4-aza-caprolactone-based polymeric compositions useful for the manufacture of biodegradable medical devices and as medical device coatings

• US 8,137,687 B2
• Filed: 08/09/2006
• Issued: 03/20/2012
• Est. Priority Date: 08/25/2005
• Status: Active Grant

• Current Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Original Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Inventors: Chen, Mingfei, Cheng, Peiwen, Udipi, Kishore
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): AL-AWADI, DANAH J
• Application Number:
  US12/064,108
• Publication Number:
  US 20080233169A1
• Time in Patent Office: 2,050 Days
• Field of Search: None
• 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 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• 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
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

N-substituted 4-aza-caprolactone biodegradable polymers, including derivatives thereof, useful for making implantable medical devices and coatings therefore are provided. The medical devices and coatings of the present invention can also be used for in situ controlled release drug delivery and are useful for treating or preventing medical conditions such as restenosis, aneurisms and vulnerable plaque.

Claims

1. A medical device comprising:

a biodegradable polymer wherein at least one monomeric unit is derived from the compound of Formula I;

2. The medical device according to claim 1 wherein R is a methyl group.

3. The medical device according to claim 1 wherein said medical device is selected from the group consisting of vascular stents, stent grafts, urethral stent, biliary stents, catheters, sutures, ocular devices, heart valves, shunts, pacemakers, bone screws and anchors, protective plates and prosthetic devices.

4. The medical device according to claim 1 wherein said biocompatible, biodegradable polymer further comprises a bioactive agent selected from the group consisting of zotarolimus, estrogens, chaperone inhibitors, protease inhibitors, protein-tyrosine kinase inhibitors, leptomycin B, peroxisome proliferator-activated receptor gamma ligands (PPARγ

), hypothemycin, bisphosphonates, epidermal growth factor inhibitors, antibodies, proteasome inhibitors, antibiotics, anti-inflammatories, anti-sense nucleotides and transforming nucleic acids.

5. The medical device according to claim 1 wherein the biodegradable polymer comprises a compound according to Formula II:

6. The medical device according to claim 5 wherein R is a methyl group and the repeating units are present in a ratio of 44:

11.8;

0.2;

44;

a;

b;

c;

d respectively.

7. The medical device according to claim 1 wherein the biodegradable polymer comprises a compound according to Formula III:

8. The medical device according to claim 7 wherein R is a methyl group and the repeating units are present in a ratio of 99:

0, 13;

0.87;

a;

b;

c respectively.

9. The medical device according to claim 1 wherein the biodegradable polymer comprises a compound according to Formula IV:

10. The medical device according to claim 9 wherein R is a methyl group and the repeating units are present in a ratio of 3:

96;

1;

a;

b;

c respectively.

11. The medical device according to any one of claims 5 to 10 wherein said medical device is selected from the group consisting of vascular stents, stent grafts, urethral stem, binary stents, catheters, sutures, ocular devices, heart valves, shunts, pacemakers, hone screws and anchors, protective plates and prosthetic devices.

12. The medical device according to any one of claims 5 to 10 wherein said biocompatible, biodegradable polymer further comprises a bioactive agent selected from the group consisting of zotarolimus, estrogens, chaperone inhibitors, protease inhibitors, protein-tyrosine kinase inhibitors, leptomycin B, peroxisome proliferator-activated receptor gamma ligands (PPARγ

), hypothemycin, bisphosphonates, epidermal growth factor inhibitors, antibodies, proteasome inhibitors, antibiotics, anti-inflammatories, anti-sense nucleotides and transforming nucleic acids.

13. A vascular stent comprising:

a biodegradable polymer wherein at least one monomeric unit is derived from the compound of Formula I;

14. The vascular stent according to claim 13 wherein said bioactive agent is zotarolimus.

15. An implantable medical device having a controlled release coating comprising a biodegradable polymer wherein at least one monomeric unit is derived from the compound of Formula I:

16. The implantable medical device according to claim 15 wherein said medical device is a vascular stent made from a biocompatible material selected from the group consisting of stainless steel, nitinol, aluminum, chromium, titanium, gold, cobalt, cobalt alloys, titanium alloys, ceramics, and of synthetic polymers.

17. A biodegradable implantable medical device comprising a biodegradable polymer wherein at least one monomeric unit is derived from the compound of Formula I:

18. A vascular stent having a controlled-release coating comprising an amphiphilic, biocompatible, biodegradable polymer wherein at least one monomeric unit is derived from the compound of Formula I:

19. A biodegradable vascular stent comprising a biodegradable polymer wherein at least one monomeric unit is derived from the compound of Formula I:

20. A monomer suitable for use in making a polymeric compound comprising the compound of Formula I:

21. A biodegradable polymer comprising a compound according to Formula II:

22. The biodegradable polymer according to claim 21 wherein R is a methyl group and the repeating units are present in a ratio of 44:

11.8;

0.2;

44;

a;

b;

c;

d respectively.

23. A biodegradable polymer comprising a compound according to Formula III:

24. The biodegradable polymer according to claim 23 wherein R is a methyl group and the repeating units are present in a ratio of 99:

0.13;

0.87;

a;

b;

c respectively.

25. A biodegradable polymer comprising a compound according to Formula IV:

26. The biodegradable polymer according to claim 25 wherein R is a methyl group and the repeating units are present in a ratio of 396:

1;

a;

b;

c respectively.

27. A polymer comprising the monomer according to Formula I and at least one other polymer repeating unit selected from the group consisting of δ

-caprolactone, dioxanone, trimethyl carbonate, amino acids, peptides and combinations thereof.