JPH095322A - Biological substance measuring instrument - Google Patents

Abstract

PURPOSE: To provide a noninvasive type biochemical substance measuring instrument which is reduced in size and weight and improved in measurement accuracy. CONSTITUTION: A biological substance measuring instrument 1 is composed of a saliva sucking port 11a which is a saliva collecting means, a sucking member 11 provided with a saliva sucking port 11a and a reduced-pressure sucking port 11b, and a vacuum pump 20. The main body of the device is constituted of a CPU, storage device, and displaying means. When the saliva sucking port 11a of the sucking member 11 is set so as to cover the opening of the submandibular gland of a patient and the saliva is filtrated with a filtrating material 12, the detection accuracy of a sensor is improved, because such a substance as the interstitial solution which comes out from the gums due to alveolar pyorrhea that hinders the biochemical analysis of the sensor is not mixed in the saliva to be measured. When the amount of a resulted product of the reductive reaction of an enzyme is measured with the sensor, the blood sugar value of the patient can be calculated from the correcting information stored in the storing device. Therefore, a noninvasive blood sugar value measuring instrument can be provided.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a biochemical substance measuring device for measuring a predetermined biochemical substance such as sugar contained in blood of a living body, and more particularly to a non-invasive biochemical substance measuring device. .

[0002]

2. Description of the Related Art Conventionally, various sensors (referred to as biosensors) have been devised which skillfully utilize the strict molecular discrimination function of enzymes, and their application has been advanced to the analysis of biologically active substances (biochemical substances) in the living body. There is. For example, in the treatment of diabetes, biosensors are revolutionizing blood glucose measurement technology. In the 1970s, a blood glucose sensor using an enzyme membrane in which glucose oxidoreductase, a glucose oxidoreductase, was immobilized on a polymer was developed. Until then, blood glucose measurement was required for several minutes to one hour or more. Now you can measure.

However, since these biosensors use blood as a substance to be measured, it is necessary for the patient to collect blood each time the measurement is performed, and the following problems remain unsolved.

That is, there is a risk of physical pain at the time of blood collection and infection with a virus that uses blood as a medium, such as hepatitis B and AIDS, which constantly gives patients and nurses a feeling of mental anxiety. Is that.

In order to solve these problems, a non-invasive method for measuring physiologically active substances using an optical method has been proposed. For example, Motoaki Nanasato et al., "Non-invasive measurement method of blood glucose level-optical method". Development of glucose sensor-, BME, Vol.5, No.
8, pp. 16-21, 1991 ”and the like.

[0006]

In the blood glucose measuring method using the optical method described above, the blood glucose level is estimated based on the absorbance of glucose, but the wavelength of the absorbed light of glucose is 9
Since it is as long as ~ 11 μm, infrared rays are required as its light source. However, since the current infrared light source, for example, an infrared laser is very large and requires a cooling device, it is difficult to make the measuring device compact and portable.

The present invention has been made in order to solve the above-mentioned problems, and its purpose is to eliminate the need for collecting blood as in the conventional case, to enable miniaturization and portability, and to obtain a sample with excellent analysis accuracy. It is to provide a chemical substance measuring device.

[0008]

[MEANS FOR SOLVING THE PROBLEMS] A biochemical substance measuring apparatus of the present invention for achieving this object is a collecting means for collecting saliva secreted into the oral cavity as a secretion of a living body, and a collecting means for collecting the saliva. A sensor that detects information related to the concentration of a predetermined biochemical substance contained in saliva, and the corresponding information related to the correlation between the concentration related to the biochemical substance in saliva and the concentration in blood is stored. Storage means, and an arithmetic means for calculating the concentration of the biochemical substance in blood based on the information related to the concentration of the biochemical substance detected by the sensor and the correspondence information stored in the storage device. A non-invasive biochemical substance measuring device provided,
The collecting means includes a vacuum pump, a saliva suction port that can be attached to the opening of the submandibular duct in the oral cavity, and a decompression suction port that is connected to the saliva suction port and is connected to the vacuum pump. And a suction member.

Here, the sensor may include at least one kind of enzyme that reacts with the biochemical substance, and an electrode for detecting an increase / decrease of a product produced by the reaction.

Further, the collecting means may be configured to be housed in the oral cavity and detachable from the sensor.

