Composition containing diamine and / or polyamine for preventing deterioration of brain function or improving brain function

Abstract

To provide a composition for preventing deterioration of brain function or improving brain function.SOLUTION: The present invention provides a composition containing diamine and / or polyamine, wherein brain function is at least one selected from the group consisting of comprehensive memory, verbal memory, visual memory, cognitive function speed, motor speed, processing speed, comprehensive attention, cognitive flexibility, response time, and executive function.SELECTED DRAWING: None

Description

Technical Field

[0001] This specification discloses a composition containing diamine and / or polyamine for preventing brain function decline or improving brain function.

Background Art

[0002] Brain function decline mainly occurs with aging, and is accompanied by various symptoms such as learning disorders, memory disorders, language disorders, anxiety disorders, insomnia, and decreased motivation. In modern times where medical development has extended the average lifespan, prevention and countermeasures against brain function decline are considered important for extending the healthy lifespan.

[0003] The diagnosis of brain function disorders is mainly classified into three categories: "healthy individuals" with no abnormalities, "dementia" in which cognitive function decline causes problems in daily life, and "mild cognitive impairment (MCI)" in which cognitive function decline is recognized but there are no problems in daily life. There is no fundamental treatment for dementia, and symptom relief and progression suppression are the main treatments. Therefore, early detection at the MCI stage, and thus prevention at the "pre-disease" stage, are important.

[0004] Diamine is a linear fatty acid hydrocarbon compound having two amines. Polyamine is a linear fatty acid hydrocarbon compound having three or more amines. Diamine and / or polyamine are known to be widely involved in the synthesis of nucleic acids and proteins and the regulation of enzyme activity (Non-Patent Document 1). In addition, Non-Patent Document 2 shows that there is a correlation between serum spermidine content and the MMSE score representing brain function level. Therefore, in humans, a clinical trial on oral administration of spermidine was conducted, but no positive results regarding cognitive function improvement were reported (Non-Patent Document 3).

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Non-Patent Literature

[0006]

Non-Patent Literature 1

Non-Patent Literature 2

Non-Patent Literature 3

Summary of the Invention

Problems to be Solved by the Invention

[0007] An object of the present invention is to provide a composition containing diamine and / or polyamine for preventing brain function decline or improving brain function.

Means for Solving the Problems

[0008] The present invention includes the following embodiments. Item 1. A composition containing diamine and / or polyamine for preventing brain function decline or improving brain function. Item 2. The composition according to Item 1, wherein the brain function is at least one selected from the group consisting of general memory, verbal memory, visual memory, cognitive function speed, motor speed, processing speed, general attention, cognitive flexibility, reaction time, and executive function. Item 3. The composition according to Item 1 or 2, wherein the subject to be administered is a person aged 40 or older. Item 4. The diamine is at least one selected from the group consisting of putrescine, cadaverine, and 1,3-diaminopropane, The polyamine is at least one selected from the group consisting of spermidine, spermine, caldine, homospermidine, aminopropylcadaverine, thermine, thermospermine, canavanine, aminopentylnorspermidine, N,N-bis(aminopropyl)cadaverine, homospermidine, caldopentamine, homocaldopentamine, caldohexamine, and homocaldohexamine spermidine. The composition according to any one of items 1 to 3. Item 5. The composition according to any one of items 1 to 4, wherein the composition is a food composition or an oral pharmaceutical composition.

Effect of the Invention

[0009] It is possible to provide a composition containing a diamine and / or a polyamine for preventing a decline in brain function or for improving brain function.

Mode for Carrying Out the Invention

[0010] 1. Composition One embodiment of the present invention relates to a composition containing a diamine and / or a polyamine for preventing a decline in brain function or for improving brain function.

[0011] A decline in brain function often occurs with aging, and various symptoms such as learning disabilities, memory disorders, language disorders, anxiety disorders, insomnia, and decreased motivation may occur concomitantly. A typical disease associated with a decline in brain function is dementia, and mild cognitive impairment (MCI) is a stage prior to that. MCI is in between healthy people and dementia, and refers to a state in which cognitive function decline is recognized but there is no impairment in daily life. The disease rate is 10-20% in people aged 65 and over, and it has been reported that about 70% of them will progress to dementia if untreated (Hiroshi Suzuki, J. Nihon Univ. Sch. Med. (2012) 71(6):385-389).

