Composition containing diamine and / or polyamine, and use thereof

Abstract

Provided is a means for preventing deterioration of brain function, improving brain function, or reducing stress. This composition contains a diamine and / or a polyamine.

Description

Compositions containing diamines and / or polyamines and uses thereof

[0001] The present specification discloses a composition containing a diamine and / or a polyamine for preventing brain function decline or improving brain function. The present specification discloses a technology for reducing stress by utilizing a diamine and / or a polyamine.

[0002] The decline in brain function often occurs primarily with aging, and can lead to a variety of symptoms, including learning disabilities, memory disorders, speech disorders, anxiety disorders, insomnia, and loss of motivation. In today's world, where medical advances are leading to an increase in average life expectancy, prevention and countermeasures for brain function decline are considered important for extending healthy life expectancy.

[0003] Brain dysfunction is broadly categorized into three types: "healthy individuals" who show no abnormalities, "dementia" in which cognitive decline interferes with daily life, and "mild cognitive impairment (MCI)" in which cognitive decline is present but does not interfere with daily life. There is no fundamental cure for dementia, and the main treatments are symptom relief and slowing progression. Therefore, early detection at the MCI stage and prevention at the "pre-disease" stage are important.

[0004] In everyday life, we are exposed to a wide range of stress, including physical and psychological stress, as well as social stress, which can cause a variety of symptoms. In today's world, where medical advances are leading to an increase in average life expectancy, prevention and countermeasures against stress are considered important for extending healthy life expectancy.

[0005] In particular, psychological stress that occurs during work has become a problem in recent years, and in order to help workers relieve and reduce stress, the implementation of stress checks was made mandatory for businesses with 50 or more employees under the revised Industrial Safety and Health Act in December 2015. In addition to this initiative, stress reduction and prevention measures have also become increasingly important in recent years.

[0006] Diamines are linear fatty acid hydrocarbon compounds containing two amines. Polyamines are linear fatty acid hydrocarbon compounds containing three or more amines. Diamines and / or polyamines are known to be widely involved in the synthesis of nucleic acids and proteins and the regulation of enzyme activity (Non-Patent Document 1). Non-Patent Document 2 shows that serum spermidine content correlates with the MMSE score, which indicates brain function level. Therefore, clinical trials on oral administration of spermidine in humans have been conducted, but no positive results have been reported regarding improvement in cognitive function (Non-Patent Document 3). Non-Patent Document 4 shows that administration of putrescine, a type of polyamine, to mice showed antidepressant effects.

[0007] International Publication No. 2021 / 200216 Japanese Patent Application Laid-Open No. 2013-79209

[0008] Shunsuke Sakai et al, Urology Bulletin (1986), 32(3): 343-350Wien Klin Wonchenschr (2020) 132:42-46JAMA Network Open. 2022;5(5)Zomkowski AD et al, Prog Neuropsychopharmacol Biol Psychiatry. 2006 Dec 30;30(8):1419-25

[0009] An objective of the present invention is to provide a composition containing a diamine and / or a polyamine for preventing a decline in brain function or improving brain function, or to provide a new means for reducing stress.

[0010] The following representative inventions are provided. Item A1. A composition comprising a diamine and / or a polyamine for preventing a decline in brain function or improving brain function. Item A2. The composition according to Item A1, wherein the brain function is one or more selected from the group consisting of overall memory, verbal memory, visual memory, cognitive function speed, motor speed, processing speed, overall attention, cognitive flexibility, reaction time, and executive function. Item A3. The composition according to Item A1 or A2, wherein the subject to be administered is 40 years of age or older. Item A4. The composition according to any one of Items A1 to A3, wherein 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, thermospermine, canavalmine, aminopentylnorspermidine, N,N-bis(aminopropyl)cadaverine, homospermine, caldopentamine, homocaldopentamine, caldohexamine, and homocaldohexaminespermidine. Item A5. The composition according to any one of Items A1 to A4, wherein the composition is a food composition or a pharmaceutical oral composition.

