POLY(ESTER AMIDE)-BASED DRUG DELIVERY SYSTEMS WITH CONTROLLED RELEASE RATE AND MORPHOLOGY

• US 20110153004A1
• Filed: 02/28/2011
• Published: 06/23/2011
• Est. Priority Date: 02/28/2006
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: PACETTI, STEPHEN DIRK, KLEINER, LOTHAR WALTER, HOSSAINY, SYED FAIYAZ AHMED, DESNOYER, JESSICA RENEE
• Granted Patent: US 8,389,044 B2
• Time in Patent Office: Days
• US Class Current: 623/1.43
• 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 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 27/34 Macromolecular materials
• 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

Abstract

A method of forming a coating on a medical device having a controlled morphology is described. A method of treating a disorder in a patient using the medical device is described.

Claims

1. A method of treating a disorder in a patient comprising implanting in a patient the medical device formed according to a method which comprises

providing a coating composition comprising a polymer and a solvent of the polymer,

applying the coating composition onto the medical device,

inducing phase inversion in the coating composition, and

causing the coating composition to form a layer of the coating on the medical device,

wherein the coating has a controlled morphology for controlling the release of an agent from the coating.

2. The method of claim 1, wherein phase inversion is induced by quenching the coating composition.

3. The method of claim 2, wherein quenching comprises evaporation of the solvent.

4. The method of claim 1, wherein the coating composition further comprises a non-solvent of the polymer.

5. The method of claim 4, wherein the non-solvent is a bioactive agent.

6. The method of claim 1, wherein the phase inversion is induced by evaporation of the solvent.

7. The method of claim 1, wherein phase inversion is induced by introducing water into the layer of the coating composition.

8. The method of claim 7, wherein the water is introduced into the layer by condensation or absorption of water into the layer.

9. The method of claim 1, wherein phase inversion is thermally induced.

10. The method of claim 9, wherein phase inversion is induced by cooling the layer of the coating composition by

(a) evaporation of the solvent,

(b) application of a cold stream of gas, or

(c) placement in a cold environment.

11. The method of claim 1, wherein the coating comprises a two-phase morphology.

12. The method of claim 11, wherein the morphology comprises a non-solvent rich phase.

13. The method of claim 12, wherein the non-solvent-rich phase is isolated or interconnected.

14. The method of claim 13, wherein

isolated non-solvent rich phase means that the phase comprises isolated non-solvent pockets, and

interconnected non-solvent rich phase means that the phase comprises a honeycomb-type or a finger-type structure.

15. The method of claim 1, wherein the polymer comprises a poly(ester amide) polymer.

16. The method of claim 1, wherein the coating composition further comprises a surfactant.

17. The method of claim 16, wherein the surfactant is selected from the group consisting of Pluronic™

, Tetronic™

, Tween surfactants, Span surfactants, Brij surfactants, Myrj surfactants, Silwet surfactants, phospholipids, Poloxamer and combinations thereof.

18. The method of claim 1, wherein the polymer has a glass transition temperature above ambient temperature.

19. The method of claim 18, wherein the polymer has a glass transition temperature above about 37°

C.

20. The method of claim 1, wherein the coating has a rough or coarse morphology or the coating has a two-phase morphology with channels or pores.

21. The method of claim 4, wherein the non-solvent is a drug.

22. The method of claim 21, wherein the drug 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.

23. The method of claim 1, wherein the coating composition further comprises a drug soluble in the polymer.

24. The method of claim 1, wherein phase inversion is induced by

(a) lyophilizing the solvent from the polymer,

(b) extracting the solvent from the polymer using a non-solvent for the polymer,

(c) extracting the solvent from the polymer using supercritical extraction,

(d) removing the solvent by vacuum heating, or

(e) removing the solvent by vacuum at room temperature.

25. The method of claim 1, wherein the medical device is a stent.

26. The method of claim 1, wherein the medical device is a bioabsorbable stent.

27. The method of claim 1, wherein the polymer has a zero order absorption rate.

28. The method of claim 1, wherein the coating has a rough or coarse morphology or a morphology with channels or pores.

29. The method of claim 23, wherein the drug has a zero order release profile.

30. The method of claim 23, wherein the drug has a rate of release which is proportional to the absorption rate of the polymer.

31. The method 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.