JP6260949B2 - Organic substance manufacturing apparatus and method - Google Patents
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Description
本発明は、烏賊骨等を原料として有機物を製造する技術に関する。 The present invention relates to a technique for producing an organic material using a bandage bone or the like as a raw material.
イカ軟骨等の烏賊骨由来のβキチン質を製造する手法が提案されている(特許文献1〜3参照)。カニまたはエビなどの甲殻類の外殻由来のαキチン質を製造する手法が提案されている(非特許文献1参照)。 A method for producing β-chitin derived from bandit bones such as squid cartilage has been proposed (see Patent Documents 1 to 3). A method for producing α-chitin derived from the outer shell of a crustacean such as crab or shrimp has been proposed (see Non-Patent Document 1).
しかし、当該手法によれば、酸・アルカリ触媒を用いるため、廃液処理および酸・アルカリ触媒と生成物の分離のための工程が必要であった。また、反応に要する時間が3時間〜3日と比較的長いため、その誘導体の製造効率の向上が望まれる。 However, according to this method, since an acid / alkali catalyst is used, a process for waste liquid treatment and separation of the acid / alkali catalyst and the product is required. In addition, since the time required for the reaction is relatively long as 3 hours to 3 days, it is desired to improve the production efficiency of the derivative.
そこで、本発明は、酸・アルカリ触媒を用いずに水だけで、烏賊骨または甲殻類の外郭を含む原料から有機物を効率的に製造しうる装置および方法を提供することを目的とする。 Therefore, an object of the present invention is to provide an apparatus and a method that can efficiently produce an organic substance from a raw material including a bandage bone or a crustacean shell using only water without using an acid / alkali catalyst.
本発明の有機物製造方法は、烏賊骨または甲殻類の外郭を含む原料由来の有機物を製造する方法であって、前記原料を亜臨界水に接触させる工程を含んでいることを特徴とする。前記方法において、亜臨界水の温度Θおよび圧力Pのそれぞれを150〜300[℃]および0.5〜8.6[MPa]のそれぞれに調節する工程と、亜臨界水が高温であるほど短くなるように前記原料と亜臨界水との接触時間Tを調節する工程と、をさらに含んでいることが好ましい。前記方法において、Θ[℃]−T[min]平面における点(150,120)、(200,60)、(250,20)および(300,2)に基づいて定義されている近似曲線にしたがって、前記原料と亜臨界水との接触時間Tが調節されることが好ましい。 The organic material production method of the present invention is a method for producing an organic material derived from a raw material including a bandit bone or crustacean shell, and includes a step of bringing the raw material into contact with subcritical water. In the method, the step of adjusting the temperature Θ and the pressure P of the subcritical water to 150 to 300 [° C.] and 0.5 to 8.6 [MPa], respectively, and the shorter the subcritical water, the shorter the temperature. It is preferable to further include a step of adjusting the contact time T between the raw material and subcritical water. In the method, according to an approximate curve defined based on points (150, 120), (200, 60), (250, 20) and (300, 2) in the Θ [° C.]-T [min] plane. The contact time T between the raw material and subcritical water is preferably adjusted.
本発明の有機物製造装置は、烏賊骨または甲殻類の外郭を含む原料由来の有機物を製造する装置であって、前記原料を水とともに出し入れ自在に収容する反応容器と、前記反応容器に収容されている水の温度に応じた信号を出力する温度センサと、前記反応容器に収容されている水の圧力に応じた信号を出力する圧力センサと、前記温度センサの出力信号および前記圧力センサの出力信号に基づき、前記反応容器に収容されている水の温度および圧力を調節して当該水を亜臨界状態に制御する制御手段と、を備えていることを特徴とする。 The organic material production apparatus of the present invention is an apparatus for producing an organic material derived from a raw material including a clam bone or a crustacean shell, wherein the raw material is accommodated in and out with water, and the reaction container is accommodated in the reaction container. A temperature sensor that outputs a signal according to the temperature of the water that is in contact, a pressure sensor that outputs a signal according to the pressure of the water contained in the reaction vessel, an output signal of the temperature sensor, and an output signal of the pressure sensor And a control means for adjusting the temperature and pressure of the water contained in the reaction vessel to control the water to a subcritical state.
