WO2019188943A1 - Composition for preventing and/or ameliorating decrease in brain blood flow - Google Patents

Abstract

Provided is a composition capable of preventing and/or ameliorating a decrease in brain blood flow. The composition for preventing and/or ameliorating a decrease in brain blood flow contains a bacterium of the genus Bifidobacterium as an active ingredient. Preferably, the bacterium of the genus Bifidobacterium is Bifidobacterium longum and/or Bifidobacterium breve. The composition is also used for cerebrovascular dementia. Preferably, the composition is also a medicinal composition or a food or beverage composition.

Description

Composition for preventing and / or improving cerebral blood flow reduction

This technique relates to a composition for preventing and / or improving cerebral blood flow reduction.

The population of middle-aged and elderly people tends to increase as society matures. As the elderly population increases, dementia has become a social problem. The improvement of quality of life and measures against locomotive syndrome have been proposed, and interest in prevention or improvement of dementia is increasing.

By the way, it is known that dementia includes Alzheimer type dementia, cerebrovascular dementia, Lewy body dementia, frontotemporal dementia and the like. Alzheimer-type dementia accounts for the main proportion, followed by cerebrovascular dementia and Lewy body dementia. Symptoms of Alzheimer-type dementia progress slowly by the loss of neurons and brain atrophy due to senile plaques and neurofibrillary tangles (Non-patent Document 1). On the other hand, symptoms of cerebrovascular dementia are caused by a decrease in cerebral blood flow in the brain due to cerebral vascular disorder, cerebral infarction, cerebral hemorrhage, etc., so that oxygen and nutrients do not reach brain neurons or neural networks. And proceed (Non-Patent Document 2).

And, in actual medical practice, cerebrovascular dementia is distinguished from Alzheimer type dementia because its treatment policy is different from neurological mutation diseases such as Alzheimer's disease (Alzheimer type dementia) and Parkinson's disease. For this reason, cerebrovascular dementia and Alzheimer's dementia are differentiated according to clinical criteria. In order to distinguish these, for example, the diagnosis and statistical manual for mental illness by the American Psychiatric Association; revised fourth edition (DSM-IV), the diagnostic criteria for Alzheimer's diagnostic criteria and vascular dementia (Vascular) Dementia; VaD) (Non-Patent Documents 1 and 2).

Cerebrovascular dementia is the most common dementia after Alzheimer's dementia. However, research and development of compounds for preventing or ameliorating Alzheimer-type dementia are being actively carried out, whereas research and development of compounds for preventing or ameliorating cerebrovascular dementia are still insufficient.

For example, in Non-Patent Document 3, cerebral blood flow and angiogenesis are evaluated on the seventh day after a chronic cerebral hypoperfusion model (BCAS) operation is performed on a mouse overexpressing the peptide hormone aderenomedullin, Further, studies on suppression of working memory failure are performed 28 days after surgery. As a result, Non-Patent Document 3 concludes that aderenomedullin can be a treatment for cerebrovascular dementia.

However, knowledge of compounds for preventing or improving cerebrovascular dementia is still insufficient.
Here, the chronic cerebral hypoperfusion model (BCAS) described above reduces the cerebral blood flow for a long period of time by attaching a coil, and the brain of the mouse falls into a chronic ischemic state, thereby inducing a cognitive decline (Non-Patent Document 4). ). And even after performing a BCAS operation, cerebral blood flow can be improved by C-RIC therapy, and a novel object recognition function can also be improved by this therapy (Non-patent Document 5). From this, the present inventors considered that if a compound capable of preventing or improving the decrease in the novel object recognition function can be searched using the BCAS model, the compound can also prevent or improve the 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. The present invention provides a composition capable of preventing and / or improving the decrease.

That is, the main object of the present technology is to provide a composition that can prevent and / or improve a decrease in cerebral blood flow.

As a result of intensive studies, the present inventors have been able to prevent and / or improve a decrease in cerebral blood flow by ingesting Bifidobacterium, and prevent and / or prevent cerebrovascular dementia. Or, it was found that it could be improved, and the present invention was completed.
That is, the present invention is as follows.

[1] A composition for preventing and / or improving cerebral blood flow reduction, comprising a Bifidobacterium bacterium as an active ingredient.
[2] A composition for preventing and / or ameliorating a symptom or disease selected from cerebrovascular dementia, dizziness, dizziness on standing, paralysis of limbs, headache, tinnitus, comprising Bifidobacterium as an active ingredient .
[3] The composition according to [1] or [2], wherein the Bifidobacterium genus bacterium is Bifidobacterium longum and / or Bifidobacterium breve.
[4] The composition according to any one of [1] to [3], wherein the composition is used for cerebrovascular dementia.
[5] The composition according to any one of [1] to [3], wherein the composition is a pharmaceutical composition or a food / beverage product composition.
[6] Bifidobacterium or use thereof for prevention and / or improvement of cerebral blood flow reduction.
[7] A method for preventing and / or improving a decrease in cerebral blood flow, comprising administering or ingesting a Bifidobacterium bacterium.
[8] Use of a bacterium belonging to the genus Bifidobacterium for producing a composition for preventing and / or improving cerebral blood flow.
[9] A method for producing a food / beverage product composition for preventing / ameliorating cerebrovascular dementia comprising the following steps (A) to (B): (A) culturing Bifidobacterium in a medium, (B) A step of subjecting the culture to freeze-drying to obtain a bacterial powder.

According to the present technology, it is possible to provide a composition capable of preventing and / or improving a decrease in cerebral blood flow. In addition, the effect described here is not necessarily limited, and may be any effect 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 interpreted narrowly. In the present specification, percentages are expressed by mass unless otherwise specified.

The present technology is a composition containing, as an active ingredient, a bacterium belonging to the genus Bifidobacterium (hereinafter also referred to as “bifidobacterium bacterium”). It is a composition for improvement. Examples of the composition include a pharmaceutical composition, a food / beverage product composition, and an animal feed composition.

The Bifidobacterium genus used in the present technology is not particularly limited. The Bifidobacterium genus used in the present technology is preferably a bacterium that can be used for probiotics that can regulate the intestinal environment of humans or non-human animals. The bacteria of the genus Fidobacterium are highly safe even if taken for a long time.