[0012] The diagnostic criteria for MCI are, for example, according to the evaluation criteria of Petersen et al. (Yasushi Yamamoto, Journal of Neurology (2011) Vol. 113, No. 6): 1. There is a complaint of memory loss by the patient or family (caregiver). 2. There is a memory impairment that cannot be explained only by the effects of aging. 3. Activities of daily living are independent. 4. General cognitive function is normal. 5. Dementia is not recognized. Treatment of dementia is more likely to be effective when started at an earlier stage. Early detection and treatment at the MCI stage may improve cognitive function and prevent the progression to dementia. From the above, the importance of earlier detection and prevention at the pre-disease stage is further emphasized.

[0013] In the Mini-Mental State Examination (MMSE), a neuropsychological test used as a cognitive function test in clinical practice, the criteria set by the US ADNI study are: 27 - 30 points: normal (not excluding the possibility of MCI), 24 - 26 points: borderline (possible to be normal, MCI, or dementia), 20 - 23 points: suspected early dementia.

[0014] Also, as a simpler dementia questionnaire, a questionnaire method that evaluates six questions by the VAS (visual analog scale) method can be adopted.

[0015] Brain functions improved by the composition according to this embodiment include, for example, cognitive functions such as general memory, verbal memory, visual memory, cognitive function speed, motor speed, processing speed, general attention, cognitive flexibility, reaction time, executive function, and simple attention. These cognitive functions can be examined by the Cognitrax test. The Cognitrax test is a cognitive function test service designed for Japan based on the cognitive function test technology developed by CNS Vital Signs in the United States.

[0016] Preferably, the composition improves one or more of the above 11 cognitive functions. More preferably, it improves two or more, three or more, four or more.

[0017] Hereinafter, each cognitive function based on the Cognitrax test will be described. "Comprehensive Memory" indicates the ability to memorize and is evaluated as the total score of verbal memory and visual memory. "Verbal Memory" indicates the ability to memorize words and is evaluated by a verbal memory test. "Visual Memory" indicates the ability to memorize figures and is evaluated by a visual memory test. "Cognitive Function Speed" indicates the ability to quickly process visual information and is evaluated as the total of the average of the right hand and the average of the left hand in the finger tapping test and the total score of the number of correct responses in the SDC test. "Motor Speed" indicates the ability to quickly repeat delicate movements and is evaluated as the total score of the average of the right hand and the average of the left hand in the finger tapping test. "Processing Speed" indicates the ability to quickly process information and is evaluated as the total score obtained by subtracting the number of incorrect responses in the SDC test from the number of correct responses in the SDC test.

[0018] "Comprehensive Attention" indicates the ability to maintain attention and respond accurately, and is evaluated as the total score of the number of Stroop incorrect responses in the Stroop test, the number of incorrect responses in the attention shift test, and the total number of missed correct responses and the number of incorrect responses in the sustained processing test.

[0019] "Cognitive Flexibility" indicates the ability to process in response to changes in instructions, and is evaluated as the total score obtained by subtracting the number of incorrect responses in the attention shift test and the number of Stroop incorrect responses in the Stroop test from the number of correct responses in the attention shift test. "Reaction Time" indicates the ability to quickly respond to instructions and is evaluated as the average value of the composite reaction time and the Stroop reaction time in the Stroop test.

[0020] "Executive Function" indicates the ability to understand rules and concepts and make decisions, and is evaluated as the total score obtained by subtracting the number of incorrect responses in the attention shift test from the number of correct (response) responses in the attention shift test. "Simple Attention" indicates the ability to pay attention for a long time, and is evaluated as the total score obtained by subtracting the number of incorrect responses in the sustained processing test from the number of correct responses in the sustained processing test.

[0021] The subject to which the composition is administered may include those who are not suspected of having reduced brain function, those who are suspected of having reduced brain function, and those who have been determined to have reduced brain function. Among the evaluation criteria of Pertersen et al., those determined to have MCI may correspond to those who are suspected of having reduced brain function. Among the evaluation criteria of Pertersen et al., those determined to have dementia may correspond to those who have been determined to have reduced brain function. Further, among the evaluation criteria of Pertersen et al., those determined to be healthy or robust may correspond to those who are not suspected of having reduced brain function.

[0022] Since the risk of reduced brain function is high in the elderly, the age of the subject to which the composition is administered is preferably 40 years old or older, more preferably 50 years old or older, 60 years old or older, 70 years old or older, or 80 years old or older.

