WO2021015289A1

WO2021015289A1 - Composition for maintaining and/or improving memory/learning ability, and food, medicine, and feed containing composition

Info

Publication number: WO2021015289A1
Application number: PCT/JP2020/028687
Authority: WO
Inventors: 聡志日暮; 健太郎野間; 郁恵森; 俊詩中野; 祐基塚田
Original assignee: 雪印メグミルク株式会社
Priority date: 2019-07-24
Filing date: 2020-07-27
Publication date: 2021-01-28
Also published as: JP2021019507A; JP6739603B1; TW202112387A

Abstract

To provide a medicine or a food and drink and a feed which are effective in preventing and/or ameliorating memory/learning ability deterioration due to aging.　Provided is a novel lactic acid bacterium having the effect of preventing and/or ameliorating memory/learning ability deterioration due to aging. Specifically, the lactic acid bacterium belongs to the heterofermentative Lactobacillus genus. More specifically, the lactic acid bacterium is characterized by being a lactic acid bacterium belonging to any of the Lactobacillus harbinensis species, Lactobacillus rhamnosus species, Lactobacillus casei species, Lactobacillus paracasei species, Lactobacillus fermentum species, Lactobacillus mucosae species, and Lactobacillus reuteri species.

Description

Compositions for maintaining and / or improving memory / learning ability and foods, medicines, feeds containing the compositions

The present invention provides a preventive / ameliorating agent for deterioration of memory / learning ability that occurs with aging (aging) and / or a preventive / ameliorating effect of deterioration of memory / learning ability that occurs with aging (aging). Regarding food and drink to have.

In 2010, the elderly population aged 65 and over exceeded 21% of the total population, and Japan entered a super-aging society. The proportion of elderly people is expected to continue to increase, reaching 40% by 2060. Under such circumstances, it is an urgent issue to deal with the problems of the increasing elderly population such as medical care and welfare.

With the increase in the elderly population, the increase in cognitive dysfunction and dementia such as deterioration of memory and learning ability of middle-aged and elderly people is regarded as a problem. In general, it is thought that the microstructure of nerve cells in the brain changes with aging, and cognitive function declines as the brain atrophies through abnormal protein deposition and cell shedding. ing. Dementia is a condition in which cognitive function is pathologically impaired due to factors such as cerebral infarction, cerebral hemorrhage, and excessive accumulation of abnormal proteins in addition to these age-related changes.

As of 2012, among the elderly aged 65 and over, the number of dementia patients is estimated to be about 4.62 million, and the number of people with mild cognitive impairment called the dementia reserve army is estimated to be about 4 million. It is said to be "the age of 8 million people with dementia."

Development of therapeutic agents for dementia is underway, but at present, it is used for the purpose of delaying the progression, and has not yet reached a radical treatment. On the other hand, in healthy elderly people and elderly people with mild cognitive impairment, which is positioned as a precursor of dementia, cognitive functions such as memory and learning ability can be improved by reviewing dietary habits and performing appropriate interventions such as exercise. It has been shown that the decline can be prevented or ameliorated, and the risk of developing dementia can be reduced (Seino Journal 111, 26-30, (2009)). For this reason, there is increasing interest in foods and drinks that can be continuously ingested in daily life, are safe, and have no side effects.

Lactic acid bacteria are widely used in fermented foods such as cheese, yogurt, and pickles, and lactic acid bacteria beverages. They can be supplied at a relatively low cost and have been mass-produced all over the world for a long time due to their high palatability. Recently, it has been attracting attention as a health food having favorable health effects such as prevention of constipation, improvement of diarrhea and other intestinal regulation, prevention of infectious diseases, and immunostimulatory effect. Regarding aging and cognitive function, Lactobacillus gasseri and Bifidobacterium longum are effective against age-related metabolic disorders (Patent 5155961, Patent 5155960), Lactobacillus reutery DSM 17938 strain. Is effective for the development of cognitive function in young mammals (Special Table 2015-503913) and the like are disclosed.

