WO2021256077A1 - 認知機能改善剤、認知機能維持剤、海馬機能改善剤及び海馬機能維持剤 - Google Patents
認知機能改善剤、認知機能維持剤、海馬機能改善剤及び海馬機能維持剤 Download PDFInfo
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- WO2021256077A1 WO2021256077A1 PCT/JP2021/016150 JP2021016150W WO2021256077A1 WO 2021256077 A1 WO2021256077 A1 WO 2021256077A1 JP 2021016150 W JP2021016150 W JP 2021016150W WO 2021256077 A1 WO2021256077 A1 WO 2021256077A1
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- bifidobacterium breve
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/51—Bifidobacterium
- A23V2400/519—Breve
Definitions
- the present invention relates to a cognitive function improving agent, a cognitive function maintaining agent, a hippocampal function improving agent, and a hippocampal function maintaining agent.
- dementia can lead to serious consequences that even threaten human dignity.
- research on the prevention and treatment of dementia is being vigorously pursued.
- Dementia is caused by various disorders caused by the death of brain cells or poor functioning due to various causes, which makes it impossible to judge things or causes a rapid deterioration of memory. It refers to a state in which life is continuously impaired.
- Neurodegenerative diseases are the most common factor in developing dementia, followed by cerebrovascular dementia. Neurodegenerative diseases are those in which abnormalities accumulate in nerve cells of the brain over a long period of time, eventually leading to cell death, and include Alzheimer's disease, frontotemporal dementia, and Lewy body dementia.
- cerebrovascular dementia is caused by cerebral infarction, cerebral hemorrhage, cerebral arteriosclerosis, etc., which causes the death of nerve cells in the brain or the destruction of nerve networks.
- Patent Document 1 describes a brain function improving agent for patients with dementia.
- Mild cognitive impairment (MCI: Mild Cognitive Impairment) is a healthy person, but cognitive decline is occurring. MCI is a reversible state and cognitive function can be restored to normal. Therefore, even if MCI is diagnosed, if the cognitive function can be improved or maintained, the transition to dementia may be delayed or prevented.
- Alzheimer's disease accounts for nearly half of dementia.
- Alzheimer-type dementia degeneration of nerve cells has been observed for more than 20 years before the onset, and it is said that nerve cells are shed and hippocampal atrophy occurs, resulting in deterioration of hippocampal function. Therefore, if hippocampal function can be improved or maintained, it may be possible to delay or prevent the onset of Alzheimer's disease.
- An object of the present invention is to provide a cognitive function improving agent or a cognitive function maintaining agent, or a hippocampal function improving agent or a hippocampal function maintaining agent for administration to a subject who has not developed dementia.
- [1] Administer to subjects who do not develop dementia and contain either or both of the cultures of Bifidobacterium Breve FERM BP-11175 and Bifidobacterium Breve FERM BP-11175 as active ingredients.
- Agent [3]
- the cognitive function according to [1] wherein the subject who does not develop dementia does not develop dementia but is concerned about a complex cognitive decline with aging. Improving agent.
- the subjects who do not develop the dementia are those who have an MMSE score of 22 or more and a total RBANS score of 65 or less or a health check score of 75 or less.
- the cognition according to [9], wherein the subject who has not developed dementia is selected from a group consisting of healthy subjects, a group consisting of mild cognitive impairment subjects, and a group consisting of healthy subjects and mild cognitive impairment subjects.
- Function maintenance agent [13] The subjects who do not develop the dementia are those who have an MMSE score of 22 or more and a total RBANS score of 65 or less or a health check score of 75 or less.
- the cognitive function maintenance agent described in. [14] The cognitive function maintaining agent according to any one of [9] to [13], which comprises 1 ⁇ 10 6 to 1 ⁇ 10 12 CFU / g of Bifidobacterium breve.
- a hippocampal function improving agent containing either or both of the cultures of Bifidobacterium Breve FERM BP-11175 and Bifidobacterium Breve FERM BP-11175 as active ingredients.
- the hippocampal function improving agent according to [17] which is to be administered to a subject who has not developed dementia.
- the hippocampus according to [18], wherein the subject who does not develop dementia is selected from a group consisting of healthy subjects, a group consisting of mild cognitive impairment subjects, and a group consisting of healthy subjects and mild cognitive impairment subjects. Function improver.
- the subjects who do not develop the dementia are those who have an MMSE score of 22 or more and a total RBANS score of 65 or less or a hippocampal health check score of 75 or less.
- the hippocampal function improving agent according to any one of [17] to [20], which comprises 1 ⁇ 10 6 to 1 ⁇ 10 12 CFU / g of Bifidobacterium breve.
- a food or drink for improving hippocampal function which comprises one or both of the cultures of Bifidobacterium Breve FERM BP-11175 and Bifidobacterium Breve FERM BP-11175.
- the subjects who do not develop the dementia are those who have an MMSE score of 22 or more and a total RBANS score of 65 or less or a hippocampal health check score of 75 or less.
- the hippocampal function maintenance agent described in. [28] The hippocampal function maintaining agent according to any one of [24] to [27], which comprises 1 ⁇ 10 6 to 1 ⁇ 10 12 CFU / g of Bifidobacterium breve. [29] A food or drink for maintaining hippocampal function, which comprises one or both of the cultures of Bifidobacterium Breve FERM BP-11175 and Bifidobacterium Breve FERM BP-11175. [30] Use of one or both of the cultures of Bifidobacterium Breve FERM BP-11175 and Bifidobacterium Breve FERM BP-11175 for the production of hippocampal function maintaining agents.
- a cognitive function improving agent or a cognitive function maintaining agent or a hippocampal function improving agent or a hippocampal function maintaining agent for administration to a subject who has not developed dementia.
- FIG. 1 is a graph showing the RBANS score before and after the test.
- FIG. 2 is a graph showing the fluctuation value of the RBANS score before and after the test.
- FIG. 3 is a graph showing the scores and fluctuation values of the head health check (JMCIS) before and after the test.
- JMCIS head health check
- the numerical range represented by "-" includes the numerical values on both sides of "-”.
- the MMSE score is a score calculated by the MMSE (Mini-Mental State Examination).
- the MMSE is an internationally widely used screening method for cognitive dysfunction in clinical and research. Orientation, verbal memory, general attention / calculation, language, and figure copying are all 30 points. The lower the MMSE score, the more the cognitive decline is progressing.