[0011] Item B1. A composition for reducing stress, comprising a diamine and / or a polyamine. Item B2. The composition of item B1, wherein the stress is mental stress. Item B3. The composition of item B1 or B2, wherein the recipient is 40 years of age or older. Item B4. The composition of any one of items B1 to B3, wherein 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, thermospermine, canavalmine, aminopentylnorspermidine, N,N-bis(aminopropyl)cadaverine, homospermine, caldopentamine, homocaldopentamine, caldohexamine, and homocaldohexaminespermidine. Item B5. The composition of any one of items B1 to B4, which is a food composition or a pharmaceutical composition. Item B6. Use of diamines and / or polyamines for reducing stress. Item B7. A method for reducing stress, comprising having a subject in need of stress reduction ingest a diamine and / or polyamine.

[0012] In one embodiment, a composition comprising a diamine and / or a polyamine for preventing brain function decline or improving brain function can be provided, hi one embodiment, a reduction in stress response can be achieved.

[0013] A1. Compositions for Preventing Brain Decline or Improving Brain Function Some embodiments of the present invention relate to compositions comprising diamines and / or polyamines for preventing brain decline or improving brain function.

[0014] Decline in brain function often occurs with aging, and can lead to a variety of symptoms, including learning disabilities, memory impairment, language disorders, anxiety disorders, insomnia, and decreased motivation. Dementia is a typical disease accompanied by decline in brain function, but its precursor is mild cognitive impairment (MCI). MCI is intermediate between healthy individuals and dementia, and refers to a state in which cognitive decline is observed but does not interfere with daily life. The incidence rate is 10-20% in people over 65, and it has been reported that if left untreated, approximately 70% of these individuals will progress to dementia (Suzuki Yutaka, Nihon University Journal of Medicine (2012) 71(6):385-389).

[0015] The diagnostic criteria for MCI, for example, according to the evaluation criteria of Petersen et al. (Yamamoto Yasuji, Journal of Neurology (2011) Vol. 113, No. 6), are as follows: 1. The individual or family member (caregiver) complains of forgetfulness; 2. The presence of memory impairment that cannot be explained solely by the effects of aging; 3. Independent ability to perform daily activities; 4. Overall cognitive function is normal; and 5. No evidence of dementia. Dementia treatment is more effective when initiated at an earlier stage, and early detection and treatment at the MCI stage can improve cognitive function and sometimes halt the progression to dementia. This further emphasizes the importance of early detection and prevention at the pre-disease stage.

[0016] The American ADNI study established the following criteria for the MMSE neuropsychological test, which is used as a cognitive function test in clinical settings: 27-30 points: healthy (does not rule out MCI), 24-26 points: borderline (possibly healthy, MCI, or dementia), and 20-23 points: suspected early dementia.

[0017] Furthermore, a simpler dementia questionnaire can be used, in which six questions are evaluated using the VAS (visual analog scale) method.

[0018] Examples of brain functions improved by the composition according to this embodiment include overall memory, verbal memory, visual memory, cognitive function speed, motor speed, processing speed, overall attention, cognitive flexibility, reaction time, executive function, and simple attention. These cognitive functions can be tested using the Cognitrax test. The Cognitrax test is a cognitive function testing service designed for Japan by Health Solutions Co., Ltd., based on the cognitive function testing technology developed by CNS Vital Signs, Inc., a U.S. company.

[0019] Preferably, the composition improves one or more of the eleven cognitive functions, more preferably two or more, three or more, or four or more.

[0020] Below, we will explain each cognitive function based on the Cognitrax test. "Overall memory" indicates the ability to remember, and is evaluated by the total score of verbal memory and visual memory. "Verbal memory" indicates the ability to remember words, and is evaluated by a verbal memory test. "Visual memory" indicates the ability to remember shapes, and is evaluated by a visual memory test. "Cognitive function speed" indicates the ability to quickly process visual information, and is evaluated by the total score of the average right and left hands in the finger tapping test and the total number of correct responses in the SDC test. "Motor speed" indicates the ability to quickly repeat fine movements, and is evaluated by the total score of the average right and left hands in the finger tapping test. "Processing speed" indicates the ability to quickly process information, and is evaluated by the total score of the number of correct responses in the SDC test minus the number of incorrect responses in the SDC test.

