Higher brain function improvers

Abstract

To provide a higher brain function improver.SOLUTION: A higher brain function improver contains at least one selected from the group consisting of Euglena, paramylon, processed paramylon, and β-1,3-glucan.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an agent for improving higher brain function, etc. [Background technology]

[0002] Higher brain functions such as selective attention and spatial working memory are related to various activities and behaviors. These functions can be reduced by diseases such as dementia in the elderly, and can also be reduced by stress, insomnia, deterioration of mental state (depression), and fatigue. In today's world where the aging population is progressing and stress and insomnia are common, there is a demand for means to improve higher brain functions.

[0003] Euglena is a microalgae belonging to the genus Euglena and is used as a food material. Euglena extracts are also applied to the skin (Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Special Publication No. 2008-526954 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide an agent for improving higher brain function. [Means for solving the problem]

[0006] As a result of intensive research in view of the above problems, the present inventors have found that the above problems can be solved by an agent for improving higher brain function that contains at least one selected from the group consisting of Euglena, paramylon, a processed paramylon product, and β-1,3-glucan. Based on this finding, further research has led to the completion of the present invention. That is, the present invention encompasses the following aspects. Item 1. An agent for improving higher brain function, comprising at least one selected from the group consisting of Euglena, paramylon, processed paramylon products, and β-1,3-glucan. Item 2. The agent for improving higher brain function according to Item 1, which contains at least one selected from the group consisting of Euglena, paramylon, and processed paramylon products. Item 3. The agent for improving higher brain function according to Item 1 or 2, which contains Euglena, and the Euglena is Euglena gracilis. Item 4. The agent for improving higher brain function according to Item 1 or 2, which contains Euglena, and the Euglena is Euglena gracilis EOD-1 strain (accession number FERM BP-11530). Item 5. The agent for improving higher brain function according to any one of Items 1 to 4, for use in improving at least one selected from the group consisting of selective attention and spatial working memory. Item 6. The agent for improving higher brain function according to any one of Items 1 to 5, for use in improving selective attention and spatial working memory. Item 7. The agent for improving higher brain function according to any one of Items 1 to 6, which is a food composition, a nutritional supplement, or a food additive. Item 8. The agent for improving higher brain function according to any one of Items 1 to 7, which is an oral composition. Item 9. An agent for improving selective attention and / or spatial working memory, comprising at least one selected from the group consisting of Euglena, paramylon, a processed paramylon product, and β-1,3-glucan. Effect of the Invention

[0007] According to the present invention, an agent for improving higher brain function can be provided. [Brief description of the drawings]

[0008] [Figure 1]The figures show the average number of digit errors (vertical axis) for the control diet group and the test diet group (horizontal axis) in the 4th set of task A in the Advanced Trail Making Test on the test day 4 weeks after intake. * indicates that the p-value in the intergroup comparison with the control diet group (Mann-Whitney U test) is less than 0.05. [Diagram 2] The figures show the average number of digit errors (vertical axis) for the control diet group and test diet group (horizontal axis) in the third set of task B in the Advanced Trail Making Test on the test day four weeks after intake. * indicates that the p-value in the intergroup comparison with the control diet group (Mann-Whitney U test) is less than 0.05. [Diagram 3] The graph shows the average values ​​(vertical axis) of the control diet group and test diet group (horizontal axis) for the average reaction time of the second set C task in the Advanced Trail Making Test on the test day 4 weeks after intake. † indicates that the p-value in the intergroup comparison with the control diet group (t-test) is less than 0.1. [Figure 4] The graph shows the average values ​​(vertical axis) of the control diet group and test diet group (horizontal axis) for the average reaction time of task C in the third set of the Advanced Trail Making Test on the test day four weeks after intake. † indicates that the p-value in the intergroup comparison with the control diet group (t-test) is less than 0.1. [Diagram 5] The figures show the average number of digit errors (vertical axis) for the control diet group and test diet group (horizontal axis) in the 4th set of task C in the Advanced Trail Making Test on the test day 4 weeks after intake. * indicates that the p-value in the intergroup comparison with the control diet group (Mann-Whitney U test) is less than 0.05. [Figure 6] The figure shows the average number of digit errors (vertical axis) for the control diet group and test diet group (horizontal axis) in the total number of digit errors in task B for four sets in the Advanced Trail Making Test on the test day four weeks after intake. * indicates that the p-value in the intergroup comparison with the control diet group (Mann-Whitney U test) is less than 0.05. [Figure 7]The total number of errors (number of blank errors + number of incorrect digit errors) in Task C of the Advanced Trail Making Test, total of 4 sets. The average value (vertical axis) of the change before and after intake for the control diet group and the test diet group (horizontal axis) is shown. * indicates that the p-value in the intergroup comparison with the control diet group (Mann-Whitney U test) is less than 0.05. [Figure 8] The graph shows the average (vertical axis) of the change in the number of incorrect digit errors in task C, a total of four sets, before and after intake for the control and test food groups (horizontal axis). † indicates that the p-value in the intergroup comparison with the control group (Mann-Whitney U test) is less than 0.1. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] In this specification, the expressions "contain" and "comprise" include the concepts of "contain", "include", "consist essentially of" and "consist only of".