Further, the suction member may be provided with a filtering means for preventing passage of a substance which obstructs the measurement of the biochemical substance.

The enzyme may include at least glucose oxidase, and the concentration of the biochemical substance detected by the sensor may be the concentration of glucose.

[0013]

In the biochemical substance measuring apparatus of the present invention having the above structure, the saliva suction port of the suction member as the collecting means is attached to the opening of the submandibular duct in the oral cavity and the vacuum pump is operated. And only saliva secreted from the submandibular gland is collected,
Information related to the concentration of a given biochemical contained in saliva collected by the sensor is detected. For example, the amount or concentration of biochemical substance itself is detected. The storage means stores information relating to the concentration in saliva and the concentration in blood regarding the predetermined biochemical substance, and the calculating means relates to the concentration of the biochemical substance detected by the sensor. The concentration of the biochemical substance in blood is calculated based on the information stored in the memory and the correspondence information stored in the storage means. That is, since saliva is collected from the opening of the submandibular duct in the oral cavity, a substance that inhibits the biochemical analysis of the sensor in the collected saliva, for example, interstitium exuding from the gums due to alveolar pyorrhea Since liquids and the like do not mix, the analysis accuracy increases.

Here, when the sensor is composed of at least one kind of enzyme that reacts with the biochemical substance and an electrode for detecting an increase / decrease of a product produced by the reaction, the saliva is detected from the sensor. A current value proportional to the concentration of the biochemical substance is detected, and the concentration can be easily detected.

Further, when the collecting means is configured to be housed in the oral cavity and attachable to and detachable from the sensor, if the sensor is removed during saliva collection, the sensor will not come into contact with the oral cavity. The adverse effect on the living body by the chemical substance of the sensor is prevented.

Further, when the suction member is provided with a filtering means for preventing passage of a substance which inhibits the measurement of the biochemical substance, the interstitial fluid or the like is sucked from the saliva suction port of the suction member in addition to saliva. Even if it is done, the interstitial fluid is removed from the saliva, and the bacteria, enzymes, etc. in the saliva are also removed, so that the analysis accuracy is further enhanced.

Further, when the enzyme contains at least glucose oxidase and the concentration of the biochemical substance detected by the sensor is the concentration of glucose, the blood sugar level of blood can be easily grasped.

[0018]

EXAMPLES Hereinafter, an example in which the present invention is embodied in a non-invasive blood glucose level measuring device 1 for measuring blood glucose level by measuring glucose concentration in saliva will be described with reference to FIGS. This will be described with reference to FIG.

FIG. 1 is a diagram showing an embodiment of the collecting means. The suction member 11 has a circular shape in which one side is expanded, and the end surface of the expanded end is a saliva suction port 11a and the end surface of the other end is a decompression suction port 11b. The saliva suction port 11a has a shape and size that can be attached to the opening of the submandibular gland duct in the oral cavity. Further, a disc-shaped filter medium 1 is provided on the inner surface of the expanded end portion closer to the decompression suction port than the saliva suction port 11a.
2 is detachably mounted. The filter medium 12 is for removing bacteria, enzymes and the like in the interstitial fluid from the gums and saliva as impurities from the saliva sucked from the saliva suction port 11a, and is a porous material made of resin, ceramic or paper. It is possible to use materials.

One end of a flexible tube 13 is attached to the decompression suction port 11b of the suction member 11, and the tube 13
The other end of the three-way stopcock 15 has a first hole 15 through a check valve 14.
a. One of the remaining two holes of the three-way stopcock 15 is connected to the saliva discharge tube 18 via the check valve 16, and the other one hole 15c is connected to the check valve 17 and the flexible tube 19. Connected to the vacuum pump 20. An exhaust port 21 is attached to the vacuum pump 20. The vacuum pump 20 may be an electric type or a manual type.

Inside the three-way stopcock 15 (saliva storage chamber)
A measuring unit of a sensor (biosensor) 30 described later is attached to the above, and this measuring unit is connected to the current measuring unit 31. The sensor 30 can be detachably provided inside the three-way stopcock 15. Further, when it is not detachably provided, it may be disposable every one to several hundreds of uses depending on the durability of the sensor. In this case, the three-way stopcock 15 will be replaced.

The suction means 11, the three-way stopcock 15, the vacuum pump 20, etc. constitute the collecting means of the present invention.

