Superoxide dismutase or superoxide dismutase mimic coating for an intracorporeal medical device

• US 20020009535A1
• Filed: 04/06/2001
• Published: 01/24/2002
• Est. Priority Date: 01/30/1998
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Buchko, Christopher J., Michal, Eugene T., Kilpatrick, Deborah L., Bigus, Stephen J.
• Granted Patent: US 6,541,116 B2
• Time in Patent Office: Days
• US Class Current: 427/2.1
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 29/048 Other specific proteins or polypeptides not covered by A61L29/045 - A61L29/047
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 31/047 Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61M 2025/0056 provided with an antibacterial agent, e.g. by coating, residing in the polymer matrix or releasing an agent out of a reservoir
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: Y10S 623/926 Synthetic
• CPC Class Codes: Y10T 428/31511 Of epoxy ether
• CPC Class Codes: Y10T 428/31536 Including interfacial reaction product of adjacent layers
• CPC Class Codes: Y10T 428/31609 Particulate metal or metal compound-containing
• CPC Class Codes: Y10T 428/31721 Of polyimide
• CPC Class Codes: Y10T 428/31855 Of addition polymer from unsaturated monomers
• CPC Class Codes: Y10T 428/31942 Of aldehyde or ketone condensation product

Abstract

A method of providing a therapeutic, diagnostic or lubricious hydrophilic coating on an intracorporeal medical device and the coated device produced thereby, wherein the coating is durable. In one embodiment, the coating comprises a polymerized base coat and a top coat having a therapeutic, diagnostic or hydrophilic agent, where the base coat has a binding component which binds to the top coat, and a grafting component which binds to the binding component and adheres to the device. In another embodiment, the coating comprises a blend of an agent, a grafting component, and salt. In one embodiment, the therapeutic agent is superoxide dismutase or a superoxide dismutase mimic. The coating of the invention may be applied to a medical device with a polymeric surface such as a polymeric catheter, or a metal device such as a stent coated with a polymeric primer or without a primer.

Claims

1. An intracorporeal medical device having a coating, the coating comprising:

a) a polymerized base coat on the device, comprising;

a binding component having at least a first functional group selected from the group consisting of isocyanate, aldehyde, oxirane, succinimide, maleimide, acetoacetoxy, aziridine, and carbodiimide; and

a grafting component selected from the group consisting of vinyl, acrylate and allyl compounds, adhered to the device and bonded to the binding component; and

b) a top coat on the base coat, comprising an agent selected from the group consisting of superoxide dismutase and a superoxide dismutase mimic, or a complex of the agent and a linking agent, the agent or the linking agent having a functional group which bonds with the binding component.

2. The coated device of claim 1 wherein the superoxide dismutase mimic comprises a manganese complex of a macrocyclic polyamine ring.

3. The coated device of claim 1 wherein the top coat agent functional group comprises a pendant ligand on the superoxide dismutase or superoxide dismutase mimic.

4. The coated device of claim 3 wherein the functional group of the pendant ligand is a primary amine.

5. The coated device of claim 1 wherein the top coat agent functional group is selected from the group consisting of amine, hydroxyl, and thiol, covalently bonded to the binding component.

6. The coated device of claim 5 wherein the binding component is selected from the group consisting of aldehyde, isocyanate, oxirane, and N-hydroxy succinimide compounds when the top coat agent or linking agent functional group is an amine group.

7. The coated device of claim 5 wherein the binding component is an isocyanate compound when the top coat agent or linking agent functional group is a hydroxyl group.

8. The coated device of claim 5 wherein the binding component is an maleimide compound when the top coat agent or linking agent functional group is a thiol group.

9. The coated device of claim 1 wherein the linking agent comprises an avidin-biotin complex having an avidin moiety bound to a biotin moiety, wherein the avidin-biotin complex is bound to the binding component and to the top coat agent.

10. The coated device of claim 1 wherein the linking agent comprises a liposome, microsponge, or microsphere containing the top coat agent.

11. The coated device of claim 1 wherein the device is a catheter.

12. The coated device of claim 1 wherein the device has a metal surface with the coating thereon.

13. The coated device of claim 12 wherein the device is selected from the group consisting of stents, guidewires, and cardiac pacing leads.

14. The coated device of claim 12 wherein the device surface has a polymeric primer coating selected from the group consisting of vinyl, acrylate and allyl compounds.

