PRODUCTS TO IMPROVE BRAIN FUNCTION

Abstract

The invention relates to a brain-enhancing preparation capable of producing brain-enhancing effects independent of sleep state. The invention relates to a brain-enhancing preparation containing at least one of the bacterial cells of Lacticaseibacillus paracasei or a processed product of these bacterial cells.

Description

Brain function enhancer, use for producing brain function enhancer, and method for enhancing brain function

[0001] The present disclosure relates to brain function enhancers.

[0002] The human brain is composed of the cerebrum, brainstem, and cerebellum, which work together to enable complex tasks, and it is known that thought, memory, and decision-making are carried out based on peripheral stimuli transmitted via the spinal cord. It is also known that in normal human life, rest and sleep help to recover from mental and physical fatigue, especially brain fatigue.

[0003] Meanwhile, in today's 24-hour society, coupled with the widespread use of the internet, longer working hours and shift work can lead to mental and physical fatigue, resulting in symptoms such as drowsiness, lethargy, stiff shoulders, headaches, back pain, abdominal pain, constipation, dizziness, hot flashes, anxiety, palpitations, eye strain, decreased memory, decreased concentration and motivation, and irritability. These health problems, which are caused by brain dysfunction, have become a social problem. These health problems are not only a sign of illness but also lead to decreased performance and an increased risk of mistakes and accidents, resulting in economic losses due to reduced production efficiency (Reference: Corporate "Health and Productivity Management" Guidebook: Promoting Health through Collaboration and Cooperation (Revised 1st Edition), Ministry of Economy, Trade and Industry, Commerce and Information Policy Bureau, Healthcare Industry Division, kenkokeiei-guidebook2804.pdf (meti.go.jp)). Rest and sleep alone are unlikely to immediately resolve these health problems caused by brain dysfunction, and non-sleep-related methods have been proposed.

[0004] For example, Patent Document 1 discloses that docosahexaenoic acid (DHA) not only improves cognitive function of the brain that has declined due to aging, dementia, brain damage, etc., but also improves the cognitive response function of the brain in healthy individuals. Patent Document 2 discloses that arachidonic acid and / or a compound containing arachidonic acid as a constituent fatty acid prevents, improves, or enhances a decline in normal response of the brain's cognitive ability. Furthermore, Patent Document 3 discloses the effect of improving brain alertness before and after tooth brushing.

[0005] Japanese Patent Laid-Open No. 10-059844 Japanese Patent Laid-Open No. 2006-502196 Japanese Patent Laid-Open No. 2011-5056

[0006] The above-mentioned prior art did not provide a brain function enhancer suitable for the lifestyles of modern people. The present inventors conducted various studies to find a component that improves human brain function, regardless of whether or not people have had enough sleep. As a result, they found that ingestion of Lacticaseibacillus genus, particularly Lacticaseibacillus paracasei cells or a processed product thereof, can improve brain function.

[0007] In order to solve the problems exemplified above, one embodiment of the present invention provides a brain function improver characterized by containing at least one of Lacticase Bacillus paracasei cells and a processed product of the cells as an active ingredient.

[0008] Furthermore, one embodiment of the present invention is characterized in that the use is at least one of Lacticase Bacillus paracasei cells and a processed product of the cells for the production of a brain function enhancer.

[0009] Furthermore, in one embodiment of the present invention, the method for improving brain function is a method for improving brain function by administering 100 mg of Lacticase Bacillus paracasei in an amount of 100 mg or more as a viable cell count. 10 The method is characterized in that the vaccine is administered orally at a dose of at least 10 ...

[0010] The brain function enhancer of the present disclosure can provide an effect of improving brain function regardless of the state of sleep.

[0011] FIG. 1 is a diagram showing an example of a questionnaire used for subjective evaluation (daytime mood index). FIG. 2 is a diagram showing the results of subjective evaluation (daytime mood index). FIG. 3 is a diagram showing the results of objective evaluation (spontaneous electroencephalogram). FIG. 4 is a diagram showing the results of objective evaluation (spontaneous electroencephalogram). FIG. 5 is a diagram showing the results of objective evaluation (P300 latency and button press reaction time). FIG. 6 is a diagram showing the relationship between subjective evaluation (amount of change in concentration) and objective evaluation (rate of change in theta waves).