FIG. 2 is a diagram showing a schematic configuration of the blood glucose level measuring device 1. The blood glucose level measuring device 1 includes a current detection unit 31 connected to a sensor 30 provided on the three-way stopcock 15 with a lead wire.
The vacuum pump 20, a calculation unit 40 that inputs a detected current value from the current detection unit and performs a predetermined calculation, and a liquid crystal display type display device 50 as an output unit that displays a blood glucose level as a calculation result. It consists of and. The current detection unit 31 applies a predetermined voltage between an anode and a cathode of a sensor described later, detects a current value, and digitally outputs the current value. The arithmetic unit 40 is composed of a CPU (arithmetic means) 41, a storage device 42 and an input / output port, and the storage device 42 is composed of a ROM in which information described later is stored and a RAM for temporarily storing the operation result. ing. This ROM stores a control program and information showing the correspondence between the saliva glucose concentration and blood glucose level shown in FIG. Further, the correspondence between the detected current value I ₀ from the sensor and the glucose concentration in saliva is also stored in the ROM.

Here, a method for collecting saliva will be described with reference to FIG. FIG. 3 is a diagram schematically showing a state in which the suction member 11 is attached to the jaw of a living body.

When collecting saliva, first the suction member 11
Is inserted under the tongue 60 in the oral cavity, and the saliva suction port 11a is arranged so as to cover the opening 63 of the submandibular duct. Here, since the saliva suction port 11a is formed to be relatively large, the opening 63 is surely covered even if the subject is roughly arranged. The submandibular gland 61 and the sublingual gland 62 are opened in this submandibular gland duct, and saliva secreted by the submandibular gland 61 leaks into the oral cavity through the submandibular gland duct.

Here, the check valves 14 and 16 are closed, the check valve 17 is opened, and the vacuum pump 20 is operated to reduce the pressure in the saliva storage chamber 15a of the three-way stopcock 15. After that, when the check valves 16 and 17 are closed and the check valve 14 is opened, the saliva in the submandibular gland 61 and the sublingual gland 62 is closed by the three-way stopcock 1.
5 is sucked into the saliva storage chamber 15d. The amount of saliva sucked in here can be adjusted to a predetermined amount according to the volume of the saliva storage chamber 15d of the three-way stopcock 15. Therefore, as described later, the glucose concentration in saliva can be calculated based on the amount of the product (the product of the reduction reaction by the enzyme) detected by the sensor 30 and the volume of the saliva storage chamber 15d. At this time, the filtering material 12 is for filtering substances that are contained in saliva and inhibit the measurement of biochemical substances, for example, polymeric substances such as bacteria and enzymes (mainly having a molecular weight of 5000 or more). By taking such a configuration,
It becomes possible to selectively collect only saliva, and remove substances that interfere with biochemical analysis, such as impurities in interstitial fluid leaching from the gums due to alveolar pyorrhea, bacteria and enzymes in the oral cavity. Is possible. As a result, it is possible to realize a blood glucose level measuring instrument with excellent analysis accuracy.

In this embodiment, an example in which a filter medium is added has been described, but the present invention is not limited to this, and if a porous material is attached to the tube 13 to provide a filter function, the number of parts is further increased. Can be reduced and the structure can be simplified. Further, since the sensor 30 is configured to be detachable as in the present embodiment, it becomes possible to prevent the chemical substances, which will be described later, contained in the sensor 30 from directly touching the oral cavity during saliva collection. Therefore, there is an advantage that the living body is not adversely affected by the chemical substance.

Next, a method of estimating the blood sugar level from the glucose concentration of saliva will be described with reference to FIG.

First, the correlation between the glucose concentration in saliva and the blood glucose level was confirmed by the following experiment.

