Coating construct containing poly (vinyl alcohol)

• US 7,601,383 B2
• Filed: 02/28/2006
• Issued: 10/13/2009
• Est. Priority Date: 02/28/2006
• Status: Expired due to Fees

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories), Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Kleiner, Lothar W., Glauser, Thierry, Pacetti, Stephen D., Hossainy, Syed Faiyaz Ahmed, DesNoyer, Jessica Renee
• Primary Examiner(s): Barr; Michael
• Assistant Examiner(s): BOWMAN, ANDREW J
• Application Number:
  US11/365,392
• Publication Number:
  US 20070202323A1
• Time in Patent Office: 1,323 Days
• Field of Search: 526/242, 427/2.3, 427/2.28, 525/60, 424/423, 528/310
• US Class Current: 427/2.1
• 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 2300/422 Anti-atherosclerotic agents
• 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 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: Y10T 428/265 1 mil or less
• CPC Class Codes: Y10T 428/31855 Of addition polymer from unsaturated monomers
• CPC Class Codes: Y10T 428/31935 Ester, halide or nitrile of addition polymer
• CPC Class Codes: Y10T 428/31938 Polymer of monoethylenically unsaturated hydrocarbon

Abstract

A method of forming a surface layer that includes a hydroxyl polymer on a substrate coating on a medical device is provided.

Claims

1. A method comprising:

providing a composition comprising a hydroxyl polymer;

providing a medical device comprising a coating;

forming a layer of the composition on the coating,

attaching a spacer to the layer to generate dangling functional-group-terminated spacer chains, and

conjugating a bioactive agent to the spacer via the functional group;

wherein the hydroxyl polymer has a structure of

2. The method of claim 1 wherein forming comprises absorbing the hydroxyl polymer onto, into or both onto and into the coating.

3. The method of claim 1 wherein P is selected from the group consisting of CH₃, polyolefin (e.g., polyethylene), poly(ethylene glycol) (PEG), poly(propylene oxide) (PPO), poly(vinylidene fluoride) (PVDF), poly(vinyl pyrrolidone) (PVP), poly((2-hydroxyl)ethyl methacrylate) (HEMA), poly(methyl methacrylate) (MMA), hyaluronic acid (HA), benzylated HA, poly(ethylene-co-vinyl alcohol) (EVAL), and combinations thereof.

4. The method of claim 1 wherein the hydroxyl polymer is poly(vinyl alcohol) (PVOH) or EVAL.

5. The method of claim 1 further comprising forming an additional layer comprising the hydroxyl polymer.

6. The method of claim 2 wherein the composition layer has a thickness from 20 angstroms to about 5 microns.

7. The method of claim 5 wherein the composition layer and the additional layer independently have a thickness from 20 angstroms to about 5 microns.

8. The method of claim 1 wherein the coating comprises a bioactive agent.

9. The method of claim 8 wherein the agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), biolimus, tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), clobetasol, pimecrolimus, imatinib mesylate, midostaurin, prodrugs thereof, co-drugs thereof, and a combination thereof.

10. The method of claim 1 wherein the hydroxyl polymer is PVOH and

wherein the composition further comprises a block copolymer comprising PVOH.

11. The method of claim 1, wherein the hydroxyl polymer is PVOH, and

wherein the composition layer further comprises a block copolymer comprising PVOH.

12. The method of claim 1 wherein the hydroxyl polymer is a block copolymer selected from the group consisting of poly(propylene oxide-co-vinyl alcohol) (PPO-co-PVOH), poly(vinylidene fluoride-co-vinyl alcohol) (PVDF-co-PVOH), EVAL, and combinations thereof.

13. The method of claim 1 further comprising

treating the composition layer to freeze-thaw cycle(s) to increase the stability of the layer.

14. The method of claim 1 wherein forming comprises:

swelling the coating with the solution of the composition, and

forming the composition layer on the coating,

wherein the composition is dissolved in a solvent capable of partially swelling the coating.

15. The method of claim 13 further comprising curing the composition layer to graft the layer to the coating.

16. The method of claim 14 wherein the composition layer further comprises maleic acid, fumaric acid, or combinations thereof.

17. The method of claim 14 wherein curing is achieved by e-beam, UV irradiation or plasma exposure.

18. The method of claim 8 wherein the composition layer further comprises a bioactive agent that is the same as the bioactive agent in the coating or different from the bioactive agent in the coating.

19. The method of claim 16 wherein the bio active agent is paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), biolimus, tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), clobetasol, pimecrolimus, imatinib mesylate, midostaurin, prodrugs thereof, co-drugs thereof, and a combination thereof.

20. The method of claim 1 wherein the hydroxyl polymer is PVOH, and the method further comprises exposing the layer to a humid environment to promote additional crystallization of the PVOH.

21. The method of claim 1 further comprising

including a material capable of minimizing the interfacial energy between the layer of hydroxyl polymer and the coating beneath so to make the surface of the hydroxyl polymer more stable;

wherein the material is poly(propylene oxide-co-vinyl alcohol) or poly(vinylidene fluoride-co-vinyl alcohol);

or

crosslinking the hydroxyl polymer using glutaldehyde.

22. The method of claim 1 wherein the spacer is poly(ethylene glycol) (PEG), the functional group is amine, carboxylic acid, or aldehyde, and

wherein the bioactive agent is a pro-healing agent, an antithrombogenic agent, a non-fouling agent, or combinations thereof.

23. The method of claim 1 wherein the hydroxyl polymer is poly(vinyl alcohol-co-(2-hydroxyl)ethyl methacrylate) (PVOH-co-HEMA), poly(vinyl alcohol-co-methyl methacrylate-co-(2-hydroxyl)ethyl methacrylate) (PVOH-co-MMA-co-HEMA), poly(vinyl alcohol-co-hyaluronic acid) (PVOH-co-HA), poly(vinyl alcohol-co-benzylated hyaluronic acid) (PVOH-co-HA-Bz), EVAL or combinations thereof.