本発明の装置および方法によれば、亜臨界水をたとえば原料としての烏賊骨に接触させるだけで、酸触媒およびアルカリ触媒を用いずに当該烏賊骨由来の有機物が短時間で効率的に製造されうる。この有機物としては、βキチンが烏賊骨の固体残渣の形で得られ、かつ、ペプチド(タンパク質)が水溶液の形で得られる。 According to the apparatus and method of the present invention, the organic matter derived from the bandit bone can be efficiently produced in a short time without using an acid catalyst and an alkali catalyst, simply by bringing subcritical water into contact with the bandit bone as a raw material, for example. sell. As this organic substance, β-chitin is obtained in the form of a solid residue of bandit bone, and a peptide (protein) is obtained in the form of an aqueous solution.
(有機物製造装置の構成)
図1に示されている本発明の一実施形態としての有機物製造装置は、蓋または扉の開閉によって原料Xおよび水の出し入れが可能な反応容器10と、反応容器10の収容物を加熱するための加熱器11と、反応容器10に接続されている排水管20と、コンピュータにより構成されている制御装置30と、を備えている。
(Configuration of organic substance manufacturing equipment)
The organic substance manufacturing apparatus as one embodiment of the present invention shown in FIG. 1 heats a reaction vessel 10 capable of taking in and out the raw material X and water by opening and closing a lid or a door, and the contents in the reaction vessel 10. Heater 11, a drain pipe 20 connected to the reaction vessel 10, and a control device 30 constituted by a computer.
反応容器10には、その内部温度に応じた信号を出力する温度センサS1と、その内部圧力に応じた信号を出力する圧力センサS2とが設けられている。排水管20には、排水管20を流れる水溶液を冷却するように構成されている冷却器22と、背圧調整バルブ21とが上流から順に設けられている。 The reaction vessel 10 is provided with a temperature sensor S1 for outputting a signal corresponding to the internal temperature and a pressure sensor S2 for outputting a signal corresponding to the internal pressure. The drain pipe 20 is provided with a cooler 22 configured to cool the aqueous solution flowing through the drain pipe 20 and a back pressure adjusting valve 21 in order from the upstream.
制御装置30は、温度センサS1の出力信号に基づき、加熱器11の発熱量を制御することにより、反応容器10に収容されている水の温度Θを調節するようにプログラムされている。制御装置30は、圧力センサS2の出力信号に基づき、背圧調整バルブ21の開度を制御することにより、反応容器10に収容されている水の圧力Pを調節するようにプログラムされている。制御装置30は、反応容器10に収容されている水の温度Θおよび圧力Pを制御して当該水を亜臨界状態に制御する。 The control device 30 is programmed to adjust the temperature Θ of the water stored in the reaction vessel 10 by controlling the amount of heat generated by the heater 11 based on the output signal of the temperature sensor S1. The control device 30 is programmed to adjust the pressure P of the water stored in the reaction vessel 10 by controlling the opening degree of the back pressure adjustment valve 21 based on the output signal of the pressure sensor S2. The control device 30 controls the water Θ and the pressure P stored in the reaction vessel 10 to control the water to a subcritical state.
反応容器10に対して液相状態または亜臨界状態の水を供給するための給水管が接続されていてもよい。 A water supply pipe for supplying liquid phase state or subcritical state water to the reaction vessel 10 may be connected.
(有機物の製造方法)
まず、蓋が開放されて原料Xとして烏賊骨(イカの骨)が水とともに反応容器10に収容され、蓋が閉塞されて反応容器10が密閉される。この状態で、制御装置30により、反応容器10内の水が亜臨界状態に維持されるようにその温度Θおよび圧力Pが制御される。これにより、水が亜臨界状態になり、亜臨界水を原料Xに接触させることができる。
(Method for producing organic matter)
First, the lid is opened, and bandit bones (squid bones) are stored in the reaction vessel 10 together with water as the raw material X, the lid is closed, and the reaction vessel 10 is sealed. In this state, the temperature Θ and the pressure P are controlled by the control device 30 so that the water in the reaction vessel 10 is maintained in the subcritical state. Thereby, water will be in a subcritical state and subcritical water can be made to contact the raw material X.
