JP2017201906A - Nutrient composition and dietary supplement - Google Patents

Nutrient composition and dietary supplement Download PDF

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JP2017201906A
JP2017201906A JP2016094504A JP2016094504A JP2017201906A JP 2017201906 A JP2017201906 A JP 2017201906A JP 2016094504 A JP2016094504 A JP 2016094504A JP 2016094504 A JP2016094504 A JP 2016094504A JP 2017201906 A JP2017201906 A JP 2017201906A
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arginine
salt
amino acid
basic amino
nutrient composition
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JP6710098B2 (en
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潤 坪田
Jun Tsubota
潤 坪田
松下 功
Isao Matsushita
功 松下
拓 西村
Hiroshi Nishimura
拓 西村
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Osaka Gas Co Ltd
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Abstract

PROBLEM TO BE SOLVED: To provide 3HB in such a form that facilitates oral administration, reduces an adverse effect on human bodies, and is available as a good energy source with immediate effectivity.SOLUTION: A nutrient composition contains a basic amino acid salt of 3HB (3 hydroxybutyric acid monomer) as a main component.SELECTED DRAWING: None

Description

本発明は、栄養剤組成物及び栄養補助食品に関する。   The present invention relates to a nutrient composition and a dietary supplement.

3ヒドロキシ酪酸やその塩(以下3HBと称する、また、3HBと称する場合、特にその単量体を指すものとする)は、もともと人の体内に存在する物質であるため生体親和性が高く、糖質に代わる画期的なエネルギー源として期待されている。また、3HBは単なるエネルギー源という役割だけでなく、様々な遺伝子の発現やタンパク質の活性に影響するシグナル伝達物質としての作用があることがわかってきた。3HBは、例えば、遺伝子発現調節作用によって、ヒストン脱アセチル化酵素を阻害することによって認知機能や、長期持続記憶を改善することが知られ、アルツハイマーの予防に有効性が確認されている。例えば、ココナツオイルに多く含まれる中鎖脂肪酸の摂取および体内での代謝により生成される3HBが、脳や体内において糖質をうまく利用できないアルツハイマー病、糖尿病の患者の症状を改善させる効果を持つことが知られている。また、3HBは体内において糖質よりも速やかにエネルギーに変換されること、細胞への脂肪や糖の吸収を抑制する効果を有することから、アスリート向けのエネルギー物質、ダイエット・健康食品分野への応用が期待できる。   Since 3-hydroxybutyric acid and its salt (hereinafter referred to as 3HB, also referred to as 3HB, especially its monomer) is a substance that is originally present in the human body, it has high biocompatibility and is a sugar. Expected to be a groundbreaking energy source instead of quality. In addition, it has been found that 3HB not only serves as a mere energy source but also acts as a signal transmitter that affects the expression of various genes and the activity of proteins. 3HB is known to improve cognitive function and long-lasting memory by inhibiting histone deacetylase, for example, by regulating gene expression, and its effectiveness in preventing Alzheimer's has been confirmed. For example, 3HB produced by ingestion and metabolism in the body of medium chain fatty acids that are abundant in coconut oil has the effect of improving the symptoms of Alzheimer's disease and diabetic patients who cannot utilize carbohydrates in the brain and body. It has been known. In addition, 3HB is converted to energy more rapidly than carbohydrates in the body and has the effect of suppressing the absorption of fat and sugar into cells, so it can be applied to energy substances for athletes, diet and health foods. Can be expected.

このような3HBは、各種微生物にポリ3ヒドロキシ酪酸(以下PHBと称する)を生産させたのち、得られたPHBを酵素等により分解することにより得ることができる(特許文献1)。   Such 3HB can be obtained by causing various microorganisms to produce poly-3-hydroxybutyric acid (hereinafter referred to as PHB) and then decomposing the obtained PHB with an enzyme or the like (Patent Document 1).

また、3HBを人に投与可能な形態としては、3HBをオリゴマーとして静脈投与可能にすることが知られている(特許文献2)。   As a form in which 3HB can be administered to humans, it is known that 3HB can be administered intravenously as an oligomer (Patent Document 2).