15. The coated device of claim 1 having about 5 to about 50 micrograms of a superoxide dismutase mimic.

16. An intracorporeal medical device having a coating, the coating comprising:

a) an agent selected from the group consisting of superoxide dismutase and a superoxide dismutase mimic; and

b) a polymerized grafting component selected from the group consisting of vinyl, acrylate, and allyl compounds, crosslinked to the agent in a crosslinked network, the crosslinked network comprising the grafting component polymerized and crosslinked in the presence of an ionic compound with at least one inorganic ion, the ionic compound being dissolvably removable from the coating.

17. A method of coating an intracorporeal medical device, comprising:

a) applying to the medical device a grafting component and a binding component, wherein the grafting component is selected from the group consisting of vinyl, acrylate and allyl compounds, and the binding component has at least a first functional group selected from the group consisting of isocyanate, aldehyde, oxirane, succinimide, maleimide, acetoacetoxy, aziridine, carboxy, and carbodiimide;

b) polymerizing the grafting component, so that the grafting component adheres to the device and bonds the binding component thereto, to form a base coat on the device; and

c) applying to the base coat a top coat having an agent selected from the group consisting of superoxide dismutase and a superoxide dismutase mimic, to covalently bond the agent to the binding component.

18. The method of claim 17 wherein polymerizing the grafting component comprises irradiating the grafting component with radiation.

19. A method of treating a patient, comprising introducing into the patient a medical device having a coating on at least a section of the device, the coating comprising

a) a polymerized base coat on the device, comprising:

a binding component having at least a first functional group selected from the group consisting of isocyanate, aldehyde, oxirane, succinimide, maleimide, acetoacetoxy, aziridine, and carbodiimide; and

a grafting component selected from the group consisting of vinyl, acrylate and allyl compounds, adhered to the device and bonded to the binding component; and

b) a top coat on the base coat, comprising an agent selected from the group consisting of superoxide dismutase and a superoxide dismutase mimic, or a complex of the agent and a linking agent, the agent or the linking agent having a functional group which bonds with the binding component.

20. The method of claim 19 wherein the method comprises prevention or inhibition of restenosis at the site of a dilated lesion, and the device comprises a stent, and including implanting the stent at the site of the dilated lesion.

21. The method of claim 19 wherein the method comprises inhibition of rupture and/or erosion of vulnerable plaque, and the device comprises a stent, and including implanting the stent at the site of the vulnerable plaque.

22. The method of claim 21 wherein the vulnerable plaque is eccentric, and the top coat extends around less than an entire circumference of the stent, and implanting the stent includes orienting the stent so that the top coat is positioned at the eccentric plaque.

23. A method of providing a coating for an intracorporeal medical device, comprising:

a) applying to the medical device a solution having a grafting component and a binding component, wherein the grafting component is selected from the group consisting of vinyl, acrylate and allyl compounds, and the binding component is selected from the group consisting of polyaziridine compounds, polycarbodiimide compounds, aldehyde compounds, and isocyanate compounds;

b) polymerizing the grafting component in the presence of the binding component by irradiating the grafting component with radiation, and bonding the grafting component to the binding component, to form a base coat on the device; and

c) applying to the base coat a solution of a top coat compound comprising an agent selected from the group consisting of superoxide dismutase and a superoxide dismutase mimic, or a complex of the agent and a linking agent, the agent or the linking agent having a functional group which bonds with the binding component, so that the top coat compound bonds to the binding component, to form the coating on the medical device.

24. An intracorporeal medical device having a coating, the coating comprising:

a) a polymerized base coat on the device formed from a solution of a binding component and a grafting component polymerized and crosslinked to the binding component on the device so that the grafting component bonds to the device,

i) the binding component being selected from the group consisting of polyaziridine compounds, polycarbodiimide compounds, aldehyde compounds, and isocyanate compounds and

ii) the grafting component being selected from the group consisting of vinyl, acrylate and allyl compounds; and

b) a top coat on the base coat, comprising an agent selected from the group consisting of superoxide dismutase and a superoxide dismutase mimic, or a complex of the agent and a linking agent, the agent or the linking agent having a functional group which bonds with the binding component and which is selected from the group consisting of carboxyl groups, hydroxy groups and amine groups, bonded to the binding component.