However, the action of heterofermentative lactic acid bacilli belonging to the genus Lactobacillus on the decline in memory and learning ability that occurs with aging is still unclear.

C. elegans Caenorhabditis elegans (hereinafter referred to as C. elegans) can sense various external stimuli and take various response behaviors by using a simple neural circuit consisting of 302 neurons. C. elegans memorizes the breeding temperature as a comfortable temperature when bred at a constant temperature, and therefore shows a habit of moving toward the past breeding temperature when placed on a temperature gradient. For example, C.I. When the elegans are placed on a temperature gradient from 17 ° C to 23 ° C without food, they move to around 23 ° C after 1 hour. Furthermore, C.I. When elegans are bred at a new temperature of 17 ° C, they acquire a memory of a new temperature of 17 ° C in about 4 hours and move to around 17 ° C on a temperature gradient (Proc. Natl. Acad. Sci. USA, 72, 4061-4065 (1975); Genetics, 169, 1437-1450 (2005); J. Neurosci. Methods, 154, 45-52 (2006)). This habit is called temperature tactics and is known to be an excellent model system that reflects the plasticity of neural functions such as memory and learning (Curr. Opin. Neurobiol., 17, 712-719 (2007)).

The inventors' past experiments on neuron destruction by laser have revealed the neurons required for thermotactic behavior, and it is known that thermotactic behavior is based on a very simple neural circuit (). Nature, 376, 344-348 (1995)). In addition, the inventor's research group analyzed the process of temperature memory formation by genome-wide microarray analysis, molecular genetic techniques, and imaging techniques. As a result, C.I. It was found that elegans receives the ambient temperature systemically via the transcription factor HSF-1 when memorizing the breeding temperature. Furthermore, it was shown that the reception of this temperature causes a change in gene expression, and as a result, the temperature signal is accumulated as a memory in the AFD neuron, which is a temperature receiving neuron of the neural circuit, via the female hormone estrogen. (Nat. Neurosci., 14, 984-92 (2011)).

Furthermore, the inventors have described the C.I. As a result of searching for cells in which orthologs function in elegans, it was found that only one CREB ortholog functions in AFD neurons (EMBO Rep., 12, 855-862 (2011)). That is, C.I. It was shown that among all neurons of elegans, AFD neurons are the only neurons with temperature memory mediated by CREB. These studies reveal some of the molecular mechanisms by which temperature memory is formed.

Although nematodes and mammals are evolutionarily distant, they have much in common in their cellular-level molecular mechanisms. It has been reported that molecules known to be involved in memory in mammals are also involved in the temperature tactics of C. elegans. For example, the memory-related factor CREB (CRH-1 in C. elegans) in mammals is involved in the acquisition of temperature memory in C. elegans (EMBO Rep., 12, 855-862 (2011)), and is involved in memory in C. elegans. Serotonin, a transmitter in the brain, controls the temperature motility of nematodes (PLoS One., 8, 1-10 (2013)), and calcineurin, a memory-related factor in mammals (RCAN-1 in nematodes). ) Has been reported to be involved in the temperature-running behavior of nematodes (J. Mol. Biol., 427, 3457-3468 (2015)).

Furthermore, there have been reports of cases in which a component that has been shown to be effective against the nervous system in nematodes also has an effect on the brain and nervous system in mammals. That is, orally ingested α-lipoic acid improves the associative learning behavior of age-related nematodes and mammals (Neurobiol. Aging., 26, 899-905 (2005); J. Med. Food. 15 , 713-7 (2012)), Orally ingested curcumin improves age-related cognitive impairment in nematodes and mammals (Neurobiol. Aging., 39, 69-81 (2016); Geroscience., 40, 73-95 (2018)) etc. have been reported.

From these things, C.I. The thermotactic behavior of elegans is considered to be a model system suitable for analyzing the molecular mechanism of temperature reception and memory.

Patent 5155961 Patent 5155960 Special table 2015-503913

The present invention relates to providing a novel lactic acid bacterium having an effect of preventing and / or ameliorating a decrease in memory / learning ability that occurs with aging (aging).