[0023] Whether the reduction of brain function can be prevented or the brain function has been improved can be determined by judging the intake effect of diamine and / or polyamine described below. If there is an intake effect of diamine and / or polyamine, it can be determined that the reduction of brain function can be prevented or the brain function has been improved.

[0024] In the present specification, diamine is a linear fatty acid hydrocarbon compound having two amines. Polyamine is a linear fatty acid hydrocarbon compound having three or more amines. Examples of diamine include putrescine, cadaverine, 1,3-diaminopropane, etc. and mixtures thereof. Examples of polyamine include spermidine, spermine, caldine, homospermidine, aminopropylcadaverine, thermine, thermospermine, canavanine, aminopentylnorspermidine, N,N-bis(aminopropyl)cadaverine, homospermine, caldopentamine, homocaldopentamine, caldohexamine, homocaldohexamine spermidine, etc. and mixtures thereof.

[0025] Diamine and / or polyamine may be added to the composition as a synthesized compound. Further, diamine and / or polyamine may be added to the composition as an extract derived from a plant containing these compounds, a constituent organism, or a purified product from the extract. The extract derived from a plant, the constituent organism, or the purified product from the extract (hereinafter also referred to as "diamine and / or polyamine composition") may contain natural components other than diamine and / or polyamine, such as saccharides such as monosaccharides, oligosaccharides, and polysaccharides, peptides, proteins, and the like. In the present invention, the diamine and / or polyamine composition refers to either an aqueous solution or a powder. The "solid content" refers to the solute content excluding water in the diamine and / or polyamine composition (solution) in the form of an aqueous solution, and includes, in addition to diamine and / or polyamine, saccharides, peptides, and salts. When the diamine and / or polyamine composition is a powder, the "solid content" refers to the entire diamine and / or polyamine composition in the form of a powder. In the present invention, "plant" refers to a plant body or a plant tissue, and "processed plant product" refers to a product obtained by processing them. "And / or" means that both may be included or either one kind may be sufficient.

[0026] As the plants and processed plant products, various ones can be used and are not particularly limited. For example, plants of the Cucurbitaceae family, Solanaceae family, Poaceae family, Brassicaceae family, Fabaceae family, Malvaceae family, Asteraceae family, Urticaceae family, Fabaceae family, Theaceae family, and their plant extracts, plant essences, processed products, etc. can be mentioned. Specifically, sweet potato, tomato, cucumber, pumpkin, melon, watermelon, tobacco, Arabidopsis thaliana, pepper, eggplant, bean, taro, spinach, carrot, strawberry, potato, rice, corn, alfalfa, wheat, barley, soybean, rapeseed, sorghum, eucalyptus, poplar, kenaf, Eucommia ulmoides, sugarcane, sugar beet, cassava, sago palm, nettle, lily, orchid, carnation, rose, chrysanthemum, petunia, torenia, forget-me-not, cyclamen, baby's breath, geranium, sunflower, miscanthus, cotton, enoki mushroom, shiitake mushroom, matsutake mushroom, reishi mushroom, other mushrooms, burdock, Agaricus, turmeric, purple carrot, citrus fruits, banana, kiwi, fruit juice, rice, wheat, barley, soybean, corn, millet, sunflower, germ extract, embryo extract, green tea, black tea, oolong tea, natto, soy milk, okara, etc. can be mentioned. Preferably, plants of the Poaceae family and Fabaceae family are used.

[0027] The plant body or plant tissue used for the production of diamine and / or polyamine compositions is not particularly limited, but is preferably a plant body or tissue in the form of seeds or in the growth process. Examples of the plant body or tissue in the form of seeds or in the growth process include the whole plant, flowers, buds, ovaries, fruits, leaves, cotyledons, stems, buds, roots, seeds, dry seeds, embryos, germ buds, and roots. Preferably, they are fruits, leaves, stems, buds, seeds, dry seeds, germ buds, and embryos, and particularly preferably, seeds, dry seeds, germ buds, and embryos. In addition, microorganisms can also be used for the production of diamine and / or polyamine compositions. In particular, it has been described that yeast contains a high concentration of polyamines, and a method for separating and purifying a polyamine-containing fraction by extracting the yeast cells and culture solution with an acid solution (Japanese Patent Laid-Open No. 10-52291). The polyamine content of the yeast reported in the patent publication (Japanese Patent Laid-Open No. 10-52291) is about 13 mg in Saccharomyces cerevisiae, about 23 mg in Saccharomyces diastaticas, and about 103 mg in Candida ulitis per 100 g of dry cells.

