WO2022070420A1

WO2022070420A1 - Glucose amount calculation method

Info

Publication number: WO2022070420A1
Application number: PCT/JP2020/037615
Authority: WO
Inventors: 徹堀田; 仁小倉; 高行浅尾; 史夫林
Original assignee: ＬｏｏｋＴｅｃ株式会社; 国立大学法人群馬大学
Priority date: 2020-10-02
Filing date: 2020-10-02
Publication date: 2022-04-07

Abstract

Provided is a glucose amount calculation method which makes it possible to measure the amount of glucose accurately by statistically utilizing the intensity of each beam irradiated along an optical axis that penetrates through a human body.　A glucose amount estimation method according to the present invention comprises: a step for irradiate a measurement site in a human body with a first beam, a second beam and a third beam that have different wavelengths from one another and receiving the first beam, the second beam and the third beam that have passed through the measurement site by a light receiving element; and a step for estimating the amount of glucose from the light intensities of the first beam, the second beam and the third beam in accordance with a conversion equation. Furthermore, in the present invention, the conversion equation performs a multi-regression analysis, in which the intensities of a first beam, a second beam and a third beam which have different wavelengths from one another and have passed through a human body and the amount of glucose in collected blood are employed as a single actual measurement data set, a plurality of actual measurement data sets are acquired with respect to different glucose amounts, and the multi-regression analysis is performed on the basis of the plurality of actual measurement data sets.

Description

Glucose amount calculation method

The present invention relates to a glucose amount calculation method for optically measuring the glucose amount inside a measured portion such as a human body.

There are invasive and non-invasive methods for detecting sugar inside the measured site. The invasive method is a method in which blood is collected from, for example, a fingertip of a human body, and the amount of glucose is measured using the blood. The non-invasive method is a method of measuring the amount of glucose with a sensor placed outside the human body without collecting blood from the human body. An invasive method is generally used for accurate glucose amount calculation, but a non-invasive method for calculating glucose amount is desired in order to reduce the pain and improve convenience of the user.

As an example of a method for measuring the amount of glucose by a non-invasive method, a method for optically measuring by irradiating a human body with near-infrared light or the like is known.

Further, as an optical measurement method of the amount of glucose, there is a method of detecting the difference in the amount of absorption of near-infrared light due to glucose. Specifically, in this method, near-infrared light is transmitted at a certain site, and the amount of glucose is measured from the transmitted light amount (for example, Patent Document 1 and Patent Document 2).

Japanese Patent No. 3093871 Japanese Patent No. 3692751

However, the method for measuring the amount of glucose by the non-invasive method described in each of the above-mentioned patent documents has a problem that the amount of glucose cannot always be measured accurately.

Specifically, in the measurement method described in Patent Document 1, since the glucose amount is calculated by the glucose oxidase method, there is a problem that the calculation of the glucose amount is complicated. Further, in the method described in Patent Document 2, although the glucose amount is measured by an optical method, the possibility of diabetes can be determined, and the glucose amount cannot be quantitatively measured.

The present invention has been made in view of such problems, and an object of the present invention is to statistically utilize the light receiving intensity of each light beam emitted along the optical axis penetrating the human body. Therefore, it is an object of the present invention to provide a glucose amount calculation method capable of accurately estimating the glucose amount.

The glucose amount calculation method of the present invention is based on a measurement step of irradiating a plurality of light rays having different wavelengths on a measured portion and measuring the intensity of the plurality of rays transmitted through the measured portion with a light receiving element, and a conversion formula. The plurality of light rays include an estimation step of estimating the amount of glucose from the received intensity of the plurality of light rays, and in the measurement step, the plurality of light rays have one optical axis defined to penetrate the measured portion. It is characterized by passing through.

Further, in the method for calculating the amount of glucose of the present invention, in the measurement step, the received intensity of the plurality of light rays, the temperature of the measured portion, and the amount of blood-collected glucose are used as one actual measurement data set, and a plurality of the actual measurements are made with respect to different glucose amounts. A plurality of the conversion formulas are created by acquiring a data set and performing multiple regression analysis based on the plurality of actual measurement data sets, and in the estimation step, a plurality of glucoses calculated using each of the above conversion formulas. It is characterized in that the glucose amount estimation result closest to the blood collected glucose amount is selected from the amount estimation result, and the conversion formula for calculating the selected glucose amount estimation result is used for the glucose amount calculation from the next time.