The present inventors have focused on the microorganisms used in foods and the components contained therein from the viewpoint of whether various functional abnormalities of the living body can be prevented or ameliorated by the food materials that can be ingested on a daily basis. As a result of intensive research to solve the problems, prevention and prevention of deterioration of memory / learning ability that occurs with aging (aging) in cells or cultures of multiple heterofermentative lactic acid bacteria of the genus Lactobacillus / Or found an action to improve, and completed the present invention. That is, the present invention has the following configuration.
(1) A composition for maintaining and / or improving memory / learning ability, which comprises cells or cultures of heterofermentative lactic acid bacilli of the genus Lactobacillus.
(2) Heterofermentative Lactobacillus of the genus Lactobacillus is Lactobacillus harbinensis (Lactobacillus harbinensis) species, Lactobacillus ramnosus species, Lactobacillus casei (Lactobacillus casei) Lactobacillus casei (Lactobacillus lactobacillus) One or more of Lactobacillus fermentum, Lactobacillus mucosae, Lactobacillus reuteri, a mixture of these, and Lactobacillus fermentum, Lactobacillus mucosae, and Lactobacillus reuteri. Alternatively, the composition for maintaining and / or improving memory / learning ability according to (1), which comprises a culture.
(3) Heterofermentative Lactobacillus of the genus Lactobacillus is Lactobacillus harbinensis (Lactobacillus harbinensis) species, Lactobacillus ramnosus species, Lactobacillus casei (Lactobacillus casei) Lactobacillus casei (Lactobacillus lactobacillus) One or more of Lactobacillus fermentum, Lactobacillus mucosae, Lactobacillus reuteri, a mixture of these, and Lactobacillus fermentum, Lactobacillus mucosae, and Lactobacillus reuteri. Alternatively, the composition for maintaining and / or improving memory / learning ability according to (1) or (2), which does not contain a culture.
(4) Heterofermentative lactic acid rods of the genus Lactobacillus are Lactobacillus acidophilus species, Lactobacillus brevis species, Lactobacillus crispatus species, Lactobacillus crispactus species. delbrueckii) species, Lactobacillus Deruburukkyi subspecies Deruburukkyi (Lactobacillus delbruekii subsp. delbruekii) species, Lactobacillus gasseri (Lactobacillus gasseri) species, Lactobacillus helveticus (Lactobacillus helveticus) species, Lactobacillus Jonsonyi (Lactobacillus johnsonii) species, Lactobacillus lactis, Lactobacillus leichmannii, Lactobacillus pentosus, Lactobacillus lactobacillus lactobacillus lactobacillus lactobacillus lactobacillus The memory / learning ability maintenance and memory / learning ability maintenance according to any one of (1) to (3), which is one of Lactobacillus salivalius species or a mixture of a plurality of types of cells, or does not contain a culture. / Or an improving composition.
(5) Lactobacillus heterofermentative lactic acid rods are Lactobacillus herbinensis SBT0796 strain, Lactobacillus ramnosus SBT2299 strain, Lactobacillus casei SBT2232 strain, Lactobacillus paracasei SBT0228 strain, Lactobacillus fermentum SBT1859 strain. The memory / learning according to any one of (2) to (4), which comprises one strain of Lactobacillus mucosae SBT2958 strain, one strain of Lactobacillus reutery SBT10010 strain, or a mixture of multiple strains of cells, or a culture. Composition for maintaining and / or improving performance.
(6) Any of (1) to (5), wherein the maintenance and / or improvement of the memory / learning ability is prevention and / or improvement of the deterioration of the memory / learning ability that occurs with aging (aging). The composition for maintaining and / or improving memory / learning ability according to.
(7) The decrease in memory / learning ability that occurs with aging (aging) does not include the decrease in memory / learning ability or the decrease in memory ability that occurs with brain disease, memory disorder, and mental illness. , (1) to (6) for maintaining and / or improving memory / learning ability.
(8) The composition for maintaining and / or improving memory / learning ability according to any one of (1) to (7), wherein the active ingredient is not a peptide component contained in a culture supernatant of a microorganism but a bacterial cell of the microorganism. ..
(9) A food for maintaining and / or improving memory / learning ability, which comprises the composition for maintaining / / or improving memory / learning ability according to any one of (1) to (8). Drugs for maintaining and / or improving ability, feeds for maintaining and / or improving memory / learning ability.
(10) Lactobacillus harbinensis SBT0796 strain with a trust number of NITE BP-02993, Lactobacillus ramnosus SBT2299 strain with a trust number of NITE BP-02994, and Lactobacillus casei SBT2232 strain with a trust number of NITE P-02995. , Lactobacillus fermentum SBT1859 strain with a trust number of NITE P-02996, or Lactobacillus reutery SBT10010 strain with a trust number of NITE BP-02997.