[0021] "Overall attention" indicates the ability to maintain attention and respond accurately, and is evaluated by the total score of the number of Stroop errors in the Stroop test, the number of incorrect answers in the attention shift test, the number of times correct answers were overlooked in the sustained processing test, and the number of incorrect responses.

[0022] "Cognitive flexibility" indicates the ability to respond to and process changes in instructions, and is evaluated by the total score obtained by subtracting the number of incorrect responses in the attention shift test and the number of incorrect Stroop responses in the Stroop test from the number of correct responses in the attention shift test. "Reaction time" indicates the ability to respond quickly to instructions, and is evaluated by the average of the composite reaction time and Stroop reaction time in the Stroop test.

[0023] "Executive function" indicates the ability to understand rules and concepts and make decisions, and is evaluated by the total score obtained by subtracting the number of incorrect responses in the attention shifting test from the number of correct responses (responses) in the attention shifting test. "Simple attention" indicates the ability to pay attention for long periods of time, and is evaluated by 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.

[0024] The subjects of administration may include those who are not suspected of brain function decline, those who are suspected of brain function decline, and those who have been determined to have brain function decline.In the evaluation criteria of Pertersen et al., those who are determined to have MCI may correspond to those who are suspected of brain function decline.In the evaluation criteria of Pertersen et al., those who are determined to have dementia may correspond to those who are determined to have brain function decline.Furthermore, in the evaluation criteria of Pertersen et al., those who are determined to be healthy or robust may correspond to those who are not suspected of brain function decline.

[0025] Since the risk of brain function decline is higher in the elderly, the target age of the person taking the composition is preferably 40 years or older, and more preferably 50 years or older, 60 years or older, 70 years or older, or 80 years or older.

[0026] Whether or not decline in brain function has been prevented or brain function has improved can be determined by assessing the effect of taking diamines and / or polyamines, as described below. If there is an effect of taking diamines and / or polyamines, it can be determined that decline in brain function has been prevented or brain function has improved.

[0027] As used herein, a diamine is a straight-chain fatty acid hydrocarbon compound having two amines. A polyamine is a straight-chain fatty acid hydrocarbon compound having three or more amines. Examples of diamines include putrescine, cadaverine, 1,3-diaminopropane, and the like, and mixtures thereof. Examples of polyamines include spermidine, spermine, caldine, homospermidine, aminopropylcadaverine, thermine, thermospermine, canavalmine, aminopentylnorspermidine, N,N-bis(aminopropyl)cadaverine, homospermine, caldopentamine, homocaldopentamine, caldohexamine, homocaldohexamine spermidine, and the like, and mixtures thereof. In one embodiment, the composition preferably contains putrescine, spermidine, and / or spermine, and more preferably contains spermidine. In one embodiment, the composition contains putrescine, spermidine, and spermine, and preferably contains these in a ratio of 1 (putrescine): 10 to 40 (spermidine): 3 to 15 (spermine) on a dry weight basis.

[0028] Diamines and / or polyamines may be included in the composition as synthesized compounds. Alternatively, diamines and / or polyamines may be added to the composition as extracts, crude products, or purified products from extracts derived from plants or microorganisms containing these compounds. Plant extracts, crude products, and purified products from extracts (hereinafter also referred to as "diamine and / or polyamine compositions") may contain components other than diamines and / or polyamines, such as sugars (e.g., monosaccharides, oligosaccharides, and polysaccharides), peptides, and proteins. The diamine and / or polyamine composition may be in either an aqueous solution or a solid (e.g., powder) form. The "solid content" refers to the solute content excluding water in the aqueous diamine and / or polyamine composition (solution), and includes diamines and / or polyamines as well as sugars, peptides, and salts. When the diamine and / or polyamine composition is in the form of a powder, the "solid content" refers to the entire powder diamine and / or polyamine composition. In one embodiment, the diamine and / or polyamine composition is preferably in the form of a plant extract. Diamines and / or polyamines from plants, or extracts or purified products containing them, can be obtained by any method. For example, they can be obtained by the method described in Patent Document 2. In the present invention, "plant" refers to a plant body or plant tissue, and "processed plant product" refers to a product obtained by processing them. "And / or" means that both are included, or either one may be used.

