JP4385194B2 - Antioxidant power measuring method, antioxidant power measuring device, antioxidant power measuring system, and use thereof - Google Patents

Description

【０１８９】
緑茶摂取２時間後の血中エピガロカテキンガレート濃度を測定したところ、摂取前３±１から６９４±８１ｐｍｏｌ／ｍｌへと顕著に増加していた。
【０１９０】
〔２−３〕フラバノール抗酸化食品（緑茶・林檎縮合型タンニン）による血管内皮機能改善効果
緑茶カテキン類と同様に強い抗酸化活性を有する林檎縮合型タンニン（アップルフェノン）との血管内皮機能改善効果を比較する目的で、喫煙者１名を対象に緑茶・アップルフェノン摂取後に反応性充血時における前腕径の変化を測定し、記録したところ（図３参照）、最大血流量は緑茶の場合は２１．６から３４．８ｍｌ／ｍｉｎ／１００ｍｌ組織量へ増加したが（図４参照）、アップルフェノンの場合は１８．０から４３．２ｍｌ／ｍｉｎ／１００ｍｌ組織量へと顕著に増加した（図５参照）。なお、図中、ＲＨＲは反応性充血を示す。
【０１９１】
〔３〕考察
成人病が生活習慣病と呼び名を変えた今日、第七の栄養素として注目を集めつつある抗酸化物質はその作用により動脈硬化等の生活習慣病の罹患率を大幅に減少させる可能性が指摘されている。動脈硬化の罹患率が高いとされるヨーロッパ諸国域での赤ワイン（アントシアニン）多摂取で有名なフランスで最も罹患率が低いことがその例である。生活習慣病や老化など酸化ストレスが主要因と考えられる健康障害の予防に、抗酸化物質の効果が期待されつつあるが、その体内での効果に関する実証的研究は乏しく、仮説や伝承に基づく健康食品ブームの域を出ない現状である。
【０１９２】
このようにポリフェノール類が活性酸素を除去することが現代では一般論として述べられている。一方、抗酸化物質の抗酸化作用による健康障害の予防とは逆に、喫煙習慣者は、タバコ煙由来に基づく酸化ストレスに曝され、血管内皮細胞の機能障害を通じて、動脈硬化を発症・進展する危険性を有することが指摘されている。
【０１９３】
これらのことを踏まえた上で、何らかのストレスにより血管内皮機能の低下した人体内、および健康な人体の両者において抗酸化物質がどのように機能するかを実証するために今回実験を行った。
【０１９４】
実験結果から、喫煙などの酸化ストレスは血管内皮機能を低下させること、緑茶に含まれる物質により低下した血管内皮機能が改善されること、また、緑茶中の抗酸化物質（フラバノール系であるカテキン）の縮合物質（林檎縮合型タンニン）を含む健康食品でより大きな改善効果を示すことがわかった。このことにより、血管内皮機能は、喫煙などの酸化ストレスに曝されることで低下し、逆に抗酸化物質により改善することがin vivoにおいて示された。この結果は、緑茶やアップルフェノンに含まれる抗酸化物質が、血管内皮機能の障害によって引き起こされる心疾患を予防し得る可能性を示唆する。
【０１９５】
さらに、本実験結果から、本発明で用いた実験方法が、経口摂取した抗酸化食品の生体内における抗酸化機能を、非侵襲的に、また簡便かつ定量的に測定・評価することができることを示している。したがって、かかる実験方法は、種々の利用法に応用できる。
【０１９６】
【発明の効果】
以上のように、本発明にかかる抗酸化物質の抗酸化力測定方法、抗酸化力測定装置、抗酸化力測定システムによれば、被験者が抗酸化物質を摂取する前後において、被験者の前腕部における腕径の変化を測定するだけで、当該抗酸化物質の被験者生体内における抗酸化力を定量的に測定・評価することができるという効果を奏する。さらに、かかる方法、装置、およびシステムは、いずれも簡便であるだけでなく、血液採取などの侵襲的な工程を必要としないため、被験者にとっては苦痛やわずらわしさを感じさせることがなく、また、方法等の実施者にとっても簡便であり、被験者および実施者の両者にとって非常に取り扱いやすいものであるという効果を奏する。
【０１９７】
それゆえ、抗酸化物質のスクリーニング方法や、抗酸化能を謳った健康食品などのin vivo評価に利用することができ、非常に有用な技術である。
【図面の簡単な説明】
【図１】（ａ）は、本発明における実施の形態にかかる抗酸化物質の抗酸化力測定方法の一例を示す工程図であり、（ｂ）は、本発明における実施の形態にかかる抗酸化物質の抗酸化力測定方法のその他の一例を示す工程図である。
【図２】（ａ）は緑茶摂取前後における反応性充血中の前腕部の血流量変化を示すグラフであり、（ｂ）は白湯（温水）摂取前後における反応性充血中の前腕部の血流量変化を示すグラフである。
【図３】（ａ）はコントロール（抗酸化物質摂取前）、緑茶摂取後、アップルフェノン摂取後において、ベースラインにおける前腕部腕径の変化を経時的にグラフ化して記録した図（動脈流入曲線（縦軸：径の変化、横軸：時間））であり、（ｂ）はコントロール、緑茶摂取後、アップルフェノン摂取後において、反応性充血における前腕部腕径の変化を経時的にグラフ化して記録した図（動脈流入曲線（縦軸：径の変化、横軸：時間））であり、（ｃ）はコントロール、緑茶摂取後、アップルフェノン摂取後において、ＮＴＧ舌下投与した場合における前腕部腕径の変化を経時的にグラフ化して記録した図（動脈流入曲線（縦軸：径の変化、横軸：時間））である。
【図４】（ａ）は緑茶摂取前後において、ベースラインにおける前腕部の血流量の変化を示すグラフであり、（ｂ）は緑茶摂取前後において、反応性充血における前腕部の血流量の変化を示すグラフであり、（ｃ）は緑茶摂取前後において、ＮＴＧ舌下投与した場合における前腕部の血流量の変化を示すグラフである。
【図５】（ａ）はアップルフェノン摂取前後において、ベースラインにおける前腕部の血流量の変化を示すグラフであり、（ｂ）はアップルフェノン摂取前後において、反応性充血における前腕部の血流量の変化を示すグラフであり、（ｃ）はアップルフェノン摂取前後において、ＮＴＧ舌下投与した場合における前腕部の血流量の変化を示すグラフである。
【図６】本発明における実施の形態にかかる抗酸化力測定システムの構成の一例を示す機能ブロック図である。
【図７】本発明における実施の形態にかかる抗酸化力測定システムの構成のその他の一例を示す機能ブロック図である。
【図８】本発明における実施の形態にかかる抗酸化力測定装置が行う処理手順の一例を示すフローチャートである。
【図９】本発明における実施の形態にかかる抗酸化力測定装置が行う処理手順のその他の一例を示すフローチャートである。
【図１０】本発明における実施の形態にかかる抗酸化力測定システムの構成のその他の一例を示す機能ブロック図である。
【符号の説明】
２ 抗酸化力測定装置
２’ 抗酸化力測定装置
３ 出力装置
１０ 抗酸化力測定システム
１Ａ 摂取前前腕径変化測定装置
１Ｂ 摂取後前腕径変化測定装置
２１Ａ 摂取前動脈流入曲線作成部（摂取前動脈流入曲線作成手段）
２１Ｂ 摂取後動脈流入曲線作成部（摂取後動脈流入曲線作成手段）
２２ 血流量変化算出部（血流量変化算出手段）
２３ 抗酸化力評価部（抗酸化力評価手段）
２４Ａ 摂取前反応性充血時血流量曲線作成部（摂取前反応性充血時血流量曲線作成手段）
２４Ｂ 摂取後反応性充血時血流量曲線作成部（摂取後反応性充血時血流量曲線作成手段）
51A・51B ストレインゲージプレチスモグラフィー
52A・52B 手首カフ
53A・53B 上腕部カフ[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for measuring the action of an antioxidant substance (for example, antioxidant food) in a living body, and more particularly to a technique suitable for a method for measuring the antioxidant power of an antioxidant substance in vivo. Is.
[0002]
[Prior art]
In recent years, the involvement of oxidative stress due to active oxygen has been pointed out as one of the causes of various diseases and aging including lifestyle-related diseases (adult diseases) such as arteriosclerosis, diabetes, and cancer.
[0003]
The active oxygen here is used medically and biologically, and is a so-called oxygen compound (singlet oxygen, superoxide anion, peroxidation) that has higher reactivity than normal oxygen molecules in the living body. Hydrogen, hydroxy radical). Such active oxygen is produced by macrophages in the human body and is used to attack foreign substances that have entered the body.
[0004]
However, excessive oxygen may be generated in the living body due to various causes such as stress in daily life, smoking, or ultraviolet rays. In such a case, active oxygen having a strong oxidizing action directly injures normal cells or acts on lipids to produce lipid peroxides that cause tissue damage in the living body. Such damage caused to the living body by active oxygen or lipid peroxide is called so-called oxidative stress.
[0005]
The degree of oxidative stress received by a living body can be determined by examining an oxidative stress index in the living body. As a method for examining this oxidative stress index, a method of measuring the blood or urine concentration of F2 isoprostane, which is a lipid excess oxidation product, is generally used (see Non-Patent Document 1). Recently, a method of measuring blood or urine concentration of 8-hydroxydeoxyguanosine, which is an index of DNA oxidative damage, as an oxidative stress index has also been performed (see Non-Patent Document 2).
[0006]
In addition, oxidative stress is thought to have an adverse effect on various organs and tissues in the living body, and among these, it has been suggested to inhibit the function of vascular endothelium. Vascular endothelium is a single cell layer composed of vascular endothelial cells on the innermost side of blood vessels, and is known to produce and secrete various physiologically active substances for the regulation and maintenance of vascular structures. It is an important organ called human endocrine organ.
[0007]
Among the physiologically active substances secreted by the vascular endothelium, nitric oxide (hereinafter sometimes simply referred to as NO) is considered to be the most important substance. NO is a gaseous free radical substance whose production and secretion are promoted by physical stimulation of vascular endothelial cells and stimulation of other physiologically active substances (for example, acetylcholine, serotonin, etc.). Smooth muscle expansion), anti-arteriosclerotic effect (inhibition of endothelial cell damage, inhibition of monocyte deposition / migration, inhibition of platelet adhesion / aggregation, inhibition of smooth muscle cell migration / proliferation, etc.). For this reason, NO is known as a so-called good factor that regulates and maintains the function of blood vessels in vivo.
[0008]
Since this NO and the above-mentioned active oxygen and lipid peroxide are very easy to react, when active oxygen and lipid peroxide are excessively present in the living body, the active oxygen and the like react with NO, and vasodilation of NO Inhibits its action and anti-arteriosclerosis. In addition, lipid peroxides directly damage blood vessels by altering membrane permeability.
[0009]
As described above, active oxygen and lipid peroxide damage the vascular endothelium directly and indirectly, and it is considered that the function of the vascular endothelium is inhibited by oxidative stress.
[0010]
In order to investigate the relationship between such oxidative stress and vascular endothelial dysfunction, studies on biological oxidative stress and endothelial dysfunction associated with regular smoking have been conducted. In this study, urinary concentration of 8-hydroxydeoxyguanosine, which is an index of DNA oxidative damage, is measured as an index of oxidative stress. In addition, plethysmography measures forearm blood flow changes, brachial artery blood vessel diameter changes by high-resolution ultrasonic echo device, and arterial pressure by arterial cannulation, and comprehensively evaluates the measurement results. Is evaluating vascular endothelial function. As a result, it has been found that there is a significant relationship between oxidative stress and vascular endothelial function disorder (see Non-Patent Document 3).
[0011]
Similarly, the relationship between vascular endothelial function and oxidative stress in renovascular hypertension has been examined, and results showing a significant relationship between oxidative stress and vascular endothelial dysfunction have been reported (Non-patent literature). 4).
[0012]
Thus, as oxidative stress is attracting attention as a cause of illness and aging, antioxidant foods having a function of suppressing oxidative stress in living bodies, health foods containing so-called antioxidant substances, as lifestyle-related disease prevention and aging countermeasures. It is supplied to many markets and its sales are increasing.