Although it does not specifically limit as Bifidobacterium genus bacteria used for this technique, For example, Bifidobacterium longum (henceforth "Bifidobacterium longum"); Bifidobacterium breve (henceforth "Bifidobacterium breve") Bifidobacterium bifidum; Bifidobacterium animalis; Bifidobacterium adolescentis and the like.
Examples of the genus Bifidobacterium used in the present 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.
One or more selected from the group consisting of these can be used.
Further, the form of the genus Bifidobacterium is not particularly limited, and may be any form such as live cells, dead cells, sterilized cells, wet bacteria, dried bacteria, and crushed materials thereof. Of these forms, a wet or dry state is not considered, but live cells and / or dead cells are preferable, and live cells are more preferable.
Of the Bifidobacterium bacteria, more preferably Bifidobacterium longum and / or Bifidobacterium breve, and among Bifidobacterium longum, Bifidobacterium longum sub Species longum is preferred from the viewpoint of efficacy. In the present technology, Bifidobacterium breve and / or Bifidobacterium longum subspecies longum are preferred.

Bifidobacterium longum subspecies longum is a bacterium present in human intestines in a wide range of ages, such as infants, children, adults and the elderly, and is highly safe.
Bifidobacterium breve is found in the age group of infants and children, is a bacterium present in the human intestine, and is highly safe. However, Bifidobacterium breve bacteria are bacteria that decrease with age and that do not decrease or exist as 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 disappears or disappears when it becomes an adult or an elderly person.

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 breve 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 an independent administrative agency, National Institute for Product Evaluation Technology, Patent Microorganism Depositary Center (NPMD) No. 2-5-8 Room 122) was deposited on January 26, 2018 under the deposit number of NITE BP-02621 under the Budapest Treaty. Bifidobacterium longum subsp. Longum ATCC BAA-999 (number: ATCC BAA-999), which is the same bacterium, is available as ATCC BAA-999 from the American Type Culture Collection (ATCC) (for example, JP 2012-223134 etc.).
[2] Bifidobacterium breve MCC1274 (Bifidobacterium breve MCC1274) is a patent biological deposit center of the National Institute of Advanced Industrial Science and Technology (currently the National Institute for Product Evaluation and Technology (NITE) Patent Biological Deposit Center ( (ODOD) (NITE-IPOD)) ((Address: 2-5-8 122, Kazusa-Kamashita, Kisarazu City, Chiba Prefecture, Japan 292-0818, Japan) on August 25, 2009, with accession number FERM BP-11175 The number is an international deposit under the Budapest Treaty.
These bacteria [1] and [2] are generally available from the above-mentioned preservation organizations or international depository organizations.

The same bacteria as the bacteria [1] and [2] are bacteria belonging to the same genus, and the base sequence of the 16S rRNA gene is 98% or more, preferably 99%, of the base sequence of the 16S rRNA gene of each of these bacteria. As mentioned above, it has 100% homology more preferably, and preferably has the same mycological property as each of these bacteria.
Furthermore, as long as the efficacy of the present technology is not impaired, bacteria bred from each of these bacteria by mutation treatment, gene recombination, selection of natural mutants, and the like may be used.

In addition, the strain specified by the strain name exemplified above is not limited to the strain itself (hereinafter also referred to as “deposited strain” for convenience of explanation) that has been deposited or registered with a predetermined institution with the strain name, Substantially equivalent strains (also referred to as “derivative strains” or “derivative strains”) are also included. That is, for example, in the above [1] “Bifidobacterium breve MCC1274 (Bifidobacterium breve MCC1274), it is not limited to the strain itself deposited with the depositary institution with the deposit number of FERM BP-11175. Substantially equivalent strains are also included, and [2] above is similar to this definition.
About a strain, “strain substantially equivalent to the deposited strain” belongs to the same species as the deposited strain, and can provide a preventive effect and / or an improved effect of cerebral blood flow reduction, which is an effect of the present technology. Means stock. The strain substantially equivalent to the deposited strain may be a derivative strain having the deposited strain as a parent strain, for example. Derivative strains include strains that have been bred from deposited strains and strains that have arisen naturally from deposited strains.

Examples of substantially the same strain and derivative strain include the following strains.
(1) Randomly amplified polymorphic DNA (RAPD method), strains identified as the same strain by the PFGE method (pulsed-field gel electrophoresis) method
(2) A strain having only a gene derived from the deposited strain, no exogenous gene, and having a DNA identity of 95% or more (preferably 98% or more) (3) A strain bred from the strain (Including genetic engineering alteration, mutation, spontaneous mutation), strains with the same trait

Bifidobacterium of the present technology can be easily propagated by culturing them.
The method of culturing Bifidobacterium of this technology is not particularly limited as long as Bifidobacterium can grow, and the method usually used for culturing Bifidobacterium can be modified as necessary. Can be used. For example, the culture temperature may be 25 to 50 ° C., preferably 30 to 40 ° C. Culturing is preferably performed under anaerobic conditions. For example, the culture can be performed while anaerobic gas such as carbon dioxide gas is aerated.

The medium for culturing the Bifidobacterium is not particularly limited, and a medium usually used for culturing the Bifidobacterium can be appropriately modified 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 molasses can be used depending on utilization. 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. Examples of the inorganic salts of the medium include sodium chloride, potassium chloride, potassium phosphate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, and ferrous sulfate. Moreover, you may use organic components, such as a peptone, a soybean powder, a defatted soybean meal, a meat extract, and a yeast extract, for the said culture medium. Moreover, the said culture medium may prepare and use a well-known culture medium, and can use MRS culture medium suitably as a culture medium which has been prepared as the said culture medium, for example.

For the Bifidobacterium of the present technology, the obtained culture may be used as it is after culturing, may be used after diluting or concentrating, and the cells recovered from the culture may be used. Bacteria may be live or dead, and may be both live and dead, but are preferably live.
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. The additional operation is preferably one in which viability of viable bacteria is high.

