JP2019150553A - In-vivo no production device - Google Patents
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Abstract
Description
本発明は、生体内ＮＯ産生装置に関し、より詳しくは、血管等の生体内でＮＯ（一酸化窒素）を産生するための生体内ＮＯ産生装置に関する。 The present invention relates to an in vivo NO production device, and more particularly to an in vivo NO production device for producing NO (nitrogen monoxide) in a living body such as a blood vessel.
生体内の血管内皮細胞で産生されるＮＯには血管拡張作用があり、動脈硬化の予防において重要な役割を担っていることが従来から知られている。ＮＯの産生量を増やすためには、運動や入浴などにより血流を増加させることが有効とされているが、従来の方法で十分な量のＮＯを産生することは困難である。 It has been conventionally known that NO produced by vascular endothelial cells in a living body has a vasodilating action and plays an important role in preventing arteriosclerosis. In order to increase the production amount of NO, it is effective to increase the blood flow by exercise or bathing, but it is difficult to produce a sufficient amount of NO by the conventional method.
一方、生体の血流を外部から制御する装置として、例えば特許文献１に開示されているように、動脈の圧迫による阻血および圧迫解除による再灌流を繰り返す構成が知られている。 On the other hand, as an apparatus for controlling the blood flow of a living body from the outside, for example, as disclosed in Patent Document 1, a configuration is known in which reperfusion is performed by ischemia due to arterial pressure and relieving pressure.
ところが、上記特許文献１の装置は、動脈の圧迫を、血液の流れが遮断される阻血に至るように、使用者の最大血圧（収縮期血圧）よりも高い圧力で行うため、これを一定期間（例えば５分程度）継続すると、使用者の痛みや不快感が過大になり易いという問題があった。更に、上記特許文献１の装置は、生体内でのアセチルコリンの産生促進を目的とするものであり、ＮＯを効率良く産生することについては、従来から十分検討されていないのが現状である。 However, the device of Patent Document 1 performs compression of an artery at a pressure higher than the user's maximum blood pressure (systolic blood pressure) so as to reach ischemia in which the blood flow is blocked. If it continues (for example, about 5 minutes), there is a problem that the user's pain and discomfort tend to be excessive. Furthermore, the device of Patent Document 1 is intended to promote the production of acetylcholine in a living body, and it has not been sufficiently studied to efficiently produce NO.
そこで、本発明は、使用者の痛みや不快感を抑制しつつ、生体内でＮＯを効率良く産生することができる生体内ＮＯ産生装置の提供を目的とする。 Then, this invention aims at provision of the in-vivo NO production apparatus which can produce NO efficiently in the living body, suppressing a user's pain and discomfort.
本発明の前記目的は、四肢のいずれかに装着されて血管を圧迫する圧迫手段と、前記圧迫手段による圧迫を基準圧力に基づいて制御する制御手段とを備え、前記基準圧力は収縮期血圧であり、前記制御手段は、前記基準圧力の４７〜９３％に圧迫圧力を設定し、前記圧迫圧力で前記圧迫手段による所定時間の圧迫を行う生体内ＮＯ産生装置により達成される。 The object of the present invention includes compression means that is attached to one of the extremities and compresses a blood vessel, and control means that controls compression by the compression means based on a reference pressure, wherein the reference pressure is systolic blood pressure. The control means is achieved by an in-vivo NO producing device that sets a compression pressure to 47-93% of the reference pressure and performs compression for a predetermined time by the compression means with the compression pressure.
この生体内ＮＯ産生装置は、前記基準圧力を使用者の操作により入力可能な入力手段を更に備えることが好ましい。 This in-vivo NO production device preferably further comprises an input means capable of inputting the reference pressure by a user operation.
前記制御手段は、前記圧迫手段による圧迫を、間隔をあけて繰り返し行うことが好ましく、前記圧迫手段による圧迫を３回繰り返して停止することがより好ましい。前記制御手段は、前記圧迫手段による圧迫を繰り返す毎に、前記圧迫圧力を前記基準圧力の４７〜７０％の範囲で段階的に増加させるように構成してもよい。 The control means preferably performs the compression by the compression means repeatedly at intervals, and more preferably stops the compression by the compression means three times. The control means may be configured to increase the compression pressure stepwise within a range of 47 to 70% of the reference pressure every time the compression by the compression means is repeated.
