JPWO2019188943A1 - Composition for prevention and / or improvement of decreased cerebral blood flow - Google Patents

Abstract

To provide a composition capable of preventing and / or ameliorating a decrease in cerebral blood flow. A composition for preventing and / or improving cerebral blood flow reduction containing a bifidobacteria as an active ingredient; preferably, the bifidobacteria are bifidobacteria longum and / or bifidobacteria. Um-Breve; also, the composition is used for cerebrovascular dementia; and preferably, the composition is a pharmaceutical composition or a food or drink composition.

Description

The present art relates to compositions for preventing and / or ameliorating decreased cerebral blood flow.

As society matures, the population of middle-aged to elderly people tends to increase. Dementia has become a social problem as the elderly population increases. Since improvement of quality of life and countermeasures for locomotive syndrome have been advocated, there is increasing interest in prevention or improvement of dementia.

By the way, it is known that dementia includes Alzheimer's dementia, cerebrovascular dementia, Lewy body dementia, frontotemporal dementia and the like. Alzheimer's dementia accounts for the main proportion, followed by cerebrovascular dementia and Lewy body dementias. Symptoms of Alzheimer-type dementia progress slowly due to amyloid plaque and neurofibrillary tangles causing nerve cell shedding and brain atrophy (Non-Patent Document 1). On the other hand, the symptom of cerebrovascular dementia is that oxygen and nutrients cannot reach nerve cells or neural networks in the brain due to a decrease in cerebral blood flow in the brain due to cerebral angiopathy, cerebral infarction, cerebral hemorrhage, etc. , Progress (Non-Patent Document 2).

In actual medical practice, cerebrovascular dementia is distinguished from Alzheimer's disease because it has a different treatment policy from neurodegenerative diseases such as Alzheimer's disease (Alzheimer's disease) and Parkinson's disease. Therefore, vascular dementia and Alzheimer's dementia are distinguished by clinical criteria. To distinguish these, for example, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Illness; the Alzheimer Diagnostic Criteria and Vascular Dementia (VaD) Diagnostic Criteria in the Revised 4th Edition (DSM-IV) It is used (Non-Patent Documents 1 and 2).

Vascular dementia is the second most common dementia after Alzheimer's disease. However, while research and development of compounds for the prevention or improvement of Alzheimer's disease is being actively carried out, research and development of compounds for the prevention or improvement of vascular dementia is still insufficient.

For example, in Non-Patent Document 3, cerebral blood flow and angiogenesis were evaluated on the 7th day after chronic cerebral hypoperfusion model (BCAS) surgery was performed on mice overexpressing the peptide hormone adelenomedulin. Furthermore, studies are being conducted on the suppression of working memory impairment 28 days after surgery. As a result, Non-Patent Document 3 concludes that adelenomedulin can be a therapeutic method for vascular dementia.

Japanese Society of Neurology https://www.neurology-jp.org/guidelinem/degl/sinkei_degl_2010_06.pdf 219-250 Chapter 5 Alzheimer's disease. Japanese Society of Neurology https://www.neurology-jp.org/guidelinem/degl/sinkei_degl_2010_07.pdf 251-294 Chapter 6 Vascular dementia. Uehara Memorial Foundation Research Report, 25 (2011) https://ueharazaidan.yoshida-p.net/houkokushu/Vol.25/pdf/152_report.pdf Shibata et al., Stroke. 35: 2598-2603, 2004 Transl. Stroke Res. (2018) 9: 51-63

However, the knowledge of compounds for the prevention or amelioration of vascular dementia is still insufficient.
Here, in the above-mentioned chronic cerebral hypoperfusion model (BCAS), the cerebral blood flow is lowered for a long period of time by attaching a coil, the mouse brain falls into a chronic ischemic state, and cognitive decline is induced (Non-Patent Document 4). ). C-RIC therapy can improve cerebral blood flow even after BCAS surgery, and this therapy can also improve novel object recognition function (Non-Patent Document 5). From this, the present inventors considered that if a compound capable of preventing or ameliorating a decrease in novel object recognition function can be searched for using a BCAS model, the compound can also prevent or ameliorate a decrease in cerebral blood flow.
Then, the present inventors utilize a chronic cerebral hypoperfusion model (BCAS) in which the cerebral blood flow in the brain is reduced by surgically attaching microcoils to the bilateral common carotid arteries to reduce cerebral blood flow. It provides a composition that can prevent and / or improve the decline.

That is, the main object of the present technology is to provide a composition capable of preventing and / or ameliorating a decrease in cerebral blood flow.

As a result of diligent studies, the present inventors can prevent and / or improve the decrease in cerebral blood flow by ingesting Bifidobacterium spp., And prevent and / or prevent cerebrovascular dementia. Alternatively, he found that it could be improved and completed the present invention.
That is, the present invention is as follows.

[1] A composition for preventing and / or ameliorating a decrease in cerebral blood flow containing a bacterium belonging to the genus Bifidobacterium as an active ingredient.
[2] A composition for preventing and / or ameliorating a symptom or disease selected from cerebrovascular dementia, dizziness, lightheadedness, paralysis of limbs, headache, tinnitus, which contains a bacterium of the genus Bifidobacterium as an active ingredient. ..
[3] The composition according to the above [1] or [2], wherein the Bifidobacterium bacterium is Bifidobacterium longum and / or Bifidobacterium breve.
[4] The composition according to any one of the above [1] to [3], wherein the composition is used for cerebrovascular dementia.
[5] The composition according to any one of the above [1] to [3], wherein the composition is a pharmaceutical composition or a food or drink composition.
[6] Bifidobacterium spp. Or use thereof for prevention and / or improvement of cerebral blood flow decrease.
[7] A method for preventing and / or improving cerebral blood flow reduction by administering or ingesting Bifidobacterium spp.
[8] Use of Bifidobacterium spp. For the production of compositions for the prevention and / or improvement of decreased cerebral blood flow.
[9] A method for producing a food or drink composition for preventing / ameliorating cerebrovascular dementia, which comprises the following steps (A) to (B): Bacteria of the genus Bifidobacterium are cultured in a medium (A), and the culture is prepared. Step of obtaining; (B) A step of subjecting the culture to freeze-drying to obtain bacterial powder.

According to the present technology, it is possible to provide a composition capable of preventing and / or ameliorating a decrease in cerebral blood flow. The effects described here are not necessarily limited, and may be any of the effects described in the present technology.

Hereinafter, preferred embodiments of the present invention will be described. However, the present invention is not limited to the following preferred embodiments, and can be freely changed within the scope of the present invention. As a result, the scope of the present technology is not narrowly interpreted. In this specification, the percentage is expressed by mass unless otherwise specified.

The present technology is a composition containing a bacterium belonging to the genus Bifidobacterium (hereinafter, also referred to as "Bifidobacterium genus bacterium") as an active ingredient, and the composition prevents and / or prevents a decrease in cerebral blood flow. It is a composition for improvement. Examples of the composition include pharmaceutical compositions, food and drink compositions, animal feed compositions and the like.

The bifidobacteria used in this technique are not particularly limited. The bifidobacteria used in this technique are preferably bacteria that can be used in probiotics that can regulate the intestinal environment of humans or non-human animals. Bifidobacterium is highly safe even when ingested for a long period of time.

