JP2010227271A - Blood sugar measuring method and device therefor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To measure a blood sugar level without being affected by the metabolic status in the body. <P>SOLUTION: By the blood sugar measuring method, a measuring probe 9 which irradiates living tissue with near-infrared light and measures the near-infrared light diffused in the living tissue is used. The measuring probe 9 is maintained at a temperature substantially equal to that of the deep part of the body which is measured by a means 23 for measuring the temperature of deep parts of the body. The near-infrared light diffused in the living tissue is measured in this state. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a blood glucose measurement method using near infrared spectroscopy and an apparatus therefor.

  Near-infrared spectroscopy is an analysis technique that uses near-infrared light having a wavelength of 800 to 2500 nm at which a harmonic overtone of the reference vibration wavelength of light due to molecular vibrations and its combined sound is observed, and has excellent permeability in a living body. It is widely used for analysis of biological components because it is non-destructive, non-invasive, and can perform quantitative and qualitative analysis in real time. Especially, blood oxygen concentration measurement represented by pulse oximeter has already been put into practical use. Widely used.

  By the way, when using near-infrared spectroscopy for measuring the concentration of biological components, near-infrared light that has been irradiated to the living tissue and diffused in the living tissue is measured, and based on the spectral signal obtained from the measurement result, Qualitative / quantitative analysis is performed, and its application to blood glucose level measurement is disclosed in Japanese Patent Application Laid-Open No. 2006-87913 (Patent Document 1).

  FIG. 3 shows a non-invasive optical blood glucose level measuring system disclosed in Patent Document 1, and near-infrared light emitted from the halogen lamp 1 is converted into a heat shielding plate 2, a pinhole 3, a lens 4, The light enters the living tissue 6 through the optical fiber bundle 5. One end of the measurement optical fiber 7 and one end of the reference optical fiber 8 are connected to the optical fiber bundle 5, and the other end of the measurement optical fiber 7 is connected to the measurement probe 9 facing the reference plate 18, The other end of the reference optical fiber 8 is connected to a reference probe 10. Further, the measurement probe 9 and the reference probe 10 are connected to the measurement-side emitter 11 and the reference-side emitter 12 via optical fibers, respectively.

  As shown in FIG. 1B, the measurement probe 9 and the reference probe 10 are composed of a plurality of light emitting fibers 20 arranged on the circumference and one light receiving fiber 19 arranged in the center. The distance L between the centers of the light emitting fiber 20 and the light receiving fiber 19 is set to 0.65 mm, for example.

  When the near-infrared spectrum measurement is performed by bringing the tip surface of the measurement probe 9 into contact with the surface of the living tissue 6 such as the forearm of the human body at a predetermined pressure, the near-infrared light incident on the optical fiber bundle 5 from the light source 1 is The light is transmitted through the measurement optical fiber 7 and irradiated from the tip of the measurement probe 9 as shown in FIG. 3B on the surface of the living tissue 6 from a plurality of light emitting fibers 20 arranged on the concentric circumference.

  The measurement light applied to the living tissue 6 is diffusely reflected in the living tissue, and a part of the diffuse reflected light is received by the light receiving fiber 19 disposed at the tip of the measurement probe 9. The received light is emitted from the measurement-side emitting body 11 through the light-receiving side optical fiber 19, enters the diffraction grating 14 through the lens 13, is dispersed, and is detected by the light-receiving element 15. After the A / D converter 16 performs AD conversion, the optical signal is input to an arithmetic device 17 such as a personal computer, and the arithmetic device analyzes the obtained spectrum data to calculate a blood glucose level. In the figure, 22 is a shutter, and 26 is a lens.

  Here, the center-to-center distance L between the light-emitting fiber 20 and the light-receiving fiber 19 is set to the above value because the spectrum of the dermis part is selected from the skin tissue having a layered structure of epidermis, dermis, and subcutaneous tissue from the surface. This is because it measures automatically.

JP 2006-87913 A

  By the way, in the near-infrared spectrum of water, the state of hydrogen bonding between water molecules changes with temperature. Even in the near-infrared spectrum of a living tissue, water is the main component of the living tissue, so that it is strongly affected by temperature changes. Therefore, in order to accurately measure the blood glucose level in a living tissue, it is necessary to perform an operation to keep the temperature of the site where the near-infrared spectrum is measured, but it has thermal metabolism that changes according to the environment and physiological state. In living tissue, the set temperature is important in order to stably measure the near infrared spectrum throughout the measurement period.

