JP2012088201A - Device and method for measuring active oxygen amount - Google Patents

Device and method for measuring active oxygen amount Download PDF

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JP2012088201A
JP2012088201A JP2010235771A JP2010235771A JP2012088201A JP 2012088201 A JP2012088201 A JP 2012088201A JP 2010235771 A JP2010235771 A JP 2010235771A JP 2010235771 A JP2010235771 A JP 2010235771A JP 2012088201 A JP2012088201 A JP 2012088201A
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Akito Shimouchi
章人 下内
Kazutoshi Nose
和利 野瀬
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Abstract

PROBLEM TO BE SOLVED: To measure an amount of active oxygen in a whole living body noninvasively and easily.SOLUTION: A device 900 for measuring an active oxygen amount comprises: hydrogen administration means 100 for administering hydrogen water in order to raise a hydrogen concentration in a living body; emitted hydrogen amount measuring means 200 for measuring a hydrogen amount emitted from the living body; active oxygen amount measuring means 300 for measuring an active oxygen amount in the living body from a difference between a hydrogen amount administered to the living body by the hydrogen administration means 100 and the hydrogen amount emitted from the living body that has been measured by the emitted hydrogen amount measuring means 200.

Description

本発明は、生体内の活性酸素量を測定する装置及び方法に関する。   The present invention relates to an apparatus and method for measuring the amount of active oxygen in a living body.

近年、癌及び生活習慣病等の疾病並びに老化等の原因の1つである生体内に存在する活性酸素を減少させる方法が研究されている。生体内の活性酸素を減少させる方法の1つとして、生体内に水素を投与して、水素と活性酸素とを反応させることが例えば非特許文献1及び非特許文献2等に提示されている。   In recent years, methods for reducing active oxygen present in the living body, which is one of the causes of diseases such as cancer and lifestyle-related diseases and aging, have been studied. As one method for reducing active oxygen in a living body, for example, Non-Patent Document 1 and Non-Patent Document 2 show that hydrogen is administered into a living body and hydrogen reacts with active oxygen.

一方で、前記のような活性酸素が原因となる疾病の予防のために、生体内の活性酸素量を測定する方法が医学分野等の種々の分野において要求されている。   On the other hand, in order to prevent diseases caused by active oxygen as described above, methods for measuring the amount of active oxygen in a living body are required in various fields such as the medical field.

従来、生体内の活性酸素量を測定する方法としては、電子スピン共鳴(Electron Spin Resonance:ESR)法が最も信頼性が高い方法として用いられている。この方法の他に、活性酸素と反応することにより発光する化学物質を用いて、その発光量を測定することによって、活性酸素の量を測定する方法が例えば特許文献1等に提示されている。また、蛍光試薬を用いて活性酸素との反応により生じた蛍光を測定することによって、活性酸素の量を測定する方法が例えば特許文献2及び特許文献3等に提示され、金属錯体と活性酸素との反応により生じる電流を測定することによって、活性酸素の量を測定する方法が例えば特許文献4及び特許文献5等に提示されている。特許文献1〜5に記載されている方法では、生体から血液を採取して、採取した血液に対して測定を行うが、その他に、発光試薬を皮膚等の生体組織の表面に塗布して、局所的に活性酸素の量を測定する方法が例えば特許文献6等に提示されている。また、活性酸素を測定するための針状のセンサを生体に刺して、生体内の血液に接触させることによって、活性酸素の量を測定する方法が例えば特許文献7等に提示されている。   Conventionally, as a method for measuring the amount of active oxygen in a living body, an electron spin resonance (ESR) method has been used as the most reliable method. In addition to this method, for example, Patent Document 1 discloses a method for measuring the amount of active oxygen by using a chemical substance that emits light by reacting with active oxygen and measuring the amount of light emitted. In addition, a method for measuring the amount of active oxygen by measuring fluorescence generated by reaction with active oxygen using a fluorescent reagent is presented in, for example, Patent Document 2 and Patent Document 3, and a metal complex, active oxygen, For example, Patent Document 4 and Patent Document 5 disclose a method for measuring the amount of active oxygen by measuring the current generated by the above reaction. In the methods described in Patent Documents 1 to 5, blood is collected from a living body and measurement is performed on the collected blood. In addition, a luminescent reagent is applied to the surface of a living tissue such as skin, A method for locally measuring the amount of active oxygen is proposed in Patent Document 6, for example. Further, for example, Patent Document 7 discloses a method for measuring the amount of active oxygen by inserting a needle-like sensor for measuring active oxygen into a living body and bringing it into contact with blood in the living body.

国際公開WO03/038429号公報International Publication WO03 / 038429 特開平10−332667号公報JP-A-10-332667 国際公開WO2005/103282号公報International Publication WO2005 / 103282 国際公開WO2004/074828号公報International Publication No. WO2004 / 074828 国際公開WO03/054536号公報International Publication No. WO03 / 045436 特開2000−333907号公報JP 2000-333907 A 特開2002−055078号公報JP 2002-055078 A

Ohsawa I 等、Nature medicine 13,688-694(2007)Ohsawa I et al., Nature medicine 13,688-694 (2007) Sato Y, Kajiyama S 等、Biochem Biophys Res Commun,375(3),346-350(2008)Sato Y, Kajiyama S, etc., Biochem Biophys Res Commun, 375 (3), 346-350 (2008)

しかしながら、従来の活性酸素の量を測定する方法であるESR法は、活性酸素種の同定及びその濃度の測定ができるが、装置が高価且つ大型であるため、導入することが容易でない。また、活性酸素の固定に必要なスピントラップ剤による煩雑な前処理を必要とする。発光又は蛍光を測定することにより活性酸素の量を測定する方法は、採血が必要であるため、針状のセンサを用いる方法と同様に観血的及び侵襲的な方法である。皮膚等に試薬を塗布する方法は、非侵襲的であるが、局所的な測定しかできず、生体内全体の活性酸素の量を測定することはできない。   However, the ESR method, which is a conventional method for measuring the amount of active oxygen, can identify active oxygen species and measure the concentration thereof, but is not easy to introduce because the apparatus is expensive and large. In addition, complicated pretreatment with a spin trap agent necessary for fixing active oxygen is required. Since the method of measuring the amount of active oxygen by measuring luminescence or fluorescence requires blood collection, it is an invasive and invasive method similar to the method using a needle sensor. The method of applying a reagent to the skin or the like is non-invasive, but can only measure locally, and cannot measure the amount of active oxygen in the whole body.

本発明は前記の問題に鑑み、その目的は、非侵襲的且つ簡便に生体内全体の活性酸素の量を測定することにある。   In view of the above problems, an object of the present invention is to non-invasively and easily measure the amount of active oxygen in the entire living body.

本発明に係る活性酸素量測定装置は、生体内の水素濃度を上昇させるために水素水を投与する水素投与手段と、生体から排気された水素量を測定する排気水素量測定手段と、水素投与手段により生体に投与された水素量と、排気水素量測定手段により測定された生体から排気された水素量との差から、生体内の活性酸素量を測定する活性酸素量測定手段とを備えている。   An active oxygen amount measuring apparatus according to the present invention includes a hydrogen administration unit that administers hydrogen water to increase the concentration of hydrogen in a living body, an exhaust hydrogen amount measurement unit that measures the amount of hydrogen exhausted from a living body, and a hydrogen administration And means for measuring the amount of active oxygen in the living body from the difference between the amount of hydrogen administered to the living body by the means and the amount of hydrogen exhausted from the living body measured by the means for measuring the amount of exhaust hydrogen. Yes.