The Bifidobacterium genus bacterium of the present technology has an effect of preventing and / or improving cerebral blood flow reduction and an effect of preventing and / or improving cerebrovascular dementia, as shown in Examples below. In addition, the Bifidobacterium bacterium or the Bifidobacterium bacterium-containing composition of the present technology is effective against the above-described symptoms or diseases caused by cerebral blood flow reduction and cerebrovascular dementia.
Therefore, the Bifidobacterium genus bacterium of the present technology is contained as an active ingredient in a composition for preventing and / or improving cerebral blood flow reduction or a composition for preventing and / or improving cerebrovascular dementia. Can be made. Moreover, the Bifidobacterium genus bacteria of this technique can be contained in the composition which anticipates the various effect mentioned above as an active ingredient, and these various compositions can also be used as a formulation.
The Bifidobacterium genus bacterium of the present technology can be used as it is, or mixed with a normal carrier or diluent that is physiologically or pharmaceutically acceptable. It can also be used.
Moreover, the Bifidobacterium genus bacteria of this technique can be used for various uses and various compositions, such as a pharmaceutical, food-drinks, and feed.

Moreover, this technique can provide the Bifidobacterium genus bacteria used for the objectives, such as prevention / improvement of the cerebral blood flow fall mentioned above, or prevention / improvement of cerebrovascular dementia, or its use. Moreover, the Bifidobacterium genus bacteria of this technique can be used as an active ingredient of the method of preventing and improving the cerebral blood flow fall, or the method of preventing and improving cerebrovascular dementia.
Moreover, the Bifidobacterium genus bacteria of this technique can be used for manufacture of the various preparations or various compositions etc. which have the effect mentioned above or intended use.
The Bifidobacterium bacterium or the Bifidobacterium bacterium-containing composition of the present technology is used for prevention, amelioration, or treatment for a symptom or disease caused by a decrease in cerebral blood flow or for cerebrovascular dementia. Is possible.

In addition, the decrease in cerebral blood flow in the present technology is a decrease in the necessary blood flow to the entire brain or a part of the brain. This is because the width of the blood vessel in the brain is narrowed or narrowed, the amount or speed of blood flow in the brain is decreased, and the like.
Examples of symptoms or diseases caused by a decrease in cerebral blood flow in the present technology include cerebrovascular dementia, dizziness, dizziness on standing, paralysis of limbs, headache, tinnitus, and the like.

Further, the Bifidobacterium genus bacterium of the present technology may be used for humans or non-human animals (preferably primates) to be applied, preferably humans and pets, more preferably humans.

Moreover, this technique may be used for therapeutic purposes or may be used 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, lifestyle-related disease prevention (for example, a reserve army in a border region), and the like.
“Prevention” refers to prevention or delay of the onset of a disease or symptom in the application subject, or a reduction in the risk of the disease or symptom to be applied.
“Improvement” refers to improvement of a disease, symptom or condition; prevention or delay of exacerbation; reversal, prevention or delay of progression.

In the present technology, in addition to the Bifidobacterium of the present technology, any components may be used in combination as necessary. What is necessary is just to use suitably the component accept | permitted in a pharmaceutical, food-drinks, feed, etc. as an arbitrary component. Examples of optional components include sugars, sugar alcohols, polysaccharides, pH adjusters, fatty acid esters, flavoring agents, fragrances, excipients, and the like.

The composition of the present technology can be produced using the Bifidobacterium bacterium of the present technology. Further, the composition of the present technology can be obtained by mixing the various raw materials of the composition with the Bifidobacterium genus bacteria of the present technology so as to have a predetermined content as described later. Further, the content or use amount of various raw materials used in the composition of the present technology may be equivalent or similar with reference to the amounts of various raw materials that are usually used in the target composition.
The composition of this technique can be manufactured using a well-known manufacturing method.

The production method of the composition of the present technology will be described below, but the production method of the present technology is not limited thereto. Thereby, a new composition can be provided, for example, as the use of the composition, for prevention / improvement of cerebral blood flow decrease, prevention / improvement of cerebrovascular dementia, prevention of dizziness, improvement, Examples include prevention / improvement of standing dizziness, prevention / improvement of limb paralysis, prevention / improvement of headache, prevention / improvement of tinnitus, and the like.

In addition, in the production method of the present technology, it is preferable to produce a food and drink composition. This is because the Bifidobacterium bacterium of the present technology is ingestible and highly safe and can be handled at the production stage. This is because it is easy to apply fermentation technology (preferably fermented milk technology), and raw materials such as milk components or assimilation components such as plants can be used as needed. Moreover, in the manufacturing method of this technique, it is also possible to provide the food-drinks composition conscious of health, and among these, the food-drinks composition for prevention / improvement of cerebrovascular dementia is suitable.

In addition, the composition of the present technology may be fermented milk. When producing the fermented milk of the present technology, the production process of the present technology may include a fermentation process using Bifidobacterium bacteria. It may also include a step of mixing a fermented product produced in 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 food and drink for adding the effect of the present technology. It can be used for foods and drinks to which an effect is added or a method for producing the same.

Further, depending on the form of the composition of the present technology (eg, tablet, capsule, tablet, etc.), the production method of the present technology may include a step for forming the form. Compositions containing Bifidobacterium can be in various forms. In this formation step, a mixture can be obtained by mixing Bifidobacterium genus bacteria and excipients. For example, in the case of a tablet, the mixture is compressed; in the case of a drink, the mixture is put into a container. Filling; in the case of capsules, filling the mixture with capsules.

The method for producing the composition of the present technology will be described as the first embodiment and the second embodiment. However, the use of the composition is not limited to the composition for preventing and improving cerebrovascular dementia. Absent.
In addition, as a manufacturing method according to the second embodiment of the present technology, a configuration overlapping with that of the first embodiment is appropriately omitted. About the process of obtaining (A) culture | cultivation in 2nd embodiment, it can carry out similarly to the process of obtaining the culture of 1st embodiment. Moreover, about the process of obtaining the (B) bacterial powder in 2nd embodiment, it can carry out similarly to the process of obtaining the bacterial powder of 1st embodiment.

