Bioabsorbable semi-crystalline polymer for controlling release of drug from a coating
The present invention provides a semi-crystalline polymer for a coating on an implantable device for controlling release of drug and methods of making and using the same.
1. An implantable device comprising a coating that comprises a semi-crystalline polymer and a bioactive agent, the semi-crystalline polymer comprising one or more crystalline domains having melting point temperature (T m s) and one or more amorphous domains having glass transition temperature (T g s);
wherein the semi-crystalline polymer is a semi-crystalline random copolymer of poly(L-lactic acid-co-caprolactone) (PLLA-CL);
and
wherein for at least one melting point, the melting point endotherm on a differential scanning calorimetry thermogram of the semi-crystalline polymer has a ratio of the height to the width of the endotherm peak at half of the height of about 0.48 or lower than 0.48.
2. The implantable device of claim 1 , wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), biolimus, tacrolimus, dexamethasone, rapamycin, 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), γ-hiridun, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, feno fibrate, and combinations thereof.
3. The implantable device of claim 1 , which is a stent.
4. The implantable device of claim 1 , which is a bioabsorbable stent.
5. The implantable device of claim 2 , which is a bioabsorbable stent.
6. A method of fabricating a coating on an implantable device, the method comprising:
forming a coating that comprises a semi-crystalline polymer and a bioactive agent, the semi-crystalline polymer comprising one or more crystalline domains having melting point temperature (T m s) and one or more amorphous domains having glass transition temperature (T g s);
wherein the semi-crystalline polymer is a semi-crystalline random copolymer of poly(L-lactic acid-co-caprolactone) (PLLA-CL);
and
wherein for at least one melting point, the melting point endotherm on a differential scanning calorimetry thermogram of the semi-crystalline polymer has a ratio of the height to the width of the endotherm peak at half of the height of about 0.48 or lower than 0.48.
7. The method of claim 6 , wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), biolimus, tacrolimus, dexamethasone, rapamycin, 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), γ-hiridun, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, feno fibrate, and combinations thereof.
8. The method of claim 6 , wherein the implantable device is a stent.
9. The method of claim 6 , wherein the implantable device is a bioabsorbable stent.
10. The method of claim 7 , wherein the implantable device is a bioabsorbable stent.
11. The implantable device of claim 2 , wherein the implantable device is a stent.
12. The implantable device of claim 11 , wherein the bioactive agent is everolimus, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), or a combination thereof.
13. The implantable device of claim 1 , wherein the semi-crystalline polymer is a poly(L-lactic acid-co-caprolactone) copolymer of a molar ratio of lactic acid to caprolactone of about 75:25.
14. The implantable device of claim 1 , wherein the bioactive agent is selected from the group consisting of biolimus, tacrolimus, rapamycin, 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), pimecrolimus, and combinations thereof.
15. The implantable device of claim 14 , wherein the bioactive agent is everolimus, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), or a combination thereof.
16. The method of claim 6 , wherein the bioactive agent is selected from the group consisting of biolimus, tacrolimus, rapamycin, 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), pimecrolimus, and combinations thereof.
17. The method of claim 16 , wherein the implantable device is a stent.
18. The method of claim 17 , wherein the bioactive agent is everolimus, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), or a combination thereof.
19. The method of claim 6 , wherein the semi-crystalline polymer is a poly(L-lactic acid-co-caprolactone) copolymer of a molar ratio of lactic acid to caprolactone of about 75:25.
20. The implantable device of claim 11 , wherein the semi-crystalline polymer is a poly(L-lactic acid-co-caprolactone) copolymer of a molar ratio of lactic acid to caprolactone of about 75:25.
21. The method of claim 17 , wherein the semi-crystalline polymer is a poly(L-lactic acid-co-caprolactone) copolymer of a molar ratio of lactic acid to caprolactone of about 75:25.