[0010] In one aspect, the present invention relates to an agent for improving higher brain function (sometimes referred to as the "agent of the present invention" in this specification) containing at least one selected from the group consisting of Euglena, paramylon, a processed paramylon product, and β-1,3-glucan. This will be described below.

[0011] 1. Euglena Euglena is a microalgae belonging to the genus Euglena, and is not particularly limited thereto. Specific examples of Euglena include Euglena gracilis (Euglena gracilis), Euglena longa , Euglena caudata , Euglena oxyuris , Euglena tripteris , Euglena proxima , Euglena viridis , Euglena sociabilis , Euglena ehrenbergii , Euglena deses , Euglena pisciformis , Euglena spirogyra , Euglena acus , Euglena geniculata , Euglena intermedia , Euglena mutabilis , Euglena sanguinea , Euglena stellata , Euglena terricola , Euglena klebsi , Euglena rubra , Euglena cyclopicola Among these, from the viewpoint of more reliably exerting the effects of the present invention, Euglena gracilis is preferred, and Euglena gracilis EOD-1 strain (internationally deposited on June 28, 2013 with the National Institute of Technology and Evaluation, International Patent Organism Depositary (NITE-IPOD, Room 120, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan, 292-0818) under the provisions of the Budapest Treaty under deposit number FERM BP-11530) is more preferred, from the viewpoint of more reliably exerting the effects of the present invention.

[0012] The form of Euglena is not particularly limited as long as it contains the cell body of Euglena or most of its components. Examples of the form of Euglena include a dry powder form of Euglena, a suspension of Euglena, and a Euglena extract, and among these, a dry powder form of Euglena is preferred.

[0013] The paramylon content of Euglena in a dry state is, for example, 50% or more, preferably 60% or more, and more preferably 70% or more.

[0014] Euglena may be of one type alone or of two or more types in combination.

[0015] 2. β-1,3-glucan, paramylon The β-1,3-glucan is not particularly limited as long as it has a single sugar chain (or sugar chain structure) as the main chain, in which glucose is linked only by β-1,3 bonds. The β-1,3-glucan is not limited to linear ones, but also includes those having branched chains.

[0016] The weight-average molecular weight of the β-1,3-glucan derivative is not particularly limited, but is, for example, 1×10 4 ~2×10 6 , preferably 5 x 10 4 ~1×10 6, more preferably 1×10 5 ~1×10 6 The weight average molecular weight can be measured by a GPC method.

[0017] Although β-1,3-glucan may be obtained by chemical synthesis, natural β-1,3-glucan produced by various organisms is preferable from the viewpoint of availability. Examples of natural β-1,3-glucan include paramylon, curdlan, laminaran, callose, lentinan, and schizophyllan. Among these, paramylon is preferable. Paramylon will be described below.

[0018] Paramylon is a β-1,3-glucan derived from Euglena, and is not particularly limited in that respect.

[0019] The Euglena from which paramylon is derived is as explained above in "1. Euglena."

