Medical device coated with a coating containing elastin pentapeptide VGVPG

• US 8,029,816 B2
• Filed: 05/10/2007
• Issued: 10/04/2011
• Est. Priority Date: 06/09/2006
• Status: Expired due to Fees

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Inventors: Kleiner, Lothar W., Tang, Yiwen, Hossainy, Syed Faiyaz Ahmed
• Primary Examiner(s): NAFF, DAVID M
• Application Number:
  US11/803,031
• Publication Number:
  US 20080038310A1
• Time in Patent Office: 1,608 Days
• Field of Search: None
• US Class Current: 424/423
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61L 2300/25 Peptides having up to 20 amino acids in a defined sequence
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• 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 31/047 Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• 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: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: B05D 3/007 : After-treatment
• CPC Class Codes: C07K 14/001 : by chemical synthesis
• CPC Class Codes: C08H 1/00 : Macromolecular products derived from proteins food proteins A23; glue, gelatine C09H
• CPC Class Codes: Y10T 428/3154 : Of fluorinated addition polymer from unsaturated monomers
• CPC Class Codes: Y10T 428/31909 : Next to second addition polymer from unsaturated monomers

Abstract

The present invention is directed to medical devices including coatings. The coatings include a topcoat which includes a copolymer comprising a block of an elastin pentapeptide. The topcoat is over a layer of poly(vinyl alcohol) on a hydrophobic coating or over a porous coating comprising pores or depots that include a bioactive agent.

Claims

1. A medical device comprising a topcoat of a copolymer on top of a coating, wherein the copolymer comprises an elastin pentapeptide VGVPG (SEQ ID NO:

1) (A) and a hydrophilic block (B),

wherein the coating comprises a layer of a hydrophobic polymer underneath a thin layer of a polymer comprising poly(vinyl alcohol) (PVOH), and the topcoat on top of the thin layer of polymer comprising PVOH.

2. The medical device of claim 1, wherein the copolymer is an ABA copolymer.

3. The medical device of claim 1, wherein the hydrophilic block comprises lysine.

4. The medical device of claim 2, wherein the hydrophilic block comprises lysine.

5. The medical device of claim 2, wherein the hydrophilic block comprises a synthetic polymer.

6. The medical device of claim 2, wherein the hydrophilic block comprises a natural polymer.

7. The medical device of claim 2, wherein the hydrophilic block is a variant of the VGVPG obtained by replacing one amino acid in VGVPG (SEQ ID NO:

1) with another amino acid.

8. The medical device of claim 4, wherein the copolymer further comprises a phosphoryl choline (PC) or poly(ethylene glycol) (PEG) pendant group,

wherein the PC or PEG is conjugated to the copolymer via lysine in the hydrophilic block.

9. The medical device of claim 5, wherein the synthetic polymer is selected from PEG, PVP (poly vinylpyrrolidinone), polyacrylamide, poly(PEG acrylate), poly (HEMA), poly(acrylic acid) and combinations of these.

10. The medical device of claim 6, wherein the natural polymer is selected from collagen, collagen derivative, hyaluronic acid, alginate and combinations of these.

11. The medical device of claim 1, wherein the copolymer further comprises an ANP peptide, a BNP peptide, an RGD peptide, a cRGD peptide, a SIKVAV peptide (SEQ ID NO:

2), a CNP peptide, a YIGSRG peptide (SEQ ID NO;

     3), a hydrolytic segment, or a combination thereof.

12. The medical device of claim 2, wherein the copolymer further comprises an ANP peptide, a BNP peptide, an RGD peptide, a cRGD peptide, a SIKVAV peptide (SEQ ID NO:

2), a CNP peptide, a YIGSRG peptide (SEQ ID NO;

     3), a hydrolytic segment, or a combination thereof.

13. The medical device of claim 1, wherein the copolymer further comprises a biodegradable linkage between the A and the B block.

14. The medical device of claim 1, wherein the copolymer further comprises a biodegradable linkage selected from poly(lactic acid) (PLA), poly(glycolic acid) (PLGA), polycaprolactone (PCL), poly(3-hydroxybutyric acid (PHB), poly(4-hydroxybutyrate (P4HB), and combinations of these.

15. The medical device of claim 1, wherein the hydrophobic polymer comprises a polymer of a fluoroolefin.

16. The medical device of claim 15, wherein the hydrophobic polymer is poly(vinylidene fluoride) (PVDF).

17. The medical device of claim 1, wherein the layer of the hydrophobic polymer further comprises a bioactive agent.

18. The medical device of claim 1, wherein the coating comprises a bioactive agent selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimetics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), 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, 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, midostaurin, vascular endothelial growth factor (VEGF), and prodrugs, co-drugs, and combinations of these.

19. The medical device of claim 17, wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimetics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), 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, 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, midostaurin, vascular endothelial growth factor (VEGF), and prodrugs, co-drugs, and combinations of these.

20. The medical device of claim 1, wherein the coating comprises a bioactive agent comprising a combination of an anti-proliferative and an anti-inflammatory.

21. The medical device of claim 17, wherein the bioactive agent comprises a combination of an anti-proliferative and an anti-inflammatory.

22. The medical device of claim 18, which is a stent.

23. The medical device of claim 19, which is a stent.

24. A method of treating, preventing or ameliorating a disorder in a patient comprising implanting in the patient the medical device of claim 18, wherein the disorder is selected from the group consisting of atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, urethra obstruction, tumor obstruction, diabetic vascular disease, and combinations thereof.

25. A method of treating, preventing or ameliorating a disorder in a patient comprising implanting in the patient the medical device of claim 19, wherein the disorder is selected from the group consisting of atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, urethra obstruction, tumor obstruction, diabetic vascular disease, and combinations thereof.