Nitric oxide generating medical devices

• US 8,067,025 B2
• Filed: 03/20/2007
• Issued: 11/29/2011
• Est. Priority Date: 02/17/2006
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Glauser, Thierry, Pacetti, Stephen D., Consigny, Paul
• Primary Examiner(s): Hartley; Michael G
• Assistant Examiner(s): SAMALA, JAGADISHWAR RAO
• Application Number:
  US11/726,135
• Publication Number:
  US 20070196424A1
• Time in Patent Office: 1,715 Days
• Field of Search: 424/400, 424/402, 424/422, 424/424, 424/42, 424/423, 424/78.27, 424/78.37, 528/373, 528/422, 528/425, 524/429, 604/265, 604/266, 510/320, 514/56, 514/149, 623/1.47, 623/1.42, 623/1.46, 428/336, 428/421, 428/422
• US Class Current: 424/423
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 2300/114 Nitric oxide, i.e. NO
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/08 Materials for coatings
• 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: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• 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 9/08 Vasodilators for multiple indications
• 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

Abstract

Medical devices having a catalyst capable of catalyzing the generation of nitric oxide attached to the medical device and methods of treating a vascular condition using the devices are provided.

Claims

1. A medical device comprising a polymer and a metal complex, the metal complex comprising a metal and at least one ligand,

wherein the polymer forms the medical device or a coating of the medical device;

wherein the at least one ligand of the metal complex covalently attaches to a surface of the medical device or the coating on the medical device via a spacer,

wherein the spacer is a phenyl group, an aryl group, a short chain peptide, biocompatible oligomer, or biocompatible polymer functionalized by a reactive group selected from carboxyl, hydroxyl, thiol, amine, acid halide, N-hydroxysuccinimide, acryloyl, and vinyl sulfone, and

wherein the polymer is a copolymer of monomers selected from 2-hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA), hydroxypropylmethacrylamide, PEG acrylate (PEGA), PEG methacrylate, 2-methacryloyloxyethylphosphorylcholine (MPC), methacrylic acid (MA), and acrylic acid (AA);

wherein the metal complex catalyzes the generation of nitric oxide in the blood stream or a tissue adjacent to the medical device wherein the medical device is a bioabsorbable polymer stent.

2. The medical device of claim 1, wherein the nitric oxide is released from a nitrosylated biomolecule present in the blood stream or a tissue adjacent to the medical device.

3. The medical device of claim 1, wherein the nitric oxide is released from a nitrosylated protein or S-nitrosothiol present in the blood stream or a tissue adjacent to the medical device.

4. The medical device of claim 1, wherein the metal complex is a copper complex.

5. The medical device of claim 1, wherein the metal complex comprises Cyclen, Cyclam, DTTCT, or a bipyrridine ligand.

6. The medical device of claim 1, wherein the metal complex is attached to the surface of the coating.

7. The medical device of claim 1, wherein the metal complex comprises an ion selected from the group consisting of Cu²⁺, Co²⁺, Ni²⁺, Zn⁺²⁺, Mn²⁺, Al³⁺, or Fe³⁺.

8. A method of treating a disorder in a patient comprising implanting in the patient the medical device of claim 1, 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, diabetic vascular disease, and combinations thereof.

9. The medical device of claim 1, further comprising one or more biobeneficial materials selected from 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-(N-1-tetrazolyl)-rapamycin(ABT-578), pimecrolimus, imatinib mesylate, midostaurin, clobetasol, bioactive RGD, CD-34 antibody, abciximab (REOPRO), progenitor cell capturing antibody, or a combination thereof.