特開2010−168595号公報JP 2010-168595 A 特開平06−321778号公報Japanese Patent Laid-Open No. 06-321778

しかし、3HBは、酸性であるため人が経口摂取するには抵抗が大きく、そのまま大量に摂取することは困難である。また、酸性度を低減すべく、金属塩として摂取することも考えられるが、このような場合、金属成分の過剰摂取が懸念され、特にナトリウム成分の取りすぎは、高血圧症や肝臓疾患等の原因となりうるので、経口摂取できたとしても大量摂取を避けたいものとなっている。
また、オリゴマーとして静脈投与する場合、経口投与に比べて侵襲性が高く、より一層人が摂取するのに抵抗が大きく、さらに、オリゴマーがアミノ酸塩とされているものの、オリゴマーが分解されつつ代謝される過程は非常に遅く、3HBのエネルギー変換についての即効性に欠けるため、用途が大きく限定されるという欠点があった。
However, since 3HB is acidic, it is highly resistant to human ingestion, and it is difficult to ingest large amounts as it is. In addition, in order to reduce acidity, it may be taken as a metal salt, but in such a case, there is concern about excessive intake of the metal component, and excessive intake of the sodium component in particular may cause hypertension or liver disease. Therefore, even if you can take it orally, you want to avoid taking a large amount.
In addition, when administered intravenously as an oligomer, it is more invasive than oral administration, and is much more resistant to human consumption. Further, although the oligomer is an amino acid salt, the oligomer is metabolized while being decomposed. The process is very slow and lacks the immediate effect on energy conversion of 3HB, so that there is a drawback that the application is greatly limited.

したがって、本発明は上記実状に鑑み、3HBを経口投与しやすく、かつ人体への悪影響を抑制し、即効性のある優良なエネルギー源として利用可能な形態で提供しうる栄養剤組成物および栄養補助食品を提供する点にある。   Therefore, in view of the above-mentioned circumstances, the present invention makes it easy to orally administer 3HB, suppresses adverse effects on the human body, and can be provided in a form that can be used as an excellent and effective energy source. The point is to provide food.

上記目的を達成するための本発明の栄養剤組成物の特徴構成は、3HB(3ヒドロキシ酪酸単量体)の塩基性アミノ酸塩を主成分として含有する点にある。   The characteristic composition of the nutrient composition of the present invention for achieving the above object is that it contains a basic amino acid salt of 3HB (3-hydroxybutyric acid monomer) as a main component.

上記構成によると、3HBは、塩基性アミノ酸により中和された形態となっており、直接摂取しても酸味が少ないので、人が経口摂取するうえで大きな抵抗にはなりにくくなっている。また、金属塩ではないため、金属成分(たとえばナトリウム)の過剰摂取の問題もない。加えて、3HB塩基性アミノ酸塩が体内で分解されて生じる塩基性アミノ酸は人体に良好な効果を発揮することが知られているので、3HBと塩基性アミノ酸との両者の人体に対する効果をともに得られる点で好ましいと考えられる。また、この3HBの塩基性アミノ酸塩は、3ヒドロキシ酪酸の単量体(モノマー)と塩基性アミノ酸との塩であるから低分子量であり、オリゴマーやポリマーを用いるのに比べて、分解速度が比較的早く、経口摂取でも短時間で血中ケトン濃度が上昇しうることが実験的に明らかになっている。   According to the above configuration, 3HB is in a form neutralized with a basic amino acid and has little acidity even when ingested directly, so that it is difficult for a person to take great resistance when ingested orally. Moreover, since it is not a metal salt, there is no problem of excessive intake of metal components (for example, sodium). In addition, since it is known that the basic amino acid produced by the decomposition of 3HB basic amino acid salt in the body exhibits a good effect on the human body, both 3HB and the basic amino acid have the effects on the human body. Therefore, it is considered preferable. The basic amino acid salt of 3HB has a low molecular weight because it is a salt of a monomer of 3-hydroxybutyric acid and a basic amino acid. Compared to the use of oligomers or polymers, the decomposition rate is comparative. It has been experimentally clarified that blood ketone levels can be increased in a short time even when taken orally.