- the RBANS score is a score calculated by RBANS (Repeatable Battery for the Assessment of Neuropsychological Status). RBANS is a nationwide standardized neuropsychological test developed by Randolph in 1998 that evaluates five cognitive areas: immediate memory, delayed memory, visuospatial / composition, language, and attention.
- Atama Health Check JMCIS (registered trademark) is a test that can easily and accurately express minute changes in cognitive function in the healthy person-boundary area-MCI area with an interactive check of about 10 minutes. Is.
- the cognitive function index is calculated using a unique algorithm and database based on information such as the subject's gender, age, years of study, and race (provided by Millenia Co., Ltd.).
- MPI score Memory Performance Index: Cognitive Function Index
- head health check score is an index that objectively indicates an individual's cognitive function evaluated and calculated by the head health check. The lower the value, the more the cognitive decline is progressing.
- FERM is a symbol indicating the NITE Patented Biological Depositary Center (NITE-IPOD; NITE International Patent Organization Organization). NITE is an abbreviation for National Institute of Technology and Evolution (National Institute of Technology and Technology).
- the cognitive function improving agent of the present invention is a cognitive function improving agent containing either or both of the cultures of Bifidobacterium Breve FERM BP-11175 and Bifidobacterium Breve FERM BP-11175 as active ingredients. ..
- the subject of administration of the cognitive function improving agent of the present invention is a subject who has not developed dementia.
- the subject is usually a human, but it can also be administered to mammals other than humans, for example, pet animals such as dogs and cats, and domestic animals such as cattle, sheep and pigs. In the following, the case where the target is a human will be described.
- any of the following subjects (1) to (4) is preferable.
- the total RBANS score is preferably 41 or less.
- the score of the head health check is preferably 50.2 or less.
- the administration route of the cognitive function improving agent of the present invention includes, for example, oral administration, intraperitoneal administration, intramuscular administration, transmucosal administration, intranasal administration, rectal administration and the like, and oral administration is particularly preferable.
- the improvement of cognitive function means that a score increase is observed in one or more of the MMSE score, the RBANS total score and the health check of the head before and after administration of the cognitive function improving agent of the present invention. ..
- a score increase is observed in each area of immediate memory, visual space / composition and delayed memory, and one or more of the comprehensive evaluation points, and visual space / composition and delay are observed. It is more preferable that an increase in score is observed in at least one area of memory.
- the active ingredient of the cognitive function improving agent of the present invention is one or both of the cultures of Bifidobacterium Breve FERM BP-11175 and Bifidobacterium Breve FERM BP-11175. Either or both of the cultures of Bifidobacterium Breve FERM BP-11175 and Bifidobacterium Breve FERM BP-11175 are used for the production of the cognitive function improving agent of the present invention.
- Bifidobacterium bleve is one of the bacteria belonging to the genus Bifidobacterium.
- Bifidobacterium breve mainly inhabits the large intestine of infants, and among the bacterial species belonging to the genus Bifidobacterium, Bifidobacterium longum subspecies infantis. ) Etc., and is known as an infant-type Bifidobacterium genus bacterium.
- the cognitive function improving agent of the present technology is used in one or both of cultures containing Bifidobacterium bleve and Bifidobacterium bleve, in which the active ingredient mainly inhabits the large intestine of infants. Therefore, it is very useful because it is excellent in safety and there is little need to worry about side effects even if it is continuously administered for a long period of time. Furthermore, it is highly safe when used in combination with other drugs.
- An equivalent strain may be used in place of Bifidobacterium Breve FERM BP-11175.
- Equivalent strain means a strain derived from the same isolate.
- Bifidobacterium Breve MCC1274 can be mentioned as a strain equivalent to Bifidobacterium Breve FERM BP-11175.
- MCC means Morinaga Culture Collection (Morinaga Milk Industry Co., Ltd.).
- Bifidobacterium Breve FERM BP-11175 can be easily obtained by culturing a for-sale strain of Bifidobacterium Breve FERM BP-11175.
- the method of culturing is not particularly limited, and culturing can be carried out under appropriate conditions according to the properties of this bacterium.
- the culture temperature is usually 25 to 50 ° C, preferably 35 to 42 ° 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 gas.
- the cells may be cultured under slightly aerobic conditions such as liquid static culture.
- the medium for culturing Bifidobacterium Breve FERM BP-11175 is not particularly limited, and a medium usually used for culturing bacteria belonging to the genus Bifidobacterium can be used.
- the carbon source for example, sugars such as glucose, galactose, lactose, arabinose, mannose, sucrose, starch, starch hydrolysate, and waste sugar honey can be used depending on the assimilation property.
- the nitrogen source for example, ammonium salts such as ammonia, ammonium sulfate, ammonium chloride and ammonium nitrate and nitrates can be used.
- the inorganic salts for example, sodium chloride, potassium chloride, potassium phosphate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, ferrous sulfate and the like can be used.
- organic components such as peptone, soybean flour, defatted soybean meal, meat extract and yeast extract may be used.
- the obtained culture may be used as it is after culturing, diluted or concentrated, or cells recovered from the culture may be used.
- Bifidobacterium Breve FERM BP-11175 not only Bifidobacterium Breve FERM BP-11175 but also a culture containing Bifidobacterium Breve FERM BP-11175 and a culture supernatant can be used as an active ingredient.
- a culture it is preferable to culture and proliferate Bifidobacterium Breve FERM BP-11175 and then remove as much as possible other than bacterial cells, and it is more preferable to use a culture consisting substantially only of bacterial cells.
- substantially composed of only bacterial cells means that 95% by mass or more of the total mass of the culture is bacterial cells in terms of wet mass.
- the culture supernatant is a portion of the culture solution obtained when Bifidobacterium Breve FERM BP-11175 is cultured, or a supernatant solution thereof, and the culture supernatant is sterilized by filtering. Is preferable.
- the cognitive function improving agent of the present invention may be composed of only the active ingredient, or may be a composition in which the active ingredient and an arbitrary ingredient other than the active ingredient are blended.
- the optional component is not particularly limited, and an additive (for example, a pharmaceutical carrier described later) conventionally blended in a pharmaceutical product can be blended.