25. An intracorporeal medical device having a coating, the coating comprising:

a) a polymerized base coat on the device, comprising;

i) a binding component having at least a first functional group selected from the group consisting of acetoacetoxy, polyaziridine, polycarbodiimide, aldehyde, isocyanate, succinimide, maleimide, oxirane, and carboxyl derivatized with carbodiimide or tresyl or succinimide; and

ii) a grafting component selected from the group consisting of vinyl, acrylate and allyl compounds, adhered to the device and bonded to the binding component; and

b) a top coat on the base coat, comprising a therapeutic, diagnostic or hydrophilic agent, or a complex of a therapeutic, diagnostic or hydrophilic agent and a linking agent, the therapeutic, diagnostic or hydrophilic agent or the linking agent having a functional group which bonds with the binding component, said functional group selected from the group consisting of carboxyl, hydroxy amine, and thiol, covalently bonded to the binding component.

26. A medical device having a top coat bonded to a base coat to form a coating, the coating comprising:

a) a polymerized base coat on the device, comprising a homomultifunctional polymer having free acrylate groups at an air interface of the base coat following curing of the base coat and prior to addition of the top coat; and

b) a top coat having an agent or a complex of the agent and a linking agent, the agent or the linking agent having a functional group bonded to the acrylate groups.

27. The medical device of claim 26 wherein the homomultifunctional polymer is selected from the group consising of urethane acrylate and epoxy acrylate.

28. The medical device of claim 26 wherein top coat agent is selected from the group consisting of superoxide dismutase, a superoxide dismutase mimic, a nitric oxide donor, and a peptide.

29. The medical device of claim 28 wherein the top coat agent comprises superoxide or a superoxide mimic, and the top coat agent functional group comprises a primary amine ligand on the superoxide dismutase or superoxide dismutase mimic.

30. The medical device of claim 26 including a mono primary amine terminated PEG bonded to the base coat acrylate groups.

31. The medical device of claim 30 wherein the top coat agent is bonded to the PEG, so that the PEG is spacer between the top coat agent and the base coat.

32. The medical device of claim 30 wherein the top coat agent and the PEG are both bonded to the base coat acrylate groups.

33. A method of coating a medical device, comprising:

a) applying to the medical device a homomultifunctional oligomer compound;

b) curing the homomultifunctional oligomer, so that the compound adheres to the device and has free acrylate groups, to form a base coat on the device; and

c) applying to the base coat a top coat having an agent or a complex of the agent and a linking agent, the agent and the linking agent having a functional group which covalently bonds with the free acrylate groups, to thereby bond the top coat to the base coat compound.

34. The method of claim 33 wherein the top coat agent is selected from the group consisting of superoxide dismutase and a superoxide dismutase mimic, and the top coat functional group comprises a primary amine ligand on the superoxide dismutase or superoxide dismutase mimic, and curing oligomer comprises irradiating the oligomer with ultra violet radiation.

35. A method of coating a medical device, comprising:

a) applying to the medical device a solution of a homomultifunctional oligomer compound having free acrylate groups, and an agent having a functional group which covalently bonds to the compound; and

b) curing the oligomer solution, to thereby polymerize the oligomer and react some of the acrylate groups with the agent functional group, to form the coating.

36. The method of claim 35 wherein the agent is selected from the group consisting of superoxide dismutase having a primary amine ligand, a superoxide dismutase mimic having a primary amine ligand, an amine functional nitric oxide donor, spermine diazeniumdiolate, and a peptide with terminal lysine or arginine units, and curing oligomer solution comprises irradiating the solution with radiation.

37. The method of claim 35 wherein the solution includes a hydrophilic compound and an ionic compound with at least one inorganic ion, and the oligomer is polymerized in the presence of the ionic compound with at least one inorganic ion, and the ionic compound with at least one inorganic ion is dissolvably removable from the coating.

38. A medical device having a coating, the coating comprising:

a) an agent; and

b) a polymerized homomultifunctional compound having polymerized acrylate groups and acrylate groups bonded to the agent.

39. The medical device of claim 38 wherein the homomultifunctional compound comprises trimethylolpropane triacrylate.

40. The medical device of claim 39 wherein the agent is the agent is selected from the group consisting of superoxide dismutase having a primary amine ligand, a superoxide dismutase mimic having a primary amine ligand, an amine functional nitric oxide donor, spermine diazeniumdiolate, and a peptide with terminal lysine or arginine units.

41. The medical device of claim 38 wherein the coating includes a hydrophilic agent and a disolvably removeable ionic compound with at least one inorganic ion.