Functionalized chemically inert polymers for coatings

• US 8,021,676 B2
• Filed: 07/08/2005
• Issued: 09/20/2011
• Est. Priority Date: 07/08/2005
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Hossainy, Syed Faiyaz Ahmed, Pacetti, Stephen Dirk
• Primary Examiner(s): Hartley; Michael G
• Assistant Examiner(s): DICKINSON, PAUL W
• Application Number:
  US11/178,196
• Publication Number:
  US 20070009565A1
• Time in Patent Office: 2,265 Days
• Field of Search: None
• US Class Current: 424/423
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• 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 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: C08F 214/22 Vinylidene fluoride
• CPC Class Codes: C08F 8/00 Chemical modification by after-treatment graft polymers, block polymers, crosslinking with unsaturated monomers or with polymers C08F251/00 - C08F299/00; of conjugated diene rubbers C08C
• CPC Class Codes: C08F 8/04 Reduction, e.g. hydrogenation
• CPC Class Codes: C08F 8/40 Introducing phosphorus atoms or phosphorus-containing groups
• CPC Class Codes: C08F 8/48 Isomerisation; Cyclisation
• CPC Class Codes: C08L 101/04 containing halogen atoms
• CPC Class Codes: Y10T 428/1393 Multilayer [continuous layer]

Abstract

Provided herein are methods for functionalizing an polymer for forming a coating and coatings and devices formed thereof or for functionalizing a coating or device surface including an polymer.

Claims

1. A method of forming a coating comprising a biofunctional compound on an implantable device, the method comprising

(a) subjecting a polymer to ozonation to form a peroxy grafted polymer,

(b) subjecting the peroxy grafted polymer to a process selected from the group consisting of reduction and thermal free radical polymerization to generate a functionalized polymer,

(c) forming a coating on the implantable device comprising the functionalized polymer without the biofunctional compound, and

(d) attaching the biofunctional compound by covalent chemical bonding to the functionalized polymer on the surface of the coating,

wherein the biofunctional compound is an RGD peptide, YIGSR peptide, ANP peptide, elastin, an endothelial progenitor cell (EPC) capturing antibody, or combinations thereof.

2. A stent comprising a coating comprising a biofunctional compound formed by a method comprising

(a) subjecting a polymer to ozonation to form a peroxy grafted polymer,

(b) subjecting the peroxy grafted polymer to a process selected from the group consisting of reduction and thermal free radical polymerization to generate a functionalized polymer,

(c) forming a coating on the implantable device comprising the functionalized polymer without the biofunctional compound, and

(d) attaching the biofunctional compound by covalent chemical bonding to the functionalized polymer on the surface of the coating,

wherein the biofunctional compound comprises hydroxyl, carboxyl, thiol or amino functionalities and is selected from a peptide, a protein, or a drug molecule.

3. The stent according to claim 2, wherein the polymer is poly(vinylidene fluoride-co-hexafluoropropene) (PVDF-HFP).

4. The stent according to claim 2, wherein the polymer is poly(vinylidene fluoride-co-hexafluoropropene) (PVDF-HFP), wherein the functionalized polymer is one of the following:

6. The stent of claim 2, wherein the coating further comprises a bioactive agent selected from the group consisting of paclitaxel, docetaxel, estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 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, 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.

7. The stent of claim 3, wherein the coating further comprises a bioactive agent selected from the group consisting of paclitaxel, docetaxel, estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 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, 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.

8. A method of treating a disorder in a patient comprising implanting in the patient the stent of claim 2, 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, ureter obstruction, tumor obstruction, and combinations thereof.

5. A stent comprising a coating formed by the method of 1.