Compositions, foods and beverages, and pharmaceuticals for preventing or improving cognitive decline.
Lactic acid bacteria from the genus Fructobacillus, particularly Fructobacillus fructosus OS-1010, are used to create compositions that enhance cognitive functions by preventing decline, demonstrating effectiveness in improving memory and learning abilities.
Patent Information
- Application Number
- JP2025264254
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-12-27
- Filing Date
- 2025-12-18
- Publication Date
- 2026-07-09
AI Technical Summary
There is a need for further options to prevent and improve cognitive decline in today's rapidly aging society, as existing technologies using microorganisms have limitations.
The use of lactic acid bacteria belonging to the genus Fructobacillus, particularly Fructobacillus fructosus strains like OS-1010, in compositions for preventing or improving cognitive decline, including their cultures, culture supernatants, and extracts.
The compositions effectively prevent and improve cognitive functions such as memory and learning ability, maintaining cognitive function comparable to that of younger individuals.
Smart Images

Figure 2026116202000001_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to a composition for preventing or improving cognitive function decline containing lactic acid bacteria, and food and drink products and pharmaceuticals containing the composition.
Background Art
[0002] According to the White Paper on the Elderly for fiscal year 2017, the number of dementia patients in 2012 was approximately 4.6 million, which corresponds to 15% of the elderly population. Further, it is estimated that one in five people, that is, 20% will develop dementia by 2025. The main factor of dementia is aging, and in the super-aged society that Japan is facing, preventing and improving cognitive function decline has become an important issue for maintaining the quality of life of the elderly.
[0003] So far, it has been reported that the decline of cognitive functions such as memory can be prevented by the action of microorganisms such as lactic acid bacteria. For example, in Patent Document 1, it has been reported that feeding Lactococcus lactis subsp. cremoris H-61 strain, which is a lactic acid bacterium, to mice for 10 months suppresses the decline of memory. Further, in Patent Document 2, it has been reported that the ingestion of Bifidobacterium bifidum OLB6378 strain, which is a bifidobacterium, improves the brain function of newborns.
Prior Art Documents
Patent Documents
[0004]
Patent Document 1
Patent Document 2
Summary of the Invention
Problems to be Solved by the Invention
[0005] While technologies already exist that use microorganisms to prevent memory decline, in today's rapidly aging society, there is a need for further options for preventing and improving cognitive decline. [Means for solving the problem]
[0006] As a result of diligent research to solve the above problems, the inventors of this invention discovered that lactic acid bacteria belonging to the genus Fructobacillus are effective in preventing and improving cognitive decline, and thus completed the present invention.
[0007] In other words, the present invention provides inventions relating to the following embodiments. [Item 1] A composition for preventing or improving cognitive decline, comprising as an active ingredient lactic acid bacteria belonging to the genus Fructobacillus, a culture of the lactic acid bacteria, the culture supernatant of the lactic acid bacteria, and / or an extract of the lactic acid bacteria. [Item 2] The composition for preventing or improving cognitive decline according to Item 1, wherein the lactic acid bacteria is Fructobacillus fructosus. [Item 3] The composition for preventing or improving cognitive decline according to item 1 or 2, wherein the lactic acid bacterium is Fructobacillus fructosus OS-1010 strain. [Item 4] A pharmaceutical product containing a composition for preventing or improving cognitive decline as described in any one of Items 1 to 3. [Item 5] Food or beverage containing a composition for preventing or improving cognitive decline as described in any one of Items 1 to 3. [Effects of the Invention]
[0008] The present invention provides a composition for preventing or improving cognitive decline. Furthermore, the present invention provides lactic acid bacteria belonging to the genus Fructobacillus, a culture of said lactic acid bacteria, the culture supernatant of said lactic acid bacteria, and / or an extract of said lactic acid bacteria as active ingredients in the composition for preventing or improving cognitive decline. The above composition exhibits effects such as preventing cognitive decline or improving cognitive function. In addition, the above composition may exhibit effects that lead to improvements in brain function, such as preventing age-related cognitive decline or improving cognitive function.