本発明に係る活性酸素量測定装置によると、水素投与手段により生体に投与された水素量と、排気水素量測定手段により測定された生体から排気された水素量との差から、生体内の活性酸素量を測定するため、非侵襲的且つ簡便に生体内全体の活性酸素の量を測定することが可能となる。   According to the active oxygen amount measuring apparatus according to the present invention, the in vivo activity is determined from the difference between the amount of hydrogen administered to the living body by the hydrogen administration means and the amount of hydrogen exhausted from the living body measured by the exhaust hydrogen amount measuring means. Since the amount of oxygen is measured, the amount of active oxygen in the whole living body can be measured noninvasively and simply.

本発明に係る活性酸素量測定装置において、排気水素量測定手段は、生体の呼気排気量を測定する呼気排気量測定手段と、生体の呼気中の水素濃度を測定する呼気水素濃度測定手段とを含み、生体から排気された水素量は、単位時間中に呼気排気量測定手段により測定された生体の呼気排気量と、該単位時間中に呼気水素濃度測定手段により測定された生体の呼気中の水素濃度との積を水素水を飲み終え再度マウスピース又はマスクを装着直後から水素濃度の測定終了時まで積分した値により算出されることが好ましい。   In the active oxygen amount measuring apparatus according to the present invention, the exhaust hydrogen amount measuring means includes an expiratory exhaust amount measuring means for measuring the exhaled breath amount of the living body and an expiratory hydrogen concentration measuring means for measuring the hydrogen concentration in the exhaled breath of the living body. The amount of hydrogen exhausted from the living body includes the amount of exhaled breath of the living body measured by the expiratory exhaust amount measuring means during the unit time and the amount of the exhaled breath of the living body measured by the expiratory hydrogen concentration measuring means during the unit time. It is preferable that the product of the hydrogen concentration is calculated by a value obtained by integrating from the time immediately after the mouthpiece or the mask is worn to the end of the measurement of the hydrogen concentration after drinking the hydrogen water.

この場合、呼気水素濃度測定手段は、呼気水素濃度測定手段は、生体が取り込むための気体が通る吸入部と前記生体から排気された呼気が通る管部とを含む呼吸回路を備えていてもよい。   In this case, the expiratory hydrogen concentration measuring means may include a breathing circuit including an inhalation part through which a gas to be taken in by the living body passes and a pipe part through which the exhaled air exhausted from the living body passes. .

さらに、この場合、管部の端部に、生体から排気された呼気を採集する容器が接続されていてもよい。   Further, in this case, a container for collecting exhaled air exhausted from the living body may be connected to the end of the tube part.

また、管部に水素濃度を測定する装置が設けられていてもよい。   Moreover, the apparatus which measures a hydrogen concentration may be provided in the pipe part.

本発明に係る活性酸素量測定装置において、呼気水素濃度測定手段は、生体の呼気を間欠的に容器に採集し、該容器内の呼気に基づいて水素濃度を測定する装置を含んでもよい。   In the active oxygen content measuring apparatus according to the present invention, the expiratory hydrogen concentration measuring means may include a device that intermittently collects exhaled breath in a living body and measures the hydrogen concentration based on the expiratory gas in the container.

本発明に係る活性酸素量測定装置において、活性酸素は、ヒドロキシルラジカル、スーパーオキサイド、過酸化水素、一重項酸素及び一酸化窒素のうちの少なくともいずれか1つを含むことが好ましい。   In the active oxygen content measuring apparatus according to the present invention, the active oxygen preferably includes at least one of hydroxyl radical, superoxide, hydrogen peroxide, singlet oxygen, and nitric oxide.

本発明に係る活性酸素量測定方法は、生体に水素水を投与する工程(a)と、生体から排気された水素量を測定する工程(b)と、生体に投与された水素量と生体から排気された水素量との差から生体内の活性酸素量を測定する工程(c)とを備えている。   The method for measuring the amount of active oxygen according to the present invention comprises a step (a) of administering hydrogen water to a living body, a step (b) of measuring the amount of hydrogen exhausted from the living body, and the amount of hydrogen administered to the living body and the living body. A step (c) of measuring the amount of active oxygen in the living body from the difference from the amount of exhausted hydrogen.

本発明に係る活性酸素量測定方法によると、生体に投与された水素量と生体から排気された水素量との差から生体内の活性酸素量を測定するため、非侵襲的且つ簡便に生体内全体の活性酸素の量を測定することが可能となる。   According to the method for measuring the amount of active oxygen according to the present invention, the amount of active oxygen in the living body is measured from the difference between the amount of hydrogen administered to the living body and the amount of hydrogen exhausted from the living body. It becomes possible to measure the total amount of active oxygen.

本発明に係る活性酸素量測定方法において、工程(b)は、生体の呼気排気量を測定する工程(b1)と、生体の呼気中の水素濃度を測定する工程(b2)とを含み、生体から排気された水素量は、単位時間中における生体の呼気排気量と生体の呼気中の水素濃度との積を水素水の投与の終了時から水素濃度の測定終了時まで積分した値により算出されることが好ましい。   In the method for measuring the amount of active oxygen according to the present invention, the step (b) includes a step (b1) of measuring the exhalation amount of the living body and a step (b2) of measuring the hydrogen concentration in the exhalation of the living body, The amount of hydrogen exhausted from the body is calculated by integrating the product of the exhaled breath volume of the living body per unit time and the hydrogen concentration in the living body breath from the end of administration of the hydrogen water until the end of measurement of the hydrogen concentration. It is preferable.

この場合、工程(b2)では、生体が取り込むための気体が通る吸入部と生体から排気された呼気が通る管部とを備えている呼吸回路を用いて生体の呼気中の水素濃度を測定してもよい。   In this case, in step (b2), the hydrogen concentration in the exhalation of the living body is measured using a breathing circuit having an inhalation part through which a gas to be taken in by the living body passes and a pipe part through which the exhaled air exhausted from the living body passes. May be.

さらに、この場合、管部の下流側の端部に接続された容器により、前記生体から排気された呼気を採集し、前記容器内の呼気に基づいて水素濃度を測定してもよい。   Further, in this case, exhaled air exhausted from the living body may be collected by a container connected to the downstream end of the tube part, and the hydrogen concentration may be measured based on the exhaled gas in the container.

また、管部を通過中の呼気に基づいて水素濃度を測定してもよい。   Alternatively, the hydrogen concentration may be measured based on the exhaled breath passing through the tube.

本発明に係る活性酸素量測定方法において、工程(b2)では、生体の呼気を間欠的に容器に採集し、該容器内の呼気に基づいて水素濃度を測定してもよい。   In the method for measuring the amount of active oxygen according to the present invention, in step (b2), exhaled breath of the living body may be intermittently collected in a container, and the hydrogen concentration may be measured based on the exhaled breath in the container.

本発明に係る活性酸素量測定方法において、活性酸素は、ヒドロキシルラジカル、スーパーオキサイド、過酸化水素、一重項酸素及び一酸化窒素のうちの少なくともいずれか1つを含むことが好ましい。   In the method for measuring the amount of active oxygen according to the present invention, the active oxygen preferably contains at least one of hydroxyl radical, superoxide, hydrogen peroxide, singlet oxygen, and nitric oxide.

本発明に係る活性酸素量測定方法によると、非侵襲的且つ簡便に生体内全体の活性酸素の量を測定することが可能となる。   According to the method for measuring the amount of active oxygen according to the present invention, the amount of active oxygen in the whole living body can be measured noninvasively and simply.

