JP2015013840A - Sleep-improving agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a sleep-improving agent which is excellent in safety, and can achieve the effect of improved sleep simply and effectively.SOLUTION: A sleep-improving agent is combined a shiitake mushroom fermentation rice bran extract prepared from a culture product obtained by culturing a shiitake mushroom mycelium with a culture medium comprising an enzymolysis product of rice bran, and a shiitake mushroom mycelium culture medium extract prepared from a culture product obtained by culturing the shiitake mushroom mycelium with the culture medium comprising a vegetable fiber raw material. The culture with the culture medium comprising the vegetable fiber raw material is preferable to be a solid culture, and the culture with the culture medium comprising the enzymolysis product of the rice bran is preferable to be a liquid culture.

Description

  The present invention relates to a sleep improving agent.

  Sleep is an essential physiological activity for humans and animals. In other words, not only for rest but also for improving quality of life (QOL), adjusting rhythm of life to relieve stress, and in order to improve health, quality “sleep” is required. In general, if the symptoms of insomnia become severe, you will need to take a sleeping pill or sleep inducer according to your doctor's prescription, but even if you do not suffer from such severe symptoms, your sleep rhythm is disturbed and you wake up. There are various dissatisfaction with "sleep", such as poor sleep, poor sleep, low concentration in the daytime, poor sleep, and not feeling well asleep, and there is a demand for "sleep" that should be improved . Therefore, it is desired to develop a sleep-improving agent that can be easily taken in daily life to improve the quality of sleep. From the viewpoint of safety, an active ingredient that can be safely ingested as food is used. It is desirable.

  Examples of sleep-improving agents that contain ingredients that are also ingested as active ingredients include, for example, a deep sleep disorder-improving agent containing glycine as an active ingredient (Patent Document 1), oral for improving sleeping or waking up containing ornithine as an active ingredient. Agent (patent document 2), composition for improving sleep quality characterized by containing γ-aminobutyric acid as an active ingredient (patent document 3), sleep inducer characterized by containing arginine (patent Document 4), a sleep disorder improving agent containing sesamin as an active ingredient (Patent Document 5) and the like are known.

JP 2006-333872 A JP 2006-342148 A JP 2007-63236 A JP 2007-230954 A JP 2010-285427 A

If a new active ingredient of a sleep improvement agent can be provided, the range of choice will spread to consumers.
The objective of this invention is providing the sleep improving agent which is excellent in safety | security and can acquire the effect of sleep improvement simply and effectively.

  The present inventors have found that a combination of extracts obtained from a culture obtained by cultivating shiitake mycelium by a specific culture method is effective in improving sleep, and have completed the present invention.

  That is, the sleep-improving agent of the present invention is obtained by cultivating shiitake mycelium in a medium containing an enzymatic degradation product of rice bran, a shiitake-fermented rice bran extract prepared from the culture, and a plant fiber raw material prepared from a plant of this family A shiitake mycelium is cultured in a medium containing, and consists of a combination with a shiitake mycelium culture medium extract prepared from the culture.

  In the sleep improving agent of the present invention, it is preferable that the enzymatic decomposition product of rice bran is a decomposition product of a polysaccharide-degrading enzyme.

  The shiitake mycelium culture medium extract preferably contains a saccharide, a protein, and a water-soluble lignin.

  Moreover, it is preferable that culture | cultivation in the culture medium containing the said vegetable fiber raw material is solid culture, and culture | cultivation in the culture medium containing the enzyme degradation product of the said rice bran is liquid culture.

  On the other hand, another aspect of the present invention is that (1) shiitake mycelium is cultured in a medium containing an enzymatic degradation product of rice bran for preparing an oral composition for the purpose of improving sleep. Shiitake fermented rice bran extract prepared and / or (2) shiitake mycelium is cultured in a medium containing plant fiber raw material, and use of shiitake mycelium culture medium extract prepared from the culture is provided. is there.

  According to the present invention, sleep that is excellent in safety and can effectively and effectively improve sleep by a combination of extracts obtained from a culture in which shiitake mycelium is cultured by a specific culture method. An improver can be provided.