According to the present invention, it is possible to prevent and / or ameliorate the deterioration of memory / learning ability that occurs with aging (aging). INDUSTRIAL APPLICABILITY The present invention is effective in improving the quality of life of elderly people who are concerned about deterioration of memory / learning ability.

C. It is a figure which showed the outline of the temperature taxis test using elegans. C. It is a figure which showed the change of the memory index with aging of elegans and the memory index of the aging adult who ingested lactic acid bacteria. It is a figure which showed the relationship between the phylogenetic tree of lactic acid bacteria and the memory index of the aging adult which ingested lactic acid bacteria. It is a figure which compared the memory index of the aging adult which ingested lactic acid bacterium by the difference in the fermentation form of lactic acid bacterium.

In the present specification, the term "maintaining and / or improving memory / learning ability" preferably means preventing and / or ameliorating the deterioration of memory / learning ability that occurs with aging (aging). More preferably, it means preventing and / or ameliorating the deterioration of memory ability that occurs with aging (aging). Furthermore, in the present specification, when "decrease in memory / learning ability that occurs with aging (aging)" or "decrease in memory ability that occurs with aging (aging)" is preferably referred to as Alzheimer's disease. Dementia such as Huntington's disease and cerebral basal nucleus disease such as Parkinson's disease, and memory disorders such as amnesia, memory loss, and Korsakov syndrome, as well as depression, anxiety, bipolar disorder, integration. Does not include memory / learning or memory loss associated with mental disorders such as dementia, sleep abnormalities, and stress disorders.

The term "composition" as used herein preferably means a pharmaceutical composition or a food composition.

The lactic acid bacterium in the present invention is characterized by using a heterofermentative lactic acid bacillus belonging to the genus Lactobacillus. As heterofermentative lactic acid rod bacteria belonging to the genus Lactobacillus, Lactobacillus habinensis species, Lactobacillus ramnosus species, Lactobacillus casei species, Lactobacillus paracasei species, Lactobacillus fermentum species, Lactobacillus mucosae species, Lactobacillus reutery species are preferred. More preferred are Lactobacillus harbinensis SBT0796, Lactobacillus ramnosus SBT2299, Lactobacillus casei SBT2232, Lactobacillus paracasei SBT0228, Lactobacillus fermentum SBT1859, Lactobacillus mucosae SBT2958. Although it is the Reutery SBT10010 strain, it is not particularly limited as long as it is a heterofermentative lactic acid bacterium having an effect of maintaining and / or improving the memory / learning ability of the present invention.

These heterofermentative lactic acid bacilli may be used alone or in combination of two or more lactic acid bacteria as appropriate. In addition, these heterofermentative lactic acid bacilli can be cultivated according to a conventional method for culturing lactic acid bacteria. As the culture medium, various media such as a milk medium, a medium containing a milk component, and a semi-synthetic medium not containing the milk component can be used. Examples of such a medium include a reduced skim milk medium and an MRS medium.