本発明によれば、使用者の痛みや不快感を抑制しつつ、生体内でＮＯを効率良く産生することができる生体内ＮＯ産生装置を提供することができる。 ADVANTAGE OF THE INVENTION According to this invention, the in-vivo NO production apparatus which can produce NO efficiently in the living body can be provided, suppressing a user's pain and discomfort.
以下、本発明の一実施形態について添付図面を参照して説明する。図１は、本発明の一実施形態に係る生体内ＮＯ産生装置の概略構成図であり、図２は、 図１に示す生体内ＮＯ産生装置のブロック図である。図１および図２に示すように、生体内ＮＯ産生装置１は、腕や脚などの四肢のいずれかに装着される圧迫装置１０と、圧迫装置１０に接続される装置本体２０とを備えている。圧迫装置１０は、本実施形態では１つとしているが、複数設けて、それぞれを四肢の異なる部位に装着可能に構成してもよい。 Hereinafter, an embodiment of the present invention will be described with reference to the accompanying drawings. FIG. 1 is a schematic configuration diagram of an in vivo NO production device according to an embodiment of the present invention, and FIG. 2 is a block diagram of the in vivo NO production device shown in FIG. As shown in FIGS. 1 and 2, the in-vivo NO production device 1 includes a compression device 10 that is attached to one of four limbs such as an arm and a leg, and a device body 20 that is connected to the compression device 10. Yes. In the present embodiment, one compression device 10 is provided, but a plurality of compression devices 10 may be provided so that each can be attached to different parts of the limbs.
圧迫装置１０は、帯状のベルト１１と、ベルト１１の内面に取り付けられた流体袋１２とを備えており、動脈の血流を抑制しようとする生体部位に流体袋１２を当接させて、ベルト１１を巻き付けた後、面ファスナー等からなる固着部１３をベルト１１の外面に押し付けることにより、圧迫装置１０を生体部位に固定することができる。圧迫装置１０としては、例えば、市販されている血圧測定用のカフを使用することができる。 The compression device 10 includes a belt-like belt 11 and a fluid bag 12 attached to the inner surface of the belt 11, and the fluid bag 12 is brought into contact with a living body site where blood flow in an artery is to be suppressed. After winding 11, the pressing device 10 can be fixed to the living body part by pressing the fixing portion 13 made of a hook and loop fastener against the outer surface of the belt 11. As the compression device 10, for example, a commercially available cuff for blood pressure measurement can be used.
装置本体２０は、プッシュボタンやダイヤル等からなる入力部２１、基準圧力等の各種情報を記憶する半導体メモリ等からなる記憶部２２、ＣＰＵ等からなる制御部２３、圧迫装置１０を駆動する駆動部２４、および液晶パネル等からなる表示部２５を備えている。入力部２１および表示部２５は、装置本体２０の外面に設けられており、記憶部２２、制御部２３および駆動部２４は装置本体２０に内蔵されている。 The apparatus main body 20 includes an input unit 21 including a push button and a dial, a storage unit 22 including a semiconductor memory that stores various information such as a reference pressure, a control unit 23 including a CPU, and a drive unit that drives the compression device 10. 24 and a display unit 25 including a liquid crystal panel or the like. The input unit 21 and the display unit 25 are provided on the outer surface of the apparatus main body 20, and the storage unit 22, the control unit 23, and the drive unit 24 are built in the apparatus main body 20.
駆動部２４は、ポンプ、弁、圧力センサ等を備えており、圧迫装置１０の流体袋１２に接続管１４を介して接続されて、流体袋１２に対するガス等の流体の供給または排出を行う。制御部２３は、記憶部２２に記憶された基準圧力に基づいて、駆動部２４の駆動を制御する。 The drive unit 24 includes a pump, a valve, a pressure sensor, and the like, and is connected to the fluid bag 12 of the compression device 10 through the connection pipe 14 to supply or discharge a fluid such as a gas to the fluid bag 12. The control unit 23 controls driving of the driving unit 24 based on the reference pressure stored in the storage unit 22.
