JP2020174615A - Composition for improving brain function - Google Patents

Abstract

To provide a composition for improving brain function having excellent improving effect of a brain function.SOLUTION: A composition for improving brain function includes a thermolysin processed product of rice bran. The thermolysin processed product may include at least one kind selected from sequence number 1 and Leu-Arg-Ala. The thermolysin processed product is a product obtained by processing compression-defatted rice bran by thermolysin, and may be a water-soluble fraction. The brain function improvement may be cognitive function improvement.SELECTED DRAWING: None

Description

The present invention relates to a composition for improving brain function containing a component derived from rice bran.

In general, rice bran is a composition in which pericarp, seed coat, germ, etc. obtained in the process of milling brown rice are aggregated, and has been used as a raw material for rice bran oil, a bran bed pickled in bran, and the like for a long time. In addition, rice bran contains useful components such as phytic acid and ferulic acid having antitumor action, antioxidant action, etc., cholesterol absorption inhibitory action, menopausal disorder improving action, ultraviolet absorption action, etc. It is known that Therefore, rice bran has conventionally been used as a raw material for pharmaceuticals, cosmetics, etc., in addition to highly nutritious health foods.

Further, in recent years, as disclosed in Patent Documents 1 and 2, for example, by allowing a specific protease to act on rice bran, an effect of improving an action useful for a living body such as an ACE inhibitory activity has been found.

Japanese Patent No. 6296722 Japanese Patent No. 6462100

An object of the present invention is to provide a composition for improving brain function, which is excellent in improving brain function.

As a result of research to solve the above-mentioned problems, the present inventors have found that a thermolysin-treated product of rice bran exerts an excellent effect of improving brain function.
In order to achieve the above object, one aspect of the present invention is characterized by containing a thermolysin-treated product of rice bran.

The thermolysin-treated product may contain at least one selected from SEQ ID NO: 1 and Leu-Arg-Ala. The thermolysin-treated product is a thermolysin-treated pressed defatted rice bran and may be a water-soluble fraction. The brain function improvement may be a cognitive function improvement.

Another aspect of the present invention is characterized by a food or drink, a drug, or a quasi-drug containing the composition for improving brain function.

According to the present invention, an excellent brain function improving effect can be exhibited.

The graph which shows the new object search rate (%) of the population of the 1st test group (rice bran thermolysin processed product + high fat diet). The graph which shows the new object search rate (%) of the population of the 2nd test group (squeezed defatted rice bran (high-fat) + high-fat diet).

Hereinafter, an embodiment embodying the composition for improving brain function of the present invention will be described. The rice bran used as a raw material for the thermolysin-treated rice bran contained in the composition for improving brain function of the present embodiment is not particularly limited, but may be, for example, rice bran itself or defatted rice bran may be applied. Examples of the defatted rice bran include defatted defatted rice bran degreased by squeezing, extracted defatted rice bran extracted using an organic solvent, and the like. Among these raw materials, pressed defatted rice bran is preferable. Examples of the method for producing squeezed defatted rice bran include a method in which lipase is inactivated by first heating the rice bran (raw rice bran) obtained after polishing (lipase inactivation treatment), and then squeezed.

The lipase inactivation treatment is carried out for the purpose of preventing oxidative deterioration of rice bran (raw rice bran) containing about 18 to 20% by mass of lipid. Usually, it is carried out by heating and roasting raw rice bran at about 70 to 130 ° C. As the squeezing treatment, a known squeezing method, for example, a method of squeezing rice bran that has been heat-roasted to about 100 to 115 ° C. with a low-temperature continuous squeezing machine (for example, trade name: Miracle Chamber manufactured by TechnoSigma) can be applied. The pressing is preferably performed until the lipid content in the defatted rice bran after pressing is about 5 to 20% by mass. Further, the drying treatment may be carried out for the purpose of reducing the water content of the rice bran before the lipase deactivation treatment and the defatted rice bran after the oil extraction. Further, it is particularly preferable that the pressed defatted rice bran is pulverized and classified by a known method to form a powder. At this time, the average particle size of the powder is preferably 5 to 200 μm, more preferably 10 to 150 μm, and most preferably 40 to 100 μm. The average particle size can be measured by the sieving method. The lipid content in the defatted rice bran is not particularly limited, but is preferably 5 to 20% by mass, more preferably 7 to 15% by mass. As the defatted rice bran, a commercially available product may be used. Examples of commercially available products include the trade name Hi-Bleff (manufactured by Saint-Blanc).