The cells separated from the obtained culture by means of collecting bacteria such as centrifugation can be used as they are as the active ingredient of the present invention. Bacterial cells that have been concentrated, dried, freeze-dried, etc. can be used, or can be killed by heat-drying or the like. Not only purely isolated cells, but also cultures, suspensions, other cell-containing substances, and cytoplasm and cell wall fractions obtained by treating cells using enzymes or physical means can be used. it can. The form of the culture is not only a culture using a medium generally used for culturing lactic acid bacteria such as a synthetic medium MRS medium (manufactured by DIFCO) and a reduced defatted milk medium, but also cheese, fermented milk, and milk. Products Dairy products such as lactic acid bacteria beverages can be exemplified, but are not particularly limited.

In formulating the memory / learning ability maintaining and / or improving agent of the present invention, the excipients, stabilizers, flavoring agents, etc. permitted in the formulation are appropriately mixed, concentrated, freeze-dried, and heat-dried. It may be a dead cell. These dried products, concentrates and pastes are also contained. In addition, as long as it does not interfere with the memory / learning ability maintenance and / or improving action of the heterofermentative lactic acid bacillus belonging to the genus Lactobacillus, it is an excipient, a binder, a disintegrant, a lubricant, a flavoring agent, and a suspending agent. , Coating agents, and any other drug can be mixed and formulated. The dosage form can be tablets, capsules, granules, powders, powders, syrups, etc., and it is desirable to administer these orally.

The composition for maintaining and / or improving the memory / learning ability of the present invention may be blended in any food or drink, or may be added to a raw material during the manufacturing process of the food or drink. Examples of foods and drinks include cheese, fermented milk, dairy products, lactic acid bacteria beverages, lactic acid bacteria beverages, butter, dairy products such as margarine, beverages such as dairy beverages, fruit juice beverages, and soft beverages, and eggs such as jelly, candy, pudding, and mayonnaise. Processed products, sweets and breads such as butter cakes, various milk powders, infant foods, nutritional compositions, etc. can be mentioned, but are not particularly limited. Further, the composition for maintaining and / or improving the memory / learning ability of the present invention can be added to the feed. Like the food and drink, it may be blended with any feed and may be added to the raw material during the feed manufacturing process.

A composition for maintaining and / or improving memory / learning ability, or a food / drink or nutritional composition for maintaining and / or improving memory / learning ability by blending cells or cultures of heterofermentative lactic acid bacilli belonging to the genus Lactobacillus. When used by blending with materials such as products and feeds or processed products of those materials, the blending ratio of the cells or cultures of heterofermentative lactic acid bacilli belonging to the genus Lactobacillus is not particularly limited, and the ease of production and It may be appropriately adjusted according to a preferable daily dose. It is determined individually in consideration of the symptoms, age, etc. of the recipient, but in the case of adults, for example, 10 to 200 g of a culture of Lactobacillus ramnosus, or 0.1 to the bacterial cells themselves. The blending amount may be adjusted so that 5,000 mg can be ingested. By ingesting in this way, a desired effect can be exhibited.

In the present invention, as a method for screening for lactic acid bacteria that prevent and / or improve the deterioration of memory / learning ability that occurs with aging (aging), C.I. A temperature taxis test using elegans was used. Generally, higher animals such as mice, rats, dogs, and monkeys are used to verify the physiological functions of food components and drugs, but this requires a great deal of labor, time, and cost, and is ethical. It is necessary to give due consideration to. As an alternative method for animal experiments, tests using cultured cells isolated from animal tissues are also being conducted.

C. C. elegans is a non-parasitic multicellular organism that lives in soil, and in addition to being easy to handle as an experimental animal, the cell lineage of about 1000 somatic cells that make up the body has been clarified. It is widely used in various research fields as a model organism because it has points and a nervous system. In particular, he has made great contributions in various research fields such as cell death, neurogenesis, development, and aging. Furthermore, in recent years, C.I., a model of various neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, and Huntington's disease. Using elegans, the search for effective medicines and food components for the prevention and improvement of these neurodegenerative diseases is underway.

