Polymeric, degradable drug-eluting stents and coatings
View Patent ↗Absorbable stents and absorbable stent coatings have been developed with improved properties. These devices preferably comprise biocompatible copolymers or homopolymers of 4-hydroxybutyrate, and optionally polylactic acid and other absorbable polymers and additives. Compositions of these materials can be used to make absorbable stents that provide advantageous radial strengths, resistance to recoil and creep, can be plastically expanded on a balloon catheter, and can be deployed rapidly in vivo. Stent coatings derived from these materials provide biocompatible, uniform coatings that are ductile, and can be expanded without the coating cracking and/or delaminating and can be used as a coating matrix for drug incorporation.
1. A biocompatible stent comprising a base coat and optionally a top coat, wherein the base coat comprises a blend of poly(4-hydroxybutyrate) (P(4HB)), and poly(lactide) (PLA), and one or more therapeutic, diagnostic or prophylactic agents.
2. The stent of claim 1 wherein the poly(lactide) (PLA) is poly(L-lactide) (PLLA) or poly(DL-lactide) (PDLLA), or combinations thereof.
3. The stent of claim 1 , wherein the ratio of P(4HB) to PLA is between about 99/1 to 1/99 w/w.
4. The stent of claim 3 , wherein the ratio of P(4HB) to PLA in the blend is selected from the group consisting of 95/5 P(4HB)/PLA w/w, 90/10 P(4HB)/PLA w/w, 85/15 P(4HB)/PLA w/w, 80/20 P(4HB)/PLA w/w, 75/25 P(4HB)/PLA w/w, 70/30 P(4HB)/PLA w/w, 65/35 P(4HB)/PLA w/w, 60/40 P(4HB)/PLA w/w, 55/45 P(4HB)PLA w/w, 50/50 P(4HB)/PLA w/w, 45/55 P(4HB)/PLA w/w, 40/60 P(4HB)/PLA w/w, 35/65 P(4HB)/PLA w/w, and 30/70 P(4HB)/PLA w/w.
5. The stent of claim 4 , wherein the ratio of P(4HB) to PLLA in the blend is selected from the group consisting of 70/30 P(4HB)/PLLA w/w, 50/50 P(4HB)/PLLA w/w, and 30/70 P(4HB)/PLLA w/w.
6. The stent of claim 1 , wherein the base coat has a thickness of from about 1 micron to about 50 microns.
7. The stent of claim 6 , wherein the base coat has a thickness of from about 3 microns to about 30 microns.
8. The stent of claim 4 , wherein the base coat has a thickness of about 20 microns.
9. The stent of claim 1 , wherein the one or more therapeutic, diagnostic or prophylactic agents is selected from the group consisting of anti-inflammatory agents, immunomodulators, antithrombin agents, anti-proliferative agents, anti-restenosis agents, anti-migratory agents, extracellular matrix modulators, antiplatelet agents, wound healing agents, endothelialization promoters, and combinations thereof.
10. The stent of claim 9 , wherein the concentration of the agent in the base coat is about 10 ng/mm 2 to 200 μg/mm 2 .
11. The stent of claim 10 , wherein the concentration of the agent in the base coat is about 0.2 μg/mm to 20 μg/mm 2 .
12. The stent of claim 9 , wherein the one or more therapeutic, diagnostic or prophylactic agents is an anti-restenosis agent selected from the group consisting of Sirolimus, Tacrolimus, Biorest, Mizoribin, Cyclosporin, Interferon γ1b, Leflunomid, Tranilast, Corticosteroide, Mycophenolic acid, Biphosphonate, and combinations thereof.
13. The stent of claim 9 , wherein the anti-restenosis agent is rapamrycin.
14. The stent of claim 1 , wherein the stent comprises a top coat.
15. The stent of claim 11 , wherein the top coat comprises P(4HB).
16. The stent of claim 11 , wherein the top coat comprises a blend of P(4HB) and PLA.
17. The stent of claim 16 , wherein the ratio of P(4HB) to PLA in the top coat is selected from the group consisting of 95/5 P(4HB)/PLA w/w, 90/10 P(4HB)/PLA w/w, 85/15 P(4HB)/PLA w/w, 80/20 P(4HB)/PLA w/w, 75/25 P(4HB)/PLA w/w, 70/30 P(4HB)/PLA w/w, 65/35 P(4HB)/PLA w/w, 60/40 P(4HB)/PLA w/w, 55/45 P(4HB)/PLA w/w, 50/50 P(4HB)/PLA w/w, 45/55 P(4HB)/PLA w/w, 40/60 P(4HB)/PLA w/w, 35/65 P(4HB)/PLA w/w, and 30/70 P(4HB)/PLA w/w.
18. The stent of claim 17 , wherein the ratio of P(4HB) to PLA in the blend is selected from the group consisting of 70/30 P(4HB)PLA w/w, 50/50 P(4HB)/PLA w/w, and 30/70 P(4HB)/PLA w/w.
19. The stent of claim 14 , wherein the top coat is substantially free of one or more therapeutic, diagnostic, or prophylactic agents.
20. The stent of claim 1 , wherein the base coat, top coat, or combinations thereof further comprise a plasticizer.
21. The stent of claim 20 , wherein the concentration of the plasticizer is from about 0 to 10% by weight of the coating, most preferably present between 0 and 5% by weight of the coating.
22. The stent of claim 20 , wherein the plasticizer is triethylcitrate.
23. The stent of claim 1 , wherein the stent is a metallic stent.
24. The stent of claim 1 , wherein the stent has improved surface integrity compared to a stent coated with PLA.
25. The stent of claim 1 , wherein the polymeric base coat, top coat, or combinations thereof, degrade in less than two years, more preferably in less than one year, and most preferably in less than six months.
26. The stent of claim 1 comprising a metal stent, wherein the base coat comprises a blend of poly(4-hydroxybutyrate) (P(4HB)), and poly(L-lactide) (PLLA).
27. The stent of claim 1 comprising an absorbable metal, durable polymer, or absorbable polymer stent.
28. The stent of claim 27 wherein the absorbable polymer stent comprises poly(4-hydroxybutyrate) or copolymer thereof.
29. A method of making the, stent of claim 1 , the method comprising coating a stent with a base coat comprising a blend of P(4HB), PLA, and one or more therapeutic, diagnostic, or prophylactic agents, and optionally coating the base coat with a top coat.
30. A method of deploying the stent of claim 1 , comprising mounting the stent on a delivery system and balloon-expanding the stent inside the body lumen.