Coatings for implantable medical devices

• US 7,919,075 B1
• Filed: 03/20/2002
• Issued: 04/05/2011
• Est. Priority Date: 03/20/2002
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Michal, Eugene T., Shah, Ashok, Hossainy, Syed F. A.
• Primary Examiner(s): Fubara; Blessing M
• Application Number:
  US10/104,769
• Time in Patent Office: 3,303 Days
• Field of Search: 424/78.03, 424/400, 424/423, 424/405, 623/1.42, 623/1.11, 623/1.45
• US Class Current: 424/78.03
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• 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 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/606 Coatings
• 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: C08F 210/02 Ethene
• CPC Class Codes: C08F 216/06 Polyvinyl alcohol ; Vinyl alcohol
• CPC Class Codes: C08F 2800/10 as molar percentages
• CPC Class Codes: C08F 2810/50 wherein the polymer is a copolymer and the modification is taking place only on one or more of the monomers present in minority
• CPC Class Codes: C08F 8/00 Chemical modification by after-treatment graft polymers, block polymers, crosslinking with unsaturated monomers or with polymers C08F251/00 - C08F299/00; of conjugated diene rubbers C08C
• CPC Class Codes: C08F 8/14 Esterification
• CPC Class Codes: C08F 8/30 Introducing nitrogen atoms or nitrogen-containing groups
• CPC Class Codes: C08F 8/32 by reaction with amines
• CPC Class Codes: C08F 8/34 Introducing sulfur atoms or sulfur-containing groups
• CPC Class Codes: C08G 18/6212 Polymers of alkenylalcohols; Acetals thereof; Oxyalkylation products thereof
• CPC Class Codes: C08G 18/711 containing oxygen in addition to isocyanate oxygen
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 2666/04 : Macromolecular compounds according to groups C08L7/00 - C08L49/00, or C08L55/00 - C08L57/00; Derivatives thereof
• CPC Class Codes: C08L 2666/14 : Macromolecular compounds according to C08L59/00 - C08L87/00; Derivatives thereof
• CPC Class Codes: C09D 151/003 : grafted on to macromolecular compounds obtained by reactions only involving unsaturated carbon-to-carbon bonds C09D151/04, C09D151/06 take precedence
• CPC Class Codes: C09D 151/06 : grafted on to homopolymers or copolymers of aliphatic hydrocarbons containing only one carbon-to-carbon double bond
• CPC Class Codes: C09D 151/08 : grafted on to macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: C09D 175/04 : Polyurethanes

Abstract

Polymer coatings for medical devices are disclosed. The polymers can include at least one unit derived from ethylene and at least one vinyl unit or acrylic unit. The coatings can have a biologically compatible compound conjugated to, or blended with, the polymer.

Claims

1. A coating for a medical device, wherein the coating comprises a biologically compatible compound conjugated to a polymer,

wherein the polymer comprises tosylated or tresylated ethylene-vinyl alcohol copolymer (EVAL), or ethylene-glycidyl methacrylate copolymer (EGMA), and

wherein the biologically compatible compound comprises a superoxide dismutase compound.

2. The coating of claim 1, wherein the superoxide dismutase compound comprises manganese(II)dichloro-aminoethylthiolated pentaazatetracyclohexacosatriene.

3. The coating of claim 1, wherein the device comprises a stent.

4. The coating of claim 1, wherein the biologically compatible compound is further conjugated to a protein or a polysaccharide.

5. The coating of claim 1 further comprising a therapeutic substance, wherein the therapeutic substance is estradiol, paclitaxel, docetaxel or rapamycin.

34. The coating of claim 1 further comprising a therapeutic substance.

35. The coating of claim 3 further comprising a therapeutic substance.

36. The method of claim 34, wherein the biologically compatible compound is further conjugated to a protein or a polysaccharide.

37. The method of claim 34 further comprising a therapeutic substance, wherein the therapeutic substance is estradiol, paclitaxel, docetaxel, or rapamycin.

6. A coating for a medical device, wherein the coating comprises a biologically compatible compound conjugated to a polymer, wherein the polymer comprises tosylated or tresylated ethylene-vinyl alcohol copolymer (EVAL), or ethylene-glycidyl methacrylate copolymer (EGMA), and

wherein the biologically compatible compound comprises a diazenium diolate compound.

7. The coating of claim 6, wherein the diazenium diolate comprises a component selected from a group consisting of 1,3-propanediamine, N-{4-[1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazino]butyl}-diazen-1-ium-1,2-diolate and 1-{N-methyl-N-[6-(N-methylammonio)hexyl]amino}diazen-1-ium-1,2-diolate.

8. The coating of claim 6, wherein the device comprises a stent.

9. The coating of claim 6, wherein the biologically compatible compound is further conjugated to a protein or to a polysaccharide.

10. The coating of claim 6 further comprising a therapeutic substance, wherein the therapeutic substance is estradiol, paclitaxel, docetaxel, or rapamycin.

18. The method of claim 9, wherein the diazenium diolate comprises a component selected from a group consisting of 1,3-propanediamine, N-{4-[1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazino]butyl}-diazen-1-ium-1,2-diolate and 1-{N-methyl-N-[6-(N-methylammonio)hexyl]amino}diazen-1-ium-1,2-diolate.

11. A method of fabricating a medical device comprising:

(a) modifying a polymer by reacting a biologically compatible compound with the polymer, wherein the polymer comprises tosylated or tresylated ethylene-vinyl alcohol copolymer (EVAL), or ethylene-glycidyl methacrylate copolymer (EGMA), and

(b) depositing the polymer on an implantable medical device;

wherein the biologically compatible compound comprises a superoxide dismutase compound.