[0009] More specifically, for example, lactic acid bacteria belonging to Fructobacillus fructosus, such as Fructobacillus fructosus strain NBRC-3516 and Fructobacillus fructosus strain OS-1010 (accession number: NITE BP-03818), cultures of said lactic acid bacteria, culture supernatants of said lactic acid bacteria, and / or extracts of said lactic acid bacteria are active ingredients in compositions for preventing or improving cognitive decline. [Brief explanation of the drawing]
[0010] [Figure 1] This figure shows the Discrimination Index (DI) in the example. The results shown in this figure explain the improvement in memory due to the intake of Fructobacillus fructosus OS-1010 strain powder. [Figure 2] This figure shows the percentage of search time for each object in the example. The results shown in this figure explain the improvement in memory and learning ability due to the ingestion of Fructobacillus fructosus OS-1010 strain powder. [Modes for carrying out the invention]
[0011] The present invention provides a composition for preventing or improving cognitive decline, containing as an active ingredient lactic acid bacteria belonging to the genus Fructobacillus, a culture of the lactic acid bacteria, the culture supernatant of the lactic acid bacteria, and / or an extract of the lactic acid bacteria. The composition for preventing or improving cognitive decline will be described in detail below. Unless otherwise specified, terms used herein shall be interpreted in the sense commonly used in the art.
[0012] Cognitive function is the ability to correctly understand, judge, process, and utilize information about things, and is indispensable for leading a smooth and appropriate daily life. Examples of cognitive function include memory, learning ability, language ability, visuospatial cognitive ability, judgment, calculation ability, and executive ability.
[0013] [1. Active Ingredients] The present invention provides a composition for preventing or improving cognitive decline, which contains a lactic acid bacterium belonging to the genus Fructobacillus, a culture of the lactic acid bacterium, the culture supernatant of the lactic acid bacterium, and / or an extract of the lactic acid bacterium as an active ingredient.
[0014] [1-1. Lactic acid bacteria belonging to the genus Fructobacillus] Examples of lactic acid bacteria belonging to the genus Fructobacillus (hereinafter also referred to as "specified lactic acid bacteria") include Fructobacillus durionis, Fructobacillus tropaeoil, Fructobacillus fructosus, Fructobacillus americanaquae, Fructobacillus apis, Fructobacillus broussonetiae, Fructobacillus cardui, and Fructobacillus evanidus. Examples include *Fructobacillus evanidus*, *Fructobacillus ficulneus*, *Fructobacillus papyriferae*, *Fructobacillus papyrifericola*, *Fructobacillus parabroussonetiae*, and *Fructobacillus pseudoficulneus*.
[0015] More specific examples of lactic acid bacteria belonging to the genus Fructobacillus include Fructobacillus fructosus, and among these, Fructobacillus fructosus strain NBRC3516 and Fructobacillus fructosus strain OS-1010 (NITE BP-03818) are particularly preferred from the perspective of preventing and improving cognitive decline, with Fructobacillus fructosus strain OS-1010 (NITE BP-03818) being especially preferred.
[0016] [1-2. Form of the Active Ingredient] The form of the active ingredient in the present invention is at least any one of the above-mentioned predetermined lactic acid bacteria, a culture of the lactic acid bacteria, a culture supernatant of the lactic acid bacteria, and an extract of the lactic acid bacteria. The active ingredient may be used alone in the form of any one of these, or may be used in combination of forms of a plurality of kinds.
[0017] [1-2-1. Preparation of Lactic Acid Bacteria] When the active ingredient is in the form of lactic acid bacteria, the active ingredient includes the cell components of the lactic acid bacteria and products inherent in or present in the lactic acid bacteria. The lactic acid bacteria may be either viable bacteria or dead bacteria. In the case of dead bacteria, the cells may be disrupted. In the case of disrupted bacteria, a part of the cell components may be removed. Further, the lactic acid bacteria may be in the form of cell powder dried by means such as freeze-drying, shelf-drying, spray-drying, etc.