[0013]
[Non-Patent Document 1]
Reilly M, Delanty N. Lawson JA, Fitzgerald GA. "Modulation of oxidant stress in vivo in chronic cigarette smokers.", Circulation 94: 19-25, 1996
[0014]
[Non-Patent Document 2]
Yin B, Whyatt RM. Perera FP. Randall MC. Cooper TB. Santella RM. Co-authored “Determination of 8-hydroxydeoxyguanosine by an immunoaffinity chromatography-monoclonal antibody-based ELISA.”, Free Radic Biol. Med. 18: 1023-1032, 1995
[0015]
[Non-Patent Document 3]
Masaki Okajima, “Study on bio-oxidative stress and endothelial dysfunction associated with habitual smoking in young Japanese men”, Journal of the Zenzen Medical Society, Kanazawa University, Vol. 110, No. 2, p159-170 (2001)
[0016]
[Non-Patent Document 4]
YUKIHITO HIGASHI et al., `` ENDOTHELIAL FUNCTION AND OXIDATIVE STRESS IN RENOVASCULAR HYPERTENSION '', The New England Journal of Medicine, Vol.346, No.25, June 20, 2002
[0017]
[Problems to be solved by the invention]
Here, since many of the health foods mentioned above are sold for functionality that suppresses oxidative stress, scientific support for the food function is widely available not only for consumers but also for the entire market and society. It has been demanded. Therefore, after antioxidant foods are ingested by humans, how much oxidative stress is suppressed in vivo, that is, a method for measuring and evaluating the antioxidant power of antioxidant foods in vivo simply and quantitatively Is needed.
[0018]
However, the method for examining the functionality of antioxidant foods by examining the oxidative stress index shown in Non-Patent Documents 1 to 4 above requires collecting blood and urine of the subject and analyzing them through a plurality of steps. It is not a simple method. In particular, in the methods described in Non-Patent Documents 3 and 4, the step of collecting blood (collecting blood) and the step of performing arterial cannulation to measure arterial pressure are invasive injuries to the living body with an injection needle or the like. Therefore, there is a problem that the subject feels pain and annoyance and is not a general-purpose method.
[0019]
In addition, although there is knowledge about the relationship between biological oxidative stress and vascular endothelial dysfunction, food is a complex substance and there is also a barrier of digestion and absorption, so the biological action of food factors is scientifically pursued However, it is said that there is a technical difficulty, and a method for measuring and evaluating the antioxidant power of an antioxidant food in vivo simply and quantitatively has not been developed. For this reason, there has been a strong demand for the development of a non-invasive method for measuring and evaluating the antioxidant power of antioxidant foods in vivo in a simple and accurate manner and its utilization method.
[0020]
The present invention has been made in view of the above problems, and its purpose is to measure the antioxidant power of an antioxidant food in vivo simply and quantitatively while being noninvasive to a subject. It is to provide a method, an apparatus, and a system that can be evaluated, and a method of using the same.
[0021]
[Means for Solving the Problems]
As a result of intensive studies in view of the above-mentioned problems, the present inventor has vascular endothelial function only by measuring and evaluating changes in blood flow before and after oral intake of antioxidant food as changes in forearm diameter by plethysmography. We have uniquely found that it is possible to evaluate to what extent the antioxidants can suppress the adverse effects of biological oxidative stress on vasodilator responses, and using this experimental system, It came to complete this invention which can measure and evaluate an antioxidant power.
[0022]
That is, in order to solve the above problems, the method for measuring the antioxidant power of an antioxidant according to the present invention causes reactive hyperemia in the forearm of the subject before the subject ingests the antioxidant, Ingestion forearm diameter change measurement step for measuring change in forearm diameter during the reactive hyperemia, and after the subject ingests the antioxidant, the subject's forearm is caused to undergo reactive hyperemia, and during the reactive hyperemia Change in forearm diameter before and after ingestion of the antioxidant substance obtained by the forearm diameter change measurement step after ingestion measuring the change in forearm diameter, and the forearm diameter change measurement step before intake and the forearm diameter change measurement step after ingestion Blood flow change calculation step for calculating the blood flow change in the forearm during reactive hyperemia before and after the intake of the antioxidant, and the antioxidant obtained by the blood flow change calculation step Based on the blood flow change in forearm during reactive hyperemia before and after ingestion of quality, is characterized by comprising a antioxidant potential measuring step of measuring the antioxidant capacity in vivo of the antioxidant, the.
[0023]
In the above method, first, the change in the forearm diameter during reactive hyperemia is measured before and after the subject ingests the antioxidant substance. Since this forearm diameter change can be regarded as a change in blood flow in the forearm, the change in blood flow during reactive hyperemia before and after the intake of the antioxidant can be calculated from the measurement results.
[0024]
Here, during reactive hyperemia, NO is produced by the vascular endothelium, but NO reacts with active oxygen and is deactivated. However, when an antioxidant is present in the blood, the antioxidant traps active oxygen, so NO is not deactivated, resulting in an increase in blood flow.
[0025]
That is, the antioxidant power in the living body of an antioxidant substance can be measured by calculating the change in blood flow during reactive hyperemia by the above method. According to the above method, it is not necessary to collect blood from the subject, and it is only necessary to measure the diameter of the forearm of the subject. Has the advantage of simplicity.
[0026]
In addition, since the change in blood flow can be determined quantitatively based on the change in forearm diameter before and after the intake of the antioxidant, it is also possible to quantitatively determine the antioxidant power of the antioxidant in the living body. .
[0027]
In addition, the forearm diameter change measuring step before ingestion and the forearm diameter change measuring step after ingestion include attaching an upper arm blood vessel occlusion means to the upper arm portion of the measurement arm of the subject and attaching a forearm diameter measuring means to the forearm portion of the measurement arm. Blocking both the brachial artery and vein with the brachial artery vascular occlusion means to block the arterial inflow and venous outflow to the forearm, releasing only the brachial artery occlusion after a certain period of time, The method includes the step of measuring the change in the forearm diameter by the forearm diameter measuring means during the reactive hyperemia after causing the subject's forearm to become reactive hyperemia by releasing the arterial inflow blockage while occluding. preferable. More preferably, the humeral blood vessel occlusion means is a cuff, and the forearm diameter measuring means is a strain gauge plethysmography, and a pressure of 200 mmHg to 260 mmHg is applied to the humeral artery and vein by the upper arm cuff. By blocking both, the arterial inflow and venous outflow to the forearm are blocked, and after 4 to 8 minutes, only the brachial artery is blocked, and the blockage of the arteries is released while closing the vein. It is preferable to include a step of measuring the change in the forearm diameter by the strain gauge plethysmography after the reactive hyperemia is caused in the forearm of the subject.
[0028]
According to said method, reactive hyperemia can be produced simply and reliably, and the change of the forearm diameter during the reactive hyperemia can be measured correctly. The “subject's measurement arm” refers to the arm on the side of the subject's arm that measures the change in the forearm diameter.
[0029]
The forearm diameter change measuring step before ingestion and the forearm diameter change measuring step after ingestion further include attaching a wrist blood vessel occlusion means to the wrist of the measurement arm of the subject and blocking the inflow of arteries to the human forearm. In addition, it is preferable to include a step of occluding both the artery and the vein by the wrist vascular occlusion means before the arterial inflow blocking is opened. More preferably, the wrist vascular occlusion means is a cuff, and is after systolic blood pressure + 30 mmHg to systolic blood pressure by the wrist cuff after the arterial inflow blocking to the human forearm and before the arterial inflow blocking is released. Preferably, the method includes applying +70 mmHg pressure to occlude both the artery and vein.
[0030]
According to the above method, an arterial blood flow measurement space described later can be created, so that more stable blood flow change data can be obtained. As a result, the antioxidant power of a more stable antioxidant can be measured.
[0031]
In addition, the blood flow change calculation step is based on the measurement result of the change in forearm diameter obtained by the forearm diameter change measurement step before intake and the forearm diameter change measurement step after intake. Compare the arterial inflow curve before and after the intake of antioxidants obtained by the arterial inflow curve creation step and the above-mentioned arterial inflow curve creation step to create curves respectively, and based on the comparison result, the response before and after the intake of antioxidants It is preferable to include a comparison calculation step of calculating a change in blood flow during hyperemia.
[0032]
According to the above method, for example, the measurement result of the change in the forearm diameter before and after the oral intake of the antioxidant food can be expressed in a graph, and the blood flow rate can be simply and quantitatively evaluated simply by comparing the results. Changes can be calculated.
[0033]
Further, the comparison calculation step calculates the maximum slope of the arterial inflow curve before and after the intake of the antioxidant obtained by the arterial inflow curve creation step, respectively, and the maximum slope of the arterial inflow curve before and after the intake of the antioxidant Preferably, this is a step of calculating a change in blood flow by calculating the difference. According to the above method, by determining the difference in the maximum slope of the arterial inflow curve before and after the intake of the antioxidant, it is possible to easily determine the change in blood flow during reactive hyperemia before and after the intake of the antioxidant. it can.
[0034]
In addition, the blood flow rate change calculating step is based on the measurement results of the change in forearm diameter obtained by the forearm diameter change measuring step before intake and the forearm diameter change measuring step after intake. Reactive hyperemia blood flow curve creation process for creating a blood flow curve at the time of hyperemia and reactive hyperemia blood flow curve before and after the intake of antioxidants obtained by the above reactive hyperemia blood flow curve creation process And a comparison calculation step of calculating a change in blood flow during reaction hyperemia before and after the intake of the antioxidant based on the comparison result.
[0035]
The comparative calculation step at this time calculates the area of the figure formed by the reactive hyperemia blood flow curve and the X axis before and after the intake of the antioxidant obtained by the reactive hyperemia blood flow curve creation step, respectively. The difference in the step of calculating the change in blood flow is calculated by calculating the difference in the area of the figure formed by the reactive hyperemia blood flow curve and the X axis before and after the intake of the antioxidant substance. It is preferable. According to the above method, it is possible to simply calculate the change in blood flow during reactive hyperemia before and after the intake of an antioxidant by simply obtaining the difference in the area of the figure before and after the intake of the antioxidant. it can.
[0036]
The antioxidant substance is preferably an antioxidant food. The intake of the antioxidant is preferably oral intake.
[0037]
In addition, in order to solve the above-described problems, the antioxidant substance measuring apparatus for antioxidant substances according to the present invention measures forearm diameter change data before ingestion that measures changes in forearm diameter during reactive hyperemia before ingestion of antioxidant substances. Ingestion based on pre-intake arterial inflow curve creation means based on pre-intake arterial influx curve and ingestion forearm diameter change data measured for forearm diameter change during reactive hyperemia after ingestion of antioxidants Post-intake arterial inflow curve creation means for creating a posterior arterial inflow curve, pre-intake arterial inflow curve created by the pre-intake arterial inflow curve creation means, and post-intake arterial inflow curve created by the post-intake arterial inflow curve creation means A blood flow change calculating means for calculating a change in blood flow during reactive hyperemia before and after the intake of the antioxidant based on the comparison result, and the blood flow change calculating means An anti-oxidant power evaluation means for evaluating the anti-oxidant power in the living body of the anti-oxidant based on the calculation result of the blood flow change during reactive hyperemia before and after the intake of the anti-oxidant. Yes.
[0038]
According to the above configuration, forearm diameter change data before and after oral intake of antioxidant food, obtained using cuff and strain gauge plethysmography, for example, is input directly or via a telecommunication line. Therefore, based on the forearm diameter change data, the change in blood flow in the forearm before and after oral intake of antioxidant food can be calculated simply and quantitatively. Can be determined easily and quantitatively.
[0039]
The blood flow rate change calculating means calculates the area of the figure formed by the pre-intake arterial inflow curve and the X axis, and the area of the figure formed by the post-intake arterial inflow curve and the X axis. It is preferable to calculate the change in blood flow by calculating the difference in the area of the figure formed by the arterial inflow curve and the X axis before and after the intake of the oxidant.
[0040]
Further, the blood flow rate change calculating means calculates the maximum slope of the pre-intake arterial inflow curve and the maximum slope of the post-intake arterial inflow curve, and a difference between the maximum slope of the arterial inflow curve before and after the intake of the antioxidant. It is preferable that the change in blood flow is calculated by calculating.
[0041]
According to said structure, since the change of a blood flow rate can be calculated more simply and correctly, as a result, the antioxidant power in the living body of an antioxidant substance (for example, antioxidant food) is simply and quantitatively determined. Can be sought.