The Bifidobacterium genus bacterium used in this technique is not particularly limited, but for example, Bifidobacterium longum (hereinafter, also referred to as "Bifidobacterium longum"); Bifidobacterium breve (hereinafter, "Bifidobacterium breve"). Bifidobacterium bifidum; Bifidobacterium animalis; Bifidobacterium adolescentis and the like.
Bifidobacterium genus bacteria used in this technology include, for example, Bifidobacterium longum subsp. Longum; Bifidobacterium breve; Bifidobacterium. Bifidobacterium longum subsp. Infantis; Bifidobacterium bifidum; Bifidobacterium animalis subsp. Animalis; Bifidobacterium animalis subsp. Lactis; Bifidobacterium adolescentis and the like.
It is possible to use one or more selected from the group consisting of these.
The form of the bacterium belonging to the genus Bifidobacterium is not particularly limited, and may be any form such as a live bacterium, a dead bacterium, a sterilized bacterium, a wet bacterium, a dried bacterium, and a crushed product thereof. Of this form, live cells and / or dead cells are preferable, and live cells are more preferable, regardless of whether they are in a wet or dry state.
Of the Bifidobacterium spp., More preferably Bifidobacterium longum and / or Bifidobacterium breve, and of the Bifidobacterium longum, Bifidobacterium longum sub. Species longum is preferred from the standpoint of efficacy. In the present art, Bifidobacterium breve and / or Bifidobacterium longum subspecies longum are preferred.

Bifidobacterium longum subspecies longum is a bacterium that exists in the human intestine in a wide range of age groups including infants, children, adults and the elderly, and is highly safe.
Bifidobacterium breve is a bacterium that is found in the age group of infants and children and is present in the human intestine, and is highly safe. However, the Bifidobacterium breve bacterium is a bacterium that decreases with age and decreases or disappears in adults and the elderly.
Bifidobacterium longum subspecies infantis is found in the age group of infants and children, is a bacterium present in the human intestine, and is highly safe. However, the bacterium is a bacterium that decreases with age and decreases or disappears in adults and the elderly.

Among the Bifidobacterium longum subspecies longum, [1] Bifidobacterium longum NITE BP-02621 (also known as Bifidobacterium longum BB536) is preferable.
Of the Bifidobacterium breve, [2] Bifidobacterium breve FERM BP-11175 (also known as Bifidobacterium bleve MCC1274) is preferable.
A mixture of one or more bacteria selected from the group consisting of these is preferred.

[1] Bifidobacterium longum NITE BP-02621 (Bifidobacterium longum BB536) is the National Institute of Technology and Evaluation Patent Microorganisms Depositary Center (NPMD) (Address: Kazusakamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818) An international deposit was made to NITE BP-02621 on January 26, 2018 in Room 2-5-8 122) under the Budapest Treaty. The same bacterium, Bifidobacterium longum subsp. Longum ATCC BAA-999 (number: ATCC BAA-999), is available as ATCC BAA-999 from the American Type Culture Collection (ATCC) (eg, Japanese Patent Application Laid-Open No. See 2012-223134 etc.).
[2] Bifidobacterium breve MCC1175 (Bifidobacterium breve MCC1274) is the Patent Organism Depositary Center of the National Institute of Industrial Technology (currently the National Institute of Technology and Evaluation (NITE) Patent Organism Depositary Center (NITE). IPOD) (NITE-IPOD)) (Address: 2-5-8 Kazusakamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818, Room 122) was entrusted with the accession number FERM BP-11175 on August 25, 2009. The number is an international deposit under the Budapest Treaty.
These bacteria [1] and [2] are generally available from the above-mentioned storage institutions or international depository institutions.

The bacterium that is the same as each of the bacteria [1] and [2] is a bacterium of the same genus, and the base sequence of the 16S rRNA gene is 98% or more, preferably 99%, that of the base sequence of the 16S rRNA gene of each of these bacteria. As described above, it more preferably has 100% homology, and preferably has the same mycological properties as each of these bacteria.
Further, as long as the efficacy of the present technology is not impaired, the bacterium may be bred from each of these bacteria by mutation treatment, gene recombination, selection of a natural mutant strain, or the like.

The strain specified by the above-exemplified strain name is not limited to the strain itself that has been deposited or registered with a predetermined institution under the strain name (hereinafter, also referred to as "deposited strain" for convenience of explanation). Substantially equivalent strains (also referred to as "derivative strains" or "derivative strains") are also included. That is, for example, the above-mentioned [1] "Bifidobacterium breve MCC1274" is not limited to the strain itself deposited with the above-mentioned depositary institution with the deposit number of FERM BP-11175. Substantially equivalent strains are also included, and the above [2] is similar to this definition.
Regarding the strain, "a strain substantially equivalent to the above-mentioned deposit strain" belongs to the same species as the above-mentioned deposit strain, and the effect of the present technology, such as a preventive effect and / or an improvement effect on cerebral blood flow decrease, can be obtained. Means a strain. The stock substantially equivalent to the deposited stock may be, for example, a derivative stock having the deposited stock as a parent stock. Derivative strains include strains bred from deposit stocks and strains naturally generated from deposit stocks.

Examples of substantially the same strains and derivatives include the following strains.
(1) Description of Probiotic infood / Health engine 43 gene
(2) A strain that possesses only the gene derived from the deposited strain, does not have a gene derived from a foreign country, and has a DNA identity of 95% or more (preferably 98% or more). Strains with the same trait (including genetically modified, mutated, spontaneous mutations)

Bifidobacterium spp. Of the present technology can be easily grown by culturing them.
The method for culturing bifidobacteria of the present technology is not particularly limited as long as the bifidobacteria can grow, and the method usually used for culturing bifidobacteria is appropriately modified as necessary. Can be used. For example, the culture temperature may be 25 to 50 ° C, preferably 30 to 40 ° C. The culture is preferably carried out under anaerobic conditions, and for example, the culture can be carried out while aerating an anaerobic gas such as carbon dioxide.

The medium for culturing the bifidobacteria is not particularly limited, and a medium usually used for culturing bifidobacteria can be appropriately modified and used as necessary. As the carbon source of the medium, for example, saccharides such as galactose, glucose, fructose, mannose, cellobiose, maltose, lactose, sucrose, trehalose, starch, starch hydrolyzate, and waste sugar honey can be used depending on the assimilation property. As the nitrogen source of the medium, for example, ammonium salts such as ammonia, ammonium sulfate, ammonium chloride and ammonium nitrate and nitrates can be used. Further, as the inorganic salts of the medium, for example, sodium chloride, potassium chloride, potassium phosphate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, ferrous sulfate and the like can be used. In addition, organic components such as peptone, soybean flour, defatted soybean meal, meat extract, and yeast extract may be used in the medium. Further, as the medium, a known medium may be prepared and used, and as the medium, for example, MRS medium can be preferably used as the prepared medium.

As the Bifidobacterium genus bacterium of the present technology, the culture obtained after culturing may be used as it is, diluted or concentrated, or cells recovered from the culture may be used. The bacterium may be a live bacterium or a dead bacterium, and may be both a live bacterium and a dead bacterium, but is preferably a live bacterium.
In addition, various additional operations such as heating and freeze-drying can be performed after culturing as long as the efficacy of the present technology is not impaired. It is preferable that the additional operation is such that the viable bacteria have a high viability.