塩基性アミノ酸による好ましい効果としては、たとえば、栄養剤組成物が3HBのアルギニン誘導体塩を主成分として含有する場合、血流改善効果などが期待できる。また、このような塩基性アミノ酸自体、高pHであるため、経口摂取するには抵抗が大きいものの、3HBの塩とすることで、お互いに相乗的に摂取抵抗を抑制できる利点もある。   As a preferable effect of the basic amino acid, for example, when the nutrient composition contains a 3HB arginine derivative salt as a main component, an effect of improving blood flow can be expected. In addition, since such a basic amino acid itself has a high pH, it is highly resistant to oral ingestion, but there is an advantage that the intake resistance can be suppressed synergistically by using a salt of 3HB.

塩基性アミノ酸としてのアルギニン誘導体としては、アルギニン、シトルリンが挙げられ、他に塩基性アミノ酸として、ヒスチジン、リシン等が挙げられる。   Arginine derivatives as basic amino acids include arginine and citrulline, and other basic amino acids include histidine and lysine.

したがって、本発明の栄養剤組成物は、即効性のある優良なエネルギー源として利用可能であるとともに、十分量の経口摂取が容易なものとなっている。そのため、粉末、顆粒、錠剤、タブレット、等の健康補助食品や、クッキー、ビスケット、グミ、チョコレート、ガムなどの機能性食品等に例示される栄養補助食品として3HBを含有させて利用することができ、3HBの利用可能性を大きく高めることができる。   Therefore, the nutrient composition of the present invention can be used as an excellent energy source with immediate effect and can be easily ingested in a sufficient amount. Therefore, 3HB can be used as a dietary supplement exemplified by health supplements such as powders, granules, tablets and tablets, and functional foods such as cookies, biscuits, gummi, chocolate and gum. The availability of 3HB can be greatly increased.

経口摂取試験の結果を示すグラフGraph showing results of oral intake test

以下に、本発明の実施形態にかかる栄養剤組成物及び栄養補助食品を説明する。尚、以下に好適な実施形態を記すが、これら実施形態はそれぞれ、本発明をより具体的に例示するために記載されたものであって、本発明の趣旨を逸脱しない範囲において種々変更が可能であり、本発明は、以下の記載に限定されるものではない。   Below, the nutrient composition and dietary supplement concerning embodiment of this invention are demonstrated. Preferred embodiments are described below, but these embodiments are described in order to more specifically illustrate the present invention, and various modifications can be made without departing from the spirit of the present invention. The present invention is not limited to the following description.

〔3HB〕
3HBは、3HB生産性のハロモナス菌を添加した発酵プロセスを行い、得られた発酵液からハロモナス菌を分離除去し、精製することにより得られる。発酵プロセスは、果汁等の糖質栄養源を含有する原料液に、3HB生産性のハロモナス菌をそのまま添加し、好気発酵、嫌気発酵を順に行うプロセス(特開2013−081403号公報等参照)として実施することができる。これにより、糖質が3HBに変換され、発酵液中に生産されることになる。
[3HB]
3HB is obtained by performing a fermentation process to which 3HB-producing halomonas are added, separating and removing halomonas from the resulting fermentation broth, and purifying. The fermentation process is a process in which 3HB-producing halomonas bacteria are added as they are to a raw material liquid containing a saccharide nutrient source such as fruit juice, and aerobic fermentation and anaerobic fermentation are performed in this order (see JP2013-081403A). Can be implemented as As a result, the sugar is converted to 3HB and produced in the fermentation broth.

