JP6710098B2 - Nutritional composition and dietary supplement - Google Patents

Description

The present invention relates to nutritional supplement compositions and dietary supplements.

3-Hydroxybutyric acid and its salts (hereinafter referred to as 3HB, and when referred to as 3HB, particularly refer to its monomer) have a high biocompatibility since they are substances originally present in the human body, and sugar It is expected as an epoch-making energy source to replace quality. Further, it has been found that 3HB has not only a role as a simple energy source, but also an action as a signal transduction substance that affects the expression of various genes and the activity of proteins. 3HB is known to improve cognitive function and long-term persistent memory by inhibiting histone deacetylase by, for example, a gene expression regulatory action, and its effectiveness in the prevention of Alzheimer has been confirmed. For example, 3HB produced by ingestion of medium-chain fatty acid contained in coconut oil and metabolism in the body has an effect of improving symptoms in patients with Alzheimer's disease and diabetes who cannot utilize sugar efficiently in the brain and body. It has been known. In addition, 3HB is converted into energy faster than carbohydrates in the body, and has the effect of suppressing absorption of fats and sugars into cells. Therefore, 3HB is used as an energy substance for athletes and applied to the diet and health food fields. Can be expected.

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).

Further, as a form in which 3HB can be administered to humans, it is known that 3HB can be intravenously administered as an oligomer (Patent Document 2).

JP, 2010-168595, A JP, 06-321778, A

However, since 3HB is acidic, it is difficult for humans to take orally, and it is difficult to take 3HB in large amounts. In addition, in order to reduce the acidity, it may be considered to be ingested as a metal salt, but in such a case, it is feared that the metal component is excessively ingested. In particular, too much sodium component is a cause of hypertension or liver disease. Therefore, even if it can be taken orally, it is desired to avoid taking large amounts.
In addition, when administered intravenously as an oligomer, it is more invasive than oral administration and more resistant to human intake.Although the oligomer is an amino acid salt, it is metabolized while being decomposed. The process is very slow and lacks immediate effect on the energy conversion of 3HB, so that there is a drawback that the use is greatly limited.

Therefore, in view of the above circumstances, the present invention is a nutritional composition and nutritional supplement that can be orally administered with 3HB, can suppress the adverse effects on the human body, and can be provided in a form that can be used as an excellent energy source with immediate effect. The point is to provide food.

Characterizing feature of the method for manufacturing the nutraceutical compositions of the present invention for achieving the above object, the manufacturing method of the nutrient composition containing as a main component a basic amino acid salt of 3HB (3-hydroxybutyric acid monomer) There
3HB (3-hydroxybutyric acid monomer)-producing Halomonas bacterium is added to a raw material liquid, aerobically fermented, and then anaerobically fermented using arginine as a neutralizing agent to ferment containing an arginine derivative salt of 3HB. The process of producing liquid,
Purifying the arginine derivative salt of 3HB from the fermentation broth,
And the step of containing the purified arginine derivative salt of 3HB .

According to the above configuration, 3HB produced by the method for producing a nutritional supplement composition is in a form neutralized with a basic amino acid and has a low sourness even when directly ingested, so that 3HB is orally ingested by humans. It is hard to become a big resistance. Further, since it is not a metal salt, there is no problem of excessive intake of metal components (for example, sodium). In addition, it is known that the basic amino acid produced by the decomposition of the 3HB basic amino acid salt in the body exerts a good effect on the human body. Therefore, both the effects of 3HB and the basic amino acid on the human body can be obtained. It is considered to be preferable in that it can be obtained. In addition, this basic amino acid salt of 3HB has a low molecular weight because it is a salt of a monomer (monomer) of 3hydroxybutyric acid and a basic amino acid, and its decomposition rate is higher than that of using an oligomer or polymer. It has been empirically revealed that blood ketone levels can be elevated in a short period of time even if taken orally.

As a preferable effect of the basic amino acid, for example, when the nutritional supplement composition contains 3HB arginine derivative salt as a main component, a blood flow improving effect and the like can be expected. Further, since such a basic amino acid itself has a high pH, it is highly resistant to oral ingestion, but the salt of 3HB has an advantage that it can synergistically suppress the ingestion resistance.

Examples of the arginine derivative as the basic amino acid include arginine and citrulline, and examples of the basic amino acid include histidine and lysine.

Therefore, the nutritional supplement composition produced by the method for producing a nutritional supplement composition of the present invention can be used as a quick-acting and excellent energy source, and can be easily orally ingested in a sufficient amount. .. Therefore, 3HB can be used by including 3HB as a dietary supplement such as powders, granules, tablets, tablets, and the like, and functional foods such as cookies, biscuits, gummi, chocolate, gum, and the like. The availability of 3HB can be greatly increased.

Graph showing the results of the oral intake test

Hereinafter, the nutritional supplement composition and the dietary supplement according to the embodiment of the present invention will be described. The preferred embodiments will be described below, but these embodiments are described for more specifically illustrating the present invention, and various modifications can be made without departing from the spirit of the present invention. However, the present invention is not limited to the following description.

[3HB]
3HB is obtained by performing a fermentation process in which a 3HB-producing Halomonas bacterium is added, separating and removing Halomonas bacterium from the obtained fermentation liquor, and purifying. The fermentation process is a process in which a 3HB-producing Halomonas bacterium is added as it is to a raw material liquid containing a sugar nutrient such as fruit juice, and aerobic fermentation and anaerobic fermentation are sequentially performed (see JP 2013-081403 A, etc.). Can be implemented as. As a result, the sugar is converted to 3HB and produced in the fermentation broth.