- the content of Bifidobacterium Breve FERM BP-11175 in the cognitive function improving agent of the present invention is not particularly limited, but the daily dose for an effective cognitive function improving effect can be reasonably ingested. It preferably contains Fidobacterium breve, more preferably 1 ⁇ 10 6 to 1 ⁇ 10 12 CFU / g. In addition, it is preferable to administer 1 to 3 g of the cognitive function improving agent of the present invention containing 1 ⁇ 10 6 to 1 ⁇ 10 12 CFU / g of Bifidobacterium Breve FERM BP-11175 per day. In addition, CFU represents a colony forming unit (Colony Forming Unit).
- the cognitive function improving agent of the present invention containing 1 ⁇ 10 6 to 1 ⁇ 10 12 CFU / g of Bifidobacterium Breve FERM BP-11175 may be administered once a day, but at least twice a day. It is preferable to administer in divided doses.
- the cognitive function improving agent of the present invention containing 1 ⁇ 10 6 to 1 ⁇ 10 12 CFU / g of Bifidobacterium Breve FERM BP-11175 is preferably continuously administered every day, for example, for 12 weeks or more. It is more preferred to be administered daily.
- the cognitive function improving agent of the present invention can be appropriately formulated into a desired dosage form according to an administration method such as oral administration or parenteral administration.
- the dosage form is not particularly limited, but in the case of oral administration, for example, a solid preparation such as a powder, a granule, a tablet, a troche, or a capsule; a liquid preparation such as a solution, a syrup, a suspension, or an emulsion. Can be transformed into.
- parenteral administration it can be formulated into, for example, a suppository, a spray, an inhalant, an ointment, a patch, an injection, or the like.
- the formulation can be carried out by a known method as appropriate depending on the dosage form.
- a formulation carrier for example, a pharmaceutically acceptable carrier
- components such as excipients, pH adjusters, colorants, and flavoring agents that are usually used for formulation can be used.
- a component having a known or future-discovered disease or symptom prevention, treatment and / or ameliorating effect can be appropriately used in combination depending on the purpose.
- 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.
- excipient examples include sugar derivatives such as lactose, sucrose, glucose, mannit, and sorbit; starch derivatives such as corn starch, horse bell starch, ⁇ -starch, dextrin, and carboxymethyl starch; crystalline cellulose and hydroxypropyl cellulose.
- binder examples include gelatin; polyvinylpyrrolidone; macrogol and the like in addition to the above-mentioned excipients.
- disintegrant examples include, in addition to the above-mentioned excipients, chemically modified starch or cellulose derivatives such as croscarmellose sodium, carboxymethyl starch sodium, and crosslinked polyvinylpyrrolidone.
- lubricant examples include talc; stearic acid; stearic acid metal salts such as calcium stearate and magnesium stearate; colloidal silica; waxes such as pea gum and gay wax; boric acid; glycol; carboxylic acid such as fumaric acid and adipic acid. Acids; Sodium carboxylates such as sodium benzoate; Sulfates such as sodium sulfate; Leucine; Lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; Stearic acids such as anhydrous silicic acid and silicate hydrate; Stearic acid derivatives and the like Can be mentioned.
- the stabilizer examples 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.
- flavoring agent examples include sweeteners, acidulants, and fragrances.
- 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.
- the cognitive function improving agent of the present invention has a known or future drug having a cognitive function improving action, a drug having an antidepressant action, a drug having an antidepressant action, and an antischizophrenia action. It can also be used in combination with drugs, drugs with antidepressant action, and the like.
- the food or drink for improving cognitive function of the present invention is a food or drink for improving cognitive function for a subject who has not developed dementia, and is Bifidobacterium Breve FERM BP-11175 and Bifidobacterium Breve FERM BP. Includes one or both of the 11175 cultures.
- the cultures of the active ingredients Bifidobacterium Breve FERM BP-11175 and Bifidobacterium Breve FERM BP-11175 are the same as the above-mentioned cognitive function improving agent of the present invention. The same is true.
- Foods and drinks may be liquid, pasty, solid, powder, etc., in addition to confectionery, 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, oils and fats, basic seasonings, complex seasonings / foods, frozen foods, confectionery, beverages, and other commercial foods.
- dairy products include fermented milk, milk drinks, lactic acid bacteria drinks, sweetened milk powder, skim milk powder, sweetened milk powder, adjusted milk powder, cream, cheese, butter, ice creams and the like.
- wheat flour products include bread crumbs, macaroni, spaghetti, noodles, cake mix, fried chicken flour, bread crumbs and the like.
- instant foods include instant noodles, cup noodles, retort / cooked foods, canned foods, microwave foods, instant soups / stews, instant miso soups / soups, canned soups, freeze-dried foods, and other instant foods. Be done.
- 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.
- processed fishery products include canned fishery products, fish hams and sausages, fish paste products, fishery delicacies, and tsukudani.
- processed livestock products include canned livestock and pastes, livestock ham and sausage.
- fats and oils include butter, margarines, vegetable oils and the like.
- the basic seasoning include soy sauce, miso, sauces, processed tomato seasonings, mirins, vinegars and the like, and the compound seasonings / foods include cooking mixes, curry ingredients, sauces, etc.
- Examples include dressings, mentsuyu, spices, and other complex seasonings.
- the frozen food include raw material frozen food, semi-cooked frozen food, and cooked frozen food.
- 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 juices, 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 foods, sprinkles, and ochazuke seaweed.
- dairy products are particularly preferable, and fermented milk is particularly preferable.
- fermented milk is particularly preferable.
- the food or drink for improving cognitive function of the present invention can be applied to foods with functional claims that display the effect of improving cognitive function.
- the cognitive function maintaining agent of the present invention is a cognitive function maintaining agent containing either or both of the cultures of Bifidobacterium Breve FERM BP-11175 and Bifidobacterium Breve FERM BP-11175 as active ingredients. ..
- the administration target, administration route, active ingredient and formulation of the cognitive function maintaining agent of the present invention are the same as those of the above-mentioned cognitive function improving agent of the present invention.
- the maintenance of cognitive function does not show a significant decrease in one or more of the MMSE score, the RBANS total score, and the health check of the head before and after the administration of the cognitive function maintaining agent of the present invention.