It is explanatory drawing which shows the brain coordinate position of a rat. It is a graph which shows the result of having investigated the influence which administration of a shiitake fermented rice bran extract (LEF) and / or a shiitake mycelium culture medium extract (LEM) has on non-REM sleep of a rat. It is a graph which shows the result of having investigated the influence which administration of a shiitake fermented rice bran extract (LEF) and / or a shiitake mycelium culture medium extract (LEM) has on the total sleep amount of a rat. It is a graph which shows the result (number of persons) which investigated the sleep improvement effect when a 2: 1 mixture of shiitake fermentation rice bran extract (LEF) and shiitake mycelium culture medium extract (LEM) was given to a person. It is a graph which shows the result (score) which investigated the sleep improvement effect when a 2: 1 mixture of a shiitake fermentation rice bran extract (LEF) and a shiitake mycelium culture medium extract (LEM) was given to a person.

  The sleep-improving agent of the present invention is obtained by inoculating and cultivating shiitake mycelium on a medium containing an enzymatic degradation product of rice bran, and a shiitake-fermented rice bran extract prepared from the culture, and a plant fiber prepared from a plant of this family It consists of a combination with Shiitake mycelium culture medium extract prepared by inoculating and cultivating Shiitake mycelium on a medium containing raw materials.

[1] Shiitake fermented rice bran extract As the rice bran used in the medium, defatted rice bran is preferable. Rice bran is added with 3 to 10 times the amount of water and stirred, followed by high-pressure steam sterilization according to a conventional method. The degrading enzyme only needs to be an enzyme that degrades the high molecular components of rice bran to some extent so that the enzyme produced by Shiitake bacteria can easily act on rice bran. For example, polysaccharides such as amylase, pectinase, hemicellulase, cellulase, and glucanase Examples include proteolytic enzymes such as degrading enzymes, proteases, and peptidases, and lignin degrading enzymes such as peroxidase, laccase, and ligninase. Of these, polysaccharide degrading enzymes are preferred. The enzyme reaction may be appropriately performed under conditions suitable for the enzyme to be used so that a decomposition product of rice bran is sufficiently generated. In this way, an enzymatic decomposition suspension of rice bran is obtained.

  On the other hand, after cultivating shiitake mycelium in a nutrient medium according to a conventional method, the culture broth is used as it is or after the mycelia is collected, and then combined with the above enzymatically-decomposed suspension of rice bran at 20 to 80 ° C. Incubate for ~ 140 hours. If necessary, the medium may contain yeast extract, dry yeast, chlorella, spirulina, corn meal, okara, and the like as nutrient components.

  After completion of the culture, the extract is preferably collected by heat treatment, and optionally subjected to pressure treatment or ultrasonic treatment. Further, the extract is filtered or centrifuged as necessary, and the filtrate or supernatant is collected to obtain a rice bran-derived component, a component that is decomposed, metabolized, or catabolized by shiitake fungus, shiitake mycelium An extract in the form of an extract containing a metabolite of the mycelia and a mycelium cell degradation product can be obtained.

The extract thus obtained was a substance mainly composed of carbohydrates, but was confirmed to have the following components.
・ Sugar: 47-74%
・ Protein: 10-18%
・ Ash content: 10-16%
・ Pentose: 4-8%

[2] Shiitake mycelium culture medium extract As the plant fiber raw material used for the medium, one prepared from a plant containing lignin is preferably used. Examples of plants containing lignin include scallops. For example, bagasse (a fibrous component of sugar cane), corn stover, wheat bran, rice bran, rice straw, and straw are preferably used. In addition, bears, bamboo, etc. can be used. Among these, a medium containing one kind selected from bagasse, bear shoots and corn stalks and rice bran is particularly preferably used. Moreover, you may make a culture medium contain a yeast extract, dry yeast, chlorella, spirulina, corn meal, okara etc. as a nutrient component as needed.

  Cultivation of shiitake mycelium is performed by inoculating mycelium or spores of shiitake fungus in a medium containing the above-mentioned plant fiber raw material.

