Antimicrobial coatings for medical devices and methods for making and using them

• US 20100285084A1
• Filed: 11/13/2007
• Published: 11/11/2010
• Est. Priority Date: 11/13/2007
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Christoferson, Laura, Jin, Eunjoo, Shah, Rajiv, Yang, Zhongping
• Granted Patent: US 8,512,731 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61L 2300/11 Peroxy compounds, peroxides, e.g. hydrogen peroxide
• CPC Class Codes: A61L 2300/208 Quaternary ammonium compounds
• 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: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Abstract

Embodiments of the invention provide methods for using compositions to inhibit microbial growth on a surface of a medical device having the composition applied thereto, to medical devices having the composition applied to a surface thereof and to methods for using the compositions to coat medical devices.

Claims

1. A method of inhibiting growth of a microorganism on a surface of a medical device comprising coating the surface of the medical device with:

(a) a first layer comprising an antimicrobial composition that includes a polypeptide that generates hydrogen peroxide upon exposure to a ligand of the polypeptide; and

(b) a second layer comprising an antimicrobial composition comprising a polymer having a quaternary amine moiety;

so that microbial growth is inhibited on the surface of the medical device when the surface is exposed to a microorganism.

2. The method of claim 1, further comprising:

identifying a susceptible surface on the medical device that is observed to be colonized in vivo by a microorganism when the device is implanted in a mammal;

coating at least 95% of the susceptible surface with the first and second layers; and

implanting the medical device in a mammal so that in vivo microbial growth is inhibited.

3. The method of claim 2, further comprising inhibiting growth of a microorganism on the surface of the medical device that is implanted in an individual having a pathological condition characterized by hyperglycemia.

4. The method of claim 1, wherein the surface is comprised of titanium.

5. The method of claim 1, wherein the polypeptide in the first layer is glucose oxidase.

6. The method of claim 1, further comprising forming the second layer from a polyurea-silicone copolymer.

7. The method of claim 1, further comprising disposing one or more further layers between the first layer and the second layer.

8. The method of claim 7, wherein a further layer disposed between the first layer and the second layer is a composition that promotes adhesion between the first and second layer.

9. The method of claim 1, further comprising disposing a further antibiotic composition on the surface of a medical device.

10. The method of claim 1, wherein a layer coated onto the surface of the medical device comprises a biodegradable polymer.

11. The method of claim 1, wherein a layer coated onto the surface of the medical device comprises a lectin that binds to a compound produced by a microorganism selected from the group consisting of Staphylococcus epidermidis, Pseudomonas aeruginosa, Streptococcus pneumoniae, Streptococcus viridans, Haemophilus influenzae, Escherichia coli, Staphylococcus aureus and Candida albicans.

12. The method of claim 2, wherein the device is a sensor for an in vivo analyte or a medication infusion device.

13. The method of claim 12, wherein the device is a glucose sensor comprising a plurality of layers, wherein at least one of the layers comprises:

an electrode having an electrochemically reactive surface area;

an analyte sensing layer that detectably alters the electrical current at the electrode in the presence of an analyte;

an adhesion promoting layer that promotes the adhesion between one or more layers of the glucose sensor;

an analyte modulating layer that modulates the diffusion of a analyte therethrough;

or

a cover layer that is impermeable to blood glucose, wherein the cover layer includes an aperture.

14. The method of claim 1, wherein the method is used to inhibit the growth of a microorganism that is capable of forming a biofilm on the surface of a medical device.

15. A method of inhibiting formation of a biofilm on a medical device that is implanted in an individual having hyperglycemia, the method comprising:

(a) identifying a surface on the medical device that is observed to be colonized by a biofilm forming microorganism; and

(b) coating the surface with;

a first layer that comprises an antimicrobial composition that includes a oxidoreductase that generates hydrogen peroxide upon exposure to a ligand for the oxidoreductase, wherein the amount of hydrogen peroxide generated by the polypeptide is proportional to the amount of ligand exposed to the polypeptide; and

a second layer disposed over the first layer that comprises an antimicrobial composition comprising a polyurea-silicone copolymer;

so that formation of a biofilm on the medical device is inhibited when the surface is exposed to the biofilm forming microorganism.