[0012] <Brain Function Enhancer> The active ingredient of the brain function enhancer according to the present disclosure is at least one of Lacticase Bacillus paracasei cells and a processed product of the cells.

[0013] In the present disclosure, the strain of Lacticase Bacillus paracasei is not particularly limited, but preferred examples include Lacticase Bacillus paracasei YIT 9018 (FERM BP-665), Lacticase Bacillus paracasei YIT 9029 (FERM BP-1366), and Lacticase Bacillus paracasei YIT 10003 (FERM BP-7707). Of these, Lacticase Bacillus paracasei YIT 9029 (FERM BP-1366) is particularly preferred in terms of its effect in improving brain function.

[0014] The above-mentioned Lacticaceobacillus paracasei YIT 9018 strain was identified as Lacticaceobacillus casei YIT 9018 (FERM BP-665, date of accession: November 14, 1984), the Lacticaceobacillus paracasei YIT 9029 strain was identified as Lacticaceobacillus casei YIT 9029 (FERM BP-1366, date of accession: May 1, 1981), and the Lacticaceobacillus paracasei YIT 10003 (FERM BP-7707) was identified as Lacticaceobacillus casei YIT 10003 (FERM BP-7707). It has been internationally deposited with the National Institute of Technology and Evaluation (National Institute of Technology and Evaluation, Room 120, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, 292-0818, Japan), which is the international depositary authority of the Budapest Treaty, under the name BP-7707, date of deposit: August 14, 2001. Lacticaseibacillus paracasei was previously classified as Lactobacillus casei, but has recently been reclassified as Lacticaseibacillus paracasei (Zheng et al., A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int. J. Syst. Evol. Microbiol. 2020 Apr; 70(4):2782-2858 DOI 10.1099 / ijsem.0.004107). In this specification, the classification of lactic acid bacteria is indicated by the new classification based on the above literature.

[0015] In the present disclosure, the term "treated bacterial cell product" refers to a product in which the bacteria (Lacticase Bacillus paracasei) used has been subjected to some kind of treatment, and the treatment is not particularly limited.

[0016] Examples of treated Lacticase Bacillus paracasei cells include cell decomposition products, etc. Specific examples include a solution of Lacticase Bacillus paracasei disrupted by ultrasonication or the like, a solution of Lacticase Bacillus paracasei treated with an enzyme, and a supernatant or solid residue separated from these by solid-liquid separation means such as filtration or centrifugation.

[0017] The processed Lacticase Bacillus paracasei cells of the present disclosure also include a nucleic acid-containing fraction obtained by dissolving Lacticase Bacillus paracasei with a surfactant or the like and then precipitating it with ethanol or the like.

[0018] Furthermore, the treated Lacticase Bacillus paracasei cells in the present disclosure also include those obtained by further performing separation and purification treatments, for example, using various types of chromatography, on the Lacticase Bacillus paracasei cell disruption solution or enzyme-treated cell solution.

[0019] Furthermore, the processed Lacticase Bacillus paracasei cells of the present disclosure also include killed cells. The killed cells can be obtained, for example, by heat treatment, treatment with drugs such as antibiotics, treatment with chemicals such as formalin, treatment with ultraviolet light, or treatment with radiation such as gamma rays. Among these treatments, ultrasonic treatment, enzyme treatment, or heat treatment is particularly preferred from the viewpoints of cost, ease of production, and stability of the resulting brain function enhancer.

[0020] On the other hand, in the present disclosure, it is more preferable to use live Lacticase Bacillus paracasei cells and processed cells thereof in particular from the viewpoint of the effect of improving brain function.

[0021] In the present disclosure, the Lacticase Bacillus paracasei cells and processed products thereof are preferably in the form of a fermented product containing Lacticase Bacillus paracasei, from the viewpoints of ease of ingestion, continuity of ingestion, effect of improving brain function, etc. Examples of the fermented product include fermented milk products as well as fermented plant liquid products such as fermented soy milk products, fermented grain juice products, and fermented fruit juice products, with fermented milk products being more preferred.