[0029] Various plants and processed plant products can be used, and are not particularly limited, including, for example, Cucurbitaceae plants, Solanaceae plants, Gramineae plants, Cruciferae plants, Leguminous plants, Malvaceae plants, Asteraceae plants, Chenopodiaceae plants, Leguminous plants, Theaceae plants, plant extracts, plant extracts, and processed products thereof. Specific examples include sweet potato, tomato, cucumber, pumpkin, melon, watermelon, tobacco, Arabidopsis thaliana, bell 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, Chenopodium album, lily, orchid, carrot ... Examples of suitable microorganisms include chrysanthemums, roses, chrysanthemums, petunias, torenia, snapdragons, cyclamen, baby's breath, geraniums, sunflowers, lawn grass, cotton, enoki mushrooms, shimeji mushrooms, matsutake mushrooms, shiitake mushrooms, mushrooms, ginseng, agaricus, turmeric, ginseng, citrus fruits, bananas, kiwifruit, fruit juices, rice, milo, tea germ extract, germ extract, green tea, black tea, oolong tea, natto, soy milk, and okara. Gramineae and legumes are preferred. Examples of suitable microorganisms include yeast, lactic acid bacteria, bifidobacteria, natto bacteria, acetic acid bacteria, koji mold, and mildew. In one embodiment, the "diamine and / or polyamine composition" is preferably derived from rice, wheat, soybean, or yeast.

[0030] The plant body or plant tissue used for producing the diamine and / or polyamine composition is not particularly limited, but is preferably a plant body or tissue in the form of a seed or in the process of growth. Examples of plant body or tissue in the form of a seed or in the process of growth include whole trees, flowers, buds, ovaries, fruits, leaves, cotyledons, stems, buds, roots, seeds, dried seeds, embryos, and roots. Fruits, leaves, stems, buds, seeds, dried seeds, embryos, and embryos are preferred, and seeds, dried seeds, embryos, and embryos are particularly preferred. Microorganisms can also be used for producing the diamine and / or polyamine composition. In particular, yeast contains high concentrations of polyamines, and polyamine-containing fractions can be separated and purified by extracting yeast cells or culture broth with an acid solution (Japanese Patent Laid-Open No. 10-52291). The polyamine contents of yeasts reported in Japanese Patent Application Laid-Open No. 10-52291 are about 13 mg for Saccharomyces cerevisiae, about 23 mg for Saccharomyces diastaticas, and about 103 mg for Candida ulitis per 100 g of dry cells.

[0031] In one embodiment, rice seeds, rice germs, wheat seeds, wheat germs, wheat embryos, soybean seeds, soybean germs, soybean embryos, soy milk and okara as processed plant products, or combinations thereof can be suitably used, and more preferably wheat seeds, wheat germs, wheat embryos, soybean seeds, soybean germs, or soybean embryos can be used.

[0032] A method for producing a diamine and / or polyamine composition includes, for example, immersing a plant and / or processed plant product in an ethanol solution and allowing it to stand or stir. This process extracts polysaccharides, polyphenols, and secondary metabolites into the ethanol. When using grains such as wheat as raw materials, the viscosity of the extract is reduced by extracting gluten, which causes viscosity increase. This also reduces the viscosity of the extract in the subsequent process described below. Furthermore, the removal of components other than diamines and / or polyamines improves the diamine and / or polyamine content per solid content in the final diamine and / or polyamine composition. The concentration of the ethanol solution in this process is preferably 20% (v / v) to 90% (v / v), more preferably 30% (v / v) to 70% (v / v). At concentrations lower than 20% (v / v), extraction of polysaccharides, polyphenols, secondary metabolites, etc. is insufficient, resulting in increased viscosity and an increased amount of diamines and / or polyamines extracted, which is undesirable. On the other hand, at concentrations higher than 90% (v / v), extraction efficiency decreases and the solids content of the diamine and / or polyamine composition increases, which is also undesirable. The treatment time varies depending on the amount of extraction, 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, components other than diamines and / or polyamines may not be sufficiently extracted in this treatment step. While there is no upper limit, the treatment time is usually 24 hours or less, preferably 12 hours or less, and even more preferably 6 hours or less.