- Means As for the maintenance of cognitive function, it is preferable that no significant score decrease is observed in each area of immediate memory, visuospatial / composition and delayed memory, and one or more of the comprehensive evaluation points, especially in RBANS. It is more preferred that no significant score reduction is observed in at least one of the constructive and delayed memory regions. In addition, it is desirable that no significant decrease in MPI score is observed in the health check of the head.
- Food and drink for maintaining cognitive function It is the same as the above-mentioned food and drink for improving cognitive function of the present invention.
- the food or drink for maintaining cognitive function of the present invention can be applied to foods with functional claims that display the effect of maintaining cognitive function.
- the "display" is performed by an expression that allows the consumer to directly recognize the above-mentioned use.
- the act of transferring a product related to food and drink or the packaging of the product that describes 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.
- the display content is a display 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).
- labeling includes health foods, functional foods, foods for the sick, enteral nutrition foods, special purpose foods, health functional foods, specified health foods, functional labeled foods, nutritional functional foods, and pharmaceutical departments. Labeling as a foreign product is also mentioned. Among these, in particular, labeling approved by the Consumer Affairs Agency, for example, a food system for specified health use, a food system with functional labeling, and labeling approved by a system similar to these can be mentioned. More specifically, labeling as a food for specified health use, labeling as a food for specified health use with conditions, labeling as a food with functional claims, labeling to the effect that it affects the structure and function of the body, labeling for reducing the risk of illness, etc. Can be mentioned.
- the wording used for displaying as described above is not limited to words such as cognitive function improvement / improvement / prevention, and other words may be related to cognition and learning. Needless to say, any wording that expresses the effect of prevention, treatment and / or improvement of a disease or symptom is included in the scope of the present technology.
- Such words include, for example, "for those who are worried about memory deterioration,” “for those who want to improve cognitive function,” “for those who are concerned about cognitive function,” and “to become Alzheimer-type dementia in the future.” "For those who want to prevent” "For those who want to improve cognitive accuracy” "For those who want to support information such as numbers, words, figures, situations” "Improve the accuracy of memory and judgment that are part of cognitive function” "For those who want to have memory” "For those who want to maintain their memory” "For those who want to support the maintenance of cognitive function in healthy middle-aged people” "For those who are concerned about forgetfulness or mild cognitive impairment (MCI)” "Forgetfulness” To make consumers aware of the effects of maintaining, promoting, and improving cognitive and learning functions, such as “for middle-aged and older people who are concerned about” and “for middle-aged and older people who are concerned about mild cognitive impairment (MCI)". It is also possible to display based on various uses.
- the hippocampal function improving agent of the present invention is a hippocampal function improving agent containing either or both of the cultures of Bifidobacterium Breve FERM BP-11175 and Bifidobacterium Breve FERM BP-11175 as active ingredients. ..
- the hippocampus is a part of the hippocampal formation, which is a part of the limbic system, and is involved in the memory and spatial learning ability of the brain.
- the hippocampus is known as the main lesion site in Alzheimer's disease. Improvements in hippocampal function are particularly significant in preventing or delaying the onset of Alzheimer's disease.
- the subject to which the hippocampal function improving agent of the present invention is administered is not particularly limited, but a subject who has not developed dementia is preferable.
- the subject who does not develop the dementia is the same as the subject to which the above-mentioned cognitive function improving agent of the present invention is administered.
- the administration route, active ingredient and formulation of the hippocampal function improving agent of the present invention are the same as those of the above-mentioned cognitive function improving agent of the present invention.
- the improvement of hippocampal function is one of the areas of immediate memory, visual space / composition, and delayed memory controlled by the hippocampus and the comprehensive evaluation point in RBANS before and after administration of the hippocampal function improving agent of the present invention.
- Food and drink for improving hippocampal function It is the same as the above-mentioned food and drink for improving cognitive function of the present invention.
- the food and drink for improving hippocampus function of the present invention can be applied to foods with functional claims that display the effect of improving hippocampal function.
- the hippocampal function maintaining agent of the present invention is a hippocampal function improving agent containing either or both of the cultures of Bifidobacterium Breve FERM BP-11175 and Bifidobacterium Breve FERM BP-11175 as active ingredients. ..
- the administration target, administration route, active ingredient and formulation of the hippocampal function maintaining agent of the present invention are the same as those of the above-mentioned hippocampal function improving agent of the present invention.
- the maintenance of hippocampal function is one of the areas of immediate memory, visual space / composition, and delayed memory controlled by the hippocampus and the overall evaluation point in RBANS before and after administration of the hippocampal function improving agent of the present invention.
- Food and drink for maintaining hippocampal function It is the same as the above-mentioned food and drink for improving cognitive function of the present invention.
- the food and drink for maintaining hippocampus function of the present invention can be applied to foods with functional claims that display the effect of maintaining hippocampal function.
- Test example of higher brain function improvement effect by ingestion of probiotics for people suspected of having mild cognitive impairment-Placebo-controlled randomized double-blind parallel group comparison study Japanese nationals aged 50 to 80 years Men and women were recruited from volunteer banks, and 80 of them who met the selection criteria and did not violate the exclusion criteria were selected based on the MMSE and RBANS scores.
- the selection criteria for the subjects are the following three. (1) Males or females of Japanese nationality between the ages of 50 and 80 (2) Those who have a MMSE score of 22 points or more (3) Those who have obtained informed consent The following 17 criteria are excluded from the subjects. ..
- MMSE score a cutoff value is generally used in which 23 points or less is suspected to be dementia, but the specificity is increased by setting the cutoff value to 22 points or less.
- MCI mild cognitive impairment
- the probiotic group took probiotic capsules (including more than 10 billion Bifidobacterium Breve FERM BP-11175 per capsule) for 16 weeks, 2 capsules / day, and the placebo group took placebo capsules (starch). (Included in capsules) was ingested 2 tablets / day for 16 weeks. After 16 weeks, RBANS and head health checks were performed again, and the scores before and after ingestion were compared.
- Bifidobacterium Breve FERM BP-11175 has the effect of maintaining and improving cognitive function that declines with aging. It is known that the hippocampus plays a role in the areas of immediate memory, visual space / composition, and delayed memory for which improvement was observed in RBANS. Therefore, it is suggested that Bifidobacterium Breve FERM BP-11175 improved the function of the hippocampus.