[0042]
In addition, in order to solve the above-described problems, the antioxidant substance measuring apparatus for antioxidant substances according to the present invention measures forearm diameter change data before ingestion that measures changes in forearm diameter during reactive hyperemia before ingestion of antioxidant substances. Based on the pre-intake reactive hyperemia blood flow curve creation means, pre-ingestion reactive hyperemia blood flow curve creation means, and after-intake forearm measured changes in forearm diameter during reactive hyperemia after antioxidant intake Based on the diameter change data, a post-ingestion reactive hyperemia blood flow curve creation means for creating a post-ingestion reactive hyperemia blood flow curve and a pre-intake reactive hyperemia blood flow curve creation means prepared by the pre-intake reactive hyperemia blood flow curve creation means Compare the reactive hyperemia blood flow curve with the post-intake reactive hyperemia blood flow curve created by the means for creating reactive hyperemia after ingestion, and based on the comparison results before and after the intake of antioxidants Reactive charge in Blood flow change calculation means for calculating a change in blood flow in the blood flow, and based on the calculation result of blood flow change during reactive hyperemia before and after the intake of the antioxidant obtained by the blood flow change calculation means The anti-oxidant power evaluation means for evaluating the anti-oxidant power in the living body may be provided.
[0043]
According to the above configuration, forearm diameter change data before and after oral intake of antioxidant food, obtained using cuff and strain gauge plethysmography, for example, is input directly or via a telecommunication line. Therefore, based on the forearm diameter change data, the change in blood flow in the forearm before and after oral intake of antioxidant food can be calculated simply and quantitatively. Can be determined easily and quantitatively.
[0044]
In addition, the blood flow rate change calculating means includes an area of a figure formed by the pre-intake reactive hyperemia blood flow curve and the X axis, and a figure formed by the post-intake reactive hyperemia blood flow curve and the X axis. The change in blood flow is calculated by calculating the area of the figure formed by the reactive hyperemia blood flow curve and the X axis before and after the intake of the antioxidant. preferable.
[0045]
According to said structure, since the change of a blood flow rate can be calculated more simply and correctly, as a result, the antioxidant power in the living body of an antioxidant substance (for example, antioxidant food) is simply and quantitatively determined. Can be sought.
[0046]
Moreover, in order to solve the above-described problems, the antioxidant substance measuring system for antioxidant substances according to the present invention includes the antioxidant substance measuring apparatus for antioxidant substances described above, and the forearm portion of the subject before taking the antioxidant substances. Inducing forearm diameter change measuring device for measuring forearm diameter change during the reactive hyperemia and ingestion forearm diameter change measuring device, after taking the antioxidant substance, to cause reactive hyperemia in the subject, A post-ingestion forearm diameter change measuring device for measuring a change in forearm diameter during the reactive hyperemia, and an output device for outputting the antioxidant power of the antioxidant measured by the antioxidant power measuring device; It is characterized by having.
[0047]
According to said system, the antioxidant power in the body of an antioxidant substance (for example, antioxidant foodstuff) can be calculated | required simply and quantitatively simply and quantitatively.
[0048]
Moreover, it is preferable that the forearm diameter change measuring device before ingestion and the forearm diameter change measuring device after ingestion each include a strain gauge plethysmography, a wrist cuff, and an upper arm cuff.
[0049]
In addition, in order to solve the above problems, a method for screening an antioxidant substance according to the present invention includes a method for measuring the antioxidant power of the antioxidant substance, an antioxidant power measuring device for the antioxidant substance, and an antioxidant substance. One of the antioxidant power measuring systems is used to screen for antioxidant substances.
[0050]
According to said method, the antioxidant substance which exhibits the outstanding antioxidant power in the living body can be selected simply and reliably.
[0051]
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a method, apparatus, and system for measuring and evaluating the antioxidant power of an antioxidant substance (for example, an antioxidant food) simply and quantitatively, and a method for using the same. For this reason, according to the present invention, it is possible to provide consumers and society with information such as how much antioxidant foods and health foods that are supplied to the market exhibit antioxidant power in living bodies. Such information can be used as a guide for consumers to select antioxidant foods and health foods that are effective in preventing lifestyle-related diseases and preventing aging. It can be said that this is a very useful invention with a strong social impact.
[0052]
Hereinafter, the method for measuring the antioxidant power of an antioxidant according to the present invention will be described, and then the apparatus, system, and usage will be described. Note that the present invention is not limited to this.
[0053]
(1) Method for measuring antioxidant power of antioxidants
The present inventor can easily and easily evaluate the antioxidant power of an antioxidant food in a living body by measuring a change in forearm diameter during reactive hyperemia using strain gauge plethysmography before and after oral intake of the antioxidant food. It was found that it can be measured quantitatively. This method is not only non-invasive for the subject, but also very simple for the practitioner.
[0054]
That is, as shown in FIG. 1, the method for measuring the antioxidant power of an antioxidant according to the present invention includes at least a forearm diameter change measuring step before intake, a forearm diameter change measuring step after intake, a blood flow change calculating step, an antioxidant, It only has to include a force measurement step.
[0055]
First, the outline of the method for measuring the antioxidant power of an antioxidant according to the present invention will be briefly described. It should be noted that the outline of the method described here has many parts common to apparatuses and systems described later.
[0056]
In the above method, first, before and after the subject ingests the antioxidant, reactive hyperemia is caused in the forearm of the subject, and the change in the forearm diameter of the subject is measured during the reactive hyperemia. “Reactive hyperemia” refers to a state in which the blood flow is significantly increased when the coronary artery is temporarily occluded and reopened. NO is released in a large amount from the blood vessels and relaxes vascular smooth muscle, and is also referred to as an intravascular independent vasodilatory reaction. At the time of this reperfusion of blood, active oxygen is also generated, which works to reduce the action of NO. However, when an antioxidant present in the living body functions during this reactive hyperemia, the antioxidant does not reduce the effect of NO by trapping active oxygen, resulting in an increase in blood flow. It will be.
[0057]
If the blood flow rate increases, the blood vessels (arteries) in the forearm portion increase accordingly, and as a result, the forearm diameter also increases. In other words, by measuring the change in forearm diameter during reactive hyperemia before and after the intake of antioxidant substances, it is possible to measure the change in blood flow in the forearm during reactive hyperemia before and after the intake of antioxidant substances. it can. That is, before and after the intake of the antioxidant substance, if the change in the forearm diameter during reactive hyperemia is large, it can be considered that the blood flow during reactive hyperemia is increasing. Since this phenomenon can be judged to be because the effect of NO is maintained in the body during reactive hyperemia, it can be evaluated that the antioxidant substance exhibits the antioxidant power. On the other hand, if the change in forearm diameter during reactive hyperemia is small before and after intake of the antioxidant substance, it can be considered that the blood flow during reactive hyperemia has not increased. Since it can be judged that the effect of NO is reduced, it can be evaluated that the antioxidant substance does not exhibit the antioxidant power in vivo.
[0058]
Therefore, according to the above method, the in vivo antioxidant power of an antioxidant substance (for example, antioxidant food) can be quantitatively measured by a non-invasive and simple method of measuring the arm diameter of the forearm. Will be able to.
[0059]
Below, each process in the antioxidant power measuring method of the antioxidant substance concerning this invention is demonstrated in detail.
[0060]
(1-1) Forearm diameter change measurement process before ingestion, Forearm diameter change measurement process after ingestion
The forearm diameter change measuring step before ingestion is a step for measuring the change in forearm diameter during the reactive hyperemia by causing reactive hyperemia in the forearm of the subject before the subject ingests the antioxidant. Specific conditions and other configurations are not particularly limited.
[0061]
The forearm diameter change measuring step after ingestion is a step in which after the subject ingests the antioxidant substance, the subject's forearm is subjected to reactive hyperemia and the change in forearm diameter during the reactive hyperemia is measured. The specific configuration is not particularly limited.
[0062]
Here, the forearm diameter change measurement process before ingestion and the forearm diameter change measurement process after ingestion differ only in whether the forearm diameter measurement is performed before or after the intake of the antioxidant, Other methods and conditions are the same. For this reason, the same method and conditions will be described in common.
[0063]
First, as the “subject”, in the present invention, a human (human) is exclusively targeted, but the present invention is not particularly limited thereto, and other animals (for example, mammals) that can measure the arm diameter are not limited thereto. It can also be applied to. In addition, the “forearm diameter” refers to a diameter in a cross section perpendicular to the long axis direction of the forearm portion of the subject or a length of one circumference.
[0064]
The phrase “before the subject ingests the antioxidant” may be any time as long as it is before the subject ingests the antioxidant, as the wording is not particularly limited.
[0065]
“After the subject ingests the antioxidant substance” may be any time after the subject ingests the antioxidant substance as long as the antioxidant substance exhibits an antioxidant action in the body of the subject. In other words, after ingesting the antioxidant substance, it may be from the start of exerting the antioxidant action in the living body before metabolic decomposition or excretion outside the body. The specific time varies depending on the kind of antioxidant substance and the ingestion method. For example, in the case of taking an antioxidant substance orally, it takes 10 minutes to 6 hours after ingesting the antioxidant substance. Particularly preferred is between 30 minutes and 4 hours.
[0066]
“To cause reactive hyperemia in the subject's forearm” means that the artery flowing into the subject's forearm is artificially occluded and opened after a certain period of time, resulting in a significant increase in blood flow in the subject's forearm. To create a state that has In addition, “to measure the change in the forearm diameter during the reactive hyperemia” is to measure the change in the arm diameter of the forearm while the reactive hyperemia occurs. As a method of “measuring the forearm diameter change”, the arm diameter may be measured at any position of the forearm, but more preferably, the forearm diameter change is measured at the position where the diameter is the thickest. Is preferred. This is because the change in the diameter can be accurately measured by measuring the change in the forearm diameter at the position where the diameter is the thickest. In addition, the diameter can be measured accurately and reproducibly by using a device or apparatus that can measure changes in the forearm diameter (for example, changes in thickness or length).
[0067]
As described above, as a method of “causing reactive hyperemia in the subject's forearm and measuring a change in forearm diameter during the reactive hyperemia”, as described above, the subject's artery is temporarily occluded and then released However, specific methods, conditions, and the like in this case can be conventionally known methods and are not particularly limited.
[0068]
Specifically, in the forearm diameter change measuring step before ingestion and the forearm diameter change measuring step after ingestion, the upper arm blood vessel occlusion means is attached to the upper arm portion of the measurement arm of the subject, and the forearm diameter measuring means is attached to the forearm portion of the measurement arm. And blocking both the brachial artery and vein by the brachial vessel occlusion means, blocking the arterial inflow and venous outflow to the forearm, and releasing only the brachial artery occlusion after a certain period of time. A step of measuring a change in the forearm diameter by the forearm diameter measuring means during the reactive hyperemia after causing the subject's forearm to open up by blocking the arterial inflow while blocking the vein. It is preferable to include. Reactive hyperemia in the forearm of the subject simply and reliably by occluding or opening the artery flowing into the forearm of the subject, that is, the artery of the upper arm of the subject by vascular occlusion means according to the above procedure Can be generated. And the change of the forearm diameter can be accurately measured by the forearm diameter measuring means during the reactive hyperemia.
[0069]
Here, “blocking” an artery or the like means to artificially stop the blood flow in the blood vessel, and its specific method is not particularly limited. For example, a method of applying pressure from the outside Can be mentioned. Also, “releasing” means releasing the occluded state of the blood vessel that has been once occluded and regenerating the blood flow. For example, a method of releasing the pressure applied from the outside can be mentioned.
[0070]
Further, the “upper arm blood vessel occlusion means” may be any device that can non-invasively open or open the blood vessel of the upper arm portion of the subject, and the specific configuration thereof is not particularly limited. For example, a blood pressure cuff can be mentioned. In addition, the “forearm diameter measuring means” may be any means that can noninvasively measure the arm diameter of the subject's forearm, and its specific configuration is not particularly limited. Examples include strain gauge plethysmography.
[0071]
In the above method, the forearm diameter is measured by closing or opening the artery while the vein is closed, but this makes it possible to focus only on the blood flow that increases due to the inflow of arterial blood flow. It is possible to accurately measure forearm diameter changes.
[0072]
In addition, `` after measuring the forearm diameter measurement means by the forearm diameter measurement means during the reactive hyperemia after the occurrence of reactive hyperemia '' means to measure the forearm diameter change during the reactive hyperemia, Although specific time etc. are not specifically limited, About 10 minutes are preferable immediately after producing reactive hyperemia, and 5 to 200 seconds are especially preferable after producing reactive hyperemia.
[0073]
More specifically, the upper arm vascular occlusion means is a cuff, and the forearm diameter measuring means is strain gauge plethysmography, and the upper arm cuff applies a pressure of 200 mmHg to 260 mmHg by the upper arm cuff. By blocking both the vein and the vein, the inflow of the artery to the forearm and the outflow of the vein are blocked. After 4 to 8 minutes, only the brachial artery is released and the blockage of the artery is released while blocking the vein. It is preferable to include the step of measuring the change in the forearm diameter by the strain gauge plethysmography during the reactive hyperemia after the reactive hyperemia has occurred in the forearm of the subject.
