Method and system for implantable glucose monitoring and control of a glycemic state of a subject

• US 7,988,630 B1
• Filed: 05/27/2010
• Issued: 08/02/2011
• Est. Priority Date: 05/14/2004
• Status: Active Grant

• Current Assignee: Flint Hills Scientific, LLC
• Original Assignee: Flint Hills Scientific, LLC
• Inventors: Frei, Mark G., Osorio, Ivan
• Primary Examiner(s): Mallari; Patricia C
• Assistant Examiner(s): JANG, CHRISTIAN YONGKYUN
• Application Number:
  US12/802,009
• Time in Patent Office: 432 Days
• Field of Search: 600/345, 600/347, 600/365, 604/48, 604/65, 604/500, 604502-504, 604/890.1, 604/891.1
• US Class Current: 600/365
• 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 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/686 Permanently implanted devices, e.g. pacemakers, other stimulators, biochips A61B5/6861 takes precedence
• CPC Class Codes: A61M 2205/50 with microprocessors or computers
• CPC Class Codes: A61M 2230/201 Glucose concentration
• CPC Class Codes: A61M 5/14244 adapted to be carried by the patient, e.g. portable on the body
• CPC Class Codes: A61M 5/16877 Adjusting flow; Devices for setting a flow rate
• 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 and system for monitoring and/or controlling a glycemic state of a subject, comprising a housing device having one or more chambers, extendable and retractable sensors, extendable and retractable catheters, insulin reservoir, neuroprotective agent reservoir, release mechanism for releasing insulin and neuroprotective agent into the subject, and a control mechanism with a processor for receiving and analyzing outputs from the sensors and for controlling the release mechanism, a clock mechanism for providing logging and/or circadian information to the processor.

Claims

1. A system for monitoring and/or controlling a glycemic state of a subject, the system comprising:

(a) at least one housing device adapted to be fully embedded internally within a subject wherein the at least one housing device includes;

(1) a self-sealing membrane,

(2) one or more sensors configured and adapted to produce a sensor output relating to a glycemic state wherein each of the one or more sensors is extendable through the self-sealing membrane into, and retractable back through the self-sealing membrane from being in direct contact with a target of a subject,

(3) a reservoir containing insulin and having an output port,

(4) an injection mechanism configured to controllably inject the insulin through the output port,

(5) a control mechanism configured to receive and analyze at least one sensor output from the one or more sensors and to responsively control the quantity of insulin injected through the output port by the injection mechanism; and

(6) an insertion mechanism controlled by the control mechanism, the insertion mechanism being configured and adapted to selectively extend at least one of the one or more sensors through the self-sealing membrane to be and to selectively retract the at least one of the one or more sensors back through the self-sealing membrane from being in direct contact with the target of the subject; and

(b) an output mechanism that is activated by the control mechanism when the control mechanism detects an impending or occurring hypoglycemia and/or hyperglycemia condition as determined by the control mechanism from the sensor outputs; and

(c) wherein the control mechanism is further configured and adapted to determine whether the performance of the at least one of the one or more sensors has deteriorated below a predetermined level whereupon the control mechanism causes the insertion mechanism to automatically;

(1) extend another at least one sensor of the one or more sensors through the self-sealing membrane such that the at least one sensor is adapted to be in direct contact with the target of the subject, and

(2) retract the deteriorated sensor back through the self-sealing membrane with the deteriorated sensor being configured to be retained fully embedded within the subject.

2. The system as described in claim 1, wherein the target is selected from the group comprising a rib of the subject, a pectoralis muscle of the subject, the cranium of the subject, and the abdominal wall of the subject.

3. The system as described in claim 1, wherein the housing device further includes:

(a) an internal analysis chamber;

(b) a byproduct storage chamber;

(c) a sampling mechanism controlled by the control mechanism, the sampling mechanism configured to extract at least one specimen from the subject and to deposit the at least one specimen into the internal analysis chamber;

(d) a transfer mechanism controlled by the control mechanism, the transfer mechanism configured to transfer the at least one specimen from the internal analysis chamber to the byproduct storage chamber.