- the Atama Health Check (JMCIS) is a test that can easily and accurately express minute changes in cognitive function in the healthy person-boundary area-MCI area with an interactive check of about 10 minutes.
- the cognitive function index is calculated using a unique algorithm and database based on information such as the subject's gender, age, years of study, and race (provided by Millenia Co., Ltd.).
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Abstract
Description
本願は、2020年6月18日に、日本に出願された特願2020-105650号に基づき優先権を主張し、その内容をここに援用する。
[2] 前記認知症を発症していない対象が、認知症を発症していないが、加齢に伴う脳の認知機能の低下が気になる対象である、[1]に記載の認知機能改善剤。
[3] 前記認知症を発症していない対象が、認知症を発症していないが、加齢に伴う複合的な認知機能の低下が気になる対象である、[1]に記載の認知機能改善剤。
[4] 前記認知症を発症していない対象が、健常者からなる群、軽度認知障害者からなる群並びに健常者及び軽度認知障害者からなる群から選択される、[1]に記載の認知機能改善剤。
[5] 前記認知症を発症していない対象が、MMSEスコアが22以上であり、かつ、RBANS合計スコアが65以下又はあたまの健康チェックのスコアが75以下である対象である、[1]に記載の認知機能改善剤。
[6] ビフィドバクテリウム・ブレーベを1×106~1×1012CFU/g含む、[1]~[5]のいずれかに記載の認知機能改善剤。
[7] ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を含む、認知症を発症していない対象のための認知機能改善用飲食品。
[8] 認知症を発症していない対象に投与するための認知機能改善剤の製造のための、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方の使用。
[10] 前記認知症を発症していない対象が、認知症を発症していないが、加齢に伴う脳の認知機能の低下が気になる対象である、[9]に記載の認知機能維持剤。
[11] 前記認知症を発症していない対象が、認知症を発症していないが、加齢に伴う複合的な認知機能の低下が気になる対象である、[9]に記載の認知機能維持剤。
[12] 前記認知症を発症していない対象が、健常者からなる群、軽度認知障害者からなる群並びに健常者及び軽度認知障害者からなる群から選択される、[9]に記載の認知機能維持剤。
[13] 前記認知症を発症していない対象が、MMSEスコアが22以上であり、かつ、RBANS合計スコアが65以下又はあたまの健康チェックのスコアが75以下である対象である、[9]に記載の認知機能維持剤。
[14] ビフィドバクテリウム・ブレーベを1×106~1×1012CFU/g含む、[9]~[13]のいずれかに記載の認知機能維持剤。
[15] ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を含む、認知症を発症していない対象のための認知機能維持用飲食品。
[16] 認知症を発症していない対象に投与するための認知機能維持剤の製造のための、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方の使用。
[18] 認知症を発症していない対象に投与するための、[17]に記載の海馬機能改善剤。
[19] 前記認知症を発症していない対象が、健常者からなる群、軽度認知障害者からなる群並びに健常者及び軽度認知障害者からなる群から選択される、[18]に記載の海馬機能改善剤。
[20] 前記認知症を発症していない対象が、MMSEスコアが22以上であり、かつ、RBANS合計スコアが65以下又はあたまの健康チェックのスコアが75以下である対象である、[18]に記載の海馬機能改善剤。
[21] ビフィドバクテリウム・ブレーベを1×106~1×1012CFU/g含む、[17]~[20]のいずれかに記載の海馬機能改善剤。
[22] ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を含む、海馬機能改善用飲食品。
[23] 海馬機能改善剤の製造のための、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方の使用。
[25] 認知症を発症していない対象に投与するための[24]に記載の海馬機能維持剤。
[26] 前記認知症を発症していない対象が、健常者及び軽度認知障害者からなる群から選択される、[25]に記載の海馬機能維持剤。
[27] 前記認知症を発症していない対象が、MMSEスコアが22以上であり、かつ、RBANS合計スコアが65以下又はあたまの健康チェックのスコアが75以下である対象である、[25]に記載の海馬機能維持剤。
[28] ビフィドバクテリウム・ブレーベを1×106~1×1012CFU/g含む、[24]~[27]のいずれかに記載の海馬機能維持剤。
[29] ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を含む、海馬機能維持用飲食品。
[30] 海馬機能維持剤の製造のための、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方の使用。
MMSEスコアは、MMSE(Mini Mental State Examination;ミニメンタルステート検査)によって算出されるスコアである。MMSEは、臨床および研究において国際的に広く用いられている認知機能障害のスクリーニング法である。見当識、言語性記憶、全般性注意・計算、言語、図形模写に関する検査で、30点満点である。MMSEスコアが低いほど認知機能低下が進んでいることを示す。
RBANSスコアは、RBANS(Repeatable Battery for the Assessment of Neuropsychological Status;アーバンス)によって算出されるスコアである。RBANSは、1998年にRandolphにより開発され、全米で標準化された神経心理学検査で、即時記憶、遅延記憶、視空間・構成、言語、注意の5つの認知領域を評価する。12個の試験から構成されており、各試験の粗点から年齢等を加味した換算表により各認知領域の評価点を算出する(レジリオ株式会社より提供)。RBANSスコアが低いほど認知機能低下が進んでいることを示す。
あたまの健康チェック(JMCIS)(登録商標)は、健常者~境界域~MCI領域の微細な認知機能の変化を10分程度の対話式チェックで簡易に高い精度で定量表現することが出来る検査である。対象者の性別、年齢、学習年数、人種などの情報を基に、独自のアルゴリズムとデータベースを用いて認知機能指数を算出する(株式会社ミレニアより提供)。あたまの健康チェックにより評価、算出される個人の認知機能を客観的に示す指数であるMPI(Memory Performance Index:認知機能指数)スコア(以下「MPIスコア」又は「あたまの健康チェックのスコア」という。)が低いほど認知機能低下が進んでいることを示す。