[0074]
When a cuff is used as the upper arm blood vessel occlusion means, the upper arm blood vessel can be easily occluded or opened, and reactive hyperemia can be easily generated. In addition, when strain gauge plethysmography is used as a forearm diameter measurement means, the tension gage (strain gauge) of the visceral mercury wound around the forearm of the subject measures the blood flow volume due to the vascular endothelium-dependent vasodilatation reaction (reactive hyperemia). A change in expansion / contraction of the forearm accompanying a change can be measured as a change in the length of the arm diameter. Furthermore, more accurate and stable measurement can be performed by setting detailed conditions as described above. For this reason, data can be acquired accurately and reproducibly by carrying out the method under the above conditions.
[0075]
Further, the forearm diameter change measuring step before ingestion and the forearm diameter change measuring step after ingestion are performed by attaching a wrist vascular occlusion means to the wrist of the measurement arm of the subject, and after blocking the arterial inflow to the human forearm, and Preferably, the method further comprises the step of occluding both the artery and vein by the wrist vascular occlusion means before the arterial inflow blocking is opened.
[0076]
According to the above method, it is possible to create an arterial blood flow measurement space in which only arterial blood flow without venous outflow occurs between the upper elbow of the subject and the wrist. Accordingly, attention can be paid only to arterial blood flow inflow in the arterial blood flow measurement space, and a change in blood flow due to the arterial blood flow in the arterial blood flow measurement space can be accurately measured as a change in forearm diameter. Further, the “wrist blood vessel occlusion means” is not particularly limited as long as it can non-invasively open or open the blood vessel of the wrist of the subject's measurement arm. For example, a blood pressure cuff can be mentioned.
[0077]
More specifically, the wrist vascular occlusion means is a cuff, and is after systolic blood pressure +30 mmHg to systolic phase by the wrist cuff after the arterial inflow blocking to the human forearm and before the arterial inflow blocking is released. Preferably, the method includes the step of applying pressure of blood pressure +70 mmHg to occlude both arteries and veins. By the above method, the artery and vein on the wrist of the subject can be reliably and simply blocked, and an arterial blood flow measurement space can be created. The term “systolic blood pressure” refers to the value of the peak of the wave when the arterial blood pressure is regarded as a wave pressure using heartbeat as an energy source. “Pressure of systolic blood pressure + 30 mmHg to systolic blood pressure + 70 mmHg” refers to a pressure between the pressure obtained by adding 30 mmHg to the systolic blood pressure and the pressure obtained by adding 70 mmHg to the systolic blood pressure.
[0078]
The order of performing the forearm diameter change measurement process before ingestion and the forearm diameter change measurement process after ingestion is not particularly limited, for example, after the forearm diameter change measurement process after ingestion, the forearm diameter change before ingestion is performed. A measurement process may be performed. That is, the forearm diameter change measuring step before ingestion is performed before the antioxidant is ingested into the subject's body in principle, but after the antioxidant is ingested into the subject's body. However, it may be performed after a period of time has passed in which it is recognized that the in vivo effect of the ingested antioxidant substance has disappeared.
[0079]
Therefore, after the subject ingests the antioxidant, the forearm diameter change measurement process after ingestion is performed, the forearm diameter change data after ingestion is acquired, the forearm diameter change measurement process before ingestion is performed after a certain period of time, and the forearm before ingestion Diameter change data can also be acquired. Thus, even when the forearm diameter change measuring step before intake after the forearm diameter change measuring step after intake is almost the same as when the forearm diameter change measuring step after intake is performed after the forearm diameter change measuring step before intake This is because a result is obtained.
[0080]
(1-2) Blood flow change calculation step
The blood flow change calculation step is based on the measurement result of the change in the forearm diameter obtained by the forearm diameter change measurement step and the after-take forearm diameter change measurement step, during reactive hyperemia before and after the intake of the antioxidant. Any process may be used as long as it is a process of calculating the blood flow change in the forearm, and the specific conditions and other configurations are not particularly limited.
[0081]
As a method of “calculating the change in blood flow based on the measurement result of the change in the forearm diameter”, for example, the change in the forearm diameter during the reactive hyperemia before and after the intake of the antioxidant is directly taken before and after the intake of the antioxidant. A method considered to be a change in blood flow during reactive hyperemia is mentioned. In addition, there is a method of calculating the change in blood flow by calculating the maximum value of the forearm diameter (maximum value on the Y axis) before and after taking the antioxidant substance, and calculating the difference between the maximum values. It is done.
[0082]
Furthermore, as described above, since the measurement result of the change in the forearm diameter before and after the intake of the antioxidant substance can be regarded as the change in the blood flow as it is, for example, along with the increase in the blood flow during the reactive hyperemia Thus, the forearm diameter increased and the forearm diameter at the time of returning to the original are measured to create an arterial inflow curve, and by reading this, the change in blood flow can be calculated as a result.
[0083]
That is, in order to calculate the change in blood flow before and after the subject ingests the antioxidant, the blood flow change calculation step was obtained by the forearm diameter change measurement step before intake and the forearm diameter change measurement step after intake. Based on the measurement result of the change in forearm diameter, an arterial inflow curve creation step for creating an arterial inflow curve before and after the intake of the antioxidant, and an artery before and after the intake of the antioxidant obtained by the arterial inflow curve creation step, respectively It is preferable to include a comparison calculation step of comparing inflow curves and calculating a change in blood flow volume during reaction hyperemia before and after intake of the antioxidant based on the comparison result. In other words, as shown in FIG. 1A, the blood flow rate change calculating step preferably includes an “arterial inflow curve creating step” and a “comparison calculating step”.
[0084]
The “arterial inflow curve creation step” is based on the measurement result of the change in the forearm diameter during reactive hyperemia before the subject ingests the antioxidant obtained by the above-mentioned forearm diameter change measurement step before intake. Based on the measurement result of the change in the forearm diameter during reactive hyperemia after the subject ingested the antioxidant obtained by the above-mentioned forearm diameter change measurement step after the intake, Any method may be used as long as it is a step of creating an arterial inflow curve after ingestion of an antioxidant substance. A method for creating the arterial inflow curve may be a conventionally known method and is not particularly limited. More specifically, for example, a strain gauge / photoplethysmograph EC6 (manufactured by DEHokanson) or a non-invasive blood vessel analysis system NIVP3 (manufactured by DEHokanson) can be used for simplicity.
[0085]
The “arterial inflow curve” as used in the present invention refers to the measurement result of the change in the forearm diameter obtained by the forearm diameter change measuring step before intake or the forearm diameter change measuring step after intake, and the vertical axis (Y axis) is the forearm. This refers to a curve expressed when recording and graphing with the length (or thickness) of the diameter and the horizontal axis (X axis) as time (for example, seconds). For example, the curve etc. which are shown to Fig.3 (a)-(c) shown in the Example mentioned later are mentioned. Note that the term “curve” here refers to a curve having a broad meaning including not only a point connecting points with a smooth curve but also a point connecting points with a straight line.
[0086]
In addition, the “comparison calculation step” compares the arterial inflow curve before the intake of the antioxidant substance and the arterial inflow curve after the intake of the antioxidant prepared by the above arterial inflow curve creation step, and the comparison result The specific method is not particularly limited as long as it is a step of calculating the change in the blood flow during reactive hyperemia before and after the intake of the antioxidant substance.
[0087]
As described above, the change in the forearm diameter of the subject and the blood flow flowing into the forearm artery are closely related. Therefore, before and after the subject ingests the antioxidant, the forearm during reactive hyperemia before and after the subject ingests the antioxidant by comparing the arterial inflow curve representing the change in the forearm diameter of the subject over time. The change in the arterial blood flow can be calculated.
[0088]
As a specific method for comparing arterial inflow curves before and after taking antioxidants and calculating changes in blood flow, for example, (1) arterial inflow curves and X-axis before taking antioxidants are formed. The area of the figure to be formed and the area of the figure formed by the arterial inflow curve after the intake of the antioxidant and the X axis are calculated and compared, and the blood during reactive hyperemia before and after the intake of the antioxidant is calculated from the difference in the area (2) Calculate the maximum slope of the arterial inflow curve before the intake of antioxidants and the maximum slope of the arterial inflow curve after the intake of antioxidants, and the difference between these maximum slopes The method of calculating the change of blood flow from the above is mentioned.
[0089]
That is, the comparison calculation step calculates the area of the figure formed by the arterial inflow curve and the X axis before and after the intake of the antioxidant obtained by the arterial inflow curve creation step, respectively, and before and after the intake of the antioxidant It is preferable to calculate the change in blood flow by calculating the difference in the area of the figure formed by the arterial inflow curve and the X axis. Examples of the method of “calculating the change in blood flow by calculating the difference in area” include a method in which the difference in area is directly converted into a numerical value and calculated as a change in blood flow.
[0090]
Here, “the figure formed by the arterial inflow curve and the X axis” is, for example, when the arterial inflow curve is graphed, the starting point of the arterial inflow curve, that is, the point where the measurement of the change in the forearm diameter is started, There is an end point of the arterial inflow curve, that is, a point at which the change of the forearm diameter has been measured, a straight line connecting the start point and the X axis, a straight line connecting the end point and the X axis, an arterial inflow curve , A figure composed of four lines on the X axis. In addition, as the “graphic figure formed by the arterial inflow curve and the X axis”, any two points in the arterial inflow curve other than the start point and the end point are adopted, and the arbitrary two points are connected to the X axis. It may be a figure composed of four lines including a straight line, an arterial inflow curve, and an X axis.
[0091]
In addition, as a method for calculating “the area of the graphic formed by the arterial inflow curve and the X-axis”, for example, a method using an integration method may be mentioned, but the method is not limited to this, and a conventionally known graphic area is used. Calculation methods can be used.
[0092]
Further, the comparison calculation step calculates the maximum slope of the arterial inflow curve before and after the intake of the antioxidant obtained by the arterial inflow curve creation step, respectively, and the maximum slope of the arterial inflow curve before and after the intake of the antioxidant Preferably, this is a step of calculating a change in blood flow by calculating the difference. As a method of “calculating the change in blood flow by calculating the difference in maximum slope”, there is a method in which the difference in maximum slope is directly converted into a numerical value and calculated as a change in blood flow.
[0093]
The “maximum slope of the arterial inflow curve” is the maximum value of the slope in the arterial inflow curve as the wording means. As a method for obtaining the maximum inclination from the arterial inflow curve, for example, a differential method or the like can be used. However, the method is not limited thereto, and the maximum inclination can be obtained from the arterial inflow curve by other known methods. Moreover, as a method for obtaining the blood flow volume from the maximum slope of the arterial inflow curve, a conventionally known method can be used, and it is not particularly limited.
[0094]
According to the above method, it is only necessary to obtain the difference in the area of the figure formed by the arterial inflow curve and the X axis before and after the intake of the antioxidant, or the difference in the maximum slope of the arterial inflow curve before and after the intake of the antioxidant. The change in blood flow during reactive hyperemia can be determined. For this reason, the change of the blood flow rate during the reactive hyperemia before and after the intake of the antioxidant substance can be easily and quantitatively determined.
[0095]
In addition, a specific method for obtaining the arterial inflow amount from the arterial inflow curve using the strain gauge / photoprestimograph EC6 (manufactured by DEHokanson) will be described below from the viewpoint. First, according to this strain gauge / photopress thymograph EC6 (manufactured by DEHokanson), when the 1% Cal button is pressed, the height on the graph (Y-axis value) is 1 ml / min / 100 ml tissue ( = 1% / min). The height per minute (Y-axis value) can be obtained from the slope of the straight line connecting the second and third beats in the arterial inflow curve. Therefore, the amount of arterial inflow per minute is obtained by dividing the height (Y-axis value) obtained here by the value of the height Y-axis on the graph of 1% Cal.
[0096]
In addition, the blood flow rate change calculating step is based on the measurement results of the change in forearm diameter obtained by the forearm diameter change measuring step before intake and the forearm diameter change measuring step after intake. Reactive hyperemia blood flow curve creation process for creating a blood flow curve at the time of hyperemia and reactive hyperemia blood flow curve before and after the intake of antioxidants obtained by the above reactive hyperemia blood flow curve creation process And a comparison calculation step of calculating a change in blood flow during reaction hyperemia before and after the intake of the antioxidant based on the comparison result. That is, as shown in FIG. 1B, the “blood flow change calculation step” may include a “reactive hyperemia blood flow curve creation step” and a “comparison calculation step”.