〔3HBアルギニン塩〕
3HBの塩基性アミノ酸塩としての3HBアルギニン塩(3HBのアルギニン誘導体塩の一例)は、上記3HBの生成プロセスにおける嫌気発酵の工程において、3HBの生成とともにpHの低下する発酵液を中和する中和剤として、アルギニンを用いることにより3HBアルギニン塩の形で溶解した発酵液として生産することができる(嫌気発酵の工程はアルカリ性での嫌気発酵4〜8時間で終了)。発酵液は、膜分離により菌体を除去することで約10%の3HBアルギニン塩を含有する上清が分離され、この上清から溶媒を留去することにより、粉末状の3HBアルギニン塩として精製される。または、3HBの生成とともにpHの低下する発酵液を中和する中和剤として水酸化カルシウムを用い、嫌気発酵後に膜分離により菌体を除去したのちに、硫酸を添加してカルシウムを硫酸カルシウム塩として沈殿除去したものに、アルギニンを添加、溶媒を留去することにより、粉末状の3HBアルギニン塩として精製される。
[3HB arginine salt]
3HB arginine salt (an example of 3HB arginine derivative salt) as a basic amino acid salt of 3HB is neutralized to neutralize a fermentation solution whose pH decreases with the formation of 3HB in the step of anaerobic fermentation in the 3HB production process. By using arginine as an agent, it can be produced as a fermentation broth dissolved in the form of 3HB arginine salt (the anaerobic fermentation process is completed in 4 to 8 hours in alkaline anaerobic fermentation). A supernatant containing about 10% of 3HB arginine salt is separated by removing the cells by membrane separation, and the fermentation liquid is purified as a powdered 3HB arginine salt by distilling off the solvent. Is done. Alternatively, calcium hydroxide is used as a neutralizing agent to neutralize the fermentation solution whose pH decreases with the formation of 3HB, and after removing the cells by membrane separation after anaerobic fermentation, sulfuric acid is added to the calcium sulfate salt. Is purified as a powdery 3HB arginine salt by adding arginine to the precipitate removed and distilling off the solvent.

〔栄養剤組成物〕
本実施形態にかかる栄養剤組成物は、得られた粉末状の3HBアルギニン塩をそのまま錠剤化して、栄養剤組成物あるいは、栄養剤組成物を含有する栄養補助食品として提供することができる。また、錠剤化にあたっては、調剤用助剤等の他の成分の添加を妨げるものではない。また栄養補助食品として提供する場合には、小麦粉、砂糖などの他の食品成分とともに加工して、クッキー、ビスケット、グミ、チョコレート、ガムなどの形態とすることができる。
[Nutrient composition]
The nutritional composition according to this embodiment can be obtained by directly tableting the obtained powdered 3HB arginine salt and providing it as a nutritional supplement or a dietary supplement containing the nutritional composition. Moreover, in tableting, the addition of other components such as a preparation aid is not prevented. Moreover, when providing as a dietary supplement, it can process with other food components, such as flour and sugar, and can be made into forms, such as a cookie, a biscuit, gummy, chocolate, gum.

〔経口摂取試験〕
60kgの体重あたり15gとなるように換算して、モニタとなる人に3HBアルギニン塩を食前に経口摂取して、継時的に血中の3HB濃度を計測した。その結果、図1に示すように、30分後には0.6mM、45分後には1mMに達し、経口摂取で短時間で3HBの血中濃度が上昇した。特許文献2では、ラット血中で30分後に700μmol/Lに達したが、ヒトに換算すると120分後に相当し、血中濃度の上昇に時間がかかるのに対し、非常に素早く血中濃度が上昇し即効性が高いことが分かった。
[Ingestion test]
Converted to 15 g per 60 kg body weight, 3HB arginine salt was orally ingested before a meal to a person to be monitored, and the 3HB concentration in blood was measured over time. As a result, as shown in FIG. 1, it reached 0.6 mM after 30 minutes and reached 1 mM after 45 minutes, and the blood concentration of 3HB increased in a short time after oral intake. In Patent Document 2, it reached 700 μmol / L after 30 minutes in rat blood, but when converted to human, it corresponds to 120 minutes later, and it takes time to increase the blood concentration, but the blood concentration is very quickly. It was found that the effect increased immediately.

