Device and method for delivery of a physiologically active substance depending on a measured physiological parameter

• US 8,303,533 B2
• Filed: 03/29/2006
• Issued: 11/06/2012
• Est. Priority Date: 03/29/2005
• Status: Expired due to Fees

• Current Assignee: Medizinische Universitaet Graz
• Original Assignee: Medizinische Universitaet Graz
• Inventors: Regittnig, Werner, Pieber, Thomas, Schaupp, Lukas, Ellmerer, Martin, Koehler, Gerd
• Primary Examiner(s): Sirmons, Kevin C
• Assistant Examiner(s): Gray, Phillip
• Application Number:
  US11/910,096
• Publication Number:
  US 20090005724A1
• Time in Patent Office: 2,414 Days
• Field of Search: 604/31, 604 65- 67, 604500-514, 600/366
• US Class Current: 604/65
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• 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 5/14528 invasively
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61M 2005/1726 the body parameters being measured at, or proximate to, the infusion site
• CPC Class Codes: A61M 2230/201 Glucose concentration
• CPC Class Codes: A61M 5/14232 Roller pumps
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• 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 device for delivery of glucose-regulating medication, particularly insulin, depending on the measured tissue glucose concentration, having a sensor for measuring the glucose concentration in tissue fluid, possibly a unit for removing fluid from subcutaneous tissue, as well as a container for the glucose-regulating medications, having a unit for subcutaneous delivery of the glucose-regulating medications, and having a unit connected to the glucose sensor for regulating the quantity of the glucose-regulating medication to be delivered depending on the measured tissue glucose concentrations. The device simulates the function of the natural pancreas and is constructed small and compact. The sensor for measuring the tissue glucose concentration or the unit for removing the tissue fluid is combined with the delivery unit for subcutaneous delivery of the glucose-regulating medication, particularly in a shared catheter, so that the measurement of the tissue glucose concentration is essentially performed at the location of the delivery of the glucose-regulating medication.

Claims

1. A device for delivery of a physiologically active substance depending on a measured physiological parameter, the device comprising:

a container for a perfusion fluid containing the physiologically active substance,

a unit for delivery of the perfusion fluid containing the physiologically active substance into the body,

a sensor for measuring the physiological parameter of the body by an analysis of the perfusion fluid after an at least partial equilibration of the perfusion fluid with a body fluid,

a unit, which is connected to the sensor by a signal line, for controlling the quantity of the physiologically active substance to be delivered depending on the measured physiological parameter,

a unit for calibrating the measurement of the physiological parameter,

wherein the sensor for measuring the physiological parameter is combined with the unit for delivery of the perfusion fluid containing the physiologically active substance in such a way that a location of the measurement of the body fluid for determining the physiological parameter in the body is in an area of influence of the delivered physiologically active substance, so that the measurement of the physiological parameter occurs essentially at the location of the delivery of the physiologically active substance, and

wherein the unit for calibrating the measurement of the physiological parameter is formed by a unit for measuring the conductivity of the perfusion fluid after an at least partial equilibration of the perfusion fluid with the body fluid.

2. The device according to claim 1,

comprising a unit for removing the perfusion fluid after the at least partial equilibration of the perfusion fluid with the body fluid.

3. The device according to claim 2,

wherein, additionally to the sensor, the unit for removing the perfusion fluid after the at least partial equilibration of the perfusion fluid with the body fluid is combined with the unit for delivery of the perfusion fluid containing the physiologically active substance, so that the measurement of the physiological parameter occurs essentially at the location of the delivery of the physiologically active substance.

4. The device according to claim 2,

wherein the sensor for measuring the physiological parameter and/or the unit for removing the perfusion fluid after the at least partial equilibration of the perfusion fluid with the body fluid is combined with the unit for delivery of the perfusion fluid containing the physiologically active substance, so that the measurement of the physiological parameter occurs essentially in the perfusion fluid after at least partial equilibration with the body fluid.

5. The device according to claim 1,

wherein the unit for delivery of the perfusion fluid containing the physiologically active substance is adapted for its delivery in at least one of the group consisting of subcutaneous tissue, cutaneous tissue, an organ, a vein, an artery, and a blood vessel.

6. The device according to claim 1,

wherein the unit for controlling the quantity of the physiologically active substance to be delivered depending on the measured physiological parameter is adapted to regulate the quantity of the physiologically active substance to be delivered depending on the measured physiological parameter.

7. The device according to claim 2,

wherein the unit for removing the perfusion fluid after the at least partial equilibration of the perfusion fluid with the body fluid comprises at least one of the group consisting of a microdialysis unit, a microperfusion unit, an ultrafiltration unit, a suction unit using a microneedle, and a transdermal extraction unit using reverse iontophoresis, ultrasound and/or osmotic pressure.

8. The device according to claim 2,

wherein the unit for removing the perfusion fluid after the at least partial equilibration of the perfusion fluid with the body fluid and the unit for delivery of the physiologically active substance are formed by a shared catheter for removing the fluid and/or measuring the physiological parameter and/or delivering the physiologically active substance.

