JPH11160301A - Device for measuring lipid peroxide in organism - Google Patents

Abstract

PROBLEM TO BE SOLVED: To estimate amount of a lipid peroxide in an organism, especially, the amount of decomposition of the lipid peroxide exceeding the amount of the aptitude lipid peroxide of the body of a subject, by measuring the amount of pentane in a breath based on a detected constituent waveform and the predetermined retention time of the pentane. SOLUTION: A condensation part 65 samples breath and at the same time condenses it. A plot column 84 with the strong polarity of a liquid phase separates the constituent of the condensed breath. A detector 85 detects a constituent waveform corresponding to the amount of each constituent being separated at the column 84. A signal-processing part 87 measures the amount of pentane in the breath based on the constituent waveform being detected by the detector 85 and the predetermined retention time of the pentane. A display part indicates the amount of the pentane being measured by the signal-processing part 87. As a result, the breath is condensed, and constituent analysis is made by the column with the strong polarity of the liquid phase, thus easily measuring the amount of the pentane in the breath being considered as the marker of the lipid peroxide in an organism.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an apparatus for measuring lipid peroxide in a living body, and more particularly to an apparatus for measuring lipid peroxide in a living body by breath analysis.

[0002]

2. Description of the Related Art Conventionally, to measure lipid peroxide in a living body, lipid peroxide in blood has been measured. When measuring lipid peroxide in blood, the Yagi method was used. In the Yagi method, plasma is heated together with phosphotungstic acid and TBA (thiobarbituric acid), and a red substance produced by combining TBA and MDA (malondialdehyde), which is a decomposition product of lipid peroxide, is measured by fluorescence. is there. This Yagi method can be said to have been established as a standard method for measuring blood lipid peroxide.

[0003]

However, in the measurement by the Yagi method, since the plasma is heated together with the metal, lipid separation is not performed, and MDA existing in the blood from the beginning is ignored. I can't deny the lack of sex.

[0004] In addition, since blood sampling is involved, the subject is forced to "pain blood sampling". For this reason, inspection cannot be performed frequently. Also, it is difficult to carry out examinations for infants.

Further, according to the Yagi method, since a pretreatment such as centrifugation of blood is required, there is an inconvenience that a long time is required until a measurement result is obtained.

[0006]

SUMMARY OF THE INVENTION The object of the present invention is to solve the disadvantages of the prior art and to estimate the amount of lipid peroxide in a living body, in particular, the amount of decomposition of lipid peroxide exceeding the appropriate amount of lipid peroxide in the body of a subject. It is an object of the present invention to provide an in-vivo lipid peroxide measuring device that can perform the measurement.

[0007]

SUMMARY OF THE INVENTION Accordingly, the present invention provides a concentrating section for collecting exhaled breath and concentrating the exhaled breath, a plot column having a strong liquid phase for separating the concentrated exhaled breath components, and A detector for detecting a component waveform corresponding to the amount of each component separated by the column, and the amount of pentane in the exhaled breath based on the component waveform detected by the detector and a predetermined retention time of pentane. And a display unit for displaying the measurement result of the amount of pentane by the signal processing unit.
This aims to achieve the above-mentioned object.

[0008] The amount of lipid peroxide in the living body correlates with pentane in the breath. Therefore, when the amount of pentane in the breath is measured, the amount of lipid peroxide decomposed in the living body can be estimated. If gas chromatography is used to measure pentane in exhaled breath, the measurement time is relatively short, and the quantitative results are linear and easy to handle. However, the amount of pentane in the breath is on the order of pg, and the sensitivity of the detector used in gas chromatography is currently n
Since it is on the order of g, the concentrating unit concentrates expiration. In addition, since the breath contains moisture, a plot column having a strong liquid phase polarity is used. Plot, porous lay
er open tubular) is generally considered to be suitable for the analysis of gases and volatiles, and also resistant to moisture. Then, when detection is performed at a predetermined temperature, flow rate, and column length, pentane and other components are satisfactorily separated in the column, and the detector detects the component waveform of each component. In gas chromatography, when the analysis is performed under the same conditions, the retention time of each component becomes the same, and therefore, identification of which substance has a peak in the component waveform is performed based on the retention time. For this reason, the signal processing unit specifies the pentane waveform from the component waveform and its holding time (retention time), and determines the amount of pentane from its peak area. The component waveform is, for example, a change in a voltage value, and a calibration curve is used to convert this into a quantity of pentane. This calibration curve is prepared in advance using standard gases having a plurality of pentane concentrations. Generally, the calibration curve of gas chromatography is linear. Regarding the correlation between pentane and in vivo lipid peroxide, various techniques can be adopted depending on the purpose of detecting pentane. For example, in the diagnosis of toxemia of pregnancy, if the amount of pentane exceeds a certain threshold, it can be determined that excessive lipid peroxide is generated and decomposed in the living body, so that the threshold amount of pentane is determined. By displaying whether or not the value has been exceeded, it becomes a sample useful for diagnosis. In this diagnosis of preeclampsia, quantification of "pentane" alone with "n-pentane" is sufficient. The term "pentane" is used herein to refer to only n-pentane (normal pentane) or
It is used as a term indicating an ambiguous concept including only i-pentane (isopentane) or both n-pentane and i-pentane. However, many refer to n-pentane.