FERMは、NITE特許生物寄託センター(NITE-IPOD;NITE Internatinal Patent Organism Depositary)を示す記号である。なお、NITEは、National Institute of Technology and Evaluation(独立行政法人製品評価技術基盤機構)の略称である。
本発明の認知機能改善剤は、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を有効成分とする認知機能改善剤である。
本発明の認知機能改善剤の投与の対象は、認知症を発症していない対象である。
前記対象は、通常ヒトであるが、ヒト以外の哺乳動物、例えば、イヌ、ネコ等のペット動物、ウシ、ヒツジ、ブタ等の家畜に投与することも可能である。以下では、対象がヒトである場合について説明する。
(1)認知症を発症していないが、加齢に伴う脳の認知機能の低下が気になる対象。
(2)認知症を発症していないが、加齢に伴う複合的な認知機能の低下が気になる対象。
(3)健常者からなる群、軽度認知障害者からなる群並びに健常者及び軽度認知障害者からなる群から選択される対象。
(4)MMSEスコアが22以上であり、かつ、RBANS合計スコアが65以下又はあたまの健康チェックのスコアが75以下である対象。前記RBANS合計スコアは、41以下が好ましい。前記あたまの健康チェックのスコアは50.2以下が好ましい。
本発明の認知機能改善剤の投与経路は、例えば、経口投与、腹腔内投与、筋肉内投与、経粘膜投与、鼻腔内投与、直腸内投与等が挙げられるが、特に、経口投与が好ましい。
本発明において、認知機能の改善は、本発明の認知機能改善剤の投与の前後で、MMSEスコア、RBANS合計スコア及びあたまの健康チェックのうち1つ以上にスコア増加が認められることを意味する。認知機能の改善としては、特に、RBANSにおいて、即時記憶、視空間・構成及び遅延記憶の各領域並びに総合評価点のうち1つ以上においてスコア増加が認められることが好ましく、視空間・構成及び遅延記憶のうち少なくとも一方の領域においてスコア増加が認められることがより好ましい。また、あたまの健康チェックにおいてMPIスコアの増加が認められることが望ましい。
本発明の認知機能改善剤の有効成分は、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方である。
ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方は、本発明の認知機能改善剤の製造のために使用される。
具体的には、例えば、培養温度は、通常、25~50℃であり、35~42℃が好ましい。また、培養は嫌気条件下で行うことが好ましく、例えば、炭酸ガス等の嫌気ガスを通気しながら培養できる。また、液体静置培養等の微好気条件下で培養してもよい。
なお、前記培養物としては、ビフィドバクテリウム・ブレーベ FERM BP-11175を培養して増殖した後、細菌体以外を極力除去したものが好ましく、実質的に細菌体のみからなるものがより好ましい。ここで、「実質的に細菌体のみからなる」とは、湿質量で、培養物の全質量の95質量%以上が細菌体であることを意味する。
培養上清とは、ビフィドバクテリウム・ブレーベ FERM BP-11175を培養した際に得られる培養液部分、又はその上澄み溶液であり、培養上清は、フィルタリングにより除菌処理されたものであることが好ましい。
前記任意成分は、特に限定されず、従来、医薬品に配合されている添加剤(例えば、後述する製剤担体など)を配合できる。
また、ビフィドバクテリウム・ブレーベ FERM BP-11175を1×106~1×1012CFU/g含む本発明の認知機能改善剤を、1日当たり1~3g投与することが好ましい。なお、CFUは、コロニー形成単位(Colony Forming Unit)を表す。
ビフィドバクテリウム・ブレーベ FERM BP-11175を1×106~1×1012CFU/g含む本発明の認知機能改善剤は、1日あたり1回の投与でも良いが、1日あたり2回以上に分けて投与されることが好ましい。
また、ビフィドバクテリウム・ブレーベ FERM BP-11175を1×106~1×1012CFU/g含む本発明の認知機能改善剤は、毎日継続して投与されることが好ましく、例えば12週間以上毎日投与されることがより好ましい。
本発明の認知機能改善剤は、経口投与や非経口投与等の投与方法に応じて適宜所望の剤形に製剤化することができる。その剤形は特に限定されないが、経口投与の場合、例えば、散剤、顆粒剤、錠剤、トローチ剤、カプセル剤等の固形製剤;溶液剤、シロップ剤、懸濁剤、乳剤等の液剤等に製剤化することができる。非経口投与の場合、例えば、座剤、噴霧剤、吸入剤、軟膏剤、貼付剤、注射剤等に製剤化することができる。本技術では、経口投与の剤形に製剤化することが好ましい。
なお、製剤化は剤形に応じて、適宜、公知の方法により実施できる。
固形製剤の場合の担体としては、例えば、賦形剤、結合剤、崩壊剤、滑沢剤、安定剤、矯味矯臭剤等が挙げられる。
なお、経口投与用の液剤の場合に使用する担体としては、水等の溶剤、矯味矯臭剤等が挙げられる。
本発明の認知機能改善用飲食品は、認知症を発症していない対象のための認知機能改善用飲食品であり、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を含む。
認知症を発症していない対象、有効成分であるビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物については、上述した本発明の認知機能改善剤と同様である。
小麦粉製品としては、例えば、パン、マカロニ、スパゲッティ、めん類、ケーキミックス、から揚げ粉、パン粉等が挙げられる。
即席食品類としては、例えば、即席めん、カップめん、レトルト・調理食品、調理缶詰め、電子レンジ食品、即席スープ・シチュー、即席みそ汁・吸い物、スープ缶詰め、フリーズ・ドライ食品、その他の即席食品等が挙げられる。
農産加工品としては、例えば、農産缶詰め、果実缶詰め、ジャム・マーマレード類、漬物、煮豆類、農産乾物類、シリアル(穀物加工品)等が挙げられる。
水産加工品としては、例えば、水産缶詰め、魚肉ハム・ソーセージ、水産練り製品、水産珍味類、つくだ煮類等が挙げられる。
畜産加工品としては、例えば、畜産缶詰め・ペースト類、畜肉ハム・ソーセージ等が挙げられる。
油脂類としては、例えば、バター、マーガリン類、植物油等が挙げられる。
基礎調味料としては、例えば、しょうゆ、みそ、ソース類、トマト加工調味料、みりん類、食酢類等が挙げられ、前記複合調味料・食品類として、調理ミックス、カレーの素類、たれ類、ドレッシング類、めんつゆ類、スパイス類、その他の複合調味料等が挙げられる。
冷凍食品としては、例えば、素材冷凍食品、半調理冷凍食品、調理済冷凍食品等が挙げられる。
菓子類としては、例えば、キャラメル、キャンディー、チューインガム、チョコレート、クッキー、ビスケット、ケーキ、パイ、スナック、クラッカー、和菓子、米菓子、豆菓子、デザート菓子、その他の菓子等が挙げられる。