C. Although elegans has a simple neural circuit, it is known to memorize and learn by associating information such as the presence or absence of food with the salt concentration and temperature in the environment placed at that time, such as associative learning and memory. It can be used as a model system for evaluating the cognitive function of (Nature, 376, 344-348 (1995)).

Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not construed as being limited to such examples.

[Test Example 1] Evaluation of lactic acid bacteria that prevent and / or improve the deterioration of memory / learning ability that occurs with aging (aging) C.I. Elegans used a wild-type N2 strain and was bred according to the "Nematode Lab Manual".
1. 1. Test Method (1) Test Bacteria Strains of heterofermentative lactic acid bacilli belonging to the genus Lactobacillus shown in Table 1 were subjected to screening.

(2) Test procedure
(i) Preparation of evaluation sample Each test bacterium of (1) above was inoculated into MRS medium and statically cultured at 37 ° C. for 16 hours. The cultured cells were centrifuged (7,000 × g, 4 ° C., 15 minutes), and the supernatant was discarded. After washing the cells with physiological saline, the wet weight of the cells was determined, and NG buffer (0.3% NaCl, 1 mM CaCl ₂ , 1 mM sulfonyl ₄ , 25 mM phosphate buffer) was adjusted to 0.05 g / ml. Resuspended in [pH 6.0]) and C.I. A sample plate was prepared by sowing 200 μl each on an elegans breeding plate (NGM plate). As a control, C.I. Escherichia coli OP50 strain, which is generally used as a diet for elegans, was used.

(ii) Preparation of aging adults ingested with lactic acid bacteria C. recovered by bleaching. Eggs of elegans were sown on a plate in which OP50 was sown and allowed to stand at 23 ° C. for 3 days to obtain young adults. The adults were collected with NG buffer, transferred to a plate in which lactic acid bacteria were sown or a plate in which OP50 was sown, and bred at 23 ° C. for 4 days to obtain aging adults.

(iii) Screening by temperature taxis test The temperature taxis test is performed by Ito H. et al. (J. Neurosci. Methods, 154, 45-52 (2006)) et al. (J. Neurosci. Methods, 154, 45-52 (2006)). Prepare two constant temperature baths, one foot of the U-shaped aluminum stand (21.5 cm x 60 cm x 1.5 cm thick) on the low temperature side (5 ° C) and the other on the high temperature side (35 ° C). By immersing in a constant temperature bath, a linear temperature gradient from about 5 ° C. to 35 ° C. was formed on the aluminum table. An agar plate placed in a square petri dish is placed on an aluminum table so that the temperature is centered at 20 ° C., and the above-mentioned young adults or aged adults are released in the center of the plate, and one hour later, C.I. The distribution of elegans was evaluated. The memory / learning ability was determined by C.I., which was located in two compartments near the breeding temperature (23 ° C.) when the plate was divided into eight equal parts in the temperature gradient direction. The proportion of elegans was evaluated as a memory index (FIG. 1). In addition, the presence or absence of a significant difference when an aged adult who ingested OP50 was used as a control was evaluated by a Danette-type multiple test (p <0.05 was judged to be significant).

2. 2. Test results
FIG. 2 shows the screening results. The memory index decreased in the aged adults compared to the young adults. Lactobacillus harbinensis SBT0796 strain, Lactobacillus ramnosus SBT2299 strain, Lactobacillus casei SBT2232 strain, Lactobacillus paracasei SBT0228 strain, Lactobacillus fermentum SBT1859 strain, Lactobacillus fermentum SBT1859 strain, which are heterofermentative lactic acid rods. Aged adults who ingested the Lactobacillus reutery SBT10010 strain had a significantly increased memory index compared to those who ingested OP50. That is, it was found that by ingesting the above-mentioned cells, it is possible to prevent and / or improve the deterioration of memory / learning ability that occurs with aging (aging).