Bifidobacterium spp. Of the present technology have a preventive and / or ameliorating effect on cerebral blood flow reduction and a preventive and / or ameliorating effect on cerebrovascular dementia, as shown in Examples described later. In addition, the Bifidobacterium genus bacterium or the Bifidobacterium genus bacterium-containing composition of the present technology is effective for the above-mentioned symptoms or diseases caused by decreased cerebral blood flow and cerebrovascular dementia.
Therefore, the Bifidobacterium bacterium of the present technology is contained as an active ingredient in a composition having a preventive and / or ameliorating effect on cerebral blood flow reduction, or a composition having a preventive and / or ameliorating effect on cerebrovascular dementia. Can be made to. In addition, the Bifidobacterium genus bacterium of the present technology can be contained as an active ingredient in the above-mentioned compositions expected to have various effects, and these various compositions can also be used as a preparation.
The Bifidobacterium bacterium of the present technology can be used as it is by the Bifidobacterium genus bacterium itself, or mixed with a usual physiologically or pharmacologically acceptable carrier or diluent. It can also be used.
In addition, the bifidobacteria of the present technology can be used for various uses such as pharmaceuticals, foods and drinks, feeds, and various compositions.

In addition, the present technology can provide bifidobacteria or their use, which are used for the purpose of preventing / ameliorating the above-mentioned decrease in cerebral blood flow or preventing / ameliorating vascular dementia. In addition, the bifidobacteria of the present technology can be used as an active ingredient in a method for preventing / ameliorating a decrease in cerebral blood flow or a method for preventing / ameliorating cerebrovascular dementia.
In addition, the Bifidobacterium genus bacterium of the present technology can be used for producing various preparations or compositions having the above-mentioned effects or intended for use.
In addition, the Bifidobacterium genus bacteria of the present technology or the Bifidobacterium genus bacteria-containing composition is used for prevention, improvement or treatment for symptoms or diseases caused by decreased cerebral blood flow or for cerebrovascular dementia. It is possible to do.

Further, the decrease in cerebral blood flow in the present technology means that the required blood flow to the entire brain or a part of the brain tissue is decreased. Reasons for this include narrowing or narrowing of blood vessels in the brain, a decrease in the amount or speed of blood flow in the brain, and the like.
Symptoms or diseases caused by decreased cerebral blood flow in the present technology include, for example, cerebrovascular dementia, dizziness, lightheadedness, paralysis of limbs, headache, tinnitus and the like.

In addition, the Bifidobacterium bacterium of the present technology may be used for human or non-human animals (preferably primates) to which it is applied, and humans and pets are preferable, and humans are more preferable.

In addition, the present technology may be used for therapeutic purposes or for non-therapeutic purposes.
"Non-therapeutic purpose" is a concept that does not include medical practice, that is, treatment of the human body by treatment. For example, health promotion, prevention of lifestyle-related diseases (for example, reserve army in the boundary area) and the like can be mentioned.
"Prevention" refers to the prevention or delay of the onset of a disease or symptom in the application, or the reduction of the risk of the disease or symptom in the application.
"Amelioration" means improvement of a disease, symptom or condition; prevention or delay of exacerbation; reversal, prevention or delay of progression.

In this technique, in addition to the Bifidobacterium genus bacterium of this technique, any component may be used in combination, if necessary. As an optional ingredient, an ingredient permitted in pharmaceutical products, foods and drinks, feeds and the like may be appropriately used. Examples of the optional component include sugars, sugar alcohols, polysaccharides, pH adjusters, fatty acid esters, flavoring agents, flavors, excipients and the like.

The composition of the present technology can be produced by using the bacterium of the genus Bifidobacterium of the present technology. In addition, the composition of the present technology can be obtained by mixing various raw materials of the composition with the bacteria of the genus Bifidobacterium of the present technology so as to have a predetermined content as described later. In addition, the content or amount of various raw materials used in the composition of the present technology may be the same or similar amount with reference to the amount of various raw materials normally used in the target composition.
The composition of the present technology can be produced by using a known production method.

The method for producing the composition of the present technology will be described below, but the method for producing the composition of the present technology is not limited thereto. Thereby, a new composition can be provided, for example, for the prevention / improvement of cerebral blood flow decrease, for the prevention / improvement of cerebrovascular dementia, for the prevention / improvement of dizziness, etc. For the prevention / improvement of dizziness, for the prevention / improvement of paralysis of limbs, for the prevention / improvement of headache, for the prevention / improvement of tinnitus, etc.

Further, in the production method of the present technology, it is preferable to produce a food or drink composition, which means that the bifidobacteria of the present technology can be ingested and is highly safe, so that they can be handled at the production stage. This is because it is easy, fermentation technology (preferably fermented milk technology) can be easily applied, and raw materials such as milk components or assimilation components such as plant-based components can be appropriately used as required. Further, in the production method of the present technology, it is possible to provide a food and drink composition conscious of health, and among these, a food and drink composition for prevention and improvement of vascular dementia is preferable.

The composition of the present technology may be fermented milk, and when the fermented milk of the present technology is produced, the production process of the production method of the present technology may include a fermentation step using Bifidobacterium spp. Alternatively, it may include the step of mixing the fermented products produced on another line.
In addition, since the composition obtained by the production method of the present technology contains the bacteria of the genus Bifidobacterium of the present technology, it can be used as a raw material for foods and drinks for adding the efficacy of the present technology. It can be used for foods and drinks with added efficacy or a method for producing the same.

Further, depending on the form of the composition of the present technology (for example, tablets, capsules, tablets, etc.), the manufacturing method of the present technology may include a step for forming the form, whereby the present technology may be used. Compositions containing Bifidobacterium spp. Can be in various forms. In this forming step, a mixture can be obtained by mixing Bifidobacterium spp. And excipients, for example, in the case of tablets, the mixture is tableted; in the case of drinks, the mixture is placed in a container. Filling; in the case of capsules, filling the capsule with the mixture;

The method for producing the composition of the present technology will be described as the first embodiment and the second embodiment, but the use of the composition is not limited to the composition for preventing / ameliorating vascular dementia. Absent.
Further, as the manufacturing method of the second embodiment of the present technology, the configuration overlapping with the first embodiment will be omitted as appropriate. The step of obtaining the culture (A) in the second embodiment can be carried out in the same manner as the step of obtaining the culture of the first embodiment. Further, the step (B) for obtaining the bacterial powder in the second embodiment can be carried out in the same manner as the step for obtaining the bacterial powder in the first embodiment.

The present technology comprises, as the production method of the first embodiment, at least one of the following steps (a) and (b) below, the method for producing a composition for preventing / ameliorating cerebrovascular dementia:
(A) Step of mixing Bifidobacterium genus bacteria and prebiotics of the present technology; or (b) Step of mixing Bifidobacterium genus bacteria and milk components of the present technology;
Can be provided.
Further, in the mixing step (a), it is preferable to further mix the milk component.