[0009]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS First, the principle of the in-vivo lipid peroxide measuring apparatus of the present embodiment will be described.

(1). As a marker for lipid peroxide in the living body, n-pentane in breath is measured. The lipid peroxide generated in the living body is processed in the liver and the like, partly decomposed into urine as MDA, and partly decomposed into n-pentane, ethane, ethylene and the like and excreted into exhaled breath. The fact that n-pentane in exhaled breath is a reliable marker of lipid peroxidation in vivo
For example, it has been established in the literature, as described in "Katsu Sagai, Biochemical vo. 150, No. 12, 1978, a new method for measuring native lipid peroxidation by breath gas analysis". Therefore, by measuring the amount of pentane in the breath, the amount of lipid peroxide decomposed in the body can be estimated.

(2). The breath is concentrated and analyzed. The amount of n-pentane in exhaled air is dilute (pg order), and the sensitivity (ng order) of a detector used in gas chromatography.
Cannot be detected. Expired air is detected by concentrating it in an adsorbent.

(3). Use a column that can completely separate isoprene and n-pentane. Specifically, PLOT (porous layer open tubular) suitable for volatile gas analysis
Use a column with strong liquid phase polarity.
PLOT columns are generally considered to be hostile to the analysis of gases and volatiles and are also resistant to moisture. In breath, isoprene is present as a major hydrocarbon component. Because of the short retention time between isoprene and pentane, good separation cannot be achieved with a normal column. However, by using a column with a strong liquid phase under appropriate conditions, isoprene and n-pentane can be well separated.

(4). Use a column that does not deteriorate much when a sample containing moisture is introduced. Generally, it is said that the liquid phase coated on the inner wall of a capillary column is deteriorated when the sample contains moisture. Since a large amount of water is contained in the exhaled breath, water vapor can be used to prevent column deterioration.

(5). Column temperature 80-130
Degrees, preferably 120 degrees. P with strong liquid phase polarity
As a result of the experiment using the LOT column, the column temperature was 110.
It was found that n-pentane and isoprene can be separated well in the range of degrees to 175 degrees. When the column temperature is high, the analysis can be performed in a shorter time, but the resolution is poor, and the deterioration of the column is faster than when the column temperature is low. Conversely, when the column temperature is low, the analysis takes time, but the resolution is improved and the column degradation is slowed. Analyzing in a shorter time is possible by controlling the column temperature by setting up a heating program.
The apparatus becomes complicated due to the control of the flow rate and the temperature. In addition, breath contains ethanol. Since the retention time of ethanol, isoprene and pentane is close, the separation from ethanol must be clear in order to separate pentane well. Isoprene and pentane are separated when the column temperature is in the range of 110 ° to 175 ° C, but it is preferably about 120 ° C to separate n-pentane and ethanol. On the other hand, depending on the configuration of the breath concentrator, ethanol may be adsorbed when the breath is concentrated, and the concentrated breath may not contain ethanol. In this case, it is sufficient to separate isoprene and pentane, so that the column temperature can be 150 ° C.

(6). The identification of the peak appearing on the chromatogram of the breath analysis as n-pentane is performed by comparison with the retention time when a standard gas is analyzed under the same conditions.
That is, when the column length, the flow rate, and the column temperature are constant, the component name of the peak appearing on the chromatogram is specified by utilizing the fact that the retention time of each component is the same. In measuring the retention time of the standard gas,
The components are identified by mass spectrometry.

