Measurement of glucose in an insulin delivery catheter by minimizing the adverse effects of insulin preservatives

• US 10,780,222 B2
• Filed: 05/31/2016
• Issued: 09/22/2020
• Est. Priority Date: 06/03/2015
• Status: Active Grant

• Current Assignee: Pacific Diabetes Technologies, Pacific Diabetes Technologies, Inc.
• Original Assignee: Pacific Diabetes Technologies, Inc.
• Inventors: Ward, William Kenneth, Cargill, Robert S, Heinrich, Gabriel, Benware, Sheila, Vreeke, Mark, Kowalski, Joseph D., Seidl, Thomas
• Primary Examiner(s): Jang, Christian
• Assistant Examiner(s): Kingsley, Sarah R
• Application Number:
  US15/169,432
• Publication Number:
  US 20160354542A1
• Time in Patent Office: 1,575 Days
• Field of Search: None
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61M 2005/1587 suitable for being connected to an infusion line after insertion into a patient
• CPC Class Codes: A61M 2230/005 Parameter used as control input for the apparatus
• CPC Class Codes: A61M 2230/201 Glucose concentration
• CPC Class Codes: A61M 5/142 Pressure infusion, e.g. using pumps
• CPC Class Codes: A61M 5/158 Needles for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body
• CPC Class Codes: A61M 5/165 Filtering accessories, e.g. blood filters, filters for infusion liquids A61M1/14 , A61M1/34, A61M1/3627, A61M1/3679, A61M1/3687 take precedence; needle sets with incorporated air inlet filters A61M5/162
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00

Abstract

This disclosure teaches the concept, and method of creating, a dual use device intended for persons who take insulin. In one embodiment, the novel device is an insulin delivery cannula, the outer wall of which contains electrodes, chemical compounds and electrical interconnects that allow continuous glucose sensing and delivery of data to a remote device. Heretofore, the main problem in attempting to sense glucose at the site of insulin delivery has been the high current resulting from oxidation by the sensor of the preservatives in the insulin formulations. One means of eliminating these interferences is to poise the indicating electrode(s) of the sensor at a bias sufficiently low to avoid the signal from oxidation of the preservatives. One way of obtaining a glucose signal at a low bias is to use an osmium-ligand-polymer complex instead of conventional hydrogen peroxide sensing. Another is to use a size exclusion filter located in line with the insulin delivery tubing in order to remove the smaller phenolic preservative molecules while allowing the larger insulin molecules to pass unimpeded. These filtration concepts can also be more broadly applied, that is, the general concept of removal of unwanted drug formulation excipients from a drug delivery system.

Claims

1. A device for delivery of an insulin or insulin analog formulation and measurement of subcutaneous glucose concentration, comprising:

a hollow tube comprising an inner lumen, an outer wall, a proximal end, and a distal end, wherein the proximal end is in fluid communication with a source of the insulin or insulin analog formulation, wherein the distal end is configured to deliver the insulin or insulin analog formulation subcutaneously, wherein the insulin or insulin analog formulation comprises an excipient comprising a phenol or cresol; and

an amperometric glucose sensor disposed on the outer wall at a location no more than 7 millimeters (mm) away from the distal end, wherein the amperometric glucose sensor comprises;

an electrode layer comprising at least one indicating electrode, wherein the electrode layer underlies a redox-catalytic layer comprising (1) an osmium-based redox mediator comprising an osmium compound covalently bound to a pyridine-based or imidazole-based ligand, and (2) an enzyme comprising glucose oxidase or glucose dehydrogenase,

wherein the osmium-based redox mediator and the enzyme allow electron transfer from subcutaneous glucose to the at least one indicating electrode sufficient to cause a response of the amperometric glucose sensor to a subcutaneous glucose concentration at an applied bias potential of no more than +250 millivolts (mV) relative to a reference electrode, and

wherein the applied bias potential of no more than +250 mV relative to the reference electrode allows the electrode layer to undergo substantially no electropolymerization of the excipient during continuous operation of at least one hour of the amperometric glucose sensor, thereby maintaining a sensitivity of the amperometric glucose sensor to the subcutaneous glucose concentration in presence of the insulin or insulin analog formulation.

2. The device of claim 1, wherein the at least one indicating electrode comprises gold, carbon, graphite, platinum, or iridium.

3. The device of claim 1, wherein the ligand is 4,4′

-dimethyl-2,2′

-bipyridine.

4. The device of claim 1, wherein the osmium-based redox mediator is bound to poly (4-vinyl pyridine) or poly (1-vinyl imidazole).

5. The device of claim 1, wherein the amperometric sensor further comprises a reference electrode disposed on the outer wall.

6. The device of claim 1, wherein the reference electrode comprises a silver/silver chloride (Ag/AgCl) reference electrode.

7. The device of claim 1, wherein the amperometric sensor further comprises an insulating layer and a metal layer, wherein the insulating layer and the metal layer are disposed on the outer wall, wherein the insulating layer is coupled to the metal layer, and wherein the metal layer is coupled to the electrode layer.

8. The device of claim 7, wherein the insulating layer comprises a polyimide or liquid crystal polymer.

9. The device of claim 7, wherein the metal layer has a thickness of at least 2 micrometers (μ

m).

10. The device of claim 7, wherein the metal layer comprises titanium, gold, or platinum.

11. The device of claim 7, wherein the electrode layer comprises a film having a thickness of less than 500 nanometers (nm).