By the production method of the first embodiment of the present technology, it is possible to obtain a composition for preventing / ameliorating cerebrovascular dementia, which is efficient in production such as cost and workability and can exert the effect of the present technology satisfactorily. it can.

In the manufacturing process of the first embodiment of the present technology, it is preferable to further mix prebiotics and / or milk components. When the prebiotics and / or milk components are mixed, any step of the manufacturing step may be used. For example, when the milk component is blended, it may be at the same time as the step (a), or may be either a pre-step or a post-step. The milk component is preferably powder. In the present technology, when producing a powdery composition, it is preferable to mix the materials of the powders to obtain a powdery composition from the viewpoint of production efficiency. However, the material is not limited to this, and it is also possible to obtain a powdery composition by mixing these materials and then performing known drying (for example, a method for drying bacteria described later).

In addition, as the production method of the second embodiment, the present technology includes the following steps (A) to (B), and a method for producing a composition for preventing / ameliorating cerebrovascular dementia:
(A) A step of culturing a Bifidobacterium genus bacterium of the present technology in a medium to obtain a culture;
(B) A step of subjecting the culture to drying to obtain bacterial powder;
Can be provided. The drying is preferably freeze-drying.

By the production method of the second embodiment of the present technology, it is possible to obtain a composition for preventing / ameliorating cerebrovascular dementia, which is efficient in production and can satisfactorily exert the effect of the present technology. Food and drink compositions, pharmaceutical compositions and feed compositions can be obtained by the production method of the second embodiment, and among them, food and drink compositions such as fermented milk and bacterial powder can be obtained from the viewpoint of production efficiency. It is preferable to obtain.

As the Bifidobacterium genus bacterium used in the production method of the present technology, the above-mentioned Bifidobacterium genus bacterium of the present technology can be used. The bifidobacteria can be cultivated to obtain a culture according to the above-mentioned method for culturing bifidobacteria of the present technology.
For example, a milk component may be mixed with the medium for culturing, or fermented milk may be appropriately fermented. In addition, lactic acid bacteria and / or other Bifidobacterium spp. May be optionally used for fermentation.

The milk component is not particularly limited, but for example, milk, buffalo milk, sheep milk, goat milk, horse milk, skim milk, skim milk concentrate, skim milk powder, concentrated milk, whole fat powder milk, cream, butter, butter milk, and the like. Examples include skim milk and milk protein, and one or more selected from the group consisting of these can be used. The milk protein is not particularly limited, and examples thereof include whey, casein, and hydrolysates thereof, and one or more selected from the group consisting of these can be used. Of the milk components, those derived from milk are preferable.

The hydrolyzate can produce a whey hydrolyzate, a casein hydrolyzate, or the like by hydrolyzing the milk component (preferably milk protein). Examples of the hydrolysis include acids / alkalis and enzymes. Of these, an enzyme is preferable, and a proteolytic enzyme is preferable as the enzyme. Examples of the proteolytic enzyme include protease, trypeptidase, chymotrypsin, plasmin, pepsin, papain, peptidase, aminopeptidase and the like. The pH at the time of the hydrolysis reaction can be appropriately adjusted to the optimum pH of the enzyme to be used, and can be carried out at, for example, pH 2-6. The temperature at the time of the hydrolysis reaction is not particularly limited, and it is usually preferably carried out in the range of 30 to 60 ° C., and the reaction time is preferably 2 to 10 hours.

The form of the Bifidobacterium genus bacterium or a culture containing the same is not particularly limited and may be either a liquid or a solid, but the dry form (for example, bacterial powder, cultured dried product, etc.) may be used. , It is suitable from the viewpoint of easy handling during manufacturing and storage. In addition, examples of the culture include the cells themselves from which the culture solution has been separated and the culture containing the cells, as described above.

The drying method is not particularly limited, but is a spray drying method (spray drying method), a retort sterilization method, a freeze sterilization method, a UHT sterilization method, a pressure sterilization method, a high pressure steam sterilization method, a dry heat sterilization method, and a distribution steam sterilization method. , Electromagnetic sterilization method, electron beam sterilization method, high frequency sterilization method, radiation sterilization method, ultraviolet sterilization method, ethylene oxide gas sterilization method, hydrogen peroxide gas plasma sterilization method, chemical sterilization method (alcohol sterilization method, formalin fixation method, electrolysis) Water treatment method) and the like.

Further, the bacterial cells may be crushed, and the crushed product may be one in which live bacteria are crushed, one in which dead bacteria are crushed, or one in which heating, freeze-drying, or the like is performed after crushing.
Of these, from the viewpoint of increasing the viable cell rate, it is preferable to subject the culture to freeze-drying, and from the viewpoint of increasing the production efficiency, it is preferable to subject the culture to spray-drying.

Further, in the composition of the present technology, a component having a known or future probiotic effect or a component assisting the probiotic effect can be used as long as the effect of the present technology is not impaired. Here, in general, probiotics refer to bacteria that have a beneficial effect in the intestine. In general, substances that serve as a selective nutrient source for bacteria that have a beneficial effect in the intestine and promote their growth are called prebiotics.
When prebiotics are used or contained in order to promote the growth of Bifidobacterium spp. Of the present technology, 1 to 1,000,000 parts by mass is preferable with respect to 100 parts by mass of the bacteria, 10 to 10, 000 parts by mass is more preferable.

As the prebiotics, for example, various proteins such as whey protein, casein protein, soybean protein, or pea protein (pea protein) or mixtures thereof, decomposition products; amino acids such as leucine, valine, isoleucine or glutamine; vitamin B6 or Vitamin C and other vitamins; creatine; citric acid; fish oil; or components such as isoleucine oligosaccharide, galactooligosaccharide, xylooligosaccharide, soybean oligosaccharide, fructo-oligosaccharide, lactulose, oligosaccharide such as human milk oligosaccharide (HMO) Etc., and one kind or two or more kinds selected from the group consisting of these may be used.
In addition, the composition of the present technology can be produced by blending the prebiotic component with the bacterium of the present technology or a culture thereof.

The "human milk oligosaccharides" that can be used in this technology include 2'-fucosyl lactose, 3-fucosyl lactose, 2', 3-difucosyl lactose, lacto-N-triose II, lacto-N-tetraose, and lacto. -N-neotetraose, lactose-N-fucopentaose I, lactose-N-neofcopentaose, lactose-N-fucopentaose II, lactose-N-fucopentaose III, lactose-N-fucopentaose V, lacto-N-neofco Pentaose V, lacto-N-difucohexaose I, lacto-N-difucohexaose II, 6'-galactosyllactose, 3'-galactosyllactose, lacto-N-hexaose and lacto-N-neohexaose, etc. Neutral human milk oligosaccharides, acidic human milk oligosaccharides such as 3'-sialyl lactose, 6'-sialyl lactose, 3-fucosyl-3'-sialyl lactose, disialyl-lacto-N-tetraose can be used. One or more selected from the group may be used.