[0020] The mass average molecular weight of paramylon is not particularly limited, but is, for example, 1×10 4 ~5×10 6 , preferably 2 x 10 4 ~1×10 6 , more preferably 5 × 10 4 ~1×10 6 , and more preferably 1×10 5 ~5×10 5 It is.

[0021] The mass average molecular weight can be measured by SEC-MALS analysis under the following conditions: Detector: Multi-angle scattering detector (DAWN HELEOS II, manufactured by Wyatt Technology) Differential refractometer detector (Optilab T-rEX, manufactured by Wyatt Technology) Columns used: 2 TSKgel α-M (Tosoh) Mobile phase: DMSO with 0.05M potassium bromide Flow rate: 0.5 mL / min.

[0022] Within Euglena cells, paramylon normally exists as paramylon particles, which are composed of triple helical structures formed by β-1,3-glucan chains highly accumulated in a certain order.

[0023] The shape of the paramylon particles is not particularly limited, but is usually a flat spheroid.

[0024] The particle size distribution of the paramylon particles is not particularly limited, but is, for example, 0.5 to 15 μm, and preferably 1 to 6 μm. The average particle size of the paramylon particles is also not particularly limited, but is, for example, 1 to 10 μm, and preferably 2 to 4 μm.

[0025] The form of paramylon is not particularly limited as long as it contains paramylon. Examples of the form of Euglena include a dry powder form of paramylon and a suspension of paramylon, and among these, a dry powder form of paramylon is preferred.

[0026] Paramylon may be used alone or in combination of two or more types.

[0027] 3. Method for producing Euglena and paramylon Euglena can be prepared in large quantities by a method including a step of culturing Euglena contained in a liquid (culturing step). The culturing step can be carried out, for example, according to a known method (for example, the method described in Japanese Patent No. 5883532). In the culturing step, Euglena microalgae are typically cultured under aerobic conditions while stirring a liquid (culture solution) containing water, Euglena, and nutrients that Euglena can utilize.

[0028] Examples of nutrients include sugars (monosaccharides such as glucose (grape sugar) and fructose (fruit sugar)), minerals (e.g., sodium, potassium, magnesium, calcium, iron, zinc, molybdenum, copper, phosphorus, nitrogen, sulfur, boron, etc.), and B vitamins (e.g., vitamin B1 (thiamine), vitamin B2 (riboflavin), niacin, pantothenic acid, vitamin B6 (pyridoxine, pyridoxal, or pyridoxamine), vitamin B12 (cyanocobalamin), folic acid, biotin, etc.). The concentration of nutrients in the culture solution is not particularly limited as long as it is a concentration that allows the survival, proliferation, etc. of Euglena.

[0029] The light conditions in the culture step are not particularly limited, and the culture step may be performed under either light or dark conditions. When cultured by heterotrophic culture, the culture is performed under dark conditions. As light conditions, a normal light intensity for growing algae can be adopted. As dark conditions, for example, 10 μmol / m 2 / s, preferably in a completely dark place with no light at all.

[0030] The culture temperature in the culture step is not particularly limited as long as it is a temperature at which Euglena can grow. The culture temperature (temperature of the culture solution) is, for example, 20°C to 35°C.

[0031] The pH of the liquid in the culture step is not particularly limited as long as it is a pH at which Euglena can grow, and examples of pH at which Euglena can grow include a pH of 3.0 to 5.5.

[0032] After the culturing step, it is preferable to concentrate the Euglena by centrifugation of the liquid, gravity separation, etc. The obtained Euglena can be subjected to additional treatment (e.g., suspension in a liquid, dispersion in water or oil, extraction into an extract, drying and powdering, etc.) depending on the desired form.

[0033] Paramylon particles can be produced by separating, isolating, or purifying from Euglena according to or in accordance with a known method (e.g., the method described in Japanese Patent No. 5883532). Paramylon particles can be easily obtained, for example, by recovering the cell contents obtained by destroying the cell membrane of Euglena. Paramylon particles may also be purified as necessary. Various methods for purifying paramylon particles are known (e.g., Japanese Patent No. 5883532), and they can be performed according to those methods. Examples of purification steps include a surfactant treatment step and a washing step. The obtained Euglena can be subjected to additional treatment (e.g., suspension in liquid, dispersion in water or oil, dry powderization, etc.) depending on the desired form.