[0022] A fermented product containing Lacticase Bacillus paracasei can be obtained, for example, by culturing Lacticase Bacillus paracasei in a dairy component such as animal milk (e.g., cow's milk), powdered milk, fat-free milk powder, or skim milk powder at a temperature of 30 to 40°C for 4 hours to 10 days. The culturing may be performed by standing, stirring, shaking, aeration, or the like. More preferably, Lacticase Bacillus paracasei is inoculated and cultured in a sterilized dairy medium, either alone or together with other microorganisms, and the culture is homogenized to obtain a fermented milk base. A separately prepared syrup solution is then added and mixed, homogenized using a homogenizer, or the like, and a flavor is added to produce the final product.

[0023] In the present disclosure, fermented products include beverages such as fermented milk and dairy lactic acid bacteria beverages as specified by the Ministerial Ordinance on Milk, Dairy, etc., as well as hard yogurt, soft yogurt, plain yogurt, etc. Furthermore, fermented products in the present disclosure also include foods and beverages that use Lacticase Bacillus paracasei, such as plain, flavored, fruit, sweet, soft, drink, solid (hard), and frozen types of fermented milk and lactic acid bacteria beverages.

[0024] In the present disclosure, these fermented products can be blended with sweeteners such as syrup as well as other various food ingredients, such as various carbohydrates, thickeners, emulsifiers, various vitamins, antioxidants, stabilizers, etc., as needed. Specific examples of these food ingredients include carbohydrates such as sucrose, glucose, fructose, palatinose, trehalose, lactose, xylose, maltose, etc.; sugar alcohols such as sorbitol, xylitol, erythritol, lactitol, palatinit, reduced starch syrup, and reduced maltose syrup; high-intensity sweeteners such as aspartame, thaumatin, sucralose, acesulfame K, and stevia; thickeners (stabilizers) such as agar, gelatin, carrageenan, guar gum, xanthan gum, pectin, locust bean gum, gellan gum, carboxymethylcellulose, soybean polysaccharides, and propylene glycol alginate; sucrose fatty acid esters; glycerin; and the like. Examples of suitable flavorings include emulsifiers such as glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, and lecithin; milk fats such as cream, butter, and sour cream; acidulants such as citric acid, lactic acid, acetic acid, malic acid, tartaric acid, and gluconic acid; various vitamins such as vitamin A, vitamin B, vitamin C, and vitamin E; minerals such as calcium, magnesium, zinc, iron, and manganese; and flavors such as yogurt, berry, orange, quince, perilla, citrus, apple, mint, grape, apricot, pear, custard cream, peach, melon, banana, tropical, herb, black tea, and coffee.

[0025] In producing the fermented product, known microorganisms other than Lacticaceae Bacillus paracasei can also be used in combination. Examples of such microorganisms include Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium animalis, Bifidobacterium suis, Bifidobacterium infantis, and Bifidobacterium adolescentis. Bifidobacterium bacteria such as B. adolescentis, Bifidobacterium catenulatum, Bifidobacterium pseudocatenulatum, Bifidobacterium lactis, Bifidobacterium globosum, Lacticaseibacillus paracasei, Lacticaseibacillus casei, Lacticaseibacillus bacillus, Lacticaseibacillus bacteria such as Lactobacillus casei, Lactobacillus gasseri, Lactobacillus acidophilus, Lactobacillus helveticus, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus delbrueckii subsp. delbrueckii subsp.Lactobacillus bacteria such as Lactobacillus delbrueckii and Lactobacillus johnsonii, Ligilactobacillus bacteria such as Ligilactobacillus salivarius, Limosilactobacillus bacteria such as Limosilactobacillus fermentum, Licorilactobacillus bacteria such as Licorilactobacillus mali, Lactiplantibacillus plantarum, Lactiplantibacillus bacteria such as Streptococcus thermophilus, Lactococcus lactis subsp. lactis ... Examples of suitable lactic acid bacteria include bacteria of the genus Lactococcus such as Lactococcus lactis subsp. cremoris, Lactococcus plantarum, Lactococcus raffinolactis, and Lactococcus cremoris, and bacteria of the genus Enterococcus such as Enterococcus faecalis and Enterococcus faecium. One or more of these lactic acid bacteria can be used, and using a combination of multiple bacteria to produce a fermented product is preferred because it is highly palatable and easy to ingest. .