[0097]
In `` reactive hyperemia blood flow curve creation step '', based on the measurement results of the change in forearm diameter obtained by the above-mentioned forearm diameter change measurement step before intake and the forearm diameter change measurement step after intake by a conventionally known method, What is necessary is just the process of creating the blood flow curve at the time of reactive hyperemia before and after the intake of the antioxidant substance. Specifically, for example, a blood flow curve at the time of reactive hyperemia may be created directly from the measurement result of the change in forearm diameter, or the forearm diameter change measurement process before intake and the forearm diameter change after intake A method of obtaining a change in blood flow from the arterial inflow curve after creating an arterial inflow curve based on the measurement result of the change in the forearm diameter obtained in the measurement step and graphing it may be used. More specifically, for example, a strain gauge / photoplethysmograph EC6 (manufactured by DEHokanson) or a non-invasive blood vessel analysis system NIVP3 (manufactured by DEHokanson) can be used for simplicity.
[0098]
The “reactive hyperemia blood flow curve” is a curve indicating changes in blood flow during reactive hyperemia, and the vertical axis (Y axis) represents changes in blood flow (for example, ml / min / 100 ml tissue). ), A curve expressed when the horizontal axis (X axis) is recorded and graphed with time (for example, seconds). For example, the curve etc. which are represented to the graph of Fig.2 (a) shown in the Example mentioned later are mentioned. Note that the term “curve” here refers to a curve having a broad meaning including not only a point connecting points with a smooth curve but also a point connecting points with a straight line.
[0099]
In the comparative calculation step, the area of the figure formed by the reactive hyperemia blood flow curve and the X axis before and after the intake of the antioxidant obtained by the reactive hyperemia blood flow curve creation step is calculated. Calculating the difference in blood flow change by calculating the difference in the area of the figure formed by the reactive hyperemia blood flow curve and the X-axis before and after intake of the antioxidant substance, Also good.
[0100]
In the comparison calculation step, the same processing as in the above comparison calculation step can be performed, and is not particularly limited. For example, a method of “calculating a change in blood flow by calculating a difference in area” includes a method in which the difference in area is directly converted into a numerical value and calculated as a change in blood flow.
[0101]
In addition, “the figure formed by the reactive hyperemia blood flow curve and the X axis” means, for example, when the reactive hyperemia blood flow curve is graphed, the starting point of the reactive hyperemia blood flow curve, that is, the forearm There is a point where the measurement of the change in diameter is started and the end point of the reactive hyperemia blood flow curve, that is, the point where the measurement of the change in the forearm diameter is completed, and a straight line connecting this start point and the X axis A figure composed of four lines of a straight line connecting the end point and the X axis, a blood flow curve during reactive hyperemia, and the X axis. As “the figure formed by the reactive hyperemia blood flow curve and the X axis”, any two points in the reactive hyperemia blood flow curve other than the start point and the end point are adopted, and the arbitrary 2 It may be a figure composed of four straight lines connecting the point and the X axis, a reactive hyperemia blood flow curve, and an X axis.
[0102]
In addition, as a method of calculating the “area of the graphic formed by the reactive hyperemia blood flow curve and the X-axis”, for example, a method using an integration method may be used, but the method is not limited to this. A known figure area calculation method can be used.
[0103]
(1-3) Antioxidant power measurement process
The antioxidant power measuring step is a step of measuring the antioxidant power of the antioxidant substance in the living body based on the change in blood flow volume of the forearm before and after the intake of the antioxidant substance obtained by the blood flow volume change calculating step. The specific method is not particularly limited.
[0104]
As described above, it can be determined that the effect of NO secreted from the vascular endothelium is maintained if the blood flow volume during reactive hyperemia after intake is increased as compared to before antioxidant intake. This is because the active oxygen is removed by the action of the antioxidant substance. That is, the greater the change in blood flow in the forearm before and after the intake of the antioxidant, the higher the ability of the antioxidant to remove active oxygen, and it can be evaluated that the antioxidant has a strong antioxidant power. On the other hand, if the change in blood flow in the forearm before and after intake of the antioxidant substance is small, the antioxidant substance's ability to remove active oxygen is not so high, and it can be evaluated that the antioxidant ability of the antioxidant substance is weak. Specifically, for example, a method of quantifying the change in blood flow obtained in the blood flow change calculation step as it is to obtain the antioxidant power of the antioxidant in the living body can be mentioned.
[0105]
The “antioxidant” in the present invention refers to a substance that can suppress, eliminate, or repair the damage of active oxygen and lipid peroxide. Specifically, vitamin C, vitamin E, A conventionally well-known antioxidant substance, such as polyphenol and (beta) -carotene, can be mentioned. Among them, there are many types of polyphenols, and examples thereof include phenylcarboxylic acid type, lignan type, curcumin type, coumarin type, and flavonoid type. Further, flavonoids include flavones, flavonols, isoflavones, flavans, flavanols (catechins), flavanones, flavonols, chalcones, anthocyanidins and the like.
[0106]
The antioxidant substance is preferably an antioxidant food. The term “antioxidant food” as used herein refers to foods generally containing antioxidant substances, and means foods in a broad sense including not only solids but also beverages.
[0107]
In addition, examples of the method of “ingesting antioxidant substance” by the subject according to the present invention include conventionally known ingestion methods such as arterial injection, intravenous injection, and oral ingestion, among which oral ingestion is preferable. This is because the antioxidant substance is generally taken orally in the form of an antioxidant food (for example, health food) containing the antioxidant substance.
[0108]
In addition, the method for measuring the antioxidant power of the antioxidant according to the present invention is a blood flow rate change calculating step as long as there is data measuring changes in the forearm diameter during reactive hyperemia before and after the subject ingests the antioxidant. And the process of measuring antioxidant power is enough. That is, as long as there is data obtained by the forearm diameter change measurement process before intake and the forearm diameter change measurement process after intake, the blood flow change calculation process and the antioxidant power measurement process can be performed based on these data. It is possible to measure the antioxidant power of an antioxidant substance in a living body. For this reason, the forearm diameter change measuring step before ingestion and the forearm diameter change measuring step after ingestion are not necessary.
[0109]
(2) Antioxidant power measuring device and antioxidant power measuring system for antioxidant substances
Next, means (apparatus, system) for carrying out the method for measuring the antioxidant power of an antioxidant according to the present invention will be described.
[0110]
The antioxidant substance measuring system for antioxidant substances according to the present invention may be a system using a conventionally known arithmetic unit such as a computer. FIG. 6 is a block diagram showing an example of the configuration of the antioxidant power measurement system 10 according to the present embodiment. As shown in the figure, the antioxidant power measurement system 10 includes a forearm diameter change measuring device 1A before ingestion, a forearm diameter change measuring device 1B after ingestion, an antioxidant power measuring device 2, and an output device 3. Yes.
[0111]
The pre-ingestion forearm diameter change measuring apparatus 1A includes a strain gauge plethysmography 51A, a wrist cuff 52A, and an upper arm cuff 53A. Similarly, the forearm diameter change measuring apparatus 1B after ingestion also includes a strain gauge plethysmography 51B, a wrist cuff 52B, and an upper arm cuff 53B.
[0112]
The pre-ingestion forearm diameter change measuring apparatus 1A is a device for causing reactive hyperemia in the forearm of the subject before the subject ingests the antioxidant substance, and measuring the change in forearm diameter during the reactive hyperemia. is there. Further, the forearm diameter change measuring apparatus 1B after ingestion is a device for measuring the change in the forearm diameter during the reactive hyperemia by causing reactive hyperemia in the forearm of the subject after the subject ingests the antioxidant substance. It is. That is, the forearm diameter change measuring device 1A before ingestion and the forearm diameter change measuring device 1B after ingestion measure the forearm diameter by causing reactive hyperemia before the subject ingests the antioxidant substance, or measure after ingestion. The only difference is in what it does, and the substantial functions are exactly the same. For this reason, it is preferable that the pre-ingestion forearm diameter change measuring device 1A and the post-ingestion forearm diameter change measuring device 1B are generally used as a single device.
[0113]
The strain gauge plethysmographs 51A and 51B are plethysmographs equipped with a mercury built-in tension gauge (strain gauge). By attaching the mercury built-in tension gauge to the subject's forearm, the change in the forearm diameter of the subject can be measured. It is measured and recorded as a change in the length of the gauge diameter. The wrist cuffs 52A and 52B are attached to the wrist of the measurement arm of the subject, and are used to occlude / release the blood vessel by applying pressure to the blood vessel or releasing the pressure from outside the living body. The upper arm cuffs 53 </ b> A and 53 </ b> B are attached to the upper arm of the subject's measurement arm, and are used to occlude / release the blood vessel by applying pressure to the blood vessel or releasing the pressure from outside the living body. For the strain gauge plethysmography 51A / 51B, the wrist cuff 52A / 52B, and the upper arm cuff 53A / 53B, a conventionally known strain gauge plethysmography or blood pressure cuff can be used and is particularly limited. is not.
[0114]
The method and operation of the forearm diameter change measuring device 1A before ingestion and the forearm diameter change measuring device 1B after ingestion measuring the change in forearm diameter during reactive hyperemia are the methods described in the above section (1-1). There is no particular limitation. That is, the forearm diameter change measuring device 1A before ingestion and the forearm diameter change measuring device 1B after ingestion can be said to be means for executing the above-mentioned “forearm forearm diameter change measuring step before intake, forearm diameter change measuring step after ingestion”. It can be said that the measurement results of the change in the measured forearm diameter (the forearm diameter change data before ingestion and the forearm diameter change data after ingestion) are output to the antioxidant power measuring apparatus 2 described later.
[0115]
Next, the antioxidant power measuring apparatus 2 that is a characteristic part of the present invention will be described. The antioxidant power measurement apparatus 2 includes a pre-intake arterial inflow curve creation unit 21A, a post-intake arterial inflow curve creation unit 21B, a blood flow rate change calculation unit 22, and an antioxidant power evaluation unit 23.
[0116]
The pre-intake arterial inflow curve creation unit 21A measured the change in the forearm diameter during reactive hyperemia before the intake of the antioxidant obtained by the pre-intake forearm diameter change measurement apparatus 1A (pre-intake forearm diameter change data) Based on the above, an arterial inflow curve before intake of an antioxidant substance (arterial inflow curve before ingestion) is created. In addition, the post-intake arterial inflow curve creation unit 21B measures the change in the forearm diameter during reactive hyperemia after the intake of the antioxidant (the forearm diameter change data after the ingestion), and the arterial inflow after the intake of the antioxidant This is for creating a curve (arterial inflow curve after ingestion).
[0117]
The method for creating an arterial inflow curve based on the results (data) of the change in the forearm diameter during reactive hyperemia by the pre-intake arterial inflow curve creation unit 21A and the post-intake arterial inflow curve creation unit 21B is described in the above ( The method described in the section 1-2) can be used and is not particularly limited. That is, the pre-intake arterial inflow curve creation unit 21A and the post-intake arterial inflow curve creation unit 21B can be referred to as means for executing the “arterial inflow curve creation step” in the blood flow change calculation step described above. It can be said that the arterial inflow curve (data) is output to the blood flow rate change calculation unit 22 described later. When the forearm diameter change measuring device 1A before ingestion and the forearm diameter change measuring device 1B after ingestion are used together in one device, the preintake arterial inflow curve creating unit 21A and the post ingestion arterial inflow curve creating unit 21B are respectively used. Then, the measurement result is obtained from the single device that is also used.
[0118]
The blood flow rate change calculation unit 22 compares the pre-intake arterial inflow curve created by the pre-intake arterial inflow curve creation unit 21A with the post-intake arterial inflow curve creation unit 21B. Based on the comparison result, the change in the blood flow during reactive hyperemia before and after the intake of the antioxidant substance is calculated. The method in which the blood flow rate change calculating unit 22 compares the pre-intake arterial inflow curve and the post-intake arterial inflow curve and calculates the change in the blood flow during reactive hyperemia before and after the intake of the antioxidant is described in (1- The method described in the section 2) can be used and is not particularly limited. That is, the blood flow rate change calculation unit 22 can also be said to be a means for executing the above-described “comparison calculation step”, and outputs the comparison calculation result (data) to the antioxidant power evaluation unit 23 described later. It can be said.