Further, in the method for calculating the amount of glucose of the present invention, in the measurement step, the temperature of the measured portion is measured, and in the estimation step, the glucose is used in addition to the received light intensity of the plurality of light rays. It is characterized by calculating the amount.

Further, in the glucose amount calculation method of the present invention, the conversion formula is characterized in that parameters stored in a storage device in advance are used.

Further, the glucose amount calculation method of the present invention is characterized in that the plurality of light rays pass through the finger web.

Further, in the glucose amount calculation method of the present invention, the conversion formula is a multiple regression formula calculated by a statistical method. Thereby, according to the glucose amount calculation method of the present invention, since the conversion formula is calculated based on the statistical method, the conversion formula based on the constitution of each subject can be obtained.

Further, in the method for calculating the amount of glucose of the present invention, in the measurement step, the first ray, the second ray and the third ray having different wavelengths are applied to the measured portion, and the first ray is transmitted through the measured portion. The intensities of the light rays, the second light rays and the third light rays are measured by the light receiving element, and in the estimation step, the light receiving intensities of the first light rays, the second light rays and the third light rays are used based on the conversion formula. , The feature is to estimate the amount of glucose.

The glucose amount calculation method of the present invention is based on a measurement step of irradiating a plurality of light rays having different wavelengths on a measured portion and measuring the intensity of the plurality of rays transmitted through the measured portion with a light receiving element, and a conversion formula. The plurality of light rays include an estimation step of estimating the amount of glucose from the received intensity of the plurality of light rays, and in the measurement step, the plurality of light rays have one optical axis defined to penetrate the measured portion. It is characterized by passing through. As a result, according to the method for measuring the amount of glucose of the present invention, when a plurality of light rays pass through one optical axis, a plurality of light rays pass through a human body portion under the same optical conditions, so that the amount of glucose can be determined. It can be measured accurately.

Further, in the glucose amount calculation method of the present invention, in the measurement step, the received intensity of the plurality of light rays, the temperature of the measured portion, and the blood collected glucose amount are used as one actual measurement data set, and a plurality of the actual measurements are made with respect to different glucose amounts. A plurality of the conversion formulas are created by acquiring a data set and performing multiple regression analysis based on the plurality of actual measurement data sets, and in the estimation step, a plurality of glucoses calculated using each of the above conversion formulas. It is characterized in that the glucose amount estimation result closest to the blood collected glucose amount is selected from the amount estimation result, and the conversion formula for calculating the selected glucose amount estimation result is used for the glucose amount calculation from the next time. As a result, according to the method for measuring the amount of glucose of the present invention, by preparing a plurality of conversion formulas, an appropriate conversion formula can be adopted according to the constitution of the subject, and the blood glucose level can be estimated accurately. Can be done.

Further, in the glucose amount calculation method of the present invention, in the measurement step, the temperature of the measured portion is measured, and in the estimation step, the glucose is used in addition to the received light intensity of the plurality of light rays. It is characterized by calculating the amount. Thereby, according to the method for measuring the amount of glucose of the present invention, the amount of glucose can be estimated more accurately by estimating the amount of glucose using the body temperature of the human body in addition to the light receiving intensity of the light rays transmitted through the human body. Can be done.

Further, in the glucose amount calculation method of the present invention, the conversion formula is characterized in that parameters stored in a storage device in advance are used. Thereby, according to the method for measuring the amount of glucose of the present invention, the conversion formula can be obtained without collecting blood by the subject himself / herself.

Further, the glucose amount calculation method of the present invention is characterized in that the plurality of light rays pass through the finger web. As a result, according to the method for measuring the amount of glucose of the present invention, the amount of glucose is calculated by using each light ray transmitted through the finger web, which has less fat, less variation in thickness between individuals, and a short transmission distance. The amount of glucose can be estimated accurately.

Further, in the method for calculating the amount of glucose of the present invention, in the measurement step, the first ray, the second ray and the third ray having different wavelengths are applied to the measured portion, and the first ray is transmitted through the measured portion. The intensities of the light rays, the second light rays and the third light rays are measured by the light receiving element, and in the estimation step, the light receiving intensities of the first light rays, the second light rays and the third light rays are used based on the conversion formula. , The feature is to estimate the amount of glucose. Thereby, according to the glucose amount calculation method of the present invention, the glucose amount can be calculated more accurately by using the first ray, the second ray and the third ray having different wavelengths.