[0034] 4. Paramylon processed products Paramylon processed products are obtained by processing paramylon, such as physical processing, chemical processing, etc., and are not particularly limited insofar as such. Examples of paramylon processed products include fibrous paramylon, amorphous paramylon, etc. Amorphous paramylon can be obtained by chemical processing according to or in accordance with known methods, for example, the method described in JP 2011-184592 A.

[0035] As the paramylon processed product, fibrous paramylon is preferable. The fibrous paramylon is described below.

[0036] Fibrous paramylon is a β-1,3-glucan derived from Euglena, and is not particularly limited as long as it is in a fibrous form. Up until now, amorphous paramylon obtained by chemically treating paramylon particles (alkali treatment, etc.) has been reported, but this is not recognized as fibrous when observed under an electron microscope, and is a mass with an indefinite shape and size, so it is not included in the category of fibrous paramylon.

[0037] The weight-average molecular weight of the fibrous paramylon is not particularly limited, but is, for example, 1×10 4 ~2×107 , preferably 1 x 10 5 ~5×10 5 It is.

[0038] The weight average molecular weight can be measured by SEC-MALS analysis using the following method: SEC apparatus: LC-10ADvp system (Shimadzu Co., Japan); column used: KD-806M (Shodex., Japan); MALS detector: DAWN HELEOSII (Wyatt Technologies, USA), eluent: 1% LiCl / DMI, Flow rate: 0.5 mL / min.

[0039] The diameter of the fibers of fibrous paramylon is not particularly limited, but is, for example, 10 to 500 nm, preferably 20 to 300 nm, and more preferably 50 to 200 nm. The diameter of the fibers of fibrous paramylon can usually be measured based on an electron microscope image of the fibrous paramylon.

[0040] The submerged volume of fibrous paramylon in water is not particularly limited, but is, for example, 30 to 300 mL / g, preferably 50 to 250 mL / g, and more preferably 70 to 200 mL / g.

[0041] The submerged volume can be measured according to or by the following method: The measurement is performed according to the method described in "Dietary Fiber - Basics and Applications - 3rd Edition, p.111, Daiichi Publishing, Tokyo (2008) Edited by the Editorial Committee of the Japanese Society for Dietary Fiber, supervised by the Japanese Society for Dietary Fiber (2008)". Specifically, it is as follows. 125 mg of the slurry test sample is weighed out in dry mass equivalent and placed in a 25 mL plastic tube, and the plastic tube is vigorously shaken by hand to stir the contents. The contents are then transferred to a 25 mL graduated cylinder and pure water is added until the total volume reaches 25 mL. After stirring the liquid in the graduated cylinder, it is left to stand at 37°C for 24 hours. This causes the sample to settle, and two layers (a layer mainly containing the settled sample (lower layer) and a layer mainly containing water (upper layer)) are formed, separated by an interface. The volume of the lower layer is calculated from the graduations on the graduated cylinder, and the resulting volume is divided by the sample mass (dry mass) to calculate the submerged volume in water (mL / g). The test is performed three or four times, and the average value and standard deviation are calculated.

[0042] Fibrous paramylon has relatively high resistance to enzymatic decomposition. For example, the amount of monomer (glucose) generated by decomposition with β-glucanase is, for example, 0.1 to 50 mg, preferably 1 to 10 mg, per 1 g of fibrous paramylon.

[0043] This amount can be measured according to or analogous to the following method: Prepare a reaction solution [test substance 30 mg (dry weight), buffer solution (Tokyo Chemical Industry Co., Ltd. B0156, potassium hydrogen phthalate-sodium hydroxide buffer (pH 4.0)) 5 mL, enzyme solution (Japan Biocon Co., Ltd. endo-1,3-β-Glucanase (enzyme content: 50 units / mL)) 0.1 mL, pure water, reaction solution volume 10 mL] and shake horizontally at 40 ° C for 24 hours at 45 rpm. After shaking, freeze and store immediately, then freeze-dry for concentration. After freeze-drying, add 0.5 mL of pure water to each sample and stir (20-fold concentration). Centrifuge (10,000G, 5 minutes, 4 ° C) and collect the supernatant twice. Measure the glucose concentration in the collected supernatant using a measurement kit (Wako Pure Chemical Industries, Glucose CII-Test Wako). Calculate the amount of glucose produced (mg) per 1 g of test substance based on the measured value.