  On the other hand, when measuring the near-infrared spectrum of skin tissue, the body surface temperature is lower than the deep body temperature, and is strongly influenced by the environmental temperature and the metabolic state in the body. For this reason, when the set temperature is inappropriate, the spectrum becomes unstable, the measurement accuracy is deteriorated by inducing excessive sweating by acting on the living tissue, and the peripheral blood circulation is reduced. Inhibition may degrade the followability of the glucose concentration of the skin tissue relative to the glucose concentration in the blood. For example, when measuring blood glucose levels during surgery in medicine, the body temperature may be controlled lower than usual in the procedure, and if the temperature of the part where the near-infrared spectrum is measured is set carelessly, accurate blood glucose level measurement is possible. There are cases where it cannot be done.

  The present invention has been made in view of these points, and provides a blood glucose measurement method and apparatus capable of measuring a blood glucose level without being affected by not only the environmental temperature but also the metabolic state in the body. It is an object to do.

  A blood glucose measurement method according to the present invention is a blood glucose measurement method using a measurement probe that irradiates a living tissue with near-infrared light and measures near-infrared light diffused in the living tissue. Blood glucose measurement according to the present invention, characterized in that the temperature of the measurement probe is maintained at substantially the same temperature as the measured deep body temperature, and near-infrared light diffused in the living tissue in this state is measured. The apparatus is a blood glucose measurement device provided with a measurement probe for irradiating a living tissue with near-infrared light and measuring the near-infrared light diffused in the living tissue, and a body depth temperature measuring means for measuring a body depth temperature; It is characterized by comprising temperature control means for maintaining the temperature of the measurement probe at substantially the same temperature as the body depth temperature measured by the body depth temperature measuring means.

  The deep body temperature is called the core temperature or deep body temperature, and indicates the temperature of the deep body that is not easily affected by the environmental temperature. On the other hand, the temperature of the surface layer that is easily affected by the environment is called body surface temperature (outer shell temperature or skin temperature). The deep body temperature is the temperature of the core of the living body (the deep part of the body such as the head cavity, thoracoabdominal cavity, etc.) where the temperature does not change even when the environment changes. As the deep body temperature, rectal temperature, oral cavity temperature, axillary temperature, tympanic temperature, and esophageal temperature are usually measured. By using catheters with a special temperature sensor, it is also measured by bladder temperature, pulmonary artery blood temperature, or the like. The rectal temperature is usually said to be 0.5 ° C. higher than the axillary temperature.

  The present invention has found the usefulness of setting the temperature of the measurement target site to the deep body temperature when measuring near-infrared light (near-infrared spectrum) diffusely reflected in living tissue. In other words, it is known that the body depth temperature does not change with respect to the change in the environmental temperature, but the distribution in the living body is known to change, and when the environmental temperature is low, the body deep part temperature is added to the core part of the body. In contrast, when the environmental temperature is high, the distribution of the deep body temperature spreads, and in some cases, the distribution extends to the deep part of the upper and lower limbs.

  Therefore, the peripheral skin temperature of the upper limbs and lower limbs will vary greatly depending on the environmental temperature and physiological condition. It is important to perform proper blood sugar level measurement.

In order to stabilize the temperature near the skin surface at the periphery of the upper limb, lower limb, etc., temperature setting should be performed assuming the case where the environmental temperature is high and low as described above. In order to stabilize the temperature of the measurement probe and its contact area with only heating means such as a heater against changes in the temperature distribution, it is effective to set the temperature near the deep body temperature. Is maintained at a temperature that matches the deep body temperature as described above, so that the skin temperature such as the skin temperature of the measurement part and the blood flow state in the skin tissue is stabilized. The infrared spectrum can be stabilized.

  Moreover, the raise of the amount of stratum corneum of the skin surface part which a measurement probe contacts can be made small by making preset temperature of a measurement probe into body deep part temperature. Stabilization of the near-infrared spectrum obtained from the skin tissue stabilizes the blood sugar level prediction and leads to improved measurement accuracy.