The present technology includes, as a production method according to the first embodiment, a method for producing a composition for preventing or improving cerebrovascular dementia, comprising at least one of the following step (a) or the following step (b):
(A) mixing the Bifidobacterium genus bacteria of the present technology and prebiotics; or (b) mixing the Bifidobacterium genus bacteria of the present technology and milk components;
Can be provided.
Furthermore, in the (a) mixing step, it is preferable to further mix milk components.

By the production method according to the first embodiment of the present technology, it is possible to obtain a composition for preventing and improving cerebrovascular dementia that can be efficiently produced in terms of cost, workability, and the like, and that the effects of the present technology can be exhibited well. 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 mixing the said prebiotic and / or milk component, any process of the said manufacturing process may be sufficient. For example, when the said milk component is mix | blended, any of the preceding process or this post process may be sufficient as the said (a) process. The milk component is preferably a powder. In the present technology, when producing a powdery composition, from the viewpoint of production efficiency, it is preferable to obtain a powdery composition by mixing powder materials. However, the present invention is not limited to this, and it is also possible to obtain a powdery composition by mixing these materials and performing known drying (for example, a method for drying bacteria described below).

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

The composition for the prevention / amelioration of cerebrovascular dementia can be obtained by the production method of the second embodiment of the present technology with high production efficiency and excellent effects of the present technology. By the production method of the second embodiment, a food / beverage product composition, a pharmaceutical composition and a feed composition can be obtained, and among these, a food / beverage product composition such as fermented milk and fungus powder is used from the viewpoint of production efficiency. It is preferred to obtain.

As the Bifidobacterium genus used in the production method of the present technology, the aforementioned Bifidobacterium genus bacterium of the present technology can be used. The Bifidobacterium bacterium can be cultured according to the above-described method of culturing the Bifidobacterium bacterium of the present technology to obtain a culture.
For example, milk components may be mixed into the culture medium, or fermented milk may be appropriately fermented. Further, lactic acid bacteria and / or other Bifidobacterium bacteria may be used as appropriate for fermentation.

The milk component is not particularly limited, for example, milk, buffalo milk, sheep milk, goat milk, horse milk, skim milk, skim concentrated milk, skim milk powder, concentrated milk, whole milk powder, cream, butter, butter milk, Condensed milk, milk protein, etc. can be mentioned, 1 type, or 2 or more types chosen from the group which consists of these can be used. Moreover, although it does not specifically limit as milk protein, For example, a whey, casein, these hydrolysates, etc. are mentioned, 1 type, or 2 or more types chosen from the group which consists of these can be used. Of the milk components, those derived from milk are preferred.

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

The form of the genus Bifidobacterium or a culture containing the same is not particularly limited and may be either liquid or solid, but the form may be in a dry form (for example, a fungus or a culture dry product). From the viewpoint of easy handling during production and storage, it is preferable. Examples of the culture include the microbial cells themselves from which the culture solution has been separated and the culture containing the microbial 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 drying method, a UHT sterilization method, an autoclave method, a high pressure steam sterilization method, a dry heat sterilization method, a flow steam disinfection 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).

In addition, the microbial cells may be crushed, and the crushed material may be crushed live bacteria or dead bacteria, or may be heated, lyophilized, or the like after crushing.
Among these, it is preferable to subject the culture to freeze-drying from the viewpoint of increasing the viable cell rate, and it is preferable to subject the culture to spray-drying from the viewpoint of increasing production efficiency.

Moreover, as long as the effect of this technique is not impaired, the component which has a probiotic effect known in the future or the component which assists a probiotic effect can be used for the composition of this technique. Here, in general, probiotics refer to bacteria that have a beneficial function in the intestine. In general, a substance that serves as a selective nutrient source for bacteria that play a beneficial role in the intestine and promotes their growth is called prebiotics.
In the case of using or containing prebiotics for promoting the growth of Bifidobacterium of the present technology, the amount is preferably 1 to 1,000,000 parts by mass with respect to 100 parts by mass of the bacteria. 000 parts by mass is more preferable.

Examples of the prebiotics include various proteins such as whey protein, casein protein, soybean protein, pea protein (pea protein) or mixtures thereof, degradation products; amino acids such as leucine, valine, isoleucine or glutamine; vitamin B6 or Vitamins such as vitamin C; creatine; citric acid; fish oil; or components such as isomaltoligosaccharide, galactooligosaccharide, xylo-oligosaccharide, soybean oligosaccharide, fructooligosaccharide, lactulose, human milk oligosaccharide (HMO) 1 type, or 2 or more types selected from the group consisting of these may be used.
The composition of the present technology can be produced by blending the prebiotic component and the bacterium of the present technology or a culture thereof.

“Human milk oligosaccharides” that can be used in the present technology include 2′-fucosyl lactose, 3-fucosyl lactose, 2 ′, 3-difucosyl lactose, lacto-N-triose II, lacto-N-tetraose, lacto -N-neotetraose, lacto-N-fucopentaose I, lacto-N-neofocopenaose, lacto-N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-fucopentaose V, lacto-N-neofco Pentaose V, lacto-N-difucohexaose I, lacto-N-difucohexaose II, 6'-galactosyl lactose, 3'-galactosyl lactose, lacto-N-hexaose and lacto-N-neohexaose Neutral human milk oligosaccharide, 3'-sialyl lacto Acidic human milk oligosaccharides such as 6'-sialyl lactose, 3-fucosyl-3'-sialyl lactose, and disialyl-lacto-N-tetraose can be used, and one or more selected from the group consisting of these can be used. May be used.

