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WO2010062211A2 - Procédé et moyens pour contrôler automatiquement une thérapie - Google Patents

Procédé et moyens pour contrôler automatiquement une thérapie Download PDF

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Publication number
WO2010062211A2
WO2010062211A2 PCT/RU2009/000436 RU2009000436W WO2010062211A2 WO 2010062211 A2 WO2010062211 A2 WO 2010062211A2 RU 2009000436 W RU2009000436 W RU 2009000436W WO 2010062211 A2 WO2010062211 A2 WO 2010062211A2
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WO
WIPO (PCT)
Prior art keywords
methods
infusion
glucose
catheter
basal
Prior art date
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Ceased
Application number
PCT/RU2009/000436
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English (en)
Russian (ru)
Other versions
WO2010062211A9 (fr
WO2010062211A3 (fr
WO2010062211A4 (fr
Inventor
Владимир Дмитриевич ЧУВАШОВ
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Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/RU2008/000577 external-priority patent/WO2009031943A1/fr
Application filed by Individual filed Critical Individual
Publication of WO2010062211A2 publication Critical patent/WO2010062211A2/fr
Publication of WO2010062211A3 publication Critical patent/WO2010062211A3/fr
Publication of WO2010062211A4 publication Critical patent/WO2010062211A4/fr
Anticipated expiration legal-status Critical
Publication of WO2010062211A9 publication Critical patent/WO2010062211A9/fr
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/172—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic
    • A61M5/1723—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic using feedback of body parameters, e.g. blood-sugar, pressure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
    • A61B5/4839—Diagnosis combined with treatment in closed-loop systems or methods combined with drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A61M2005/14208—Pressure infusion, e.g. using pumps with a programmable infusion control system, characterised by the infusion program

