Bioabsorbable coating with tunable hydrophobicity

• US 20090036978A1
• Filed: 08/01/2007
• Published: 02/05/2009
• Est. Priority Date: 08/01/2007
• Status: Active Grant

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Pham, Nam D., Kleiner, Lothar W., Tang, Yiwen, Stankus, John, Trollsas, Mikael, Hossainy, Syed Faiyaz Ahmed, Maslanka, Bozena Zofia, Ngo, Michael H.
• Granted Patent: US 8,961,589 B2
• Time in Patent Office: Days
• US Class Current: 623/1.490
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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 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: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The present invention relates to implantable medical devices coated with polymer having tunable hydrophobicity and their use in the treatment of vascular diseases.

Claims

1. An implantable medical device, comprising:

a device body;

an optional primer layer disposed over the device body;

a drug reservoir layer disposed over the device body or the primer layer, if opted, wherein the drug reservoir layer comprises a polymer and one or more therapeutic agent(s) and further wherein the hydrophobicity of the polymer is matched to that of the therapeutic agent(s).

2. The implantable medical device of claim 1, wherein the polymer is a copolymer comprising a first monomer selected from the group consisting of L-lactide, D-lactide, D,L-lactide and meso-lactide and a second monomer selected from the group consisting of lactone, ε

-caprolactone, δ

-valerolactone, 1,4-dioxan-2-one, 1,5-dioxepan-2-one, 1,4,6-trioxaspiro]4.4]nonane and trimethyl carbonate, wherein

the first monomer, the second monomer or both is/are optionally substituted with a moiety selected form the group consisting of C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, partially or fully fluorinated derivatives of any of the preceding and combinations thereof so as to match the hydrophobicity of the polymer to that of the therapeutic agent.

3. The implantable medical device of claim 2, wherein the therapeutic agent is everolimus.

4. The implantable medical device of claim 3, wherein the polymer is selected from the group consisting of poly(L-lactide-co-ε

-caprolactone) and poly(L-lactide-co-trimethylene carbonate).

5. The implantable medical device of claim 4, wherein the polymer comprises poly(L-lactide-co-ε

-caprolactone) polymer.

6. The implantable medical device of claim 5, wherein the poly(L-lactide-co-ε

-caprolactone) constitutional unit molar ratio is from about 70;

30 to about 50;

50.

7. The implantable medical device of claim 6, wherein the poly(L-lactide-co-ε

-caprolactone) has a average molecular weight from about 50,000 to about 500,000 Daltons.

8. The implantable medical device of claim 7, wherein the poly(L-lactide-co-ε

-caprolactone) has a solubility parameter less than about 11.5 (cal/cm³)^1/2.

9. The implantable medical device of claim 1, wherein the drug reservoir layer has a coating thickness from about 1 um to about 10 um.

10. The implantable medical device of claim 1, wherein the drug to polymer wt/wt ratio is from about 1.0:

0.5 to about 1.0;

10.0.

11. The implantable medical device of claim 1, wherein the drug dose is from about 5-200 microgram/cm² to about 20-100 microgram/cm².

12. The implantable medical device of claim 1, wherein the device is a stent,

13. A method of treating a vascular disease, comprising:

deploying in the vasculature of a patient in need thereof an implantable medical device, wherein the device comprises;

a device body;

an optional primer layer disposed over the device body;

a drug reservoir layer disposed over the device body or the primer layer, if opted, wherein the drug reservoir layer comprises a polymer and one or more therapeutic agent(s) and further wherein the hydrophobicity of the polymer is matched to that of the therapeutic agent(s).

14. The method of claim 13, wherein the polymer is a copolymer comprising a first monomer selected from the group consisting of L-lactide, D-lactide, D,L-lactide and meso-lactide and a second monomer selected from the group consisting of lactone, ε

-caprolactone, δ

-valerolactone, 1,4-dioxan-2-one, 1,5-dioxepan-2-one, 1,4,6-trioxaspiro[4.4]nonane and trimethyl carbonate, wherein

the first monomer, the second monomer or both is/are optionally substituted with a moiety selected form the group consisting of C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, partially or fully fluorinated derivatives of any of the preceding and combinations thereof so as to match the hydrophobicity of the polymer to that of the therapeutic agent.

15. The method of claim 14, wherein the therapeutic agent is everolimus.

16. The method of claim 15, wherein the polymer is selected from the group consisting of poly(L-lactide-co-ε

-caprolactone) and poly(L-lactide-co-trimethylene carbonate).

17. The method of claim 16, wherein the polymer comprises poly(L-lactide-co-ε

-caprolactone) polymer.

18. The method of claim 17, wherein the poly(L-lactide-co-ε

-caprolactone) constitutional unit molar ratio is from about 70;

30 to about 50;

50.

19. The method of claim 18, wherein the poly(L-lactide-co-ε

-caprolactone) has a average molecular weight from about 50,000 to about 500,000 Daltons.

20. The method of claim 19, wherein the poly(L-lactide-co-ε

-caprolactone) has a solubility parameter less than about 11.5 (cal/cm³)^1/2.

21. The method of claim 13, wherein the drug reservoir layer has a coating thickness from about 1 um to about 10 um.

22. The method of claim 13, wherein the drug to polymer wt/wt ratio is from about 1.0:

0.5 to about 1.0;

10.0.

23. The method of claim 13, wherein the drug dose is from about 5-200 microgram/cm² to about 20-100 microgram/cm².

24. The method of claim 13, wherein the device is a stent,

25. The method of claim 13, wherein the vascular disease is atherosclerosis.

26. The method of claim 13, wherein the vascular disease is restenosis.

27. The method of claim 13, wherein the vascular disease is vulnerable plaque.

28. The method of claim 13, wherein the vascular disease is peripheral vascular disease.

29. The method of claim 13, wherein the vascular disease is late stent thrombosis.