An example of the manufacturing method of the present technology will be described below, but the present technology is not limited to this.
Example 1 of the production method of the present technology is a method for producing a bacterial powder or a molded product (for example, supplement) containing the Bifidobacterium genus bacteria of the present technology.
A step of anaerobically culturing Bifidobacterium bacteria in a medium, a step of concentrating the culture solution, freeze-drying, and obtaining a freeze-dried powder (bacterial powder). Thereby, it is possible to provide a bacterial powder for uses such as prevention and improvement of cerebral blood flow reduction. At this time, the culture solution containing Bifidobacterium bacteria may be spray-dried to form a granular powder. The bacterium of the present technology is blended so as to obtain a predetermined amount of cells in the composition.
Moreover, when manufacturing the supplement and tablet of this technique, the process which mixes the culture solution and excipient | filler containing Bifidobacterium genus bacteria and an excipient | filler, and the process shape | molded in the said predetermined shape can be included. Examples of the molding step include tableting, and examples of tableting include 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 of producing a milk beverage or dairy product containing the Bifidobacterium bacterium of the present technology.
As Example 2 of the manufacturing method of the present technology, a step of mixing the bacterial powder obtained in Example 1 of the above-described manufacturing method with milk or skim milk is performed. At this time, (A) milk protein 3.5 mass% or more, (B) milk fat 3.5 mass% or less, (C) carbohydrate 5.0 mass% or more, and (D) calcium 0.15 mass% or more. Adjust to include. Moreover, the bacteria of this technique in the said powder are mix | blended so that it may become a predetermined cell amount. Thereby, the milk drink or dairy product for uses, such as a cerebral blood-flow fall prevention / improvement, can be provided.

Example 3 of the production method of the present technology is a method for producing fermented milk containing Bifidobacterium bacteria of the present technology.
As Example 3 of the production method of the present technology, the step of adding the bacterial powder obtained in Example 1 of the above-described production method to a fermented milk raw material to obtain fermented milk containing Bifidobacterium bacteria of the present technology Do. Or the process which obtains fermented milk which mixes the said powdered powder and fermented milk and obtains fermented milk containing the Bifidobacterium genus bacteria of this technique is performed. Fermentation conditions and a compounding quantity are adjusted so that the microbial cell amount of the bacterium of this technique in the said composition may become predetermined | prescribed microbial cell amount. Thereby, fermented milk or fermented products for uses such as prevention and improvement of cerebral blood flow reduction can be provided.

The content or use amount of Bifidobacterium (live or dead) of the present technology is not particularly limited, but is preferably 1 × 10 ³ to 1 × 10 ¹² (CFU / g or CFU / mL, or cells (cells) / g or cells (cells) / mL), more preferably 1 × 10 ⁵ to 1 × 10 ¹¹ (CFU / g or CFU / mL, or cells (cells) / g or cells (Number) / mL), more preferably 1 × 10 ⁷ to 1 × 10 ¹⁰ (CFU / g or CFU / mL, or cells / number or cells / number). CFU indicates a colony forming unit.
The content or use 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 CFU / mL, or cells (cells) / g or cells (cells) / mL), more preferably 1 × 10 ⁵ to 1 × 10 ¹¹ (CFU / g or CFU / mL, or cells (cells) / g or cells (Number) / mL), more preferably 1 × 10 ⁷ to 1 × 10 ¹⁰ (CFU / g or CFU / mL, or cells / number or cells / number).
The content or use 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 CFU / mL, or cells (cells) / g or cells (cells) / mL), more preferably 1 × 10 ⁵ to 1 × 10 ¹¹ (CFU / g or CFU / mL, or cells (cells) / g or cells (Number) / mL), more preferably 1 × 10 ⁷ to 1 × 10 ¹⁰ (CFU / g or CFU / mL, or cells / number or cells / number).

The administration target is usually preferably a human, but includes mammals other than humans, for example, pet animals such as dogs and cats, and livestock such as cows, sheep and pigs.

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

In addition, 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 preferably once a day because it is simple and effective.
In addition, the Bifidobacterium genus bacterium of the present technology is highly safe and can be administered or ingested before symptoms or diseases caused by decreased cerebral blood flow are observed. Moreover, it is preferable from a viewpoint of prevention for this technique to administer or ingest before the symptom or disease resulting from a cerebral blood flow fall is recognized.
In addition, the Bifidobacterium genus bacterium of the present technology can be easily administered or ingested before symptoms such as a decrease in cerebral blood flow are observed. Therefore, it is preferable.
In the present technology, it is preferable to administer or ingest one week before (more preferably two weeks before) a symptom such as a decrease in cerebral blood flow from the viewpoint of easily obtaining a preventive effect and a subsequent improvement effect.
In the present technology, when symptoms such as cerebral blood flow reduction are observed, administration or ingestion over a long period is preferable from the viewpoint of efficacy, more preferably 2 weeks or more, and further preferably 4 weeks or more. It is preferable from the viewpoint of easily obtaining an improvement effect.

[Pharmaceutical composition]
When the Bifidobacterium genus bacterium is used for a pharmaceutical composition or a pharmaceutical use, the pharmaceutical may be administered either orally or parenterally, but oral administration and administration acting on the mucous membrane are preferred. Examples of parenteral administration include injection (blood, skin, muscle, etc.), rectal administration, inhalation and the like. Examples of the dosage form for oral administration include tablets, capsules, troches, 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, components such as excipients, pH adjusters, colorants, flavoring agents and the like that are usually used for formulation can be used in addition to Bifidobacterium bacteria. Furthermore, a component having an effect of preventing or treating a known or future disease can be used in combination according to the purpose.

Furthermore, depending on the administration method, it can be appropriately formulated into a desired dosage form. 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. For parenteral administration, it can be formulated into suppositories, sprays, ointments, patches, injections and the like.

In addition, formulation can be performed by a known method as appropriate according to the dosage form. In the formulation, only the casein enzyme-treated product or each separated / purified fraction may be formulated, or may be formulated by appropriately blending a formulation carrier.

In addition, 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, and flavoring agents.

Examples of the excipient include sugar derivatives such as lactose, sucrose, glucose, mannitol and sorbit; starch derivatives such as corn starch, potato starch, α-starch, dextrin and carboxymethyl starch; crystalline cellulose, hydroxypropyl cellulose, Cellulose derivatives such as hydroxypropylmethylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, magnesium magnesium magnesium silicate; phosphate derivatives such as calcium phosphate; And carbonate derivatives such as calcium; sulfate derivatives such as calcium sulfate and the like.

Examples of the binder include gelatin, polyvinyl pyrrolidone, macrogol and the like in addition to the above excipients.