(7). Quantitative determination of n-pentane is performed by comparing peak area values if it is confirmed that it is within the range of the calibration curve with the standard gas.

Hereinafter, embodiments of the present invention will be described with reference to the drawings.

FIG. 1 is a block diagram showing a configuration of an in-vivo lipid peroxide measuring apparatus according to the present invention. The in-vivo lipid peroxide measuring apparatus includes a concentrating unit 65 that collects the expired air and concentrates the expired air, a plot column 84 having a strong liquid phase that separates the concentrated expiratory components, and the column 8.
A detector 85 for detecting a component waveform corresponding to the amount of each component separated in step 4, and a pentane in the exhaled breath based on the component waveform detected by the detector 85 and a predetermined holding time of the pentane. A signal processing unit 87 for measuring the amount of pentane, and a display unit 88 for displaying the measurement result of the amount of pentane by the signal processing unit 87.

In one embodiment, the signal processing unit 87
A retention time storage means 87A for measuring the retention time of the pentane when the standard gas containing pentane is introduced into the plot column 84 and storing the retention time of the pentane; And a pentane amount calculating means 87B for measuring the amount of the pentane in accordance with the area of the peak including the retention time stored in the retention time storage section 87A when the pentane is introduced.

FIG. 2 is a flowchart showing an example of a process for creating a calibration curve of pentane. First, the signal processing unit 8
7 measures the retention time of the pentane when the standard gas containing pentane is introduced into the plot column 84 (step S1). This identifies pentane, for example, by performing mass spectrometry under the same conditions.
Next, based on the retention time, a plurality of standard gases having different concentrations of pentane are analyzed (step S2), and a peak area of pentane for each concentration is calculated (step S2).
3, means for calculating area by concentration). Further, a calibration curve for the pentane is created based on the area information for each concentration (step S4, calibration curve creating means).

In one embodiment, the signal processing unit 87
However, when the concentration of pentane in the breath exceeds a predetermined concentration, it is determined that there is excessive lipid peroxide for the body of the subject in the body of the subject who has discharged the breath, and the determination result is determined. A determination result display control unit for controlling display on the display unit;

FIG. 3 is an explanatory diagram showing an example of display control on the display unit 88. Pentane in the breath serves as a marker for the amount of lipid peroxide decomposed in the living body. Generally, when the amount of lipid peroxide that exceeds the amount of lipid peroxide that can be normally accumulated in the body is generated, the lipid peroxide is decomposed and the concentration of pentane in the breath increases. Therefore, whether or not excessive lipid peroxide is generated in the body for the patient can be determined based on whether or not the amount of pentane in the breath exceeds the standard amount. This information is useful for diagnosing medical practices.

For this reason, when the calculated amount of pentane is smaller than the predetermined standard amount, the signal processing section 87 displays "Pentane amount below standard" as shown in FIG. Displays the amount of pentane. At this time, based on the relationship between the chemical structure of lipid peroxide and the chemical structure of pentane, it is also possible to calculate and display the amount of lipid peroxide decomposed in vivo. On the other hand, when the amount of pentane is equal to or larger than the standard, the fact that the amount of pentane is equal to or larger than the standard is displayed as shown in FIG. At this time, attention may be called for, for example, setting the background to red.

In the case shown in FIGS. 3 (A) and 3 (B), the number for identifying the subject and the examination date and time may be displayed simultaneously. If the signal processing unit manages the subject's number and the examination date and time and stores them in a storage unit or the like (not shown), it is possible to display a graph in which the vertical axis represents the amount of pentane and the horizontal axis represents time. This display example is shown in FIG. By performing such display, useful information for diagnosis can be transmitted to the doctor in charge of the subject.

FIG. 4 is a partially sectional front view showing the structure of the concentration section. The concentrating unit 65 includes a container holding unit 2 that detachably holds a breath collection container K in which the breath A is sealed, and a collection tube H that collects the components of the breath stored in the breath collection container.
And the expiration stored in the expiration collection container K to pipes 51 and 52
And a pump 11 for sucking the liquid into the collection tube through the pump.
At this time, the exhalation A is dehumidified by the dehumidifier 12. The collection tube H is kept at a constant temperature by a thermostat.