[0044] Fibrous paramylon has a relatively low solubility in alkaline solutions. For example, fibrous paramylon does not dissolve in a 0.1 to 0.3 M aqueous solution of sodium hydroxide. Here, "does not dissolve" means, for example, that the absorbance (660 nm) of the solution after suspending fibrous paramylon in the aqueous solution (for example, immediately after suspension to after 1 hour) is, for example, 0.1 or more, preferably 1.0 or more.

[0045] Solubility can be measured according to or by the following method: 250 mg (dry weight) of the test substance is suspended in 10 mL of test solution (pure water, 0.1 M NaOH aqueous solution, 0.3 M NaOH aqueous solution) in a vial. After shaking the vial vigorously by hand for 20 seconds and after shaking it on a shaker at 80 rpm for 1 hour, the absorbance of the liquid in the vial at 660 nm is measured. The absorbance is measured using a spectrophotometer V-730 manufactured by JASCO Corporation.

[0046] The relative value of the crystallinity of fibrous paramylon to that of granular paramylon (crystallinity of fibrous paramylon / crystallinity of granular paramylon) is, for example, 0.60 to 0.90, and preferably 0.65 to 0.80.

[0047] Crystallinity can be measured according to or in accordance with the following method: XRD measurement is performed on the test substance. The conditions are as follows: Equipment: PANalytical X'Pert3 Powder, tube voltage: 45 kV, tube current: 40 mA, measurement range: 5.005 to 50.018°, measurement interval: 0.013°, analysis software: HighScore. The crystallinity is analyzed based on the ratio of the intensity of the amorphous part to the intensity of the crystalline part at 2θ = 5 to 80°. The analysis is performed after removing the background caused by the device from each measurement device (background setting Auto, bending factor 0, granularity 100), and the amorphous part is determined by the tangent line passing through 2θ = 14, 29°. The conditions of the pending factor and granularity that determine each amorphous part are 0 / 20.

[0048] The fibrous paramylon may be in a form dispersed in a solvent such as water, or in a dry form. Even if the fibrous paramylon is in a dry form, it can be redispersed in water.

[0049] In this specification, the term "dry form" refers to a form having a moisture content of 15% by mass or less, preferably 10% by mass or less, and more preferably 5% by mass or less.

[0050] As the fibrous paramylon, a defibrated product of paramylon particles obtained by physically defibrating the paramylon particles can be preferably used. In addition, a defibrated product of Euglena obtained by applying the defibration treatment to Euglena can also be used as the fibrous paramylon.

[0051] The defibration treatment is not particularly limited as long as it is a treatment that can defibrate the β-1,3 glucan present in the paramylon particles without breaking the hydrogen bonds (for example, by breaking only 10% or less, 5% or less, 2% or less, or 1% or less of the hydrogen bonds of the β-1,3 glucan), or can unravel a part or all of the β-1,3-glucan chain present in the paramylon particles or the triple helix structure formed by the β-1,3-glucan chain. It is preferable to defibrate the paramylon particles to form a fiber by hardly breaking the hydrogen bonds of the β-1,3 glucan present in the paramylon particles. A known treatment that can grind (shear) or pulverize (preferably grind (shear)) fine particles such as paramylon particles can be used as the defibration treatment.

[0052] The defibration treatment can be carried out using known devices such as a grinder (shearing machine) and a pulverizer. Devices used in the defibration treatment include, for example, a stone mill type grinder, a jet mill, a twin-screw kneader, a high-pressure homogenizer, a high-pressure emulsifier, a twin-screw extruder, and a bead mill. Among these, preferred are a stone mill type grinder and a bead mill.