[0028] In the present invention, rice seeds, rice germ buds, wheat seeds, wheat germ buds, wheat embryos, soybean seeds, soybean germ buds, soybean embryos, and plant processed products such as soy milk, okara, or a combination thereof can be preferably used, and more preferably, wheat seeds, wheat germ buds, wheat embryos, soybean seeds, soybean germ buds, or soybean embryos can be used.

[0029] As a method for producing a diamine and / or polyamine composition, for example, it refers to a process of immersing plants and / or plant processed products in an ethanol solution and allowing them to stand or stirring them. Through this process, polysaccharides, polyphenols, and secondary metabolites are extracted into ethanol. When using cereals such as wheat as raw materials, gluten, which causes an increase in viscosity, is extracted, resulting in a decrease in the viscosity of the extract in this process and further suppressing the viscosity of the extract in the next process described below. Also, by removing components other than diamine and / or polyamine, the diamine and / or polyamine content per solid content in the final diamine and / or polyamine composition can be improved. The concentration of the ethanol solution in this process is preferably 20% (v / v) or more and 90% (v / v) or less, more preferably 30% (v / v) or more and 70% (v / v) or less. At a concentration lower than 20% (v / v), the extraction of polysaccharides, polyphenols, secondary metabolites, etc. becomes insufficient, leading to an increase in viscosity and an increase in the extraction amount of diamine and / or polyamine, which is not preferable. On the other hand, at a concentration higher than 90% (v / v), the extraction efficiency decreases and the solid content of the diamine and / or polyamine composition increases, so it is also not preferable. The treatment time varies depending on the extraction amount, but it is preferably 10 minutes or more, more preferably 30 minutes or more, and even more preferably 1 hour or more. If it is shorter than 10 minutes, components other than diamine and / or polyamine in this treatment process may not be sufficiently extracted. The upper limit is not restricted, but it is usually carried out within 24 hours or less, preferably within 12 hours or less, and even more preferably within 6 hours or less.

[0030] Since diamine and / or polyamine is difficult to be extracted into ethanol, after treating plants and / or plant processed products with ethanol, diamine and / or polyamine is mostly contained in the plant residue rather than the liquid fraction. Therefore, as a preferred embodiment of the present invention, the liquid fraction is separated from the plant residue and precipitate by centrifugation and / or filtration separation, and the plant residue and precipitate are recovered for treatment in the next process.

[0031] The step of "treating a plant and / or a processed plant product with water" refers to the step of immersing the plant and / or the processed plant product in water and extracting a composition containing diamine and / or polyamine from the plant and / or the processed plant product. "Water" refers to water without adding an acid solution or an alkali solution. This step may be carried out with static standing or stirring. The treatment time varies depending on the extraction amount, but is preferably 10 minutes or more, more preferably 30 minutes or more, and even more preferably 1 hour or more. If it is shorter than 10 minutes, a sufficient amount of diamine and / or polyamine composition may not be extracted in this treatment step. The upper limit is not restricted, but it is usually carried out within 24 hours or less, preferably within 12 hours or less, and particularly preferably within 6 hours or less. Even if it is treated for 24 hours or more, the extraction amount of the diamine and / or polyamine composition tends to reach saturation, and the amount that can be newly extracted thereafter is considered limited.

[0032] The step of "treating a plant and / or a processed plant product under acidic conditions" refers to the step of immersing the plant and / or the processed plant product in an acidic solution with a pH of 6 or less and extracting an extract containing diamine and / or polyamine by static standing and / or stirring. From the viewpoints of reducing the salt concentration of the final composition and preventing the corrosion of the stainless steel tank, weak acid conditions are preferred. Specifically, it is preferable to carry out the step between pH 3.0 and pH 6.0, and more preferably between pH 4.0 and pH 6.0. The pH in the present invention is based on the value measured 10 minutes after standing or stirring after adding an acid or an acid solution.

