JPH0268070A - Artificial pancreas device - Google Patents

Abstract

PURPOSE:To facilitate the automatic maintenance of the measured blood sugar value to a prescribed value with the artificial pancreas device provided with an arithmetic circuit having the computation equation for calculating a glucose dosing rate by improving the computation equation for the glucose dosing rate so as to execute a glucose clamp method in a good condition. CONSTITUTION:The arithmetic circuit to calculate the glucose dosing rate is so constituted as to compute the glucose dosing rate per 1 minute in accordance with the equation. In the equation, GIR(t): the glucose dosing rate (mg/min/kg) per 1 minute and 1kg weight at the time (t), BG(t): the blood sugar value (mg/100ml) at the time (t). DELTABG(t): the change rate (mg/100ml/min) of the blood sugar value at the time (t), GA: coefft. of proportional action (100ml/min/kg), GB: coefft. of derivative action (100ml/kg), GC: correction term (mg/min/kg), GC1: correction term value (mg/min/kg) of one minute before the time (t), GD: target blood sugar value (mg/100ml) of glucose control, a, b: the coefft. (dimensionless) to determine the extent of correction. The correction term promptly responds even with the slight fluctuation in the blood sugar value and automatically changes the glucose dosing rate. The blood sugar value is thus maintained and controlled at the constant value.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to an improvement in an artificial pancreas equipped with an insulin infusion device based on a fixed insulin infusion program and a glucose infusion device based on a fixed glucose infusion program. In particular, the present invention relates to an artificial pancreas device that automatically converts a correction term in an arithmetic expression for creating a predetermined glucose injection program in response to changes in blood sugar level over time, and maintains and controls the blood W value at a predetermined value.

[Conventional technology]

Conventionally, the applicant has developed a device for artificially injecting insulin or glucose into patients with insulin secretion dysfunction, such as diabetic patients, based on a fixed program. ``Improved artificial pancreas device'' (Japanese Patent Publication No. 63-1059) and ``Artificial Pancreas Device'' (Japanese Patent Publication No. 63-1060) were developed and patent applications were filed.

However, as shown in the above-mentioned "Improved Artificial Pancreas Device," the arithmetic circuit that calculates the amount of glucose injected calculates the amount of glucose injected per minute using the following formula. has.

GJR(t): Glucose injection amount per minute kg body weight at time t (ng/Iin/kq) Cp: Number of l (1001/I+lin 7kg) Cd: Coefficient (100
IIl 7kg) BGp: Control target blood ¥P value (rng/10
0n l)BG(t-τ): Blood sugar level τ minutes before time t (Illl]/100m1) ΔBG(t-υ): Rate of change in blood sugar level τ minutes before time t (no/100n+l/n+in ) τ: Waiting time (
nin).

In the calculation formula for the glucose injection amount, the injection amount corresponding to the difference between the blood sugar level and the control target value! The total amount of glucose injected per minute is determined from the addition of the amount of injection (proportional action of blood sugar level) and the amount of injection corresponding to the rate of change of blood sugar (differential action of blood sugar level).

In recent years, DeFronzo et al.
(Glucose clamp technique:
aIllethod for quantifyi
ng 1nsul+n 5ecret1onand
resistance, Am J Physiol
237:E214-223, 1979) is often used. The following two methods have been shown for this glucose clamp method. First, the hyperglycemic clamp method (Hype
The purpose is to measure the sensitivity of pancreatic islet of Langerhans β cells to glucose using a method called glycernic clamp. In this method, the subject first takes a prescribed amount of glucose slimming for 14 minutes, and the blood sugar level increases by +125111 g/100 from the basal level.
The blood glucose level is maintained at a constant level by increasing the blood glucose level to 1111 and then controlling the glucose infusion rate for about 2 hours. Normally, the blood sugar level to be maintained is about 200-2201g
/100nl. Therefore, this method is based on the principle that at a constant blood sugar level, internal glucose production is completely suppressed, so the amount of glucose injected matches the amount of glucose metabolism; It serves as an index that quantitatively reflects the intake of insulin, and by measuring the plasma insulin concentration, the sensitivity of pancreatic Langerhans islet β cells to glucose loading can be evaluated.

The second is euglycemic clamp technique (ELI).
The purpose of this method is to measure tissue sensitivity to exogenous insulin. In this method, the subject is first primed with insulin, and after about 10 minutes, a predetermined insulin infusion is maintained.