[0018] The lactic acid bacteria can be obtained by a production method including a step of culturing one or more of the above-mentioned predetermined lactic acid bacteria in a medium (sometimes referred to as the "culturing step"), and a step of separating and recovering the cells (sometimes referred to as the "separation and recovery step"). In the separation and recovery step, the separation and recovery method includes, for example, solid-liquid separation and cell washing. The production method may include a step of drying the cells of the lactic acid bacteria (sometimes referred to as the "drying step"). Further, the production method may include a step of disrupting the lactic acid bacteria (sometimes referred to as the "cell disruption step").
[0019] Examples of the medium in the culturing step include those used for subculture (pre-culture medium) and those used for production culture (main culture medium). The main culture medium can be prepared by further containing additives based on the medium used as the pre-culture medium. Regarding the properties of the medium, it is preferably a liquid medium, but an agar medium may also be used. The medium contains a carbon source, and in addition to the carbon source, it contains a nitrogen source, minerals, etc.
[0020] Carbon sources include carbohydrates and carbohydrate materials. Carbohydrates include sugars (monosaccharides, disaccharides, oligosaccharides), polysaccharides, and sugar alcohols. Specific examples of carbohydrates include lactose, sucrose, glucose, starch, xylitol, and dextrose. Carbohydrate materials can be any organic composition containing carbohydrates, such as milk and its processed products (skim milk powder, whey, milk powder, condensed milk, etc.), soy milk and its processed products (soy milk hydrolysate, etc.), grains, fruits, and vegetables. Milk can be derived from any mammal such as cows, goats, sheep, buffalo, camels, llamas, donkeys, yaks, horses, and reindeer. Carbohydrates may be isolated or contained in carbohydrate materials. For example, fructose (carbohydrate) may be used in the form contained in fruits (carbohydrate materials). Among these carbon sources, glucose is preferred. These carbon sources may be used individually or in combination of multiple types.
[0021] The concentration of the carbon source in the culture medium is not particularly limited and can be set appropriately depending on the type of medium and culture method, but for example, 0.5 to 4 w / w%, preferably 1 to 3 w / w%, and more preferably 1.5 to 2.5 w / w% can be cited.
[0022] Any inorganic or organic nitrogen source can be used as the nitrogen source. Examples include yeast extract (such as brewer's yeast), meat extract, proteins such as casein; protein hydrolysates such as peptone (such as protease peptone), peptides, and nitrogen-containing salts such as ammonium salts (such as ammonium citrate) and nitrates. These nitrogen sources may be used individually or in combination.
[0023] The concentration of the nitrogen source in the culture medium is not particularly limited and can be set appropriately according to the type of medium and culture method, but for proteins, for example, 0.3 to 4 w / w%, preferably 0.5 to 3 w / w%, and more preferably 1 to 2 w / w%; for peptides, for example, 0.1 to 2 w / w%, preferably 0.3 to 1.8 w / w%, and more preferably 0.5 to 1.5 w / w%; and for nitrogen-containing salts, for example, 0.03 to 1.5 w / w%, preferably 0.05 to 1 w / w%, and more preferably 0.1 to 0.5 w / w%.
[0024] Examples of minerals include manganese (e.g., manganese salts such as manganese sulfate), zinc, iron, sodium (e.g., sodium salts such as sodium acetate), potassium (e.g., potassium salts such as dipotassium bisulfate and dipotassium hydrogen phosphate), magnesium (e.g., magnesium salts such as magnesium sulfate), calcium, phosphorus (e.g., phosphates such as dipotassium hydrogen phosphate), sulfur (e.g., sulfates such as manganese sulfate, potassium bisulfate, and magnesium sulfate), and trace elements. Among these minerals, manganese, sodium, magnesium, and potassium are preferred. These minerals may be used individually or in combination.
[0025] The concentration of minerals in the culture medium is not particularly limited and can be set appropriately according to the type of culture medium and culture method, but examples include: for manganese salts, 0.001 to 0.01 w / w%, preferably 0.003 to 0.008 w / w%; for sodium salts, 0.05 to 1.5 w / w%, preferably 0.1 to 1 w / w%; for magnesium salts, 0.001 to 0.02 w / w%, preferably 0.005 to 0.015 w / w%; for potassium salts, 0.05 to 1 w / w%, preferably 0.1 to 0.5 w / w%; for phosphates, 0.05 to 1 w / w%, preferably 0.1 to 0.5 w / w%; and for sulfates, 0.001 to 0.04 w / w%, preferably 0.005 to 0.02 w / w%.
