Bio-Degradable Block Co-Polymers for Controlled Release

• US 20090304767A1
• Filed: 06/05/2008
• Published: 12/10/2009
• Est. Priority Date: 06/05/2008
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: Boden, Mark, Sikes, Courtney
• Granted Patent: US 8,652,506 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• 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 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• 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 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08G 63/08 Lactones or lactides
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

A block or graft copolymer includes a first block, and a second block different from the first block, wherein the first block is a poly(lactide-glycolide) copolymer. The polymers may be formulated in compositions with drug components for use in coating medical devices such as stents. Different blocks of the block or graft copolymer degrade in the body at different rates. The drug release profile from the coating is a combination the individual release rates of the different blocks and so can be controlled by controlling the selection and relative amounts of the respective blocks.

Claims

1. A block or graft copolymer comprising at least a first block and a second block different from the first block, wherein the first block is a poly(lactide-glycolide) copolymer and the second block is a member of the group consisting of lactide-glycolide copolymer having a higher percentage of lactide than the first block copolymer, polylactide homopolymer, poly(trimethylene carbonate), poly(caprolactone), poly(β

-butyrolactone), poly(δ

-valerolactone), and poly(tyrosine carbonate).

2. A block or graft copolymer as in claim 1 wherein the first and second blocks are characterized by respective degradation rates when the block copolymer is placed in the body of a subject, the degradation rate of the first block being greater than the degradation rate of the second block.

3. A block or graft copolymer as in claim 2 further comprising at least one third block, the third blocks being characterized by a degradation rate when the block copolymer is placed in the body of a subject animal that is different from the respective degradation rates of the first and second blocks.

4. A block or graft copolymer as in claim 1 wherein the first block is a poly(lactide-glycolide copolymer having a lactide:

glycolide ratio in the range of 25;

75 to 60;

40.

5. A block or graft copolymer as in claim 4 wherein the second block is a poly(lactide-glycolide copolymer having a lactide:

glycolide ratio in the range of 70;

30 to 99;

1.

6. A block or graft copolymer as in claim 1 wherein the second block is a lactide-glycolide copolymer having a higher percentage of lactide than the first block copolymer, the block copolymer further comprising at least one third block selected from the group consisting of polylactide homopolymer, poly(caprolactone), poly(hydroxybutyrate), poly(hydroxyvalerate), poly(trimethylene carbonate) and poly(tyrosine carbonate).

7. A block or graft copolymer as in claim 1 wherein the second block is a polylactide homopolymer, the block copolymer further comprising at least one third block selected from the group consisting of poly(caprolactone), poly(hydroxybutyrate), poly(hydroxyvalerate), poly(trimethylene carbonate) and poly(tyrosine carbonate).

8. A block or graft copolymer comprising at least a first block and a second block different from the first block, wherein the first block is a poly(lactide-glycolide) copolymer and each different block of the block copolymer is hydrophobic.

9. A block or graft copolymer as in claim 8 wherein the second block is a member of the group consisting of lactide-glycolide copolymer having a higher percentage of lactide than the first block copolymer, polylactide homopolymer, poly(trimethylene carbonate), poly(caprolactone), poly(β

-butyrolactone), poly(δ

-valerolactone), and poly(tyrosine carbonate).

10. A block or graft copolymer as in claim 8 wherein each different block of the block copolymer is solid at 37°

C.

11. A composition comprising a polymer and a drug component distributed in the polymer material wherein the polymer material is a block or graft copolymer comprising at least one first block of a poly(lactide-glycolide) copolymer that elutes the drug component at a first rate when the composition is placed in the body of a subject, and the block copolymer comprising at least one second block that elutes the drug at a second, slower rate when the composition is placed in the body of a subject.

12. A composition as in claim 11 wherein the drug component is dissolved in, suspended in, conjugated with, or ionically linked to the block copolymer

13. A composition as in claim 11 wherein the drug component is essentially uniformly distributed in said block or graft copolymer.

14. A composition as in claim 11 wherein:

the second block of said block or graft copolymer is a member of the group consisting of lactide-glycolide copolymer having a higher percentage of lactide than the first block copolymer, polylactide homopolymer, poly(trimethylene carbonate), poly(caprolactone), poly(β

-butyrolactone), poly(δ

-valerolactone), and poly(tyrosine carbonate), or

each different block of the block copolymer is hydrophobic.

15. A composition as in claim 11 wherein said drug component comprises a restonosis-inhibiting drug.

16. A composition as in claim 11 wherein the drug component is present therein in an amount of from about 0.1 to about 40% of the composition weight.

17. An implantable medical device having a coating thereon wherein the coating comprises a block or graft copolymer that comprises at least a first block and a second block different from the first block wherein the first block is a poly(lactide-glycolide) copolymer.

18. An implantable medical device as in claim 17 wherein said coating is a composition comprising said block or graft copolymer and a drug component distributed in said block or graft copolymer.

19. An implantable medical device as in claim 17 wherein said one first block elutes the drug component at a first rate when the composition is placed in the body of a subject, and the second block elutes the drug at a second, slower rate when the composition is placed in the body of a subject.

20. An implantable medical device as in claim 17 wherein the device is a member of the group consisting of sutures, pumps, stents, stent-grafts, grafts, heart valves, shunts, vascular access ports, pacemakers, defibrillators, electrodes, and leads.

21. An implantable medical device as in claim 17 wherein the device is a stent.

22. A stent as in claim 21 wherein the drug component comprises a restenosis-inhibiting drug.

23. A stent as in claim 21 wherein the drug component comprises at least one member of the group consisting of paclitaxel, derivatives of paclitaxel, rapamycin, everolimus, tacrolimus, dexamethoasone, estradiol, ABT-578 (Abbott Laboratories), trapidil, liprostin, Actinomycin D, Resten-NG, Ap-17, clopidogrel, and Ridogrel.

24. An implantable medical device as in claim 17 wherein:

the second block of said block or graft copolymer is a member of the group consisting of lactide-glycolide copolymer having a higher percentage of lactide than the first block copolymer, polylactide homopolymer, poly(trimethylene carbonate), poly(caprolactone), poly(β

-butyrolactone), poly(δ

-valerolactone), and poly(tyrosine carbonate), or

each different block of the block copolymer is hydrophobic.