As an example of the manufacturing method of the present technology, the present technology will be described below, but the present technology is not limited thereto.
Example 1 of the production method of the present technology is a production method of a bacterial powder or a molded product (for example, a supplement) containing a bacterium belonging to the genus Bifidobacterium of the present technology.
A step of anaerobically culturing Bifidobacterium spp. In a medium, a step of concentrating the culture solution, freeze-drying, and a step of obtaining a freeze-dried powder (bacterial powder) are performed. Thereby, it is possible to provide bacterial powder for use such as prevention / improvement of cerebral blood flow decrease. At this time, the culture solution containing Bifidobacterium spp. May be spray-dried to form a granular powder. The bacteria of the present technology are blended so as to have a predetermined amount of cells in the composition.
In addition, when producing a supplement or tablet of the present technology, a step of mixing a culture solution containing Bifidobacterium spp. And an excipient to obtain a mixture and a step of molding into the predetermined shape can be included. Examples of the molding step include tableting, and examples of tableting include, for example, compression molding of a mixture of powder and granules to obtain a tablet.

Example 2 of the production method of the present technology is a method for producing a milk beverage or a dairy product containing a Bifidobacterium genus bacterium of the present technology.
As Example 2 of the production method of the present technology, a step of mixing the bacterial powder obtained in Example 1 of the above-mentioned production method with milk or skim milk is performed. At this time, (A) milk protein 3.5% by mass or more, (B) milk fat 3.5% by mass or less, (C) carbohydrate 5.0% by mass or more, and (D) calcium 0.15% by mass or more. Adjust to include. In addition, the bacteria of the present technology in the powder are blended so as to have a predetermined amount of cells. Thereby, it is possible to provide a milk drink or a dairy product for use such as prevention / improvement of cerebral blood flow decrease.

As an example 3 of the production method of the present technology, there is a production method of fermented milk containing a bacterium of the genus Bifidobacterium of the present technology.
As an example 3 of the production method of the present technology, a step of adding the bacterial powder obtained in Example 1 of the above-mentioned production method to a fermented milk raw material to obtain fermented milk containing a Bifidobacterium genus bacterium of the present technology is performed. Do. Alternatively, a step of mixing the bacterial powder and fermented milk to obtain fermented milk containing the Bifidobacterium genus bacterium of the present technology is performed. Fermentation conditions and blending amounts are adjusted so that the amount of bacterial cells of the present technology in the composition becomes a predetermined amount of bacterial cells. This makes it possible to provide fermented milk or fermented products for purposes such as prevention / improvement of cerebral blood flow reduction.

The content or amount of Bifidobacterium spp. (Live or dead) of the present technology is not particularly limited, but is preferably 1 × 10 ³ to 1 × 10 ¹² (CFU / g or) in the composition. CFU / mL, or cells (pieces) / g or cells (pieces) / mL), more preferably 1 × 10 ⁵ to 1 × 10 ¹¹ (CFU / g or CFU / mL, or cells (pieces) / g or cells) (Pieces) / mL), more preferably 1 × 10 ⁷ to 1 × 10 ¹⁰ (CFU / g or CFU / mL, or cells (pieces) / g or cells (pieces) / mL). CFU indicates Colony forming unit.
The content or amount of Bifidobacterium longum (live or dead) of the present technology is not particularly limited, but is preferably 1 × 10 ³ to 1 × 10 ¹² (CFU / g or) in the composition. CFU / mL, or cells (pieces) / g or cells (pieces) / mL), more preferably 1 × 10 ⁵ to 1 × 10 ¹¹ (CFU / g or CFU / mL, or cells (pieces) / g or cells) (Pieces) / mL), more preferably 1 × 10 ⁷ to 1 × 10 ¹⁰ (CFU / g or CFU / mL, or cells (pieces) / g or cells (pieces) / mL).
The content or amount of Bifidobacterium breve (live or dead) of the present technology is not particularly limited, but is preferably 1 × 10 ³ to 1 × 10 ¹² (CFU / g or) in the composition. CFU / mL, or cells (pieces) / g or cells (pieces) / mL), more preferably 1 × 10 ⁵ to 1 × 10 ¹¹ (CFU / g or CFU / mL, or cells (pieces) / g or cells) (Pieces) / mL), more preferably 1 × 10 ⁷ to 1 × 10 ¹⁰ (CFU / g or CFU / mL, or cells (pieces) / g or cells (pieces) / mL).

The administration target is usually preferably human, but includes mammals other than humans, such as pet animals such as dogs and cats, and domestic animals such as cattle, sheep and pigs.

The daily dose of bifidobacteria (live or dead) of the present technology is not particularly limited, but 1 × 10 ³ to 1 × 10 ¹² CFU / day (or cells (pieces) /) / day. 1 × 10 ⁵ to 1 × 10 ¹¹ CFU / day (or cells (pieces) / day) is more preferable, and 1 × 10 ⁷ to 1 × 10 ¹⁰ CFU / day (or). It is more preferably cells (pieces) / day).

The administration interval of the present technology is not particularly limited, and may be once a day or may be divided into a plurality of times, but once a day is preferable because it is convenient and effective.
In addition, since the Bifidobacterium genus bacterium of the present technology is highly safe, it can be administered or ingested before symptoms or diseases caused by decreased cerebral blood flow are observed. Further, it is preferable to administer or ingest this technique before symptoms or diseases caused by decreased cerebral blood flow are observed, from the viewpoint of prevention.
In addition, it is easy to improve the symptoms after the decrease in cerebral blood flow by administering or ingesting the Bifidobacterium genus bacteria of the present technology before the symptoms such as the decrease in cerebral blood flow are observed, as shown in the examples below. Therefore, it is preferable.
This technique is preferably administered or ingested one week before (more preferably two weeks before) before symptoms such as decreased cerebral blood flow are observed, from the viewpoint of easily obtaining a preventive effect and a subsequent improving effect.
Further, in this technique, after symptoms such as decreased cerebral blood flow are observed, long-term administration or ingestion is preferable from the viewpoint of efficacy, more preferably 2 weeks or more, still more preferably 4 weeks or more. It is preferable from the viewpoint that the improvement effect can be easily obtained.

[Pharmaceutical composition]
When Bifidobacterium spp. Are used in a pharmaceutical composition or pharmaceutical use, the drug may be administered orally or parenterally, but oral administration and administration that acts on the mucous membrane are preferable. Parenteral administration includes, for example, injection (blood, skin, muscle, etc.), rectal administration, inhalation, and the like. Dosage forms for oral administration include, for example, tablets, capsules, lozenges, syrups, granules, powders, ointments and the like.
The usage and dosage in the pharmaceutical composition of the present technology are as described above.

In addition to the bacteria of the genus Bifidobacterium, components such as excipients, pH adjusters, colorants, and flavoring agents that are usually used in formulation can be used in the formulation. Furthermore, components having a preventive or therapeutic effect on diseases known or found in the future can be used in combination depending on the purpose.

Further, it can be appropriately formulated into a desired dosage form according to the administration method. For example, in the case of oral administration, it can be formulated into solid preparations such as powders, granules, tablets and capsules; liquid preparations such as solutions, syrups, suspensions and emulsions. In the case of parenteral administration, it can be formulated into a suppository, a spray, an ointment, a patch, an injection, or the like.

In addition, formulation can be carried out by a known method as appropriate depending on the dosage form. At the time of formulation, only the casein enzyme-treated product or each separated / purified fraction may be formulated, or a formulation carrier may be blended as appropriate.