Definitions

  • the invention relates to medicine, namely, methods of control and intensive care used in critical situations or in emergency situations, for example, diabetes (hundreds of millions of patients). These include the international application PCT / RU2008 / 00057 "Method for monitoring the insulin therapy of diabetes" from 08/25/2008, and a similar application RU 2007132513 from 08/28/2007. Priority has been requested for both applications with respect to the figure and paragraphs 1-
  • the intensity of therapy is determined by the frequency of medication, sometimes for life. This requires continuous monitoring of the effectiveness of medication, as well as ongoing monitoring of drug administration.
  • the traditional diabetes intensive care method is based on manually injecting the patient under the skin
  • Medtronic launched the world's first integrated Paradigm 722 system - an insulin pump with real-time electrochemical glucose monitoring.
  • the system is protected by patents, for example AT363228T, WO0049941 and international application WO 2006/122048 Al. These documents relate to the prototypes of the proposed invention and are cited by reference.
  • the disadvantages of the system include the high cost of consumables (interchangeable sensor + interchangeable catheter, $ 100 for three days) and the need for a 4-fold daily blood sampling to calibrate the monitor. This equipment retains the main drawback of all known methods - the need for frequent blood sampling to assess the effectiveness of therapy.
  • the aim of this invention is the development of tools and methods that eliminate the above limitations in practice for various diseases and contribute to the creation of an automatic therapy system with negative feedback between the monitor and the pump. 5
  • control methods and intensive care tools for diabetes and / or other diseases including a programmable pump for infusion of a drug solution into a patient’s body through a connection device (see WO 2006/122048 Al double insert device) with an optical and / or electrochemical sensor body fluid or whole blood characteristics are characterized as follows. 10
  • the means are designed so that:
  • the catheter line is located under the skin
  • the sensor is located inside the tube.
  • a catheter passes infusions, such as insulin, through passageways in the base and at the outlet end of the catheter.
  • the side wall of the pipe contains a well-wettable porous material and / or holes for passing through, such as glucose.
  • the catheter is designed so that the base contains a sensor washed by a fluid flowing from the flow cavity through the passage opening into a removable ampoule.
  • the double insert is fixed to the lid of the intradermal port implanted under the patient’s skin.
  • the hypodermic part of the port contains a stable base and an elastic mesh for circular protection of the double insert from spasms and other loads.
  • the double insert device is designed as an artificial shunt of a blood vessel, with the infusion site located at the beginning of the blood flow, and the measurement site, for example, optical, is located further. 25
  • the solution for infusion and / or perfusion contains glucose or another controlled biomarker with a target concentration, for example, equal to the average value for the prescribed range of therapy, or in particular equal to zero.
  • the double insert device is designed so that infusions flow through the measurement site.
  • ADC analog-to-digital converter
  • the ADC output is connected to a microcontroller (MCU).
  • MCU contains conversion frequency divider for synchronization of the basal program
  • the divider divides each therapy session into intervals T k n , p is the number of the current medication interval, k is the session number.
  • the basal program distributes equal volumes of each infusion evenly, for example, during the day with an hourly interval T k n .
  • the MCU contains a program for calculating in real time the average signal current ⁇ sign n ( ⁇ ) to estimate the duration ⁇ and the effect of each infusion on the calculation result.
  • the microcontroller is connected to a data input device from an external measurement source, for example, from a blood glucose meter.
  • a controlled biomarker such as a blood glucose level
  • a target level of MCU therapy lowers the biomarker level, for example, using a bolus infusion of short (ultra) insulin.
  • a basal interval of medication such as diabetes, for at least 30 minutes.
  • the minimum medication interval is at least 15 minutes.
  • a managed biomarker such as blood glucose
  • the biomarker level is increased. For example, inform the patient: "Eat 15 grams of rapidly soluble carbohydrates (glucose tablets)." twenty
  • Fig. 2 The subcutaneous portion of the double insert device.
  • Fig. 3 Intradermal port with double insert device.
  • this invention relates to an intensive care control system, for example, diabetes, including a pump, sensor, and glucose monitor.
  • an intensive care control system for example, diabetes, including a pump, sensor, and glucose monitor.
  • the sensor and monitor are a sensor and a monitor for determining the level of glucose in the blood and / or body fluid of the user.
  • pump therapy has been widely used in recent years.
  • the concentration of glucose in the blood changes with diseases of the pancreas, thyroid gland, pituitary gland, adrenal glands, kidneys, liver, intestines, with traumatic, toxic irritation of the central nervous system and in a number of other pathological conditions.
  • FIG. 1 The principal design of the claimed method in the case of subcutaneous and / or intramuscular infusion is shown in Figure 1.
  • 1 Patient's body; 2 - A patch for fixing 3 on the patient's body; 3 - Device for connecting a cannula of a catheter with a glucose sensor at the measurement site; 4 - catheter; 5 - Pump with a software and computing unit and a glucose monitor; 6 - Signal cable for glucose sensor.
  • FIG. 1 is presented in PCT Priority Application, which is incorporated herein by reference.
  • the catheter cannula connecting device to the sensor is called a double insert device, as described in WO 2006/122048 Al and is cited as a reference.
  • the figure 2 shows the subcutaneous part of the double insert.
  • the figure 3 shows a diagram of its input into the patient’s body through the intradermal port.
  • a double insert such as a coaxial catheter, is designed so that:
  • the base 16 of the catheter has passage holes for infusion and / or perfusion and is fixed to the patient’s skin.
  • a catheter line 12 is placed under the skin.
  • the sensor 11 is placed inside the pipeline.
  • the side wall 9 of the pipeline contains a well-wettable porous material '8 and / or holes through which passive diffusion of substances (for example, glucose) occurs along their concentration gradient.
  • Enzymes are immobilized, including in the film membrane 7, for example, from albumin. It is attached, for example, to the surface of the electrodes 10, 20.
  • the body fluid 18 diffuses through the holes in the wall 9 into the layer 7 containing the enzyme, forming an electrically active substance detected by the sensor 11.
  • the permeability of membranes for most substances is determined by the size of the pores and / or holes (die cut-offsize).
  • the flow cavity between the sensor 11 and the side wall 9 passes an infusion, for example, of insulin solution 14, through the passageways 13 at the outlet end of the catheter 12 and the passageways through base 16.
  • the catheter is designed so that the base 16 contains a sensor 20, washed by a fluid flowing through a passageway into a removable ampoule 21.
  • the catheter is, for example, a polyurethane tube with an outer diameter of 1.5 mm and a length of 10 mm.
  • a catheter is inserted into the patient's body using a penetrating needle.
  • An isotonic solution for infusion enters through the orifice in the flow cavity.
  • the liquid solution is passed through the infusion system 15 with a pump 5 at a speed of, for example, 0.5 microliters / min.
  • a specialized solution CMS perfusion fluid, CMA Microdialysis, Solpa, Swedep
