WO2021096450A1

WO2021096450A1 - A tracking device for diabetes patients

Info

Publication number: WO2021096450A1
Application number: PCT/TR2019/051145
Authority: WO
Inventors: Ahmet Aydin; Umut KOKBAS
Original assignee: Cukurova Universitesi
Current assignee: Cukurova Universitesi
Priority date: 2019-11-13
Filing date: 2019-12-20
Publication date: 2021-05-20
Anticipated expiration: 2022-05-13

Abstract

The invention relates to an integrated device in which insulin and glucagon pumps and continuous blood glucose measurement systems produced to improve the quality of life of diabetic patients work in harmony with each other. Thanks to this device, the amount of insulin or glucagon determined by continuous measurement is injected into the person without the intervention of the person and blood glucose is kept at a safe level.

Description

A TRACKING DEVICE FOR DIABETES PATIENTS

TECHNICAL FIELD OF THE INVENTION The invention relates to an integrated device in which insulin and glucagon pumps and continuous blood glucose measurement systems produced to improve the quality of life of diabetic patients work in harmony with each other. Thanks to this device, the amount of insulin or glucagon determined by continuous measurement is injected into the person without the intervention of the person and blood glucose is kept at a safe level.

PRIOR ART

As a result of the increasingly prolonged lifespan of societies, on the one hand, and the proliferation of sedentary life in societies, the incidence of diabetes, which develops as a chronic metabolic disorder due to the lack and/or inadequate secretion of insulin hormone, which balances the level of glucose in the blood, is increasing globally and there are 425 million adults with diabetes according to today's statistics.

In the diagnosis of diabetes, glycosylated haemoglobin (HbAic) level is examined in order to determine the highest glucose level of individuals for 120 days on average. HbAic is formed by binding blood glucose to haemoglobin Ai via the valine at the N-terminal end of the beta chain without the need for an enzyme. It affects the accuracy of the test result in patients with haemoglobin disorders. Hemoglobinopathies affect the accuracy and reliability of the test result in 3 ways, as HbAic testing is a test based on normal haemoglobin; · They may cause changes in HBA conversion to HbAic in glycolyzed form,

• They may cause abnormal appearance in the cross-motograph, resulting in incorrect interpretation of the results,

• They can increase the hemolysis susceptibility of red blood cells, reducing the time required for glycosylation and resulting in inaccurate low HbAic results. Continuous glucose measurement in diagnosis and monitoring of diabetes disease is more accurate than the suggestive tests, e.g. HbAic.

Diabetes patient provides easy and inexpensive glycemia control to self-monitor an individual at home. The detection of low blood glucose and high blood glucose attacks and the necessary measures are important to delay or prevent the development of complications and early diagnosis of diseases. It helps educate the patient in conjunction with nutrition, exercise and blood glucose levels, reduces hospitalization frequency and bedtime, and ensures a more flexible life. Blood glucose monitoring at home reduces the cost of tracking and treatment of diabetes over a short and long period. This practice has a positive impact on ensuring glycemic control in a diabetic individual. It allows the desired glycemic control levels to be reached. It enables the identification of hypoglycemia and hyperglycemia by diabetes children/adolescents. It helps organize and manage habits (nutrition, exercise, drug dose). It guides healthcare professionals in the execution of the treatment plan. It increases the level of knowledge of diabetic patients about lifestyle and medical treatment on glycemic control.

Since the pancreas does not function in individuals with type 1 diabetes, insulin should be administered on the one hand and blood glucose should be monitored regularly on the other. Blood glucose measurement frequency is determined according to the status of diabetes, for this purpose fasting blood glucose should be checked at least 4 times a day before meals and before bedtime, and blood glucose monitoring should be performed once a week at 3:00 a.m. Measurements are recommended both before and 2 hours after meals. Today, blood glucose monitoring can be performed with a drop of blood taken from the finger with a device called glucometer and results can be obtained within 5 seconds.