9. The device according to claim 8,

wherein the catheter is formed by one of the group consisting of a microdialysis catheter, a microperfusion catheter, an ultrafiltration catheter, and an iontophoresis/reverse iontophoresis catheter.

10. The device according to claim 8,

wherein the catheter is formed by a double-lumen catheter, a perfusion fluid or a mixture of a perfusion fluid and the fluid removed from the body being suctioned through one lumen and the physiologically active substance being delivered via the other lumen.

11. The device according to claim 2,

wherein the sensor is integrated in the unit for removing the perfusion fluid after the at least partial equilibration of the perfusion fluid with the body fluid and/or in the unit for delivery of the physiologically active substance.

12. The device according to claim 1,

wherein a unit for conveying the perfusion fluid containing the physiologically active substance from the container for the perfusion fluid containing the physiologically active substance to the unit for delivery of the physiologically active substance is provided.

13. The device according to claim 2,

wherein a unit for conveying a perfusion fluid and/or the fluid removed from the body from the unit for removing the perfusion fluid after the at least partial equilibration of the perfusion fluid with the body fluid to the sensor is provided.

14. The device according to claim 7,

wherein the unit for conveying the perfusion fluid containing the physiologically active substance is simultaneously usable for conveying the perfusion fluid and/or the fluid removed from the body from the unit for removing the perfusion fluid after the at least partial equilibration of the perfusion fluid with the body fluid to the sensor.

15. The device according to claim 1,

wherein multiple containers for perfusion fluid containing physiologically active substance, preferably of different concentrations of the physiologically active substance, are provided.

16. The device according to claim 1,

wherein a container for a neutral solution is provided.

17. The device according to claim 16,

wherein the at least one container for the perfusion fluid containing the physiologically active substance and the container for the neutral solution are connected to a changeover switch, which is connected to the unit for controlling the quantity of the physiologically active substance to be delivered depending on the measured physiological parameter, so that the quantity of the physiologically active substance delivered is adjustable by actuating the changeover switch.

18. The device according to claim 17,

wherein the at least one container for the perfusion fluid containing the physiologically active substance and the container for the neutral solution are connected to a mixer, which is connected to the unit for controlling the quantity of the physiologically active substance to be delivered depending on the measured physiological parameter, so that the delivered quantity of the physiologically active substance is adjustable by actuating the mixer.

19. The device according to claim 1,

wherein at least one container for collecting analyzed perfusion fluid and/or fluid removed from the body is provided.

20. The device according to claim 19,

wherein the collecting container and the at least one container for the perfusion fluid containing the physiologically active substance and/or the container for the neutral solution are each formed by a shared container having a movable wall for separating the perfusion fluid containing the physiologically active substance and/or the neutral solution from the collected perfusion fluid and/or the fluid removed from the body.

21. The device according to claim 1,

wherein the at least one container for the perfusion fluid containing the physiologically active substance, and optionally the container for the neutral solution, is or are implemented as refillable.

22. The device according to claim 1, wherein the unit for calibrating the measurement of the physiological parameter is adapted to determine a degree of equilibration of the perfusion fluid with the body fluid.

23. The device according to claim 1, wherein the at least one container for the perfusion fluid containing the physiologically active substance, a container for a neutral solution, a container for collecting analyzed fluid removed from the body, the unit for delivery of the perfusion fluid containing the physiologically active substance, the unit for controlling the quantity of the physiologically active substance to be delivered, and the calibration unit are positioned in a shared housing.

24. A method for the delivery of a physiologically active substance depending on a measured physiological parameter, the method comprising:

delivering a perfusion fluid containing the physiologically active substance into a body,

measuring the physiological parameter of the body in such a way that a location of measurement of the body fluid for determining the physiological parameter in the body is in an area of influence of the delivered physiologically active substance by an analysis of the perfusion fluid after an at least partial equilibration of the perfusion fluid with a body fluid, and

controlling the quantity of the physiologically active substance delivered depending on the measured physiological parameter by way of a sensor and a signal line,

wherein the physiological parameter is measured essentially at the location at which the physiologically active substance is delivered.

25. The method according to claim 24,

comprising removing the perfusion fluid from the body after the at least partial equilibration of the perfusion fluid with the body fluid.

26. The method according to claim 24,

wherein the physiological parameter is measured essentially in the perfusion fluid after an at least partial equilibration with the body fluid.

27. The method according to claim 24,

wherein the physiologically active substance is mixed with a neutral solution before the delivery.

28. The method according to claim 24,

wherein the physiologically active substance is mixed with a neutral solution in subcutaneous tissue.

29. The method according to claim 24,

wherein the physiologically active substance is mixed with a neutral solution in predefined ratios and provided for delivery in the predefined mixing ratios.

30. The method according to claim 24,

wherein the measurement of the physiological parameter is calibrated, preferably permanently.