16. The method of claim 15, wherein the device is a glucose sensor comprising a plurality of layers, wherein at least one of the layers comprises:

an electrode having an electrochemically reactive surface area;

an analyte sensing layer that detectably alters the electrical current at the electrode in the presence of an analyte;

an adhesion promoting layer that promotes the adhesion between one or more layers of the glucose sensor;

an analyte modulating layer that modulates the diffusion of a analyte therethrough;

or

a cover layer that is impermeable to blood glucose, wherein the cover layer includes an aperture.

17. The method of claim 15, further comprising coating the medical device with a biodegradable polymer that is observed to degrade at a predetermined rate within an in vivo environment.

18. The method of claim 16, further comprising disposing an adhesion promoting layer between the first layer and the second layer.

19. The method of claim 15, wherein the oxidoreductase is glucose oxidase and the method further comprises immobilizing the glucose oxidase on the surface of the medical device using a procedure that results in the glucose oxidase having a oxidoreductase activity that is at least equal to the oxidoreductase activity observed when the glucose oxidase is immobilized on the surface via glutaraldehyde crosslinking.

20. A method of inhibiting microbial growth on a medical device that is implanted in a diabetic individual, the method comprising coating a surface of the medical device with at least two antimicrobial compositions, wherein the antimicrobial compositions include:

a first layer comprising a glucose oxidase composition, wherein the glucose oxidase is disposed in the first layer so as to generate hydrogen peroxide upon exposure to glucose in the individual; and

the first layer is disposed on the device so as to allow hydrogen peroxide generated by the glucose oxidase in the first layer to diffuse away from the glucose oxidase and contact a microorganism attempting to grow on the medical device and inhibit its growth;

wherein the amount of hydrogen peroxide generated by the glucose oxidase fluctuates in response to fluctuating glucose levels within the individual; and

a second layer comprising a polyurea-silicone copolymer composition having a quaternary amine, wherein the second layer is disposed on the medical device in a location such that the quaternary amine in the second layer inhibits the growth of a microorganism that contacts the second layer;

so that microbial growth on the implanted medical device is inhibited.

21. A method of inhibiting formation of a biofilm on a medical device that is implanted in an individual having a pathological condition characterized by ischemia, the method comprising:

(b) identifying a surface on the medical device that is observed to be colonized by a biofilm forming microorganism; and

(b) coating the surface with;

a first layer that comprises an antimicrobial composition that includes a oxidoreductase that generates hydrogen peroxide upon exposure to a ligand for the oxidoreductase;

so that formation of a biofilm on the medical device is inhibited when the surface is exposed to the biofilm forming microorganism.

22. The method of claim 21, further comprising inhibiting an anti-inflammatory response in the individual in which the device is implanted by coating the medical device with a second layer that comprises an anti-inflammatory steroid composition.

23. The method of claim 21, wherein the pathological condition is heart disease.

24. The method of claim 21, wherein the surface on the medical device an electronic lead of a pacemaker.

25. The method of claim 21, wherein the oxidoreductase is lactate oxidase.

26. The method of claim 25, wherein the lactate oxidase is disposed on the medical device in a location such that:

hydrogen peroxide generated by the lactate oxidase fluctuates in response to fluctuating lactate levels within the individual; and

hydrogen peroxide generated by the lactate oxidase diffuses away from the lactate oxidase and contacts a microorganism attempting to grow on the medical device so as to inhibit its growth.

27. An implantable medical device having a surface coated with an antimicrobial composition that includes a oxidoreductase that generates hydrogen peroxide upon exposure to a ligand for the oxidoreductase disposed on the device, wherein the antimicrobial composition is disposed on the surface of the device so as to allow hydrogen peroxide generated by the oxidoreductase to diffuse away from the oxidoreductase and contact a microorganism attempting to grow on the medical device, thereby inhibiting the growth of the microorganism.

28. The implantable medical device of claim 27, wherein the oxidoreductase is lactate oxidase.

29. The implantable medical device of claim 27, wherein a surface of the medical device is further coated with a dexamethasone composition.

30. The implantable medical device of claim 27, wherein the surface coated with an antimicrobial composition is disposed on an electronic lead.