Poly(ester amide)-based drug delivery systems with controlled release rate and morphology

• US 8,377,107 B2
• Filed: 02/28/2011
• Issued: 02/19/2013
• Est. Priority Date: 02/28/2006
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Kleiner, Lothar Walter, DesNoyer, Jessica Renee, Pacetti, Stephen Dirk, Hossainy, Syed Faiyaz Ahmed
• Primary Examiner(s): Yuan, Dah-Wei
• Assistant Examiner(s): BOWMAN, ANDREW J
• Application Number:
  US13/037,169
• Publication Number:
  US 20110200660A1
• Time in Patent Office: 722 Days
• Field of Search: 427/2.25, 427/2.12, 427/2.13, 427/2.31, 623/1.38, 514/449, 523/113, 604/500, 430/66, 424/423
• US Class Current: 623/1.1
• 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 medical device having a controlled morphology is described.

Claims

1. A medical device comprising a coating 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 morphology for controlling the release of an agent from the coating,

wherein the polymer comprises a poly(ester amide) selected from the group consisting of PEA-TEMPO, PEA-Benzyl, a poly(ester amide) of 0.5 L-Leucine (cyclohexanediol) 0.5 L-Leucine (hexanediol) sebacinate, and a poly(ester amide) of phenyl alainine (propanediol) sebacinate.

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

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

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

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

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

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

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

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

10. The medical device 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 medical device of claim 1, wherein the coating comprises a two-phase morphology.

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

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

14. The medical device 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 medical device of claim 1, wherein the coating composition further comprises a surfactant.

16. The medical device of claim 15, wherein the surfactant is selected from the group consisting poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), tetra-functional block copolymers based on ethylene oxide and propylene oxide, polysorbate surfactants, sorbitan based surfactants, polyethylene based surfactants, trisiloxane based surfactants, phospholipids, Poloxamer and combinations thereof.

17. The medical device of claim 1, wherein the polymer has a glass transition temperature above ambient temperature.

18. The medical device of claim 17, wherein the polymer has a glass transition temperature above about 37°

C.

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

20. The medical device of claim 4, wherein the non-solvent is a drug.

21. The medical device of claim 20, 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.

22. The medical device of claim 1, wherein the coating composition further comprises a drug soluble in the polymer.

23. The medical device 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.

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

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

26. The medical device of claim 1, wherein the polymer has a zero order absorption rate.

27. The medical device of claim 1, wherein the coating has a rough or coarse morphology or a morphology with channels or pores.

28. The medical device of claim 22, wherein the drug has a zero order release profile.

29. The medical device of claim 22, wherein the drug has a rate of release which is proportional to the absorption rate of the polymer.

30. The medical device of claim 1, wherein the solvent is selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, 1-butanol, dimethyl acetamide, tetrahydrofuran, dimethyl formamide, dichloromethane, dimethyl sulfoxide, chloroform, trichloroethane, tetrachloroethane, trichloroethylene, and combinations thereof.

31. The medical device of claim 1, wherein the non-solvent is selected from the group consisting of water, dioxane, cyclohexanone, methyl ethyl ketone, benzene, toluene, xylene, pentane, hexane, heptane, octane, cyclohexane, acetone, and combinations thereof.