[0033] Examples of the acidic solution used for treatment under acidic conditions include at least one acidic solution selected from the group consisting of hydrochloric acid, sulfuric acid, nitric acid, acetic acid, phosphoric acid, citric acid, lactic acid, propionic acid, butyric acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, malic acid, tartaric acid, benzoic acid, sulfosalicylic acid, and formic acid. From the viewpoints of use in cosmetics, foods, pharmaceuticals, quasi-drugs, and animal feeds, it is preferable to use an acidic solution of hydrochloric acid and / or citric acid, and it is particularly preferable to use an acidic solution of citric acid.

[0034] The step of treating the plant and / or the processed plant under acidic conditions is carried out by performing the step of adding an acid or an acid solution and allowing it to stand or stirring it one or more times. A preferred embodiment of the present invention is a step including performing the step of adding an acid or an acid solution and allowing it to stand or stirring it a plurality of times. Since the amount of the acid or the acid solution to be added varies depending on the type and amount of the plant or the processed plant, it is better to divide it into a plurality of times while measuring the pH in order to minimize the amount of the acid or the acid solution to be added. In addition, when the acidic solution reacts with the plant or the processed plant, some neutralization occurs. However, by adding the acid or the acid solution little by little, the corrosiveness of the acidic solution to stainless steel due to the neutralization reaction is alleviated, and the burden on the stainless steel tank is reduced.

[0035] The treatment time under acidic conditions can be appropriately set according to the extraction amount of the diamine and / or polyamine composition. Generally, it is preferably 10 minutes or more, more preferably 30 minutes or more, and still more preferably 1 hour or more. If it is shorter than 10 minutes, a sufficient amount of diamine and / or polyamine composition in this treatment step may not be extracted. The upper limit is not limited, but usually it is 24 hours or less, preferably 12 hours or less, and particularly preferably 6 hours or less. Even if it is treated for 24 hours or more, it is considered that the extraction amount of the diamine and / or polyamine composition tends to be saturated, and the amount that can be newly extracted thereafter is limited.

[0036] The step of treating the plant and / or the processed plant under acidic conditions is preferably carried out after the step of treating the plant and / or the processed plant with water. In an example of the embodiment of the present invention, after the step of treating the plant and / or the processed plant with water, an acid or an acid solution is added to the aqueous solution to make it acidic, and the step of continuously treating the plant and / or the processed plant under acidic conditions is carried out.

[0037] The present invention includes a step of separating and collecting a liquid fraction. This step is a process of treating a plant and / or a plant processed product under water and acidic conditions, and then separating and collecting the liquid fraction from the plant residue and precipitate by centrifugation and / or filtration. The recovered liquid fraction contains a large amount of diamine and / or polyamine, and becomes a diamine and / or polyamine composition.

[0038] The present invention includes a step of adjusting the pH of a solution under acidic conditions to pH 6.5 to pH 7.5 as needed. This step can be performed either before or after the step of separating and collecting the liquid fraction, but it is preferably performed after the step of separating and collecting the liquid fraction. The pH adjustment can be carried out by adding an alkaline solution. Examples of the alkaline solution include sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium hydroxide, calcium hydroxide, calcium carbonate, barium hydroxide, and ammonia solutions. From the perspective of the safety of the salts generated upon neutralization to the human body, it is preferable to use sodium hydroxide.

[0039] The form of the diamine and / or polyamine composition is provided in the form of an aqueous solution or a powder. The powder of the diamine and / or polyamine composition can be obtained by treating a plant and / or a plant processed product under water and acidic conditions, and treating the liquid fraction recovered by centrifugation or filtration by spray drying or vacuum freeze-drying.

[0040] The composition may be prepared by combining a carrier or an additive in addition to the diamine and / or polyamine. The composition is preferably a food composition or a pharmaceutical composition for oral administration.

[0041] Examples of the carrier and additive used in the preparation of the composition include various types commonly used in ordinary drugs according to the dosage form of the composition, such as excipients, binders, disintegrants, lubricants, coloring agents, flavoring agents, odor-correcting agents, surfactants, and the like.