An oral glucose tolerance test (Oral Gluco) was carried out using a healthy adult male (32 years old) without alveolar pyorrhea as a subject.
se Tolerance Test, OGTT), blood and saliva 1
Samples were taken at 0 minute intervals for 2 hours. In the oral glucose tolerance test, 75 g of glucose solution (Treran G, Takeda Pharmaceutical Co., Ltd.) was given to a subject who had been fasted for 6 hours, and the residue in the oral cavity was washed by gargle. During the test, he remained still and no side effects were observed. For blood collection,
Surflolycine (thickness: 20) with three-way stopcock connected
(Gauge) was inserted into a vein, and physiological saline containing 2 cc of heparin was intravenously infused at 25 cc / h so as not to be blocked by a thrombus. Blood was collected with this three-way stopcock, and 2 cc of blood in leucine was discharged every time and then blood was collected. The saliva was collected by inserting a roll watte (dental cotton) under the tongue and collecting mainly mixed saliva of the submandibular and sublingual glands for 5 minutes each time. Saliva collected by compressing this roll wattle with a disposable syringe took 30 minutes with a pressure-type ultrafiltration machine (Millicat 2-LCC, Japan Millipore Co., Ltd.) with a molecular weight cutoff of 5000 to remove bacteria and enzymes. It was filtered and stored at room temperature (about 25 ° C).

Blood glucose was measured by a biochemical automatic analyzer (Hitachi, 7170) each time blood was drawn. Saliva sugar was measured using an enzyme method reagent for glucose measurement (Wako Pure Chemical Industries, Ltd., Glucose C2-Test Wako). 100 μl of saliva was mixed with 3.0 ml of the enzymatic reagent and stirred, and color was developed by heating at 37 ° C. for 5 minutes. Then, the absorbance at a wavelength of 505 nm was measured with a spectrophotometer (U-3200, Hitachi, Ltd.), and converted into glucose concentration by a calibration curve (glucose concentration = absorbance / 0.0129) obtained in advance. The measurement accuracy of the enzyme method reagent is ± 2% at a high concentration of 100 mg / dl or more, 1-1.
It is ± 10% at a low concentration of 0 mg / dl.

FIG. 4 shows the results of measuring the time course of blood glucose and salivary sugar in the oral glucose tolerance test. Fasting blood sugar and salivary sugar are 92 mg / dl and 1.16 mg / dl, respectively.
In all cases, the initial values were restored after 90 minutes. The maximum values of blood sugar and salivary sugar are 142 mg / dl each,
It was 5.95 mg / dl, and the time delay of salivary sugar with respect to blood glucose was confirmed to be 40 minutes. The results of this test show that a correlation between blood sugar and salivary sugar is recognized, and fluctuations in blood sugar 50
mg / dl could be identified by the change in salivary sugar.
That is, it is understood that the glucose concentration of saliva has a correlation with blood glucose. Therefore, the subject fasts and drinks for about 1 hour for saliva collection in order to measure the blood glucose level.

Regarding the correlation between glucose concentration in saliva and blood glucose level, some studies have been conducted so far as listed below.

1) COReuterving: Pilocarpine-stimula
ted salivary flow rate and salivary glucose concent
ration in alloxan diabetic rats. Influence of sever
ity and duration of diabetes, Acta Physiol Scand,
126, pp.511-515,1986. 2) LNForbat, RECollins, GKMaskell, PHSonk
sen: Glucose concentrations in parotid fluid and ven
ous blood of patientsattending a diabetic clinic,
Journal of the Royal Society of Medicine, 74, pp.725
-728, 1981. The correlation between the glucose concentration in saliva and the blood glucose level at that time obtained in the above experiment is stored in the ROM, and the graph shown in FIG. 8 is an example thereof. Also, this R
The correspondence between the detected current value detected by the sensor 30 and the glucose concentration in saliva at that time is also stored in the OM. This detected current value I ₀ is proportional to the glucose concentration in saliva.

Current value I detected by the sensor 30
_{Based on 0} and the correspondence information stored in the ROM, the CPU 4
1 calculates the glucose concentration in saliva, calculates the blood glucose level corresponding to the glucose concentration, and displays it on the display device 50. Here, instead of displaying on the display device 50, the blood glucose level can be printed on the printing device, and in short, the blood glucose level may be output to the subject.

Next, the sensor (enzyme sensor; also referred to as biosensor) 30 of this embodiment will be described with reference to FIGS.