次に、上記の構成を備える生体内ＮＯ産生装置１の作動を説明する。本実施形態の生体内ＮＯ産生装置１は、使用者が血圧計により予め測定する等して把握する自身の収縮期血圧（最大血圧）を、入力部２１の操作により基準圧力として入力することができる。入力された基準圧力は、記憶部２２に格納される。記憶部２２に格納される基準圧力は、必ずしも入力部２１から入力された情報に限定されるものではなく、例えば、生体内ＮＯ産生装置１を他の血圧計等の機器に接続したり、生体内ＮＯ産生装置１に血圧計の機能を付加する等して、収縮期血圧が記憶部２２に自動的に格納されるように構成してもよい。あるいは、記憶部２２に過去に格納された基準圧力を、使用者の識別ＩＤの入力等により取り出して使用することもできる。 Next, the operation of the in-vivo NO production device 1 having the above configuration will be described. The in-vivo NO producing device 1 of the present embodiment can input its own systolic blood pressure (maximum blood pressure), which is grasped by the user by measuring in advance with a sphygmomanometer or the like, as a reference pressure by operating the input unit 21. it can. The input reference pressure is stored in the storage unit 22. The reference pressure stored in the storage unit 22 is not necessarily limited to the information input from the input unit 21. For example, the in-vivo NO production device 1 may be connected to other devices such as a sphygmomanometer, A systolic blood pressure may be automatically stored in the storage unit 22 by adding a function of a sphygmomanometer to the internal NO production device 1. Or the reference pressure stored in the memory | storage part 22 in the past can also be taken out and used by the input of a user's identification ID, etc.
ついで、使用者が四肢のいずれかの部位に圧迫装置１０を巻き付けて固定した後、入力部２１の開始ボタンを押圧すると、制御部２３は、使用者の基準圧力から流体袋１２の圧迫圧力を設定し、この圧迫圧力で圧迫装置１０による所定時間の圧迫を行う。この後、制御部２３が圧迫装置１０による圧迫を解除すると、抑制された血流の急激な変動によって血管内皮細胞にずり応力が作用し、血管内皮細胞からＮＯが放出される。生体部位を圧迫する所定時間は、その後の圧迫解除により血管拡張反応が生じる時間であれば特に限定されないが、例えば１〜１０分間であり、入力部２１の操作により連続的あるいは段階的（例えば１０秒毎）に変更可能にしてもよい。圧迫圧力は、後述するように基準圧力の４７〜９３％の範囲に設定されることが好ましく、動脈が阻血に至らない収縮期血圧よりも、更に低い圧力に設定される。このような設定圧力では、静脈系が主に圧迫される。圧迫圧力の基準圧力に対する割合は、上記の数値範囲内で予め記憶部２２に記憶された値を使用してもよく、あるいは、入力部２１の操作によって上記の数値範囲内で連続的あるいは段階的（例えば５刻み）に変更可能に構成することで、使用者が適宜選択した値を使用してもよい。 Next, when the user wraps and fixes the compression device 10 around any part of the limb and presses the start button of the input unit 21, the control unit 23 changes the compression pressure of the fluid bag 12 from the reference pressure of the user. The pressure is set and the compression device 10 performs compression for a predetermined time with this compression pressure. Thereafter, when the control unit 23 releases the compression by the compression device 10, shear stress acts on the vascular endothelial cells due to the rapid fluctuation of the suppressed blood flow, and NO is released from the vascular endothelial cells. The predetermined time for compressing the living body part is not particularly limited as long as it causes a vasodilatation reaction by the subsequent release of the pressure, but is, for example, 1 to 10 minutes, and is continuous or stepwise (for example, 10 It may be changeable every second). The compression pressure is preferably set in the range of 47 to 93% of the reference pressure, as will be described later, and is set to a pressure lower than the systolic blood pressure at which the artery does not cause ischemia. At such a set pressure, the venous system is mainly compressed. As the ratio of the compression pressure to the reference pressure, a value stored in the storage unit 22 in advance within the above numerical range may be used, or continuously or stepwise within the above numerical range by operating the input unit 21. By configuring so as to be changeable (for example, in increments of 5), a value appropriately selected by the user may be used.