4. The system as described in claim 3, wherein:

(a) the sampling mechanism includes one or more catheters configured to extract from the subject, and to deposit into the internal analysis chamber, the at least one specimen; and

wherein

(b) the insertion mechanism is further configured to extend at least one of the one or more catheters from, and/or retract the at least one of the one or more catheters into, the housing device.

5. The system as described in claim 4, wherein the at least one of the one or more catheters includes at least two substantially identical catheters and wherein the at least two substantially identical catheters are alternatively disposed with one of the at least two substantially identical catheters being extended while another one of the at least two substantially identical catheters is retracted into a sensor cleaning chamber.

6. The system as described in claim 5, wherein the dispositions of the at least two substantially identical catheters are periodically alternated after a predetermined period of time.

7. The system as described in claim 5, wherein the dispositions of the at least two substantially identical catheters are alternated when the control mechanism determines that the performance of the one of the at least two substantially identical catheters has deteriorated below a predetermined level.

8. The system as described in claim 3, wherein at least one of the one or more sensors is disposed within the internal analysis chamber.

9. The system as described in claim 8, wherein the sampling mechanism includes at least one micro-needle configured to operatively acquire the specimen from the target of the body of the subject and deposit that specimen within the internal analysis chamber.

10. The system as described in claim 3, wherein the byproduct storage chamber includes a port having external access.

11. The system as described in claim 1, wherein the housing device further includes:

(a) a second reservoir separately containing one or more compounds that restores glucose concentration to normalcy or is neuroprotective, the second reservoir having at least one second output, and wherein

(b) the injection mechanism is further configured to controllably inject at least one of the one or more compounds through a corresponding one of the at least one second output, and wherein

(c) the control mechanism is further configured to control the quantity of the at least one of the one or more compounds injected through the corresponding one of the at least one second output.

12. The system as described in claim 11, wherein:

(a) one or more of the at least one second output is a catheter, and wherein

(b) the insertion means is further configured to extend the one or more catheters from, and/or retract the one or more catheters into, the housing device.

13. The system as described in claim 12, further comprising at least one self-resealing membrane through which the at least one of the one or more catheters is extendable and retractable.

14. The system as described in claim 11, wherein one of the one or more catheters that restores glucose concentration to normalcy is selected from substances that promote gluconeogenesis or glycogenolysis, or decrease insulin resistance.

15. The system as described in claim 11, wherein the one or more compounds that is neuroprotective is selected from a group comprising barbiturates, benzodiazepines, topiramate, gabapentin, tiagabine or lamotrigine.

16. The system as described in claim 1, wherein the target of the body of the subject is a tissue or organ selected from a set consisting of a blood, plasma, cerebrospinal fluid, extracellular fluid, a brain, a muscle, the liver, and a small intestine.

17. The system as described in claim 1, wherein the housing device further includes a sensor cleaning chamber configured to rejuvenate at least one of the one or more sensors.

18. The system as described in claim 1, wherein the housing device further includes a calibration chamber configured to calibrate the system.

19. The system as described in claim 1, wherein the housing device further includes a replacement sensor chamber containing one or more second sensors, the replacement sensor chamber configured to selectively replace at least one of the one or more sensors.

20. The system as described in claim 1, further comprising prevention means for preventing deposition of unwanted substances on the at least one of the one or more sensors.

21. The system as described in claim 1, further comprising removal means for removing unwanted substances from the at least one of the one or more sensors.

22. The system as described in claim 1, wherein the at least one of the one or more sensors includes at least two substantially identical sensors being used redundantly to detect spurious analysis thereof.

23. The system as described in claim 1, further including one or more second sensors in communication with the control mechanism and adapted to be in communication with one or more selected sites of the body of the subject.