  In the case of solid culture, the water content is adjusted to 60 to 80%, sterilized by autoclaving according to a conventional method, then inoculated with mycelia, for example, 3 to 6 in a culture room conditioned at 18 to 25 ° C. Incubate for months. The medium in which the mycelium has spread is desirably transferred to the temperature treatment chamber and subjected to a temperature change treatment. In the temperature change treatment, for example, the mixture is first heated at 30 to 34 ° C. for 24 to 48 hours, and then transferred to a low temperature chamber and treated for 3 to 5 days. After that, when it is transferred to a culture chamber, the generation of fruiting bodies starts.

After completion of the culture, the mycelium is preferably self-digested and the culture is extracted using the mycelium-external enzyme produced by the mycelium. As a preferable method, in the case of a solid medium, the medium after culturing is crushed, a small amount of water is added as necessary, and the mycelium is self-digested by enzymatic action at 30 to 60 ° C. for 3 to 6 hours. . Subsequently, this crushed material is infiltrated with warm water or hot water of 50 ° C. or higher, and an active ingredient is extracted. The extraction can also be carried out under a high pressure such as 120 ° C. under a pressurized vapor pressure of 1 kg / cm ² , for example. The extract suspension thus obtained is preferably filtered or centrifuged to collect the filtrate or supernatant, thereby obtaining a degradation product of the medium, a metabolite of shiitake mycelium, a degradation product of mycelium cells, and the like. An extract in the form of an extract containing it can be obtained.

  In the case of liquid culture, the plant fiber raw material is finely pulverized, and if necessary, other nutrients such as rice bran are added and a medium is prepared so that the raw material is 5 to 20% by weight, and then aeration stirring is performed. By culturing or shaking culture, culturing is preferably performed at a temperature of 20 to 28 ° C. for about 1 week to 2 months. The culture is terminated when the pH of the medium is lowered to 3.5 to 5 and the mycelium is prevalent in the medium.

After completion of the culture, preferably, the whole culture is treated at 30 to 60 ° C. for 3 to 6 hours to self-digest the mycelium to obtain a liquid suspension culture. Subsequently, water is added as necessary, and the extract is collected by heating at 50 ° C. or higher, sometimes under high-pressure conditions (for example, under a pressurized vapor pressure of 1 kg / cm ² ). In addition, this extract is filtered or centrifuged as necessary, and the filtrate or supernatant is collected to extract a degradation product of the medium, a metabolite of shiitake mycelium, a degradation product of mycelium cells, etc. An extract in the form of a liquid can be obtained.

The extract thus obtained was a substance mainly composed of carbohydrates, but was confirmed to have the following components.
・ Sugar: 30-50%
・ Protein: 8-15%
・ Water-soluble lignin: 20-40%

  The shiitake fermented rice bran extract and shiitake mycelium culture medium extract obtained by the above method can be converted into a product as it is or as a liquid by concentrating the extract. It can also be pulverized by a method such as spray drying. When the extract in the form of an extract is dried, a fine powder is obtained, which can be further pulverized into ultrafine particles. Further, it may be commercialized in the form of powder, granule, tablet, capsule, liquid, jelly or the like by a conventional method.

  The sleep improving agent of the present invention needs to be used in combination with a shiitake fermented rice bran extract and a shiitake mycelium culture medium extract. That is, as shown in the examples described later, each of them alone has no effect of improving sleep, and the effect is exhibited only when combined. The ratio of shiitake fermented rice bran extract and shiitake mycelium culture medium extract is preferably 0.5: 1 to 20: 1 in terms of solid content, and preferably 1: 1 to 10: 1. Is more preferable, and 2: 1 to 5: 1 is most preferable.

  The method of combination is not particularly limited as long as it is provided so that the user can take it in combination. Of course, it may be in the form of a composition in which a shiitake fermented rice bran extract and a shiitake mycelium culture medium extract are mixed at a predetermined blending ratio, or, for example, shiitake fermented rice bran extract and shiitake The mycelium culture medium extract may be packaged separately and provided to be taken at the same time when used.