  The deep body temperature measured by the deep body temperature measuring means is preferably any of the eardrum temperature, rectal temperature, oral cavity temperature, or axillary temperature. In addition, it is useful that the temperature control means holds the measurement probe in a range of ± 1 ° C. of the measured deep body temperature.

  In the present invention, in order to maintain the temperature of the measurement probe that measures the diffuse reflected light of near-infrared light irradiated to the skin tissue at the same temperature as the user's body depth temperature, The skin condition such as the blood flow condition in the skin tissue can be stabilized, and the accuracy of blood glucose measurement can be increased accordingly.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows an example of an embodiment of the present invention, where (a) is a schematic view and (b) is a cutaway side view of a measurement probe portion. It is explanatory drawing which shows the estimation result of a blood glucose level same as the above. The conventional example is shown, (a) is a block diagram, (b) is an end view of the measurement probe.

  The present invention will be described in detail based on an example of an embodiment. A blood glucose measurement device according to the present invention is basically the same as the device disclosed in Patent Document 1, and a near-infrared spectrum measurement for skin tissue is performed. In this way, the blood glucose level is non-invasively measured using the change in glucose concentration in the dermal tissue in the skin tissue as a substitute characteristic.

  However, the apparatus differs from the apparatus in that a deep body thermometer 23 is provided, and a heating means (heater) 24 and a temperature measuring means 25 such as a thermocouple are provided. The heating means 24 and the temperature measuring means 25 are arranged in a cylindrical holder 22 that holds the measuring probe 9 in the center.

  The holder 22 is provided with a double-sided adhesive tape 25 on one surface serving as a skin contact surface, and is attached to the skin surface with the double-sided adhesive tape 25, thereby bringing the end surface of the measurement probe 9 into contact with the skin surface. The heating means 24 and the temperature measuring means 25 provided in the holder 22 and the deep body thermometer 23 are connected to a temperature control unit built in the apparatus main body 30.

  The temperature control unit operates the heating means 24 so that the body temperature measured by the body depth thermometer 23 and the temperature measuring means 25 disposed on the holder 22 coincide with each other. If the total temperature 23 is a rectal thermometer and the measurement temperature is 67.0 ° C. in a state where 6 cm is inserted into the subject's rectum from the anus, for example, the operation of the heating means 24 so that the holder 22 also maintains 37.0 ° C. To control. And while the holder 22 affixed on the skin surface is maintaining the said temperature, the blood glucose measurement based on a near-infrared spectrum is performed. At this time, the portion of the skin where the measurement probe 9 and the holder 22 are in contact with each other is also maintained at the above temperature.

  The measured deep body temperature and the temperature of the holder 22 do not have to coincide with each other accurately, and accurate measurement is possible as long as they are within a range of ± 1 ° C. In addition, when the ambient temperature is 20 ° C or lower and the deep body temperature is unlikely to be distributed to the vicinity of the measurement part, or when it is necessary to lower the body temperature than usual for surgery or the like, the deep body temperature is set to T ° C. When doing, it is more preferable to set the set temperature to be held in the holder 22 to be lower than the measured body deep temperature within a range of T ° C to (T-1) ° C. Conversely, for subjects with poor peripheral circulation, it is better to set the temperature higher within the range of T ° C. to (T + 1) ° C. with respect to the measured deep body temperature T ° C.

  For the creation of a calibration model for obtaining a blood glucose level, difference spectrum data similar to the method disclosed in Patent Document 1 may be used. In other words, the difference spectrum data set is added to the initial near-infrared spectrum measured during blood glucose measurement (usually the near-infrared spectrum measured at the start of measurement), and a spectrum data set for creating a calibration model is created computationally. To do. The calibration model used for blood glucose level estimation is created by PLS regression analysis using the blood glucose level as a target variable and the spectrum data set for creating a calibration model as explanatory variables. The blood glucose level is estimated by substituting the absorbance at each wavelength of the near-infrared spectrum measured in this calibration model.