The results of the memory index of nematodes that ingested lactic acid bacteria were applied to a phylogenetic tree created based on the 16s rRNA sequence of lactic acid bacteria, and it was verified whether there was a correlation between the strain of lactic acid bacteria and the memory index. As a result, the tendency of the memory index value differs among the clusters of the phylogenetic tree, and it belongs to the genus Lactobacillus as compared with the homofermentative strains belonging to the genus Lactobacillus and the strains belonging to the genus Leuconostoc and the genus Bifidobacterium. Heterofermentative strains showed high values (Figs. 3 and 4). It was shown that the components produced by heterofermentative lactic acid bacteria may improve the temperature memory of C. elegans.

(Example 1) Production of agent (granule) for maintaining and / or improving memory / learning ability Lactobacillus reutery SBT10010 strain edible synthetic medium (0.5% yeast extract, 0.1% trypticase soybean peptone addition) ) Was ingested in an amount of 5% by weight, cultured at 38 ° C. for 15 hours, and then the cells were collected by centrifugation. The recovered cells were freeze-dried to obtain a freeze-dried powder of the early cells. 1 g of this freeze-dried powder was mixed with 5 g of lactose and molded into granules to obtain an agent for maintaining and / or improving the memory / learning ability of the present invention.

(Example 2) Manufacture of agent (powder) for maintaining and / or improving memory / learning ability The lactobacillus obtained in Example 1 above in accordance with the provisions of the 13th revised Japanese Pharmacopoeia Manual of Formulation "Powder". -400 g of lactose (Japanese Pharmacopoeia) and 600 g of potato starch (Japanese Pharmacopoeia) were added to 10 g of lyophilized powder of Reutery SBT10010 strain and mixed uniformly to produce an agent for maintaining and / or improving memory / learning ability of the present invention.

(Example 3) Production of nutritional composition for maintaining and / or improving memory / learning ability A synthetic medium in which Lactobacillus reutery SBT10010 strain is edible (0.5% yeast extract, 0.1% trypticase soybean peptone added) After ingesting 5% by weight and culturing at 37 ° C. for 15 hours, the cells were collected by centrifugation, and the collected cells were lyophilized. To 40 g of vitamin C or an equal amount mixture of vitamin C and citric acid, 100 g of granulated sugar, and 60 g of an equal amount mixture of cornstarch and lactose, 40 g of the freeze-dried powder of this freeze-dried powder was added and mixed. The mixture was packed in a bag to produce a nutritional composition for maintaining and / or improving memory / learning ability of the present invention.

(Example 4) Production of beverage for maintaining and / or improving memory / learning ability After 1 g of Lactobacillus reutery SBT10010 strain obtained in Example 3 above was dissolved in 699 g of deionized water and then heated to 40 ° C. The mixture was stirred and mixed at 9,500 rpm for 20 minutes with an ultra disperser (ULTRA-TURRAX T-25; manufactured by IKA Japan). After adding 100 g of maltitol, 2 g of acidulant, 20 g of reduced starch syrup, 2 g of flavor and 176 g of deionized water, the mixture is filled in a 100 ml glass bottle, sterilized at 95 ° C. for 15 seconds, and then sealed to maintain the memory / learning ability of the present invention. And / or 10 bottles of improving beverage (containing 100 ml) were produced.

(Example 5) Production of feed for maintaining and / or improving memory / learning ability Soybean meal 12 kg, skim milk powder 14 kg, soybean oil 4 kg, corn oil 2 kg, palm oil 23.2 kg, corn starch 14 kg, wheat flour 9 kg, bran 2 kg, 5 kg of vitamin mixture, 2.8 kg of cellulose, and 2 kg of mineral mixture were blended, sterilized at 120 ° C. for 4 minutes, and 10 kg of lactobacillus reutery SBT10010 strain obtained in Example 3 was blended to store and learn the present invention. A feed for maintaining and / or improving performance was produced.