Thermolysin is a neutral metalloproteinase derived from Bacillus thermoproteolitics and has an EC number of 3.4.24.27. As the thermolysin, one extracted and purified from the above-mentioned microorganism may be used, one biochemically synthesized may be used, or a commercially available product may be used. Examples of commercially available products include those manufactured by Peptide Institute, Ltd., Wako Pure Chemical Industries, Ltd., and the like.

The treatment conditions for obtaining the thermolysin-treated product are not particularly limited as long as the thermolysin activity can be obtained, and various conditions such as temperature, pH, and time can be appropriately set. As a treatment method, for example, water is added as a solution to the rice bran raw material, the pH is adjusted if necessary, and then a predetermined amount of thermolysin is added. The amount of thermolysin added can be appropriately set in consideration of the treatment conditions, the ratio with the raw material, the titer of the enzyme, and the like. As the rice bran raw material during the thermolysin treatment, rice bran or defatted rice bran as the rice bran raw material may be applied as it is, or a water extract (water-soluble fraction) of the rice bran raw material may be applied. The water extract of the rice bran raw material is a liquid composition (composed of water and the extracted rice bran component) obtained by extracting the rice bran raw material with water. The water extraction conditions are not particularly limited, and examples thereof include a method of immersing (or stirring) the rice bran raw material in water at about 10 to 50 ° C. for about 1 to 24 hours.

As the treatment conditions for thermolysin, for example, rice bran raw material and thermolysin can be mixed with water and then reacted at about 37 ° C. with gentle stirring for about 10 to 30 hours. After the treatment, the thermolysin may be inactivated. The deactivation treatment of thermolysin can be performed, for example, by heating (for example, treatment at 100 ° C. for about 10 to 20 minutes).

The thermolysin-treated product is a composition obtained by treating rice bran with thermolysin as described above, and is a composition containing a degradation product (particularly a peptide) of a protein derived from rice bran whose molecular weight is reduced by thermolysin. Such peptides preferably include those of about 10 kDa or less. More specifically, it more preferably contains at least one selected from SEQ ID NO: 1 (Val-Tyr-Thr-Pro-Gly) and Leu-Arg-Ala.

When the treatment liquid after the thermolysin treatment contains oil, it is preferable to take out a water-soluble fraction further containing a rice bran proteolytic product. Such a water-soluble fraction contains a component that exerts a brain function improving effect. The water-soluble fraction can be obtained by, for example, centrifuging the treatment liquid after the thermolysin treatment. Further, it is preferable that the treatment liquid after the thermolysin treatment is collected as a filtrate from which the insoluble fraction has been removed by filtration.

The form of use of the thermolysin-treated product of rice bran is not particularly limited, and the treatment solution obtained as described above may be applied as it is as a composition for improving brain function in a liquid form, and concentrated by distillation or the like. It may be applied as a liquid, or it may be dried by freeze-drying or the like and applied in the form of a solid substance.

The composition for improving brain function containing a thermolysin-treated product of rice bran exerts an excellent effect of improving brain function, especially when taken orally. The composition for improving brain function of the present embodiment is applied for improving cognitive disorders such as brain dysfunction, particularly memory disorder, attention disorder, executive dysfunction, and social behavior disorder. Specifically, it is used for the treatment, improvement, and prevention of dementia that develops cognitive impairment.

Specific examples of dementia include Alzheimer's disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia, and alcohol-related dementia. Improvement of dementia includes improvement of core symptoms of dementia such as memory disorder, attention disorder, executive dysfunction, and social behavior disorder, as well as delusion, depression, wandering, insomnia, hallucination, and decreased motivation. It also includes improvement of peripheral symptoms.

The application form of the composition for improving brain function is not particularly limited, and is applied as, for example, food and drink, pharmaceuticals, and quasi-drugs. The thermolysin-treated product of rice bran may be used as it is as a food or drink or a pharmaceutical material, or may be used as a product after appropriately blending a carrier, an additive or the like that is acceptable in terms of pharmacy or food hygiene.

When the composition for improving brain function of the present embodiment is applied to foods and drinks such as foods and beverages, for example, food additive compositions, various confectioneries, gums, tablets, capsules (soft capsules, hard capsules), various processed foods. , Applicable to various beverages, etc. The form can be appropriately designed according to the material to be applied, and can be configured as, for example, a solid state such as powder or granule, a paste, or a liquid.