〔官能試験〕
(方法)
アルギニン(市販品)、3HB(精製品)、3HBアルギニン塩(上記実施例)について、それぞれ苦み、酸味および旨みに関して順位法(酸味、苦み、旨みが少ないと感じたのが1、また苦み、酸味、旨みが多いと感じたものが4の4段階表示)で評価し、比較した。3HBは、pH調整に従来通りNaOHを用いて最終3HBNa塩として回収したものを、電気透析、イオン交換により脱塩して精製し、単離したものを使用した。
アルギニン、3HB、3HBアルギニン塩を各100mg秤量し1mlの水に溶解して、各パネラーにより苦み、酸味および旨みについてそれぞれ官能試験を実施した。
[Sensory test]
(Method)
For arginine (commercial product), 3HB (purified product), and 3HB arginine salt (above examples), the ranking method (1 sourness, bitterness, and umami was felt with little bitterness, bitterness, and umami, bitterness, sourness) Evaluation was made on the basis of a 4-level display (4). 3HB was used as a final 3HBNa salt recovered using NaOH for pH adjustment in the conventional manner, desalted by electrodialysis and ion exchange, purified and isolated.
Arginine, 3HB, and 3HB arginine salts were weighed 100 mg each and dissolved in 1 ml of water, and each panelist conducted a sensory test for bitterness, sourness and umami.

(結果)
表1(苦み)、表2(酸味)、表3(旨み)に関する官能試験結果を示す。表1、表2、表3の結果をもとに苦み、酸味、旨みの評価を実施した。アルギニンは酸味が無いが苦みが高く、一方3HBは苦みが無いが酸味が高い結果が得られた。しかし、3HBアルギニン塩は酸味、苦みを感じず、旨みを感じる結果が得られ、明らかな有意差が認められ、手軽に食べられることがわかった。
(result)
The sensory test result regarding Table 1 (bitterness), Table 2 (acidity), and Table 3 (umami) is shown. Based on the results of Table 1, Table 2, and Table 3, bitterness, sourness, and taste were evaluated. Arginine has no acidity but high bitterness, while 3HB has no bitterness but high acidity. However, it was found that 3HB arginine salt did not feel sour and bitter, but a result of feeling umami was obtained, a clear significant difference was observed, and it was easy to eat.

Figure 2017201906
Figure 2017201906

Figure 2017201906
Figure 2017201906

Figure 2017201906
Figure 2017201906

また、3HBはアルツハイマーの予防、癌の予防、アスリート向けのエネルギー物質として有効性が認められているが、現在は3HB塩もしくはエステルとして摂取する必要がある。3HBの金属塩では、金属成分の取りすぎになるし、エステルは製造プロセスが複雑でありまた体内での酵素分解が必要で即効性に乏しい。本発明では、アミノ酸塩として摂取できることから、金属成分(特にナトリウム)の取り過ぎが無く、摂取し易い。また、体内で3HBとアミノ酸に分かれてそれぞれ効果が期待できる。例えば、塩基性アミノ酸のアルギニンは、血流向上機能がある。
さらに、アルギニンは、摂取すると一酸化窒素が増えて、血管を拡張させる作用が知られている。一酸化窒素は、活性酸素が存在すると活性酸素の還元に使われ、その効果が消失するため、アルギニンを摂取する場合は、抗酸化剤(還元剤)との同時接種が好ましい。
また、3HBは体内ではアセト酢酸に変換するが、その際に補酵素のNADを必要とし、NADHができる。NADHは還元力があり、3HBアルギニンとして摂取することで、アルギニンの酸化を抑制し、アルギニン単体よりも、血管拡張効果を高めることが可能となり相乗効果があると考えられる。
3HB has been recognized as an effective energy substance for Alzheimer's prevention, cancer prevention, and athletes, but now it must be ingested as a 3HB salt or ester. With 3HB metal salt, too much metal component is taken, and ester has a complicated manufacturing process and requires enzymatic degradation in the body, so that it is poor in immediate effect. In the present invention, since it can be ingested as an amino acid salt, it is easy to ingest without taking too much metal component (especially sodium). Moreover, it can be divided into 3HB and amino acids in the body, and the effects can be expected. For example, the basic amino acid arginine has a blood flow improving function.
Furthermore, arginine is known to have an action of expanding blood vessels by increasing nitric oxide when ingested. Nitric oxide is used to reduce active oxygen in the presence of active oxygen, and its effect disappears. Therefore, when ingesting arginine, simultaneous inoculation with an antioxidant (reducing agent) is preferable.
In addition, 3HB is converted into acetoacetic acid in the body, and at that time, NAD which is a coenzyme is required, and NADH can be produced. NADH has a reducing power, and when taken as 3HB arginine, it suppresses the oxidation of arginine and can enhance the vasodilatory effect as compared with arginine alone, and is considered to have a synergistic effect.