The breath collection container K is a bag-like container made of fluororesin, polyester, or the like that stores breath in a sealed interior. The breath collection container K is maintained at a constant temperature (about 60 ° C.) by a thermostat 90. The thermostat 90 has a heat insulating structure against the outside and a heat source (not shown) for keeping the internal temperature constant. The constant-temperature bath 90 enables the expiration enrichment operation to be performed at a constant temperature for the plurality of exhalation collection containers K, and the effect of the outside air temperature during the enrichment operation can be effectively suppressed.

A dehumidifier 12 is connected between the pipe 51 and the pipe 52 on the downstream side of the container holder 2. The dehumidifier 12 cools the passing exhaled air A in order to remove moisture contained in the exhaled air A.

The downstream end of the pipe 52 is connected to the first end.
Is connected to the collection tube holding section. The first collecting tube holding unit is provided with a holding unit main body 30 having one end connected to an end of the pipe 52 and a sealing member 35a provided at the other end of the holding unit main body 30. And a holding member 35. The holding member 35 penetrates from one side to the other side, is connected at one end to the first collection tube holding portion 3, and has the other end to which one end of the collection tube H can be freely inserted. It is an insertion hole. Two O-rings are provided inside the insertion hole, thereby holding one end of the inserted collection tube H and enhancing sealing performance.

The collecting tube H is a glass tube or a stainless steel tube, and is filled with an adsorbent H1 for adsorbing a breath component. The adsorbent H1 is, for example, a porous polymer, graphite carbon, or the like.

The thermostats 70 and 71 have a function of cooling the collection tube H held in the first collection tube holding portion 3 and the second collection tube holding portion 4 to a predetermined temperature, and A cooling unit 70 and a temperature control unit 71 are provided. The heating and cooling unit 70
2 and the lower side 73, and the upper side 72 and the lower side 73 sandwich the collection tube H. Therefore, the collection tube H can be easily attached to and detached from the heating and cooling unit 70.

The upper side 72 includes a heat insulating material 721 and a heat transfer material 722.
And so on. The lower side 73 includes a heat insulating material 731, a heat transfer material 732, a Peltier element 733, a radiation fin 734, and the like. The heat insulating materials 721 and 731 are made of glass wool, and the heat transfer materials 722 and 732 and the radiation fins 734
Is made of aluminum.

A thermocouple 735 is embedded inside the heat transfer material 732. The thermocouple 735 supplies a voltage corresponding to the temperature t of the heat transfer material 732, that is, the collection tube H, to the temperature control unit 7.
Output to 1. The temperature control unit 71 includes, for example, a microcomputer, a temperature control program stored in a memory of the microcomputer, and a DC voltage power supply. The operation of the temperature control section 71 is to control the conduction of the Peltier element 733 so that the temperature t of the collection tube H output from the thermocouple 735 becomes a constant value tC.

At the downstream side of the incubator 7, the above-mentioned collection tube H
A second collection tube holding unit 4 for holding the other end of the collection tube is provided. The second collection tube holding unit 4 includes a holding unit main body 40 and a holding member 41 connected thereto. The holding member 41 is provided with the holding member 3 of the first collection tube holding portion 3 described above.
5 has the same structure. The holding section main body 40 is connected to the pipe 56 via the joint 56 a and is held by the attaching / detaching mechanism 42.

The attachment / detachment mechanism 42 includes a fixing member 43 for maintaining a fixed distance from the first collection tube holding section 3, and a fixing member 43.
Guide rods 44, 45 protruding toward the first collection tube holding part 3 from the side, a moving member 46 holding the holding part main body 40 and movable along the guide rods 44, 45,
A compression spring 47 for urging the moving member 46 toward the first collection tube holding portion 3. The moving member 46 is
A handle or the like (not shown) is provided and can be moved manually.

In order to connect the collection tube H, first, the moving member 46 is moved toward the fixed member 43 against the restoring force of the compression spring 47. Subsequently, one end of the collection tube H is fitted into the holding member 35 of the first collection tube holding unit 3. Finally, the compression spring 4
The moving member 46 is returned to the collection tube H side by the restoring force of 7.
Thereby, the other end of the collection tube H is fitted into the holding member 41 of the second collection tube holding portion 4. The compression spring 47 firmly fixes the collection tube H by its restoring force.

In order to separate the collecting tube H, first, the moving member 46 is moved toward the fixed member 43 against the restoring force of the compression spring 47. Thereby, the other end of the collection tube H is detached from the holding member 41. Subsequently, one end of the collection tube H is detached from the holding member 35 of the first collection tube holding unit 3. Finally, the moving member 46 is returned to the collection tube H side by the restoring force of the compression spring 47.