12. The method of claim 11, wherein the superoxide dismutase compound comprises manganese(II)dichloro-aminoethylthiolated pentaazatetracyclohexacosatriene.

13. The method of claim 11, wherein the biologically compatible compound further comprises a diazenium diolate or hyaluronic acid.

14. The method of claim 11, wherein the device comprises a stent.

15. The method of claim 11, wherein the superoxide dismutase compound comprises manganese(II)dichloro-aminoethylthiolated pentaazatetracyclohexacosatriene.

16. The method of claim 11 further comprising a therapeutic substance, wherein the therapeutic substance is estradiol, paclitaxel, docetaxel, or rapamycin.

24. The method of claim 14, wherein the device comprises a stent.

29. The method of claim 16, wherein the biologically compatible compound is conjugated to a protein or a polysaccharide.

17. A method of fabricating a medical device comprising:

(a) modifying a polymer by reacting a biologically compatible compound with the polymer, wherein the polymer comprises tosylated or tresylated ethylene-vinyl alcohol copolymer (EVAL), or ethylene-glycidyl methacrylate copolymer (EGMA), and

(b) depositing the polymer on an implantable medical device;

wherein the biologically compatible compound comprises a diazenium diolate compound.

19. The method of claim 17, wherein the biologically compatible compound further comprises a polysaccharide comprising a component selected from a group consisting of heparin, heparin containing hydrophobic counter-ion, chitosan, and hyaluronic acid.

20. The method of claim 19, wherein the therapeutic substance is taxol, estradiol, paclitaxel, docetaxel, or rapamycin.

21. The method of claim 17, wherein the biologically compatible compound is further conjugated to a protein or a polysaccharide.

22. The method of claim 17 further comprising a therapeutic substance, wherein the therapeutic substance is estradiolg paclitaxel, docetaxel, or rapamycin.

23. A method of fabricating a medical device comprising:

(a) forming a polymeric coating on an implantable medical device, wherein the polymer comprises tosylated or tresylated ethylene-vinyl alcohol copolymer (EVAL), or ethylene- glycidyl methacrylate copolymer (EGMA), and

(b) modifying the coating by reacting the polymer with a biologically compatible compound, wherein the biologically compatible compound comprises a superoxide dismutase compound.

25. The method of claim 23, further comprising a therapeutic substance contained in the coating wherein the therapeutic substance is estradiol, paclitaxel, docetaxel, or rapamycin.

26. The method of claim 23, wherein the device comprises a stent.

27. The method of claim 23, wherein the biologically compatible compound is further conjugated to a protein or a polysaccharide.

28. A method of fabricating a medical device comprising:

(a) forming a polymeric coating on an implantable medical device, wherein the polymer comprises tosylated or tresylated ethylene-vinyl alcohol copolymer (EVAL), or ethylene- glycidyl methacrylate copolymer (EGMA), and

(b) modifying the coating by reacting the polymer with a biologically compatible compound, wherein the biologically compatible compound comprises a diazenium diolate compound.

30. The method of claim 28, wherein the device comprises a stent.

31. The method of claim 28 further comprising a therapeutic substance contained in the coating wherein the therapeutic substance is estradiol, paclitaxel, docetaxel, or rapamycin.

32. The method of claim 28, wherein the biologically compatible compound is further conjugated to a protein or a polysaccharide.

38. The method of claim 30, wherein the medical device comprises a stent.

42. The method of claim 30, wherein the biologically compatible compound is conjugated to a protein or a polysaccharide.

43. The coating of claim 42, wherein the medical device comprises a stent.

44. The method of claim 32, wherein the biologically compatible compound is conjugated to a protein or a polysaccharide.

45. The coating of claim 42 further comprising a therapeutic substance,

wherein the therapeutic substance is estradiol, paclitaxel, docetaxel, or rapamycin.

46. The method of claim 30 further comprising a therapeutic substance.

47. The coating of claim 31 further comprising a therapeutic substance.

33. A method of fabricating a medical device comprising forming a coating on the device, wherein the coating comprises a biologically compatible compound conjugated to a polymer comprising tosylated or tresylated ethylene-vinyl alcohol copolymer (EVAL) or ethylene-glycidyl methacrylate copolymer (EGMA)

wherein the biologically compatible compound comprises a superoxide dismutase compound, a diazenium diolate, or hyaluronic acid;

and,

wherein the diazenium diolate comprises a component selected from a group consisting of 1,3-propanediamine, N- {4-[1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazino] butyl}-diazen-1-ium-1,2-diolate and 1-{N-methyl-N-[6-(N-methylammonio)hexyl]amino}diazen-1-ium- 1,2-diolate.

39. The method of claim 33, wherein the biologically compatible compound is further conjugated to a protein or a polysaccharide.

40. The method of claim 33 further comprising a therapeutic substance, wherein the therapeutic substance is estradiol, paclitaxel, docetaxel, or rapamycin.

41. A coating for a medical device, wherein the coating comprises a biologically compatible compound conjugated to a polymer comprising tosylated or tresylated ethylene-vinyl alcohol copolymer (EVAL), or ethylene-glycidyl methacrylate copolymer (EGMA),

wherein the biologically compatible compound comprises a superoxide dismutase compound, a diazenium diolate, or hyaluronic acid;

and

wherein the diazenium diolate comprises a component selected from a group consisting of 1,3-propanediamine, N-{4-[1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazino]butyl}-diazen 1-ium- 1,2-diolate and 1-{N-methyl-N-[6-(N-methylammonio)hexyl]amino }diazen- 1-ium 1,2-diolate.

48. The coating of claim 41 further comprising a therapeutic substance,

wherein the therapeutic substance is estradiol, paclitaxel, docetaxel, or rapamycin.