It is a conceptual diagram which shows the basic structure of the glucose amount measuring apparatus used in the glucose amount calculation method which concerns on embodiment of this invention. It is a flowchart which shows the glucose amount calculation method which concerns on embodiment of this invention. It is a figure which shows the glucose amount calculation method which concerns on embodiment of this invention, (A), (B) and (C) are side views which show the situation which we measure while moving a light emitting point. It is a graph which shows the glucose amount calculation method which concerns on embodiment of this invention. It is a figure which shows the glucose amount calculation method which concerns on other embodiment of this invention, (A) is a flowchart, (B) is a block diagram which conceptually shows the said method. It is a figure which shows the glucose amount calculation method which concerns on embodiment of this invention, (A) is a schematic diagram which shows a finger web, (B) is a graph which shows the result of having measured the glucose amount with a fingertip, (C). ) Is a graph showing the result of measuring the glucose amount with the finger web.

The glucose amount calculation method of this embodiment will be described with reference to FIG. FIG. 1 is a conceptual diagram showing a basic configuration of a glucose amount calculation device 10 used in the glucose amount calculation method of the present embodiment. Here, the amount of glucose is the amount of glucose in blood or interstitium. In addition, the amount of glucose may be referred to as a blood glucose level or the like.

With reference to FIG. 1, the glucose amount calculation device 10 includes a light emitting unit 11 that emits a light ray used for measurement, a lens 14 that is an optical element that guides a light ray emitted from the light emitting unit 11 to a measured portion 18, and a lens 14. A light receiving unit 19 that receives light rays transmitted through the measured portion 18, an arithmetic control unit 17 that calculates the amount of glucose based on the output of the light receiving unit 19, a storage unit 13, a display unit 15, and an operation input unit 12. , And a temperature measuring unit 21.

The function of the glucose amount calculation device 10 is to measure the glucose amount of the human body by a non-invasive method by transmitting light rays through the human body which is the measurement site.

The light emitting unit 11 emits a light beam having a predetermined wavelength in order to measure the amount of glucose. The light emitting unit 11 has a first light emitting unit 111, a second light emitting unit 112, and a third light emitting unit 113 that emit light rays having different wavelengths. The first light emitting unit 111, the second light emitting unit 112, and the third light emitting unit 113 are each composed of a light emitting diode. For example, the wavelength of the first light ray emitted from the first light emitting unit 111 is 1310 nm, the wavelength of the second light ray emitted from the second light emitting unit 112 is 1450 nm, and the wavelength of the second light ray emitted from the third light emitting unit 113 is 1. The wavelength of the three rays is 1550 nm.

Further, the light emitting unit 11 is moved in the left-right direction by an actuator (not shown). By moving the light emitting unit 11, any one of the first light emitting unit 111, the second light emitting unit 112, and the third light emitting unit 113 can be arranged on the same optical axis 22. Here, the case where the second light emitting unit 112 is arranged on the axis of the optical axis 22 is shown.

The first ray is a ray that is not absorbed by the components in the living body, and the second and third rays are the rays that are absorbed by glucose, protein and water in the living body. By measuring the optical path length of the optical axis 22 with the first ray, the influence of the optical path length on the absorption rate of each ray can be measured, the influence of the optical path length can be eliminated, and the glucose amount can be calculated accurately. be able to.

In the present embodiment, the first light ray, the second light ray, and the third light ray are irradiated from the light emitting unit 11 to the light receiving unit 19 along the optical axis 22. That is, the propagation path and the propagation length of the first ray, the second ray, and the third ray inside the measured portion 18 are the same.

By sharing the optical axis 22 with each light ray as described above, the amount of glucose can be accurately measured. Specifically, according to the Lambert-Beer law, the amount of glucose is calculated by the following formula 1.
Equation 1: C = -log ₁₀ (I / I ₀ ) / (0.434 × μ _a × r)

In the above equation 1, C is the amount of glucose, I is the emitted light power, I ₀ is the incident light power, μ _a is the extinction coefficient of the skin, and r is the optical path length.

In the present embodiment, by sharing the optical axis 22 between the first ray, the second ray, and the third ray, the optical path length r is made the same, so that the unknown number to be calculated is reduced, and glucose is accurately and easily calculated. The quantity C can be obtained.