亜臨界水の温度Θは150〜300[℃]の範囲に含まれるように制御され、かつ、亜臨界水の圧力Pは0.5〜8.6[MPa]の範囲に含まれるように制御されることが好ましい。 The temperature Θ of the subcritical water is controlled to be included in the range of 150 to 300 [° C.], and the pressure P of the subcritical water is controlled to be included in the range of 0.5 to 8.6 [MPa]. It is preferred that
亜臨界水が高温であるほど亜臨界水による原料Xの処理時間Tが短くなるように調節されることが好ましい。たとえば、原料Xと亜臨界水との接触時間Tは、亜臨界水温度Θに基づき、図2に示されている曲線にしたがって制御されることが好ましい。この曲線は、Θ[℃]−T[min]平面における点(150,120)、(200,60)、(250,20)および(300,2)に基づいて定義されている近似曲線である。近似法としては、多項式近似または指数近似などが採用されうる。たとえば、指数近似の場合、当該曲線は関係式(1)のように表わされる。 It is preferable to adjust so that the processing time T of the raw material X by subcritical water becomes short, so that subcritical water is high temperature. For example, the contact time T between the raw material X and the subcritical water is preferably controlled according to the curve shown in FIG. 2 based on the subcritical water temperature Θ. This curve is an approximate curve defined based on points (150, 120), (200, 60), (250, 20), and (300, 2) in the Θ [° C.]-T [min] plane. . As an approximation method, polynomial approximation or exponential approximation can be adopted. For example, in the case of exponential approximation, the curve is expressed as the relational expression (1).
T=exp(−α(Θ−β))‥(1)。 T = exp (−α (Θ−β)) (1).
当該接触時間Tの経過後、背圧調整バルブ21が開放されて排水管20を通じて反応容器10から水が導出される。そして、反応容器10の蓋が開放され、βキチンが固体残渣の形態で得られる。また、ペプチドが、反応容器10から流出して冷却器22において冷却された水(ペプチド水溶液)の形態で得られる。 After the contact time T has elapsed, the back pressure adjustment valve 21 is opened and water is led out from the reaction vessel 10 through the drain pipe 20. Then, the lid of the reaction vessel 10 is opened, and β-chitin is obtained in the form of a solid residue. Further, the peptide is obtained in the form of water (peptide aqueous solution) that has flowed out of the reaction vessel 10 and cooled in the cooler 22.
(実施例)
(Θ,P)=(150,0.5)、(200,1.5)、(250,4.1)および(300,8.6)のそれぞれの条件下で、第1〜第4実施例のそれぞれの亜臨界水処理が実施された。
(Example)
First to fourth implementations under the conditions of (Θ, P) = (150, 0.5), (200, 1.5), (250, 4.1) and (300, 8.6) Each subcritical water treatment in the examples was performed.
図3(a)、図3(b)図4(a)および図4(b)のそれぞれには、第1〜第4実施例のそれぞれの亜臨界水処理条件と原料Xの固体残渣重量との関係が示されている。図3(a)、図3(b)図4(a)および図4(b)から、Θが高温であるほど、亜臨界処理時間の延長に伴う固体残渣重量の減少率が上昇することがわかる。 3 (a), FIG. 3 (b), FIG. 4 (a) and FIG. 4 (b) respectively show the subcritical water treatment conditions and the weight of the solid residue of the raw material X in the first to fourth embodiments. The relationship is shown. From FIG. 3 (a), FIG. 3 (b), FIG. 4 (a) and FIG. 4 (b), it can be seen that the higher the Θ, the higher the reduction rate of the solid residue weight with the extension of the subcritical processing time. Recognize.
図3(a)から、Θ=150[℃]の場合、亜臨界処理時間が120[min]に至っても、固体残渣の重量が本来的なβキチンの含有量(烏賊骨の約30%を占める。)よりも多く、当該固体残渣にはその他の有機物(ペプチド)が残存していることがわかる。図3(b)から、Θ=200[℃]の場合、亜臨界処理時間が60[min]に至っても、固体残渣の重量が本来的なβキチンの含有量(烏賊骨の約30%を占める。)よりも多く、当該固体残渣にはその他の有機物(ペプチド)が残存していることがわかる。 From FIG. 3 (a), in the case of Θ = 150 [° C.], even if the subcritical processing time reaches 120 [min], the weight of the solid residue is the original β-chitin content (about 30% of the bandit bone). It can be seen that other organic substances (peptides) remain in the solid residue. From FIG. 3B, in the case of Θ = 200 [° C.], even if the subcritical processing time reaches 60 [min], the solid residue weight is less than the original β-chitin content (about 30% of the bandit bone). It can be seen that other organic substances (peptides) remain in the solid residue.