[0026] In the present disclosure, at least one of the Lacticase Bacillus paracasei cells and the processed Lacticase Bacillus paracasei cells may be a commercially available fermented product containing Lacticase Bacillus paracasei. As an example, a fermented milk food product containing live Lacticase Bacillus paracasei cells manufactured by Yakult Honsha can be preferably used. Specific examples include Yakult products such as "Yakult," "New Yakult," "Yakult 400," "Yakult 1000," and "Y1000," as well as "Joa," "Sofur," and "Pretio." Yakult products are particularly preferred because they contain a high number of live Lacticase Bacillus paracasei cells.

[0027] In the present disclosure, at least one of the Lacticase Bacillus paracasei cells and the processed product thereof may be a commercially available pharmaceutical product. For example, a pharmaceutical product containing live Lacticase Bacillus paracasei cells manufactured by Yakult Honsha Co., Ltd. can be suitably used. A specific example of such a pharmaceutical product is "Yakult BL Intestinal Regulatory Medicine."

[0028] The daily intake of the brain function enhancer of the present disclosure is 10 or less in terms of the viable cell count of Lacticase Bacillus paracasei. 5 cfu or more is preferred, and 10 8 cfu or more is more preferable, and 10 10 More preferably, 10 cfu or more 11 The number of days for which the ingestion is carried out is preferably 5 days or more, more preferably 2 weeks or more, even more preferably 4 weeks or more, and particularly preferably 8 weeks or more.

[0029] In addition, the brain function enhancer of the present disclosure preferably has a density of Lacticaceae Bacillus paracasei per dose that is at least a predetermined value. 5 cfu / 100 mL or more is preferred, and 10 8 cfu / 100 mL or more is more preferable, and 10 10 cfu / 100 mL or more is more preferable, and 10 11cfu / 100 mL or more is particularly preferred. The inventors of the present invention have considered the effect of specifying the density of Lacticase Bacillus paracasei in a single ingestion as follows: The reason why density improves brain function is not clear in detail, but according to the studies of the inventors of the present invention, when the density of Lacticase Bacillus paracasei is ingested at a certain value or more, it is speculated that the stimulation of specific gastric endocrine cells is enhanced. It is thought that substances secreted from stimulated gastric endocrine cells stimulate the afferent vagus nerve, thereby exerting an effect on brain function.

[0030] Furthermore, it is particularly preferred that the brain function enhancer of the present disclosure be taken continuously at the aforementioned single-intake density in the aforementioned daily intake amount for the aforementioned number of days of intake.

[0031] The brain function enhancer of the present disclosure can be administered orally or parenterally, with oral administration being preferred. For administration, a composition containing the active ingredient can be mixed with a solid or liquid non-toxic pharmaceutical carrier suitable for administration by oral administration, rectal administration, injection, or other methods, and administered in the form of a conventional pharmaceutical formulation. Examples of such formulations include solid formulations such as tablets, granules, powders, and capsules; liquid formulations such as solutions, suspensions, and emulsions; and lyophilized formulations. These formulations can be prepared using conventional pharmaceutical techniques. Examples of the non-toxic pharmaceutical carrier include glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glycerides, polyethylene glycol kaloyl, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid esters, amino acids, gelatin, albumin, water, and physiological saline. Conventional additives such as stabilizers, humectants, emulsifiers, binders, isotonicity agents, and excipients can also be added as needed.

[0032] As a result of intensive research and trial and error, the present inventors have discovered that when at least one of Lacticase Bacillus paracasei cells and a processed product thereof is ingested, it shows an excellent effect of improving brain function. Specific examples of the effect of improving brain function include an effect of improving attention function, an effect of improving alertness, and an effect of improving response to stimuli. More specifically, examples of the effect include maintaining concentration and quickly responding to stimuli.