The lens 14 measures the first light beam, the second light ray, and the third light ray emitted from the first light emitting unit 111, the second light emitting unit 112, and the third light emitting unit 113 by the refraction action and the diffraction action thereof. Lead to site 18.

The measurement site 18 is a site where the glucose amount is measured by the glucose amount calculation device 10 of the present embodiment. Specifically, as the measurement site 18, a fingertip, an earlobe, a finger web, or the like can be adopted. As will be described later, the finger web to be measured is preferably a finger web containing a small amount of fat, having a small individual difference in thickness, and having no thick blood vessels formed.

The light receiving portion 19 is, for example, a semiconductor element made of a photodiode, and a light receiving portion (not shown) is formed which receives the first light ray, the second light ray, and the third light ray transmitted through the measured portion 18 and detects the intensity thereof. There is. The light receiving unit 19 transmits signals corresponding to the light receiving intensities of the first light ray, the second light ray, and the third light ray to the arithmetic control unit 17.

The storage unit 13 is a semiconductor storage device or the like including a RAM or a ROM, and executes a calculation formula, parameters, estimation results, and a glucose amount calculation method according to the present embodiment for calculating the glucose amount from the output value of the light receiving unit 19. I remember the program to do it.

The operation input unit 12 is a part where the subject gives an instruction to the calculation control unit 17, and is composed of a switch, a touch panel, and the like.

The temperature measuring unit 21 is a part that measures the body temperature of the subject by coming into contact with the body of the subject.

The calculation control unit 17 is composed of a CPU, performs various calculations, and controls the operation of each part constituting the glucose amount calculation device 10. Specifically, the arithmetic control unit 17 irradiates the first light ray, the second light ray, and the third light ray from the first light emitting unit 111, the second light emitting unit 112, and the third light emitting unit 113 of the light emitting unit 11. Further, the arithmetic control unit 17 estimates the amount of glucose based on the electric signals input from the light receiving unit 19, the temperature measuring unit 21, and the like, using a conversion formula which is a multiple regression formula described later. Further, the arithmetic control unit 17 may display the calculated glucose amount on the display unit 15. For example, by displaying the glucose amount on the display unit 15 which is a liquid crystal monitor, the user who uses the glucose amount calculation device 10 can know the change of his / her own glucose amount in real time. Further, in the step of performing the measurement described later, the arithmetic control unit 17 moves the light emitting unit 11 in order to arrange the light emitting points of each light emitting unit in the axial shape of the optical axis 22.

A method of estimating the glucose amount of a subject using the glucose amount calculation device 10 will be described with reference to the flowchart of FIG. 2 and also with reference to FIG. 1 described above. Here, the subject collects blood and irradiates each light beam to calculate the parameters of the multiple regression equation, which is a conversion formula used for estimating the amount of glucose, and uses this conversion formula to calculate the parameters of the subject from the output value of the light receiving unit 19. The amount of glucose is estimated. Here, as the parameter of the multiple regression equation, a parameter stored in advance in the storage unit 13 of the glucose amount calculation device 10 can be used, whereby the convenience of the subject can be improved. Further, each of the following steps is executed based on the program stored in the storage unit 13.

In step S10, first, the amount of glucose is measured from the blood collected from the subject. This blood collection is for calculating the parameters of the multiple regression equation, and by collecting blood first, it is not necessary to collect blood in the next measurement.

In step S11, next, the intensity and body temperature of the light beam passing through the finger web of the subject are measured. Specifically, the arithmetic control unit 17 emits a first light ray, a second light ray, and a third light ray from the first light emitting unit 111, the second light emitting unit 112, and the third light emitting unit 113 of the light emitting unit 11. The wavelengths of the first ray, the second ray and the third ray are as described above. Further, as shown in FIG. 1, by moving the light emitting unit 11 along the left and right rear, the first light ray, the second light ray, and the third light ray are irradiated along the optical axis 22.

The emitted first ray, second ray and third ray are applied to a predetermined portion of the measured portion 18 by the lens 14. The first ray, the second ray, and the third ray incident on the measured portion 18 are absorbed, attenuated, and reflected inside the human body, and then a part of them pass through the human body and reach the light receiving portion 19. The light receiving unit 19 transmits an electric signal corresponding to the light receiving intensity to the arithmetic control unit 17 for each wavelength band of the first light ray, the second light ray, and the third light ray. Here, instead of the lens 14, each light beam can be focused and irradiated using a pinhole.