本発明の第1の実施形態に係る活性酸素量測定装置の構成を示す模式図である。It is a schematic diagram which shows the structure of the active oxygen amount measuring apparatus which concerns on the 1st Embodiment of this invention. 本発明の第1の実施形態に係る活性酸素量測定装置の生体に対する実施態様を示す模式図である。It is a schematic diagram which shows the embodiment with respect to the biological body of the active oxygen content measuring apparatus which concerns on the 1st Embodiment of this invention. 本発明の第1の実施形態に係る活性酸素量測定装置の活性酸素量測定手段の構成を示すブロック図である。It is a block diagram which shows the structure of the active oxygen content measuring means of the active oxygen content measuring apparatus which concerns on the 1st Embodiment of this invention. 本発明の第2の実施形態に係る活性酸素量測定装置の生体に対する実施態様を示す模式図である。It is a schematic diagram which shows the embodiment with respect to the biological body of the active oxygen content measuring apparatus which concerns on the 2nd Embodiment of this invention. 本発明の第1の実施例において測定された呼気中の水素濃度の変化を示すグラフである。It is a graph which shows the change of the hydrogen concentration in the expiration | expired_air measured in the 1st Example of this invention.

(第1の実施形態)
本発明の第1の実施形態に係る活性酸素量測定装置及び方法について図面を参照しながら説明する。
(First embodiment)
An active oxygen amount measuring apparatus and method according to a first embodiment of the present invention will be described with reference to the drawings.

図1に示すように、本発明の第1の実施形態に係る活性酸素量測定装置900は、水素投与手段100と、排気水素量測定手段200と、活性酸素量測定手段300とを備え、これらを組み合わせてなる。   As shown in FIG. 1, an active oxygen amount measuring apparatus 900 according to the first embodiment of the present invention includes a hydrogen administration unit 100, an exhaust hydrogen amount measuring unit 200, and an active oxygen amount measuring unit 300. A combination of

前記水素投与手段100は、内部に水素水120が貯留される密閉容器110を有し、この密閉容器110の上部には開口130が設けられており、開口130は該開口130の密閉及び開放を繰り返して行うことのできる蓋140により閉じられている。密閉容器110は、水素が透過しにくい材料からなり、アルミニウムパウチ等であることが好ましい。   The hydrogen administration means 100 has a sealed container 110 in which hydrogen water 120 is stored, and an opening 130 is provided at the top of the sealed container 110, and the opening 130 seals and opens the opening 130. It is closed by a lid 140 that can be repeated. The sealed container 110 is made of a material that does not easily allow hydrogen to pass through, and is preferably an aluminum pouch or the like.

水素水120は、通常の水よりも多くの水素が溶解している水である。密閉容器110内の水素水120の水素濃度は、生体内の水素濃度を十分に上昇させるために0.2mM〜0.79mM(飽和濃度)程度であることが好ましい。また、水素水120の水素濃度は、水素濃度を計測する際に最も取り扱いやすい約0.4mMであることがより好ましい。このような水素水120を生体に飲水させることにより、生体内に水素を投与することが可能となる。水素水120の水素濃度は、水素水120の調製時から投与時までにおいて変化しているおそれがある。このため、生体に水素水120を投与すると共にその水素水120の一部を取り、ガラス瓶等の密封容器に入れ、例えば約30分間震盪させて、気相及び液相の水素が平衡に達した状態において気相中の少量の気体を注射器で取り、この水素濃度を例えば半導体水素センサ等により測定することが好ましい。   The hydrogen water 120 is water in which more hydrogen is dissolved than normal water. The hydrogen concentration of the hydrogen water 120 in the sealed container 110 is preferably about 0.2 mM to 0.79 mM (saturated concentration) in order to sufficiently increase the hydrogen concentration in the living body. Further, the hydrogen concentration of the hydrogen water 120 is more preferably about 0.4 mM which is most easily handled when measuring the hydrogen concentration. By allowing the living body to drink such hydrogen water 120, hydrogen can be administered into the living body. The hydrogen concentration of the hydrogen water 120 may change from the time of preparation of the hydrogen water 120 to the time of administration. For this reason, the hydrogen water 120 was administered to the living body and a part of the hydrogen water 120 was taken and placed in a sealed container such as a glass bottle, and shaken for about 30 minutes, for example, so that the gas phase and liquid phase hydrogen reached equilibrium. In a state, it is preferable to take a small amount of gas in the gas phase with a syringe and measure the hydrogen concentration with, for example, a semiconductor hydrogen sensor.

前記排気水素量測定手段200は、例えば、生体が口にくわえることができ、生体が取り込むための気体が通る吸入部となる一方向弁付きマウスピース10、及び該一方向弁付きマウスピース10に接続され、排気された呼気が通る管部としての下流管12を含む呼吸回路50と、例えば半導体水素センサ又はガスクロマトグラフィ等である水素濃度測定装置16とを含む呼気水素濃度測定手段70を備えている。さらに、前記排気水素量測定手段200は、呼気排気量測定手段としての流量計15をも備えている。   The exhaust hydrogen amount measuring means 200 includes, for example, a mouthpiece 10 with a one-way valve that can be inserted into the mouth of a living body and serves as an inhalation part through which a gas to be taken in by the living body, and the mouthpiece 10 with a one-way valve. A breathing hydrogen concentration measuring means 70 including a breathing circuit 50 including a downstream pipe 12 as a pipe portion through which the exhausted exhaled gas is connected and a hydrogen concentration measuring device 16 such as a semiconductor hydrogen sensor or a gas chromatography is provided. Yes. Further, the exhaust hydrogen amount measuring means 200 also includes a flow meter 15 as expiratory exhaust amount measuring means.

図2に示すように、一方向弁付きマウスピース10は、生体が口にくわえる部分であるマウスピース部と気体の流路となる気道部とを有している。この気道部の一端側には上流管11が接続され、他端側には生体から排気された呼気が通る管部である下流管12が接続されている。上流管11から一方向弁付きマウスピース10に流れる気体を生体は取り込み、その後、生体が排出した呼気は下流管12に流れる。このようにするために、一方向弁付きマウスピース10には、気体を上流管11から下流管12へ一方向に流すための弁が設けられている。すなわち、この弁により、気体は一方向弁付きマウスピース10を介して上流管11から下流管12にのみ流れ、逆流はしない。上流管11の一方向弁付きマウスピース10と反対側の端部には、ガス供給装置及びリザーババッグ等を接続させてもよく、また、厳密な測定をしない場合は、大気中の水素は微量であるため、特に何も接続させることなく、室内の空気が上流管11内に流れるようにしてもよい。また、上流管11を設けずに、一方向弁付きマウスピース10に生体が取り込むための気体が直接に流れるようにしてもよい。この場合においても弁により、生体の呼気のみが下流管12に流れる。下流管12の一方向弁付きマウスピース10と反対側の端部には呼気を採集するための容器であるバッグ13が接続されている。このバッグ13の材料は、例えば、ポリエチレン、ポリフッ化ビニル及びアルミニウム等を用いることができ、特に、水素が透過しにくい材料であるアルミニウム製のバッグを用いることが好ましく、また、ダグラスバッグ等を用いても構わない。また、下流管12には、前記流量計15が設けられており、流量計15は、例えば、熱線式流量計等であることが好ましい。バッグ13に採集された呼気から、例えば前記水素濃度測定装置16を用いて呼気中の水素濃度が測定される。なお、一方向弁付きマウスピース10を用いる場合、生体の鼻から呼気が漏れることを防ぐノーズクリップ14を、生体の鼻に装着させることが好ましい。   As shown in FIG. 2, the mouthpiece 10 with a one-way valve has a mouthpiece portion which is a portion where a living body is attached to the mouth and an airway portion which becomes a gas flow path. An upstream pipe 11 is connected to one end side of the airway part, and a downstream pipe 12 that is a pipe part through which exhaled air exhausted from the living body passes is connected to the other end side. The living body takes in the gas flowing from the upstream pipe 11 to the mouthpiece 10 with a one-way valve, and then the exhaled air discharged by the living body flows to the downstream pipe 12. In order to do this, the mouthpiece 10 with a one-way valve is provided with a valve for flowing gas from the upstream pipe 11 to the downstream pipe 12 in one direction. That is, by this valve, gas flows only from the upstream pipe 11 to the downstream pipe 12 through the mouthpiece 10 with a one-way valve, and does not flow backward. A gas supply device, a reservoir bag, or the like may be connected to the end of the upstream pipe 11 opposite to the mouthpiece 10 with a one-way valve. Therefore, the indoor air may flow into the upstream pipe 11 without connecting anything. Moreover, you may make it the gas for a living body to take in into the mouthpiece 10 with a one-way valve directly flow without providing the upstream pipe 11. Even in this case, only the exhaled breath of the living body flows to the downstream pipe 12 by the valve. A bag 13, which is a container for collecting exhaled breath, is connected to the end of the downstream pipe 12 opposite to the one-way valved mouthpiece 10. For example, polyethylene, polyvinyl fluoride, aluminum, and the like can be used as the material of the bag 13, and it is particularly preferable to use an aluminum bag that is a material that hardly permeates hydrogen, and a Douglas bag or the like. It doesn't matter. Further, the downstream pipe 12 is provided with the flow meter 15, and the flow meter 15 is preferably, for example, a hot-wire flow meter or the like. From the exhaled breath collected in the bag 13, for example, the hydrogen concentration in the exhaled breath is measured using the hydrogen concentration measuring device 16. In addition, when using the mouthpiece 10 with a one-way valve, it is preferable to attach the nose clip 14 which prevents exhalation from leaking from the living body's nose to the living body's nose.