圧迫装置１０による生体部位の圧迫は、１回のみであってもよいが、間隔をあけて繰り返し行うことが好ましい。圧迫を繰り返す場合の間隔（圧迫が解除される時間）は、特に限定されないが、血流増加により血管径が最大拡張に至ることが可能な時間であることが好ましく、例えば１〜１０分間であり、入力部２１の操作により連続的あるいは段階的（例えば１０秒毎）に変更可能にしてもよい。圧迫の繰り返し回数も特に制限はないが、繰り返し回数が多すぎるとＮＯ産生の効果が生じ難くなることから、２〜５回であることが好ましく、後述するように３回が最も好ましい。圧迫回数についても、入力部２１の操作により変更可能に構成することができる。圧迫を繰り返す場合の圧迫時間および圧迫解除時間は、圧迫の繰り返し毎に同じであってもよく、あるいは、圧迫の繰り返し毎に変化させてもよい。 Although the compression of the living body part by the compression apparatus 10 may be performed only once, it is preferably performed repeatedly at intervals. The interval when the compression is repeated (the time when the compression is released) is not particularly limited, but is preferably a time that allows the blood vessel diameter to reach maximum expansion due to an increase in blood flow, for example, 1 to 10 minutes. The operation may be changed continuously or stepwise (for example, every 10 seconds) by operating the input unit 21. There are no particular restrictions on the number of repetitions of compression, but if the number of repetitions is too large, the effect of NO production is less likely to occur. The number of compressions can also be configured to be changed by operating the input unit 21. The compression time and the compression release time when the compression is repeated may be the same every time the compression is repeated, or may be changed every time the compression is repeated.
図３は、大腿部の圧迫によるＮＯ代謝産物の測定結果を示している。被験者の収縮期血圧である１２８ｍｍＨｇを基準圧力とし、圧迫圧力をパラメータとして、５分間の圧迫および３分間の圧迫解除を３回繰り返した後の静脈でのＮＯ２血中濃度をGriess法により測定することで、ＮＯの産生量を推量した。圧迫圧力は、６０ｍｍＨｇ、９０ｍｍＨｇ、１２０ｍｍＨｇとしており、これらは基準圧力に対してそれぞれ約４７％、約７０％、約９３％である。 FIG. 3 shows the measurement results of NO metabolites by thigh compression. The NO 2 blood concentration in the vein after repeating 5 minutes of compression and 3 minutes of compression release 3 times is measured by Griess method using 128 mmHg which is the systolic blood pressure of the subject as a reference pressure and the compression pressure as a parameter. Thus, the production amount of NO was estimated. The compression pressure is 60 mmHg, 90 mmHg, and 120 mmHg, which are about 47%, about 70%, and about 93%, respectively, with respect to the reference pressure.
図３に示すように、圧迫圧力を基準圧力の４７〜９３％にしたときに、ＮＯが良好に産生されていることを確認した。圧迫圧力を基準圧力の９３％よりも高くして基準圧力に近づけると、圧迫時間の間に生じる痛みや不快感が過大になる一方、ＮＯの産生量は基準圧力の７０％のときをピークに減少傾向にあることから、圧迫圧力を基準圧力の４７〜９３％に設定することが好ましい。特に、圧迫圧力を基準圧力の４７〜７０％に設定すると、痛みや不快感を十分抑制しつつＮＯ産生を促すことができるため、より好ましい。圧迫を繰り返し行う場合、圧迫の繰り返しによって痛みや不快感を徐々に感じ難くなるため、繰り返し毎の圧迫圧力を、基準圧力の４７〜７０％の範囲で段階的に増加させることが好ましい。例えば、この割合に関する入力部２１からの入力値をＡとすると、入力部２１から入力等された基準圧力に対して、１回目の圧迫圧力は基準圧力の（Ａ−２０）％に、２回目の圧迫圧力は基準圧力の（Ａ−１０）％に、３回目の圧迫圧力は基準圧力のＡ％に、それぞれ設定することができる。上記の各割合は固定された値でもよく、例えば、１回目の圧迫圧力は基準圧力の５０％に、２回目の圧迫圧力は基準圧力の６０％に、３回目の圧迫圧力は基準圧力の７０％に、それぞれ設定することもできる。 As shown in FIG. 3, it was confirmed that NO was produced satisfactorily when the compression pressure was 47 to 93% of the reference pressure. When the compression pressure is set higher than 93% of the reference pressure and brought close to the reference pressure, the pain and discomfort generated during the compression time become excessive, while the NO production peaked at 70% of the reference pressure. Since the pressure tends to decrease, the compression pressure is preferably set to 47 to 93% of the reference pressure. In particular, it is more preferable to set the compression pressure to 47 to 70% of the reference pressure because NO production can be promoted while sufficiently suppressing pain and discomfort. When repeatedly performing compression, it is difficult to feel pain and discomfort gradually due to repeated compression. Therefore, it is preferable to increase the compression pressure for each repetition in a range of 47 to 70% of the reference pressure. For example, when the input value from the input unit 21 relating to this ratio is A, the first compression pressure is (A-20)% of the reference pressure with respect to the reference pressure input from the input unit 21 and the like. The compression pressure can be set to (A-10)% of the reference pressure, and the third compression pressure can be set to A% of the reference pressure. Each of the above ratios may be a fixed value. For example, the first compression pressure is 50% of the reference pressure, the second compression pressure is 60% of the reference pressure, and the third compression pressure is 70% of the reference pressure. % Can also be set respectively.