The uses of foods and drinks are not particularly limited, and are so-called general foods, health foods, functional foods, nutritional supplements, supplements, foods for the sick, special-purpose foods, health functional foods, nutritional functional foods, and specified health foods. , Applicable as foods with functional claims. When labeling food and drinks for use, the labeling specified by various laws, enforcement regulations, guidelines, etc. can be mentioned. In food and drink, the indication of use includes not only the indication on packages such as packaging and containers, but also the indication on advertising media such as pamphlets.

In addition to the indication of improvement or prevention of brain function, the indication of the use of the composition for improving brain function of the present embodiment includes the indication of improvement or prevention of the above-mentioned core symptom and peripheral symptom. It also includes labeling suggesting these improvements or preventions. For example, display such as maintenance, support, or improvement of memory, attention, judgment, and spatial cognition, which are part of cognitive function. More specifically, it memorizes information about things that you see and hear, such as words, numbers, figures, colors, position information, and faces, and maintains or supports the ability to remember (memory), helps memorize information, or improves accuracy, short-term. Expressions such as maintaining or supporting memory (ability to retain information in a short time and process it at the same time), maintaining attention (speed and accuracy of office work), and maintaining efficiency of calculation work can be mentioned.

When the composition for improving brain function of the present embodiment is used as a drug or a quasi-drug, it can be administered by ingestion (oral ingestion) or enteral administration. The dosage form is not particularly limited, but may be configured as, for example, powder, powder, granule, tablet, capsule, pill, suppository, liquid or the like. Further, excipients, bases, emulsifiers, solvents, stabilizers and the like may be blended as additives.

The effect of the composition for improving brain function of the present embodiment will be described.
(1) In the present embodiment, it is configured to contain a thermolysin-treated product of rice bran. Therefore, it can exert an excellent effect of improving brain function. In particular, it has an excellent effect on improving cognitive function. Furthermore, in the case of a decline in cognitive function due to lifestyle habits such as a high-fat diet, short-term intake can contribute to the recovery of cognitive function.

The above embodiment may be changed as follows.
-The composition for improving brain function of the above-described embodiment is not only applied to patients for the purpose of improving symptoms related to brain function, but also prevents deterioration of symptoms, delays deterioration of symptoms, and causes deterioration of brain function in healthy subjects. It shall also include ingestion for the purpose of prevention. It may also be applied to domestic animals other than humans.

-In the composition for improving brain function of the above embodiment, the amount of the thermolysin-treated rice bran contained in the drug, quasi-drug, or food or drink is not particularly limited as long as the effect of the present invention can be obtained, and the solid content. It can be configured to contain, for example, 0.1 to 100% by mass, preferably 1 to 90% by mass. In addition, the daily intake and the intake period can be appropriately set according to the purpose, condition, and the like.

When prepared from pressed defatted rice bran as a raw material in the thermolysin-treated rice bran blended in the composition for improving brain function of the above embodiment, γ-oryzanol, which is an oily component in the rice bran raw material, is, for example, 50 mg / 100 g. Ferulic acid may be prepared to be (solid content) or less, preferably 25 mg / 100 g (solid content) or less, and ferulic acid, for example, 100 mg / 100 g (solid content) or less.

The embodiment will be described in more detail with reference to test examples below, but the present invention is not limited thereto.
(Preparation of thermolysin-treated rice bran)
As the raw material rice bran, the trade name Hibref manufactured by Saint-Blanc was used. Hybref is a squeezed defatted rice bran that has been defatted by squeezing the rice bran. As the thermolysin, one manufactured by Peptide Institute (Code3504) was used.

First, the rice bran raw material was mixed with ultrapure water so as to be 30 g / L, and thermolysin was added to this so as to be 0.4 g / L. Then, the mixture was enzymatically treated in a 37 ° C. incubator using a stirrer while stirring at 250 r.p.m. for 20 hours. Next, it was immersed in a boiling water bath and treated for 15 minutes to inactivate the enzyme. Then, the mixture was centrifuged at 7150 r.p.m. (8000 × g) for 15 minutes at 15 ° C. to perform solid-liquid separation. The pH of the obtained supernatant was adjusted to 7.0 using NaOH, and the filter paper No. Filtration was carried out using 2 (manufactured by Advantech), and the obtained filtrate was lyophilized. The freeze-dried product was used as a rice bran thermolysin-treated product. It has been confirmed by ultrafiltration that the rice bran thermolysin-treated product contains a peptide of about 10 kDa or less. In addition, it has been confirmed by amino acid sequence analysis that the peptides of SEQ ID NO: 1 and Leu-Arg-Ala are contained.

(Measurement of cognitive function)
The test method was based on the mouse object recognition test method (Marianne. Leger et al., Nature Protocols 8 (12), 2531-2537, 2013).