[0119]
Based on the calculation result of the change in blood flow during reactive hyperemia before and after the intake of the antioxidant obtained by the blood flow rate change calculation unit 22, the antioxidant power evaluation unit 23 determines the antioxidant power of the antioxidant in the living body. It is to be evaluated (measured). The method for evaluating (measuring) the antioxidant power of the antioxidant substance in the living body by the antioxidant power evaluation unit 23 can use the method described in the above section (1-3), and is not particularly limited. That is, the antioxidant power evaluation unit 23 can be said to be a means for executing the above-mentioned “antioxidant power measuring step”, and outputs the measurement (evaluation) result (data) to the output device 3 described later. It can be said that.
[0120]
Subsequently, specific functions of various members of the antioxidant power measuring apparatus 2 will be described according to the flowchart in FIG. 8, and an example of specific data processing performed by the antioxidant power measuring apparatus 2 in the present embodiment will be described. To do.
[0121]
First, in step S1, the forearm diameter change measuring device 1A before ingestion and the forearm diameter change measuring device 1B after ingestion measure the change in forearm diameter during reactive hyperemia before and after the subject ingests the antioxidant, respectively. Data of the forearm diameter change measurement result (foretake forearm diameter change data) and post-intake forearm diameter change measurement result data (after-intake forearm diameter change data) are sent to the antioxidant power measuring apparatus 2.
[0122]
Next, in step S2, the pre-intake arterial inflow curve creation unit 21A, based on the pre-intake forearm diameter change data obtained in step S1, the arterial inflow curve before intake of the antioxidant (pre-intake arterial inflow curve). Create
[0123]
Subsequently, in step S3, the post-intake arterial inflow curve creation unit 21B, based on the post-intake forearm diameter change data obtained in step S1, the arterial inflow curve after intake of the antioxidant (post-intake arterial inflow curve). Create
[0124]
Next, in step S4, the blood flow rate change calculation unit 22 calculates the maximum slope of the pre-intake arterial inflow curve obtained in step S2, and calculates the maximum slope of the post-intake arterial inflow curve obtained in step S3. .
[0125]
Next, in step S5, the difference between the maximum slope in the pre-intake arterial inflow curve and the maximum slope in the post-intake arterial inflow curve obtained in step S4 is obtained, and the blood flow change is determined based on the difference in the maximum slope. Is calculated.
[0126]
Subsequently, in step S6, the antioxidant power evaluation unit 23 calculates the antioxidant substance in the living body based on the calculation result of the change in blood flow during reactive hyperemia before and after the intake of the antioxidant substance obtained in step S5. Measure and evaluate antioxidant capacity.
[0127]
Finally, in step S7, the antioxidant power evaluation unit 23 outputs the measurement / evaluation result of the antioxidant power in the living body of the antioxidant substance obtained in step S6 to the output device 3.
[0128]
Further, an antioxidant power measuring apparatus 2 ′ having another configuration will be described with reference to FIG. The antioxidant power measuring device 2 ′ includes a pre-intake reactive hyperemia blood flow curve creation unit 24 A, a post-ingestion reactive hyperemia blood flow curve creation unit 24 B, a blood flow change calculator 22, and an anti-oxidation power evaluation unit 23. ing.
[0129]
The blood flow curve creation unit 24A during reactive hyperemia before ingestion measured the change in forearm diameter during reactive hyperemia before ingestion of antioxidants obtained by the forearm diameter change measurement apparatus 1A before ingestion (the forearm before ingestion). Based on the diameter change data), a blood flow curve at the time of reactive hyperemia before intake of the antioxidant substance (a blood flow curve at the time of reactive hyperemia before ingestion) is created. Moreover, the blood flow curve creation unit 24B at the time of reactive hyperemia after intake measures the change in forearm diameter during reactive hyperemia after the intake of antioxidant substances (forearm diameter change data after intake) based on the intake of antioxidant substances This is for creating a blood flow curve at the time of reactive hyperemia (a blood flow curve at the time of reactive hyperemia after ingestion).
[0130]
Based on the results (data) of the change in the forearm diameter during reactive hyperemia, the reactive hyperemia blood flow curve creation unit 24A and the post-intake reactive hyperemia blood flow curve creation unit 24B before the intake The method for creating the blood flow curve is not particularly limited, and the method described in the above section (1-2) can be used. That is, the pre-intake reactive hyperemia blood flow curve creation unit 24A and the post-intake reactive hyperemia blood flow curve creation unit 24B perform the “reactive hyperemia blood flow curve creation step” in the blood flow change calculation step described above. It can be said that it is a means for executing, and it can be said that the created arterial inflow curve (data) is output to the blood flow rate change calculation unit 22 described later.
[0131]
The blood flow change calculation unit 22 is created by the pre-ingestion reactive hyperemia blood flow curve created by the pre-intake reactive hyperemia blood flow curve creation unit 24A and the post-intake reactive hyperemia blood flow curve creation unit 24B. The blood flow curve during reactive hyperemia after ingestion is compared, and the change in blood flow during reactive hyperemia before and after the intake of the antioxidant is calculated based on the comparison result. The method in which the blood flow rate change calculating unit 22 compares the pre-intake arterial inflow curve and the post-intake arterial inflow curve and calculates the change in the blood flow during reactive hyperemia before and after the intake of the antioxidant is described in (1- The method described in the section 2) can be used and is not particularly limited. That is, the blood flow rate change calculation unit 22 can also be said to be a means for executing the above-described “comparison calculation step”, and outputs the comparison calculation result (data) to the antioxidant power evaluation unit 23 described later. It can be said.
[0132]
The antioxidant power evaluation unit 23 has the same function as that described above, and thus description thereof is omitted.
[0133]
Next, specific functions of various members of the antioxidant power measuring apparatus 2 shown in FIG. 7 will be described with reference to the flowchart in FIG. 9, and specific data processing performed by the antioxidant power measuring apparatus 2 in the present embodiment. An example will be described.
[0134]
First, in step S1, the forearm diameter change measuring device 1A before ingestion and the forearm diameter change measuring device 1B after ingestion measure the change in forearm diameter during reactive hyperemia before and after the subject ingests the antioxidant, respectively. Data of the forearm diameter change measurement result (before-intake forearm diameter change data) and post-intake forearm diameter change measurement result data (after-intake forearm diameter change data) are sent to the antioxidant power measuring apparatus 2 ′.
[0135]
Next, in step S2, the blood flow curve at the time of reactive hyperemia before ingestion, based on the forearm diameter change data before ingestion obtained in step S1, the reactive hyperemia blood flow before ingestion of the antioxidant is obtained. Create a curve (reactive hyperemia blood flow curve before ingestion).
[0136]
Subsequently, in step S3, the post-ingestion reactive hyperemia blood flow curve creation unit 24B performs reactive hyperemia blood flow after ingestion of the antioxidant based on the post-ingestion forearm diameter change data obtained in step S1. Create a curve (reactive hyperemia blood flow curve after ingestion).
[0137]
Next, in step S4, the blood flow rate change calculation unit 22 uses the pre-intake reactive hyperemia blood flow curve obtained in step S2 and the area of the graphic formed by the X axis, and the post-intake reaction obtained in step S3. The area of the figure formed by the blood flow curve during sexual hyperemia and the X axis is calculated.
[0138]
Next, in step S5, the area of the figure formed by the pre-intake reactive hyperemia blood flow curve and the X axis obtained in step S4, and the post ingestion reactive hyperemia blood flow curve and the X axis are formed. The difference with the area of the figure to be calculated is calculated, and the change in the blood flow during reactive hyperemia before and after the intake of the antioxidant is calculated based on the difference in the area.
[0139]
Subsequently, in step S6, the antioxidant power evaluation unit 23 calculates the antioxidant substance in the living body based on the calculation result of the change in blood flow during reactive hyperemia before and after the intake of the antioxidant substance obtained in step S5. Measure and evaluate antioxidant capacity.
[0140]
Finally, in step S7, the antioxidant power evaluation unit 23 outputs the measurement / evaluation result of the antioxidant power in the living body of the antioxidant substance obtained in step S6 to the output device 3.
[0141]
The output device 3 is for outputting the measurement / evaluation result of the antioxidant power in the living body of the antioxidant substance obtained by the antioxidant power measuring device 2 (or 2 ′) performing the above-described processing to the outside. is there. Further, the output device 3 includes an arterial inflow curve created by the pre-intake arterial inflow curve creation unit 21A and a post-intake arterial inflow curve creation unit 21B, a pre-intake reactive blood flow curve creation unit 24A, and a post-intake reactivity. Information related to the operation of the antioxidant power measuring device 2 including the blood flow curve at the time of hyperemia created by the blood flow curve creation unit 24B at the time of hyperemia or the result of comparison / calculation by the blood flow change calculator 22 It is also possible to display various types of information such as measurement results during measurement. Specifically, various display devices such as a known CRT display and a liquid crystal display are preferably used, but are not particularly limited.
[0142]
The output device 3 may be provided with a printing unit. The printing means records (printing / image forming) image information that can be displayed on the output device 3 on a recording material such as PPC paper. Specifically, known image forming apparatuses such as an ink jet printer and a laser printer are preferably used, but are not particularly limited. Note that the output device 3 is not limited to the printing unit and the like, and may include other output units.
[0143]
Furthermore, as shown in FIG. 10, the antioxidant substance measurement system 10 for antioxidant substances according to the present embodiment may include, for example, an input device 11 and a storage device 12.
[0144]
The input device 11 is not particularly limited as long as it can input information related to the operation and operation of the antioxidant power measuring device 2 and the antioxidant power measuring system 10, and includes a keyboard, a tablet, a scanner, and the like. Conventionally known input means can be suitably used. For example, the forearm diameter change data before ingestion and the forearm diameter change data after ingestion are input to the antioxidant power measuring device 2 by the input device 11 to measure the forearm diameter change measuring device 1A before ingestion and the forearm diameter change measurement after ingestion. The antioxidant power of an antioxidant can be measured without obtaining forearm diameter change data before ingestion and forearm diameter change data after ingestion from the apparatus 1B.
[0145]
The storage device 12 stores various information (data, operation information, control information, calculation results, other information, etc.) used in the antioxidant power measuring device 2 and the antioxidant power measuring system 10. Specifically, for example, semiconductor memories such as RAM and ROM, magnetic disks such as floppy (registered trademark) disks and hard disks, optical disk systems such as CD-ROM / MO / MD / DVD, IC cards (memory cards) Conventionally, various known storage means such as a card system such as an optical card can be suitably used.
[0146]
The storage device 12 may be integrated with the antioxidant power measuring device 2 and the antioxidant power measuring system 10 and may be a single device, but it is a separate external storage device. Further, a configuration in which both the integrated storage device 12 and the external storage device are provided may be employed. For example, the integrated storage device 12 includes a built-in hard disk or a floppy (registered trademark) disk drive, a CD-ROM drive, a DVD-ROM drive, etc. incorporated in the device. Examples include an attached hard disk and the above-mentioned various disk drives.
[0147]
Furthermore, as shown in FIG. 10, the antioxidant power measurement system 10 may include a communication device 13 so that various types of information can be input / output via a communication network including the Internet. The communication device 13 is connected to a communication network and can transmit and receive various types of information. In FIG. 10, an antioxidant power measurement system 10, a personal computer (PC) 61, and a server 62 in the same premises are connected to a communication line 60 to form a bus-type LAN (local area network). A LAN is also connected to a PC 61 in another area via the Internet.
[0148]
The specific configuration of the communication device 13 is not particularly limited, and a known LAN card, LAN board, LAN adapter, modem, or the like can be suitably used.
[0149]
As the PC 61, a known personal computer equipped with a communication means such as a modem can be suitably used, and the PC 61 is not limited to a desktop type or a notebook type. The PC 61 has a basic configuration including a display unit such as a CRT display or a liquid crystal display and an input unit such as a keyboard or a mouse. For convenience of explanation, a display unit and an input unit (not shown) provided in the PC 61 are expressed as a PC display unit / PC input unit.
[0150]
The PC 61 may be provided with hardware (for example, various input means such as a scanner and various output means such as a printer) that can be externally attached to a general personal computer.
[0151]
The specific configuration of the server 62 is not particularly limited as long as it is a computing device such as a PC 61 that is a client configuring the LAN and a computer that can provide services to the antioxidant power measurement system 10. Further, the server 62 may also serve as a database server or a file server.
[0152]
The specific configuration of the communication line 60 is not particularly limited, and a conventionally known general communication line can be used. Also, the type of LAN constructed using this communication line 60 is not limited to the bus type, and may be a conventionally known type such as a star type or a ring type.