[0026] In addition to the components mentioned above, the culture medium may also contain other components such as vitamins (e.g., B vitamins), surfactants (e.g., nonionic surfactants (e.g., Tween), anionic surfactants (e.g., SDS), antibacterial agents (e.g., triclosan), and antibiotics (e.g., monesin). These other components may be used individually or in combination. Among these other components, surfactants are preferred, and nonionic surfactants are more preferred.
[0027] The concentrations of other components in the culture medium are not particularly limited and can be set appropriately depending on the type of other components, the type of culture medium, the culture method, etc. However, if a surfactant is included, the concentration of the surfactant can be, for example, 0.01 to 0.5 w / w%, preferably 0.05 to 0.3 w / w%.
[0028] The culture conditions are not particularly limited, as long as they are conditions under which lactic acid bacteria belonging to the genus Fructobacillus can grow.
[0029] The culture temperature can be any temperature that is optimal for the lactic acid bacteria belonging to the genus Fructobacillus to be cultured, for example, 26-40°C, preferably 27-38°C, more preferably 28-36°C, and even more preferably 29-34°C. The culture time can be set appropriately according to the type of lactic acid bacteria belonging to the genus Fructobacillus to be cultured, for example, 4-48 hours, preferably 8-36 hours, and more preferably 12-24 hours.
[0030] Regarding the operations during cultivation, it is not necessary to stir the culture medium during cultivation. Furthermore, as an example of a specific cultivation procedure, the above cultivation can be performed as a production culture (main culture) for a certain period of time, and before that, an expansion culture (pre-culture) can be performed with a small amount of medium (for example, 1 / 6 to 1 / 4 of the main culture medium by volume). The culture conditions for the pre-culture can be set appropriately according to the type of lactic acid bacteria belonging to the genus Fructobacillus, and the above conditions can be adopted. In addition, in the main culture, the culture obtained in the pre-culture can be inoculated into the main culture medium so that the OD660 is, for example, 0.01 to 0.04, preferably 0.01 to 0.03.
[0031] In the separation and recovery process, the culture medium can be separated into solid and liquid components by methods such as filtration using filter paper, centrifugation, decantation, screw press, roller press, rotary drum screen, belt screen, vibrating screen, multi-plate vibrating filter, vacuum dehydration, pressure dehydration, belt press, centrifugal concentration dehydration, and multi-disc dehydration, and the obtained bacterial cells can be washed.
[0032] In the drying process, the microbial cells can be dried using drying methods such as freeze-drying, shelf drying, and spray drying.
[0033] In the cell disruption step, the microbial cells are disrupted by any method (for example, ultrasonic disruption). The microbial cells may be dried. In the cell disruption step, some of the microbial components may be removed from the disrupted cells.
[0034] [1-2-2. Lactic acid bacteria culture] If the active ingredient is in the form of a lactic acid bacteria culture, the active ingredient includes a culture medium component containing the lactic acid bacteria along with the products of the lactic acid bacteria. The lactic acid bacteria culture may be a culture prepared using one of the specified lactic acid bacteria alone, a culture prepared using a combination of multiple species, or a mixture of a culture prepared using one species alone and a culture prepared using another species alone.
[0035] The culture medium components in the culture may have some of the components used to cultivate the lactic acid bacteria removed. Furthermore, the lactic acid bacteria in the culture may be either live or dead. In the case of dead bacteria, the cells may be crushed. If the cells are crushed, some of the cell components may be removed.
[0036] Lactic acid bacteria cultures can be obtained by a manufacturing method that includes the above-described culture step. In addition to the culture step, this manufacturing method may also include the above-described separation and recovery step, drying step, and / or cell disruption step. Details of each step are as described in "1-2-1. Preparation of Lactic Acid Bacteria" above.
