JPS60108050A - Insulin injection in artificial pancreas - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

Detailed Description of the Invention [Field of Application of the Invention] The present invention relates to a method for injecting insulin into artificial pancreatic islets used for the treatment of so-called insulin-dependent diabetic patients in whom abnormalities occur in the amount or quality of insulin secreted in the body. .

[The amount of invention]

The concentration of sugar in human blood (hereinafter referred to as blood sugar level) needs to be maintained within a certain range in order for humans to live healthy lives. Therefore, the human body has a blood sugar level control mechanism that works to keep blood sugar levels at an appropriate level. However, if a failure occurs in the blood sugar level control mechanism, the blood sugar level becomes abnormal. Among these, a disease in which blood sugar levels become abnormally high is called diabetes. There are still many unknowns about the ultimate cause of diabetes. However, diabetes is caused not only by insulin-dependent diabetes caused by the above-mentioned insulin abnormality, but also by 1. Non-insulin-dependent diabetes mellitus is also known to be caused by abnormalities in quality. Insulin is a hormone that lowers blood sugar levels, and it is known that insufficient secretion of insulin causes diabetes.

Currently, for insulin-dependent diabetic patients, insulin is administered using a syringe at a dosage of 1 to 3 times a day.
Treatment methods in which W patients inject themselves are widely used.

However, since this treatment method intermittently injects insulin into the body, it is difficult to completely eliminate the 11.5 period, which indicates hyperglycemia, and various diabetes-specific complications caused by hyperglycemia may occur. It is said that it is difficult to sufficiently prevent the onset of the disease.

Therefore, research and development are being carried out on therapeutic equipment as shown in FIG. This involves attaching a blood sugar level sensor 12 to a diabetic patient 1o, using information from this sensor 12 to calculate the required injection amount of a drug such as di-insulin in a control calculation unit 14, and injecting insulin via a drug injection mechanism 16. It is injected into patients to control their blood sugar levels. This treatment device is an artificial pancreatic islet because it replaces the function of a group of cells called islets of Langerhans in the pancreas that secrete various hormones involved in controlling blood sugar levels in the human body (c). It is called.

Insulin secretion of people who are not diabetic patients and who have a normal blood sugar level control function (hereinafter referred to as healthy people) has a characteristic called biphasic. These are the four characteristics that become especially clear when a healthy person is given an intravenous injection of glucose to intentionally raise their blood sugar level to a steep level. After that, the amount of insulin secretion increases rapidly; forms a peak.Then, the amount of insulin secretion decreases once and increases again to form a second peak.This phenomenon is called biphasic. The insulin secretion characteristic curve is roughly as shown in FIG.

Based on this characteristic, it is thought that the amount of insulin secretion in a healthy person is determined mainly by the absolute value and the rate of change over time of the blood sugar level. This property defines the blood value at time t as p (t)
, the amount of insulin secreted is q(ri), it is approximated by a mathematical model having a transfer function expressed by the following equation (1).

However, here, P(8) and Q(S) are each p(
t), q(t) is a function obtained by Laplace transform.

(1) For this mathematical model, an example of the response of q(ri) when (1)(t) is changed stepwise is shown in FIG.

Various methods of calculating the amount of insulin to be injected into the artificial pancreatic islet described above have been studied. All of these are devised to exhibit this two-phase secretion characteristic in some kind of cedar.

A copy of data published as an example of treatment using artificial pancreatic islets is shown in Figure 4. At the beginning of the treatment, the blood sugar level, which was high at about 300 to 120 dt, was lowered to a range of 80 to 120 dt, which is said to be the appropriate value, by injection of insulin, and after that, it was smoothly controlled and the treatment was sufficiently effective. I understand that there is something.

It can be seen that, except at the beginning of treatment, patients are particularly sensitive to changes in blood sugar levels and need to change the amount of insulin injected. On the other hand, the time lag between the maximum point of the insulin injection curve and the corresponding minimum point of the blood sugar level curve is 20 to 45 minutes, and the rate of change in blood sugar level over time is -10 η/dt at the most rapid point. /minute.