[0053] The defibration treatment can be performed in a wet or dry manner. The wet defibration treatment is preferable because it allows the fibrous paramylon to be dispersed in the solution more efficiently. When performing the wet defibration treatment, the solvent is not particularly limited as long as it is a solvent capable of dispersing the fibrous paramylon, and water is preferably used.

[0054] The defibration treatment may be performed using one type of material alone or a combination of two or more types. In addition, the paramylon may be partially defibrated, and as long as it contains defibrated paramylon, it is within the scope of the present invention.

[0055] 5.Applications At least one selected from the group consisting of Euglena, paramylon, a paramylon processed product, and β-1,3-glucan (hereinafter sometimes referred to as the "active ingredient of the present invention") has an effect of improving higher brain functions. Therefore, the active ingredient of the present invention can be used to improve higher brain functions.

[0056] In addition, "improvement" refers to improvement or alleviation of a symptom or condition, prevention or delay of worsening of a symptom or condition, and reversal, prevention or delay of progression of a symptom or condition.

[0057] Higher brain functions refer to cognitive processes and actions such as perception, memory, learning, thinking, and judgment. The active ingredient of the present invention can be suitably used to improve selective attention, spatial working memory, and the like, among higher brain functions. The active ingredient of the present invention can preferably improve selective attention, spatial working memory, and the like during fatigue.

[0058] The active ingredient of the present invention can preferably be used for comprehensive applications including multiple applications (two or more, more preferably three or more, even more preferably four or more, still more preferably five or more, and even more preferably six or more) among various applications.

[0059] Selective attention is the ability to choose important information from various pieces of information and pay attention to it. Some examples of reactions, behaviors, activities, etc. related to selective attention are shown below. -Respond when your name is called in a conversation with many people. -You can talk to a specific person even when many people are talking. Find the files you need among many others. - Find your destination building among many others. ·Find signs and information about your destination when traveling. · Look for hazard signs at construction sites. Find the book you want to know at the bookstore.

[0060] Spatial working memory is the ability to temporarily store and process information in relation to space and location while performing a task. Some examples of reactions, behaviors, and activities that involve spatial working memory are shown below. - Temporarily put away things like glasses, keys, or cell phone and pick them up later. -Can remember paths in a maze that have already been taken and avoid repeating them. - You can be told where the store you want to go is and go there without taking notes. - In sports, play while keeping track of the positions of teammates and opponents.

[0061] Furthermore, the active ingredient of the present invention has the following uses, purposes and targets: (a) Maintain, enhance, support, or improve attention (b) Maintain, enhance, support, or improve cognitive function (c) Maintain, enhance, support, or improve the ability to quickly recognize important events (d) Maintain, enhance, support, or improve your ability to quickly find what you need. (e) Maintain, enhance, support, or improve the ability to focus on important information within a pool of information (f) Maintaining, enhancing, supporting, or improving working memory (g) Maintain, enhance, support, and improve working memory (h) Maintain, enhance, support and improve the ability to quickly recognize, simultaneously process and act on visual information obtained. (i) Maintain, enhance, support and improve the ability to temporarily store and process information about space and place It can be used for such purposes.

[0062] The agent of the present invention can be used in various fields, for example, as a food composition (including health foods, health promoting agents, nutritional supplements (supplements, etc.)), food additives, cosmetics, cosmetic additives, medicines, reagents, feed, etc. The agent of the present invention is preferably an oral composition.

[0063] The form of the agent of the present invention is not particularly limited, and may be in a form that is commonly used for each application depending on the application.

[0064] When the agent of the present invention is intended for use as a food composition, the agent may take the form of liquid, gel or solid foods, for example, beverages such as juice, soft drinks, tea, soup and soy milk, salad oil, dressing, yogurt, jelly, pudding, furikake, powdered milk for infants, cake mix, dairy products (e.g., powder, liquid, gel, solid, etc.), bread and confectionery (e.g., cookies, etc.).

[0065] When the agent of the present invention is used as a cosmetic product, examples of the form of the agent include milky lotion, cosmetic liquid, face cream, hand cream, lotion, body soap, shampoo, rinse, cosmetic gel, pack, foundation, lip cream, and facial cleanser.