[0037] [1-2-3. Culture supernatant of lactic acid bacteria] If the active ingredient is in the form of a culture supernatant of lactic acid bacteria, the active ingredient includes a culture medium component containing the products of the lactic acid bacteria. The culture supernatant of lactic acid bacteria may be a culture supernatant prepared using one of the specified lactic acid bacteria alone, a culture supernatant prepared using a combination of multiple species, or a mixture of a culture supernatant prepared using one species alone and a culture supernatant prepared using another species alone.
[0038] The culture medium components contained in the culture supernatant may have some of the culture medium components used to cultivate the lactic acid bacteria removed.
[0039] The culture supernatant of lactic acid bacteria can be obtained by a manufacturing method that includes the culture step and the isolation and recovery step described above. In addition to the culture step and the isolation and recovery step, this manufacturing method may also include the drying step and / or cell disruption step described above. Details of each step are as described in "1-2-1. Preparation of Lactic Acid Bacteria" above.
[0040] [1-2-4. Lactic acid bacteria extract] When the active ingredient is in the form of a lactic acid bacteria extract, the active ingredient is a multi-component composition obtained by subjecting the above-mentioned lactic acid bacteria or lactic acid bacteria culture to an extraction process. Examples of extraction solvents used in preparing the extract include water; monohydric lower alcohols having 1 to 4 carbon atoms such as ethanol and isopropanol; polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, and glycerin; and polar solvents such as mixtures thereof. Furthermore, the temperature conditions during extraction are preferably room temperature (for example, 5 to 35°C, preferably 20 to 30°C). Specific methods for preparing the extract include, for example, preparing a suspension containing the above-mentioned lactic acid bacteria or lactic acid bacteria culture or pulverized thereof in an extraction solvent, and obtaining an extract by solid-liquid separation of the suspension, or, if necessary, drying the extract to obtain a powder.
[0041] [1-3. Content of active ingredients] The amount of active ingredients contained in the composition for preventing or improving cognitive decline of the present invention is not particularly limited and can be appropriately determined depending on the effect to be imparted.
[0042] The content of the active ingredient in the composition for preventing or improving cognitive decline of the present invention may be, for example, 0.00001 to 50% by weight, preferably 0.0001 to 5% by weight, based on the dry weight of lactic acid bacteria belonging to the genus Fructobacillus. The above dry weight equivalent refers to the dry weight of the active ingredient if the active ingredient is lactic acid bacteria or a culture of lactic acid bacteria; if the active ingredient is a culture supernatant of lactic acid bacteria, it refers to the dry weight of the lactic acid bacteria used to obtain the culture supernatant; and if the active ingredient is an extract, it refers to the dry weight of the lactic acid bacteria used to obtain the extract.
[0043] [2. Other ingredients] The present invention's composition for preventing or improving cognitive decline may contain, as needed, other pharmacological components in addition to the above-mentioned active ingredients. Examples of such pharmacological components include anti-inflammatory agents, antioxidants, bactericides, cooling agents, vitamins, mucopolysaccharides, and the like.
[0044] Furthermore, the compositions for preventing or improving cognitive decline of the present invention may or may not contain bases and / or additives as necessary to achieve the desired formulation. Such bases and / or additives are not particularly limited to the extent that they are pharmaceutically acceptable, but examples include aqueous bases such as water and monohydric lower alcohols having 1 to 4 carbon atoms (ethanol, isopropanol, etc.); oily bases such as naturally derived oils (vegetable oils, animal oils, processed oils thereof), mineral oils, ester oils, fatty acid alkyl esters, fatty acids, fatty acid esters, and higher alcohols; surfactants; polyhydric alcohols (glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, etc.); and additives such as cooling agents, preservatives, fragrances, colorants, viscosity modifiers, pH adjusters, wetting agents, stabilizers, antioxidants, UV absorbers, chelating agents, adhesives, buffers, solubilizers, and preservatives.