Continuous blood glucose monitoring is also important for gestational diabetes monitoring. The fetus is fed with the nutrients it receives from its mother through the placenta. Elevated glucose in a diabetic mother increases the blood glucose directly to the fetus. The baby responds by increasing insulin secretion. Insulin is also a hormone that stimulates growth. From the 24-28 weeks of pregnancy, insulin secretion increases, foetal growth accelerates, and birth weight increases to over 4,000 grams. There are many risks such as shoulder dislocations, nerve injuries, respiratory distress, low glucose and jaundice that may occur during childbirth for the baby called a large baby. For this reason, some precautions should be taken for the healthy growth and development of the fetus. Against the risk of gestational diabetes, the prospective mother must monitor blood glucose as recommended by her physician and the measured values should be recorded in a diary.

According to the International Diabetes Federation (IDF) 2017 estimates, there are 425 million people affected by diabetes worldwide, and 4 million of them die in the same year. Diabetic patients should continuously measure their blood glucose levels and maintain their blood glucose levels with insulin supplementation. The method commonly used for this procedure is to drain a small amount of blood from the finger with the help of a lancet and to drain it onto a sensor called a disposable strip and to measure blood glucose with the help of a portable glucometer. This procedure, which should be performed several times a day, has both methodological and psychological difficulties in terms of use by the patients and if the measurement is not performed regularly, blood glucose may reach risky levels without realizing it. Another disadvantage is that the amount of insulin to be given during insulin supplementation is unknown, so the same amount of insulin is constantly given, which prevents effective control.

LIST OF FIGURES

1. Perspective View of the Devices 2. Alternating Injection System

Meanings of Numbers Shown in Figures

1. Insulin Capsule

2. Glucagon Capsule 3. Micro-Electrode Needles

4. Electronic Components

5. Battery

6. Rotary Connection Disk

7. Micro-Electrode Needle and Pump Hose Port 8. Pump Hose

BRIEF DESCRIPTION OF THE INVENTION

Thanks to the present invention, insulin and glucagon pumps and continuous blood glucose measurement systems produced to improve the quality of life of diabetic patients are integrated to work in harmony with each other and the amount of insulin or glucagon determined by continuous measurement is injected into the person without the intervention of the person and the blood glucose is tried to be kept at a safe level.

The device defined within the scope of the present invention comprises a small wearable sensor system operating with the principle of bioelectrochemical analysis. Thanks to this system, the potential changes of biochemical reactions on the surface of microelectrodes are measured and the values of certain parameters in the blood are determined and evaluated by the artificial intelligence algorithm on the hardware. This system, which operates without the need for personal intervention, can send notifications to the user's mobile phone via Bluetooth and system operating parameters can be set over the phone.

DETAILED DESCRIPTION OF THE INVENTION

As a result of the research, it is seen that only blood glucose is measured and analyses are made according to this measurement. However, in addition to this, the measurement of insulin and glucagon in the blood both determines the amount of insulin or glucagon that the device needs to be given to control blood glucose and it is seen that it will increase the success in predicting the value of blood glucose in the future. When we look at the device/systems and research already developed for diabetes follow-up, it is seen that they are based on glucose follow-up and insulin supplementation. However, it is evident that glucagon levels are as important as glucose and insulin in the development and progression of diabetes. This is one of the most significant differences and advantages of the present invention compared to the glucose monitoring systems available in the available literature and the existing market.

Various studies are being carried out on continuous glucose monitoring (CGM) to overcome the problems identified in the previous art and to control blood glucose more effectively. In this method, a sensor with a certain life span is placed on the patient and the sensor receives continuous measurement throughout its life. Despite this, the first commercial model has been released in 2000, but it is still not widely used. Problems of accuracy, sensor life, calibration, difficulty in use and interpretation of data prior to widespread use have been eliminated by the present invention.

There are no systems containing nanomaterials in the existing devices. The system of the present invention is based on a biosensor containing nanomaterial and modified microelectrodes. With the help of this nanomaterial, the more precise measurement can be made and a longer-lasting sensor has been developed.

Despite the fact that single enzyme and two enzyme studies are quite common in biosensor studies, no sensor study has been found that can yield results for all three enzymes separately on a single device, and this feature brings an important innovation to the field of the present invention.

In addition to the glucose measurement with the developed device, the amount of insulin or glucagon that the person needs to be given with the help of the measured insulin and glucagon levels is also optimally determined. Thus, thanks to the micropump, insulin capsule (1) and glucagon capsule (2), the device can act as the artificial pancreas and automatically inject the required insulin or glucagon in accordance with the lifestyle without the intervention of the person.