前記活性酸素量測定手段300は、測定された生体の呼気中の水素量と生体に投与された水素量との差を算出し、活性酸素量を算出する手段である。具体的に、活性酸素量測定手段300は、例えば図3に示すように、生体に投与された水素水120の体積と前記のように投与前に測定した水素濃度との積から算出された投与水素量を入力する投与水素量入力部310と、測定された生体の呼気中の水素量を入力する排出水素量入力部320と、投与水素量入力部310及び排出水素量入力部320に入力した数値から生体内において消費された水素量を算出する生体内水素量演算部330とを備えている。さらに、活性酸素量測定手段300は、生体内水素量演算部330により算出された数値から生体内の活性酸素量を算出する生体内活性酸素量演算部340と、該生体内活性酸素量演算部340により算出された結果を表示する表示部350とを備えている。生体の呼気中の水素量と生体に投与された水素量との差は、生体内の活性酸素と反応して消失した水素量であるため、この値を用いて活性酸素量を算出することができる。なお、ここでいう活性酸素とは、例えば、ヒドロキシルラジカル、スーパーオキサイド、過酸化水素、一重項酸素及び一酸化窒素等を含む。   The active oxygen amount measuring means 300 is a means for calculating the amount of active oxygen by calculating the difference between the measured amount of hydrogen in the breath of the living body and the amount of hydrogen administered to the living body. Specifically, the active oxygen amount measuring means 300 is, for example, as shown in FIG. 3, an administration calculated from the product of the volume of the hydrogen water 120 administered to the living body and the hydrogen concentration measured before administration as described above. The dose hydrogen input unit 310 for inputting the hydrogen amount, the discharged hydrogen amount input unit 320 for inputting the measured hydrogen amount in the expiration of the living body, the dose hydrogen amount input unit 310, and the discharged hydrogen amount input unit 320 are input. And an in-vivo hydrogen amount calculation unit 330 that calculates the amount of hydrogen consumed in the living body from the numerical value. Furthermore, the active oxygen amount measuring means 300 includes an in vivo active oxygen amount calculating unit 340 that calculates the in vivo active oxygen amount from the numerical value calculated by the in vivo hydrogen amount calculating unit 330, and the in vivo active oxygen amount calculating unit. And a display unit 350 for displaying the result calculated by 340. Since the difference between the amount of hydrogen in the breath of the living body and the amount of hydrogen administered to the living body is the amount of hydrogen that has disappeared by reacting with the active oxygen in the living body, the amount of active oxygen can be calculated using this value. it can. The active oxygen here includes, for example, hydroxyl radical, superoxide, hydrogen peroxide, singlet oxygen, nitric oxide and the like.

次に、このような活性酸素量測定装置900を用いて生体内の活性酸素量を測定する使用態様について説明する。   Next, a usage mode in which the amount of active oxygen in a living body is measured using such an active oxygen amount measuring apparatus 900 will be described.

まず、密閉容器110の蓋140を開口130から取り外して開口130を開放させ、密閉容器110に充填されている水素水120を生体に飲水させることにより、生体内に水素を投与する。その後、生体の鼻にノーズクリップ14を着用し、一方向弁付きマウスピース10のマウスピース部を口にくわえた状態で生体に呼吸させる。これにより、生体が吸気する際は、上流管11から一方向弁付きマウスピース10に流れる気体が生体内に取り込まれる。取り込んだ気体を生体が排気する際は、生体から排出された呼気のみが下流管12を流れる。その結果、生体の呼気のみが呼気を採集するための容器であるバッグ13に採集される。生体から排出された呼気は、所定の単位時間毎に間欠的にバッグ13に採集すればよい。所定の単位時間とは、例えば30秒〜10分、特に、活性酸素量の測定精度及び生体の負担を考慮すると、90秒〜3分であることが好ましい。生体から排出された呼気は、単位時間毎に間欠的にバッグ13に採集すればよく、バッグ13の容量は、所定の単位時間内の呼気を採集できる程度の容量であればよく、例えば、容量が100mL〜10Lであるバッグを用いることができる。本実施形態では、一方向弁付きマウスピース10及び下流管12を含む呼吸回路50を用いてバッグ13に呼気を採集するような構成を説明したが、呼吸回路50を用いることなく、生体の呼気を直接にバッグ13等の容器に採集してもよい。また、一方向弁付きマウスピース10を用いる際には、生体の鼻にノーズクリップ14を装着させることが好ましいが、一方向弁付きマウスピース10の代わりに口及び鼻を覆うような一方向弁付きマスクを用いてもよく、この場合、ノーズクリップ14を生体の鼻に装着させる必要はない。   First, the lid 140 of the sealed container 110 is removed from the opening 130, the opening 130 is opened, and the hydrogen water 120 filled in the sealed container 110 is drunk by the living body, whereby hydrogen is administered into the living body. Thereafter, the nose clip 14 is worn on the nose of the living body, and the living body is breathed with the mouthpiece portion of the mouthpiece 10 with the one-way valve held in the mouth. Thereby, when the living body inhales, the gas flowing from the upstream pipe 11 to the mouthpiece 10 with the one-way valve is taken into the living body. When the living body exhausts the taken-in gas, only the exhaled air discharged from the living body flows through the downstream pipe 12. As a result, only the exhalation of the living body is collected in the bag 13 which is a container for collecting exhalation. The exhaled air discharged from the living body may be collected in the bag 13 intermittently every predetermined unit time. The predetermined unit time is preferably, for example, 30 seconds to 10 minutes, particularly 90 seconds to 3 minutes in consideration of the measurement accuracy of the amount of active oxygen and the burden on the living body. The exhaled air discharged from the living body may be collected in the bag 13 intermittently every unit time, and the capacity of the bag 13 may be a capacity that can collect exhaled air within a predetermined unit time. Can be used. In the present embodiment, the configuration in which exhalation is collected in the bag 13 using the breathing circuit 50 including the mouthpiece 10 with the one-way valve and the downstream pipe 12 has been described. May be collected directly in a container such as the bag 13. Moreover, when using the mouthpiece 10 with a one-way valve, it is preferable to attach the nose clip 14 to the nose of the living body, but the one-way valve that covers the mouth and nose instead of the mouthpiece 10 with the one-way valve. An attached mask may be used. In this case, it is not necessary to attach the nose clip 14 to the nose of the living body.

