Nanobead releasing medical devices

• US 8,048,441 B2
• Filed: 06/25/2007
• Issued: 11/01/2011
• Est. Priority Date: 06/25/2007
• Status: Expired due to Fees

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Hines, Lionel G., Jayasinghe, Dudley, Orosa, Dennis, Craig, Charles H., Papp, John E.
• Primary Examiner(s): Wax; Robert A
• Assistant Examiner(s): AL-AWADI, DANAH J
• Application Number:
  US11/823,007
• Publication Number:
  US 20080317813A1
• Time in Patent Office: 1,590 Days
• Field of Search: None
• US Class Current: 424/423
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/624 Nanocapsules
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 31/18 Materials at least partially X-ray or laser opaque
• 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

Abstract

Medical devices comprising nanobeads encapsulating one or more bioactive agents and methods of use thereof are provided.

Claims

1. A medical device comprising a coating, the coating comprising nanobeads embedded in the coating, and the coating comprising a polymer and a material selected from the group consisting of ceramic materials, bioglass, and combinations thereof;

wherein the coating provides for a controlled release of a bioactive agent or agents encapsulated in the nanobeads, and the nanobeads comprise the one or more bioactive agents and a matrix, the one or more bioactive agents dispersed in the matrix of the nanobeads and the nanobeads being without a shell surrounding the matrix.

2. The medical device of claim 1, wherein the nanobeads comprise a first plurality of nanobeads that encapsulate a first bioactive agent and a second plurality of nanobeads that encapsulate a second bioactive agent, which is different from the first bioactive agent.

3. The medical device of claim 2, wherein the coating comprises:

a first layer comprising the first plurality of nanobeads, and

a second layer comprising the second plurality of nanobeads.

4. The medical device of claim 2, wherein the nanobeads further comprise a third plurality of nanobeads that encapsulate a third bioactive agent which is different from both the first and second bioactive agents.

5. The medical device of claim 4, wherein the coating comprises:

a first layer comprising the first plurality of nanobeads,

a second layer comprising the second plurality of nanobeads, and

a third layer comprising the third plurality of nanobeads.

6. The medical device of claim 1, wherein the nanobeads comprise more than three different types of nanobeads, and

wherein each of the different types of nanobeads incorporates a bioactive agent that is the same as or different from a bioactive agent included in the other types of the nanobeads.

7. The medical device of claim 6, wherein the coating comprises more than three different layers of coating, and

wherein each of the different types of nanobeads is included in a different layer of the more than three different layers of coating.

8. The medical device of claim 1, wherein at least one bioactive agent is 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, 40-O-tetrazole-rapamycin, 40-epi-(N-1-tetrazolyl)-rapamycin (ABT-578), TAFA-93, biolimus-7, biolimus-9, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof.

9. The medical device of claim 2, wherein the first bioactive agent and the second bioactive agent are independently 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, 40-O-tetrazole-rapamycin, 40-epi-(N-1-tetrazolyl)-rapamycin (ABT-578), TAFA-93, biolimus-7, biolimus-9, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof.

10. The medical device of claim 1, wherein the first bioactive agent, the second bioactive agent, and the third bioactive agent are independently 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, 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), TAFA-93, biolimus-7, biolimus-9, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof.

11. The medical device of claim 1, which is a stent.

12. The medical device of claim 1, further comprising nanobeads chemically attached to the surface of the medical device.

13. The medical device of claim 1, wherein the nanobeads comprise a magnetic material which optionally comprises a biocompatible coating.

14. The medical device of claim 13, wherein the nanobeads are capable of being directed to a target site by an external magnetic source.

15. The medical device of claim 5, wherein at least one of the first, second and third layers is formed by application of a slurry.

16. A method of treating a disorder in a patient comprising implanting in the patient the medical device of claim 1 and causing the nanobeads to release from 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, and combinations thereof.