図4(a)から、Θ=250[℃]の場合、亜臨界処理時間が30[min]に至ると固体残渣の重量が本来的なβキチンの含有量とほぼ同じになることがわかる。図4(b)から、Θ=300[℃]の場合、亜臨界処理時間が3[min]に至ると固体残渣の重量が本来的なβキチンの含有量よりも少なく、βキチンが分解されて水に溶出していることがわかる。 FIG. 4A shows that when Θ = 250 [° C.], the weight of the solid residue becomes almost the same as the content of β-chitin when the subcritical processing time reaches 30 [min]. From FIG. 4B, in the case of Θ = 300 [° C.], when the subcritical processing time reaches 3 [min], the weight of the solid residue is less than the original content of β-chitin, and β-chitin is decomposed. It can be seen that it is eluted in water.
図5(a)および図5(b)のそれぞれには、第2および第4実施例のそれぞれの亜臨界水処理条件と原料Xの固体残渣のXRD測定結果との関係が示されている。図5から、Θが高温であるほど、固体残渣のXRDパターンがβキチンのXRDパターンに迅速に近似していくこと、ひいてはβキチンの固体残渣の形での回収または製造効率が上昇することがわかる。 Each of FIG. 5A and FIG. 5B shows the relationship between the subcritical water treatment conditions of the second and fourth examples and the XRD measurement result of the solid residue of the raw material X. From FIG. 5, it can be seen that the higher the Θ, the faster the solid residue XRD pattern closely approximates the β-chitin XRD pattern, and hence the higher the recovery or production efficiency of the β-chitin solid residue. Recognize.
図6(a)および図6(b)のそれぞれには、第2および第4実施例のそれぞれの亜臨界水処理条件と原料Xの固体残渣の分子量測定結果との関係が示されている。図6から、固体残渣として得られるβキチンの分子量が、Θが高温であるほど迅速に減少し、亜臨界処理条件(P,Θ,T)の制御によって、得られるβキチンの分子量が制御されうることがわかる。 6A and 6B show the relationship between the subcritical water treatment conditions of the second and fourth examples and the molecular weight measurement result of the solid residue of the raw material X, respectively. From FIG. 6, the molecular weight of β-chitin obtained as a solid residue decreases more rapidly as Θ is higher, and the molecular weight of β-chitin obtained is controlled by controlling subcritical processing conditions (P, Θ, T). I can understand.
図7(a)および図7(b)のそれぞれには、第2および第4実施例のそれぞれの亜臨界水処理により得られたペプチドおよび炭素量の定量結果との関係が示されている。ペプチド(タンパク質)はLowry法により定量され、炭素量はTOC(全有機体炭素計)を用いて定量された。図7から、Θが高温であるほど、ペプチドおよび炭素量がともに早期に増大すること、ひいてはペプチドの水溶液の形での回収または製造効率が上昇することがわかる。 FIG. 7 (a) and FIG. 7 (b) show the relationship between the peptides obtained by the respective subcritical water treatments of the second and fourth examples and the quantitative results of the carbon amount. Peptides (proteins) were quantified by the Lowry method, and the amount of carbon was quantified using TOC (total organic carbon meter). From FIG. 7, it can be seen that the higher the Θ, the faster the peptide and carbon content both increase, and the higher the recovery or production efficiency of the peptide in the form of an aqueous solution.
図8(a)および図8(b)のそれぞれには、第2および第4実施例のそれぞれのの亜臨界水処理により得られたペプチドの分子量との関係が示されている。分子量はゲル濾過法により測定された。図8から、亜臨界処理条件(P,Θ,T)の制御によって、得られるペプチドの分子量が制御されうることがわかる。 FIG. 8 (a) and FIG. 8 (b) show the relationship between the molecular weights of the peptides obtained by the respective subcritical water treatments of the second and fourth examples. The molecular weight was measured by gel filtration. FIG. 8 shows that the molecular weight of the obtained peptide can be controlled by controlling the subcritical processing conditions (P, Θ, T).
図9には、第2および第4実施例のそれぞれの亜臨界水処理により得られたペプチドのACE阻害活性(血圧降下作用)の測定結果が一点鎖線および二点鎖線のそれぞれにより示されている。ACE阻害活性は、Chengらの方法(Cheung et al., Binding of peptide substrates and inhibitors of angiotensin−converting enzyme:Importance of the COOH−terminal dipeptide sequence, J Biol Chem.,255,401(1980)参照)の改変方法にしたがって測定された。 In FIG. 9, the measurement results of the ACE inhibitory activity (blood pressure lowering action) of the peptides obtained by the subcritical water treatment of the second and fourth examples are shown by the one-dot chain line and the two-dot chain line, respectively. . The ACE inhibitory activity was determined by the method of Cheng et al. Measured according to the modified method.