[0045] [3. Formulation and Product Classification] The formulation form of the composition for preventing or improving cognitive decline of the present invention is not particularly limited and may be liquid, semi-solid (cream, gel, ointment, paste), solid (granules, fine granules, powder, tablet, capsule), etc. Furthermore, the composition for preventing or improving cognitive decline of the present invention may be a non-emulsified formulation such as an aqueous formulation or an oily formulation, or an emulsified formulation such as an oil-in-water emulsion or a water-in-oil emulsion.
[0046] Furthermore, product classifications of the composition for preventing or improving cognitive decline according to the present invention include food and beverages and pharmaceuticals. Specifically, the food and beverages of the present invention contain the composition for preventing or improving cognitive decline. Also, the pharmaceuticals of the present invention contain the composition for preventing or improving cognitive decline.
[0047] While not particularly limited to food and beverages, examples include fermented milk (such as drinkable yogurt), lactic acid bacteria beverages, milk beverages (such as coffee milk and fruit milk), tea-based beverages (such as green tea, black tea, and oolong tea), fruit and vegetable-based beverages (beverages containing fruit juices such as orange, apple, and grape, and vegetable juices such as tomato and carrot), alcoholic beverages (such as beer, sparkling wine, and wine), carbonated beverages, soft drinks, and water-based beverages; and processed foods such as fermented milk (such as set-type yogurt and soft yogurt), confectionery, instant foods, and seasonings.
[0048] Furthermore, functional foods can also be cited as food and beverages. Functional foods refer to foods that have a certain function on the living body, and examples include health functional foods such as Foods for Specified Health Uses (including conditionally designated FOSHU [Foods for Specified Health Uses]) and nutrient function foods, foods with functional claims, foods for special dietary uses, nutritional supplements, health supplements, supplements (for example, in various dosage forms such as tablets, coated tablets, sugar-coated tablets, capsules and liquids), and beauty foods (for example, diet foods). Moreover, functional foods may also be foods for special dietary uses such as foods for the sick, powdered milk for pregnant and lactating women, infant formula, foods for the elderly, and foods for nursing care.
[0049] Pharmaceuticals include oral preparations, as well as topical preparations (including quasi-drugs) that include skin preparations and mucosal preparations. Dosage forms of oral preparations include tablets, coated tablets, sugar-coated tablets, capsules, and liquids, while dosage forms of topical preparations include liquids (including lotions, sprays, aerosols, and emulsions), foams, ointments, creams, gels, and patches.
[0050] Among these product categories, food and beverages are preferred from the viewpoint of further enhancing the effect of preventing and improving cognitive decline.
[0051] [4.Application] The present invention's composition for preventing or improving cognitive decline is used for purposes such as maintaining, improving, and enhancing cognitive function, and maintaining, improving, and enhancing memory.
[0052] [5.Dose] When the composition for preventing or improving cognitive decline of the present invention is administered orally, the amount of the active ingredient is, for example, 0.01 to 200 mg / kg / day, preferably 0.1 to 20 mg / kg / day, and can be administered orally 1 to 5 times a day. [Examples]
[0053] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.
[0054] [Test Example 1: Preparation of Lactic Acid Bacteria Powder] Fructobacillus fructosus OS-1010 strain was inoculated into 30 ml of Difco MRS medium (pre-culture medium) and cultured statically at 30°C for 24 hours. The resulting culture solution was inoculated into 1 L of MRS medium (main culture medium) to achieve an OD660 of 0.02 and cultured with stirring at 30°C for 12 hours at pH 6.0-7.0. The resulting culture solution was centrifuged to collect the bacterial cells. The collected cells were washed with 1 L of 0.85 w / w% KCl aqueous solution. The washed cells were centrifuged again to collect the remaining cells. After sterilization, the collected cells were freeze-dried to obtain lactic acid bacteria powder.
[0055] [Test Example 2: Preparation of Evaluation Mice] Twenty 83-week-old male C57BL / 6J mice were prepared and divided into two groups of 10 mice each to ensure uniform average body weight. As Comparative Example 1, one group of mice was given free access to D10012G (Research Diet Co., Ltd., referred to as "standard feed"). As Example 1, the other group of mice was given free access to D10012G (referred to as "standard feed + 2% lactic acid bacteria"), which was formulated with 2% by weight of the lactic acid bacteria powder obtained in Example 1. Furthermore, as Reference Example 1, ten 30-week-old male C57BL / 6J mice were prepared separately and given free access to D10012G. The experimental animals were kept at a temperature of 22±2℃ and under a 12-hour light-dark cycle (light period from 7 to 19 o'clock).