[0066] In the case where the agent of the present invention is used for pharmaceutical purposes, examples of the form of the agent include ointments, liquids for external use (liniments, lotions, etc.), sprays (aerosols for external use, pump sprays, etc.), creams, gels, patches (plasters, tapes such as plasters (reservoir type, matrix type, etc.), poultices, patches, microneedles, etc.), eye drops, eye ointments, nasal drops, suppositories, semi-solid rectal preparations, enemas, and other preparation forms suitable for parenteral intake (particularly, preparation forms for external use); tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, lozenges, jelly drops, etc.), pills, granules, fine granules, powders, hard capsules, soft capsules, dry syrups, liquids (including drinks, suspensions, syrups), and jellies, and other preparation forms suitable for oral intake (oral preparation forms).

[0067] When the agent of the present invention is used as an additive, a health promoting agent, a nutritional supplement (such as a supplement), etc., the agent may be in the form of, for example, a tablet (including an orally disintegrating tablet, a chewable tablet, an effervescent tablet, a lozenge, a jelly-like drop, etc.), a pill, a granule, a fine granule, a powder, a hard capsule, a soft capsule, a dry syrup, a liquid (including a suspension and a syrup), a jelly, etc.

[0068] The agent of the present invention may further contain other components as necessary. The other components are not particularly limited as long as they are components that can be blended into food compositions (including health foods, health promotion agents, and nutritional supplements (supplements, etc.)), food additives, cosmetics, cosmetic additives, medicines, reagents, feeds, etc., and include, for example, bases, carriers, solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants, lubricants, thickeners, colorants, flavors, chelating agents, etc.

[0069] The content of the active ingredient in the agent of the present invention depends on the application, mode of use, state of the subject to which it is applied, etc., and is not limited, but can be, for example, 0.0001 to 100% by mass, preferably 0.001 to 50% by mass.

[0070] The amount of the agent of the present invention to be applied (e.g., administered, ingested, inoculated, etc.) is not particularly limited as long as it is an effective amount that exhibits a higher brain function improving effect, and is usually 0.1 to 10,000 mg / kg body weight per day as the dry weight of the active ingredient. The above application amount is preferably applied once or more times a day (e.g., 1 to 3 times), and can be appropriately increased or decreased depending on age, pathology, and symptoms.

[0071] In a preferred embodiment of the present invention, the amount of Euglena applied (dry weight) is preferably 100 to 1000 mg per day, more preferably 250 to 750 mg, and even more preferably 400 to 600 mg. Application is preferably once a day, and more preferably every day. The application period is preferably 3 days or more, more preferably 1 week or more, even more preferably 2 weeks or more, and even more preferably 3 weeks or more. Since the active ingredient of the present invention is naturally derived and highly safe, there is no particular upper limit to the application period, but it may be, for example, 3 years, 1 year, 6 months, 3 months, or 2 months. EXAMPLES

[0072] The present invention will be described in detail below based on examples, but the present invention is not limited to these examples.

[0073] Manufacturing Example 1 The test food was made into capsules using dried powder (manufactured by Kobelco Eco-Solutions, paramylon content 70% or more) of Euglena gracilis EOD-1 strain (National Institute of Technology and Evaluation, Patent Organism Depositary Center (NITE-IPOD)) with the following composition, and capsules containing dextrin were manufactured as a control food.

[0074] [Table 1]