With reference to FIG. 3, the matter of irradiating each light beam while displacing the light emitting unit 11 in step S11 will be described. FIG. 3A shows a situation in which the second light emitting unit 112 irradiates the second light beam, FIG. 3B shows a situation in which the first light emitting unit 111 irradiates the first light beam, and FIG. 3C shows a situation in which the first light emitting unit is irradiated. It shows the situation where the third light beam is emitted from the third light emitting unit 113. Here, the light rays are irradiated along the optical axis 22 in the order of the second light emitting unit 112, the first light emitting unit 111, and the third light emitting unit 113, but this order can be changed.

With reference to FIG. 3A, when irradiating the second light beam from the second light emitting unit 112, first, the arithmetic control unit 17 causes the light emitting point of the second light emitting unit 112 to overlap with the optical axis 22. The light emitting unit 11 is moved to. When the light emitting point of the second light emitting unit 112 overlaps with the optical axis 22, the arithmetic control unit 17 emits a second light ray from the second light emitting unit 112. The emitted second light ray travels along the optical axis 22, passes through the measured portion 18, and then irradiates the light receiving portion 19. An electric signal indicating the intensity of the second light ray received by the light receiving unit 19 is transmitted to the arithmetic control unit 17.

With reference to FIG. 3B, the arithmetic control unit 17 then moves the light emitting unit 11 to the right by an actuator (not shown) so that the light emitting point of the first light emitting unit 111 is set to the axis of the optical axis 22. Overlay. When the light emitting point of the first light emitting unit 111 overlaps with the optical axis 22, the arithmetic control unit 17 emits a first light ray from the first light emitting unit 111. The emitted first light ray travels along the optical axis 22, passes through the measured portion 18, and then irradiates the light receiving portion 19. An electric signal indicating the intensity of the first light ray received by the light receiving unit 19 is transmitted to the arithmetic control unit 17.

With reference to FIG. 3C, the arithmetic control unit 17 then moves the light emitting unit 11 to the left by an actuator (not shown) so that the light emitting point of the third light emitting unit 113 becomes the axis of the optical axis 22. Overlay. When the light emitting point of the third light emitting unit 113 overlaps with the optical axis 22, the arithmetic control unit 17 emits a third light ray from the third light emitting unit 113. The emitted third light ray travels along the optical axis 22, passes through the measured portion 18, and then irradiates the light receiving portion 19. An electric signal indicating the intensity of the third light ray received by the light receiving unit 19 is transmitted to the arithmetic control unit 17.

Further, based on the instruction of the calculation control unit 17, the temperature measurement unit 21 measures the body temperature of the subject, and the electric signal indicating the body temperature is transmitted to the calculation control unit 17.

The above-mentioned step S11 is performed a plurality of times with respect to a plurality of glucose amounts for the multiple regression analysis described later.

In step S12, the parameters of the multiple regression equation are obtained based on the result of step S11.

The amount of blood-collected glucose measured in step S11 is shown in Table 1 below.

In Table 1, from the left, the amount of blood glucose collected, the temperature of the part to be measured, the light receiving intensity of the first light having a wavelength of 1310 nm, the light receiving intensity of the second light having a wavelength of 1450 nm, and the light receiving intensity of the third light having a wavelength of 1550 nm. It shows the light receiving intensity and the estimated amount of glucose. Here, blood sampling, body temperature measurement, light reception of each light ray passing through the human body, and estimation of glucose amount based on the light reception intensity were performed while changing the blood sampling glucose amount of the subject by administering sugar or the like.

In this embodiment, multiple regression analysis is performed based on the results in Table 1, and each parameter of the multiple regression equation, which is a conversion equation, is calculated. In this embodiment, the multiple regression equation shown in Equation 2 below is adopted as a conversion equation for estimating the amount of glucose.
Equation 2: Estimated glucose amount = section + β1 × temperature of the part to be measured + β2 × first ray output voltage + β3 × second ray output voltage + β4 × third ray output voltage

The parameters constituting the equation 2 are stored in the storage unit 13 and used for estimating the glucose amount.

The analysis results by the above multiple regression analysis are shown in Table 2 below. Table 2 includes Table 2-1 and Table 2-2 and Table 2-3. Table 2-1 shows regression statistics, Table 2-2 shows analysis of variance, and Table 2-3 shows regression coefficients and the like by regression analysis.