[0033] Since diamines and / or polyamines are difficult to extract with ethanol, after treating a plant and / or a processed plant product with ethanol, the diamines and / or polyamines are found in large amounts in the plant residue rather than in the liquid fraction. Therefore, in a preferred embodiment of the present invention, the liquid fraction is separated from the plant residue and precipitate by centrifugation and / or filtration, and the plant residue and precipitate are recovered and subjected to the next step.

[0034] The "step of treating a plant and / or a processed plant product with water" refers to a step of immersing the plant and / or the processed plant product in water to extract a composition containing diamines and / or polyamines from the plant and / or the processed plant product. "Water" refers to water to which no acid or alkaline solution has been added. This step may be allowed to stand or may be stirred. The treatment time varies depending on the amount of extraction, but is preferably 10 minutes or more, more preferably 30 minutes or more, and even more preferably 1 hour or more. If the treatment time is shorter than 10 minutes, a sufficient amount of diamine and / or polyamine composition may not be extracted in this treatment step. While there is no upper limit, the treatment time is usually 24 hours or less, preferably 12 hours or less, and particularly preferably 6 hours or less. Even if treatment is carried out for 24 hours or more, the amount of diamine and / or polyamine composition extracted will tend to saturate, and the amount that can be newly extracted thereafter will be limited.

[0035] The "step of treating a plant and / or a processed plant product under acidic conditions" refers to a step of immersing a plant and / or a processed plant product in an acidic solution of pH 6 or less and extracting an extract containing diamines and / or polyamines by standing and / or stirring. Weakly acidic conditions are preferred from the viewpoints of reducing the salt concentration in the final composition and preventing corrosion of the stainless steel tank. Specifically, the step is preferably carried out at a pH between 3.0 and 6.0, more preferably between 4.0 and 6.0. The pH in the present invention is based on the value measured 10 minutes after the addition of the acid or acid solution and standing or stirring.

[0036] The acidic solution used for the treatment under acidic conditions may be 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 viewpoint of use in cosmetics, foods, pharmaceuticals, quasi-drugs, and animal feed, 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.

[0037] The process of treating plants and / or processed plant products under acidic conditions involves adding an acid or acid solution and allowing it to stand or stir once or multiple times. A preferred embodiment of the present invention is a process that includes adding an acid or acid solution and allowing it to stand or stir multiple times. The amount of acid or acid solution added varies depending on the type and amount of plant or processed plant product. Therefore, in order to ensure that the amount of acid or acid solution added is the minimum required, it is better to add the acid or acid solution in multiple batches while measuring the pH. Furthermore, when the acidic solution reacts with the plant or processed plant product, some neutralization occurs. However, by adding the acid or acid solution in small amounts, the neutralization reaction reduces the corrosiveness of the acidic solution to stainless steel, thereby reducing the burden on the stainless steel tank.

[0038] The treatment time under acidic conditions can be appropriately set based on the amount of diamine and / or polyamine composition extracted, but is generally preferably 10 minutes or more, more preferably 30 minutes or more, and even more preferably 1 hour or more. If the treatment time is shorter than 10 minutes, a sufficient amount of diamine and / or polyamine composition may not be extracted in this treatment step. There is no upper limit, but it is usually 24 hours or less, preferably 12 hours or less, and particularly preferably 6 hours or less. Even if treatment is carried out for 24 hours or more, the amount of diamine and / or polyamine composition extracted will tend to saturate, and the amount that can be newly extracted thereafter will be limited.

[0039] The step of treating the plant and / or processed plant product under acidic conditions is preferably carried out after the step of treating the plant and / or processed plant product with water. In one embodiment of the present invention, after the step of treating the plant and / or processed plant product with water, an acid or acid solution is added to the aqueous solution to create acidic conditions, and then the step of treating the plant and / or processed plant product under acidic conditions is carried out successively.

[0040] The present invention includes a step of separating and collecting a liquid fraction. This step involves treating a plant and / or a processed plant product with water under acidic conditions, and then separating and collecting the liquid fraction from plant residues and sediments by centrifugation and / or filtration. The collected liquid fraction contains a large amount of diamines and / or polyamines, resulting in a diamine and / or polyamine composition.