In the enzyme sensor 30, a base material 31 is provided with an electrode 32 made of a highly conductive material, and a protective electrode 33 made of a water resistant material is provided thereon. Examples of the material of the electrode 32 include noble metals such as gold, silver, platinum and platinum,
Metallic materials such as copper and aluminum are considered. Also,
It is desirable that the protective electrode 33 provided to prevent moisture from adhering to and corroding the electrode 32 itself does not contribute to the chemical reaction, and carbon or the like is considered as a material. However, when the enzyme sensor is used as a disposable sensor, it is not necessary to provide the protective electrode 33 for cost reduction. Further, a protective film 34 made of a polymer or the like is provided at a portion where the protective electrode 33 is not attached to the electrode 32. Further, an enzyme film 35 is provided on the protective electrode 33. The enzyme membrane 35 is covered with a separation membrane 36 in order to prevent the enzyme membrane 35 from changing with time. The separation membrane 36
Can be omitted for cost reduction. The glucose concentration is detected by the saliva adhering to the enzyme film 35, and the portion of the enzyme film 35 serves as the measuring portion of the sensor.

An example of the two-dimensional shape of the enzyme sensor 30 is shown in FIG. FIG. 6 shows a state where the enzyme membrane 35 and the separation membrane 36 are omitted in order to clarify the shapes of the electrode 32 and the protective electrode 33. Also,
The electrode 32 and the protective electrode 33 are the anodes 32a and 33, respectively.
a and cathodes 32b and 33b. Then, the enzyme film 35 is formed inside the portion indicated by the dotted line B. Then, the anode 32a and the cathode 32
b is connected to the current measuring unit 31 by a lead wire, and a predetermined voltage is applied. When a predetermined voltage is applied to the anode terminal and the cathode terminal, the product (H ₂ O ₂ ) by the chemical reaction described below is electrolyzed.

The electrode 32, the protective electrode 33, and the protective film 34 can be formed by a method such as screen printing, etching, or thermal spraying.
In addition, the base material 11, the base material of the enzyme membrane 35, and the separation membrane 3
As the material of 6, the materials listed in the table of FIG. 7 can be considered.

Next, a method for producing the enzyme membrane 35 and the separation membrane 36 will be described step by step below.

1. Preparation of electrode 1) 1 [g] of carboxymethyl cellulose (hereinafter abbreviated as CMC) is added little by little to 1 [L] of pure water while
After stirring for 2 hours, the mixture was left to stand overnight to obtain 0.1% by weight of CMC.
Make a solution.

2) 0.1 per unit area on the protective electrode 33.
Apply 8 [μL / mm ² ] of CMC.

3) In order to prevent the deterioration of the electrodes, the CMC layer is formed by drying at a temperature as low as possible, for example, 40 ° C. for 1 hour.

2. Dissolution of enzyme For example, when a blood glucose sensor is prepared, 10 [mg] glucose oxidase is mixed with 67 [mL] pure water to prepare a 10 [μM] enzyme solution. At this time, in order to prevent the inactivation of the enzyme, it is preferable that the magnetic stirrer is not used and the mixture is slowly stirred by hand.

3. Immobilization of enzyme 1) 16.463 [g] potassium ferricyanide (potassium hexacyanoferrate (3), K ₃ [Fe (CN) ₆ ])
Is mixed with 1 [L] of pure water to prepare a 50 [mM] potassium ferricyanide solution.

2) A mixed aqueous solution is prepared by adding 10 [mL] of each of CMC solution, enzyme solution and potassium ferricyanide solution in a ratio of 1: 1: 1.

3) 1.0 [μL / mm ² ] per unit area of the mixed aqueous solution was dropped on the CMC layer, and then 1 at 40 ° C.
After drying for an hour, the enzyme film 35 is created.

4. Preparation of Separation Membrane (If Necessary) 1) 1 [g] of polyvinylpyrrolidone (hereinafter abbreviated as PVP) was mixed with 100 [g] of ethanol and stirred for about 1 hour, Make a 1 wt% PVP solution.

2) A PVP solution is spread on the enzyme membrane 35 by 0.4 [μL / mm ² ] per unit area and dried at 40 ° C. for 20 minutes to form a separation membrane 36.

Since the chemical substances constituting the enzyme film 35 are stored in the solid state as described above, it is possible to obtain an enzyme film having a small change with time. The enzyme immobilized on the enzyme membrane of this example is not limited to the glucose oxidase, and various enzymes such as oxidoreductase and hydrolase can be used, and as a result, biobiochemistry other than glucose can be used. Substances such as ethanol, lactic acid,
It is possible to realize a sensor that measures uric acid, urea, neutral fat, total cholesterol, or pyruvic acid.