[0033] The effects of the brain function enhancer of the present disclosure can be confirmed by at least one of subjective evaluation and objective evaluation.

[0034] Specific examples of subjective evaluation include a questionnaire by a subject, etc. More specifically, a questionnaire including items such as fatigue, alertness, motivation, concentration, optimism, and anxiety is administered to subjects who have taken the brain function enhancer of the present disclosure and those who have not, and the results are compared to confirm the above-mentioned effects.

[0035] Specific examples of objective evaluation include measurement of spontaneous electroencephalograms and measurement of event-related potentials.

[0036] Spontaneous brain waves are constantly observed, and the level of alertness varies depending on the intensity of α, β, θ, and δ waves, which are classified by frequency. Delta waves (δ) are at 0.5 to 4 Hz, theta waves (θ) are at 4 to 8 Hz, alpha waves (α) are at 8 to 13 Hz, and beta waves (β) are at 13 Hz or higher. Beta waves are dominant when the brain is in an active state, but alpha waves emerge when the brain is relaxed. Furthermore, theta waves increase during meditation and sleep, while delta waves predominate during deep sleep. The effects of improving brain function according to the present disclosure can be confirmed by measuring spontaneous brain waves such as delta waves, theta waves, alpha waves, and beta waves. For example, a decrease in the intensity of theta waves outside of sleep indicates improved brain function, more specifically, improved brain alertness. Specifically, when the intensity of theta waves measured when the brain function enhancer of the present disclosure is taken is lower than the intensity of theta waves when not taken, it can be said that brain function has improved (wakefulness has improved). Furthermore, the ratio of beta waves to alpha waves (β / α) of spontaneous electroencephalograms can also be used as an index of improved brain function, specifically, attention. More specifically, when the ratio (β / α) when the brain function enhancer of the present disclosure is taken is higher than the ratio when not taken, it can be said that brain function has improved (attention has improved).

[0037] Furthermore, event-related potentials are potential fluctuations induced in human electroencephalograms by mental activity. Because these potential fluctuations occur after the application of a stimulus, such as a mental task, they reflect human mental function and are useful for objective evaluation. The effects of the brain function enhancer of the present disclosure can be confirmed by measuring P300, N400, or the like as event-related potentials. In particular, the event-related potential of the present disclosure is preferably the event-related potential P300. The event-related potential P300 is an event-related potential that appears as a potential with a positive peak approximately 300 milliseconds (ms) after stimulation in an oddball task that requires the subject to pay attention to sensory stimuli that appear irregularly from among multiple types of stimuli. Specifically, the effects of the brain function enhancer of the present disclosure can be confirmed by shortening the P300 latency (the time from stimulation to its peak). It is generally known that P300 latency is prolonged when brain function is impaired due to aging, depression, dementia, or other conditions. Therefore, if it is confirmed that the peak latency is shortened by taking the brain function enhancer of the present disclosure, it can be said that the brain processing speed has increased, and the level of alertness and concentration has improved. Furthermore, as a result of the inventors' ongoing experiments, the event-related potential P300 is generally composed of multiple components, and is not often detected as a single peak. However, in the experiments of the present disclosure, it was found that taking the brain function enhancer of the present disclosure increases the detection rate of the peak of the event-related potential P300. If taking the brain function enhancer of the present disclosure improves the detection rate of the peak of the event-related potential P300, it can be said that it has contributed to assisting in the acquisition of P300 latency data.

[0038] The brain function enhancer of the present disclosure has an effect of improving brain function, regardless of the duration or quality of sleep. In other words, even if a subject is not getting enough sleep or is dissatisfied with their sleep (for example, difficulty falling asleep, waking up in the middle of the night, not feeling refreshed, excessive daytime sleepiness, etc.), taking the brain function enhancer of the present disclosure is advantageous in that it is expected to improve brain function.