In the first test group, a normal diet (control), a high-fat diet, and a high-fat diet containing 0.4% by mass of the above-mentioned rice bran thermolysin-treated product were applied to each mouse population (n = 5-8) for one week. Gave. In addition, in the second test group, each population of mice (n = 5-) was provided with a normal diet, a high-fat diet, and a high-fat diet containing 0.4% by mass of pressed defatted rice bran (high-bluff) not treated with thermolysin. 8) was given for one week respectively.

As the mouse used in the test, a 10-week-old male ddY mouse was used. As a normal diet, MF feed (manufactured by Orientalbio Co., Ltd.) was used, and as a high-fat diet, HFD-60 (manufactured by Orientalbio Co., Ltd.) consisting of the components shown in Table 1 was used. A high-fat diet containing a rice bran component was prepared based on the composition of HFD-60 as shown in Table 1. In addition, the total ferulic acid and γ-oryzanol contents of the rice bran thermolysin-treated product and the pressed defatted rice bran (Hybref) blended in the high-fat diet were measured by HPLC, respectively. The results are shown in Table 2.

On the 6th day of breeding, one mouse in each population was placed in a box of a predetermined size and adapted to the environment for 5 minutes (acclimation 1). Twenty-four hours later, the mouse was placed in a box in which two objects were placed one on each side, and after the two objects were allowed to act until the total search time for both objects reached 20 seconds, they were taken out of the box and returned to the cage. (Familiarization 2). At this time, the two objects in the box are the same and are blocks or flasks. One hour later, the mouse was placed in a box in which one of the two objects was replaced with an object of another shape, and the mouse was moved until the total search time of both objects reached 20 seconds. The ratio (%) of the search time for the mouse was calculated.

It should be noted that whether the new object is on the right side or the left side was tested so as to be completely random. The test box was placed in a compartment separated by a partition, and the tester observed the behavior from outside the partition through a video camera placed above the box so that it could not be seen by the mouse. All of this test was conducted in a facility set at 23 ° C., which was set to have a 12-hour light period and a 12-hour dark period.

Mean ± standard deviation was calculated for the population of each test group. The results of the population of the first test group (rice bran thermolysin-treated product + high-fat diet) are shown in FIG. The results of the population of the second test group (squeezed defatted rice bran (high-fat) + high-fat diet) are shown in FIG. * Indicates p <0.05 (tukey's multiple test).

As shown in FIGS. 1 and 2, it is confirmed that the ratio of the search time for new objects is large in the mice fed with a normal diet. Then, it is confirmed that when a high-fat diet is given, the ratio of the search time for new objects is lower than that in the case of a normal diet. In other words, it is confirmed that cognitive function declines due to lifestyle-related disorders, especially dietary habits. In such an environment where cognitive function declined, a significant increase in the search time for new objects was observed in the population in which the rice bran thermolysin-treated product was added to the high-fat diet (Fig. 1). In other words, the recovery of cognitive function was observed by ingestion of the rice bran thermolysin-treated product. On the other hand, no recovery of cognitive function was observed in the population to which the pressed defatted rice bran (Hybref) not treated with thermolysin was added to the high-fat diet (Fig. 2). It was suggested that the components produced by treating rice bran with thermolysin contributed to the recovery of cognitive function. In addition, as shown in Table 2, the rice bran thermolysin-treated product has a significantly lower content of ferulic acid and γ-oryzanol than the pressed defatted rice bran, suggesting the involvement of other components in the recovery of cognitive function. It was.

(Prescription example)
An example of prescription using a rice bran thermolysin-treated product is shown below.
<Prescription example 1: Tablets>
Rice bran thermolysin treated product: 10% by mass
Excipients (crystalline cellulose, etc.): 90% by mass
(100% by mass in total)
<Prescription example 2: Beverage>
Rice bran thermolysin treated product: 10% by mass
Juice: 30% by mass
Water: 60% by mass
(100% by mass in total)

Claims (5)

A composition for improving brain function containing a thermolysin-treated product of rice bran. The composition for improving brain function according to claim 1, wherein the thermolysin-treated product contains at least one selected from SEQ ID NO: 1 and Leu-Arg-Ala. The composition for improving brain function according to claim 1 or 2, wherein the thermolysin-treated product is a thermolysin-treated pressed defatted rice bran and is a water-soluble fraction. The composition for improving brain function according to any one of claims 1 to 3, wherein the improvement of brain function is improvement of cognitive function. A food or drink, a drug, or a quasi-drug containing the composition for improving brain function according to any one of claims 1 to 4.