  • the catheter type CMA70 used for similar purposes in clinical practice, has pores of 20 kilodaltons in size.
  • the portion of the solution containing the recovered substances flows along the side wall into the lid of the catheter. There it accumulates in a removable vial 21.
  • the reaction time of the sensors 10 and 20 to diffusion, for example glucose, is approximately the same due to the well-wetted side wall.
  • a catheter located in the extracellular fluid mimics the function of a blood vessel (capillary). Continuous renewal of the solution in the membrane area supports the transmembrane concentration gradient.
  • the ampoule is replaced by the following.
  • Express analysis of the main clinical markers (glucose, lactate, pyruvate, glutamate, glycerol and urea), including the prescribed medicine, is carried out, for example, by enzymatic methods.
  • This analysis reflects the biochemical profile of the tissue fluid during dialysate collection and is therefore always retrospective. For this, it is necessary to take into account the accumulation time of dialysate in an ampoule with a volume of, for example, 30 microliters, which can be up to 100 minutes at a perfusion rate of 0.3 microliters / min.
  • the double insert device is fixed in the cover 22 of the intradermal port implanted under the patient’s skin.
  • the mount provides for mounting / dismounting of the double insert.
  • the subcutaneous part of the port contains a stable base 17 and an elastic mesh 19 for circular protection of the double insert from spasms and other loads.
  • An analogue of the proposed invention is intended for measuring glucose levels by optical methods and is cited as reference. G. G. Vosquet, Gerald L. Saute, Ashkod Gowda, Regg Ms Nisseskohls, Sokhi Rastegar METAL DETAILS DETAILS DETAILS DETAILS USED Date of Rathept: Aug. 20, 2002.
  • the double-insert device is designed as an artificial shunt of a blood vessel, and the place of infusion of the drug is located at the beginning of the blood flow, and the place of measurement, for example, optical, is located a little further.
  • analogue of such an implantable therapy management system device is described in US6, 122, 536 and US 6,438,397 Bl and cited as reference.
  • the analogue two different veins are used, one for the optical sensor, the other for the infusion of the drug.
  • an artificial vessel due to blood flow, provides a difference in the measurement results of the sensor covering it, which occurs after each infusion.
  • This design uses the method described in cl. 1 of priority application PCT / RU2008 / 00057, and expands the possibilities of applying the claimed invention.
  • Figure 4 illustrates the various possibilities of applying the main method of therapy management.
  • the infusion solution contains glucose or another control biomarker with a concentration, for example, corresponding to the middle of the prescribed target range of therapy, or equal to zero.
  • the double insert device is configured so that all infusions flow through the measurement site.
  • the previous volume is displaced from the measurement zone and replaced with the next volume of isotonic solution. Due to the concentration gradient that arises in this case, glucose molecules diffuse into the measurement zone until an equilibrium state is reached.
  • the duration of the process is units and tens of seconds.
  • ADC digital measurement transducer
  • the ADC output is connected to a microcontroller (MCU).
  • MCU contains a conversion frequency divider to synchronize the basal program.
  • the MCU output is connected to a basal and bolus infusion administration program.
  • the divider divides each therapy session into intervals T k n , p is the number of the current medication interval, k is the session number.
  • the basal program distributes equal volumes of each infusion of the drug evenly, for example, during the day with an hourly interval T k n.
  • the uniform distribution of the basal dose and the equal volume of each bolus and basal infusion unify the measurement conditions.
  • the measurement procedure is partially combined with the medication procedure. These circumstances are used for the working verification of current measurements at time intervals between the current infusion entries as described below.
  • the MCU contains a program for calculating the current average signal values ⁇ sign n (t) and estimating the duration ⁇ of the effect of each infusion on the measurement results homage ⁇ whyce ⁇ k sign ( ⁇ ). It uses it to determine the duration of the intervals T k n , mj where t is the number of the current measurement interval on each interval T k n .
  • the second input of the MCU is connected to a data input device from an external measurement source, for example, a home glucose meter.
  • an external measurement source for example, a home glucose meter.
  • the MCU contains a differential calibration program using traditional pair measurement methods and linear calculation of calibration coefficients. Calculates the current levels of the managed biomarker at each interval T k n , m within each interval T n .
  • the above calculation of current differences is essentially a method of working verification of the current level of systematic average deviation in the results of electronic measurements.
  • the means of verification is the infusion of the drug into the measurement area.
  • the physicotechnical properties of such preparations are, as a rule, guaranteed by the manufacturer.
  • Calibration is carried out with each infusion, which automatically eliminates the influence of all random factors on the value of the systematic average deviation in the results of determining the differential current of the sensor and, accordingly, the glucose level.
  • calibration coefficients are used, preferably determined by the point-to-point method. The duration of such a session depends on the need, for example, to replace the infusion system or reservoir with the solution, or other reasons that clearly change the measurement conditions and therefore require a new calibration.
  • PARADIGM REAL TIME the session lasts up to three days. At the same time, calibration reduces the number of blood samples for analysis, almost an order of magnitude.
  • Negative feedback algorithms significantly reduce the effect of possible changes in the scale of measurements on the control error relative to a given equilibrium point (for example, the middle of the target range of therapy). With the target width commonly practiced in diabetes, the accuracy requirements are a few mmol / L units.
  • the solution used in some applications contains glucose with a concentration equal to the middle of the target range.
  • Such a solution improves the accuracy of glucose determinations in the middle of the target range and, accordingly, reduces the errors of the regulatory system.
  • the discussed invention provides negative feedback algorithms described below.
  • a controlled biomarker for example, a blood glucose level
  • a target therapy level for example, using short (ultra) insulin.
  • the basal interval of medication for example, in diabetes, is at least 30 minutes.
  • a managed biomarker such as blood glucose
  • the MCU informs the patient: "Eat 15 grams of rapidly soluble carbohydrates (glucose tablets).” See figure 4, and, for example, Nuroglusemia update di-tebes: Buttre-lo-sugar (2008) Mauo Slip-retriev on Japan, 2009 form http: //www.mavocl ⁇ ic.com/health/hypoglycemia/DA00063
  • the bolus rule provides additional verification of measurement results, essentially considering the patient’s current lifestyle.
  • the correction of the basal program by the proposed method automatically tracks slow pathological changes in the patient's body.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Physics & Mathematics (AREA)
  • Medical Informatics (AREA)
  • Hematology (AREA)
  • Surgery (AREA)
  • Molecular Biology (AREA)
  • Anesthesiology (AREA)
  • Pathology (AREA)
  • Biophysics (AREA)
  • Vascular Medicine (AREA)
  • Emergency Medicine (AREA)
  • Optics & Photonics (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Diabetes (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • External Artificial Organs (AREA)

