Implantable enzyme-based monitoring system having improved longevity due to improved exterior surfaces

• US 20050193860A1
• Filed: 03/31/2005
• Published: 09/08/2005
• Est. Priority Date: 10/20/1997
• Status: Active Grant

• Current Assignee: Alfred E. Mann Foundation For Scientific Research
• Original Assignee: Alfred E. Mann Foundation For Scientific Research
• Inventors: Schulman, Joseph H., Byers, Charles L., Adomian, Gerald E., Colvin, Michael S.
• Granted Patent: US 7,722,913 B2
• Time in Patent Office: Days
• US Class Current: 75/10.19
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors

Abstract

An implantable enzyme-based monitoring system suitable for long term in vivo use to measure the concentration of prescribed substances such as glucose is provided. In one embodiment, the implantable enzyme-based monitoring system includes at least one sensor assembly, an outer membrane surrounding the sensor assembly and having a window therein, and a polymeric window cover affixed to the outer membrane and covering the window. Preferably, the outer membrane of the monitoring system is silicone and the window cover is a polymer of 2-hydroxyethyl methacrylate (HEMA), N,N,-dimethylaminoethyl methacrylate (DMAEMA) and methacrylic acid (MA). Also provided herein is an implantable enzyme-based monitoring system having at least one sensor assembly, an outer membrane surrounding the sensor assembly and a coating affixed to the exterior surface of the outer membrane, wherein the coating resists blood coagulation and protein binding to the exterior surface of the outer membrane. Preferably, the coating is polyethylene glycol (PEG) and heparin in an 80:20 molar ratio. Finally, provided herein is a method of coating the exterior surface of the outer membrane of an implantable enzyme-based monitoring system comprising the steps of forming hydroxyl groups on the silicone surface by plasma etching; reacting the silicone surface with amino functionalized silane, thereby forming amino groups on the silicone surface; simultaneously, covalently binding polyethylene glycol (PEG) and heparin to the amino groups; and ionically binding heparin to the monitoring system surface.

Claims

1-12. -12. (canceled)

13. A method of coating the exterior surface of an implantable monitoring system comprising the steps of:

a) forming hydroxyl groups on the exterior surface of the monitoring system;

b) binding amino groups to the hydroxyl groups;

c) simultaneously covalently binding heparin and polyethylene glycol (PEG) to the amino groups; and

d) ionically binding heparin to the monitoring system surface.

14. A method of coating the exterior surface of an implantable monitoring system according to claim 13, wherein the hydroxyl groups are formed by plasma etching of the exterior surface of the monitoring system.

29. A method of coating the exterior surface of an implantable monitoring system according to claim 14, wherein the amino groups are bound to the hydroxyl groups by reacting with amino functionalized silane.

32. A method of coating the exterior surface of an implantable monitoring system according to claim 13, wherein the final molar ratio of heparin to polyethylene glycol (PEG) is 20 to 80.

16. A method of coating the exterior surface of an implantable monitoring system, wherein the exterior surface is comprised of silicone, the method comprising the steps of:

a) forming hydroxyl groups on the silicone surface by plasma etching;

b) reacting the silicone surface with amino functionalized silane, thereby forming amino groups on the silicone surface;

c) simultaneously, covalently binding polyethylene glycol (PEG) and heparin to the amino groups; and

d) ionically binding heparin to the monitoring system surface.

17. An implantable monitoring system having a coating on its exterior surface, which coating resists blood coagulation and protein binding to the exterior surface of the outer membrane and is applied to the surface by the method of claim 16.

18-28. -28. (canceled)