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

As the lubricant, for example, talc; stearic acid; stearic acid metal salts such as calcium stearate and magnesium stearate; colloidal silica; waxes such as pea gum and geirow; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid Carboxylic acid sodium 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 anhydrous silicic acid and silicic acid hydrate; starch derivatives and the like It is done.

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

Examples of the flavoring agent include sweeteners, acidulants, and fragrances.
In addition, as a carrier used in the case of a liquid for oral administration, a solvent such as water, a flavoring agent and the like can be mentioned.

[Food and beverage composition]
The present technology can provide a food / beverage product composition containing Bifidobacterium as an active ingredient. The food / beverage product composition of the present technology can be used for prevention and improvement of cerebrovascular dementia, dizziness, dizziness on standing, paralysis of limbs, headache, tinnitus, and the like. For example, there are health foods, functional foods, and the like based on applications such as prevention and / or improvement of cerebral blood flow reduction.

Furthermore, infant formula can be mentioned as a food-drinks composition which concerns on this technique. Formulas for childcare include infant formulas for infants 0-12 months, follow-up milk for infants 6 to 9 months and younger infants (up to 3 years old), at birth Formulated milk for low birth weight infants targeting newborns (low birth weight infants) weighing less than 2500 g, various therapeutic milks used for the treatment of infants with pathological conditions such as milk allergy and lactose intolerance Point to.

When Bifidobacterium is used for food or drink for humans or animals, it can be prepared by adding it to a known food or drink, or it is mixed with a raw material for food or drink to produce a new food or drink. You can also.
The usage method, usage amount, and content in the food and beverage composition of the present technology are as described above.

The foods and drinks may be in the form of liquids, pastes, solids, powders, etc., in addition to tablet confections, liquid foods, feeds (including for pets), etc. Processed products, processed livestock products, milk / dairy products, fats and oils, basic seasonings, compound seasonings / foods, frozen foods, confectionery, beverages, and other commercial products.

Examples of flour products include bread, macaroni, spaghetti, noodles, cake mix, fried flour, bread crumbs and the like.
Examples of instant foods include instant noodles, cup noodles, retort / cooked food, cooking canned food, microwave food, instant soup / stew, instant miso soup / soup, canned soup, freeze-dried food, other instant foods, etc. It is done.
Examples of processed agricultural products include canned agricultural products, canned fruits, jams and marmalades, pickles, boiled beans, dried agricultural products, cereals (cereal processed products), and the like.
Examples of processed fishery products include canned fishery products, fish hams and sausages, marine products, marine delicacies, and tsukudani.
Examples of livestock processed products include canned livestock, pastes, livestock meat ham, sausage and the like.
Examples of milk / dairy products include processed milk, milk beverages, yogurts, lactic acid bacteria beverages, cheese, ice creams, prepared powdered milks, creams, and other dairy products.
Examples of the fats and oils include butter, margarine, vegetable oil and the like.
Basic seasonings include, for example, soy sauce, miso, sauces, tomato processed seasonings, mirins, vinegars, etc., and the above mixed seasonings and foods include cooking mix, curry ingredients, sauces, Examples include dressings, noodle soups, spices, and other complex seasonings.
Examples of the frozen food include raw material frozen food, semi-cooked frozen food, cooked frozen food, and the like.
Examples of the confectionery include caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pie, snacks, crackers, Japanese confectionery, rice confectionery, bean confectionery, dessert confectionery, and other confectionery.

Examples of beverages include carbonated beverages, natural fruit juices, fruit juice drinks, soft drinks with fruit juice, fruit drinks, fruit drinks with fruits, vegetable drinks, soy milk, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks Sports drinks, nutritional drinks, alcoholic drinks, other taste drinks, and the like.
Examples of commercially available foods other than the above include baby food, sprinkles, and green tea paste.

In addition, the food and drink defined in the present technology can be provided and sold as a food and drink displaying health applications.
The “display” act includes all acts for informing the consumer of the use, and if the expression can remind the user of the use, the purpose of the display, the content of the display, the display Regardless of the target object / medium, etc., all fall under the “display” act of this technology.

In addition, it is preferable that the “display” is performed by an expression that allows the consumer to directly recognize the use. Specifically, it is the act of transferring, displaying, importing, displaying, or importing products that are related to food or drinks or products that describe the use, on advertisements, price lists, or transaction documents. For example, an act of describing and displaying the above uses or distributing them, or describing the above uses in information including the contents and providing them by an electromagnetic (Internet or the like) method can be given.

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

In addition, “labeling” includes health food, functional food, enteral nutrition food, special purpose food, health functional food, food for specified health use, nutrition functional food, functional label food, quasi-drug, etc. A display is also included. Among these, in particular, there are indications approved by the Consumer Affairs Agency, for example, indications approved under the food system for specific health use, a similar system, and the like. Examples of the latter include a display as a food for specified health use, a display as a conditionally specified food for specified health use, a display indicating that it affects the structure and function of the body, and a display for reducing disease risk. More specifically, indications as foods for specified health (especially indications for health use) and regulations stipulated in the Health Promotion Act Enforcement Regulations (April 30, 2003 Ministry of Health, Labor and Welfare Ordinance No. 86) A similar display is a typical example.

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

Examples of the raw material of the feed include cereals such as corn, wheat, barley, and rye; bran such as bran, wheat straw, rice bran, and defatted rice bran; and manufactured porridges such as corn gluten meal and corn jam meal; Animal feeds such as whey, fish meal, and bone meal; yeasts such as beer yeast; mineral feeds such as calcium phosphate and calcium carbonate; fats and oils; amino acids; In addition, examples of the form of the feed include pet animal feed (pet food, etc.), livestock feed, fish feed, and the like.