[0042] When preparing the composition in the form of an oral solid preparation such as tablets, powders, granules, pills, capsules, etc., excipients such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid, methylcellulose, glycerin, sodium alginate, gum arabic, etc. can be used as carriers; binders such as simple syrup, glucose solution, starch solution, gelatin solution, polyvinyl alcohol, polyvinyl ether, polyvinyl pyrrolidone, carboxymethyl cellulose, shellac, methylcellulose, ethylcellulose, water, ethanol, potassium phosphate, etc.; disintegrants such as dried starch, sodium alginate, agar powder, laminaran powder, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, monoglyceride stearate, starch, lactose, etc.; disintegration inhibitors such as sucrose, stearic acid, cocoa butter, hydrogenated oil, etc.; absorption promoters such as sodium lauryl sulfate, etc.; humectants such as glycerin, starch, etc.; adsorbents such as starch, lactose, kaolin, bentonite, colloidal silicic acid, etc.; lubricants such as purified talc, stearates, boric acid powder, polyethylene glycol, etc. can be used.

[0043] Here, tablets include oral tablets (naked tablets, sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets, double tablets, multi-layer tablets, etc.), chewable tablets (including those to be taken while chewing in the mouth), buccal tablets (including those to be taken after dissolving in the mouth like troches, etc.), sublingual tablets, and buccal tablets.

[0044] When preparing the above-mentioned formulation or preparation in the form of an oral solid preparation of pills, excipients such as glucose, lactose, starch, cocoa butter, hardened vegetable oil, kaolin, talc, etc. can be used as carriers; binders such as gum arabic powder, tragacanth powder, gelatin, etc.; disintegrants such as laminaran, agar, etc. can be used.

[0045] When preparing the above-mentioned formulation or preparation in the form of an oral solid preparation of capsules, the capsules are prepared by mixing the active ingredient with various carriers exemplified above and filling them into hard capsules, soft capsules, etc.

[0046] When the above-mentioned compounding agent or preparation is a liquid agent, it only needs to have a liquid state, and it may be an aqueous or oily suspension, solution, syrup, elixir, or drink. The liquid agent is prepared according to a conventional method using ordinary additives. Also, the container for filling the liquid agent is not limited as long as it can be sealed, and it may be a glass container, an aluminum container, or a plastic container.

[0047] The intake amount of the composition can be 0.1 mg / day to 10 mg / day, preferably 0.3 mg / day to 5 mg / day, more preferably 0.5 mg / day to 3 mg / day, in terms of the amount of diamine and / or polyamine per adult. The composition is preferably taken in divided doses of 2 to 3 times a day. The intake of the composition can be carried out, for example, daily, every other day, every three days, every four days, every five days, once a week, once every two weeks, once every three weeks, once every four weeks. Preferably, it is preferable to take the composition daily.

[0048] The intake amount of the composition can be 0.08 mg / day to 8 mg / day, preferably 0.24 mg / day to 4 mg / day, more preferably 0.4 mg / day to 2.4 mg / day, in terms of the amount of spermidine per adult. The composition is preferably taken in divided doses of 2 to 3 times a day. The intake of the composition can be carried out, for example, daily, every other day, every three days, every four days, every five days, once a week, once every two weeks, once every three weeks, once every four weeks. Preferably, it is preferable to take the composition daily.

[0049] 2. Judgment of the intake effect of diamine and / or polyamine One embodiment of the present invention relates to a method (hereinafter referred to as the "judgment method") for judging the intake effect of diamine and / or polyamine in a subject who has taken diamine and / or polyamine.

[0050] The determination method includes obtaining the score value of the brain function index of the subject at a first time point before or during the intake of diamine and / or polyamine, and obtaining the score value of the same index as the brain function index at a second time point during or after the intake of diamine and / or polyamine after the first time point for the same subject. In the determination method, when the score value at the second time point is equal to or higher than the score value at the first time point, it suggests that the intake of diamine and / or polyamine is effective. Also, when the value at the second time point is lower than the value at the first time point, it suggests that the intake of diamine and / or polyamine is not effective. The score value of the brain function index can be obtained by the MMSE or the questionnaire regarding cognitive function using the VAS method described in 1. above.

[0051] That the score value at the second time point is equal to or higher than the score value at the first time point is intended to mean that the score value at the second time point is the same as or higher than the first score value. That the score value at the second time point is lower than the score value at the first time point is intended to mean that the score value at the second time point is lower than the first score value.

Example

[0052] Examples are shown below to explain the present invention in more detail. However, the present invention is not construed as being limited to the examples.