図４は、大腿部の圧迫の繰り返し回数をパラメータとしたときのＮＯ代謝産物の測定結果を示している。圧迫圧力は９０ｍｍＨｇとして、５分間の圧迫および３分間の圧迫解除を繰り返したときのＮＯの産生量を、図３に示す測定結果の場合と同様の測定方法で求めたところ、３回目までは圧迫を行う毎にＮＯ産生量は増加したが、４回目および５回目においては、ＮＯ産生量が圧迫前の値と同等であった。すなわち、圧迫を３回繰り返した後に停止することで、ＮＯを効率良く産生できることを確認した。 FIG. 4 shows the measurement results of NO metabolites when the number of repetitions of thigh compression is used as a parameter. When the compression pressure was 90 mmHg and the amount of NO produced when the compression for 5 minutes and the release of the compression for 3 minutes were repeated was determined by the same measurement method as in the measurement results shown in FIG. 3, it was compressed until the third time. The amount of NO production increased each time the test was performed, but in the fourth and fifth times, the NO production amount was equivalent to the value before compression. That is, it was confirmed that NO can be efficiently produced by stopping after repeating the compression three times.
本発明の効果を確認するため、歩行運動の前後におけるＮＯ産生量の変化を図５に示す。図５は、被験者の歩行前のＮＯ代謝産物と、３０分早足歩き後のＮＯ代謝産物とを、図３に示す測定結果の場合と同様の測定方法で求めた結果を示している。図５に示すように、歩行運動後のＮＯ産生量は、歩行運動前のＮＯ産生量に対して約１．５倍に増加している。この測定結果を、図３に示す測定結果と対比させると、図３に示す圧迫圧力が基準圧力の４７〜９３％である場合のＮＯ産生量は、いずれも図５に示す歩行運動後のＮＯ産生量の平均値を上回っており、本実施形態の生体内ＮＯ産生装置１を、図３の場合の圧迫条件下で使用することで、早足歩きを３０分した場合よりも多量のＮＯが産生することが明らかになった。 In order to confirm the effect of this invention, the change of NO production amount before and behind a walking exercise is shown in FIG. FIG. 5 shows the results obtained by measuring the NO metabolite before walking of the subject and the NO metabolite after walking fast for 30 minutes by the same measurement method as in the measurement result shown in FIG. As shown in FIG. 5, the NO production amount after walking exercise is increased by about 1.5 times the NO production amount before walking exercise. When this measurement result is compared with the measurement result shown in FIG. 3, the NO production amount when the compression pressure shown in FIG. 3 is 47 to 93% of the reference pressure is NO in the walking exercise shown in FIG. 5. The amount of production exceeds the average value, and the in-vivo NO production device 1 of this embodiment is used under the compression condition in the case of FIG. 3, so that a larger amount of NO is produced than when fast walking is performed for 30 minutes. It became clear to do.
図６は、本実施形態の生体内ＮＯ産生装置を被験者が継続的に使用した場合の脈拍数および血圧の変化を示している。９０ｍｍＨｇの圧迫圧力による５分間の圧迫および３分間の圧迫解除の３回の繰り返しを１セットとして、５月前半から毎日１セットを行い、半月毎に脈拍数、最低血圧および最高血圧を測定した。図６に示すように、脈拍数および血圧は、いずれも使用開始から１か月程度を経過すると低下傾向を示しており、ＮＯによる自立神経系への介入効果が示唆された。 FIG. 6 shows changes in the pulse rate and blood pressure when the subject continuously uses the in vivo NO production device of the present embodiment. Three sets of 5 minutes of compression with 90 mmHg pressure and 3 minutes of release of compression were taken as one set, and one set was performed every day from the first half of May, and the pulse rate, diastolic blood pressure and systolic blood pressure were measured every half month. As shown in FIG. 6, both the pulse rate and blood pressure showed a tendency to decrease after about one month from the start of use, suggesting an intervention effect on the independent nervous system by NO.