The enzyme immobilization method has been described by taking the physical adsorption method as an example, but the enzyme immobilization method is not limited to this. For example, Shuichi Suzuki, Ion electrode and enzyme electrode, Kodansha Scientific, 1981, 11 As disclosed in May, a carrier binding method such as an ionic binding method or a covalent binding method, a crosslinking method, an encapsulation method, or the like may be used. In addition, various modifications can be considered without departing from the spirit of the present invention.

Although potassium ferricyanide, which is a chemical substance used in the enzyme membrane of the present example and contributing to electrolysis, is generally called a mediator, it is not limited to this potassium ferricyanide and various ionized substances, That is, it is possible to use a metal or a complex.

Next, the operation of this embodiment will be described.

When the saliva of the submandibular gland 61 and the sublingual gland 62 is sucked into the saliva storage chamber 15d in the three-way stopcock 15 as described above, the saliva adheres to the measuring portion of the enzyme sensor 30. As a result, The saliva becomes an electrolyte, and the enzyme fixed on the enzyme film 35, such as glucose oxidase, is dissolved in the saliva. As a result, the enzyme catalyzes the following chemical reaction.

[0055]

[Equation 1]

At this time, a predetermined voltage is applied between the anode 32a and the cathode 32b of the electrode 32, and H ₂ O ₂ produced by the above chemical reaction (product of the enzymatic reduction reaction)
Electrolysis occurs on the basis of. The following chemical reactions take place.

[0057]

[Equation 2]

At this time, the current flowing between the anode 32a and the cathode 32b is measured by the current measuring unit 31, and its value is a value proportional to the amount of H ₂ O ₂ generated. That is,
The amount of H ₂ O ₂ generated is detected. As can be seen from the formula (1), the amount of H ₂ O ₂ is proportional to the amount of β-D-glucose, that is, glucose, and thus the current value I ₀ is equal to the amount of glucose contained in the sweat. It turns out to be proportional.

On the other hand, since the amount of saliva attached to the measuring portion of the sensor 30 is equal to the volume of the saliva storage chamber 15a in the three-way stopcock 15, the saliva is detected based on the detected current value I ₀ and saliva amount. The glucose concentration in it can be calculated. Since the correspondence relationship between the current value I ₀ and the glucose concentration in saliva is stored in the ROM of the storage device 42, the glucose concentration in saliva is calculated based on the detected current value I _0. Become.

The blood glucose level is calculated based on the detected current value I ₀ and the correspondence information in the ROM, and is visually displayed on the display device 50.

Here, in the present embodiment, the detected current value I ₀ is once converted into the glucose concentration in saliva and further converted into the blood glucose level. However, the detected current value I ₀ (in saliva) is stored in the ROM. It is also possible to directly store the blood glucose level by storing the correspondence relationship between the glucose amount) and the blood glucose level as it is. This is because the amount of saliva collected is approximately constant,
This is because the amount of glucose detected becomes equivalent to its concentration.

According to this example, by using the substance contained in saliva secreted into the oral cavity as the substance to be measured,
It is possible to provide a biochemical substance measuring device that is compact and lightweight and suitable for portability. Further, since impurities contained in saliva can be removed, detection accuracy can be improved.

The present invention is not limited to the blood glucose level measuring device of the above-mentioned embodiment, and as described above, various enzymes including oxidoreductase and hydrolase are used for the enzyme sensor 30. As a result, it is possible to realize a biochemical substance measuring device for measuring biochemical substances other than glucose, such as ethanol, lactic acid, uric acid, urea, neutral fat, total cholesterol, or pyruvic acid.

[0064]

As is clear from the above description,
According to the biochemical substance measuring device of the present invention, when the saliva suction port of the suction member as the collecting means is attached to the opening of the submandibular gland duct in the oral cavity and the vacuum pump is operated, it is secreted from the submandibular gland. Information about the concentration of the predetermined biochemical substance contained in the saliva collected by the sensor is detected by the sensor, and the storage means stores the information about the concentration in the saliva of the predetermined biochemical substance and the concentration in the blood. The correspondence information between the biochemical substance and the concentration of the biochemical substance in the blood is stored based on the information on the concentration of the biochemical substance detected by the sensor and the correspondence information stored in the storage unit. Is configured to calculate. For this reason, saliva is collected from the opening of the submandibular gland duct in the oral cavity, so there is no need to collect blood as in the past, and it is possible to miniaturize and carry it, and to collect sensor in the saliva collected. The substance that inhibits the biochemical analysis of E. coli, for example, interstitial fluid that exudes from the gum due to alveolar pyorrhea does not mix, so that the analysis accuracy can be improved.

