Implantable medical devices with a topcoat layer of phosphoryl choline acrylate polymer for reduced thrombosis, and improved mechanical properties

• US 20080286332A1
• Filed: 05/14/2007
• Published: 11/20/2008
• Est. Priority Date: 05/14/2007
• Status: Abandoned Application

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Pacetti, Stephen D.
• Application Number:
  US11/803,651
• Publication Number:
  US 20080286332A1
• Time in Patent Office: Days
• US Class Current: 424/424
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• 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 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• 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: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to implantable medical devices coated with phosphoryl choline acrylate polymer topcoat layer, an acrylate copolymer layer containing a therapeutic agent, 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 one or more therapeutic agents; and

a topcoat layer disposed as an outermost layer over the drug reservoir layer, wherein the topcoat layer comprises a phosphoryl choline acrylate polymer.

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

3. The implantable medical device of claim 1, wherein the phosphoryl choline acrylate polymer comprises poly(2-(methacryloyloxyethyl)-2-(trimethylammoniumethyl)-phosphate, inner salt)-co-(n-dodecylmethacrylate)-co-(hydroxypropylmethacrylate)-co-(3-trimethoxysilyl)propylmethacrylate).

4. The implantable medical device of claim 1, wherein the (trimethylammoniumethyl)-phosphate, inner salt)/(n-dodecylmethacrylate)/(hydroxypropylmethacrylate)/(3-trimethoxysilyl)propylmethacrylate) constitutional unit wt/wt ratio is from about 28.8:

50.7;

15.3;

5.3.

5. The implantable medical device of claim 1, wherein the phosphoryl choline acrylate polymer is substantially amorphous.

6. The implantable medical device of claim 1, wherein the drug reservoir layer comprises acrylate or methacrylate polymer.

7. The implantable medical device of claim 6, wherein the acrylate or methacrylate polymer has an average molecular weight of about 20,000 to about 600,000 Daltons.

8. The implantable medical device of claim 6, wherein the acrylate or methacrylate polymer comprises poly(butyl methacrylate).

9. The implantable medical device of claim 6, wherein the drug reservoir layer comprises poly(acrylate) or poly(methacrylate) having the formula:

wherein;

m=0.005 to 0.90

n=0.10 to 0.995

m+n=1

x=65 to 6960

R₁ and R₂ are independently selected from the group consisting of hydrogen and methyl; and

,

Hydrocarbon Group is selected from the group consisting of an unsaturated or saturated, branched or straight chain C₁ to C₁₆ aliphatic, a cycloaliphatic or an aromatic moiety.

10. The implantable medical device of claim 9, wherein the Polar Group is selected from the group consisting of an alkyl ether and an amide.

11. The implantable medical device of claim 10, wherein the alkyl ether is selected from the group consisting of:

12. The implantable medical device of claim 10, wherein the amide is selected from the group consisting of:

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 one or more therapeutic agents; and

a topcoat layer disposed as an outermost layer over the drug reservoir layer, wherein the topcoat layer comprises a phosphoryl choline acrylate polymer.

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

15. The method of claim 13, wherein the phosphoryl choline acrylate polymer comprises poly(2-(methacryloyloxyethyl)-2-(trimethylammoniumethyl)-phosphate, inner salt)-co-(n-dodecylmethacrylate)-co-(hydroxypropylmethacrylate)-co-(3-trimethoxysilyl)propylmethacrylate).

16. The method of claim 13, wherein the (trimethylammoniumethyl)-phosphate, inner salt)/(n-dodecylmethacrylate)/(hydroxypropylmethacrylate)/(3-trimethoxysilyl)-propylmethacrylate) constitutional unit wt/wt ratio is from about 28.8:

50.7;

15.3;

5.3.

17. The method of claim 13, wherein the phosphoryl choline acrylate polymer is substantially amorphous.

18. The method of claim 13, wherein the drug reservoir layer comprises acrylate or methacrylate polymer.

19. The method of claim 18, wherein the acrylate or methacrylate polymer has an average molecular weight of about 20,000 to about 600,000 Daltons.

20. The method of claim 18, wherein the acrylate or methacrylate polymer comprises poly(butyl methacrylate).

21. The method of claim 18, wherein the drug reservoir layer comprises poly(acrylate) or poly(methacrylate) having the formula:

Wherein;

m=0.005 to 0.90

n=0.10 to 0.995

m+n=1

x=65 to 6960

R₁ and R₂ are independently selected from the group consisting of hydrogen and methyl; and

,

Hydrocarbon Group is selected from the group consisting of an unsaturated or saturated, branched or straight chain C₁ to C₁₆ aliphatic, a cycloaliphatic or an aromatic moiety.

22. The implantable medical device of claim 21, wherein the Polar Group is selected from the group consisting of an alkyl ether and an amide.

23. The implantable medical device of claim 22, wherein the alkyl ether is selected from the group consisting of:

24. The implantable medical device of claim 22, wherein the amide is selected from the group consisting of:

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.