生体から排出された呼気を採集すると共に、下流管12に設けられた流量計15により呼気排気量を測定する。しかしながら、安静時の呼気排気量は、同一の個体において日差変動はほぼ認められないため、流量計15を設けずに、別途、安静時の呼気排気量を測定しても構わない。   While collecting the exhaled air discharged from the living body, the exhaled air exhaust amount is measured by the flow meter 15 provided in the downstream pipe 12. However, since the daily expiratory volume at rest is not substantially changed in the same individual, the expiratory volume at rest may be separately measured without providing the flow meter 15.

前記活性酸素量測定手段300の排出水素量入力部320により入力させる、生体から排出された水素量は、採集された呼気に対して、水素濃度測定装置16を用いて水素濃度を測定し、測定された水素濃度と呼気排気量とを基に算出することができる。なお、水素水を生体に投与する前に、予め、生体の呼気中の水素濃度を測定し、この濃度の値を水素水の投与後に測定した呼気中の水素濃度の値から引くことにより、水素水の投与に起因する呼気中の水素濃度を算出することが好ましい。具体的に、生体から排気された水素量は、所定の単位時間に採集した呼気中の水素濃度と単位時間中の呼気排気量との積を測定開始時から測定終了時まで積分した値により算出される。言い換えると、所定の単位時間に採集した呼気中の水素濃度と単位時間中の呼気排気量との積により単位時間当たりの呼気中の水素量を算出し、各単位時間当たりの呼気中の水素量の総和により、生体から排出された水素量を算出する。ここで、水素量とは、例えば、質量、体積、濃度及びモル数等の一般的な量を含むがこれらに限られない。   The amount of hydrogen discharged from the living body input by the discharged hydrogen amount input unit 320 of the active oxygen amount measuring means 300 is measured by measuring the hydrogen concentration using the hydrogen concentration measuring device 16 with respect to the collected exhaled air. It can be calculated on the basis of the hydrogen concentration and the exhaled exhaust amount. Prior to the administration of hydrogen water to the living body, the hydrogen concentration in the breath of the living body is measured in advance, and the value of this concentration is subtracted from the value of the hydrogen concentration in the breath measured after the administration of the hydrogen water. It is preferable to calculate the hydrogen concentration in the breath due to the administration of water. Specifically, the amount of hydrogen exhausted from a living body is calculated by integrating the product of the concentration of hydrogen in exhaled breath collected during a predetermined unit time and the amount of exhaled breath during a unit time from the start of measurement to the end of measurement. Is done. In other words, the amount of exhaled hydrogen per unit time is calculated by calculating the amount of exhaled hydrogen per unit time by the product of the concentration of exhaled hydrogen collected in a given unit time and the amount of exhaled breath during the unit time. The amount of hydrogen discharged from the living body is calculated by the sum of the above. Here, the amount of hydrogen includes, but is not limited to, general amounts such as mass, volume, concentration, and number of moles.

次に、投与水素量入力部310に生体に投与された水素量を入力し、排出水素量入力部320に生体から排出された呼気中の水素量を入力する。そして、例えば、生体に投与された水素量と算出された生体から排出された水素量との差より、生体内水素量演算部330から生体内において消費された水素量を算出する。生体内活性酸素量演算部340は、例えば、生体内において消費された水素量の値と所定の係数との積を求める、又は生体内において消費された水素量の値を所定の関数に代入することによって、生体内水素量演算部330により算出された数値から生体内の活性酸素量を算出し、算出された生体内の活性酸素量は表示部350に表示される。   Next, the amount of hydrogen administered to the living body is input to the administration hydrogen amount input unit 310, and the amount of hydrogen in the expired air discharged from the living body is input to the discharged hydrogen amount input unit 320. Then, for example, the amount of hydrogen consumed in the living body is calculated from the in-vivo hydrogen amount calculation unit 330 based on the difference between the amount of hydrogen administered to the living body and the calculated amount of hydrogen discharged from the living body. The in vivo active oxygen amount calculation unit 340 obtains, for example, the product of the amount of hydrogen consumed in the living body and a predetermined coefficient, or substitutes the value of the amount of hydrogen consumed in the living body into a predetermined function. Accordingly, the amount of active oxygen in the living body is calculated from the numerical value calculated by the in-vivo hydrogen amount calculating unit 330, and the calculated amount of active oxygen in the living body is displayed on the display unit 350.

以上のようにして、生体内の活性酸素量が測定される。本発明の第1の実施形態に係る活性酸素量測定装置及び方法によると、非侵襲的且つ簡便に生体内全体の活性酸素の量を測定することができる。   As described above, the amount of active oxygen in the living body is measured. According to the apparatus and method for measuring the amount of active oxygen according to the first embodiment of the present invention, the amount of active oxygen in the whole living body can be measured noninvasively and simply.

(第2の実施形態)
以下に、本発明の第2の実施形態に係る活性酸素量測定装置及び方法について図面を参照しながら説明する。なお、本実施形態において第1の実施形態と同一の部材については説明を省略する。
(Second Embodiment)
The active oxygen amount measuring apparatus and method according to the second embodiment of the present invention will be described below with reference to the drawings. In addition, in this embodiment, description is abbreviate | omitted about the member same as 1st Embodiment.

図4に示すように、本実施形態に係る活性酸素量測定装置では、第1の実施形態と異なり、生体から排気された呼気が通る管部である下流管12に流量計15が配設されているだけでなく、該流量計15の近くの下流管12に水素濃度測定装置16が接続されている。なお、下流管12の端部には前記第1の実施形態におけるバッグ13が接続されていない。また、一方向弁付きマウスピースではなく、口及び鼻を覆うような一方向弁付きマスク20が用いられている。一方向弁付きマスク20には、一方向弁付きのマウスピースと同様に、下流から上流への逆流を防ぐ弁が設けられている。なお、一方向弁付きマスク20の代わりに一方向弁付きマウスピースを用いても構わない。水素濃度測定装置16は、下流管12から呼気が流れるように接続された例えば半導体水素センサ等であり、これにより、生体から排出された呼気が下流管12に流れるのと共に呼気排気量及び呼気中の水素濃度を連続的にモニタリングすることができる。このようにすると、呼気を採集するためのバッグは必要ではないが、室内の空気等が下流管12内に水素濃度測定装置16が設けられている領域付近にまで混入しないように、例えば下流管12の長さを十分に長くしてもよいし、他の手段を用いてもよい。このような構成とすることによって、第1の実施形態よりも簡便に生体内の活性酸素量を測定できる。   As shown in FIG. 4, in the active oxygen amount measuring apparatus according to the present embodiment, unlike the first embodiment, a flow meter 15 is disposed in a downstream pipe 12 that is a pipe portion through which exhaled air exhausted from a living body passes. In addition, a hydrogen concentration measuring device 16 is connected to the downstream pipe 12 near the flow meter 15. The bag 13 in the first embodiment is not connected to the end of the downstream pipe 12. Moreover, the mask 20 with a one-way valve which covers a mouth and a nose is used instead of the mouthpiece with a one-way valve. As with the mouthpiece with a one-way valve, the one-way valve-equipped mask 20 is provided with a valve that prevents backflow from downstream to upstream. A mouthpiece with a one-way valve may be used instead of the mask with one-way valve 20. The hydrogen concentration measuring device 16 is, for example, a semiconductor hydrogen sensor or the like connected so that exhaled gas flows from the downstream pipe 12. As a result, exhaled gas discharged from the living body flows into the downstream pipe 12, and the exhaled gas volume and the exhaled gas. The hydrogen concentration of can be continuously monitored. In this way, a bag for collecting exhalation is not necessary, but for example, the downstream pipe is used so that indoor air or the like does not enter the vicinity of the region where the hydrogen concentration measuring device 16 is provided in the downstream pipe 12. The length of 12 may be made sufficiently long, or other means may be used. By setting it as such a structure, the amount of active oxygen in a living body can be measured more simply than 1st Embodiment.