As is clear from Table 2, since all P-values are 0.05 or less, it can be judged that the regression coefficient is significant, and the glucose amount is accurately estimated by the multiple regression equation shown in Equation 2 above. be able to.

FIG. 4 is a graph showing the relationship between the estimated glucose amount and the blood sampling glucose amount. The horizontal axis of this graph shows the amount of blood-collected glucose, and the vertical axis shows the estimated amount of glucose. In this graph, the calibration curve is shown by a solid line, and the line with a ± 5% error is shown by a dotted line.

In step S13 and step S14, the glucose amount is estimated using the above conversion formula. Specifically, referring to FIG. 1, the arithmetic control unit 17 first receives from the first light emitting unit 111, the second light emitting unit 112, and the third light emitting unit 113 of the light emitting unit 11 along the optical axis 22. The measured portion 18 is irradiated with the first ray, the second ray, and the third ray toward the measured portion 18. The first ray, the second ray, and the third ray are attenuated, reflected, and absorbed inside the measured portion 18, and a part of the first ray, the second ray, and the third ray pass through the measured portion 18 and reach the light receiving portion 19. The light receiving unit 19 transmits an electric signal indicating the intensities of the first light ray, the second light ray, and the third light ray that have reached the light receiving unit 19 to the arithmetic control unit 17. Further, an electric signal indicating the temperature of the measured portion 18 measured by the temperature measuring unit 21 is also transmitted to the arithmetic control unit 17. The arithmetic control unit 17 uses the conversion formula shown in the above equation 2 based on the electric signal indicating the intensity of the first ray, the second ray, and the third ray, and the electric signal indicating the body temperature of the measured portion 18. Then, the amount of glucose is estimated.

Table 3 shows the results of estimating the glucose amount by the same subjects as in Table 1 on different days by the methods shown in steps S13 and S14. That is, here, the person who collected blood, irradiated with light, and measured the body temperature in order to derive the conversion formula and the person who estimates the glucose amount using the conversion formula are the same person. As is clear from Table 3, since the estimated glucose amount estimated by the estimation method according to the present embodiment is extremely close to the blood sampling glucose amount, it can be determined that accurate estimation is performed.

Table 4 shows the results of estimating the glucose amount by the methods shown in steps S13 and S14 by a subject different from Table 1 (subject for calculating the conversion formula). As is clear from Table 4, even if the subject for deriving the conversion formula and the subject for estimating the glucose amount using the conversion formula are different, the estimated glucose amount and the blood sampling glucose amount are close to each other, so even in this case. Accurate estimates have been made.

Further, in the graph of FIG. 4, the blood sampling glucose amount and the estimated glucose amount used for calculating the calibration curve are shown by white circles. The values in Tables 4 and 5 are shown by black circles. As is clear from this graph, the measurements for other subjects and for any day are located in the area sandwiched by lines with an error of approximately ± 5%. Therefore, the glucose amount can be estimated accurately by the estimation method using the above conversion formula.

A method for estimating the amount of glucose according to another form will be described with reference to FIG. The outline of the method for estimating the amount of glucose described here is the same as above, but the above-mentioned method is to improve the estimation accuracy by preparing a plurality of conversion formulas and selecting a conversion formula suitable for the subject. different. FIG. 5A is a flowchart showing a method for estimating the amount of glucose according to the present embodiment, and FIG. 5B is a block diagram conceptually showing the calculation method in the present embodiment.

With reference to FIG. 5A, in step S20, a plurality of conversion formulas are prepared. Specifically, as shown in FIG. 5B, a plurality of multiple regression equations are obtained by collecting blood and applying each light beam using the glucose amount calculation device 10 and measuring the body temperature for different subjects. Here, for subject A, subject B, subject C, and subject D, by performing irradiation of each ray, body temperature measurement, and multiple regression analysis, the light receiving intensities of the first ray, the second ray, and the second ray for each subject are performed. , And obtain an actual measurement data set consisting of body temperature. From each of these actually measured data sets, the parameters of the multiple regression equation A, the multiple regression equation B, the multiple regression equation C, and the multiple regression equation D are derived.