The pipe 56 reciprocates in the left-right direction in FIG. 1 at the same time as the second collection pipe holding section 4 when the collection pipe H is attached and detached. For this reason, a connecting portion 57 a having a cylinder structure is formed at one end of the pipe 57 connected in communication with the pipe 56. The connecting portion 57a is a cylindrical member having an inner diameter substantially equal to the outer diameter of the pipe 56, and is capable of inserting the pipe 56 therein and slidable inside the pipe 56. Further, a sealing member such as an O-ring (not shown) is interposed between the connecting portion 57a and the pipe 56,
Thereby, the pipe 56 can freely reciprocate while maintaining airtightness with respect to the pipe 57.

The pressure sensor 13 is connected between the pipe 57 and the pipe 53 via a T-shaped pipe 13a. The pressure sensor 13 is, for example, a piezoelectric type using a piezoelectric effect that generates a voltage when a pressure is applied to a piezoelectric element, and detects a pressure p between the second collection tube holding unit 4 of the exhalation A and the suction pump 11. The corresponding electric signal is transmitted to the operation control unit 8
Output to

On the downstream side of the pressure sensor 13, a mass flow controller 14 as a flow meter for detecting the flow rate f of the exhalation A passing through the collection tube H and outputting it to the operation control unit 8 is provided. Is provided with a flow rate integrating section 15 for integrating the flow rate f.

The mass flow controller 14 is provided with a mass flow meter for measuring the mass (mass flow rate) of gas flowing per unit time by being urged by the suction pump 11 disposed on the downstream side through a pipe 58, and A control valve is provided to hold the set flow rate and output an electric signal corresponding to the measured flow rate to the operation control unit 8 and the flow rate integrating unit 15. The flow integrating unit 15 receives the electric signal of the flow rate output from the mass flow controller 14 and integrates the flow rates to calculate the integrated flow rate.

As described above, the suction pump 11 urges the flow of expiration throughout the apparatus by performing suction, and exhausts the expiration sucked from the pipe 59. The suction pump 11 is a rotary pump driven by a DC motor, and can change the suction force by changing the rotation speed of the DC motor. The DC motor is used because the rotation speed can be easily changed by changing the applied voltage. The pipes 56, 57, 53,
Numerals 58 and 59 denote gas flow paths, both of which are made of fluororesin or the like.

The pump control section 11a comprises, for example, a microcomputer, its program, and a DC voltage power supply. The pump control unit 11a has a function of changing the supply voltage to the suction pump 11 by an operation command signal from the operation control unit 8 or manually. Thereby, the rotation speed of the DC motor of the suction pump 11 is controlled, and the suction force is adjusted.

The operation control unit 8 includes, for example, a sequencer, P
C and the like, and the mass flow controller 14 and the suction pump 1
1 and an operation of a display 8a to be described later. This figure 4
When the concentrating unit shown in (1) is used, the expiration can be satisfactorily concentrated.

FIG. 5 is a flow chart showing the desorption of the concentrated breath in the collecting tube.
It is explanatory drawing which shows an example of the analyzer which measures the amount of pentane using a plot column. The breath analyzer includes a carrier gas cylinder 60 filled with a carrier gas, a standard gas cylinder 62 filled with a standard gas for measuring the retention time of pentane, etc., and a desorber for desorbing the breath component adsorbed on the collection tube. A sample valve 80 for selecting a flow path; a plot column 84 having a strong liquid phase polarity; and a detector 86 for detecting a component separated by the plot column 84 and outputting a component waveform. I have. This detector is connected to a signal processing unit 87, and the processing result of the signal processing unit 87 is displayed on a display unit 88.

The desorption section 65 includes a collection tube support 65A for supporting the collection tube H, a secondary concentration tube 65B for adsorbing the breath sample therein, and a secondary concentration tube support for supporting the secondary concentration tube 65B. And a body 65C. The collecting tube support 65A includes:
A collection tube heater for desorbing the breath sample adsorbed in the collection tube H is incorporated. The secondary concentrating tube support 65C is
A secondary concentrator cooler for adsorbing the breath sample from which the collection tube H has been desorbed to the secondary concentrator tube 65B, and a breath sample adsorbed in the secondary concentrator tube 65B by heating the secondary concentrator tube 65B And a secondary concentrating tube heater. The heater is, for example, an electric heater, and the cooler cools using, for example, liquid nitrogen. When the secondary concentration is performed, the peak of the component waveform generated by the detector clearly appears.