Further, as the preparation carrier, various organic or inorganic carriers can be used depending on the dosage form. Examples of the carrier in the case of a solid preparation include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents and the like.

Examples of excipients include sugar derivatives such as lactose, sucrose, glucose, mannit, and sorbit; starch derivatives such as corn starch, horse bell starch, α-starch, dextrin, and carboxymethyl starch; crystalline cellulose, hydroxypropyl cellulose, and the like. Cellulous derivatives such as hydroxypropylmethyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose calcium; gum arabic; dextran; purulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, magnesium aluminometasilicate; phosphate derivatives such as calcium phosphate; carbonic acid Carbonate derivatives such as calcium; sulfate derivatives such as calcium sulfate can be mentioned.

Examples of the binder include gelatin; polyvinylpyrrolidone; macrogol and the like in addition to the above-mentioned excipients.

Examples of the disintegrant include, in addition to the above-mentioned excipients, chemically modified starch or cellulose derivatives such as croscarmellose sodium, carboxymethyl starch sodium, and crosslinked polyvinylpyrrolidone.

Examples of the lubricant include talc; stearic acid; metal stearate salts such as calcium stearate and magnesium sulfate; colloidal silica; waxes such as pea gum and gay wax; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid. Sodium carboxylic acid salts such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic acid anhydride and silicate hydrate; starch derivatives and the like. Be done.

Examples of the stabilizer include paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalconium chloride; acetic anhydride; and sorbic acid.

Examples of the flavoring agent include sweeteners, acidulants, and flavors.
Examples of the carrier used in the case of a liquid preparation for oral administration include a solvent such as water, a flavoring and odorant, and the like.

[Food and drink composition]
The present technology can provide a food or drink composition containing a bacterium of the genus Bifidobacterium as an active ingredient. The food and drink composition of the present technology can be applied to the prevention and improvement of cerebrovascular dementia, dizziness, lightheadedness, paralysis of limbs, headache, tinnitus and the like. For example, it is a health food, a functional food, etc. whose concept is to prevent and / or improve a decrease in cerebral blood flow.

Further, as a food and drink composition according to the present technology, infant formula can be mentioned. Infant milk powder for infants from 0 to 12 months, follow-up milk for infants from 6 to 9 months and younger children (up to 3 years old), at birth Formulated milk powder for low-birth-weight babies weighing less than 2500 g (low-birth-weight babies), various therapeutic milks used to treat babies with morbidity such as milk allergy and lactose intolerance. Point to.

When bifidobacteria are used in foods and drinks for humans or animals, they can be prepared by adding them to known foods and drinks, or they are mixed with the raw materials of foods and drinks to produce new foods and drinks. You can also do it.
The method of use, the amount used, and the content of the food and drink composition of the present technology are as described above.

The foods and drinks may be in the form of liquid, paste, solid, powder, etc., in addition to tablets, liquid foods, feeds (including those for pets), etc., for example, flour products, instant foods, processed agricultural products, marine products. Examples include processed products, processed livestock products, milk / dairy products, fats and oils, basic seasonings, complex seasonings / foods, frozen foods, confectionery, beverages, and other commercial products.

Examples of wheat flour products include bread crumbs, macaroni, spaghetti, noodles, cake mixes, fried chicken flour, bread crumbs and the like.
Examples of instant foods include instant noodles, cup noodles, retort / cooked foods, canned foods, microwave foods, instant soups / stews, instant miso soup / soups, canned soups, freeze / dried foods, and other instant foods. Be done.
Examples of processed agricultural products include canned agricultural products, canned fruits, jams and marmalades, pickles, boiled beans, dried agricultural products, cereals (processed grain products), and the like.
Examples of processed marine products include canned marine products, fish hams and sausages, fish paste products, marine delicacies, and boiled fish.
Examples of processed livestock products include canned livestock and pastes, livestock ham and sausage.
Examples of dairy products include processed milk, milk drinks, yogurts, lactic acid bacteria drinks, cheese, ice creams, formula milk powders, creams, and other dairy products.
Examples of fats and oils include butter, margarines, vegetable oils and the like.
Examples of basic seasonings include soy sauce, miso, sauces, processed tomato seasonings, mirins, vinegars, etc., and examples of the complex seasonings / foods include cooking mixes, curry ingredients, sauces, and the like. Examples include dressings, mentsuyu, spices, and other complex seasonings.
Examples of frozen foods include raw material frozen foods, semi-cooked frozen foods, and cooked frozen foods.
Examples of confectionery include caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese confectionery, rice confectionery, bean confectionery, dessert confectionery, and other confectionery.

Beverages include, for example, carbonated beverages, natural fruit juices, fruit juice beverages, refreshing beverages containing fruit juice, fruit meat beverages, fruit beverages containing fruit grains, vegetable beverages, soymilk, soymilk beverages, coffee beverages, tea beverages, powdered beverages, concentrated beverages. , Sports beverages, nutritional beverages, alcoholic beverages, other favorite beverages and the like.
Examples of commercially available foods other than the above include baby food, sprinkle, ochazuke seaweed and the like.

In addition, the foods and drinks defined in the present technology can also be provided and sold as foods and drinks labeled for health use.
The "display" act includes all acts for informing the consumer of the use, and if the expression can remind or analogize the use, the purpose of the display, the content of the display, and the display. Regardless of the object, medium, etc., all fall under the "display" act of this technology.

Further, it is preferable that the "display" is performed by an expression that allows the consumer to directly recognize the above-mentioned use. Specifically, the act of transferring a product related to food and drink or the packaging of the product with the above-mentioned use, displaying it for delivery, transfer or delivery, and importing it, advertising on the product, price list or transaction documents Examples include the act of describing the above-mentioned use and displaying or distributing it, or describing the above-mentioned use in the information containing these and providing it by an electromagnetic (Internet, etc.) method.

On the other hand, as the display content, it is preferable that the display is approved by the government or the like (for example, a display obtained based on various systems established by the government and performed in a manner based on such approval). In addition, it is preferable to attach such display contents to packaging, containers, catalogs, pamphlets, promotional materials such as POPs at sales sites, and other documents.

In addition, "labeling" includes health foods, functional foods, enteric nutritional foods, special purpose foods, health functional foods, specified health foods, nutritional functional foods, functional foods, non-medicinal products, etc. The display is also mentioned. Among these, in particular, labeling approved by the Consumer Affairs Agency, for example, a labeling approved by a food system for specified health use, a system similar to this, and the like can be mentioned. Examples of the latter include labeling as a food for specified health use, labeling as a food for specified health use as a condition, labeling to the effect that it affects the structure and function of the body, labeling for reducing the risk of illness, and the like. More specifically, the labeling as a food for specified health use (especially the labeling for health uses) stipulated in the Health Promotion Law Enforcement Regulations (April 30, 2003, Ministry of Health, Labor and Welfare Ordinance No. 86) and this A similar display is a typical example.

[Feed composition]
When Bifidobacterium is used as a feed, it can be prepared by adding it to a known feed, or it can be mixed with a feed material to produce a new feed.
The method of use, the amount used, and the content of the feed composition of the present technology are as described above.