Thanks to the fact that the device has Artificial Intelligence supported software, it can learn the lifestyle of the person and adapt itself to the lifestyle of the patient day by day. In this way, customized treatment can be monitored by applying individual injections.

Besides, with the help of software, the amount of insulin or glucagon that the patient needs to be given with the support of insulin and guanine measurements to regulate this level rather than just providing the blood glucose level to the patient appears. This results in an automated system that does not require interpretation, unlike systems that only have blood glucose output and require interpretation. And with artificial intelligence support, it can work independently of the phone.

The embedded system on the instrument measures potential changes in biochemical reactions on the surface of the microelectrodes determines the values of certain blood parameters and evaluates these measurements with the artificial intelligence algorithm operating on the embedded system. It also sends regular notifications to the person's mobile phone via Bluetooth when required.

The flexibility of embedded system software in the device means that unlike other continuous glucose measurement systems, the system is also configured to address gestational diabetes patients.

Average Absolute Relative Error (MARD) in existing systems is around 9%. The recommendation is intended to allow the system to have an error of 1%.

The instrument is calibrated during production and does not require any subsequent calibration that must be performed by the patient. The system is easier to use because it does not need calibration and therefore glucose measurement from glare.

In addition to measuring glucose, the device can also provide an optimal determination of the amount of insulin or glucagon that should be given to the individual with the help of insulin and glucagon levels to be measured. This means that the self- contained micro-pump can act as an artificial pancreas thanks to insulin capsule (1) and glucagon capsule (2), and can automatically inject the needed insulin or glucagon in accordance with a person's lifestyle. This provides the artificial intelligence function of the device.

The dose setting of existing insulin pumps that work in accordance with CGM devices is not a continuous update. In addition, artificial algorithms, which provide advanced glucose prediction with the help of CGM, require that the individual input information about the nutrients that are constantly consumed in the system. However, the recommended system is that insulin and glucagon, not only glucose, are to be constantly measured, providing more parameters to capture changes in the individual's lifespan.

For example, the rhythm in the measured parameters will be captured, depending on when a person eats food at his or her life pace and when it is moving. Therefore, until 30 minutes later, the level of glucose in the blood will be highly accurate and the necessary injections will be based on the person's current need, rather than the fixed-dose. Therefore, unlike other systems, the dozing will be as needed instead of fixed-dose. The amount of dose to be delivered will also be determined by the measured parameters without the need to enter additional information. The system is only required during the initial setup phase for occupational information that can show the patient's age, gender, weight, type of disease and daily tempo.

The appliance is secured by the micro-electrode needles (3) in the device that will be attached to a person's arm in the form of an armband, entering the skin. The glucose, insulin and glucagon in the blood are measured at adjustable times (for example every 5, 10 or 15 minutes) using micro-electrode needles (3) and electronic components (4). These measurement results are evaluated by the artificial intelligence-assisted algorithm in the embedded system in the electronic component and are injected into the individual by the pump, taking the amount of insulin or glucagon, insulin capsule (1) or glucagon capsule (2) needed to regulate blood glucagon. Micro-electrode needles (3) are used during the injection.

Insulin Capsule (1) is replaceable. To regulate blood glucose, insulin is automatically injected into the individual from the capsule (1 ) as much as the individual needs. The Glucagon Capsule (2) is also similarly changeable and is automatically injected into the individual from glucagon capsule (2) as much as the individual needs to regulate blood glucose.

In patients receiving Glucagon insulin supplement, the glucose is injected in an emergency and infrequent situation where the blood glucose is very low. Therefore, only one electrode will be used for glucagon injection, but three of the microelectrode needles (3) are used alternately for insulin injection to prevent the payment of continuous injection at the same location. Therefore, the electrode lifetime is extended by 6 months. When the micro-electrode needles (3) have reached the end of their life, they can be easily replaced without having to change the rest of the equipment. Micro-Electrode Needles (3) use four micro-electrode needles. The central reference and counter electrode of these needles are the active electrodes, three of which are used for measuring glucose, insulin and glucagon. The reference electrode is used as glucagon and the active electrodes are used as a microneedle (3) for insulin injection in sequence. These electrodes are coated with antimicrobial peptide to prevent bacterial growth and to prolong its service life. Once the electrodes have reached the end of their life, only the electrode can be replaced without having to replace the rest of the equipment. The reference and counter electrode will be a single electrode together. The active electrodes for glucose, insulin and Glucagon will be separate. The measurement is performed in order for glucose, insulin and glucagon. The basic principle for measurement is to set the active electrode voltage to have different values within a range according to the reference and to measure the current that occurs on the active electrode at each set voltage.