[0041] The present invention includes a step of adjusting the acidic solution 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 is preferably performed after the step of separating and collecting the liquid fraction. The pH can be adjusted by adding an alkaline solution. Examples of alkaline solutions include solutions of sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium hydroxide, calcium hydroxide, calcium carbonate, barium hydroxide, and ammonia. From the perspective of the safety of the salt generated upon neutralization to the human body, it is preferable to use sodium hydroxide.

[0042] The diamine and / or polyamine composition is provided in the form of an aqueous solution or powder, and the powder of the diamine and / or polyamine composition can be obtained by treating a plant and / or a processed plant product with water under acidic conditions, recovering the liquid fraction by centrifugation or filtration, and then treating the recovered liquid fraction by spray drying or vacuum freeze drying.

[0043] 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 an orally administered pharmaceutical composition. When the composition is a food composition, its form is not particularly limited, and it may be in the form of a health food such as a tablet (including a coated tablet), a capsule, a powder, a granule, or a drink. It may also be in the form of a soft drink, a tea drink, a dairy product such as yogurt or a lactic acid bacteria drink, a seasoning, a processed food, a dessert, a confectionery (e.g., gum, candy, jelly), or the like.

[0044] Examples of carriers and additives used in preparing the composition include various types of carriers and additives commonly used in conventional pharmaceuticals, depending on the dosage form of the composition, such as excipients, binders, disintegrants, lubricants, colorants, flavoring agents, odorants, surfactants, etc.

[0045] When the composition is prepared as an oral solid preparation such as a tablet, powder, granule, pill, or capsule, carriers may be used, for example, excipients such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid, methylcellulose, glycerin, sodium alginate, or gum arabic; or binders such as simple syrup, glucose solution, starch solution, gelatin solution, polyvinyl alcohol, polyvinyl ether, polyvinylpyrrolidone, carboxymethylcellulose, shellac, methylcellulose, ethylcellulose, water, ethanol, or potassium phosphate. Disintegrants such as mixtures, dry starch, sodium alginate, agar powder, laminaran powder, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, stearic acid monoglyceride, starch, and lactose; disintegration inhibitors such as sucrose, stearic acid, cocoa butter, and hydrogenated oil; absorption promoters such as sodium lauryl sulfate; moisturizers such as glycerin and starch; adsorbents such as starch, lactose, kaolin, bentonite, and colloidal silicic acid; and lubricants such as purified talc, stearates, boric acid powder, and polyethylene glycol.

[0046] Here, tablets include oral tablets (plain tablets, sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets, double-layered tablets, multi-layered tablets, etc.), chewable tablets (including those that are taken by chewing in the oral cavity), lozenges (including those that are taken after dissolving in the oral cavity, such as lozenges), sublingual tablets, and buccal tablets.

[0047] When the compounding agent or preparation is a solid oral preparation in the form of a pill, the carrier that can be used in the preparation includes, for example, excipients such as glucose, lactose, starch, cacao butter, hardened vegetable oil, kaolin, talc, etc.; binders such as powdered gum arabic, powdered tragacanth, gelatin, etc.; disintegrants such as laminaran, agar, etc.

[0048] When the compounding agent or formulation is an oral solid preparation in the form of a capsule, the capsule is prepared by mixing the active ingredient with the various carriers exemplified above and filling the mixture into a hard capsule, a soft capsule, or the like.

[0049] When the compounded agent or preparation is a liquid, it need only be in a liquid form, and may be an aqueous or oily suspension, solution, syrup, elixir, or drink. The liquid is prepared using conventional additives in a conventional manner. The container into which the liquid is filled is not limited as long as it can be sealed, and may be a glass container, an aluminum container, or a plastic container.

[0050] In one embodiment, the content of the diamine and / or polyamine contained in the composition is not limited, but may be, for example, 0.01% by mass to 10% by mass, preferably 0.05% by mass to 7% by mass, and more preferably 0.05% by mass to 4% by mass, calculated on a dry weight basis.