[0039] <Method for Producing Brain Function Enhancer> The method for producing the brain function enhancer of the present disclosure is described below. In the method for producing the brain function enhancer of the present disclosure, it is preferable to use Lacticase Bacillus paracasei YIT 9029 (FERM BP-1366) as at least one of Lacticase Bacillus paracasei cells and a treated product thereof.

[0040] <Method for Improving Brain Function> The method for improving brain function according to the present disclosure will be described below. 10 The method includes a step of administering orally at least 1000 cfu / day of the vaccine for at least four consecutive weeks.

[0041] In addition, in the method for improving brain function according to the present disclosure, the density of Lacticase Bacillus paracasei in a single intake is 10 or less in terms of viable cell count. 10 It is preferable to include a step of orally administering the virus in an amount of cfu / 100 mL or more.

[0042] More specifically, the method for improving brain function is preferably a method for reducing the intensity of theta waves or a method for shortening the P300 latency of the event-related potential. Note that the methods for measuring spontaneous electroencephalograms and event-related potentials are as described above, and therefore will not be described here.

[0043] The present invention will now be described in more detail with reference to examples, but the present invention is not limited to the following examples.

[0044] Example 1 (Preparation of Test Drink) A skim milk powder solution inoculated with Lacticaceae Bacillus paracasei YIT 9029 strain (LcS) and fermented at 37°C was added with the other ingredients shown in Table 1 below, and then homogenized and filled into containers to obtain a test drink. The bacterial count of Lacticaceae Bacillus paracasei in 100 mL of this test drink was 10 11 cfu. This was stored in a refrigerator (10°C or below) until use.

[0045] Reference Example 1 (Preparation of Placebo Drink) A placebo drink was prepared using the same manufacturing method as the test drink, except that it did not contain Lacticase Bacillus paracasei. The ingredients were as shown in Table 1. In addition, taking into consideration that sugar is metabolized during the production of the test drink and lactic acid is produced, the raw materials for the placebo drink contained lactic acid instead of glucose-fructose corn syrup.

[0046]

[0047] Twelve healthy subjects (5 men, 7 women, ages 40 to 59) dissatisfied with their sleep were given the test beverage prepared in Example 1 and the placebo beverage prepared in Reference Example 1. Dissatisfaction with sleep felt by the subjects included difficulty falling asleep, waking up in the middle of the night, not feeling refreshed when waking up, and excessive daytime sleepiness.

[0048] The human study of the present disclosure was conducted with due consideration and in accordance with the spirit of the Declaration of Helsinki. After explaining the study details, 12 healthy individuals who agreed to participate were randomly assigned to Group I (placebo-preceding group) and Group II (test-preceding group) (Group I: n = 6, Group II: n = 6). As shown in Table 2 below, Group I consumed 100 mL of the placebo beverage prepared in Reference Example 1 daily after dinner for four weeks, while Group II consumed the test beverage in the same manner (Period 1). During the final week of Period 1, daytime mood indices were assessed, and spontaneous electroencephalograms and event-related potentials were measured. Subjects in Groups I and II then discontinued beverage intake for four weeks (washout period). After the washout period, Group I consumed the test beverage and Group II consumed the placebo beverage for four weeks (Period 2). During the final week of Period 2, daytime mood indices were assessed, and spontaneous electroencephalograms and event-related potentials were measured (double-blind, crossover study).

[0049]

[0050] Subjective assessment (daytime mood index) Daytime physical fatigue, motivation, concentration, and optimism were assessed using a questionnaire using a visual analog scale (VAS). Taking concentration as an example, as shown in Figure 1, the left end of a 100 mm long black line was designated "completely unable to concentrate (poor)" and the right end was designated "extremely able to concentrate (good)," with the subject marking an "X" at the point they felt best fit their own state. The distance (mm) from the left end to the "X" was used as the variable for that item (VAS mm).