本発明の第2の実施形態に係る活性酸素量測定装置及び方法によると、非侵襲的且つ簡便に生体内全体の活性酸素の量を測定することができる。   According to the active oxygen amount measuring apparatus and method according to the second embodiment of the present invention, the amount of active oxygen in the whole living body can be measured non-invasively and simply.

(第1の実施例)
本発明に係る活性酸素量測定装置及び方法を用いた第1の実施例について説明する。
(First embodiment)
A first embodiment using the apparatus and method for measuring the amount of active oxygen according to the present invention will be described.

本実施例は、成人7名を被験者として、それぞれの生体内の活性酸素量の測定を行った。測定は、早朝に被験者が空腹の状態で行った。   In this example, the amount of active oxygen in each living body was measured using seven adults as subjects. Measurements were taken early in the morning with the subject hungry.

本実施例では呼吸回路を用い、該呼吸回路は、高純度空気配管、ガス流量調整器、リザーババッグ、コネクタ、一方向弁付きマウスピース、蛇腹ホース及びダグラスバッグが順次接続されたものである。また、呼吸回路の一方向弁付きマウスピースよりも下流側(呼気側)に熱線式流量計を設けて、呼気排気量を自動で測定できるようにした。   In this embodiment, a breathing circuit is used, and the breathing circuit comprises a high-purity air pipe, a gas flow regulator, a reservoir bag, a connector, a mouthpiece with a one-way valve, a bellows hose, and a Douglas bag. In addition, a hot-wire flow meter is provided on the downstream side (exhalation side) of the mouthpiece with the one-way valve of the breathing circuit so that the exhalation exhaust amount can be automatically measured.

被験者は安静座位の状態でノーズクリップをつけ、一方向弁付きマウスピースを口にくわえ、口呼吸を行った。まず、水素水を飲む前に、通常時の呼気中の水素濃度(ベースライン)を測定するために、19分間の安静換気を行い、排出された呼気を採集し、以下に説明する方法と同一の方法により呼気中の水素濃度を測定した。続いて、一旦、一方向弁付きマウスピースを口から外し、0.4mM〜0.7mMの水素水500mLを1分間で飲んだ後、60分間の分時呼気排気量と呼気中の水素濃度とを測定した。ここで、呼気中の水素濃度は、ダグラスバッグから2分間隔で呼気を採集し、ガスクロマトグラフ半導体検知法を用いた水素センサにより測定した。なお、水素水の飲水の直前に、実際に飲水する水素水のうち50μLを採取し、22mLパイレックス(登録商標)性容器に入れ、直ちに閉栓し、30分以上の震盪後にヘッドスペース(容器内の気相部)の水素濃度を測定することにより、水素水に溶存している水素濃度を測定した。これにより、実際に飲んだ水素水の水素量を算出した。なお、ヘッドスペースの水素濃度は、呼気中の水素濃度の測定と同様にガスクロマトグラフ半導体検知法により測定した。   The subject put on a nose clip in a resting position, put a mouthpiece with a one-way valve in his mouth, and performed mouth breathing. First, before drinking hydrogen water, in order to measure the hydrogen concentration (baseline) in exhaled air at normal times, perform 19 minutes of rest ventilation, collect the exhaled exhaled air, and the method described below The hydrogen concentration in exhaled breath was measured by the method of Subsequently, the mouthpiece with a one-way valve is once removed from the mouth, and after drinking 500 mL of 0.4 mM to 0.7 mM hydrogen water for 1 minute, the minute expiration exhalation amount for 60 minutes and the hydrogen concentration in the expiration Was measured. Here, the hydrogen concentration in the exhalation was measured with a hydrogen sensor using a gas chromatograph semiconductor detection method by collecting exhalations from the Douglas bag at intervals of 2 minutes. Immediately before drinking hydrogen water, 50 μL of the hydrogen water to be actually drunk is collected, put into a 22 mL Pyrex (registered trademark) container, immediately closed, and after 30 minutes or more of shaking, the headspace (inside the container) The hydrogen concentration dissolved in the hydrogen water was measured by measuring the hydrogen concentration in the gas phase part). Thus, the amount of hydrogen water actually drunk was calculated. The hydrogen concentration in the head space was measured by a gas chromatograph semiconductor detection method in the same manner as the measurement of the hydrogen concentration in exhaled breath.

このように測定した結果、図5に示す呼気水素濃度曲線が得られた。水素水の投与に伴う排気された水素量の総量は、0分(水素水の飲水終了直後)から60分までにおける呼気水素濃度曲線とベースラインとの間の面積と60分間の分時呼気排気量との積として求めた。但し、早朝空腹で未消化食物残渣物が少ない場合は、ベースラインの変動はほとんど認められない場合が多いが、60分時における水素濃度の値がベースライン以下の場合及びベースラインよりも上昇している場合もある。このため、ベースラインのそれぞれの計測値及び60分時の水素濃度の値から回帰直線(ベースライン回帰直線)を求め、呼気水素濃度曲線とベースライン回帰直線との差をとり、これと呼気排気量との積により水素水由来の呼気水素量とした。すなわち、(呼気水素濃度曲線−ベースライン回帰直線)の0分から60分までの積分値と60分間の分時呼気排気量との積により、水素水の投与に伴う排気された水素量の総量を求めることができる。以上により、実際に生体内に取り込んだ水素量と排気された水素量の総量から生体内に取り込まれ活性酸素と反応した水素量が推定できる。その結果、[表1]に示すように、投与された水素のうち平均59±9%が呼気中に排気されることが分かった。   As a result of the measurement, the breath hydrogen concentration curve shown in FIG. 5 was obtained. The total amount of hydrogen exhausted with the administration of hydrogen water is the area between the breath hydrogen concentration curve and the baseline from 0 minutes (immediately after the end of drinking of hydrogen water) to 60 minutes, and 60 minutes of minute exhalation. Calculated as the product of the quantity. However, if there is little undigested food residue due to early morning hunger, there is often little change in the baseline, but the hydrogen concentration at 60 minutes is below the baseline or higher than the baseline. Sometimes it is. For this reason, a regression line (baseline regression line) is obtained from each measured value of the baseline and the hydrogen concentration value at 60 minutes, and the difference between the expiratory hydrogen concentration curve and the baseline regression line is obtained, and this is exhaled. The amount of exhaled hydrogen derived from hydrogen water was determined by the product with the amount. That is, the product of the integral value from 0 minute to 60 minutes of (expiratory hydrogen concentration curve-baseline regression line) and the minute breath exhalation amount for 60 minutes gives the total amount of exhausted hydrogen accompanying administration of hydrogen water. Can be sought. From the above, the amount of hydrogen taken into the living body and reacted with active oxygen can be estimated from the total amount of hydrogen actually taken into the living body and the amount of exhausted hydrogen. As a result, as shown in [Table 1], it was found that an average of 59 ± 9% of the administered hydrogen was exhausted during expiration.