(Example 6) Production of fermented milk for maintaining and / or improving memory / learning ability A synthetic medium in which Bifidobacterium reutery SBT10010 strain is edible (0.5% yeast extract, 0.1% trypticase soybean peptone addition) ) Was ingested in an amount of 5% by weight, cultured at 37 ° C. for 17 hours, and then the cells were collected by centrifugation and lyophilized. 5 g of the lyophilized cells, 1700 g of skim milk powder, 300 g of glucose, and 7695 g of deionized water were mixed and kept at 95 ° C. for 2 hours for heat sterilization. This was cooled to 37 ° C., 300 g of a lactic acid bacterium starter (Lb. Casei) was inoculated, stirred and mixed, and then fermented to pH 4.0 in an incubator maintained at 37 ° C. After reaching pH 4.0, the mixture was cooled to 10 ° C. or lower to produce 10 kg of fermented milk for maintaining and / or improving the memory / learning ability of the present invention.

(1) Lactobacillus harbinensis SBT0796 shares (receipt number: NITE ABP-02993, receipt date: July 13, 2020, original contract date: June 26, 2019), contractor: Chiba, Japan 292-0818 2-5-8 Kazusakamatari, Kisarazu City, Chiba Prefecture, National Institute of Technology and Evaluation Patent Microorganisms Depositary Center (NPMD).
(2) Lactobacillus ramnosus SBT2299 shares (receipt number: NITE ABP-02994, receipt date: July 13, 2020, original contract date: June 26, 2019), contractor: Chiba, Japan 292-0818 2-5-8 Kazusakamatari, Kisarazu City, Chiba Prefecture, National Institute of Technology and Evaluation Patent Microorganisms Depositary Center (NPMD).
(3) Lactobacillus casei SBT2232 shares (trust number: NITE P-02995, trust date: June 26, 2019), trustee: 2-5-8 Kazusakamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 , National Institute of Technology and Evaluation Patent Microorganisms Depositary Center (NPMD).
(4) Lactobacillus fermentum SBT1859 shares (trust number: NITE P-02996, trust date: June 26, 2019), trustee: 2-5 Kazusakamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 8. National Institute of Technology and Evaluation Patent Microorganisms Depositary Center (NPMD).
(5) Lactobacillus reutery SBT10010 shares (receipt number: NITE ABP-02997, receipt date: July 13, 2020, original contract date: June 26, 2019), contractor: 〒292-0818 Chiba, Japan 2-5-8 Kazusakamatari, Kisarazu City, Chiba Prefecture, National Institute of Technology and Evaluation Patent Microorganisms Depositary Center (NPMD).

Claims

A composition for maintaining and / or improving memory / learning ability, which comprises cells or cultures of a heterofermentative lactic acid bacillus of the genus Lactobacillus.
Heterofermentative Lactobacillus of the genus Lactobacillus is Lactobacillus harbinensis (Lactobacillus harbinensis) species, Lactobacillus rhamnosus species, Lactobacillus casei (Lactobacillus casei) Lactobacillus casei (Lactobacillus casei) , Lactobacillus fermentum species, Lactobacillus mucosae species, Lactobacillus reuteri species, or a mixture of multiple types of cells. The composition for maintaining and / or improving memory / learning ability according to claim 1.
Lactobacillus heterofermentative lactic acid rods are Lactobacillus herbinensis SBT0796 strain, Lactobacillus ramnosus SBT2299 strain, Lactobacillus casei SBT2232 strain, Lactobacillus paracasei SBT0228 strain, Lactobacillus fermentum SBT1859 strain, Lactobacillus fermentum SBT1859 strain. The composition for maintaining and / or improving memory / learning ability according to claim 1, which comprises one strain of Mukosae SBT2958 strain, one strain of Lactobacillus reutery SBT10010 strain, or a mixture of a plurality of strains of cells, or a culture.
A food for maintaining and / or improving memory / learning ability, a food for maintaining / / maintaining memory / learning ability, and / or, which comprises the composition for maintaining and / or improving memory / learning ability according to any one of claims 1 to 3. Drugs for improving, memory / learning ability maintenance and / or feed for improvement.
Lactobacillus harbinensis SBT0796 strain with a trust number of NITE BP-02993, Lactobacillus ramnosus SBT2299 strain with a trust number of NITE BP-02994, or Lactobacillus reutery SBT10010 strain with a trust number of NITE BP-02997.