[0056] [Test Example 3: Assessment of Cognitive Function (Novel Object Recognition Test)] When rodents such as mice perceive a novel object, they approach it out of a desire to explore, engaging in exploratory behaviors such as examining its shape and smelling it. On the other hand, rodents either do not engage in exploratory behavior towards objects they remember, or the time spent exploring them (exploration time) is shorter compared to when they encounter a novel object. The novel object recognition test utilizes this property and is a test method that can evaluate memory. This example test evaluates the effect of lactic acid bacteria powder on memory using the novel object recognition test.
[0057] Using the mice described in Test Example 2, a novel object recognition test was conducted under the following conditions. (1) The novel object recognition test was conducted over a 5-day period from day 56 to day 60 after the start of feeding. (2) During the novel object recognition test, mice were left in the box for 10 minutes each day for habituation. (3) On the fourth day of the same test, one object (X) and one object (Y) were placed in the box, and the mice were left there for 10 minutes. (4) On the fifth day of the same experiment, object (Y) was changed to object (Z), and the mice were left undisturbed for 10 minutes, and the search times for object (X) and object (Z) were measured. In this case, object (X) was a known object, and object (Z) was a novel object. The ratio of the search time for the novel object (Z) to the total search time was calculated and used as an indicator of memory and learning ability. Specifically, the Discrimination Index (DI), which is the ratio of the difference in search time between the novel object and the known object to the total search time for all objects (discrimination index), was calculated using the following formula (1). ·DI = (Search time for object (Z) - Search time for object (X)) / (Search time for object (Z) + Search time for object (X)) Equation (1)
[0058] The results of the DI (Diffusion Index) are shown in Figure 1. A higher DI indicates better memory retention.
[0059] Furthermore, the percentage of search time for each object was calculated using the following equations (2) and (3), and is shown in Figure 2. • Percentage of search time for novel objects (%) = {(Search time for object (Z)) / (Search time for object (Z) + Search time for object (X))} × 100 Equation (2) • Percentage of search time relative to known objects (%) = {(Search time for object (X)) / (Search time for object (Z) + Search time for object (X))} × 100 Equation (3)
[0060] A higher ratio of search time for novel objects, i.e., a higher value of equation (2), indicates higher cognitive function (especially memory and learning ability). Conversely, a higher ratio of search time for known objects, i.e., a higher value of equation (3), indicates lower cognitive function (especially memory and learning ability).
[0061] As shown in Figure 1, the DI value of mice that ingested lactic acid bacteria (Example 1) was higher than that of mice that did not ingest lactic acid bacteria (Comparative Example 1). Furthermore, the DI value of Example 1 was similar to that of young mice (Reference Example 1). From this, it can be said that ingesting lactic acid bacteria maintained or improved memory to a level similar to that of young mice.
[0062] As shown in Figure 2, in mice that did not ingest lactic acid bacteria (Comparative Example 1), there was almost no difference in the proportion of time spent searching for novel objects compared to the proportion of time spent searching for known objects. On the other hand, in mice that ingested lactic acid bacteria (Example 1) and young mice (Reference Example 1), the proportion of time spent searching for novel objects was higher than the proportion of time spent searching for known objects. From this, it can be explained that the intake of lactic acid bacteria maintained or improved memory and learning ability to the same level as that of young mice.
[0063] [Test Example 4: Confirmation of Effects on Humans] Human trials were conducted to verify the effect of ingesting tablets containing lactic acid bacteria powder of Fructobacillus fructosus OS-1010 strain on improving cognitive function. The lactic acid bacteria powder used was the same as that prepared in Test Example 1. The lactic acid bacteria powder content in each tablet was 15%.