具体的には、0.2[mg/mL]牛血清アルブミンを含む100[mM]ホウ酸ナトリウム(pH8.3)で溶解した0.05[units/mL]ウシ肺臓由来ACE 25[μL]が試料25[μL]に添加かつ混合され、37[℃]で5[min]にわたりプレインキュベーションが行われた。0.5[M]塩化ナトリウムを含む100[mM]ホウ酸ナトリウム(pH8.3)で溶解した8.3[mM]ヒプリル−L−ヒスチジル−L−ロイシン(基質)75[μL]が当該混合溶液に添加かつ混合され,37[℃]で90[min]にわたり反応が促進された。アセトニトリル:メタノール:酢酸=5:5:1の混合溶媒で溶解した10[μg/mL]カプトプリル溶液250[μL]が当該混合溶液に添加かつ混合され、その反応が停止された。基質がACEによって加水分解されて生じた馬尿酸がHPLC法にしたがって定量され、ACE阻害活性が測定された。 Specifically, 0.05 [units / mL] bovine lung-derived ACE 25 [μL] dissolved in 100 [mM] sodium borate (pH 8.3) containing 0.2 [mg / mL] bovine serum albumin The sample was added to and mixed with 25 [μL], and pre-incubation was performed at 37 [° C.] for 5 [min]. 8.3 [mM] Hipril-L-histidyl-L-leucine (substrate) 75 [μL] dissolved in 100 [mM] sodium borate (pH 8.3) containing 0.5 [M] sodium chloride was mixed. The reaction was added to and mixed with the solution, and the reaction was promoted at 37 [° C.] for 90 [min]. A 10 [μg / mL] captopril solution 250 [μL] dissolved in a mixed solvent of acetonitrile: methanol: acetic acid = 5: 5: 1 was added to and mixed with the mixed solution, and the reaction was stopped. Hippuric acid produced by hydrolysis of the substrate by ACE was quantified according to the HPLC method, and ACE inhibitory activity was measured.
当該測定にはHPLCが用いられ、分析用カラムにはJ’sphere−ODS−M80(4.6 mm×250 mm)(YMC, Kyoto, Japan)が用いられた。分析は室温で行われた。各試料溶液が10[μL]インジェクトされ、分析条件は流速0.7[mL/min]に調節され、移動相には20[%]メタノール/80[%]20[mM]リン酸アンモニウム緩衝液(pH3.2)が用いられた。馬尿酸は検出波長228[nm]において検出された。本条件で馬尿酸のピークは17[min]付近に出現するため、このピーク面積に基づきACE阻害活性が以下の式にしたがって算出された。 HPLC was used for the measurement, and J'sphere-ODS-M80 (4.6 mm × 250 mm) (YMC, Kyoto, Japan) was used for the analytical column. Analysis was performed at room temperature. Each sample solution was injected 10 [μL], the analysis conditions were adjusted to a flow rate of 0.7 [mL / min], and the mobile phase was 20 [%] methanol / 80 [%] 20 [mM] ammonium phosphate buffer. A liquid (pH 3.2) was used. Hippuric acid was detected at a detection wavelength of 228 [nm]. Since the peak of hippuric acid appears around 17 [min] under these conditions, the ACE inhibitory activity was calculated according to the following formula based on this peak area.
ACE阻害活性[%]=((−試料のピーク面積)−(+試料のピーク面積))/((−試料のピーク面積))×100
図9から、Θが高温であるほどACE阻害活性の高いペプチドが早期に得られること、ひいては亜臨界処理条件(P,Θ,T)の制御によってACE阻害活性の高いペプチドを選択的に製造しうることがわかる。
ACE inhibitory activity [%] = ((− sample peak area) − (+ sample peak area)) / ((− sample peak area)) × 100
From FIG. 9, peptides having a high ACE inhibitory activity can be obtained earlier by controlling the subcritical processing conditions (P, Θ, T) as peptides having a higher ACE inhibitory activity are obtained earlier as Θ is higher. I can understand.
