Use of an equilibrium intravascular sensor to achieve tight glycemic control

• US 8,088,097 B2
• Filed: 11/20/2008
• Issued: 01/03/2012
• Est. Priority Date: 11/21/2007
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: GluMetrics, Inc.
• Inventors: Markle, William H., Markle, David R.
• Primary Examiner(s): Mendez, Manuel
• Application Number:
  US12/274,617
• Publication Number:
  US 20090177143A1
• Time in Patent Office: 1,139 Days
• Field of Search: 424/9.6, 424/1.11, 424/1.65, 424/9.1, 514/765, 604 65- 67, 604131-133
• US Class Current: 604/66
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/412 Detecting or monitoring sepsis
• CPC Class Codes: A61M 5/16827 controlling delivery of multiple fluids, e.g. sequencing, mixing or via separate flow-paths infusion of multiple fluids without using a controller A61M5/1407
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00

Abstract

A method for achieving tight glycemic control in a patient in need thereof is disclosed. The method comprises deploying an equilibrium glucose sensor within a blood vessel in the patient, coupling the sensor to a monitor that displays the blood glucose concentration, and administering a blood glucose regulator when the blood glucose concentration varies outside of the predetermined concentration range. The blood glucose regulator is administered in an amount sufficient to return the blood glucose concentration to within the predetermined concentration range, thereby achieving tight glycemic control.

Claims

1. A method for maintaining glycemic control in a patient in need thereof, comprising:

deploying an equilibrium glucose sensor within a blood vessel in the patient, wherein the equilibrium glucose sensor comprises a fluorophore and a glucose binding moiety;

coupling the sensor to a monitor that displays patient'"'"'s blood glucose concentration;

and

manually administering a blood glucose regulator when the blood glucose concentration varies outside of a predetermined concentration range, wherein the blood glucose regulator is administered in an amount sufficient to return the blood glucose concentration to within the predetermined concentration range, thereby maintaining glycemic control.

2. The method of claim 1, wherein an alarm signal is generated when the blood glucose concentration varies outside of the predetermined concentration range.

3. The method of claim 1, wherein the monitor displays a rate and direction of change in the blood glucose concentration.

4. The method of claim 3, wherein the blood glucose concentration has a rising or falling trend and the blood glucose regulator is administered in an amount sufficient to reverse the rising or falling trend.

5. The method of claim 4, wherein an alarm signal is generated when the rate and direction of change in the blood glucose concentration varies outside a predetermined range.

6. The method of claim 1, wherein the predetermined concentration range is from about 60 to about 180 mg/dl glucose.

7. The method of claim 6, wherein the predetermined concentration range is from about 60 to about 130 mg/dl glucose.

8. The method of claim 7, wherein the predetermined concentration range is from about 80 to about 110 mg/dl.

9. The method of claim 1, wherein the blood glucose regulator is insulin or an analog or derivative thereof.

10. The method of claim 1, wherein blood glucose regulator is glucose.

11. The method of claim 1, wherein the fluorophore is chosen from the group consisting of a fluorescent organic dye, an organometallic compound, a metal chelate, a fluorescent conjugated polymer, quantum dots or nanoparticles, and combinations of the above.

12. The method of claim 1, wherein the fluorophore is a fluorescent dye.

13. The method of claim 12, wherein the fluorescent dye is capable of being excited by light of a wavelength greater than about 400 nm.

14. The method of claim 12, wherein the fluorescent dye is stable against photo-oxidation, hydrolysis, and biodegradation.

15. The method of claim 12, wherein the fluorescent dye comprises a HPTS-triCysMA dye.

16. The method of claim 13, wherein the fluorescent dye comprises SNARF-1.

17. The method of claim 12, wherein the fluorescent dye comprises SNAFL-1.

18. The method of claim 12, wherein the fluorescent dye comprises TSPP.

19. The method of claim 12, wherein the fluorescent dye and the analyte glucose binding moiety are physically immobilized within a semi-permeable membrane.

20. The method of claim 19, wherein the fluorescent dye and the glucose binding moiety are sufficiently greater in size than glucose, wherein the semi-permeable membrane allows passage of glucose but blocks passage of the fluorescent dye and the glucose binding moiety.

21. The method of claim 12, wherein the fluorescent dye and the glucose binding moiety are physically immobilized within a hydrogel matrix.

22. The method of claim 12, wherein the fluorescent dye and the glucose binding moiety are covalently bonded to a hydrogel matrix.

23. The method of claim 12, wherein the fluorescent dye and the glucose binding moiety are covalently bonded to each other.

24. The method of claim 1, wherein the glucose binding moiety comprises a boronic acid functionalized viologen quencher.

25. The method of claim 24, wherein the boronic acid functionalized viologen quencher comprises a 3,3′

-oBBV quencher.

26. The method of claim 1, wherein the equilibrium glucose sensor comprises an optical fiber.

27. The method of claim 26, wherein the optical fiber is coupled to a light source.

28. The method of claim 27, wherein the optical fiber is coupled to an emission light detector.

29. The method of claim 1, wherein glucose binding to the glucose binding moiety causes a change in fluorescence lifetime of the fluorophore, wherein said change is related to the blood glucose concentration.

30. The method of claim 1, wherein the equilibrium glucose sensor is configured to simultaneously measure blood glucose concentration and blood pH.

31. The method of claim 30, wherein the monitor is further configured to correct the blood glucose concentration for changes in blood pH prior to displaying the blood glucose concentration.

32. A method for maintaining glycemic control in a patient in need thereof, comprising;

providing an analyte sensor capable of simultaneously measuring blood glucose concentration and blood pH, the analyte sensor comprising an indicator system disposed along a distal end portion of an optical fiber, wherein the indicator system comprises;

a fluorescent dye that exists in at least first and second different forms depending on pH, wherein the different forms can be distinguished based on their respective first and second emissions, and

a glucose binding moiety operably coupled to the fluorescent dye, wherein glucose binding causes an optical change in either in a fluorescence emission intensity or a fluorescence emission lifetime, wherein the optical change is related to the blood glucose concentration;

wherein a ratio of said first and second emissions is independent of the blood glucose concentration; and

deploying at least the distal end portion of the analyte sensor in the patient;

coupling the analyte sensor to a controller configured to monitor the emission signals, determine blood glucose concentration based on the optical change, determine blood pH based on a ratio of the acid and base emissions, and perform real-time correction of the blood glucose concentration for changes in blood pH; and

administering a blood glucose regulator when the blood glucose concentration varies outside of a predetermined concentration range, wherein the blood glucose regulator is administered in an amount sufficient to return the blood glucose concentration to within the predetermined concentration range, thereby maintaining glycemic control.

33. A method for maintaining glycemic control in a patient in need thereof, comprising:

deploying an equilibrium glucose sensor in the patient, wherein the equilibrium glucose sensor comprises a fluorophore and a glucose binding moiety and wherein the equilibrium glucose sensor is configured to generate a continuous signal related to a blood glucose concentration and a rate and direction of change in the blood glucose concentration;

coupling the sensor to a monitor that displays a rate and direction of change in the blood glucose concentration;

determining based on the rate and direction of change in the blood glucose concentration whether intervention is warranted; and

intervening if warranted by administering an amount of a blood glucose regulator sufficient to prevent the blood glucose concentration from varying outside a target range, thereby maintaining glycemic control.

34. The method of claim 33, wherein the monitor displays both the rate and direction of change in the blood glucose concentration and continuous, real-time blood glucose concentration.