The exhaled air component desorbed by the desorption section 65 is introduced into the port 1 of the sample valve 80 via the pipe 1a. In the position of the valve shown in FIG. 5, the expiration component is introduced into the pre-column 82 via the port 8. The components that have passed through the pre-column 82 are introduced into the main column 84. In the analysis of pentane, for example, the analysis cannot be terminated at the place where pentane appears, and the analysis must be continued until the appearance of hexane having a long retention time, for example. In the example shown in FIG. 5, when pentane passes through the main column 84, hexane stays in the precolumn 82. Therefore, the flow path is changed by rotating the sample valve, and the residual components such as hexane remaining in the precolumn 82 are purged. Thereby, the detection time of pentane can be reduced. Alternatively, hexane or the like may be caused to appear early by raising the column temperature after the elapse of the retention time in which pentane is detected.

To analyze the standard gas, the sample valve 80 is rotated from the position shown in FIG. 5, and the standard gas cylinder 62 is rotated through the pipe 6a, the port 6, the port 5, and the pipe 5a.
Is introduced into the main column 84, which is a plot column. The control unit 83 controls the electromagnetic valve 64
The flow path is changed by opening and closing B and 64C and changing the operating position of the sample valve.

Next, selection of a column will be described with reference to chromatograms obtained by analyzing standard gas and exhaled air.
In the following chromatogram, the column length is 25 m, and the flow rate is 6 ml / min. And FIG. 6 is a chromatogram of a standard gas when the column is set at 140 ° C. using a plot column having a strong liquid phase polarity.
Pentane (nP) and isoprene (I) are completely separated (degree of separation = 2.8). PoraPLOT U 0.53mm id × 25m, d.
f. = 20 μm was used. In this column, the column temperature is 1
Even at 75 ° C., separation was good (separation degree R = 2.
5).

FIG. 7 shows a plot column (PoraPL) having a weak polarity.
The temperature was set to 140 ° C. using OT Q). In this case, isoprene and n-pentane are not separated (separation degree R =
0.75). Medium-polarity plot columns (Po
When raPLOT S) was used, the separation R between isoprene and n-pentane was 0.9, and no separation was achieved. For this reason, in order to analyze the amount of pentane in the breath in the in vivo lipid peroxide measuring device, it is desirable to use a PLOT column having a strong liquid phase polarity. FIG. 8 shows an example of actual analysis of expiration w. As shown in FIG. 8, n-
Pentane n-P and isoprene I are well separated. In the figure, i-P is isopentane.

In order to separate isoprene and pentane from the breath, a plot column having a strong liquid phase is used.
Analysis can be performed at a high column temperature of 175 ° C.
When the column temperature is set to a high temperature, the time required for analysis is shortened because the retention time of each component is shortened, which is preferable. However, if the column temperature is set to a high temperature, the deterioration of the column is accelerated. Therefore, in order to separate isoprene and n-pentane, the temperature of the plot column must be 80 to 175 degrees, preferably 1 degree.
Preferably, the angle is about 50 degrees.

However, subsequent experiments revealed that n-pentane and ethanol did not separate at around 150 degrees. Ethanol and n-pentane
As shown in FIG. 9, when the column temperature is 100 ° C., the separation is complete, and even when the column temperature is 120 ° C., the separation is good (FIG. 10). However, as shown in FIG. 11, when the column temperature is 130 ° C., the degree of separation between n-pentane and ethanol decreases, and when the column temperature is 150 ° C., ethanol and n-pentane are not separated.
For this reason, in order to separate ethanol and n-pentane, the column temperature must be 80 ° C. to 130 ° C., preferably 120 ° C.
It is preferable that the temperature be around ° C. FIG. 13 shows an example of actual analysis of expiration.

On the other hand, ethanol may be lost in the process of concentrating and desorbing breath. That is, when the concentrated air or the desorbing portion adsorbs to the constituent elements and the like, and the second concentrated breath is desorbed, ethanol may not be contained at all. This depends on the configuration of the concentration section and the desorption section. In such a case, there is no need to consider the separation of ethanol and n-pentane, so that the temperature can be set to a temperature at which n-pentane and isoprene can be separated.