Figure 2012088201
Figure 2012088201

他の実験により皮膚から排気される水素の総量は投与された水素水の0.1%程度とごくわずかであることが分かっている。さらに、水素水の飲水中における水素のリークは最大1%以下であることも分かっている。従って、生体内において、投与された水素のうち約40%が活性酸素により消費されていることが推定できた。成人7名の水素消費量は29±12(SD)nmol/kg(体重)/min又は1.0±0.3(SD)μmol/m2(体表面積)/minであった。この量が活性酸素量に相当するものと推定された。   Other experiments have shown that the total amount of hydrogen exhausted from the skin is negligible, on the order of 0.1% of the administered hydrogen water. It has also been found that hydrogen leakage in drinking water of hydrogen water is no more than 1%. Therefore, it was estimated that about 40% of the administered hydrogen was consumed by active oxygen in vivo. The hydrogen consumption of 7 adults was 29 ± 12 (SD) nmol / kg (body weight) / min or 1.0 ± 0.3 (SD) μmol / m 2 (body surface area) / min. This amount was estimated to correspond to the amount of active oxygen.

(第2の実施例)
以下に、本発明に係る活性酸素量測定装置及び方法を用いた第2の実施例について説明する。
(Second embodiment)
The second embodiment using the active oxygen amount measuring apparatus and method according to the present invention will be described below.

本実施例は、55歳の健康成人男性を被験者として運動負荷に伴う活性酸素量の変化を測定した。被験者は、第1の実施例と同様に早朝の空腹の状態で測定を行った。本実施例においても呼吸回路を用い、該呼吸回路は、ガス流量調整器として大流量のものを用いた以外は第1の実施例と同一である。   In this example, the change in the amount of active oxygen accompanying exercise load was measured in a 55-year-old healthy adult male. The subject measured in the early hungry state in the same manner as in the first example. Also in this embodiment, a breathing circuit is used, and the breathing circuit is the same as that of the first embodiment except that a gas flow rate regulator having a large flow rate is used.

被験者は、まず、自転車エルゴメータの上において安静座位の状態(無負荷、ペダルをこがない状態)で70分間保ち(運動負荷前)、次いで、20ワットの負荷量でペダルを70分間(ベースラインの測定のための10分間を含む)漕ぎ(運動負荷中)、次に無負荷でエルゴメータの上において安静座位の状態で70分間保った(運動負荷後)。これらの時間の呼気中の水素量を測定した。運動負荷前、運動負荷中及び運動負荷後のベースラインの測定は10分間で行い、その最後の1分間で水素水を飲水し、水素水飲水終了直後の時間を0分として、以後60分間の呼気中の水素量の総量を求めた。呼気中の水素量の総量は第1の実施例と同一の方法により算出した。   The subject first kept on the bicycle ergometer in a resting position (no load, not pedaled) for 70 minutes (before exercise), and then held the pedal at a load of 20 watts for 70 minutes (baseline). Rowing (including 10 minutes for measurement) and then kept in a resting position on the ergometer with no load for 70 minutes (after exercise). The amount of hydrogen in the breath during these times was measured. Baseline measurements before, during and after exercise are taken in 10 minutes, drinking hydrogen water in the last minute, with 0 minutes immediately after the end of drinking water, and 60 minutes thereafter The total amount of hydrogen in the exhalation was determined. The total amount of hydrogen in the exhalation was calculated by the same method as in the first example.

その結果、[表2]に示すように、水素水により生体内に取り込まれた水素の総量は、運動負荷前、運動負荷中及び運動負荷後のそれぞれにおいて267μmol、261μmol及び249μmolとほぼ等しく、呼気水素総排気量はそれぞれ159μmol、110μmol及び215μmolとなり、水素消費量はそれぞれ108μmol、152μmol及び34μmolとなった。すなわち、水素消費量は、運動前と比較し運動中に上昇し、運動終了後は運動前よりもさらに低下することが分かった。   As a result, as shown in [Table 2], the total amount of hydrogen taken into the living body by hydrogen water is approximately equal to 267 μmol, 261 μmol and 249 μmol before, during and after exercise, respectively. The total hydrogen displacement was 159 μmol, 110 μmol and 215 μmol, respectively, and the hydrogen consumption was 108 μmol, 152 μmol and 34 μmol, respectively. That is, it was found that the hydrogen consumption increased during exercise compared with before exercise, and further decreased after exercise, compared with before exercise.

Figure 2012088201
Figure 2012088201

本実施例における運動負荷は、早足に相当する有酸素運動の負荷レベルである。運動中は生体内の代謝が亢進するため、活性酸素量は増大するものの、運動後には運動前よりも低下することが明らかとなり、生体にとって有酸素負荷の運動は健康効果があることが推測できた。   The exercise load in the present embodiment is a load level of aerobic exercise corresponding to rapid walking. It is clear that the amount of active oxygen increases during exercise due to increased metabolism in the living body, but it decreases after exercise compared to before exercise. It was.

本発明に係る活性酸素量測定方法は、非侵襲的且つ簡便に生体内全体の活性酸素の量を測定することができ、特に、生体内の活性酸素量を測定する装置及び方法等に有用である。   The method for measuring the amount of active oxygen according to the present invention can noninvasively and simply measure the amount of active oxygen in the entire living body, and is particularly useful for an apparatus and method for measuring the amount of active oxygen in the living body. is there.

10 一方向弁付きマウスピース(吸入部)
11 上流管
12 下流管(管部)
13 バッグ(容器)
14 ノーズクリップ
15 流量計(呼気排気量測定手段)
16 水素濃度測定装置
20 一方向弁付きマスク
50 呼吸回路
70 呼気水素濃度測定手段
100 水素投与手段
110 密閉容器
120 水素水
130 開口
140 蓋
200 排気水素量測定手段
300 活性酸素量測定手段
310 投与水素量入力部
320 排出水素量入力部
330 生体内消費水素量演算部
340 生体内活性酸素量演算部
350 表示部
900 活性酸素量測定装置
10 Mouthpiece with one-way valve (suction part)
11 Upstream pipe 12 Downstream pipe (pipe part)
13 Bag (container)
14 Nose clip 15 Flow meter (exhalation exhaust gas measuring means)
16 Hydrogen concentration measuring device 20 Mask with one-way valve 50 Breathing circuit 70 Expiratory hydrogen concentration measuring means 100 Hydrogen dosing means 110 Sealed container 120 Hydrogen water 130 Opening 140 Lid 200 Exhaust hydrogen amount measuring means 300 Active oxygen amount measuring means 310 Dosing hydrogen amount Input unit 320 Exhaust hydrogen amount input unit 330 In vivo consumed hydrogen amount calculation unit 340 In vivo active oxygen amount calculation unit 350 Display unit 900 Active oxygen amount measuring device

Claims (14)

