Hydrophilic, swellable coatings for biosensors

• US 20030069383A1
• Filed: 08/06/2002
• Published: 04/10/2003
• Est. Priority Date: 03/27/1995
• Status: Active Grant

• Current Assignee: Christian C. Decker, John J. Mastrototaro, William Peter Van Antwerp
• Original Assignee: Christian C. Decker, John J. Mastrototaro, William Peter Van Antwerp
• Inventors: Decker, Christian C., Mastrototaro, John J., Van Antwerp, William Peter
• Granted Patent: US 6,784,274 B2
• Time in Patent Office: Days
• US Class Current: 528/77
• 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
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: C08G 18/4833 Polyethers containing oxyethylene units
• CPC Class Codes: C08G 18/61 Polysiloxanes
• CPC Class Codes: C08G 18/6674 with compounds of group C08G18/3203
• CPC Class Codes: C08G 77/458 containing polyurethane sequences
• CPC Class Codes: C08J 2323/06 Polyethene
• CPC Class Codes: C08J 5/2287 After-treatment
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: Y10T 428/31551 Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]

Abstract

Methods for reducing the electrode impedance of implantable biosensors by coating the surface of the biosensor with a uniform hydrogel which allows unimpeded water movement around the sensor are provided. The surface coatings are compositions which are biocompatible and are capable of water uptake of at least 120% of their weight, more preferably at least 200% of their weight. Upon the uptake of water, the hydrogels used in the present invention will also swell and provide a layer of water around the electrodes to which the hydrogels are attached. The hydrogels can be prepared from (a) a diisocyanate, (b) a hydrophilic polymer which is a hydrophilic diol, a hydrophilic diamine, or a combination thereof, and optionally, (c) a chain extender.

Claims

1. A method of reducing electrode impedance of an implantable biosensor comprising coating said biosensor with a hydrogel, wherein said hydrogel is formed from a reaction mixture of:

(a) a diisocyanate, said diisocyanate comprising about 50 mol % of the reactants in said mixture;

(b) a hydrophilic polymer which is a member selected from the group consisting of a hydrophilic polymer diol, a hydrophilic polymer diamine and combinations thereof; and

optionally;

(c) a chain extender,

said hydrogel having a water pickup of from about 120% to about 400% by weight.

2. A method in accordance with claim 1, wherein said coating is by spin coating, dipping or spraying.

3. A method in accordance with claim 1, wherein said hydrophilic polymer is a poly(ethylene)glycol. selected from the group consisting of PEG 600, PEG 2000, Jeffamine D-230, Jeffamine ED-600, Jeffamine ED-900 and Jeffamine D-2000.

4. A method in accordance with claim 1, wherein said diisocyanate is a member selected from the group consisting of isophorone diisocyanate, 1,6-hexamethylene diisocyanate and 4,4′

-methylenebis(cyclohexyl isocyanate).

5. A method in accordance with claim 1, wherein said chain extender is selected from the group consisting of an alkylene diol, an alkylene diamine, an aminoalkanol and combinations thereof.

6. A method in accordance with claim 1, wherein said chain extender is selected from the group consisting of butanediol, ethylenediamine, hexamethylenediamine, 1,2-diaminocyclohexane and isophoronediamine.

7. A method in accordance with claim 1, wherein said diisocyanate is 1,6-hexamethylene diisocyanate and said hydrophilic polymer is selected from the group consisting of Jeffamine ED-600, Jeffamine D-2000 and PEG 2000 and is present in an amount of about 40 to about 50 mol %.

8. A method in accordance with claim 1, wherein said diisocyanate is 1,6-hexamethylene diisocyanate, said hydrophilic polymer is selected from the group consisting of Jeffamine ED-600, Jeffamine D-2000 and PEG 2000 and is present in an amount of about 40 to about 50 mol % and said chain extender is butanediol and is present in an amount of about 2.5 to about 10 mmol %.

9. An implantable biosensor having a hydrogel coating, said coating prepared from a reaction mixture of:

(a) a diisocyanate, said diisocyanate comprising about 50 mol % of the reactants in said mixture;

(b) a hydrophilic polymer which is a member selected from the group consisting of a hydrophilic polymer diol, a hydrophilic polymer diamine and combinations thereof; and

optionally;

(c) a chain extender;

wherein said coating has a water pickup of from about 120% to about 400% by weight.

10. An implantable biosensor in accordance with claim 9, wherein said hydrophilic polymer is a poly(ethylene)glycol selected from the group consisting of PEG 600, PEG 2000, Jeffamine D-230, Jeffamine ED-600, Jeffamine ED-900 and Jeffamine D-2000.

11. An implantable biosensor in accordance with claim 9, wherein said diisocyanate is a member selected from the group consisting of isophorone diisocyanate, 1,6-hexamethylene diisocyanate and 4,4′

-methylenebis(cyclohexyl isocyanate).

12. An implantable biosensor in accordance with claim 9, wherein said chain extender is selected from the group consisting of an alkylene diol, an alkylene diamine, an aminoalkanol and combinations thereof.

13. An implantable biosensor in accordance with claim 9, wherein said chain extender is selected from the group consisting of butanediol, ethylenediamine, hexamethylenediamine, 1,2-diaminocyclohexane and isophoronediamine.

14. An implantable biosensor in accordance with claim 9, wherein said diisocyanate is 1,6-hexamethylene diisocyanate and said hydrophilic polymer is selected from the group consisting of Jeffamine ED-600, Jeffamine D-2000 and PEG 2000 and is present in an amount of about 40 to about 50 mmol %.

15. An implantable biosensor in accordance with claim 9, wherein said diisocyanate is 1,6-hexamethylene diisocyanate, said hydrophilic polymer is selected from the group consisting of Jeffamine ED-600, Jeffamine D-2000 and PEG 2000 and is present in an amount of about 40 to about 50 mol % and said chain extender is butanediol and is present in an amount of about 2.5 to about 10 mol %.