〔別実施形態〕
下記の別実施形態は、矛盾が生じない限り、複数を組み合わせて上記実施形態に適用できる。なお、本発明の範囲は、これら実施形態に限定されるものではない。
[Another embodiment]
Other embodiments described below can be applied to the above embodiments in combination, as long as no contradiction arises. The scope of the present invention is not limited to these embodiments.

(1)
上記実施形態においては、3HBの発酵プロセスによる製造過程で中和剤としてアルギニンを用いることでアルギニン塩を製造したが、これに限らず、精製された3HBをアルギニンと反応させて3HBアルギニンとすることもできるし、中和剤として水酸化カルシウムを用いて3HBカルシウム塩とした後、アルギニン硫酸塩を反応させて3HBアルギニンを得ることもできる。いずれも簡便な方法で3HBアルギニンを製造することができ好ましい。
(1)
In the above embodiment, arginine salt was produced by using arginine as a neutralizing agent in the production process by 3HB fermentation process, but not limited thereto, purified 3HB is reacted with arginine to form 3HB arginine. Alternatively, 3HB arginine can also be obtained by reacting with arginine sulfate after making 3HB calcium salt using calcium hydroxide as a neutralizing agent. In any case, 3HB arginine can be produced by a simple method, which is preferable.

また、上述の例では3HBアルギニンを例示したが、他の塩基性アミノ酸塩であってもよく、このような場合、上述の実施の形態におけるアルギニンに代えて、他の塩基性アミノ酸としてのシトルリン、ヒスチジン、リシンを用いることで、3HBシトルリン、3HBヒスチジン、3HBリシンが得られることは明らかである。これらは、3HBアルギニンと同様に、3HBの酸性度が緩和されるとともに、経口摂取するうえでの抵抗となりにくくなり、また、3HBと、シトルリン、ヒスチジン、リシンそれぞれの固有の効果を同時に発現させられる効果が期待される。   In the above example, 3HB arginine is exemplified, but other basic amino acid salts may be used. In such a case, instead of arginine in the above embodiment, citrulline as another basic amino acid, It is clear that 3HB citrulline, 3HB histidine, and 3HB lysine can be obtained by using histidine and lysine. Similar to 3HB arginine, the acidity of 3HB is reduced, resistance to oral ingestion is less likely, and the unique effects of 3HB and citrulline, histidine, and lysine can be expressed simultaneously. Expected to be effective.

本発明の栄養剤組成物は、即効性のある優良なエネルギー源として利用可能であるとともに、経口摂取容易なものとなっているので、粉末、顆粒、錠剤、タブレット、等の健康補助食品や、クッキー、ビスケット、グミ、チョコレート、ガムなどの機能性食品等に例示される栄養補助食品に含有させて利用することができ、3HBの利用可能性を大きく高めることができる。   The nutritional composition of the present invention can be used as an excellent energy source with immediate effect and can be easily taken orally, so health supplements such as powders, granules, tablets, tablets, It can be used by being added to a dietary supplement exemplified by functional foods such as cookies, biscuits, gummi, chocolate, and gum, and the availability of 3HB can be greatly increased.

Claims (3)

3HB(3ヒドロキシ酪酸単量体)の塩基性アミノ酸塩を主成分として含有する栄養剤組成物。   A nutritional composition containing a basic amino acid salt of 3HB (3-hydroxybutyric acid monomer) as a main component. 3HB(3ヒドロキシ酪酸単量体)のアルギニン誘導体塩を主成分として含有する栄養剤組成物。   A nutrient composition containing an arginine derivative salt of 3HB (3-hydroxybutyric acid monomer) as a main component. 請求項1または2に記載の栄養剤組成物を含有する栄養補助食品。   A dietary supplement containing the nutrient composition according to claim 1 or 2.
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