生体内の水素濃度を上昇させるために水素水を投与する水素投与手段と、
前記生体から排気された水素量を測定する排気水素量測定手段と、
前記水素投与手段により前記生体に投与された水素量と、前記排気水素量測定手段により測定された前記生体から排気された水素量との差から、前記生体内の活性酸素量を測定する活性酸素量測定手段とを備えていることを特徴とする活性酸素量測定装置。
Hydrogen administration means for administering hydrogen water to increase the concentration of hydrogen in the living body;
Exhaust hydrogen amount measuring means for measuring the amount of hydrogen exhausted from the living body;
Active oxygen for measuring the amount of active oxygen in the living body from the difference between the amount of hydrogen administered to the living body by the hydrogen administering means and the amount of hydrogen exhausted from the living body measured by the exhaust hydrogen amount measuring means An active oxygen amount measuring apparatus comprising: a quantity measuring means.
前記排気水素量測定手段は、前記生体の呼気排気量を測定する呼気排気量測定手段と、前記生体の呼気中の水素濃度を測定する呼気水素濃度測定手段とを含み、
前記生体から排気された水素量は、単位時間中に前記呼気排気量測定手段により測定された前記生体の呼気排気量と、該単位時間中に前記呼気水素濃度測定手段により測定された前記生体の呼気中の水素濃度との積を前記水素水の投与の終了時から水素濃度の測定終了時まで積分した値により算出されることを特徴とする請求項1に記載の活性酸素量測定装置。
The exhaust hydrogen amount measuring means includes expiratory exhaust amount measuring means for measuring the exhaled breath amount of the living body, and expiratory hydrogen concentration measuring means for measuring the hydrogen concentration in the exhaled breath of the living body,
The amount of hydrogen exhausted from the living body is the amount of exhaled breath of the living body measured by the expiratory exhaust amount measuring means during a unit time and the amount of the living body measured by the expiratory hydrogen concentration measuring means during the unit time. 2. The active oxygen amount measuring apparatus according to claim 1, wherein the product of the hydrogen concentration in the exhaled breath is calculated by a value obtained by integrating the product from the end of administration of the hydrogen water to the end of measurement of the hydrogen concentration.
前記呼気水素濃度測定手段は、前記生体が取り込むための気体が通る吸入部と前記生体から排気された呼気が通る管部とを含む呼吸回路を備えていることを特徴とする請求項2に記載の活性酸素量測定装置。   3. The breath hydrogen concentration measuring means includes a breathing circuit including an inhalation part through which a gas to be taken in by the living body passes and a pipe part through which exhaled air exhausted from the living body passes. Active oxygen content measuring device. 前記管部の下流側の端部に、前記生体から排気された呼気を採集する容器が接続されていることを特徴とする請求項3に記載の活性酸素量測定装置。   The active oxygen amount measuring device according to claim 3, wherein a container for collecting exhaled air exhausted from the living body is connected to an end portion on the downstream side of the tube portion. 前記管部に水素濃度を測定する装置が設けられていることを特徴とする請求項3に記載の活性酸素量測定装置。   The apparatus for measuring the amount of active oxygen according to claim 3, wherein a device for measuring a hydrogen concentration is provided in the pipe portion. 前記呼気水素濃度測定手段は、前記生体の呼気を間欠的に容器に採集し、該容器内の呼気に基づいて水素濃度を測定する装置を含むことを特徴とする請求項2に記載の活性酸素量測定装置。   The active oxygen according to claim 2, wherein the expiratory hydrogen concentration measuring means includes a device that intermittently collects the exhaled breath of the living body into a container and measures the hydrogen concentration based on the expiratory gas in the container. Quantity measuring device. 前記活性酸素は、ヒドロキシルラジカル、スーパーオキサイド、過酸化水素、一重項酸素及び一酸化窒素のうちの少なくともいずれか1つを含むことを特徴とする請求項1〜6のうちのいずれか1項に記載の活性酸素量測定装置。   The active oxygen includes at least one of hydroxyl radical, superoxide, hydrogen peroxide, singlet oxygen, and nitric oxide, according to any one of claims 1 to 6. The active oxygen amount measuring apparatus described. 生体に水素水を投与する工程(a)と、
前記生体から排気された水素量を測定する工程(b)と、
前記生体に投与された水素量と前記生体から排気された水素量との差から前記生体内の活性酸素量を測定する工程(c)とを備えていることを特徴とする活性酸素量測定方法。
A step (a) of administering hydrogen water to a living body;
Measuring the amount of hydrogen exhausted from the living body (b);
And (c) measuring the amount of active oxygen in the living body from the difference between the amount of hydrogen administered to the living body and the amount of hydrogen exhausted from the living body. .
前記工程(b)は、前記生体の呼気排気量を測定する工程(b1)と、前記生体の呼気中の水素濃度を測定する工程(b2)とを含み、
前記生体から排気された水素量は、単位時間中における前記生体の呼気排気量と該単位時間中の前記生体の呼気中の水素濃度との積を前記水素水の投与の終了時から水素濃度の測定終了時まで積分した値により算出されることを特徴とする請求項8に記載の活性酸素量測定方法。
The step (b) includes a step (b1) of measuring the exhalation volume of the living body, and a step (b2) of measuring a hydrogen concentration in the exhalation of the living body,
The amount of hydrogen exhausted from the living body is the product of the exhalation amount of the living body during the unit time and the hydrogen concentration in the exhalation of the living body during the unit time of the hydrogen concentration from the end of administration of the hydrogen water. The method for measuring the amount of active oxygen according to claim 8, wherein the active oxygen amount is calculated by a value integrated until the end of the measurement.
前記工程(b2)では、前記生体が取り込むための気体が通る吸入部と前記生体から排気された呼気が通る管部とを備えている呼吸回路を用いて前記生体の呼気中の水素濃度を測定することを特徴とする請求項9に記載の活性酸素量測定方法。   In the step (b2), the concentration of hydrogen in the exhaled breath of the living body is measured using a breathing circuit including an inhaling part through which a gas to be taken in by the living body passes and a pipe part through which exhaled air exhausted from the living body passes. The method for measuring the amount of active oxygen according to claim 9. 前記管部の下流側の端部に接続された容器により、前記生体から排気された呼気を採集し、前記容器内の呼気に基づいて水素濃度を測定することを特徴とする請求項10に記載の活性酸素量測定方法。   11. The exhaled air exhausted from the living body is collected by a container connected to the downstream end of the pipe part, and the hydrogen concentration is measured based on the exhaled gas in the container. Method for measuring the amount of active oxygen in 前記管部を通過中の呼気に基づいて水素濃度を測定することを特徴とする請求項10に記載の活性酸素量測定方法。   The method for measuring the amount of active oxygen according to claim 10, wherein the hydrogen concentration is measured based on exhaled air passing through the pipe portion. 前記工程(b2)では、前記生体の呼気を間欠的に容器に採集し、該容器内の呼気に基づいて水素濃度を測定することを特徴とする請求項9に記載の活性酸素量測定方法。   The method for measuring the amount of active oxygen according to claim 9, wherein in the step (b2), exhaled breath of the living body is intermittently collected in a container, and the hydrogen concentration is measured based on the exhaled breath in the container. 前記活性酸素は、ヒドロキシルラジカル、スーパーオキサイド、過酸化水素、一重項酸素及び一酸化窒素のうちの少なくともいずれか1つを含むことを特徴とする請求項8〜13のうちのいずれか1項に記載の活性酸素量測定方法。   The active oxygen includes at least one of hydroxyl radical, superoxide, hydrogen peroxide, singlet oxygen, and nitric oxide, according to any one of claims 8 to 13. The active oxygen content measuring method as described.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014032053A (en) * 2012-08-02 2014-02-20 National Cerebral & Cardiovascular Center Measurement method for in-vivo active oxygen amount
JP2020156884A (en) * 2019-03-27 2020-10-01 株式会社日本トリム Dissolved hydrogen water generation apparatus and dissolved hydrogen water generation method

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014032053A (en) * 2012-08-02 2014-02-20 National Cerebral & Cardiovascular Center Measurement method for in-vivo active oxygen amount
JP2020156884A (en) * 2019-03-27 2020-10-01 株式会社日本トリム Dissolved hydrogen water generation apparatus and dissolved hydrogen water generation method
WO2020195480A1 (en) * 2019-03-27 2020-10-01 株式会社日本トリム Dissolved hydrogen water generation device and dissolved hydrogen water generation method
CN113412128A (en) * 2019-03-27 2021-09-17 日本多宁股份有限公司 Hydrogen-dissolved water generation device and hydrogen-dissolved water generation method
JP7011619B2 (en) 2019-03-27 2022-01-26 株式会社日本トリム Dissolved hydrogen water generator and dissolved hydrogen water generation method

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