[0051] Objective Assessment (Spontaneous EEG and Event-Related Potentials) Spontaneous EEG measurements were conducted in a shielded room in the morning and afternoon of a random day during the final week of the first and second periods. A biosignal recording device (Polymate, Miyuki Giken Co., Ltd.) was used for measurements. Silver-plate electrodes were placed at three locations on the head: Fz (midfrontal), Cz (central midline), and Pz (parietal midline) according to the International 10-20 electrode placement method. Reference electrodes were placed on both ears, and two ground and reference electrodes were placed on the forehead. Electrode impedance was 10 kΩ or less. With the subject seated in a chair and fixating a point on a monitor, EEG recordings were conducted in the resting, eyes-open state for 2 minutes, followed by EEG recordings during an auditory oddball task for 5 minutes. Three sets of EEG recordings were conducted, as shown in Table 3 below. Finally, EEG recordings were conducted in the resting state with eyes closed for 2 minutes.

[0052]

[0053] In the auditory oddball task, two short tones (100 msec presentation time) of 2,000 Hz and 1,000 Hz were used as auditory stimuli, with an appearance rate of 20% and 80%, respectively, and presented at intervals of once every 2.0 seconds, a total of 150 times. Subjects were instructed to press a button when they heard the 2,000 Hz auditory stimulus (target stimulus), and the reaction time from the presentation of the target stimulus to the button press was also measured.

[0054] For frequency analysis of spontaneous EEG, artifacts such as eye movements were removed using a 0.5-30 Hz band-pass filter. Fourier transform was performed on 120,000 points during the resting state (2 minutes) and 300,000 points during oddball task performance (5 minutes). Power spectrum analysis was then performed in each frequency band (θ waves: 4-8 Hz, α waves: 8-13 Hz, β waves: 13-30 Hz) (resting state: μV 2 / 2min, oddball task: μV 2 / 5 min). Mathematical analysis software (MATLAB) was used for analysis. Event-related potential P300 acquisition and analysis were performed in accordance with the guidelines of the Japanese Society of Clinical Neurophysiology. Analysis software (EP Travel Light, Rupro Light Systems, Ltd.) was used to calculate the arithmetic mean of the waveforms observed during 30 target stimulus presentations. P300 consists of two or more components, and when P300a and P300b were observed, P300b, which appears in response to the target stimulus, was selected over P300a, which appears in response to the deviant stimulus.

[0055] Considerations regarding daytime mood indices The results are shown in Figure 2. All daytime mood index items (fatigue, motivation, concentration, and optimism) showed improvements in performance when the test beverage was consumed compared to when the placebo beverage was consumed, regardless of the time of measurement (morning or afternoon). Concentration in the afternoon, in particular, was significantly improved when the test beverage was consumed. Comparing the morning and afternoon, performance on the daytime mood index items generally decreased, but afternoon scores when the test beverage was consumed increased to the same level as morning scores when the placebo was consumed. In other words, it was confirmed that the decrease in afternoon performance was suppressed by the consumption of the test beverage, and performance was maintained at the same level as in the morning.

[0056] Observations on spontaneous EEG The results are shown in Figure 3. The intensity of theta waves was lower when the test beverage was consumed than when the placebo beverage was consumed, and this phenomenon was particularly noticeable in the afternoon. A similar trend was confirmed both in the resting, eyes-open state and when performing an oddball task. Figure 4 shows the ratio of beta waves to alpha waves (β / α). It was observed that this ratio was higher when the test beverage was consumed compared to when the placebo beverage was consumed, both during the oddball task and in the resting, eyes-open state. In other words, it was confirmed that ingestion of the test beverage improved alertness and attention. Note that there was no change in alpha waves, and some subjects experienced a higher ratio due to an increase in beta waves.

[0057] The results of the event-related potential (P300 latency) and button press reaction time are shown in Figure 5. A shorter P300 latency was observed in subjects receiving the test beverage compared to those receiving the placebo beverage at all three sites: the central midline (Cz), the frontal midline (Fz), and the parietal midline (Pz). Furthermore, a tendency for button press reaction time in the auditory oddball task to be shorter was observed in subjects receiving the test beverage compared to those receiving the placebo beverage. This confirms that test beverage consumption improved response to stimuli. Furthermore, button press reaction time was 365.9 msec in the morning and 381.6 msec in the afternoon after placebo consumption, whereas it was 349.2 msec in the morning and 356.0 msec after test beverage consumption. The variability of test beverage consumption was smaller than that of placebo consumption. This indicates that the test beverage suppressed the decline in performance in the afternoon, maintaining performance at a similar level to that in the morning.

