Anti-inflammatory biosensor for reduced biofouling and enhanced sensor performance

• US 7,153,265 B2
• Filed: 04/22/2002
• Issued: 12/26/2006
• Est. Priority Date: 04/22/2002
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Vachon, David J.
• Primary Examiner(s): Marmor, II, Charles A
• Assistant Examiner(s): Natnithithadha, Navin
• APPLICATION: US 20030199837A1
• Time in patent office: 1709 Days
• Field of Search: 600/345, 600/347, 600/353, 600/354, 600/365, 600/366, 600/372, 600/373, 600/377, 600/300, 600/309, 600/310, 600/316, 600395-397, 600/362
• US Class Current: 600/365
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

A biosensor including an external surface, and an accessory material in close proximity to the external surface. The accessory material includes a coating containing a hydrophilic material and/or a fiber modified to deliver a therapeutic agent. The biosensor modifies a biological response to the biosensor upon contact with a tissue, such as upon implantation into the skin of a subject, thereby reducing biofouling, inflammation and other undesirable tissue responses that interfere with biosensor performance. The biosensor can be any biocompatible sensor, suitable for short- or long-term use. Preferably, the biosensor is an enzymatic or electrochemical sensor, such as a glucose sensor. Also provided are a method of producing a biosensor and a method of delivering a biologically active substance to a subject.

Claims

1. A biosensor comprising an analyte sensor having an external surface, and an accessory material coated with a hydrophilic polymer provided in proximity to the external surface, wherein the accessory material modifies the biological response of a tissue that is in contact with the biosensor, wherein the accessory material is a fiber modified to deliver dexamethasone or a salt thereof.

2. The biosensor of claim 1, wherein the biological response comprises protein deposition, inflammation or proliferation of macrophages or foreign body giant cells.

3. The biosunsor of claim 1, wherein the hydrophilic polymer comprises polyhydroxyethylmethacrylate (PHEMA), polyurethane, polysaccharide, polyacrylamide, or polyurea.

4. The biosensor of claim 1, wherein the hydrophilic polymer comprises polyethylene oxide (PEO).

5. The biosensor of claim 4, wherein the PEO comprises a polyurethane, polyurea or a cross-linked PEO.

6. The biosensor of claim 1, wherein the salt is a sodium phosphate or acetate salt.

7. The biosensor of claim 1, which comprises an enzymatic, molecular recognition, oprochemical or electrochemical sensor.

8. The biosensor of claim 1, which comprises a glucose sensor.

9. The biosensor of claim 1, wherein the fiber comprises cotton, polypropylene, polyurethane, polyester, polylacric acid (PLA), polyglycolic acid (PGA), or a co-polymer of lactic acid and glycolic acid (PLGA).

10. The biosensor of claim 1, further comprising an additional therapeutic agent, which additional agent comprises an anti-inflammatory, anti-bacterial, anti-viral, anti-coagulant, anti-proliferative or disinfecting agent, or a growth factor.

11. The biosensor of claim 1, wherein the fiber is affixed to a distal end of the biosensor.

12. The biosensor of claim 11, wherein the fiber is affixed to the distal end of the biosensor by passage through a hole in the biosensor.

13. The biosensor of claim 1, wherein the fiber is affixed to the biosensor by insertion into a groove in the biosensor.

14. A method of delivering a biologically active substance to a subject comprising implanting a biosensor of claim 1 into a tissue of the subject, wherein the accessory niaterial comprises the biologically active substance.

15. The method of claim 14, wherein the biologically active substance additionally comprises a cytokine, growth factor or therapeutic agent.

16. A biosensor comprising a sensor having an external surface, and an accessory material provided in proximity to the external surface, wherein the accessory material modifies the biological response of a tissue that is in contact with the biosensor, wherein the accessory material is a fiber modified to deliver a therapeutic agent, and wherein the therapeutic agent comprises cefazolin or benzalkonium chloride, wherein the fiber comprises cotton, polypropylene polyurethane, polyesrer, polylactic acid (PLA), polyglycolic acid (PGA), or a co-polymer of lactic acid and glycolic acid (PLGA).

17. The biosensor of claim 16, further comprising an additional therapeutic agent, which additional agent comprises an anti-inflammatory, anti-bacterial, anti-viral, anti-coagulant, anti-proliferative or disinfecting agent, or a growth factor.

18. A biosensor comprising an sensor having an external surface, and an accessory material provided in proximity to the external surface, wherein the accessory material modifies the biological response of a tissue that is in contact with the biosensor, wherein the accessory material is a fiber modified to deliver dexamethasone or a salt thereof, wherein the biosensor comprises an enzymatic, molecular recognition, oprochemical or electrochemical sensor.

19. A biosensor comprising an sensor having an external surface, and an accessory material provided in proximity to the external surface, wherein the accessory material modifies the biological response of a tissue that is in contact with the biosensor, wherein the accessory material is a fiber modified to deliver dexamethasone or a salt thereof, wherein the biosensor comprises a glucose sensor.

20. A biosensor comprising a sensor having an external surface, and an accessory material provided in proximity to the external surface, wherein the accessory material modifies the biological response of a tissue that is in contact with the biosensor, wherein the accessory material is a fiber modified to deliver a therapeutic agent, and wherein the therapeutic agent comprises cefazolin or benzalkonium chloride, the biosensor further comprising an additional therapeutic agent, which additional agent comprises anti-inflammatory, anti-bacterial, anti-viral, anti-coagulant, anti-proliferative or disinfecting agent, or a growth factor.

21. A method of producing a biosensor, comprising:

providing an accessory material in close proximity to the biosensor;

modifiying the biological response of a tissue that is in contact with the biosensor using the accessory material,

delivering dexamethasone or a salt thereof, cefazolin or benzalkonium chloride using the accessory material; and

coating the fiber with a hydrophilic polymer.

22. The method of claim 21, wherein the biosensor is an analyte sensor.

23. The method of claim 22, wherein the polymer comprises a polyurethane, acrylate, polyester or cross-linked PEO.

24. The method of claim 22, wherein the coating comprises spraying or painting the polymer onto the fiber.

25. The method of claim 21, wherein the fiber is further modified to deliver an additional therapeutic agent.

26. A biosensor produced by the method of claim 21.