When the sensor is composed of at least one kind of enzyme that reacts with the biochemical substance and an electrode for detecting an increase / decrease of the product produced by the reaction, the sensor can detect saliva in saliva. The current value proportional to the concentration of the biochemical substance is detected, the concentration can be easily detected, and the circuit configuration can be simplified and the cost can be reduced.

Further, when the collecting means is configured to be housed in the oral cavity and detachable from the sensor, the sensor does not come into direct contact with the oral cavity. Also has the effect of being able to eliminate the effect on the living body and being practical.

Further, when the suction member is provided with a filtering means for preventing passage of a substance that inhibits the measurement of biochemical substances, the interstitial fluid and the like are temporarily sucked from the saliva suction port of the suction member in addition to saliva. Even if it is done, the interstitial fluid is removed from the saliva, and the bacteria, enzymes, etc. in the saliva are also removed, so that the analysis accuracy is further enhanced.

When the enzyme contains at least glucose oxidase and the concentration of the biochemical substance detected by the sensor is the concentration of glucose, it becomes possible to easily grasp the blood glucose level of blood. .

[Brief description of drawings]

FIG. 1 is a diagram showing a configuration of an embodiment of a collecting means of the present invention.

FIG. 2 is a diagram showing a schematic configuration of a blood glucose level measuring device 1 of the present embodiment.

FIG. 3 is an explanatory diagram showing a method of collecting saliva.

FIG. 4 is a diagram illustrating a correlation between a glucose concentration in saliva and a blood glucose level.

FIG. 5 is a configuration diagram showing an example of an enzyme sensor.

FIG. 6 is a plan view showing only an electrode portion of the enzyme sensor.

FIG. 7 is a diagram showing a material table for a base material, an enzyme membrane, and a separation membrane of an enzyme sensor.

8 is a diagram showing a correspondence relationship between a glucose concentration in saliva and a blood glucose level stored in a storage device 42. FIG.

[Explanation of symbols]

 1 Blood glucose level measuring device (biochemical substance measuring device) 10 Collection means 11 Suction member 11a Saliva suction port 11b Decompression suction port 12 Filtration material (filtration means) 20 Vacuum pump 30 Sensor 41 CPU 42 Storage device 50 Display unit

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI Technical display location G01N 27/28 G01N 27/28 P 27/327 33/66 A 27/416 7823-4B C12Q 1 / 26 33/66 7823-4B 1/54 // C12Q 1/26 G01N 27/30 353R 1/54 27/46 336Z

Claims (5)

[Claims] 1. A collection means for collecting saliva secreted into the oral cavity as a living body's secretion, and information related to the concentration of a predetermined biochemical substance contained in the saliva collected by the collection means is detected. A sensor, a storage unit that stores correspondence information regarding the correlation between the concentration in saliva and the concentration in blood regarding the biochemical substance, and information related to the concentration of the biochemical substance detected by the sensor. Based on the correspondence information stored in the storage means and the storage means, a non-invasive biochemical substance measuring device comprising a calculating means for calculating the concentration of a biochemical substance in blood, wherein the collecting means is A vacuum pump and a saliva suction port that can be attached to the opening of the submandibular duct in the oral cavity,
A biochemical substance measuring device, comprising: a suction member that is connected to the saliva suction port and that includes a decompression suction port that is connected to the vacuum pump. 2. The sensor comprises at least one enzyme that reacts with the biochemical substance, and an electrode for detecting an increase / decrease of a product produced by the reaction. 1. The biochemical substance measuring device according to 1. 3. The biochemical substance measuring apparatus according to claim 1, wherein the collecting unit is configured to be housed in the oral cavity and detachable from the sensor. 4. The biochemical substance measuring substance according to any one of claims 1 to 3, wherein the suction member is provided with a filtering means for preventing passage of a substance which inhibits the measurement of the biochemical substance. . 5. The biochemical substance according to claim 1, wherein the enzyme contains at least glucose oxidase, and the concentration of the biochemical substance detected by the sensor is the concentration of glucose. measuring device.