[0153]
Although not shown, the LAN may include other terminals such as a shared printer. In addition, although not shown, the communication network including the LAN may include various portable terminals capable of communication.
[0154]
In the network having the above configuration, for example, after the antioxidant power measurement (evaluation) in the living body of the antioxidant substance is performed in the antioxidant power measurement system 10, the measurement (evaluation) result is simply stored in the antioxidant power measurement system 10 ( In other words, it can be transmitted not only by the output device 3 etc.) but also to the PC 61 via the LAN. In the PC 61, the result obtained from the antioxidant power measurement system 10 can be displayed on the PC display unit or printed by the printer, and further, the above measurement result can be processed by the input from the PC input unit. You can also. That is, the communication device 13 functions not only as a communication unit but also as an input unit of the antioxidant power measurement system 10.
[0155]
In particular, in the method for measuring the antioxidant power of an antioxidant substance according to the present invention in a remote place away from the place where the antioxidant power measuring device 2 is located, the forearm diameter change measuring step before intake and the forearm diameter change after intake After measuring the forearm diameter change data before ingestion and the forearm diameter change data after ingestion, the antioxidative power measurement 2 (antioxidant power measurement) existing at a remote location via the network (Internet) using the PC 61 When transmitting the forearm diameter change data before ingestion and the forearm diameter change data after ingestion to the system 10) or receiving the measurement (evaluation) results of the antioxidant power of the antioxidant, It is possible to provide a service for providing the method for measuring the antioxidant power of the antioxidant according to the present invention to any customer existing in the field.
[0156]
Further, when the PC 61 is connected to the antioxidant power measurement system 10 via the LAN, if there is one antioxidant power measurement system 10 in a medical institution, research facility, etc., other doctors and researchers Can share the antioxidant power measurement system 10 via an information terminal such as the PC 61. Therefore, the present invention can be implemented more efficiently.
[0157]
Further, when the server 62 also serves as a database server or a file server, the antioxidant power measurement results of the antioxidants made via the communication network are accumulated in the server 62 via the communication network. be able to. As a result, sharing of information proceeds and the measurement result can be used more effectively.
[0158]
In addition, in the present invention, the blood flow change calculation step (arterial inflow curve creation step, comparative calculation step) and the antioxidant force measurement step in the method for measuring the antioxidant strength of an antioxidant substance are carried out by a program on a computer. However, the recording medium that records the program includes a medium that fluidly carries the program so as to be downloaded from a communication network. For example, if the program of the blood flow rate change calculating step and the antioxidant power measuring step is recorded in the recording means of the server 62, the antioxidant power measuring system 10 appropriately receives the blood flow rate change calculating step and the antioxidant from the server 62. A program for the force measurement process may be downloaded and used. However, when the antioxidant power measurement system 10 downloads a program from a communication network, the download program is stored in the antioxidant power measuring device 2 main body in advance or installed from another recording medium. It is like that.
[0159]
Further, when connected to the server 62 via a communication network, such as the PC 61, the PC 61 itself can be controlled by downloading the blood flow rate change calculation process and the antioxidant power measurement process from the server 62. The oxidizing power measuring device 2 and the antioxidant power measuring system 10 can be used.
[0160]
Therefore, each block (member, device) of the antioxidant power measuring device 2 and the antioxidant power measuring system 10 according to the present embodiment may be configured by hardware logic or using a CPU as follows. It may be realized by software.
[0161]
That is, the antioxidant power measuring apparatus 2 includes a CPU (central processing unit) that executes instructions of a control program for realizing each function, a ROM (read only memory) that stores the program, and a RAM (random access) that expands the program. memory), a storage device (recording medium) such as a memory for storing the program and various data. The object of the present invention is a record in which the program code (execution format program, intermediate code program, source program) of the control program of the antioxidant power measuring device 2 which is software for realizing the above-described functions is recorded so as to be readable by a computer This can also be achieved by supplying the medium to the antioxidant power measuring apparatus 2 and reading and executing the program code recorded on the recording medium by the computer (or CPU or MPU).
[0162]
Examples of the recording medium include a tape system such as a magnetic tape and a cassette tape, a magnetic disk such as a floppy (registered trademark) disk / hard disk, and an optical disk such as a CD-ROM / MO / MD / DVD / CD-R. Card system such as IC card, IC card (including memory card) / optical card, or semiconductor memory system such as mask ROM / EPROM / EEPROM / flash ROM.
[0163]
Further, the antioxidant power measuring apparatus 2 may be configured to be connectable to a communication network, and the program code may be supplied via the communication network. The communication network is not particularly limited. For example, the Internet, intranet, extranet, LAN, ISDN, VAN, CATV communication network, virtual private network, telephone line network, mobile communication network, satellite communication A net or the like is available. Also, the transmission medium constituting the communication network is not particularly limited. For example, even in the case of wired such as IEEE 1394, USB, power line carrier, cable TV line, telephone line, ADSL line, etc., infrared rays such as IrDA and remote control, Bluetooth, etc. (Registered trademark) , 802.11 wireless, HDR, mobile phone network, satellite line, terrestrial digital network, etc. can also be used. The present invention can also be realized in the form of a carrier wave or a data signal sequence in which the program code is embodied by electronic transmission.
[0164]
(3) Method of measuring antioxidant power of antioxidant substances, antioxidant power measuring device, and usage of antioxidant power measuring system
As described above, according to the antioxidant power measuring method, antioxidant power measuring apparatus, and antioxidant power measuring system according to the present invention, before and after the subject ingests the antioxidant, Only by measuring the change in arm diameter, the antioxidant power of the antioxidant substance in the living body of the subject can be quantitatively measured and evaluated. Further, the method, the device, and the system are not only simple, but also do not require an invasive process such as blood collection, and thus are very easy to handle for both the subject and the practitioner. There is.
[0165]
For this reason, the antioxidant power measuring method, antioxidant power measuring apparatus, and antioxidant power measuring system according to the present invention can be used in, for example, a screening method for antioxidant substances. That is, the screening method for antioxidant substances according to the present invention screens antioxidant substances using any one of the antioxidant power measuring method, antioxidant power measuring apparatus and antioxidant power measuring system. Any method may be used, and specific methods, conditions, and the like are not particularly limited.
[0166]
According to the screening method described above, for example, by allowing a subject to orally ingest a food group that appears to be usable as an antioxidant food, a food that actually exhibits excellent antioxidant ability in vivo is conveniently and non-invasively selected. can do. Therefore, the antioxidant substance and antioxidant food obtained by the screening method have been proven to be effective in the living body, and can be highly evaluated in the market.
[0167]
In addition, the antioxidant substance acquired by the said screening method is also contained in this invention. That is, the novel antioxidant substance according to the present invention only needs to be obtained by the screening method.
[0168]
In addition, as the public notices that oxidative stress is detrimental to health, antioxidant foods and health foods that have an antioxidant function are increasing in both types and quantities, and the antioxidant power of these foods is evaluated appropriately. The development of the method is strongly sought, but the antioxidant power measuring method, antioxidant power measuring device, and antioxidant power measuring system according to the present invention can meet this demand.
[0169]
The present invention also includes an oxidative stress measurement method in which a blood pressure cuff is wrapped around a human forearm to measure the blood flow in the forearm during reactive hyperemia.
[0170]
In the above oxidative stress measurement method, the wrist cuff is set to systolic blood pressure + 30 mmHg to systolic blood pressure + 70 mmHg, the upper arm cuff is set to 10 to 60 mmHg, the forearm vein is blocked, and the baseline is measured. May be.
[0171]
In the above oxidative stress measurement method, the upper arm cuff is set to 200 to 260 mmHg, the forearm artery flow is completely blocked, and the wrist cuff is set to systolic blood pressure +30 mmHg to systolic blood pressure +70 mmHg after 3 to 5 minutes. Then, after 1 to 3 minutes, the upper arm cuff may be set to 30 to 50 mmHg, the change in arm diameter may be measured for 5 to 200 seconds after the setting, and this may be used as the change in blood flow.
[0172]
Further, in the above oxidative stress measurement method, the oxidative stress measurement method may determine that the oxidative stress is less as the forearm diameter increases.
[0173]
In addition, a method for quantitatively measuring the antioxidant power of an antioxidant food using the above oxidative stress measurement method is also included in the present invention.
[0174]
Furthermore, an apparatus for measuring the blood flow volume of the forearm during the reactive hyperemia by wrapping a blood pressure cuff around the human forearm is also included in the present invention.
[0175]
Embodiments will be described below in more detail with reference to the accompanying drawings. Of course, the present invention is not limited to the following examples, and it goes without saying that various aspects are possible in detail. Further, the present invention is not limited to the above-described embodiments, and various modifications can be made within the scope shown in the claims, and the present invention is also applied to the embodiments obtained by appropriately combining the disclosed technical means. It is included in the technical scope of the invention.
[0176]
【Example】
In this example, we focused on green tea and applephenone (extracted from apple berries) that contain abundant flavanol antioxidants (catechins and condensed tannins), which are considered to have strong antioxidant power, and their antioxidant in vivo effects. Was evaluated by measuring the forearm blood flow non-invasively and analyzing the in vivo effects of oral intake of green tea and applephenone.
[0177]
[1] Research method
[1-1] Research target
Twenty-one healthy boys (average age 33 ± 1 years) with smoking habits (2 packs / day / year or more) and 10 healthy non-smokers (average age 32 ± 1 years) were used as subjects. All patients obtained written consent for this study and received approval from the National Cardiovascular Center Ethics Committee.
[0178]
[1-2] Measurement of forearm blood flow by strain gauge plethysmography
The subject was allowed to rest on the bed for 15-30 minutes, during which time blood pressure and pulse were measured. Measure the thickest diameter of the measuring arm, attach a tension gauge (strain gauge) with a length 2 to 3 cm less than that value, attach the cuff of the sphygmomanometer (wrist cuff 52A) to the wrist of the measuring arm, and the plethysmograph on the upper arm The cuff (upper arm cuff 53A) connected to the tee was wound. Blood flow was determined as a change in forearm diameter.
[0179]
[1-3] Baseline measurement
The wrist cuff was clamped at systolic blood pressure + 50 mmHg, and the upper arm cuff 53A was measured by measuring the degree of increase in forearm diameter for 2 minutes by applying pressure at 40 mmHg (forearm vein blocking).
[0180]
[1-4] Measurement of vascular endothelium-dependent blood flow increase response
After resting for 5 minutes after the baseline blood flow measurement, 240 mmHg pressure is applied to the upper arm cuff 53A to completely block the forearm artery inflow, and after 4 minutes the wrist cuff 52A is subjected to the same pressure as during baseline measurement. 1 minute later, the upper arm cuff 53A was returned to 40 mmHg, and the change in the forearm diameter was recorded for 3 minutes. After opening the forearm arterial blockage, blood flow increases more rapidly than the baseline (reactive hyperemia), because nitric oxide (NO) produced from vascular endothelial cells relaxes vascular smooth muscle It represents a vascular endothelium-dependent vasodilator response.
[0181]
[1-5] Measurement of blood vessel endothelium independent blood flow increase response
After reactive hyperemia disappeared, the patient remained at rest for 15 minutes, wrist cuff 52A was similarly clamped, and nitroglycerin (NTG: 0.3 mg) was administered sublingually. The change in forearm diameter was measured and recorded for 5 minutes in the same manner as in the baseline measurement. The increase in blood flow after nitroglycerin administration results from exogenous NO directly relaxing vascular smooth muscle, indicating vascular endothelium-independent vasodilation.
[0182]
[1-6] Effect of flavanol antioxidant food
We investigated the effects of oral ingestion of green tea and applephenone as flavanol antioxidant foods containing catechins and condensed tannins. 8 g of green tea was soaked in 40 ml of water, and the solution eluted at 90 ° C. for 5 minutes was orally administered. 20 ml of apple-condensed tannin “apple phenone (honey / seed ginseng extract / royal jelly mixed solution)” was orally administered. Antioxidant concentrations of flavanols in green tea (in vitro) and blood (in vivo) after drinking green tea / apple phenone were measured by high performance liquid chromatography.
[0183]
Baseline blood flow measurement, vascular endothelium-dependent blood flow increase response, and vascular endothelium-independent blood flow increase response were repeated in the same manner 2 hours after ingestion of green tea and 45 minutes after ingestion of applephenone, respectively. In addition, since the intake of green tea requires a drinking load of about 400 ml, the same amount of white hot water (hot water) was ingested as a control, and the same test was performed. Comparison between groups of each measured value was performed by ANOVA analysis.