亜臨界水の採用によって、酸触媒およびアルカリ触媒がなくてもβキチンおよびペプチドを抽出可能であるが、必要に応じて酸触媒またはアルカリ触媒を反応容器10等の反応系に共存させてもよい。 By using subcritical water, β-chitin and peptides can be extracted without an acid catalyst and an alkali catalyst. However, an acid catalyst or an alkali catalyst may coexist in a reaction system such as the reaction vessel 10 if necessary. .
(本発明の他の実施形態)
原料Xとして烏賊骨ではなく甲殻類の外郭(カニ殻)が用いられ、(Θ,P)=(300,8.6)、(350,16.6)および(400,37.1)のそれぞれの条件下で亜臨界水処理が実施された。図10には、各亜臨界水処理条件と原料Xの固体残渣重量との関係が、実線、一点鎖線および二点鎖線のそれぞれにより示されている。図10から、Θが高温であるほど、亜臨界処理時間の延長に伴う固体残渣重量の減少率が上昇することがわかる。
(Other embodiments of the present invention)
Crustacean shell (crab shell) is used as raw material X instead of bandit bone, (Θ, P) = (300, 8.6), (350, 16.6) and (400, 37.1) respectively Subcritical water treatment was carried out under the following conditions. In FIG. 10, the relationship between each subcritical water treatment condition and the solid residue weight of the raw material X is shown by a solid line, a one-dot chain line, and a two-dot chain line, respectively. From FIG. 10, it can be seen that the higher the Θ is, the higher the reduction rate of the solid residue weight with the extension of the subcritical processing time.
10‥反応容器、11‥加熱器、20‥排水管、21‥背圧調整バルブ、22‥冷却器、30‥制御装置、S1‥温度センサ、S2‥圧力センサ、X‥原料。 DESCRIPTION OF SYMBOLS 10 ... Reaction container, 11 ... Heater, 20 ... Drain pipe, 21 ... Back pressure control valve, 22 ... Cooler, 30 ... Control device, S1 ... Temperature sensor, S2 ... Pressure sensor, X ... Raw material.
Claims (4)
前記原料を亜臨界水に接触させる工程と、
前記亜臨界水の温度Θ[℃]および圧力P[MPa]のそれぞれを(Θ,P)=(200,1.5)および(Θ,P)=(300,8.6)のそれぞれに可変的に調節することにより、ACE阻害活性が制御されたペプチドを前記有機物として得る工程と、を含んでいることを特徴とする方法。 A method for producing an organic material derived from a raw material including a bandage bone or a crustacean shell,
Contacting the raw material with subcritical water;
The temperature Θ [° C.] and the pressure P [MPa] of the subcritical water can be changed to (Θ, P) = (200, 1.5) and (Θ, P) = (300, 8.6) , respectively. And obtaining a peptide whose ACE inhibitory activity is controlled as the organic substance by regulating the ACE inhibitory activity.
前記原料を水とともに出し入れ自在に収容する反応容器と、
前記反応容器に収容されている水の温度に応じた信号を出力する温度センサと、
前記反応容器に収容されている水の圧力に応じた信号を出力する圧力センサと、
前記温度センサの出力信号および前記圧力センサの出力信号に基づき、前記反応容器に収容されている水の温度および圧力を調節して当該水を亜臨界状態に制御する制御手段と、を備え、
前記制御手段が、前記亜臨界水の温度Θ[℃]および圧力P[MPa]のそれぞれを(Θ,P)=(200,1.5)および(Θ,P)=(300,8.6)のそれぞれに可変的に調節することにより、前記反応容器においてACE阻害活性が制御されたペプチドを前記有機物として得ることを特徴とする装置。 An apparatus for producing organic materials derived from raw materials including clam bones or crustacean shells,
A reaction vessel for freely storing and removing the raw material together with water;
A temperature sensor that outputs a signal corresponding to the temperature of the water stored in the reaction vessel;
A pressure sensor that outputs a signal corresponding to the pressure of water contained in the reaction vessel;
Control means for adjusting the temperature and pressure of the water stored in the reaction vessel based on the output signal of the temperature sensor and the output signal of the pressure sensor to control the water to a subcritical state,
The control means sets the temperature Θ [° C.] and the pressure P [MPa] of the subcritical water to (Θ, P) = (200, 1.5) and (Θ, P) = (300, 8.6), respectively. ) , The peptide whose ACE inhibitory activity is controlled in the reaction vessel is obtained as the organic substance.
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