  The effective dosages of shiitake fermented rice bran extract and shiitake mycelium culture medium extract are 0.1 to 10 g and 0.01 to 10 g, respectively, per day for an adult when ingested. If the dose is smaller than this, a sufficient effect is hardly obtained, and if the dose is larger than this, loose stool or abdominal bloating may occur. However, there is no problem in safety even if the dose is larger than the above.

  On the other hand, the scope of the present invention includes the use of the shiitake fermented rice bran extract and / or the shiitake mycelium culture medium extract when preparing an oral composition for the purpose of improving sleep. For example, it is a case where the shiitake fermented rice bran extract and / or the shiitake mycelium culture medium extract is used as a raw material for a health food tablet for improving sleep. The total amount of the shiitake fermented rice bran extract and / or the shiitake mycelium culture medium extract can be arbitrarily determined, but is 1 to 100% by mass, more preferably 10 to 75% by mass, most preferably in the composition. Is 20 to 50% by mass.

  EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but these examples do not limit the scope of the present invention.

<Production Example 1> (Preparation of shiitake fermented rice bran extract (hereinafter referred to as “LEF”))
2 kg of rice bran was placed in a 50 L fermenter and 12 L of water was added. Sterilized at 121 ° C. for 30 minutes with stirring.

  After cooling to 40 ° C., 1 g of “uniase” which is an enzyme agent mainly composed of starch saccharifying amylase, 2 g of “maseroteam” which is an enzyme agent containing pectinase, hemicellulase and the like at high titer, and an enzyme agent containing cellulase 2 g of Cellulase Onozuka 3S (both from Yakult Pharmaceutical Co., Ltd.) were dissolved in 500 mL of water and added after filtration sterilization. After reacting for 4 hours, the same amount of shiitake fungus liquid culture solution (cultured on Marz liquid medium for 45 days) and the above-mentioned rice bran enzyme-degraded suspension was mixed and gradually raised to 60 ° C. Reacted overnight. A water-soluble portion was removed from the reaction solution by centrifugation and spray-dried.

  LEF was a beige fine powder with a faint sweetness. As a result of analyzing the components, the water content is 3.7% (heat loss method), the ash content is 13.4% (direct ashing method), the total sugar is 55.5% (phenol sulfate method), the protein is 15.6% (Duma method) The pentose was 6% (orcine-iron chloride-hydrochloric acid method).

<Production Example 2> (Preparation of shiitake mycelium culture medium extract (hereinafter referred to as “LEM”))
Dry bagasse and defatted rice bran were mixed at a mass ratio of 9: 1, and water was added to 70 mass%. After mixing, it was sterilized by packing in a polypropylene bag. After cooling, Shiitake mushroom was inoculated and cultured at 22 ° C. Shiitake fungus spread on the culture medium consisting of dried bagasse and defatted rice bran, and the whole culture medium was crushed and extracted with warm water just before the fruit body (mushroom) was formed. The extract was sterilized by filtration and spray-dried.

<Test Example 1>
(1) Electrode implantation treatment SD male rats (9 to 11 weeks old) were anesthetized with isoflurane (introduction 5%, maintenance 2%), and the scalp was incised through the midline to expose the skull. According to Paxinos et al.'S brain map (see Fig. 1), on the frontal cortex (A: 2.0mm, L: 2.0mm) as an electroencephalogram measurement electrode (B: Bregma is 0 in Fig. 1, A: Anteroposterior (forward direction) 2.0mm, L: Laterally (lateral position, 2.0mm brain coordinate position), and occipital cortex (P: 2.0mm, L: 2.0mm) (B: Bregma is 0 in Fig. 1) , P: posteriorly (backward) 2.0mm, L: Laterally (2.0mm brain coordinate position), screw electrode at the left and right symmetrically, two screws as anchors, and indifferent electrode A screw electrode was embedded near the cerebellum. Furthermore, as an electrode for electromyogram measurement, a urethane coat conducting wire in which a part of urethane was peeled off from the priest muscle and solder was attached was passed through and tied and fixed.