24. The system as described in claim 23, wherein the one or more second sensors is selected from a set of monitors consisting of a metabolic sensor, an electrical sensor, a chemical sensor, an optical sensor, or another type of monitor wherein the one or more second sensors is located at one or more selected sites of the body of the subject.

25. The system as described in claim 24, wherein the one or more second sensors operatively monitors differences in glucose concentration at the one or more selected sites of the body of the subject.

26. The system as described in claim 25, wherein the one or more selected sites of the body of the subject are selected from a set of sites consisting of portal/hepatic circulation sites, intraparenchymal recording sites of a liver, external carotid and vessel/compartment sites having high blood flow rate and high tolerance for embolization, and intracranial structure sites including a brain.

27. The system as described in claim 24, wherein the one or more second sensors operatively monitors glucose clearance rates between the one or more selected sites of the body of the subject.

28. The system as described in claim 24, wherein the one or more second sensors operatively monitors functional state of the body of the subject at the one or more selected sites of the body of the subject.

29. The system as described in claim 24, wherein the one or more second sensors includes at least two second sensors located at two or of the one or more selected of the body of the subject.

30. The system as described in claim 29, wherein sensings are taken from the at least two second sensors simultaneously.

31. The system as described in claim 29, wherein sensings are taken from the at least two second sensors in a temporally synchronized manner to thereby account for temporal differences between the sensings at the two or of the one or more selected of the body of the subject.

32. The system as described in claim 23, wherein:

(a) the one or more second sensors monitor the one or more selected sites for autonomic indices and/or cerebral indices; and

(b) the control mechanism utilizes a multifactorial approach for individualized adaptive control of the glycemic state in the subject.

33. The system as described in claim 32, wherein the autonomic indices are hormonal and/or electrical.

34. The system as described in claim 32, wherein the cerebral indices are electrical or cognitive signals and are correlated with glucose concentration in at least one of the one or more selected sites.

35. The system as described in claim 34, wherein the output mechanism is activated by the control mechanism when the control mechanism detects an impending or occurring neuroglycopenia from sensor outputs which correlate changes in measures of cognitive performance with glucose measurements.

36. The system as described in claim 23, wherein at least one of the one or more selected sites is selected to monitor firing patterns of various neurons in the brain of the subject in order to gain instantaneous real time information regarding the glycemic state of the subject.

37. The system as described in claim 23, wherein at least one of the one or more selected sites is a brain of the subject for measuring glucose concentration and/or neuronal electrical activity, and clearance rates for monitoring and controlling the glycemic state of the subject.

38. The system as described in claim 23, wherein at least one of the one or more selected sites is a cerebrospinal fluid of the subject for measuring glucose concentration and clearance rates for monitoring and controlling the glycemic state of the subject.

39. The system as described in claim 23, wherein at least one of the one or more selected sites is an extracellular fluid of the subject for measuring glucose concentration and clearance rates for monitoring and controlling the glycemic state of the subject.

40. The system as described in claim 23, wherein at least one of the one or more selected sites is selected from a set of sites of the subject consisting of a gastrointestinal tract, in or over an eye, a portal vein, a hepatic vein and a carotid system.

41. The system as described in claim 1, wherein the control mechanism is configured to operatively conduct an electrochemical analysis in order to analyze glucose for monitoring and controlling the glycemic state in a subject.

42. The system as described in claim 1, wherein the control mechanism is configured to operatively conduct an optical analysis in order to analyze glucose for monitoring and controlling the glycemic state in a subject.

43. The system as described in claim 42, wherein the optical analysis is selected from a set of analyses consisting of optical absorption, spectroscopy, polarimetry, fluorescence, and spectrophotometry.

44. The system as described in claim 1, wherein the control mechanism is configured to operatively conduct an analysis of indices selected from a set of indices consisting of local insulin levels, osmolality, glucosuria, and concentrations of other substances in plasma, blood, or tissue including, but not limited to, blood oxygen levels, ketones, interleukins, lactic acid, free incretins, free fatty acids, glycated hemoglobin, epinephrine, cortisol, glucagon, and neurotransmitters or neuromodulators, in order to assess glycemic state and glucoregulatory response to control the glycemic state of the subject.