In steps S21 and S22, the estimated glucose amount A and the estimated glucose amount B are used by using the multiple regression equation A, the multiple regression equation B, the multiple regression equation C, and the multiple regression equation D by using the glucose amount calculation device 10. , Estimated glucose amount C and estimated glucose amount D. Specifically, referring to FIG. 1, the arithmetic control unit 17 first receives from the first light emitting unit 111, the second light emitting unit 112, and the third light emitting unit 113 of the light emitting unit 11 along the optical axis 22. The measured portion 18 is irradiated with the first ray, the second ray, and the third ray toward the measured portion 18. The light receiving unit 19 transmits an electric signal indicating the intensities of the first light ray, the second light ray, and the third light ray that have reached the light receiving unit 19 to the arithmetic control unit 17. Further, an electric signal indicating the temperature of the measured portion 18 measured by the temperature measuring unit 21 is also transmitted to the arithmetic control unit 17. Next, the arithmetic control unit 17 uses the multiple regression equation A and multiple regression based on the electric signal indicating the intensity of the first ray, the second ray, and the third ray, and the electric signal indicating the body temperature of the measured portion 18. Estimated glucose amount A, estimated glucose amount B, estimated glucose amount C, and estimated glucose amount D are estimated using the formula B, the multiple regression equation C, and the multiple regression equation D. Also, for the selection in step S23, the subject is sampled to obtain the blood glucose amount.

In step S23, the estimated glucose amount closest to the blood-collected glucose amount is selected from the estimated glucose amount A, the estimated glucose amount B, the estimated glucose amount C, and the estimated glucose amount D. This selection is made by the operation of the operation input unit 12 by the subject or by the arithmetic control unit 17. For example, if the estimated glucose amount A is the closest to the blood sampling glucose amount, the glucose amount is estimated using the multiple regression equation A from the next estimation by selecting the operation input unit 12 of the subject.

In step S24, the glucose amount is estimated using the selected multiple regression equation A. Specifically, the arithmetic control unit 17 first receives the first light emitting unit 111, the second light emitting unit 112, and the third light emitting unit 113 of the light emitting unit 11 from the light emitting unit 11 to the measured portion 18 along the optical axis 22. A light ray, a second light ray, and a third light ray are emitted toward the measured portion 18. Further, an electric signal indicating the temperature of the measured portion 18 measured by the temperature measuring unit 21 is also transmitted to the arithmetic control unit 17. The arithmetic control unit 17 is a multiple regression equation selected as described above based on an electric signal indicating the intensity of the first ray, the second ray, and the third ray, and an electric signal indicating the body temperature of the measured portion 18. The amount of glucose is estimated using A.

With reference to FIG. 6, the matter that the finger web is suitable as the measured site to be irradiated with each light beam for estimating the glucose amount will be described. 6 (A) is a schematic diagram showing a subject's hand, FIG. 6 (B) is a graph showing an error grid in which the amount of glucose is estimated using a fingertip, and FIG. 6 (C) is a graph showing an error grid using a finger web. It is a graph which shows the error grid which estimated the amount of glucose. In FIGS. 6 (B) and 6 (C), the horizontal axis shows the blood glucose amount, and the vertical axis shows the estimated glucose amount measured by the method according to the present embodiment.

With reference to FIG. 6A, the finger web is a membranous portion formed between the fingers of the human body, and in the present embodiment, the finger web formed between the index finger and the thumb of the hand. Was adopted as the measured site for measuring the amount of glucose. Here, a finger web formed between other fingers can also be adopted as a measurement site.

With reference to FIG. 6B, the dots showing the measurement results are distributed away from the reference line shown by the broken line. The reason for this is considered to be that the thickness of the fingertips varies greatly from person to person and the optical path length differs due to this, and that the thick blood vessels existing at the fingertips have an adverse effect.

On the other hand, referring to FIG. 6C, dots indicating the measurement results are distributed in the vicinity of the reference line indicated by the broken line. The reason for this is that the finger web has a thickness of about 2 mm to 4 mm, the difference between individuals is small, the fat content is extremely low, and there are no thick blood vessels inside, so measurement can be performed with capillaries and dermis. Because. Further, when the finger web is adopted as the measurement site, the optical path length can be shortened, and the glucose amount can be measured with low output light.

With reference to Table 5, the matters that the finger web is suitable as the measurement site will be described from the viewpoint of the fat content.

In Table 5, the fat-containing sample 1 (epidermis 0.2 mm, dermis 0.8 mm, fat 1.5 mm) and the fat-free donate 2 (epidermis 0.2 mm, dermis 0.8 mm, no fat) are listed. The result of measuring the transmission | transmission of the 1st ray, the 2nd ray and the 3rd ray is shown. As an example, the sample 1 is the fingertip of the human body, and the sample 2 is the finger web.