[0058] The P300 latency shown in Figure 5 was measured in the morning. Because the event-related potential P300 is composed of multiple components, it may be difficult to identify the peak, especially in afternoon measurements, or the amplitude may be shallow and the peak itself may not be visible. In this example, measurements were taken in both the morning and afternoon, and the detection frequency and detection rate of the peak corresponding to the event-related potential P300 were analyzed. The analysis results are shown in Table 4.

[0059]

[0060] As shown in Table 4 above, the peak detection rate in afternoon measurements tended to be lower than that in the morning. Meanwhile, the peak detection rate tended to be higher when the test beverage was consumed compared to when the placebo beverage was consumed. In other words, it was confirmed that the consumption of the test beverage contributed to the acquisition of P300 latency data. In Table 4, P represents the significance probability in Fisher's exact test, and the total number of detections represents the percentage of times a peak corresponding to the event-related potential P300 could be detected out of a total of 36 measurements, each performed three times on 12 subjects.

[0061] Relationship Between Subjective and Objective Assessments We examined the correlation between subjective assessment methods (daytime mood index) and objective assessment methods (spontaneous EEG). Figure 6 shows the relationship between the change in afternoon concentration (horizontal axis, VAS mm) when consuming the test beverage compared to when consuming a placebo beverage, and the rate of change in theta wave intensity during rest with eyes closed (vertical axis, ratio) for 12 subjects. As shown in Figure 6, a negative correlation was observed between the two, indicating that the subjective and objective indices changed in conjunction with the consumption of the test beverage. Note that Figure 6 only illustrates the results for concentration among the daytime mood indices, but correlations with spontaneous EEG were also confirmed for other mood indices.

[0062] Although the preferred embodiments of the present disclosure have been described in detail above, the present disclosure is not limited to such examples. It is clear that a person skilled in the art to which the present disclosure pertains can conceive of various modified or altered examples within the scope of the technical ideas described in the claims, and it is understood that these also naturally fall within the technical scope of the present disclosure.

Claims

1. A brain function enhancer comprising at least one of Lacticaceae Bacillus paracasei cells and a processed product of said cells as an active ingredient.

2. The brain function enhancing agent according to claim 1, wherein the Lacticaceae Bacillus paracasei is Lacticaceae Bacillus paracasei YIT 9029 (FERM BP-1366).

3. The daily intake amount is 10 or more in terms of the viable cell count of Lacticaceae Bacillus paracasei. 10 The brain function enhancer according to claim 1 or 2, wherein the amount of the brain function enhancer is 100% or more.

4. The density of the Lacticaceae Bacillus paracasei in one intake is 10 10 The brain function enhancer according to claim 1 or 2, wherein the cfu / 100 mL or more.

5. The brain function enhancer according to claim 1 or 2, which is at least one of an attention enhancer, an alertness enhancer, an agent for enhancing a stimulant response, and an agent for maintaining performance.

6. Use of at least one of Lacticaceae Bacillus paracasei cells and a processed product thereof for the production of a brain function enhancer.

7. The use according to claim 6, wherein the Lacticaceae Bacillus paracasei is Lacticaceae Bacillus paracasei YIT 9029 (FERM BP-1366).

8. Lacticaceae Bacillus paracasei viable cell count 10 10 A method for improving brain function comprising orally ingesting at least cfu / day for at least four consecutive weeks.

9. The density of the Lacticaceae Bacillus paracasei in one intake is 10 10 The method for improving brain function according to claim 8, wherein the subject is ingested in an amount of at least cfu / 100 mL.

10. The method for improving brain function according to claim 8 or 9, wherein the improvement in brain function is a reduction in the intensity of theta waves.

11. The method for improving brain function according to claim 8 or 9, wherein the improvement in brain function is a shortening of the P300 latency of an event-related potential.

12. Use of at least one of Lacticaceae Bacillus paracasei cells and a processed product thereof for assisting in the acquisition of event-related potential P300 latency.

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