[0075] Test Example 1 (1) Subjects Among those registered in the subject bank of the institution responsible for conducting the study, healthy men and women aged 20 to 65 years old were screened, who experienced fatigue in their daily lives, who had received an explanation of the study in advance, were able to understand its contents, and agreed to its purpose, and who could provide written consent. However, the following subjects were excluded from the study: those suffering from or with a history of severe cardiovascular, hepatic, renal, respiratory, endocrine or metabolic disorders; those with chronic fatigue syndrome (CFS) or those judged by the principal investigator to have severe fatigue such as sudden chronic fatigue; those suffering from chronic illnesses and receiving outpatient treatment; those with mental illnesses such as depression or schizophrenia; those with sleep disorders requiring treatment; those who may have an allergic reaction to the test foods; those who regularly use medicines or quasi-drugs with the efficacy of recovering from fatigue or providing nutrition during physical fatigue; those who regularly use functional foods that display functionality related to fatigue; heavy alcohol drinkers (those who consume 60 g or more of pure alcohol per day); those with a BMI of less than 17 or 30 or more; those who have consumed 200 mL of alcohol within one month or 400 mL of alcohol within three months prior to the start of the study. Those who had drawn more than 100 mL of blood (such as blood donations), those who had participated in other clinical trials within the past three months, those currently participating in other clinical trials, those who were pregnant or breastfeeding, or those planning to become pregnant, and those who the principal investigator deemed inappropriate were excluded. As a result, 66 people aged 22 to 62 participated in this study. These 66 people were assigned to two groups by the person in charge of allocation, a third party who was not directly involved in the study. The allocation method was to assign random numbers generated for randomization to the subjects, and the subjects were assigned to the two groups in ascending order of numbers.

[0076] (2) Test meal There were two types of test foods, a test food and a control food (placebo) (Production Example 1). The test food was a food containing Euglena gracilis EOD-1 strain, and the control food (placebo) was a food not containing Euglena gracilis EOD-1 strain. Each test food was packed in an aluminum-coated bag with 14 tablets, and an identification code was printed on the aluminum-coated bag to distinguish it from other products and test foods of other studies. It was confirmed by the Institutional Review Board (IRB) that the test food and placebo could not be distinguished by appearance or taste.

[0077] The test food was ingested at two tablets (containing 500 mg of Euglena gracilis EOD-1 strain (350 mg of paramylon derived from Euglena gracilis EOD-1 strain)) once a day with dinner for four weeks. If the test food was not ingested at dinner, the subjects were asked to take it before going to bed that day.

[0078] (3) Study design The study design was a randomized, double-blind, parallel group comparative study. Daily fatigue load was administered on the test day at the start of intake and on the test day four weeks after intake. Daily fatigue load was administered in four sets (four hours), consisting of a 30-minute 2-back task and a 30-minute Advanced Trail Making Test (ATMT), each set lasting one hour. After the four hours of daily fatigue load, a four-hour recovery period was set. Instructions for the 2-back task and ATMT were also administered before the test day of this study.

[0079] In the 2-back task, letters are randomly displayed on the screen every 3 seconds, and participants are asked to answer whether the currently displayed letter is the same as the letter displayed two letters ago.

[0080] Regarding the ATMT, Task A involved pressing numbers 1 to 25 fixed on a screen in order, Task B involved pressing the numbers in the same order, and when a target number was pressed, the number disappeared and a new number appeared in a random position (when 1 was pressed, 1 disappeared and 26 appeared, when 2 was pressed, 2 disappeared and 27 appeared), and Task C involved pressing a target number and changing the order of all the numbers. Tasks A, B, and C were repeated in this order. Selective attention could be evaluated by comparing the reaction time and number of errors in Task C. Tasks A and B could also be used to evaluate the combined abilities of selective attention and spatial working memory.

[0081] In addition, the mean reaction time, number of trials, and number of errors (number of blank-pressing errors + number of incorrect-digit-pressing errors) for each of the four sets of the ATMT (ABC task) were evaluated in total before and after intake.

[0082] (4) Test results Some of the results are shown in Figures 1 to 8. The test diet group achieved better results in all tasks A to C than the control diet group. This shows that taking Euglena can improve higher brain functions such as selective attention and spatial working memory.

Claims

1. A selective attention improving agent containing Euglena for application to subjects including healthy individuals.

2. The selective attention improving agent described in claim 1, wherein the Euglena is Euglena gracilis.

3. The selective attention improving agent described in claim 1, wherein the Euglena is Euglena gracilis EOD-1 strain (accession number FERM BP-11530).

4. The selective attention improving agent according to any one of claims 1 to 3, which is a food composition, a nutritional supplement, or a food additive.

5. The selective attention improving agent according to any one of claims 1 to 4, which is an oral composition.

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