As different voltages are applied, the current value to be measured varies depending on the amount of substance being measured in the environment. The voltage rating and the current rating at which the maximum current rating is obtained itself shows the amount of media in the environment. After calibration of the system with known quantities, this measurement will measure the amount of glucose, insulin and glucagon in the environment. The digital analogue converter for setting the active electrode voltage uses a current-to-voltage converter to convert current into voltage and an analogue digital converter to measure the voltage as a result of the conversion. These operations are controlled by the microcontroller. The circuits required for measurement are located in the electronic component (4). To measure glucose, insulin and glucagon, the active electrodes are prepared accordingly. Prepared for glucose measurement by immobilizing glucose oxidase and hydrogen peroxidase enzymes on the electrode surface. Glucagon and insect electrodes are prepared by the bonding of the assay with a specific antibody to the analyte that is analyzed, which is fixed to the electrode surface according to the immunosensor principle of operation.

To prevent edema, the microelectrode sends the insulin from the needles (3), which is taken from the capsule to the rear end of the needle currently used in the injection, by applying pressure to the insulin it, to enable the alternating use of active electrode ones from the needles. The micro-electrode needle located at the rear end of the needle to be used for the time in injection and the pump hose connection point (7) is set to match the flow by rotating the hose (8) from the pump with a rotary disc (6). This rotating mechanism enables the injection to be interleaved between the active electrodes.

The power required for system operation is supplied by the rechargeable battery module (5). The Bluetooth module in the electronic component (4) allows the system to establish a connection with the telephone. This allows data to be imported from the system and allows adjustments to be made to the system over the telephone.

Electronic Component (4) the circuit components that allow the measurement, the embedded system code and the microcontroller software that operates the artificial intelligence algorithm are contained in this section. The Bluetooth module in this section is also used to establish a connection with the telephone. This allows data to be retrieved from the system and configured over the telephone.

Claims

1. An armband-shaped diabetes tracking device for diabetes patients, characterized in that comprising;

- An insulin capsule (1), - A glucagon capsule (2),

- A reference coated with an antimicrobial peptide with a lid that can be opened and closed by electronic control for both measurement and injection, glucose oxidase and hydrogen peroxidase enzymes immobilized to the electrode surface for one glucose measurement, four interchangeable active microelectrode needles (3) immobilized to the electrode surface according to the immuno-spheric working principle, prepared by binding the analyte with the specific antibody to the analyte,

- Digital analogue converter for adjusting active electrode voltage, current- voltage converter for converting current to voltage and analogue numerical converter for measuring voltage obtained as a result of the conversion, circuit components enabling measurement, microcontroller software running embedded system code and artificial intelligence algorithm, the electronic component containing micropumps (4),

- and a battery (5).

2. A microcontroller of Claim 1 , characterized in that comprising;

- enabling injection by designating the dose according to the needs of a person by way of estimation of the level of glucose in the blood based on the parameters measured depending on when the person eats food and when he/she is mobile and to determine the dose according to the needs of the person in addition to the professional knowledge that reveals the patient's age, gender, weight, disease type and daily pace,

- determination of the amount of insulin or glucagon that needs to be given with the support of insulin and glucagon measurements to regulate the blood glucose level, - allowing the microelectrode needles (3) to hit different regions by checking the covers at the back end of the microelectrodes to prevent edema,

- and inclusion of artificial intelligence-assisted software that provides regular notification to a person's mobile phone via the Bluetooth module.

3. The microelectrode needles (3) of claim 2 are characterized in that comprising, a hose (8) from the pump paired by rotating it (6) to the microelectrode needle and pump hose port (7) at the back end of the needle to which the flow is to be provided.