Glucose infusion is started after in-one priming and the amount of glucose infusion is controlled to maintain blood glucose levels at basal levels for approximately 2 hours. Normally, blood glucose levels maintained are approximately 80-9011 (1/100111). Therefore, this method is based on the principle that under a constant blood sugar level, the amount of glucose injected matches the amount of glucose metabolized,
Tissue sensitivity to exogenous insulin can be evaluated from the amount of glucose metabolism.

[Problem to be solved by the invention]

However, in the glucose clamp method mentioned above,
Based on this principle, controlling the amount of glucose injected is a very important issue in order to minimize fluctuations in blood sugar level and maintain it at a predetermined value.

The procedure for glucose clamping using deflation, etc. is as follows:
Blood of the subject is collected every 5 minutes using a syringe, the blood glucose level is measured using the blood, and the infusion setting dial of the glucose infusion pump is adjusted based on the measured blood glucose level, and glucose is injected. I'm adjusting the amount.

Therefore, blood sugar levels, which in principle should be kept constant, fluctuate greatly.
Furthermore, this series of operations cannot be completed by a single operator and is extremely complicated.

Therefore, when an artificial pancreas device equipped with an arithmetic circuit having the glucose injection method described above is adapted to the glucose clamp method to control the amount of glucose injected to maintain a predetermined blood sugar level, the glucose injection method Since it is made up of the sum of proportional action and differential action, it has the disadvantage that it does not correct the amount of glucose injected when the blood sugar level fluctuates slightly.

Therefore, the purpose of this project is to develop an artificial pancreas device with an improved formula for calculating the amount of glucose injected so that the glucose clamp method can be performed in good condition in an artificial pancreas device equipped with a calculation circuit that has a calculation formula for calculating the amount of glucose injected. To provide pancreatic equipment.

[Means to solve the problem]

An artificial pancreas device according to the present invention includes: a glucose sensor that continuously measures a blood sugar level; an arithmetic circuit that calculates an insulin injection amount and a glucose injection amount according to the measured blood sugar level; an insulin injection device and a glucose injection device; In an artificial pancreas device that includes a controller that controls an insulin injection device and a glucose injection device based on the calculation value calculated by the calculation circuit, the calculation circuit that calculates the glucose injection amount calculates the glucose injection amount per minute using the following formula: GIR(t)=GA(GO-BG(t))-08・A
BG(t)+GC However, in the formula, each symbol has the following meaning.

GIR(t): Glucose injection amount per 1 kg body weight per minute at time t (Ilc+/min 7 kg) 8G(t): Blood sugar level at time t (l'1g/1
00m1) ABG(t): Rate of change in blood sugar level at time t (I
HI/100m1/min) GA: Proportional action coefficient (100ml/min/kQ)
GB: Differential operating coefficient (100n+l/k(1)GC:
Correction term (lnQ/min 7kg) GC,: Correction term value 1 minute before time t (n+g/l1in/k(1) GO=Glucose control target blood sugar level (1g/100+nl) a, b: Degree of correction The present invention is characterized in that it is configured to perform calculations based on determined coefficients (dimensionless).

[Effect]

According to the artificial pancreas device according to the present invention, the arithmetic circuit calculates the amount of glucose injected corresponding to the difference between the measured blood sugar level and the glucose control target blood sugar level, the amount of glucose corresponding to the rate of change of the blood sugar level, and the amount of glucose 1 minute ago The total amount of glucose injected per minute is calculated from the sum of the three terms, which is the difference between the correction term value and the value calculated based on the rate of change in the measured blood sugar level at the current time. can be found. Therefore, the correction term automatically changes the amount of glucose injected in response to even slight fluctuations in the blood sugar level, thereby making it possible to maintain and control the blood sugar level at a constant level. Note that various correction calculations can be performed by changing each parameter during the glucose injection method, and a sufficient function can be exhibited for maintaining and controlling the blood sugar level in the glucose clamp method.

〔Example〕

Next, embodiments of the artificial pancreas device according to the present invention will be described in detail below with reference to the accompanying drawings.

FIG. 1 is a system diagram showing the basic configuration of the artificial pancreas device of the present invention. That is, in FIG. 1, the blood sugar level signal measured by the glucose sensor 12 for the subject 10 is as follows.
The data is configured to be transferred to the controller 14.

Next, the output of the controller 14 operates the calculation circuit Fi@ 16 in which Glodaram is incorporated, which calculates the amount of insulin to be injected and the amount of glucose to be injected based on the blood sugar level, to calculate the amount of glucose to be injected into the subject 10. The calculation result is then transferred to the controller 14 again. Therefore, the controller 14 is configured to drive and control the glucose infusion pump 18 for injecting glucose into the subject 10, thereby injecting an appropriate amount of glucose from the glucose storage tank 20 into the subject 10.