As raw materials for the feed, for example, cereals such as corn, wheat, barley, and rye; bran such as bran, wheat bran, rice bran, and defatted rice bran; production lees such as corn gluten meal and corn jam meal; defatted milk powder, Animal feeds such as whey, fish flour, and bone meal; yeasts such as beer yeast; mineral feeds such as calcium phosphate and calcium carbonate; fats and oils; amino acids; sugars and the like. Examples of the form of the feed include pet food (pet food and the like), livestock feed, fish feed and the like.

As described above, this technology can be used in a wide range of fields such as foods and drinks, food and drink compositions, functional foods, pharmaceuticals, and feeds.

The present technology can also adopt the following configurations.
[1] A composition for preventing and / or improving cerebral blood flow reduction containing Bifidobacterium spp. As an active ingredient; or prevention of symptoms or diseases (including these reserves) caused by cerebral blood flow reduction. -Selected from the group consisting of cerebrovascular dementia, dizziness, lightheadedness, paralysis of limbs, headache, and ringing in the ears, which contains a composition used for improvement / treatment or a bacterium belonging to the genus Bifidobacterium as an active ingredient. A composition used for the prevention / amelioration / treatment of a species or two or more symptoms or diseases.
[2] For use in prevention and / or improvement of cerebral blood flow reduction; or for prevention / improvement / treatment of symptoms or diseases (including these reserves) caused by cerebral blood flow reduction; or Bifidobacterium for use in the prevention, amelioration, and treatment of one or more symptoms or diseases selected from the group consisting of cerebrovascular dementia, dizziness, lightheadedness, paralysis of limbs, headache, and tinnitus. Genus bacteria.
[3] For prevention and / or improvement of cerebral blood flow reduction; or for prevention / improvement / treatment of symptoms or diseases (including these reserves) caused by cerebral blood flow reduction; or cerebral blood vessels Bifidobacterium spp. For use in the prevention, amelioration, and treatment of one or more symptoms or diseases selected from the group consisting of sexual dementia, dizziness, lightheadedness, paralysis of limbs, headache, and tinnitus. Use of.
[4] Methods for the prevention and / or improvement of cerebral blood flow reduction by administering or ingesting Bifidobacterium spp.; Or for symptoms or diseases (including these reserves) caused by cerebral blood flow reduction. Methods for prevention / improvement / treatment; or prevention of one or more symptoms or diseases selected from the group consisting of cerebrovascular dementia, dizziness, lightheadedness, paralysis of limbs, headache, tinnitus. Methods for improvement and treatment.
[5] Compositions used for the production of compositions for the prevention and / or improvement of cerebral blood flow reduction; or for the prevention / improvement / treatment of symptoms or diseases (including these reserves) caused by cerebral blood flow reduction. For the prevention / improvement / treatment of one or more symptoms or diseases selected from the group consisting of cerebrovascular dementia, dizziness, lightheadedness, paralysis of limbs, headache, tinnitus. Use of Bifidobacterium spp. For the production of the compositions used.

[6] A method for producing a composition for preventing / ameliorating cerebrovascular dementia, which comprises at least one of the following steps (a) and (b) below:
(A) Step of mixing bifidobacteria and prebiotics, or
(B) A step of mixing bifidobacteria (preferably powdered milk) and milk components (preferably milk powder).
As the milk component, powdered milk is preferable.
At the time of the step (a), it is preferable to further mix the milk component in either the pre-step of the step (a) or the post-step of the step (a).
[7] A method for producing a composition for preventing / ameliorating cerebrovascular dementia, which comprises the following steps (A) to (B):
(A) Step of culturing Bifidobacterium spp. In a medium to obtain a culture;
(B) A step of subjecting the culture to drying to obtain bacterial powder.
After the steps (A) and (B), it is preferable to include (C) a step of mixing the bacterial powder and prebiotics to obtain a composition.
Further, the composition is preferably a food and drink composition.
Further, the medium is more preferably a medium containing a milk component, whereby the number of cells can be increased to increase the recovery rate, or in some cases, fermented milk can be obtained to obtain its flavor and efficacy. it can.
Further, the drying is more preferably freeze-drying from the viewpoint of increasing the viable cell rate.

[8] In any one of the above [1] to [7], preferably, the composition is used for cerebrovascular dementia; or a symptom caused by a decrease in cerebral blood flow or The disease is vascular dementia; or prevention of one or more symptoms or disorders selected from the group consisting of vascular dementia, dizziness, lightheadedness, paralysis of limbs, headache, tinnitus.・ It is used for improvement and treatment.
[9] In any one of the above [1] to [8], preferably, the composition is a pharmaceutical composition or a food or drink composition; or the composition is for non-therapeutic purposes; Alternatively, the use, administration or ingestion of the Bifidobacterium spp. Is for non-therapeutic purposes.
[10] In any one of the above [1] to [9], preferably, the Bifidobacterium genus bacterium is Bifidobacterium longum and / or Bifidobacterium breve. More preferably, the Bifidobacterium bacterium is Bifidobacterium longum and / or Bifidobacterium breve.
[11] In any one of the above [1] to [10], preferably, when the Bifidobacterium spp. Is administered or ingested, the administration or ingestion is recognized as a decrease in cerebral blood flow. Before and / or long-term continuation after decreased cerebral blood flow; the administration or ingestion is before the symptom or disease is recognized and / or after the symptom or disease is recognized. It continues for a long time.
[12] In any one of the above [1] to [11], the symptom or disease caused by the decrease in cerebral blood flow is from cerebrovascular dementia, dizziness, lightheadedness, paralysis of limbs, headache, tinnitus. One or more selected from the group.
[13] In any one of the above [1] to [12], the composition is any one of a pharmaceutical composition, a food and drink composition, milk powder (for example, infant formula, etc.), or a supplement. Is.

Hereinafter, the present invention will be described in more detail with reference to Examples and the like, but the present invention is not limited to these Examples.

〔experimental method〕
Chronic cerebral hypoperfusion model (BCAS model) Verification of effect on cerebral blood flow reduction Using mice with microcoils attached to both common carotid arteries (BCAS mice), Bifidobacterium longum NITE BP-02621 And the effect of improving cerebral blood flow reduction of Bifidobacterium Breve FERM BP-11175 was examined.
Bifidobacterium Longum NITE BP-02621 and Bifidobacterium Breve FERM BP-11175 were obtained from the International Depositary Organization.

A 10-week-old (week-old) C57BL / 6J mouse was used in the test. Bifidobacterium longum NITE BP-02621 and Bifidobacterium Breve FERM BP-11175 were each ^{administered at 1 × 10 9} CFU / day from 1 week before BCAS surgery, and continued to be administered 30 days after surgery. A new object recognition test was performed on the eyes.
In BCAS surgery, specifically, mice were anesthetized by intraperitoneal administration of medetomidine hydrochloride 0.3 mg / kg, midazolam 4 mg / kg, and butorphanol tartrate 5 mg / kg, and then the neck was opened and the bilateral common carotid arteries were dissected. A microcoil with an inner diameter of 0.18 mm was attached. In the sham surgery group, the neck was opened, the carotid artery was exposed, and then sutured.
In the behavioral test, the time for the mouse to search for a new object was measured, and the ratio to the total time for searching for the object was used as an index of cognitive function.