Thus, the present 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 employ the following configurations.
[1] A composition for preventing and / or improving cerebral blood flow reduction containing Bifidobacterium as an active ingredient; or preventing symptoms or diseases (including these reserves) caused by cerebral blood flow reduction 1 selected from the group consisting of cerebrovascular dementia, dizziness, dizziness, dizziness, paralysis of limbs, headache, tinnitus, containing composition used for improvement / treatment or Bifidobacterium as an active ingredient A composition used for prevention, amelioration, or treatment of a species or two or more symptoms or diseases.
[2] For use in the prevention and / or improvement of cerebral blood flow reduction; or for use in the prevention, improvement or treatment of symptoms or diseases (including these reserves) resulting from cerebral blood flow reduction; or Bifidobacterium for use in the prevention / amelioration / treatment of one or more symptoms or diseases selected from the group consisting of cerebrovascular dementia, dizziness, dizziness on standing, paralysis of limbs, headache, tinnitus Genus bacteria.
[3] For prevention and / or improvement of cerebral blood flow reduction; or prevention / improvement / treatment of symptoms or diseases (including these reserves) caused by cerebral blood flow reduction; or cerebral blood vessels Bifidobacterium for use in the prevention, amelioration, or treatment of one or more symptoms or diseases selected from the group consisting of sexual dementia, dizziness, dizziness on standing, paralysis of limbs, headache, tinnitus Use of.
[4] A method for preventing and / or improving cerebral blood flow reduction by administering or ingesting a Bifidobacterium bacterium; or a symptom or disease caused by cerebral blood flow reduction (including these reserve forces) Method for prevention / improvement / treatment; or prevention or prevention of one or more symptoms or diseases selected from the group consisting of cerebrovascular dementia, dizziness, dizziness on standing, paralysis of limbs, headache, tinnitus Methods for improvement and treatment.
[5] A composition used for the manufacture of a composition for preventing and / or improving cerebral blood flow; or for preventing, improving or treating symptoms or diseases (including these reserves) caused by decreased cerebral blood flow Or for the prevention, amelioration, or treatment of one or more symptoms or diseases selected from the group consisting of cerebrovascular dementia, dizziness, dizziness on standing, paralysis of limbs, headache, tinnitus Use of Bifidobacterium for the production of the composition used.

[6] A method for producing a composition for preventing or improving cerebrovascular dementia, comprising at least one of the following step (a) or the following step (b):
(A) a step of mixing Bifidobacterium and prebiotics, or
(B) A step of mixing Bifidobacterium bacteria (preferably bacterial powder) and milk components (preferably powdered milk).
The milk component is preferably powdered milk.
In the step (a), it is preferable that a milk component is further mixed in either the step before the step (a) or the step after the step (a).
[7] A method for producing a composition for preventing or improving cerebrovascular dementia, comprising the following steps (A) to (B):
(A) culturing Bifidobacterium in a medium to obtain a culture;
(B) A step of subjecting the culture to drying to obtain a bacterial powder.
It is preferable that after the step (A) and the step (B), (C) a step of mixing the fungus powder and prebiotic to obtain a composition.
Moreover, the said composition has a suitable food-drinks composition.
Further, the medium is more preferably a medium containing a milk component, thereby increasing the number of cells and increasing the recovery rate, or in some cases fermented milk, to obtain its flavor and efficacy. it can.
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 cerebrovascular dementia; or prevention of one or more symptoms or diseases selected from the group consisting of cerebrovascular dementia, dizziness, dizziness on standing, 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 and beverage composition; or the composition is for non-therapeutic purposes; Alternatively, the use, administration or ingestion of the Bifidobacterium is a non-therapeutic purpose.
[10] In any one of the above [1] to [9], preferably, the Bifidobacterium 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 is administered or ingested, the administration or ingestion recognizes a decrease in cerebral blood flow. Before and / or continued for a long time after cerebral blood flow decline; the administration or ingestion is before symptoms or diseases are recognized and / or after symptoms or diseases are recognized It is continued 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, dizziness on standing, paralysis of limbs, headache, tinnitus One or more selected from the group consisting of:
[13] In any one of the above [1] to [12], the composition is any one of a pharmaceutical composition, a composition for food and drink, a milk powder (for example, an infant formula), or a supplement. It is.

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

〔experimental method〕
Verification of the effect of chronic cerebral hypoperfusion model (BCAS model) on cerebral blood flow reduction Bifidobacterium longum NITE BP-02621 using mice (BCAS mice) with microcoils attached to both common carotid arteries And Bifidobacterium breve FERM BP-11175 were examined for the effect of improving cerebral blood flow reduction.
Bifidobacterium longum NITE BP-02621 and Bifidobacterium breve FERM BP-11175 were obtained from an international depository.

C57BL / 6J mice of 10 weeks of age (weeks when obtained) were used for the test. Bifidobacterium longum NITE BP-02621 and Bifidobacterium breve FERM BP-11175 were each administered at 1 × 10 ⁹ CFU / day one week before the BCAS surgery, and then continued for 30 days after surgery. A novel object recognition test was performed on the eyes.
Specifically, the BCAS operation was performed by anesthetizing a mouse by intraperitoneal administration of medetomidine hydrochloride 0.3 mg / kg, midazolam 4 mg / kg, butorphanol tartrate 5 mg / kg, then the neck was opened and the bilateral common carotid arteries were detached. A microcoil with an inner diameter of 0.18 mm was attached. In the sham operation group, the neck was opened and 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, Bifidobacterium longum NITE BP-02621 and Bifidobacterium breve FERM BP-11175 were administered to BCAS mice, compared with the group in which BCAS mice were administered physiological saline. The new object search time was as long as that of azilsartan. From this, it was shown that cerebral blood flow reduction is also improved by ingesting Bifidobacterium longum and / or Bifidobacterium breve (for example, refer to Non-Patent Documents 4 and 5). . In addition, since azilsartan, a positive control, is known to have an effect of improving cerebral blood flow reduction, it can be said that if the reduction of recognition of new objects can be improved, cerebral blood flow reduction can also be improved. .
As described above, Bifidobacterium longum NITE BP-02621 and Bifidobacterium breve FERM BP-11175 have been found to have an effect of improving cerebral blood flow, thereby causing symptoms caused by cerebral blood flow reduction. Alternatively, prevention and improvement of diseases (for example, cerebrovascular dementia and paralysis of limbs) can be expected.