However, in the present invention, based on the blood sugar level measured by the glucose sensor 12, the amount of glucose to be injected is calculated by the calculation circuit 16 using the following equation.

GIR(t)=GA{GD-BG(t))-GB ・
ΔBGft) 10C... (1) Once, In the formula, each symbol has the following meaning.

GIR(t): at time t. 11 minutes, 1101
Glucose infusion amount per body weight (rnQ/min/kg) 8Gft): Blood sugar level at time t (mg/IQO
ml) ΔBG(t): Rate of change in blood sugar level at time t (t
ng/1001/n+in) G^: Proportional action coefficient (100m1/nin/k
g) GB: Differential operating coefficient (100El 7kg) GC:
Correction term (mc+/min 7kg) GC,: Axis positive term value 1 minute before time t (rag/min /k(+) GD Nigel course control target blood sugar level (n+g/10011) a, b: Degree of correction (dimensionless) In the embodiment shown in FIG.
The arithmetic formula for calculating the insulin injection amount in "Artificial Pancreas Device" (Japanese Patent Publication No. 58-44382) and "Artificial Pancreas Device" (Japanese Patent Publication No. 63-1060) is applied to the calculation circuit 16, and the insulin injection pump 22 is controlled via the controller 14. It can be controlled and configured to inject an appropriate amount of insulin from the insulin reservoir 24 to the subject 10.

In addition, the “improved artificial pancreas device” previously proposed by the applicant
The amount of glucose injected can also be controlled by applying the arithmetic formula for calculating the amount of glucose injected in (Japanese Patent Publication No. 63-1059).

Based on the above-mentioned calculation formula (1), for example, the measured blood sugar level BG
is 80111! ; ln per minute from l/1001111
The calculation results for each minute of the glucose injection amount GIR when the glucose injection amount GIR decreases at a rate of q/100ml are shown on a graph according to the setting example of each parameter as shown in FIG. As is clear from FIG. 2, it can be seen that the amount of glucose injected changes immediately in response to extremely slight fluctuations in blood sugar level.

Although preferred embodiments of the present invention have been described above, the present invention is not limited to the above-described embodiments, and it goes without saying that various design changes can be made without departing from the spirit of the present invention. .

〔Effect of the invention〕

As is clear from the embodiments described above, according to the present invention,
It is particularly effective when performing the glucose clamp method on diabetic patients, and it is easy to automatically maintain the measured blood glucose level at a predetermined value, and it is useful for controlling the operation of this type of artificial pancreas device. The effect of reducing labor is extremely large.

[Brief explanation of the drawing]

FIG. 1 is a system diagram showing an embodiment of the artificial pancreas device according to the present invention, and FIG. 2 is a response characteristic diagram of the amount of glucose injected to fluctuations in the measured blood sugar level based on the calculation formula for the amount of glucose injected in the device of the present invention. It is. 10... Subject 12... Glucose sensor 14... Controller 16... Arithmetic circuit 18... Glucose infusion pump 20... Glucose storage tank 22... Insulin infusion pump 24... Insulin storage tank FIG. FIG, 2 GA-0,1,0,3,0,5° (7B Haze 0 GO=l!t.

Claims (1)

[Claims] (1) A glucose sensor that continuously measures blood sugar levels, a calculation circuit that calculates an insulin injection amount and a glucose injection amount according to the measured blood sugar level, an insulin injection device, a glucose injection device, and calculations calculated by the calculation circuit. In an artificial pancreas device consisting of a controller that controls an insulin injection device and a glucose injection device based on the value, an arithmetic circuit that calculates the glucose injection amount calculates the glucose injection amount per minute using the following formula: GIR (t) = GA { GD-BG(t)}-GB・ΔB
G(t)+GCHowever, GC=GC_1-{BG(t)+a・ΔBG(t)-G
D}/{b} In the formula, each symbol has the following meaning. GIR(t): Glucose injection amount per 1 kg body weight per minute at time t (mg/min/k9) BG(t): Blood sugar level at time t (mg/100ml) ΔBG(t): Blood sugar level at time t Rate of change (mg/
100ml/min) GA: Proportional action coefficient (100ml/min/kg) GB
: Differential operating coefficient (100l/mg) GC: Correction term (mg/min/kg) GC_1: Correction term value 1 minute before time t (mg/min/kg) GD: Glucose control target blood sugar level (mg/100ml) ) a, b: An artificial pancreas device characterized in that it is configured to perform calculations based on coefficients (dimensionless) that determine the degree of correction.