飲料類としては、例えば、炭酸飲料、天然果汁、果汁飲料、果汁入り清涼飲料、果肉飲料、果粒入り果実飲料、野菜系飲料、豆乳、豆乳飲料、コーヒー飲料、お茶飲料、粉末飲料、濃縮飲料、スポーツ飲料、栄養飲料、アルコール飲料、その他の嗜好飲料等が挙げられる。
前記以外の市販食品としては、例えば、ベビーフード、ふりかけ、お茶漬けのり等が挙げられる。
本発明の認知機能維持剤は、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を有効成分とする認知機能維持剤である。
本発明において、認知機能の維持は、本発明の認知機能維持剤の投与の前後で、MMSEスコア、RBANS合計スコア及びあたまの健康チェックのうち1つ以上に有意なスコア減少が認められないことを意味する。認知機能の維持としては、特に、RBANSにおいて、即時記憶、視空間・構成及び遅延記憶の各領域並びに総合評価点のうち1つ以上において有意なスコア減少が認められないことが好ましく、視空間・構成及び遅延記憶のうち少なくとも一方の領域において有意なスコア減少が認められないことがより好ましい。また、あたまの健康チェックにおいてMPIスコアの有意な減少が認められないことが望ましい。
上述した本発明の認知機能改善用飲食品と同様である。
本発明の認知機能維持用飲食品は、認知機能維持効果を表示する機能性表示食品に応用できる。
また、本技術で定義される飲食品等は、特定の用途(特に保健の用途)や機能が表示された飲食品として提供・販売されることも可能である。
「表示」行為には、需要者に対して前記用途を知らしめるための全ての行為が含まれ、前記用途を想起・類推させうるような表現であれば、表示の目的、表示の内容、表示する対象物・媒体等の如何に拘わらず、全て本技術の「表示」行為に該当する。
本発明の海馬機能改善剤は、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を有効成分とする海馬機能改善剤である。
前記認知症を発症していない対象は、上述した本発明の認知機能改善剤の投与対象と同様である。
本発明において、海馬機能の改善は、本発明の海馬機能改善剤の投与の前後で、RBANSにおいて、海馬が司る即時記憶、視空間・構成及び遅延記憶の各領域並びに総合評価点のうち1つ以上においてスコア増加が認められることが好ましく、視空間・構成及び遅延記憶のうち少なくとも一方の領域においてスコア増加が認められることが好ましい。
上述した本発明の認知機能改善用飲食品と同様である。
本発明の海馬機能改善用飲食品は、海馬機能改善効果を表示する機能性表示食品に応用できる。
本発明の海馬機能維持剤は、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を有効成分とする海馬機能改善剤である。
本発明において、海馬機能の維持は、本発明の海馬機能改善剤の投与の前後で、RBANSにおいて、海馬が司る即時記憶、視空間・構成及び遅延記憶の各領域並びに総合評価点のうち1つ以上において有意なスコア減少が認められないことが好ましく、視空間・構成及び遅延記憶のうち少なくとも一方の領域において有意なスコア減少が認められないことがより好ましい。
上述した本発明の認知機能改善用飲食品と同様である。
本発明の海馬機能維持用飲食品は、海馬機能維持効果を表示する機能性表示食品に応用できる。
50歳以上80歳未満の日本国籍の男性及び女性をボランティアバンクから集め、選択基準を満たし、除外基準に抵触しない方の中で、MMSEとRBANSのスコアに基づいて80名を選抜した。
被験者の選択基準は下記の3つである。
(1)50歳以上80歳未満の日本国籍の男性または女性
(2)MMSEのスコアが22点以上の方
(3)インフォームドコンセントを取得できた方
被験者の除外基準は下記の17個である。
(1)認知症と診断されている方
(2)現在、医師の管理下において、運動または食事療法を行っている方
(3)試験食品によりアレルギー発症のおそれがある方
(4)薬物依存、アルコール依存の現病または既往のある方
(5)精神障害(うつ病など)や睡眠障害等で通院中、または過去に精神疾患の既往がある方
(6)夜間勤務または交代制勤務の方
(7)食事、睡眠等の生活習慣が極度に不規則な方
(8)極端な偏食をしている方
(9)糖尿病、肝疾患(肝炎)、腎疾患、心疾患等の重篤な疾患、甲状腺疾患、副腎疾患、その他代謝性の重篤な疾患の現病、既往又は合併症を有する方
(10)認知機能に影響を及ぼす健康食品、サプリメント、及び医薬品を使用している方
(11)消化管の手術を受けたことのある方(虫垂炎を除く)
(12)同意取得日から遡って3ヵ月以内に他の臨床試験(研究)に参加していた方、あるいは試験期間中に他の臨床試験(研究)に参加する計画がある方
(13)同意取得日から遡って1ヵ月以内に200mLあるいは3ヵ月以内に400mLを超える採血、成分献血を行った方
(14)現在、妊娠又は授乳をしている、又は、試験期間中にその可能性のある方
(15)各種調査票への記録遵守が困難な方
(16)スクリーニング時の臨床検査値及び計測値から、被験者として不適当と判断された方
(17)その他、試験責任医師が被験者として不適当と判断した方
その上で、RBANSのスコアが低い方を中心に選抜し、軽度認知障害(MCI)の疑いがある方80名を選抜した。
選抜した80名は、あたまの健康チェックを実施した後、性別・年齢・RBANSのスコアを割付因子とした層別ランダム化により、プロバイオティクス群(ビフィドバクテリウム・ブレーベ FERM BP-11175摂取群)とプラセボ群の2群に均等に分けられた。試験食品として、表1に示す2種類のカプセル食品を作製した。プロバイオティクス群はプロバイオティクスカプセル(ビフィドバクテリウム・ブレーベ FERM BP-11175をカプセル1個あたり100億個以上含む)を16週間、2個/日摂取し、プラセボ群はプラセボカプセル(デンプンをカプセルに含む)を16週間、2個/日摂取した。16週間後、再度RBANS及びあたまの健康チェックを実施し、摂取前後の点数を比較した。
RBANSの変動値に関しても、評価点合計、即時記憶、視空間・構成、遅延記憶の領域において、ビフィドバクテリウム・ブレーベ FERM BP-11175摂取群が改善した(図2)。
また、あたまの健康チェックも同様にビフィドバクテリウム・ブレーベ FERM BP-11175摂取群の改善が前後比較ならびに変動値において認められた(図3)。
なお、RBANSで改善が認められた即時記憶、視空間・構成、遅延記憶の領域はいずれも海馬が機能を担うことが知られている。そのためビフィドバクテリウム・ブレーベ FERM BP-11175は海馬の機能を改善したことが示唆される。
Claims (30)
- ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を有効成分とする、認知症を発症していない対象に投与するための認知機能改善剤。
- 前記認知症を発症していない対象が、認知症を発症していないが、加齢に伴う脳の認知機能の低下が気になる対象である、請求項1に記載の認知機能改善剤。
- 前記認知症を発症していない対象が、認知症を発症していないが、加齢に伴う複合的な認知機能の低下が気になる対象である、請求項1に記載の認知機能改善剤。
- 前記認知症を発症していない対象が、健常者からなる群、軽度認知障害者からなる群並びに健常者及び軽度認知障害者からなる群から選択される、請求項1に記載の認知機能改善剤。