[3HB arginine salt]
The 3HB arginine salt (an example of an arginine derivative salt of 3HB) as a basic amino acid salt of 3HB is a neutralizing agent that neutralizes a fermentation solution whose pH decreases with the production of 3HB in the anaerobic fermentation step in the above 3HB production process. By using arginine as an agent, it can be produced as a fermentation liquor dissolved in the form of 3HB arginine salt (the anaerobic fermentation process is completed in 4 to 8 hours in anaerobic fermentation in alkaline condition). The fermentation liquor is separated into a supernatant containing about 10% 3HB arginine salt by removing the cells by membrane separation, and the solvent is distilled off from the supernatant to purify it as a powdery 3HB arginine salt. To be done. Alternatively, calcium hydroxide is used as a neutralizing agent for neutralizing a fermented liquor whose pH decreases with the production of 3HB, and after removing bacterial cells by membrane separation after anaerobic fermentation, sulfuric acid is added to the calcium sulfate calcium sulfate salt. After the precipitation is removed, arginine is added, and the solvent is distilled off, whereby the powdery 3HB arginine salt is purified.

[Nutrient composition]
The nutritional supplement composition according to the present embodiment can be provided as a nutritional supplement composition or a dietary supplement containing the nutritional supplement composition by tableting the obtained powdery 3HB arginine salt as it is. In addition, tableting does not prevent addition of other components such as an auxiliary agent for preparation. When it is provided as a dietary supplement, it can be processed with other food ingredients such as wheat flour and sugar to be in the form of cookies, biscuits, gummi, chocolate, gum and the like.

[Oral intake test]
It was converted to 15 g per 60 kg of body weight, and the person serving as a monitor was orally ingested with 3HB arginine salt before meals, and the 3HB concentration in blood was continuously measured. 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 in rat blood after 30 minutes, but it corresponds to 120 minutes after conversion into human, and it takes time to increase the blood concentration, but the blood concentration is very quick. It turned out to be high and the immediate effect was high.

[Sensory test]
(Method)
Arginine (commercially available product), 3HB (purified product), and 3HB arginine salt (the above-mentioned example) were ranked in terms of bitterness, sourness, and taste (sourness, bitterness, and taste were less than 1; However, the ones that were felt to have a lot of taste were evaluated and compared according to 4 scale of 4). As 3HB, what was recovered as the final 3HBNa salt using NaOH as usual for pH adjustment, desalted by electrodialysis and ion exchange, purified, and isolated was used.
100 mg each of arginine, 3HB and 3HB arginine salt was weighed and dissolved in 1 ml of water, and each panelist conducted a sensory test for bitterness, sourness and umami.

(result)
The sensory test results regarding Table 1 (bitterness), Table 2 (sourness), and Table 3 (umami) are shown. The bitterness, sourness, and umami were evaluated based on the results of Table 1, Table 2, and Table 3. Arginine has no sourness but high bitterness, while 3HB has no bitterness but high sourness. However, it was found that 3HB arginine salt was not sour and bitter, but the taste was delicious, and there was a clear significant difference, making it easy to eat.

Further, 3HB has been confirmed to be effective as an energy substance for prevention of Alzheimer's disease, prevention of cancer, and athletes, but it is necessary to ingest it now as 3HB salt or ester. The metal salt of 3HB has too much metal component, and the ester has a complicated manufacturing process and requires enzymatic decomposition in the body, and thus has poor immediate effect. In the present invention, since it can be ingested as an amino acid salt, it is easy to ingest without excessive intake of metal components (particularly sodium). In addition, 3HB and amino acid are divided in the body, and each effect can be expected. For example, the basic amino acid arginine has a blood flow improving function.
In addition, arginine is known to increase the amount of nitric oxide when ingested, thereby expanding blood vessels. Nitric oxide is used for reducing 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, but in that case, NAD, which is a coenzyme, is required, and NADH is formed. NADH has a reducing power, and when ingested 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.

[Another embodiment]
As long as no contradiction arises, a plurality of the following other embodiments can be combined and applied to the above embodiments. The scope of the present invention is not limited to these embodiments.

(1)
In the above embodiment, the arginine salt was produced by using arginine as the neutralizing agent in the production process of the 3HB fermentation process, but the present invention is not limited to this, and purified 3HB is reacted with arginine to form 3HB arginine. Alternatively, it is possible to obtain 3HB arginine by reacting arginine sulfate with 3HB calcium salt using calcium hydroxide as a neutralizing agent. Both are preferable because 3HB arginine can be produced by a simple method.

Further, in the above example, 3HB arginine was illustrated, but other basic amino acid salts may be used, and in such a case, instead of arginine in the above-mentioned 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, these alleviate the acidity of 3HB and are less likely to resist oral ingestion, and can simultaneously exhibit the unique effects of 3HB and citrulline, histidine, and lysine. Expected to be effective.

The nutritional supplement composition of the present invention can be used as a good energy source with immediate effect, and since it is easily ingested, health supplements such as powder, granules, tablets, tablets, and the like, It can be used by including it in nutritional supplements such as functional foods such as cookies, biscuits, gummies, chocolates and gums, and can greatly increase the availability of 3HB.

Claims (2)

A method for producing a nutritional supplement composition containing a basic amino acid salt of 3HB (3 hydroxybutyric acid monomer) as a main component ,
3HB (3-hydroxybutyric acid monomer)-producing Halomonas bacterium is added to a raw material liquid, aerobically fermented, and then anaerobically fermented using arginine as a neutralizing agent to ferment containing an arginine derivative salt of 3HB. A process of producing liquid,
Purifying the arginine derivative salt of 3HB from the fermentation broth,
And a step of containing the purified arginine derivative salt of 3HB . A step of incorporating the nutrient composition prepared by the method of claim 1 Symbol placement of nutritional compositions, method for producing a dietary supplement.

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