〔Results and discussion〕
As a result, each administration of Bifidobacterium longum NITE BP-02621 and Bifidobacterium Breve FERM BP-11175 to BCAS mice was a positive control as compared with the group in which saline was administered to BCAS mice. A new object search time equivalent to that of azilsartan was observed. From this, it was shown that oral ingestion of Bifidobacterium longum and / or Bifidobacterium breve also improves cerebral blood flow reduction (see, for example, Non-Patent Documents 4 and 5). .. In addition, it is known that azilsartan, which is a positive control, has an effect of improving the decrease in cerebral blood flow. From this, it can be said that if the decrease in recognition of new objects can be improved, the decrease in cerebral blood flow can also be improved. ..
As described above, Bifidobacterium longum NITE BP-02621 and Bifidobacterium Breve FERM BP-11175 have an improving effect on the decrease in cerebral blood flow, and thus the symptoms caused by the decrease in cerebral blood flow. Alternatively, prevention and improvement of diseases (for example, cerebrovascular dementia and paralysis of limbs) can be expected.

As described above, the Bifidobacterium genus bacteria of the present technology (more preferably, Bifidobacterium longum and / or Bifidobacterium breve) exert a preventive / ameliorating effect on the decrease in cerebral blood flow. To do. The composition of the present technology is a composition used for reducing cerebral blood flow and / or a composition used for cerebrovascular dementia, etc., and the composition is for pharmaceuticals, foods and drinks, etc. It can be used for a wide range of purposes such as feed and pets.

[Manufacturing Example 1]
Bifidobacterium longum NITE BP-02621 and / or Bifidobacterium Breve FERM BP-11175 bacteria were added to 3 mL of MRS liquid medium, anaerobically cultured at 37 ° C. for 16 hours, concentrated and lyophilized. Drying is performed to obtain a freeze-dried powder (bacterial powder) of the bacterium. While uniformly mixing the bacterial powder and milk or skim milk, (A) milk protein 3.5% by mass or more, (B) milk fat 3.5% by mass or less, (C) carbohydrate 5.0% by mass. The above and (D) calcium are adjusted to contain 0.15% by mass or more. As a result, a composition for preventing / improving cerebral blood flow reduction containing bifidobacteria is obtained. The intake of bacteria should be 1 × 10 ⁸ to 1 × 10 ¹⁰ CFU / kg body weight / day, and 200 mL should be ingested daily for 1 to 4 weeks or more.
It can be ingested as a food and drink composition (milk drink), and can also be ingested as a food and drink composition (milk drink) for prevention and improvement of vascular dementia, and prevents and prevents a decrease in cerebral blood flow. It can be expected to have an improving effect and a preventive / improving effect on cerebrovascular dementia.

[Manufacturing Example 2]
Bifidobacterium longum NITE BP-02621 and / or Bifidobacterium Breve FERM BP-11175 bacteria were added to 3 mL of MRS liquid medium, anaerobically cultured at 37 ° C. for 16 hours, concentrated and lyophilized. After drying, the bacterial granules (bacterial powders) are obtained as a composition for preventing / improving cerebral blood flow reduction (granular or tablet). The granular bacterial powder is ingested daily for one week or more so that the intake of the bacterial powder is 1 × 10 ⁸ to 1 × 10 ^{10 CFU / kg body weight / day.}
It can be ingested as a food and drink composition, and can also be used as a food and drink composition (granular or tablet) for prevention and improvement of vascular dementia, and prevents and improves cerebral blood flow reduction. It can be expected to be effective and prevent / improve vascular dementia.
When obtaining the bacterial powder, it is also possible to obtain spray-dried bacterial powder by "spray drying" instead of "freeze-drying".

[Manufacturing Example 3]
Bifidobacterium longum NITE BP-02621 and / or Bifidobacterium Breve Ferment BP-11175 bacteria were added to 3 mL of MRS liquid medium, anaerobically cultured at 37 ° C. for 16 hours, concentrated and lyophilized. After drying, the bacterial granules (bacterial powder) are added to the fermented milk raw material to obtain fermented milk. The fermented milk for preventing / improving the decrease in cerebral blood flow is ingested daily for one week or more so that ^{the intake of bacteria is 1 × 10 8} to 1 × 10 ^{10 CFU / kg body weight / day.}
It can also be ingested as fermented milk for the prevention / improvement of cerebrovascular dementia, and can be expected to have the effect of preventing / improving cerebral blood flow and the effect of preventing / improving cerebrovascular dementia.

[Manufacturing Example 4]
The bacterial powder obtained in the above [Production Example 2] (the bacterial powder may be either a freeze-dried product and / or a spray-dried product) is mixed with probiotics to obtain a bacterial and probiotic mixture. .. Human milk oligosaccharides are used as the probiotics. Probiotics have the advantage of facilitating the growth of the bacteria used.
The bacterium and the mixture of probiotics should be ingested daily for at least one week so that the intake of the bacterium is 1 × 10 ⁸ to 1 × 10 ^{10 CFU / kg body weight / day.}
It can also be ingested as a food and drink composition for prevention / improvement of vascular dementia, and can be expected to have an effect of preventing / improving cerebral blood flow reduction and an effect of preventing / improving vascular dementia.

(1) Bifidobacterium longum NITE BP-02621 strain (trust number: NITE BP-02621) (consignment date: January 26, 2018), contractor: Kazusakamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 Foot 2-5-8 Room 122, National Institute of Technology and Evaluation Patent Microorganisms Depositary Center (NPMD).
(2) Bifidobacterium Breve FERM BP-11175 strain (trust number: FERM BP-11175) (consignment date: August 25, 2009), contractor: Kazusakamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 2-5-8, National Institute of Advanced Industrial Science and Technology Patent Organism Depositary Center (currently Incorporated Administrative Agency Product Evaluation Technology Infrastructure Organization (NITE) Patent Organism Depositary Center (IPOD) (NITE-IPOD)).

Claims (9)

A composition for preventing and / or improving cerebral blood flow reduction containing a Bifidobacterium genus bacterium as an active ingredient. A composition for preventing and / or ameliorating a symptom or disease selected from cerebrovascular dementia, dizziness, lightheadedness, paralysis of limbs, headache, tinnitus, which contains a bacterium of the genus Bifidobacterium as an active ingredient. The composition according to claim 1 or 2, wherein the Bifidobacterium bacterium is Bifidobacterium longum and / or Bifidobacterium breve. The composition according to any one of claims 1 to 3, wherein the composition is used for cerebrovascular dementia. The composition according to any one of claims 1 to 4, wherein the composition is a pharmaceutical composition or a food or drink composition. Bifidobacterium or its use for the prevention and / or amelioration of decreased cerebral blood flow. A method for preventing and / or ameliorating decreased cerebral blood flow by administering or ingesting Bifidobacterium spp. Use of Bifidobacterium spp. For the production of compositions for the prevention and / or improvement of decreased cerebral blood flow. Method for producing food and drink composition for prevention / improvement of cerebrovascular dementia, which comprises the following steps (A) to (B):
(A) Step of culturing Bifidobacterium spp. In a medium to obtain a culture;
(B) A step of subjecting the culture to freeze-drying to obtain bacterial powder.