[0053] 1. Subjects for study

[0054] In this study, those who met all of the following conditions were selected as subjects, and the effect of improving cognitive function when continuously taking polyamine-containing capsules (hereinafter referred to as "this test food") for 12 weeks was evaluated. · Having received a sufficient explanation about the purpose and content of this study, having the ability to consent, Volunteering of their own free will after fully understanding and consenting to participate in writing · Healthy Japanese people aged 40 or older at the time of consent acquisition · Those who are aware of forgetting things · The MMSE score is 24 or higher during screening

[0055] 2. Test method (1) Test design a. Randomization: Randomized comparison b. Blinding: Double - blind c. Control: Placebo control d. Allocation: Parallel - group comparison In this test, 60 subjects were allocated to the following test groups, 30 in each group. Group I: Took 9 tablets of Test Food A every day for 12 weeks, 3 tablets each after breakfast, lunch, and dinner. Group II: Took 9 tablets of Test Food B every day for 12 weeks, 3 tablets each after breakfast, lunch, and dinner. (2) Overview of foods and others used in this test a. Test foods Test Foods A and B are either polyamine - containing capsules (2700 mg, 9 capsules, containing 1.1 mg of polyamine as the active ingredient) or placebo (2700 mg, 9 capsules). Each test food was formulated with excipients and put into dark - colored capsules so that the contents of the capsules could not be distinguished from the outside appearance at all. b. Ingredient / raw material label · Polyamine - containing capsule: 409 mg of wheat germ extract, 372 mg of starch hydrolyzate, 149 mg of sodium citrate, 1734 mg of dextrin, 36 mg of calcium stearate · Placebo: 149 mg of sodium citrate, 2515 mg of dextrin, 36 mg of calcium stearate (3) Evaluation items The evaluation items were as follows. a. Primary evaluation item (Primary endpoint) · Cognitive function test (Cognitrax) b. Secondary evaluation item (Secondary endpoint) · Mini - Mental State Examination (MMSE) · Visual Analogue Scale (VAS) questionnaire regarding cognitive function · Urinary polyamine · Polyamines in blood c. Safety evaluation items · Subjective findings (lifestyle diary) · Objective findings (interview) (4) Allocation method This study was conducted as a randomized comparison so that there would be no differences in medical backgrounds among the test groups due to allocation. The person in charge of allocation assigned 30 people to each of Group I and Group II based on the median scores of MMSE and age at the time of screening. (5) Test flow, schedule, and methods for obtaining samples and information a. Samples (information) and acquisition methods Information was collected on each test day using the following methods. Consent of the test subjects: Name of the consenting person, date of consent acquisition Background of the test subjects: Age (date of birth), gender, etc. Questionnaire at the time of examination (exercise and diet the previous day, physical condition and diet on the day, etc.) Physical examination: Height (only at the pre-intake test), weight, BMI Urine test: Polyamine amount in urine Blood test: Polyamine amount in blood Lifestyle diary (daily test food intake status and physical condition during the test period, etc.) b. Schedule The above examinations were conducted according to the following schedule.

[0056]

Table 1

[0057] Subjects during the test were asked to pay attention to the following points.

[0058] · Do not significantly change your previous eating habits, exercise, and other lifestyle habits. Avoid taking new medications, health functional foods (foods for specified health uses, foods with functional claims, and foods with nutritional functions), etc. that may affect cognitive function. · During the test period, avoid polyamine-containing supplements other than the test food and natto (one pack per day) Avoid consuming more than the specified amount of natto (more than 1 pack per day) or soy milk (more than 1 pack (about 200 mL) per day). · On the day before the examination, avoid strenuous exercise and finish eating by 21:00. Also, avoid overeating, excessive drinking, smoking, and staying up late. · On the day of the examination, avoid excessive exercise until the examination is completed. · On the day of the examination, if you have an acute illness with symptoms such as fever, diarrhea, or vomiting, cancel the test.

[0059] · Do not disclose any information you may have about this test to a third party. In particular, do not provide information using SNS (such as Facebook, Twitter, Instagram, LINE, etc.).