- 前記認知症を発症していない対象が、MMSEスコアが22以上であり、かつ、RBANS合計スコアが65以下又はあたまの健康チェックのスコアが75以下である対象である、請求項1に記載の認知機能改善剤。
- ビフィドバクテリウム・ブレーベを1×106~1×1012CFU/g含む、請求項1~5のいずれか1項に記載の認知機能改善剤。
- ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を含む、認知症を発症していない対象のための認知機能改善用飲食品。
- 認知症を発症していない対象に投与するための認知機能改善剤の製造のための、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方の使用。
- ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を有効成分とする、認知症を発症していない対象に投与するための認知機能維持剤。
- 前記認知症を発症していない対象が、認知症を発症していないが、加齢に伴う脳の認知機能の低下が気になる対象である、請求項9に記載の認知機能維持剤。
- 前記認知症を発症していない対象が、認知症を発症していないが、加齢に伴う複合的な認知機能の低下が気になる対象である、請求項9に記載の認知機能維持剤。
- 前記認知症を発症していない対象が、健常者からなる群、軽度認知障害者からなる群並びに健常者及び軽度認知障害者からなる群から選択される、請求項9に記載の認知機能維持剤。
- 前記認知症を発症していない対象が、MMSEスコアが22以上であり、かつ、RBANS合計スコアが65以下又はあたまの健康チェックのスコアが75以下である対象である、請求項9に記載の認知機能維持剤。
- ビフィドバクテリウム・ブレーベを1×106~1×1012CFU/g含む、請求項9~13のいずれか1項に記載の認知機能維持剤。
- ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を含む、認知症を発症していない対象のための認知機能維持用飲食品。
- 認知症を発症していない対象に投与するための認知機能維持剤の製造のための、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方の使用。
- ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を有効成分とする、海馬機能改善剤。
- 認知症を発症していない対象に投与するための、請求項17に記載の海馬機能改善剤。
- 前記認知症を発症していない対象が、健常者からなる群、軽度認知障害者からなる群並びに健常者及び軽度認知障害者からなる群から選択される、請求項18に記載の海馬機能改善剤。
- 前記認知症を発症していない対象が、MMSEスコアが22以上であり、かつ、RBANS合計スコアが65以下又はあたまの健康チェックのスコアが75以下である対象である、請求項18に記載の海馬機能改善剤。
- ビフィドバクテリウム・ブレーベを1×106~1×1012CFU/g含む、請求項17~20のいずれか1項に記載の海馬機能改善剤。
- ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を含む、海馬機能改善用飲食品。
- 海馬機能改善剤の製造のための、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方の使用。
- ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を有効成分とする、海馬機能維持剤。
- 認知症を発症していない対象に投与するための請求項24に記載の海馬機能維持剤。
- 前記認知症を発症していない対象が、健常者からなる群、軽度認知障害者からなる群並びに健常者及び軽度認知障害者からなる群から選択される、請求項25に記載の海馬機能維持剤。
- 前記認知症を発症していない対象が、MMSEスコアが22以上であり、かつ、RBANS合計スコアが65以下又はあたまの健康チェックのスコアが75以下である対象である、請求項25に記載の海馬機能維持剤。
- ビフィドバクテリウム・ブレーベを1×106~1×1012CFU/g含む、請求項24~27のいずれか1項に記載の海馬機能維持剤。
- ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方を含む、海馬機能維持用飲食品。
- 海馬機能維持剤の製造のための、ビフィドバクテリウム・ブレーベ FERM BP-11175及びビフィドバクテリウム・ブレーベ FERM BP-11175の培養物のいずれか一方又は両方の使用。
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CN202310052444.9A CN115944656A (zh) | 2020-06-18 | 2021-04-21 | 认知功能改善剂、认知功能维持剂、海马体功能改善剂和海马体功能维持剂 |
JP2022532341A JP7189393B2 (ja) | 2020-06-18 | 2021-04-21 | 認知機能改善剤、認知機能維持剤、海馬機能改善剤及び海馬機能維持剤 |
AU2021293331A AU2021293331A1 (en) | 2020-06-18 | 2021-04-21 | Cognitive function improving agent, cognitive function maintaining agent, hippocampus function improving agent, and hippocampus function maintaining agent |
US18/009,966 US20230218686A1 (en) | 2020-06-18 | 2021-04-21 | Cognitive Function Improving Agent, Cognitive Function Maintaining Agent, Hippocampus Function Improving Agent, and Hippocampus Function Maintaining Agent |
CN202180042471.7A CN115803039A (zh) | 2020-06-18 | 2021-04-21 | 认知功能改善剂、认知功能维持剂、海马体功能改善剂和海马体功能维持剂 |
BR112022025078A BR112022025078A2 (pt) | 2020-06-18 | 2021-04-21 | Agentes de aperfeiçoamento e de manutenção da função cognitiva e da função do hipocampo, alimentos ou bebidas de aperfeiçoamento e de manutenção da função cognitiva e da função do hipocampo, e, uso de uma ou ambas de bifidobacterium breve ferm bp-11175 e uma cultura de bifidobacterium breve ferm bp-11175 |
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