalt chromium, nickel chromium iron alloy, niobium, niobium alloy, zirconium and zirconium alloy.

4. The implantable medical device according to claim 1, wherein the hydrophilic polymer is selected from the group consisting of polyvinylpyrrolidone, poly(carboxymethyl cellulose) and poly[N-(2-hydroxypropyl)methacrylamide].

5. The implantable medical device according to claim 1, wherein the amphiphilic polymer is selected from the group consisting of poly(n-butyl methacrylate-phosphorylcholine), poly(ester amide)-phosphorylcholine, polylactide-phosphorylcholine, polylactide-phosphorylcholine, polyethylene glycol-poly(caprolactone)-di- or tri-blocks, polyethylene glycol-polylactide di- or tri-blocks and polyethylene glycol-poly(lactide-glycolide) di-or tri-blocks.

6. The implantable medical device according to claim 1, wherein the reservoir layer comprises one or more bioactive agents selected from the group consisting of an antiproliferative agent, an anti-inflammatory agent, an antineoplastic, an antimitotic, an antiplatelet, an anticoagulant, an antifibrin, an antithrombin, a cytostatic agent, an antibiotic, an anti-allergic agent, an anti-enzymatic agent, an angiogenic agent, a cyto-protective agent, a cardioprotective agent, a proliferative agent, an ABC A1 agonist and an antioxidant or any combination thereof.

7. The implantable medical device according to claim 1 further comprising a rate-controlling layer disposed over the drug reservoir layer, wherein if the reservoir layer comprises a hydrophilic polymer the rate-controlling layer comprises an amphiphilic polymer and the topcoat layer comprises a hydrophilic polymer or alternatively if the reservoir layer comprises an amphiphilic polymer the rate-controlling layer comprises a hydrophilic polymer and the topcoat layer comprises an amphiphilic polymer.

8. The implantable medical device according to claim 1, wherein the soluble coating solvates completely within about 14 days after deployment of the implantable medical device.

9. The implantable medical device according to claim 1, wherein the soluble coating solvates completely within about 1 to 3 days after deployment of the implantable medical device.

10. The implantable medical device according to claim 1, wherein about 80% of the bioactive agent releases from the soluble coating within about 1 to 3 days after deployment of the implantable medical device.

16. A method for treating or preventing a vascular disease comprising implanting the medical device according to claim 1 in a vessel of a patient in need thereof.

17. The method according to claim 16, wherein the vascular disease is atherosclerosis, restenosis, vulnerable plaque or peripheral arterial disease.

11. A soluble coating for an implantable medical device comprising:

a primer layer comprising either a hydrophilic polymer or an amphiphilic polymer;

a reservoir layer disposed over the primer layer, wherein if the primer layer comprises a hydrophilic polymer the reservoir layer comprises an amphiphilic polymer or alternatively if the primer layer comprises an amphiphilic polymer the reservoir layer comprises a hydrophilic polymer; and

a topcoat layer disposed over the drug reservoir layer, wherein if the reservoir layer comprises a hydrophilic polymer the topcoat layer comprises an amphiphilic polymer or alternatively if the reservoir layer comprises an amphiphilic polymer the topcoat layer comprises a hydrophilic polymer,

wherein the soluble coating solvates completely within about 30 days after deployment of the implantable medical device.

12. The soluble coating according to claim 11, wherein the hydrophilic polymer is selected from the group consisting of polyvinylpyrrolidone, poly(carboxymethyl cellulose) and poly[N-(2-hydroxypropyl)methacrylamide].

13. The soluble coating according to claim 11, wherein the amphiphilic polymer is selected from the group consisting of poly(n-butyl methacrylate-phosphorylcholine), poly(ester amide)-phosphorylcholine, polylactide-phosphorylcholine, polylactide-phosphorylcholine, polyethylene glycol-poly(caprolactone)-di- or tri-blocks, polyethylene glycol-polylactide di- or tri-blocks and polyethylene glycol-poly(lactide-glycolide) di-or tri-blocks.

14. The soluble coating according to claim 11, wherein the reservoir layer comprises one or more bioactive agents selected from the group consisting of an antiproliferative agent, an anti-inflammatory agent, an antineoplastic, an antimitotic, an antiplatelet, an anticoagulant, an antifibrin, an antithrombin, a cytostatic agent, an antibiotic, an anti-allergic agent, an anti-enzymatic agent, an angiogenic agent, a cyto-protective agent, a cardioprotective agent, a proliferative agent, an ABC A1 agonist or an antioxidant or any combination thereof.