[0064] (1) Exam Content This study involved 12 healthy men and women aged 40 or older as subjects. Participants were given one tablet containing lactic acid bacteria powder of Fructobacillus fructosus OS-1010 strain daily for 12 weeks. Cognitive function tests using the Cognitrax test were conducted before tablet administration and 12 weeks after administration.
[0065] [Cognitrax test] The Cognitrax test is a cognitive function testing service designed for Japan by Health Solution Co., Ltd., based on cognitive function testing technology developed by CNS Vital Signs, Inc. in the United States. It uses 10 types of tests (verbal memory test, visual memory test, finger tapping test, SDC test, Stroop test, attention shift test, sustained processing test, facial recognition test, logical thinking test, and 4-part sustained processing test) to calculate standardized scores for each cognitive domain (neurocognitive index (NCI), overall memory, verbal memory, visual memory, cognitive speed, reaction time, overall attention, cognitive flexibility, processing speed, executive function, social cognition, logical thinking, working memory, sustained attention, simple attention, and motor speed).
[0066] The composition of each tablet used in the test is as follows: [Tablet composition] Reduced maltose syrup; 70mg Sorbitol; 29 mg Cellulose; 64 mg Silicon dioxide; 3 mg Calcium stearate; 4 mg Lactobacillus fructosus OS-1010 strain lactic acid bacteria powder; 30 mg Total (1 tablet): 200mg
[0067] (2) Test results The analysis was performed excluding two subjects whose intake rate did not meet the standard. Table 1 shows the results for representative test items. The intake rate refers to the percentage of days on which the subject was taken out of the "take one tablet per day for 12 weeks" regimen. The "standard intake rate" was set at 80%.
[0068] [Table 1] * Paired t-test (p<0.05) † Neurocognitive Index; an index that indicates overall cognitive function as the average of scores for overall memory, cognitive speed, reaction time, overall attention, and cognitive flexibility.
[0069] According to the results in Table 1, ingestion of Fructobacillus fructosus OS-1010 strain resulted in significant improvements in neurocognitive index, overall memory, visual memory, and cognitive function speed. Furthermore, some improvement was observed in verbal memory, overall attention, cognitive flexibility, processing speed, and logical thinking.
[0070] Cognitive function is the ability to correctly understand, judge, process, and utilize information about things, and as mentioned above, it includes, for example, memory, learning ability, language ability, visuospatial cognitive ability, judgment, calculation ability, and executive function. The "neurocognitive index," "overall memory," "visual memory," and "cognitive function speed," which showed significant improvements, can be said to be indicators that comprehensively evaluate these cognitive functions. More specifically, "visual memory" is an indicator related to memory and visuospatial cognitive ability, and "cognitive function speed" is an indicator related to judgment, calculation ability, and executive function. In addition, "verbal memory," "overall attention," "cognitive flexibility," "processing speed," and "logical thinking," which also showed improvements in scores, correspond to elements that constitute cognitive function. Therefore, the improvement in scores such as the "neurocognitive index" after taking Fructobacillus fructosus OS-1010 strain supports the idea that cognitive functions such as memory, learning ability, language ability, visuospatial cognitive ability, judgment, calculation ability, and executive function were improved.
[0071] Based on the above, it can be concluded that the Fructobacillus fructosus OS-1010 strain is effective in preventing or improving cognitive decline in healthy individuals.
Claims
1. A composition for preventing or improving cognitive decline, comprising a lactic acid bacterium belonging to the genus Fructobacillus, a culture of the lactic acid bacterium, the culture supernatant of the lactic acid bacterium, and / or an extract of the lactic acid bacterium as an active ingredient.
2. The composition for preventing or improving cognitive decline according to claim 1, wherein the lactic acid bacterium is Fructobacillus fructosus.
3. The composition for preventing or improving cognitive decline according to claim 1 or 2, wherein the lactic acid bacterium is Fructobacillus fructosus OS-1010 strain.
4. Food and beverages containing the composition for preventing or improving cognitive decline described in claim 1 or 2.
5. A pharmaceutical product containing the composition for preventing or improving cognitive decline described in claim 1 or 2.
Citation Information
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Memory loss inhibitor containing lactic acid bacterium belonging to genus lactococcus
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