FIG. 14 is a graph showing the measurement results of blood lipid peroxide and breath pentane. In order to confirm the relationship between the lipid peroxide in blood and the amount of pentane in the breath, the amount of pentane in the breath was measured at the same time as blood collection, using a pregnant woman as a subject.
The collected blood was measured for the amount of lipid peroxide in plasma by the Yagi method. The following was found from the measurement results shown in FIG.

First, subjects diagnosed with toxemia of pregnancy have high values of both lipid peroxide in blood and pentane in breath.
Therefore, measurement of pentane in the breath can be used as a marker for the amount of lipid peroxide generated or decomposed in the living body. Second, some cases of poisoning during pregnancy have low blood lipid peroxide levels. This suggests that there is an individual difference in the processing capacity of lipid peroxide. In addition, chronological examination revealed that those who had high pentane expiration due to preeclampsia had reduced pentane expiration early after parturition. A close examination of subjects who did not reduce their expiratory pentane level after delivery revealed that the patient had not only preeclampsia but also a mixed preeclampsia with other diseases. This point suggests that the in-vivo lipid peroxide measurement device according to the present embodiment provides useful information for diagnosis.

On the other hand, even if the pentane level in the breath decreased after delivery, the lipid peroxide in the blood did not decrease. This is because lipid peroxide is processed in the liver, etc., partly decomposed into urine as MDA, and partly decomposed into pentane, ethane, ethylene, etc., and metabolized to exhaled breath. For example, it is conceivable to update the processing and excretion functions for this as a biological reaction. Therefore, it is considered that lipid peroxide does not increase and only pentane, which is a decomposition product, increases. In other words, it can be considered that lipid peroxide is not decomposed as long as the living body has a sufficient capacity to process and excrete lipid peroxide, and therefore, the pentane value during exhalation does not increase. Therefore, it is considered that the amount of pentane in the breath indicates the amount of lipid peroxide excessively generated and decomposed in the living body. For this reason,
According to the present embodiment, the adverse effect on the body due to excessive lipid peroxide in the body can be found early and accurately.

Furthermore, it can be interpreted that lipid peroxide in the living body damages the vascular endothelium, causing an increase in blood pressure and renal damage. And it is considered that this change has become chronic in diabetes and hypertension due to arteriosclerosis. From such a point, the in-vivo lipid peroxide measuring apparatus according to the present embodiment, which can quickly and easily inspect that excessive lipid peroxide is generated and decomposed in the living body, can be detected early and diagnosed early. It is useful for.

In the present invention, as described above, breath is concentrated, and a pentane in the breath is detected by using a column having a strong liquid phase, and this pentane is used as a marker for lipid peroxide in a living body. It is characterized by points. Therefore, the method of concentration, the flow path for sending the breath component desorbed to the plot column, and the like can be appropriately changed in design, and are not limited to the configurations shown in FIGS. 4 and 5. For example, at a medical site, a plurality of concentrating units may be provided, and only one breath analyzer shown in FIG. 5 may be provided. In addition, if the switching to the standard gas and the purging of the pre-column are not performed, FIG. The configuration can be further simplified.

[0058]

Since the present invention is constructed and functions as described above, according to the present invention, since breath is concentrated and the component is analyzed using a column having a strong liquid phase polarity, the marker for lipid peroxide in the living body is used. It is possible to easily measure the amount of pentane in the breath, which is considered to be
Since the patient's pain in the test can be eliminated, it can be measured as many times a day as necessary,
Even in infants, etc., lipid peroxide in the living body can be measured, and furthermore, if lipid peroxide is excessively generated in the living body, pentane in the breath will rise, so that diseases related to lipid peroxide will occur. It is possible to provide an unprecedented excellent in vivo lipid peroxide measurement device capable of performing measurement useful for early diagnosis of lipase.

[Brief description of the drawings]

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

FIG. 2 is a flowchart showing an example of a pentane calibration curve creation process according to the configuration shown in FIG. 1;

3A and 3B are explanatory diagrams showing examples of display by the display unit shown in FIG. 1; FIG. 3A shows a case where the amount of pentane is below a standard; FIG. 3B shows a case where the amount of pentane is above a standard; FIG. 3C is a diagram showing the transition of the amount of pentane in a time series.