15. The soluble coating according to claim 11 further comprising a rate-controlling layer disposed over the drug reservoir layer, wherein if the reservoir layer comprises a hydrophilic polymer the rate-controlling layer comprises an amphiphilic polymer and the topcoat layer comprises a hydrophilic polymer or alternatively if the reservoir layer comprises an amphiphilic polymer the rate-controlling layer comprises a hydrophilic polymer and the topcoat layer comprises an amphiphilic polymer.

18. A soluble implantable medical device comprising alternating layers of hydrophilic and amphiphilic polymers.

19. The implantable medical device according to claim 18, wherein the hydrophilic polymer is selected from the group consisting of polyvinylpyrrolidone, poly(carboxymethyl cellulose) and poly[N-(2-hydroxypropyl)methacrylamide].

20. The implantable medical device according to claim 18, wherein the amphiphilic polymer is selected from the group consisting of poly(n-butyl methacrylate-phosphorylcholine), poly(ester amide)-phosphorylcholine, polylactide-phosphorylcholine, polylactide-phosphorylcholine, polyethylene glycol-poly(caprolactone)-di- or tri-blocks, polyethylene glycol-polylactide di- or tri-blocks and polyethylene glycol-poly(lactide-glycolide) di-or tri-blocks.

21. The implantable medical device according to claim 18 further comprising one or more bioactive agents integrated into the structure of or adhered to the surface of the device.

22. The implantable medical device according to claim 21, wherein the one or more bioactive agents are selected from the group consisting of an antiproliferative agent, an anti-inflammatory agent, an antineoplastic, an antimitotic, an antiplatelet, an anticoagulant, an antifibrin, an antithrombin, a cytostatic agent, an antibiotic, an anti-allergic agent, an anti-enzymatic agent, an angiogenic agent, a cyto-protective agent, a cardioprotective agent, a proliferative agent, an ABC A1 agonist or an antioxidant or any combination thereof.

23. A method for fabricating an implantable medical device comprising a soluble coating comprising:

providing a device body;

disposing a primer layer over the device body wherein the primer layer comprises either a hydrophilic polymer or an amphiphilic polymer;

disposing a reservoir layer over the primer layer, wherein if the primer layer comprises a hydrophilic polymer the reservoir layer comprises an amphiphilic polymer or alternatively if the primer layer comprises an amphiphilic polymer the reservoir layer comprises a hydrophilic polymer; and

disposing a topcoat layer over the reservoir layer, wherein if the reservoir layer comprises a hydrophilic polymer the topcoat layer comprises an amphiphilic polymer or alternatively if the reservoir layer comprises an amphiphilic polymer the topcoat layer comprises a hydrophilic polymer.

24. The method according to claim 23, wherein the device body comprises a soluble stent, a metal stent or a bare polymer stent.

25. The method according to claim 24, wherein the metal stent material is selected from the group consisting of stainless steel, nitinol, tantalum, tantalum alloy, titanium, titanium alloy, cobalt chromium, nickel chromium iron alloy, niobium, niobium alloy, zirconium and zirconium alloy.

26. The method according to claim 23, wherein the hydrophilic polymer is selected from the group consisting of polyvinylpyrrolidone, poly(carboxymethyl cellulose) and poly[N-(2-hydroxypropyl)methacrylamide].

27. The method according to claim 23, wherein the amphiphilic polymer is selected from the group consisting of poly(n-butyl methacrylate-phosphorylcholine), poly(ester amide)-phosphorylcholine, polylactide-phosphorylcholine, polylactide-phosphorylcholine, polyethylene glycol-poly(caprolactone)-di- or tri-blocks, polyethylene glycol-polylactide di- or tri-blocks and polyethylene glycol-poly(lactide-glycolide) di-or tri-blocks.

28. The method according to claim 23, wherein the reservoir layer comprises one or more bioactive agents selected from the group consisting of an antiproliferative agent, an anti-inflammatory agent, an antineoplastic, an antimitotic, an antiplatelet, an anticoagulant, an antifibrin, an antithrombin, a cytostatic agent, an antibiotic, an anti-allergic agent, an anti-enzymatic agent, an angiogenic agent, a cyto-protective agent, a cardioprotective agent, a proliferative agent, an ABC A1 agonist and an antioxidant or any combination thereof.

29. The method according to claim 23 further comprising:

disposing a rate-controlling layer over the drug reservoir layer, wherein if the reservoir layer comprises a hydrophilic polymer the rate-controlling layer comprises an amphiphilic polymer and the topcoat layer comprises a hydrophilic polymer or alternatively if the reservoir layer comprises an amphiphilic polymer the rate-controlling layer comprises a hydrophilic polymer and the topcoat layer comprises an amphiphilic polymer.