(2) Measurement environment The measurement of the electroencephalogram and electromyogram of a rat was performed by placing the rat in an acrylic observation box (length 30 cm, width 30 cm, height 30 cm) without restraint. This observation box was placed in a soundproof shield box.

(3) Examination of mixing ratio LEF and LEM prepared in Production Example 1 and Production Example 2 were mixed at a mass ratio of 1: 1, 2: 1, 3: 1, 4: 1, 5: 1, 10: 1. A sample was prepared.

(4) Administration method Each sample (1 g / kg body weight) was orally administered to a rat one week after the electrode implantation treatment using a stomach tube, and measurement was started immediately after administration. On the other day, the same rat was orally administered with distilled water and the amount of sleep was measured and used as control data.

(5) Measurement of electroencephalogram and electromyogram The electroencephalogram and electromyogram were measured for 6 hours from 10.30 am to 4.30 pm using a data analysis device ("PowerLab", manufactured by AD Instruments).

  (6) The sleep and awakening stage is awakening, non-REM sleep, and REM sleep. The sleep analysis research program (“SleepSign3.0”, Kissei Comtech Co., Ltd.) is used to analyze 10 seconds as 1 epoch. The ratio of each state and the total amount of sleep were measured.

(7) Results FIG. 2 shows non-REM sleep, and FIG. 3 is a graph showing the results of measuring the effect on total sleep.

  As shown in FIGS. 2 and 3, single administration of LEF or LEM had no significant effect on rat sleep. In contrast, a mixture of LEF and LEM shows a tendency to increase sleep in rats, and by increasing the mixing ratio of LEF, the effect of sleep tends to be enhanced, and LEF: LEM is 4: 1. In the case, the rate of increase in sleep volume was maximized. At 5: 1 and 10: 1, the effect was attenuated and REM sleep tended to decrease.

<Test Example 2>
Test substance mixed with LEM and LEF in a ratio of 2: 1 to 13 adult men and women (7 men, 6 women, average age 41.6 years) who are dissatisfied with sleep at 1.5 g / day. Evaluate sleep state at the end of daily intake in 5 stages: worse (-2 points), slightly worse (-1 points), unchanged (0 points), slightly improved (1 point), improved (2 points) did. The five survey items were sleep, depth of sleep, sleep time, deep sleep, and awakening.

  FIG. 4 shows the result of the number of subjects who made each evaluation for each of the survey items, and FIG. 5 shows the result of the cumulative value of the evaluation points for each of the survey items.

  As shown in FIG. 4, the proportion of improved persons is 61.5% for the sleeping item, 58.3% for the sleeping depth item, and 69 for the sleeping time item when the improvement and improvement are combined a little. 2%, 69.2% in the item of deep sleep, and 53.8% in the item of awakening. There were no cases of deterioration (including slight deterioration). Therefore, it became clear that the sleep improvement effect is brought about by the combined intake of LEM and LEF for humans who are dissatisfied with sleep (see FIGS. 4 and 5).

Claims (5)

  Shiitake mycelium is cultured in a medium containing an enzymatic degradation product of rice bran, and shiitake mycelium is cultured in a medium containing a shiitake fermented rice bran extract prepared from the culture and a plant fiber raw material prepared from a plant of this family. A sleep-improving agent comprising a combination with a shiitake mycelium culture medium extract prepared from the culture.   The sleep-improving agent according to claim 1, wherein the enzyme-decomposed product of rice bran is a decomposed product of a polysaccharide-degrading enzyme.   The sleep-improving agent according to claim 1 or 2, wherein the shiitake mycelium culture medium extract contains a saccharide, a protein, and a water-soluble lignin.   The sleep according to any one of claims 1 to 3, wherein the culture of the rice bran in the medium containing the enzymatic degradation product is a liquid culture, and the culture in the medium containing the plant fiber raw material is a solid culture. Improver.   To prepare an oral composition for the purpose of improving sleep, (1) shiitake mycelium is cultured in a medium containing an enzymatic degradation product of rice bran, shiitake fermented rice bran extract prepared from the culture, and / or Or (2) Use of an extract of shiitake mycelium culture medium prepared by culturing shiitake mycelium in a medium containing plant fiber raw material.