Next, the results of blood glucose measurement in a state where the holder 22 that holds the measurement probe 9 and contacts the skin of the measurement target site is held at substantially the same temperature as the deep body temperature will be described.
[Example 1]
FIG. 3 shows a graph comparing the blood glucose level a derived in this example with the blood glucose level b measured by blood sampling. The bias correction of the estimated blood glucose level was made so that the measured blood glucose level and the estimated blood glucose level matched at one point at the start of measurement (during calibration). The set temperature of the holder 22 was also set to the deep body temperature (rectal temperature: 37.0 ° C.) measured during calibration. The temperature of the holder 22 was controlled at 37.0 ± 0.1 ° C. during the measurement period of about 6 hours. The room temperature (environmental temperature) during the measurement period was in the range of 24.0 to 25.0 ° C.

The correlation coefficient between the blood glucose level a measured in this example and the blood glucose level b measured by blood sampling was 0.93. It can be seen that the blood glucose level measured in this example well follows the change in blood glucose level measured by blood sampling.
[Example 2]
In the present embodiment, the environmental temperature is 18.5 ° C. and less than 20 ° C., and it is considered that the possibility that the deep body temperature is distributed to the vicinity of the measurement portion is extremely low. Therefore, the holder 22 for holding the measurement probe 9 The value (37.0 ° C.) obtained from the rectal thermometer 23 of the subject was set to a value (36.0 ° C.) lower by −1 ° C. than the reference. The set temperature is determined at the start of blood glucose level measurement, and this set temperature is not changed until the end of the measurement.

  In this case, the correlation coefficient between the blood glucose level measured in this example and the blood glucose level measured by blood sampling was 0.90. As in Example 1, it can be seen that the blood glucose level measured in the present example closely follows the change in blood glucose level measured by blood sampling.

The set temperature may be set low depending on not only the environmental temperature but also the condition of the subject's clothes. In any case, since it is not necessary to place an excessive load on the temperature control means and the control temperature is stabilized, the temperature of the measurement part is determined based on the deep body temperature, so that the skin is not disturbed without inhibiting the peripheral circulation. The organization can be kept stable.
[Example 3]
In this example, the basic configuration is the same as that of Example 1, but an eardrum thermometer that measures the eardrum temperature is used as the deep body thermometer 23. This eardrum thermometer is not directly connected to the apparatus main body 21 and is used as an apparatus attached to the apparatus.

  Body temperature measurement with the tympanic thermometer was performed during calibration in the same manner as in Example 1, and the measured value was manually input to the apparatus body. The set temperature of the measurement probe 9 was set to the same value (37.0 ° C.) as the deep body temperature measured with the tympanic thermometer because the environmental temperature was 25.0 ° C. The set temperature is determined at the start of blood glucose level measurement, and this set temperature is not changed until the end of the measurement.

  The correlation coefficient between the blood glucose level measured in this example and the blood glucose level measured by blood sampling is 0.92, and the blood glucose level measured in this example follows the change measured by blood sampling as in the other examples. You can see that

  As the deep body thermometer 23, a rectal thermometer that measures rectal temperature and an eardrum thermometer that measures eardrum temperature are shown, but in addition, a device that measures oral cavity temperature or axillary temperature may be used.

9 Measurement probe 23 Body thermometer 24 Heating means

Claims (4)

  In a blood glucose measurement method using a measurement probe that irradiates a living tissue with near-infrared light and measures near-infrared light diffused in the living tissue, the temperature is substantially the same as the body temperature measured by the body temperature measuring means. A method for measuring blood glucose, characterized in that the temperature of the measurement probe is held and near infrared light diffused in the living tissue in this state is measured.   In a blood glucose measurement device equipped with a measurement probe that irradiates a living tissue with near-infrared light and measures near-infrared light diffused in the living tissue, a body depth temperature measuring means for measuring a body depth temperature, and a body depth temperature A blood glucose measurement device comprising temperature control means for maintaining the temperature of the measurement probe at substantially the same temperature as the deep body temperature measured by the measurement means.   The blood glucose measuring device according to claim 2, wherein the body deep part temperature measured by the body deep part temperature measuring means is any of an eardrum temperature, a rectal temperature, an oral temperature, or an axillary temperature.   4. The blood glucose measurement device according to claim 2, wherein the temperature control means holds the measurement probe in a range of ± 1 ° C. of the measured deep body temperature.

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