[0184]
[2] Results
[2-1] Forearm arterial vascular endothelium dependent blood flow increase response in smoking habits (vascular endothelial function)
The forearm blood flow is expressed as ml / min / 100 ml forearm tissue volume (ml / min / 100 ml tissue). The average value of baseline forearm arterial blood flow was almost the same as 4.9 ± 0.3 ml / min / 100 ml tissue volume for both smokers and non-smokers.
[0185]
The maximum blood flow during reactive hyperemia in a smoker is 16.9 ± 1.1 ml / min / 100 ml tissue volume, compared to 24.9 ± 1.6 ml / min / 100 ml tissue volume in non-smokers. There was a significant decrease (P <0.01). These results indicate that smokers have reduced vascular endothelium-dependent vasodilator responses in the forearm arteries.
[0186]
[2-2] Improvement of vascular endothelial function by ingestion of green tea
One week later, the smoker was ingested with 400 ml of green tea and the change in forearm diameter during the same reactive hyperemia was measured. As a result, the maximum blood flow was 21.11 ± 1.1 ml / min / 100 ml from the tissue volume. It significantly increased to 3 ± 1.3 ml / min / 100 ml tissue volume (P <0.01) (see FIG. 2A). One week later, when 400 ml of white hot water (warm water) was ingested and the change in forearm diameter during the same reactive hyperemia was measured, no increase in the maximum blood flow was observed (FIG. 2 (b)). Neither green tea nor white water intake increased forearm blood flow after sublingual administration of NTG. Neither showed significant changes in systolic blood pressure, diastolic blood pressure, heart rate, fasting lipids, or glucose. This indicates that green tea-derived components improve the decreased vascular endothelium-dependent blood flow response in smokers.
[0187]
When catechins and vitamins contained in the green tea extract used were measured, many types of catechins (total catechin concentration: 173.1 mg / dl) including epigallocatechin gallate were detected (see Table 1 below). ).
[0188]
[Table 1]

[0189]
When the blood epigallocatechin gallate concentration was measured 2 hours after ingestion of green tea, it was remarkably increased from 3 ± 1 before ingestion to 694 ± 81 pmol / ml.
[0190]
[2-3] Improvement of vascular endothelial function by flavanol antioxidant food (green tea / apple condensed tannin)
For the purpose of comparing vascular endothelial function improvement effect with apple condensed tannin (apple phenone) which has strong antioxidant activity as well as green tea catechins, the forearm at the time of reactive hyperemia after intake of green tea / apple phenone in one smoker When the change in diameter was measured and recorded (see Fig. 3), the maximum blood flow increased from 21.6 to 34.8ml / min / 100ml tissue volume for green tea (see Fig. 4), but for apple phenone Markedly increased from 18.0 to 43.2 ml / min / 100 ml tissue mass (see FIG. 5). In the figure, RHR indicates reactive hyperemia.
[0191]
[3] Consideration
Today, when adult disease has been renamed lifestyle-related disease, it has been pointed out that antioxidants, which are attracting attention as the seventh nutrient, may significantly reduce the prevalence of lifestyle-related diseases such as arteriosclerosis. ing. An example of this is the lowest incidence in France, which is famous for high consumption of red wine (anthocyanin) in the European countries that have a high incidence of arteriosclerosis. Antioxidants are expected to be effective in preventing health disorders that are thought to be mainly caused by oxidative stress such as lifestyle-related diseases and aging, but there are few empirical studies on the effects in the body, and health based on hypotheses and traditions. The current situation is not out of the food boom.
[0192]
In this way, it is generally stated that polyphenols remove active oxygen. On the other hand, contrary to the prevention of health disorders due to the antioxidant action of antioxidants, smoking habits are exposed to oxidative stress derived from tobacco smoke and develop and progress atherosclerosis through dysfunction of vascular endothelial cells It has been pointed out to be dangerous.
[0193]
Based on these facts, we conducted this experiment to demonstrate how antioxidants function both in the human body, whose vascular endothelial function is reduced by some stress, and in the healthy human body.
[0194]
Experimental results show that oxidative stress such as smoking reduces vascular endothelial function, improves vascular endothelial function due to substances contained in green tea, and antioxidants in green tea (catechins that are flavanols) It was found that the health food containing the condensate (apple condensed tannin) showed a greater improvement effect. As a result, it has been shown in vivo that vascular endothelial function is decreased by exposure to oxidative stress such as smoking, and conversely, it is improved by antioxidants. This result suggests that antioxidants contained in green tea and apple phenone may prevent heart diseases caused by impaired vascular endothelial function.
[0195]
Furthermore, from the results of this experiment, it can be seen that the experimental method used in the present invention can measure and evaluate the antioxidant function in vivo of antioxidant foods taken orally in a non-invasive, simple and quantitative manner. Show. Therefore, this experimental method can be applied to various usages.
[0196]
【The invention's effect】
As described above, according to the antioxidant power measuring method, antioxidant power measuring apparatus, and antioxidant power measuring system according to the present invention, before and after the subject ingests the antioxidant, Only by measuring the change in the arm diameter, it is possible to quantitatively measure and evaluate the antioxidant power of the antioxidant substance in the subject body. Furthermore, since such methods, devices, and systems are not only simple but do not require an invasive process such as blood collection, the subject does not feel pain or annoyance, It is easy for the practitioner of the method and the like, and it is very easy to handle for both the subject and the practitioner.
[0197]
Therefore, it is a very useful technique that can be used for screening methods for antioxidant substances and in vivo evaluation of health foods with high antioxidant ability.
[Brief description of the drawings]
FIG. 1 (a) is a process diagram showing an example of a method for measuring antioxidant power of an antioxidant according to an embodiment of the present invention, and FIG. 1 (b) is an antioxidant according to an embodiment of the present invention. It is process drawing which shows another example of the antioxidant power measuring method of a substance.
FIG. 2 (a) is a graph showing changes in blood flow in the forearm during reactive hyperemia before and after ingestion of green tea, and (b) blood flow in the forearm during reactive hyperemia before and after ingestion of white hot water (warm water). It is a graph which shows a change.
FIG. 3 (a) is a graph of changes in forearm arm diameter at baseline after control (before antioxidant intake), after taking green tea and after taking applephenone (arterial inflow curve ( Vertical axis: change in diameter, horizontal axis: time)), and (b) graphed changes in forearm arm diameter in reactive hyperemia after control, ingestion of green tea, and ingestion of applephenone and recorded. (C) is a change in forearm arm diameter after sublingual administration of NTG after control, green tea intake, and apple phenone intake after arterial inflow curve (vertical axis: change in diameter, horizontal axis: time). Is a graph (arterial inflow curve (vertical axis: change in diameter, horizontal axis: time)) recorded as a graph over time.
FIG. 4 (a) is a graph showing changes in blood flow in the forearm at the baseline before and after ingestion of green tea, and (b) shows changes in blood flow in the forearm in reactive hyperemia before and after ingestion of green tea. (C) is a graph which shows the change of the blood flow volume of the forearm part at the time of administering NTG sublingual before and after green tea ingestion.
FIG. 5 (a) is a graph showing changes in blood flow in the forearm at the baseline before and after ingestion of apple phenone, and (b) shows changes in blood flow in the forearm in reactive hyperemia before and after ingestion of apple phenone. (C) is a graph which shows the change of the blood flow volume of the forearm part when NTG is administered sublingually before and after apple phenone intake.
FIG. 6 is a functional block diagram showing an example of the configuration of the antioxidant power measurement system according to the embodiment of the present invention.
FIG. 7 is a functional block diagram illustrating another example of the configuration of the antioxidant power measurement system according to the embodiment of the present invention.
FIG. 8 is a flowchart showing an example of a processing procedure performed by the antioxidant power measuring apparatus according to the embodiment of the present invention.
FIG. 9 is a flowchart showing another example of a processing procedure performed by the antioxidant power measuring apparatus according to the embodiment of the present invention.
FIG. 10 is a functional block diagram showing another example of the configuration of the antioxidant power measurement system according to the embodiment of the present invention.
[Explanation of symbols]
2 Antioxidant power measuring device
2 'Antioxidant power measuring device
3 Output device
10 Antioxidant power measurement system
1A Forearm diameter change measuring device before ingestion
1B Forearm diameter change measuring device after ingestion
21A pre-intake arterial inflow curve creation part (pre-intake arterial inflow curve creation means)
21B Post-intake arterial inflow curve creation unit (post-intake arterial inflow curve creation means)
22 Blood flow rate change calculation unit (blood flow rate change calculation means)
23 Antioxidant power evaluation part (Antioxidant power evaluation means)
24A Reactive hyperemia blood flow curve creation section before ingestion (reactive hyperemia blood flow curve creation means before ingestion)
24B Reactive hyperemia blood flow curve creation section after ingestion (reactive hyperemia blood flow curve creation means after ingestion)
51A ・ 51B Strain gauge plethysmography
52A / 52B wrist cuff
53A / 53B Upper arm cuff

Claims (6)

A pre-intake arterial inflow curve creation means for creating a pre-intake arterial inflow curve based on pre-intake forearm diameter change data measured for changes in forearm diameter during reactive hyperemia prior to antioxidant intake, and after antioxidant intake Based on post-intake forearm diameter change data measured for forearm diameter change during reactive hyperemia, created by post-intake arterial inflow curve creation means and pre-intake arterial inflow curve creation means Blood flow during reactive hyperemia before and after the intake of antioxidants based on the comparison result of the pre-intake arterial inflow curve and the post-intake arterial inflow curve created by the post-intake arterial inflow curve Based on the calculation result of the blood flow change during reactive hyperemia before and after the intake of the antioxidant obtained by the blood flow change calculation means, Antioxidant power measuring device antioxidants, characterized in that it comprises an anti-oxidizing power evaluating means for evaluating the antioxidant capacity in vivo of antibodies oxidant, the. The blood flow change calculation means calculates a maximum slope of the pre-intake arterial inflow curve and a maximum slope of the post-intake arterial inflow curve, and calculates a difference between the maximum slope of the arterial inflow curve before and after the intake of the antioxidant. The apparatus according to claim 1 , wherein a change in blood flow is calculated. Create pre-intake reactive hyperemia blood flow curve based on pre-ingestion forearm diameter change data based on changes in forearm diameter during reactive hyperemia before antioxidant intake And post-ingestion reactive hyperemia blood flow curve based on post-ingestion forearm diameter change data based on measures and forearm diameter change data measured during reactive hyperemia after antioxidant intake A flow curve creation means, a pre-ingestion reactive hyperemia blood flow curve created by the pre-intake reactive hyperemia blood flow curve creation means, and a post-intake reactive hyperemia blood flow curve creation means created by the pre-intake reactive hyperemia blood flow curve creation means A blood flow rate change calculating means for comparing a blood flow curve during reactive hyperemia and calculating a change in blood flow during reactive hyperemia before and after the intake of the antioxidant based on the comparison result, and the blood flow change calculating means By An anti-oxidant power evaluation means for evaluating the anti-oxidant power in the living body of the anti-oxidant based on the calculation result of blood flow change during reactive hyperemia before and after the intake of the anti-oxidant, Antioxidant power measuring device for antioxidants. The blood flow rate change calculating means includes an area of a figure formed by the pre-intake reactive hyperemia blood flow curve and the X axis, and an area of a figure formed by the post-intake reactive hyperemia blood flow curve and the X axis. And the change in blood flow is calculated by calculating the difference in the area of the figure formed by the reactive hyperemia blood flow curve and the X-axis before and after the intake of the antioxidant substance. The antioxidant power measuring apparatus for antioxidant substances according to claim 3 . The antioxidant substance measuring apparatus of the antioxidant substance according to any one of claims 1 to 4 , and before the intake of the antioxidant substance, reactive hyperemia is caused in the forearm of the subject, and during the reactive hyperemia Ingestion forearm diameter change measuring device for measuring changes in forearm diameter, and for causing reactive hyperemia in the forearm of the subject after ingestion of antioxidants, and measuring changes in forearm diameter during the reactive hyperemia An anti-oxidant substance comprising: a forearm diameter change measuring device after ingestion of an anti-oxidant; and an output device for outputting the antioxidant power of the antioxidant substance measured by the antioxidant power measuring device. Antioxidant power measurement system. Anti of claim 5, characterized in that it comprises respectively the intake prior forearm diameter change measurement device and after ingestion forearm diameter change measurement unit, a strain gauge plethysmography, and the wrist cuffs, and upper arm cuff Antioxidant power measurement system for oxidants.

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