As described above, the Bifidobacterium genus bacterium (more preferably, Bifidobacterium longum and / or Bifidobacterium breve) of the present technology exhibits an effect of preventing and improving cerebral blood flow reduction. To do. And the composition of this technique is a composition used for a cerebral vascular dementia etc. used for a cerebral blood flow fall, and the said composition is for pharmaceuticals, food-drinks, It can be used for a wide range of uses such as feed and pet.

[Production Example 1]
Bifidobacterium longum NITE BP-02621 and / or Bifidobacterium breve FERM BP-11175 bacteria are added to 3 mL of MRS liquid medium, anaerobically cultured at 37 ° C. for 16 hours, and the culture solution is concentrated and frozen. Drying is performed to obtain a freeze-dried powder (bacterial powder) of the bacteria. (A) Milk protein 3.5 mass% or more, (B) Milk fat 3.5 mass% or less, (C) Carbohydrate 5.0 mass%, mixing the said bacterial powder and milk or skim milk uniformly. It adjusts so that it may contain more than the above and (D) calcium 0.15 mass%. As a result, a composition for preventing and improving cerebral blood flow reduction containing bifidobacteria is obtained. The ingestion amount of bacteria is 1 × 10 ⁸ to 1 × 10 ¹⁰ CFU / kg body weight / day, and 200 mL is ingested every day for 1 to 4 weeks or more.
It can be ingested as a food / beverage composition (milk drink), can also be ingested as a food / beverage composition (milk drink) for the prevention / improvement of cerebrovascular dementia, The improvement effect and the prevention / improvement effect of cerebrovascular dementia can be expected.

[Production Example 2]
Bifidobacterium longum NITE BP-02621 and / or Bifidobacterium breve FERM BP-11175 bacteria are added to 3 mL of MRS liquid medium, anaerobically cultured at 37 ° C. for 16 hours, and the culture solution is concentrated and frozen. Drying is performed to obtain a granular form (bacterial powder) of the bacterium as a composition for preventing or improving cerebral blood flow reduction (granular or tablet form). The granular bacterial powder is ingested every day for one week or longer with a bacterial intake of 1 × 10 ⁸ to 1 × 10 ¹⁰ CFU / kg body weight / day.
It can be ingested as a food / beverage composition, and can also be used as a food / beverage composition (granular or tablet) for the prevention / improvement of cerebrovascular dementia. Expected to be effective and prevent / improve cerebrovascular dementia.
When obtaining the bacterial powder, it is also possible to obtain spray-dried bacterial powder by “spray drying” instead of “freeze drying”.

[Production Example 3]
Bifidobacterium longum NITE BP-02621 and / or Bifidobacterium breve FERM BP-11175 bacteria are added to 3 mL of MRS liquid medium, anaerobically cultured at 37 ° C. for 16 hours, and the culture solution is concentrated and frozen. Drying is performed, and the bacterial granules (bacterial powder) are added to the fermented milk raw material to obtain fermented milk. The fermented milk for preventing or improving the decrease in cerebral blood flow is ingested daily for 1 week or more with a bacterial intake of 1 × 10 ⁸ to 1 × 10 ¹⁰ CFU / kg body weight / day.
This can be ingested as fermented milk for prevention / improvement of cerebrovascular dementia, and can be expected to have an effect of preventing / improving cerebral blood flow reduction and an effect of preventing / improvement of cerebrovascular dementia.

[Production Example 4]
The bacterial powder obtained in [Production Example 2] (the bacterial powder may be either a lyophilized product and / or a spray-dried product) and probiotics are mixed to obtain a bacterial and probiotic mixture. . Human milk oligosaccharide is used as the probiotic. Probiotics have the advantage of easily growing the bacteria used.
The bacteria and the probiotic mixture are ingested every day for one week or longer with a bacteria intake of 1 × 10 ⁸ to 1 × 10 ¹⁰ CFU / kg body weight / day.
This can also be ingested as a food or beverage composition for preventing or improving cerebrovascular dementia, and can be expected to have an effect of preventing or improving cerebral blood flow reduction and preventing or improving cerebrovascular dementia.

(1) Bifidobacterium longum NITE BP-02621 strain (Accession number: NITE BP-02621) (Accession date: January 26, 2018), Contractor: Kazusa-Kama, Kisarazu City, Chiba Prefecture, Japan 292-0818 2-5-8, Room 122, National Institute for Product Evaluation Technology Patent Microorganism Depositary Center (NPMD).
(2) Bifidobacterium breve FERM BP-11175 strain (Accession number: FERM BP-11175) (Accession date: August 25, 2009), Contractor: Kazusa-Kama, Kisarazu City, Chiba Prefecture, Japan 292-0818 Foot 2-5-8, National Institute of Advanced Industrial Science and Technology Patent Biological Depositary Center (currently National Institute for Product Evaluation Technology (NITE) Patent Biological Depositary Center (IPOD) (NITE-IPOD)).

Claims (9)

1. A composition for preventing and / or improving cerebral blood flow reduction, comprising a Bifidobacterium bacterium as an active ingredient.
2. A composition for preventing and / or improving a symptom or disease selected from cerebrovascular dementia, dizziness, dizziness on standing, paralysis of limbs, headache, tinnitus, containing Bifidobacterium as an active ingredient.
3. The composition according to claim 1 or 2, wherein the Bifidobacterium bacterium is Bifidobacterium longum and / or Bifidobacterium breve.
4. The composition according to any one of claims 1 to 3, wherein the composition is used for cerebrovascular dementia.
5. The composition according to any one of claims 1 to 4, wherein the composition is a pharmaceutical composition or a food / beverage product composition.
6. Bifidobacterium or use thereof for prevention and / or improvement of cerebral blood flow reduction.
7. A method for preventing and / or improving cerebral blood flow reduction by administering or ingesting Bifidobacterium.
8. Use of Bifidobacterium bacteria for the manufacture of a composition for preventing and / or improving cerebral blood flow reduction.
9. A method for producing a food or beverage composition for preventing or improving cerebrovascular dementia, comprising the following steps (A) to (B):
   (A) culturing Bifidobacterium in a medium to obtain a culture;
   (B) A step of subjecting the culture to freeze-drying to obtain a bacterial powder.