FIG. 4 is an explanatory diagram showing an example of an exhalation concentration unit in the configuration shown in FIG. 1;

FIG. 5 is an explanatory diagram showing a flow path to a plot column according to the configuration shown in FIG. 1;

FIG. 6: 140 ° C. using strongly polar plot columns
5 is a chromatogram showing an example of analyzing a standard gas in FIG.

FIG. 7: 140 ° C. using a less polar plot column
5 is a chromatogram showing an example of analyzing a standard gas in FIG.

FIG. 8: 150 ° C. using a strongly polar plot column.
5 is a chromatogram showing an example of analyzing the expired air concentrated in FIG.

FIG. 9: 100 ° C. using strongly polar plot columns
5 is a chromatogram showing an example of analyzing a standard gas containing ethanol in FIG.

FIG. 10. 120 using strong polar plot columns.
It is a chromatogram which shows the example which analyzed the standard gas containing ethanol at ° C.

FIG. 11. Using a polar plot column, 130
It is a chromatogram which shows the example which analyzed the standard gas containing ethanol at ° C.

FIG. 12 shows 150 using a highly polar plot column.
It is a chromatogram which shows the example which analyzed the standard gas containing ethanol at ° C.

FIG. 13 is a chromatogram obtained by analyzing breath containing ethanol.

FIG. 14 is an explanatory view showing the relationship between pentane in breath and lipid peroxide in blood.

[Explanation of symbols]

 65 Concentrator 84 Plot column 85 Detector 87 Signal processor 88 Display

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁶ Identification symbol FI // G01N 33/497 G01N 33/497 A (72) Inventor Akira Yanagida 2-1, Sakuranamiki, Tsuzuki-ku, Yokohama-shi, Kanagawa Prefecture Suzuki Inside the Technical Research Institute Co., Ltd. (72) Inventor Mitsuhiro Negami 2-1 Sakuranamiki, Tsuzuki-ku, Yokohama-shi, Kanagawa Prefecture Within the Suzuki Research Institute Co., Ltd. issue

Claims (6)

[Claims] 1. A concentrating unit for collecting and concentrating breath, a plot column having a strong liquid phase for separating components of the concentrated breath, and an amount of each component separated by the plot column. A signal processing unit that measures the amount of pentane in the breath based on the component waveform detected by the detector and a predetermined holding time of pentane, A display unit for displaying a measurement result of the amount of pentane by the signal processing unit. 2. When the concentrated breath contains ethanol, the temperature of the plot column is set to 80 to 130 ° C. when the length of the plot column is set to 25 m. 2. The in vivo lipid peroxide measurement device according to 1. 3. When ethanol is not contained in the concentrated exhaled breath, when the length of the plot column is 25 m, the temperature of the plot column is raised from 80 ° C. to 175 ° C.
2. The in-vivo lipid peroxide measurement device according to claim 1, wherein the measurement is performed in degrees. 4. A retention time storage means for measuring a retention time of the pentane when a standard gas containing pentane is introduced into the plot column and storing the retention time of the pentane; Volume measurement means for measuring the amount of the pentane according to the area of the peak including the retention time stored in the retention time storage unit when the exhaled breath is introduced into the plot column. The in-vivo lipid peroxide measurement device according to claim 1. 5. The retention time storage means for measuring the retention time of the pentane when a standard gas containing pentane is introduced into the plot column and storing the retention time of the pentane, wherein the signal processing unit comprises: A concentration-based area calculating means for measuring the peak area of the component waveform when the gas contains pentane having a predetermined concentration, and measuring the peak area for each of a plurality of concentrations by changing the concentration of the pentane; Calibration curve creation means for creating a calibration curve for the pentane based on the area information for each concentration measured by the area calculation means, and the holding time storage unit when the concentrated breath is introduced into the plot column Quantitative measurement for measuring the amount of pentane according to the area of the peak including the stored retention time and the calibration curve created by the calibration curve creating means. 2. The in-vivo lipid peroxide measurement device according to claim 1, further comprising a determination unit. 6. When the concentration of pentane in the exhaled air exceeds a predetermined concentration, the signal processing unit may include excessive lipid peroxide in the body of the subject who has exhaled the exhaled breath. The in-vivo lipid peroxide measurement device according to claim 4 or 5, further comprising a determination result display control unit that determines that there is an object and controls the display unit to display the determination result on the display unit.