Thus, after a relatively long reaction lag time (or "dead time" in control theory terminology) when the human body does not respond to an insulin injection, it becomes extremely sensitive despite the long response lag time. You can see that it reacts. Therefore, it is not easy to control blood sugar levels using insulin injection alone. Therefore, as shown in the treatment example in FIG. 4, in order to prevent hypoglycemia caused by an excessive drop in blood sugar level due to insulin injection, a blood sugar increasing agent such as glucose is often used in combination. (When blood sugar falls below 50 my/dt, abnormalities appear in brain function. In addition, long-term continuation of severe hypoglycemia leaves irreversible damage in the brain.) In this way, insulin injection in conventional artificial pancreatic islets This method has the drawback of requiring the injection of a drug that increases blood sugar levels in addition to insulin. That is, the conventional method of injecting insulin into artificial pancreatic islets has the drawback of injecting too much insulin.

Although there is various debate as to whether or not diabetic patients have a disorder in the secretion of hormones that have the effect of increasing blood sugar levels, many diabetic patients currently only take insulin as a drug. Due to the fact that people use insulin for their daily lives, it is thought that it is sufficient to use only insulin for artificial pancreatic islets.

[Purpose of the invention]

An object of the present invention is to provide a method for injecting insulin into an artificial pancreatic islet, which can appropriately control the amount of insulin injected into a diabetic patient.

[Summary of the invention]

The present invention was made in consideration of the fact that when insulin is injected into the human body, there is a long unresponsive time from the insulin injection until the blood sugar level changes. Predicting the sugar concentration after the non-response time until the sugar content changes, calculating the amount of insulin to be injected to the diabetic patient based on the predicted sugar concentration, and administering the insulin to the diabetic patient. The system is designed to ensure that the amount of insulin injected is appropriate.

[Embodiments of the invention]

A preferred embodiment of the method for injecting insulin into an artificial pancreatic islet according to the present invention will be described in detail with reference to the accompanying drawings.

FIG. 5 is an explanatory diagram of an embodiment of the method for injecting insulin into an artificial pancreatic islet according to the present invention.

In FIG. 5, the blood sugar level y (t) in the human body 20 is measured by the blood sugar sensor 22 and inputted to the injection amount calculation unit 24 as a measurement signal x (t). The insulin injection amount determined by the injection amount calculation unit 24 is sent to the insulin pump 26 as an insulin injection signal V(), and insulin is injected into the human body 20 in an amount of U().
Here, the insulin injection signal V (here, the state estimation calculation unit 2
8 is input. In this state Jib, established performance) 1 part 28,
Based on the insulin injection signal v(t), the blood sugar level of the human body 20 after a dead time (non-response time) due to insulin being injected as much as possible is estimated, and the estimated value is converted into the predicted value 2 (
input as injection) 6 to the calculation unit 24. The injection calculation unit 24 adjusts the amount of insulin to be injected based on the manually input predicted value 2.

Here, y(ritoX(su) and V(ritou(t)) are
Physically, they are completely different signals, but in terms of the precept model, they are the same signal. In other words, x (t) = y (t) Old and old... (2) u (t
)=v(t) (3).

In addition, the Laplace transformed functions of x(t), y(t), u(t), and v(t) are expressed as X(S) and Y(S), respectively.
), U(S).

When V(S), it becomes. G (8) is a transfer function indicating the insulin response characteristics of the human body 20. As mentioned earlier, G (
8) includes the dead time element from insulin injection until the blood sugar level starts to decrease, so if the dead time is Tl, then G(S)=H(8) ・e-? ” ' −・・−−−−
--(5).

Here, the predicted value output by the state estimation calculation unit 26 is expressed as z(t
), and its Laplace-transformed function is Z (S), and if the state jm definite operation unit 28 is configured to have the characteristic, then X(S) = Z (S) −e −Kl ′ −−・
−Old・−(7)x(t+τri) = Z (t)・
・・・The group becomes (8). In other words, it is possible to predict future blood sugar levels based on the current amount of insulin injected.

Therefore, the predicted value Z (t) can also be expressed as the insulin injection amount:
If used for this purpose, it is possible to prevent insulin over-infusion, which causes hypoglycemia, and eliminate the need for a mechanism for increasing blood sugar levels such as glucose.

FIG. 6 shows another embodiment of the method for injecting insulin into an artificial pancreatic islet according to the present invention. In this embodiment, the time lag calculating section 30 and the changeover switch 32 are inserted between the Eiri mouse operating section 24 and the insulin pump 26. and,
The changeover switch 32 selectively connects the insulin pump 26 to the time lag performance section 30'' or the constant d light generation section 34. The constant generator 34 instructs the insulin pump 26 to inject a predetermined amount of insulin into the human body 20, as will be described in detail later.