45. The system as described in claim 1, wherein the control mechanism includes a processor.

46. The system as described in claim 45, wherein the processor includes a control algorithm.

47. The system as described in claim 46, wherein the control algorithm is adaptive to individual glycemic state characteristics of the subject.

48. The system as described in claim 47, wherein adaptation of the control algorithm to the individual glycemic state characteristics of the subject can occur either online or offline.

49. The system as described in claim 47, wherein adaptation of the control algorithm to the individual glycemic state characteristics of the subject includes information gathered by the control mechanism from monitoring the subject.

50. The system as described in claim 47, wherein adaptation of the control algorithm to the individual glycemic state characteristics of the subject includes information gathered by the control mechanism in regard to the subject'"'"'s response to application of the control algorithm.

51. The system as described in claim 46, wherein the control algorithm is configured to automatically control insulin delivery in real-time to the subject.

52. The system as described in claim 45, where the processor includes a real-time clock and non-volatile memory configured to store and log information processed by the control mechanism.

53. The system as described in claim 52, wherein the information stored and logged in the non-volatile memory includes beginning time, ending time, and intensity of selected portions of the information processed by the control mechanism.

54. The system as described in claim 52, wherein the information stored and logged in the non-volatile memory includes failure detection in regard to one or more components of the system.

55. The system as described in claim 45, wherein the processor is configured to monitor and detect abnormal glucose changes of the subject by performing digital, analog and/or signal analyses of the sensor outputs of the one or more sensors.

56. The system as described in claim 1, wherein the housing device further includes:

(a) a second reservoir separately containing a plurality of glucose-lowering agents, each with a corresponding second output port;

(b) the injection mechanism is further configured to inject each of the plurality of glucose-lowering agents through its corresponding second output port; and

(c) wherein the control mechanism is further configured to select and to independently control the quantity and rate of injection of each of the plurality of glucose-lowering agents injected through its corresponding second output port as determined by the control mechanism from at least one of the outputs.

57. The system as described in claim 56, wherein the plurality of glucose-lowering agents includes a rapid acting insulin formulation, an intermediate acting insulin formulation, and a slow acting insulin formulation.

58. The system as described in claim 56, wherein the locations of the injections from the plurality of the glucose-lowering agents are situated at two or more parts of the body of the subject.

59. The system as described in claim 1, wherein the output mechanism includes a warning mechanism that is configured to operatively alert the subject as to the impending or occurring hypoglycemia or hyperglycemia condition.

60. The system as described in claim 59, wherein the warning mechanism includes an audible recorded message.

61. The system as described in claim 1, wherein

(a) the control mechanism includes an output element;

and wherein

(b) the system further comprises;

(1) an external component; and

(2) a communication link connecting the output element in communication with the external component wherein information can be transferred between the control mechanism and the external component.

62. The system as described in claim 61, wherein a communication media of the communication link is an electrical conductor arrangement.

63. The system as described in claim 61, wherein a communication media of the communication link is wireless transmission.

64. The system as described in claim 61, wherein the information transferred between the control mechanism and the external component is one or more of a set consisting of information for programming the control mechanism, information stored in the control mechanism, monitoring information, failure information, warning information, and information regarding therapy treatment provided by the control mechanism.

65. The system as described in claim 61, wherein the communication link between the control mechanism and the external component includes the ability to transfer and communicate warning information to “

911”

.

66. The system as described in claim 61, wherein the information transferred between the control mechanism and the external component includes information to administer cognitive testing of the subject in order to determine the subject'"'"'s state of awareness, said information comprising a determination of a high risk for low glucose concentration, a high risk for high glucose concentration, a glucose concentration that reaches or exceeds a prespecified threshold, or prespecified times of when the subject is at highest risk of neuroglycopenia.