Abstract

L'invention concerne des équipements de pompage de thérapie intensive de diabète ou d'autres maladies. Selon l'invention, on a mis au point des moyens de contrôle automatique des changements courants dans le corps du patient. La procédure de vérification utilise un procédé à écoulement et s'utilise en conjonction avec une procédure de programmes basal et bolus de contrôle de la pompe lors d'une thérapie en temps réel. On a créé des algorithmes de rétroaction négative pour contrôler automatiquement la thérapie. On utilise des moyens d'écoulement nécessaire pour effectuer des mesures supplémentaires au moyen d'outils externes. L'invention élimine la nécessité d'effectuer des prises de sang fréquentes pour les analyses courantes.
PCT/RU2009/000436 2008-08-25 2009-08-21 Procédé et moyens pour contrôler automatiquement une thérapie Ceased WO2010062211A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
RUPCT/RU2008/000577 2008-08-25
PCT/RU2008/000577 WO2009031943A1 (fr) 2007-08-28 2008-08-25 Procédé de surveillance de l'insulinothérapie du diabète

Publications (4)

Publication Number Publication Date
WO2010062211A2 true WO2010062211A2 (fr) 2010-06-03
WO2010062211A3 WO2010062211A3 (fr) 2010-12-02
WO2010062211A4 WO2010062211A4 (fr) 2011-01-20
WO2010062211A9 WO2010062211A9 (fr) 2012-11-15

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PCT/RU2009/000436 Ceased WO2010062211A2 (fr) 2008-08-25 2009-08-21 Procédé et moyens pour contrôler automatiquement une thérapie

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Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7806886B2 (en) * 1999-06-03 2010-10-05 Medtronic Minimed, Inc. Apparatus and method for controlling insulin infusion with state variable feedback
US20050022274A1 (en) * 2003-04-18 2005-01-27 Robert Campbell User interface for infusion pump remote controller and method of using the same
WO2006108809A1 (fr) * 2005-04-13 2006-10-19 Novo Nordisk A/S Systeme ou dispositif medical montable sur la peau
US20060253085A1 (en) * 2005-05-06 2006-11-09 Medtronic Minimed, Inc. Dual insertion set
WO2008038274A1 (fr) * 2006-09-29 2008-04-03 Medingo Ltd. Système destiné à fournir un liquide par détection électrochimique de niveaux de concentration d'analyte
US8814822B2 (en) * 2007-05-07 2014-08-26 Roche Diagnostics Operations, Inc. Reciprocating delivery of fluids to the body with analyte concentration monitoring

Also Published As

Publication number Publication date
WO2010062211A9 (fr) 2012-11-15
WO2010062211A3 (fr) 2010-12-02
WO2010062211A4 (fr) 2011-01-20

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