Let w(t) be the output of the time lag operator tiT, 930, let its Laplace-transformed function be W(8), and let the dead time caused here be τ2. Therefore, W(
t) is input, =H(S) ・e”1+r2” =・・−・−・−(1
01X(S)=Z(s)e−(f+ 10r2)a ・+
＋＋＋＋＋4. (11)x(t+τ1+72) =
Z (i) ”・−, , (12) Here, the predicted value 2 (i) detects a dangerous sign, that is, the predicted blood sugar level shows an excessively low value, and then starts administering insulin. Let α be the time required to reduce the injection volume to a safe value, and set it to τ2−α ・・・・・・α order. Generally speaking, τ2(τ1.0..111..a The effect on the control system of increasing τ and the dead time due to the establishment of the the output of the constant generator 34 to the insulin pump 2.
6 and quickly reduce the insulin dose to a safe value.

That is, the constant generating section 34 stores in advance the amount of insulin that is safe to give to the human body 2o, and the constant generating section 3
4 instructs the insulin pump 26 to deliver this amount of insulin to the human body 20. As described above, in this example, compared to the previous example, a time margin of τ2 is provided with respect to the response time on the artificial pancreatic islet side when danger is predicted. As mentioned above, the human body's response to insulin occurs after a relatively long dead time, but once the response begins, it proceeds at a fairly rapid rate.

Therefore, a dead time τ2 is provided between calculating the insulin injection amount and giving an injection instruction, and the predicted value z(t)
When the changeover switch 32 shows a dangerous sign, the safety for the human body 20 is improved by switching the changeover switch 32 to the constant generator 34 side. Furthermore, in the insulin injection method according to this embodiment, for reasons such as improving safety, it is more effective to implement the injection amount calculation section 24 and the state estimation calculation section 28 using separate and independent hardware. .

〔Effect of the invention〕

As explained above, according to the present invention, the amount of insulin injected into a diabetic patient can be made appropriate.

[Brief explanation of the drawing]

Figure 1 is an explanatory diagram of the conventional method of injecting insulin into artificial pancreatic islets, Figure 2 is a conceptual diagram of the biphasic secretion characteristics of insulin secretion in response to rapid increases in blood sugar levels in the blood of the human body, and Figure 3 is An explanatory diagram of a mathematical model of a system with compatibility characteristics, Fig. 4 is a diagram showing a treatment example of blood sugar level control using an artificial pancreatic islet, and Fig. 5 is an explanation of an example of the insulin injection method in an artificial pancreatic islet according to the present invention. FIG. 6 is a diagram showing another embodiment of the method for injecting insulin into an artificial pancreatic islet according to the present invention. 20...Human body, 22...Blood sugar sensor, 24...Injection amount calculation section, 26...Insulin pump, 28...
- State estimation calculation unit, 30... Time lag calculation unit, 32
. . . Selector switch, 34 . . . Constant generator. Agent Patent Attorney Tatsuyuki Unuma 1st place, 20th place, 3rd place, 4th place, 1st place

Claims (1)

[Claims] 1. Detecting the sugar concentration in the blood of a diabetic patient, calculating the amount of insulin to be injected into the diabetic patient according to the detected sugar concentration, and administering the calculated amount of insulin to the diabetic patient. In the method of injecting insulin into an artificial pancreatic islet, the amount of sugar after a non-response period from the insulin injection to the diabetes patient until the sugar concentration changes is predicted, and the insulin injection based on the predicted sugar concentration is calculated. A method for injecting insulin into an artificial pancreatic islet, the method comprising calculating an injection amount and injecting it into the diabetic patient. 2. Insulin injection to the diabetic patient is performed after calculating the amount of insulin to be injected and after a dead time sufficiently smaller than the non-response time has elapsed in the case of a one-dose condition, so that the predicted calculated sugar concentration is If the value of insulin is at a risk of causing hypoglycemia, after calculating the amount of insulin to be injected, a predetermined amount that is safe to inject into the diabetic patient is immediately administered. The method for injecting insulin into the artificial pancreatic islet according to item 1.