[0060] (6) Exclusion Criteria Subjects who met the following criteria were excluded from the test. 1) Those with chronic diseases receiving drug treatment and those with a history of severe diseases 2) Those suffering from cancer, familial adenomatous polyposis, or Helicobacter pylori infection 3) Those with allergies to the test food, etc. (Since the test food contains wheat germ extract, especially those with allergies to wheat, etc.) 4) Those who usually consume a large amount of polyamine-containing supplements 5) Those who consume more than 1 pack of natto per day 6) Those who consume more than 1 pack (about 200 mL) of soy milk per day 7) Those who regularly use pharmaceuticals or health functional foods (foods for specified health uses, foods with functional claims, and foods with nutritional functions) that may affect cognitive function 8) Those who participated in another test within 1 month before the start of this test or those who plan to participate in another test after consenting to this test 9) Those determined to be ineligible by the principal investigator and the representative of the test 10) Those who are breastfeeding, pregnant, or have a plan or hope to become pregnant during the study period

[0061] (7) Methods of Statistical Analysis

[0062] Regarding the obtained evaluation results, in principle, for continuous data, the Shapiro-Wilk test was used to examine normality. For paired data, when normality was shown, a paired t-test was performed; when normality was not shown, the Wilcoxon signed-rank test was performed. For unpaired data, when normality was shown, an F-test was used to test for variance, followed by a Student’s t-test (with equal variances) or an Aspin-Welch’s t-test (without equal variances); when normality was not shown, the Mann-Whitney U-test was performed. For ordinal data with many levels, for paired data, the Wilcoxon signed-rank test was performed; for unpaired data, the Mann-Whitney U-test was performed. For ordinal data with few levels or nominal data, for paired data, the McNemar test was performed; for unpaired data, Fisher's direct method or χ 2 test was performed according to the number of data. When multiple comparisons were necessary, the Bonferroni method, Tukey method, Dunnett method, etc. were used according to the data format. In addition, analysis of variance, correlation coefficient testing, and subgroup analysis were also performed as needed. Regarding the safety evaluation items, in principle, only within-group comparisons of the values before and after ingestion and between-group comparisons of the values before and after ingestion were performed, and between-group comparisons of the differences before and after ingestion were not performed. In a two-sided test, a significance level of less than 5% was determined as "statistically significant difference", and 5% or more and less than 10% was determined as "tendency". Statistical analysis was mainly performed using R, but was also performed using IBM SPSS Statistics (ver. 25) as needed.

[0063] 3. Test Results 3-1. Efficacy Evaluation (Primary Evaluation Item)

[0064] Among the 60 test participants, 11 who dropped out due to personal reasons and 1 who deviated from the test plan compliance were excluded, and the remaining 48 were used as the subjects for efficacy analysis. Table 2 shows the background of the subjects for efficacy analysis.

[0065]

Table 2

[0066] The analysis results of the cognitive function test were shown in Table 3.

[0067] Regarding general memory, cognitive function speed, and motor speed, significant improvements were observed in the polyamine intake group compared with the placebo intake group. Also, regarding verbal memory and visual memory, a significant improvement tendency was observed in the polyamine intake group compared with the placebo intake group.

[0068]

Table 3

[0069] 3-2. Efficacy evaluation (secondary evaluation items)

[0070] Similar to the primary evaluation items, among the 60 test participants, 11 who dropped out due to personal reasons and 1 who deviated from the test plan compliance were excluded, and the remaining 48 were used as the subjects for efficacy analysis. The analysis results of the VAS questionnaire were shown in Table 4. Regarding the questions related to cognitive function speed, a significant improvement effect was observed in the polyamine intake group compared with the placebo intake group.

[0071]

Table 4

[0072] 3-3. Safety evaluation items The analysis results of the safety evaluation were shown in Table 5. A significant decrease in body weight and BMI was observed in both the polyamine intake group and the placebo intake group, but no significant difference was observed by group comparison.

[0073]

Table 5

Claims

1. A composition comprising a diamine and / or a polyamine for preventing brain function decline or improving brain function.

2. The composition according to claim 1, wherein the brain function is one or more selected from the group consisting of general memory, verbal memory, visual memory, cognitive function speed, motor speed, processing speed, general attention, cognitive flexibility, reaction time, and executive function.

3. The composition according to claim 1, wherein the subject to be administered is a person aged 40 or older.

4. The diamine is at least one selected from the group consisting of putrescine, cadaverine, and 1,3-diaminopropane, and the polyamine is at least one selected from the group consisting of spermidine, spermine, caldine, homospermidine, aminopropylcadaverine, thermine, thermospermidine, canavanine, aminopentylnorspermidine, N,N-bis(aminopropyl)cadaverine, homospermine, caldopentamine, homocaldopentamine, caldohexamine, and homocaldohexaminespermidine. The composition according to claim 1.

5. The composition according to claim 1, wherein the composition is a food composition or an oral pharmaceutical composition.

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