The simulation conditions here are that the number of light rays is 5000, the number of scatterings is 1000 per one, the diameter of the incident light on the skin is φ1.5 mm, and the diameter of the light receiving surface is φ3 mm or φ1 mm.

As shown in Table 5, in the first light beam having a wavelength of 1310 nm, the transmittance of the sample 2 is 3.4 times the transmittance of the sample 1. Further, in the second light beam having a wavelength of 1450 nm, the transmittance of the sample 2 is 6.2 times the transmittance of the sample 1. Further, in the third light beam having a wavelength of 1550 nm, the transmittance of the sample 2 is 3.5 times the transmittance of the sample 1.

From the above, for example, the sample 1 which is a fingertip has a low transmittance of the first to third rays, so that it is not suitable as a site for measuring the amount of glucose. Furthermore, considering that the fat content varies greatly among individuals, it is clear that the amount of fat affects the transmittance, which makes it more difficult to estimate the glucose content.

On the other hand, since the sample 2 which is a finger web has an extremely low fat content, it allows the first ray, the second ray, and the third ray to pass through well, and the glucose amount is accurately determined based on the intensity of each passing ray. Can be estimated to. Moreover, even if the subject is obese, the fat contained in the finger web does not increase extremely. Therefore, if the glucose amount is estimated using each light ray transmitted through the finger web, the glucose amount can be accurately estimated without being affected by whether or not the subject is obese.

Although the embodiments of the present invention have been shown above, the present invention is not limited to the above embodiments.

For example, in the above-described embodiment, the glucose amount is calculated using the first ray, the second ray, and the third ray having different wavelengths, but the two rays (for example, the first ray having a wavelength of 1310 nm and the wavelength are different. The amount of glucose can also be calculated using a third ray) at 1550 nm.

10 Glucose amount calculation device 11 Light emitting unit 111 First light emitting unit 112 Second light emitting unit 113 Third light emitting unit 12 Operation input unit 13 Storage unit 14 Lens 15 Display unit 17 Calculation control unit 18 Measured part 19 Light receiving unit 21 Temperature measuring unit 22 Optical axis

Claims

A measurement step in which a plurality of light rays having different wavelengths are irradiated to a measured portion and the intensity of the plurality of rays transmitted through the measured portion is measured by a light receiving element.
It comprises an estimation step of estimating the amount of glucose from the light receiving intensities of the plurality of light rays based on the conversion formula.
In the measurement step, the glucose amount calculation method is characterized in that the plurality of light rays pass through one optical axis defined so as to penetrate the measured portion.
In the measurement step, the light receiving intensity of the plurality of light rays, the temperature of the measured portion, and the blood sampling glucose amount are used as one actual measurement data set, and a plurality of the actual measurement data sets are acquired for different glucose amounts, and the plurality of actual measurement data are obtained. By performing multiple regression analysis based on the set, multiple of the above conversion formulas can be created.
In the estimation step, the glucose amount estimation result closest to the blood-collected glucose amount was selected from the plurality of glucose amount estimation results calculated using each of the conversion formulas, and the selected glucose amount estimation result was calculated. The method for calculating a glucose amount according to claim 1, wherein the conversion formula is used for estimating the amount of glucose from the next time.
In the measurement step, the temperature of the measured portion is measured, and the temperature is measured.
The glucose amount calculation method according to claim 1 or 2, wherein in the estimation step, the glucose amount is calculated using the temperature in addition to the light receiving intensity of the plurality of light rays.
The glucose amount calculation method according to claim 1, wherein the conversion formula uses a parameter stored in a storage device in advance.
The glucose amount calculation method according to any one of claims 1 to 4, wherein the plurality of light rays pass through the finger web.
The glucose amount calculation method according to any one of claims 1 to 5, wherein the conversion formula is a multiple regression formula calculated by a statistical method.
In the measurement step, the first ray, the second ray, and the third ray having different wavelengths are applied to the measured portion, and the first ray, the second ray, and the third ray transmitted through the measured portion. The intensity of is measured with a light receiving element,
Claims 1 to 6, wherein in the estimation step, the amount of glucose is estimated from the light receiving intensities of the first ray, the second ray, and the third ray based on the conversion formula. The glucose amount calculation method according to any one.