図７は、本実施形態の生体内ＮＯ産生装置を被験者が継続的に使用した場合の血糖値（ＨｂＡ１ｃ値）の変化を示している。図６の測定と同様の圧迫条件で４月前半から５月末まで毎日１セットを行い、６月からは１日２セットに増やして体重およびＨｂＡ１ｃ値を毎月測定したところ、７月前半の時点では、体重は６月から増加して開始時とほとんど同じである一方、ＨｂＡ１ｃ値は低下傾向を示しており、ＮＯによる自立神経系への介入効果が示唆された。 FIG. 7 shows a change in blood glucose level (HbA1c value) when the subject continuously uses the in-vivo NO production device of the present embodiment. Under the same compression conditions as in Fig. 6, one set was performed daily from the first half of April to the end of May, and from June, the weight and HbA1c values were increased every month to two sets per day. While the body weight increased from June and was almost the same as that at the start, the HbA1c value showed a tendency to decrease, suggesting the effect of NO intervention on the autonomic nervous system.
図８は、本実施形態の生体内ＮＯ産生装置の使用による血管年齢（ｂａＰＷＶ値）の変化を示している。被験者が年１回の定期健康診断で測定したｂａＰＷＶ値は、生体内ＮＯ産生装置の使用開始により大幅に低下しており、血管年齢の改善が示唆された。 FIG. 8 shows changes in blood vessel age (baPWV value) due to the use of the in vivo NO production apparatus of this embodiment. The baPWV value measured by the subject in a regular health check once a year was significantly reduced by the start of use of the in vivo NO production device, suggesting an improvement in blood vessel age.
１ 生体内ＮＯ産生装置
１０ 圧迫装置
２０ 装置本体
２１ 入力部
２３ 制御部
DESCRIPTION OF SYMBOLS 1 In-vivo NO production apparatus 10 Compression apparatus 20 Apparatus main body 21 Input part 23 Control part
Claims (5)
前記圧迫手段による圧迫を基準圧力に基づいて制御する制御手段とを備え、
前記基準圧力は収縮期血圧であり、
前記制御手段は、前記基準圧力の４７〜９３％に圧迫圧力を設定し、前記圧迫圧力で前記圧迫手段による所定時間の圧迫を行う生体内ＮＯ産生装置。 A compression means that is attached to one of the limbs and compresses the blood vessel;
Control means for controlling the compression by the compression means based on a reference pressure,
The reference pressure is systolic blood pressure;
The in-vivo NO production apparatus, wherein the control means sets a compression pressure to 47 to 93% of the reference pressure, and performs compression for a predetermined time by the compression means with the compression pressure.
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| US20050159690A1 (en) * | 2003-12-29 | 2005-07-21 | Jacob Barak | Method and apparatus for assisting vascular flow through external compression synchronized with venous phasic flow |
| JP2014028109A (en) * | 2012-06-28 | 2014-02-13 | Ｋａａｔｓｕ Ｊａｐａｎ株式会社 | Pressurization/depressurization control system, control method therefor, and method for strengthening of blood vessel |
| JP2017209453A (en) * | 2016-05-27 | 2017-11-30 | 株式会社ユネクス | Ultrasound cross-sectional image measuring device |
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| US20050159690A1 (en) * | 2003-12-29 | 2005-07-21 | Jacob Barak | Method and apparatus for assisting vascular flow through external compression synchronized with venous phasic flow |
| JP2014028109A (en) * | 2012-06-28 | 2014-02-13 | Ｋａａｔｓｕ Ｊａｐａｎ株式会社 | Pressurization/depressurization control system, control method therefor, and method for strengthening of blood vessel |
| JP2017209453A (en) * | 2016-05-27 | 2017-11-30 | 株式会社ユネクス | Ultrasound cross-sectional image measuring device |
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