[0051] The intake amount of the composition is not particularly limited, but can be, for example, 0.1 mg / day to 10 mg / day, preferably 0.3 mg / day to 5 mg / day, and more preferably 0.5 mg / day to 3 mg / day, converted into the amount of diamine and / or polyamine per adult. The composition is preferably taken in two to three divided doses per day. The composition can be taken, for example, every day, every two days, every three days, every four days, every five days, every week, every two weeks, every three weeks, or every four weeks. It is preferable to take the composition daily.

[0052] The intake amount of the composition is not particularly limited, but can be, for example, 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, more preferably 0.5 mg / day to 2.0 mg / day, more preferably 0.6 mg / day to 1.5 mg / day, and more preferably 0.7 mg / day to 1.2 mg / day, in terms of the amount of spermidine per adult. In one embodiment, the composition is preferably taken two to three times a day. In one embodiment, the composition can be taken, for example, every day, every two days, every three days, every four days, every five days, every week, every two weeks, every three weeks, or every four weeks. In one embodiment, the composition is preferably taken daily.

[0053] A2. Determination of the Effect of Ingestion of Diamine and / or Polyamine In one embodiment, there is provided a method for determining the effect of ingestion of diamine and / or polyamine (effect of preventing brain function decline or effect of improving brain function) in a subject who has ingested diamine and / or polyamine (hereinafter referred to as "determination method").

[0054] The assessment method includes obtaining a brain function index score for a subject at a first time point before or during the ingestion of diamines and / or polyamines, and obtaining the same brain function index score for the same subject at a second time point after the first time point during or after the ingestion of diamines and / or polyamines. In the assessment method, if the score at the second time point is equal to or higher than the score at the first time point, it suggests that the ingestion of diamines and / or polyamines was effective. Furthermore, if the score at the second time point is lower than the score at the first time point, it suggests that the ingestion of diamines and / or polyamines was ineffective. The brain function index score can be obtained by a cognitive function questionnaire using the MMSE or VAS method described in 1 above.

[0055] "The score value at the second time point is equal to or greater than the score value at the first time point" means that the score value at the second time point is equal to or greater than the first score value. "The score value at the second time point is lower than the score value at the first time point" means that the score value at the second time point is lower than the first score value. The diamine and / or polyamine, etc. are as described in A1 above.

[0056] B1. Stress-Reducing Composition In one embodiment, a stress-reducing composition is provided. "Stress" generally refers to a state in which a mental or physical reaction (stress response) occurs due to a stimulus (also referred to as a stressor). Such stimuli include physical stimuli such as cold, noise, radiation, and weather changes; chemical stimuli such as drugs, metals, and oxygen deficiency; biological stimuli such as bacterial infection and inflammation; physical stimuli caused by disease or disability such as pain and fever; and social and mental stimuli such as tension, anxiety, and fear arising from interpersonal relationships in society and at home.

[0057] Stress reactions include mental stress reactions (e.g., irritability, anxiety, decreased concentration, agitation, anger, decreased satisfaction, etc.) and physical stress reactions (e.g., joint pain, headache, stiff shoulders, back pain, eye fatigue, palpitations, shortness of breath, stomach pain, loss of appetite, constipation, diarrhea, insomnia, sweating, etc.).

[0058] Stress reduction means reducing or alleviating the severity of a stress response. The type of stress response targeted by the stress-reducing composition is not particularly limited, but in one embodiment, a psychological stress response is preferred. The cause of the stress response targeted by the stress-reducing composition is not particularly limited, but in one embodiment, social and psychological stimuli (stressors) are preferred. In one embodiment, the stress response is preferably a stress response measured by a VAS (visual analog scale) questionnaire, the Japanese Self-Perceived Stress Questionnaire (JPSS), and / or the Brief Occupational Stress Questionnaire (BJSQ). In one embodiment, the stress response is preferably a psychological stress response caused by a decline in self-management ability (e.g., time management ability, work management ability).

[0059] The presence or absence and degree of stress-reducing effects of a stress-reducing composition can be measured using a VAS (visual analog scale) questionnaire, the Japanese Self-Perceived Stress Questionnaire (JPSS), and / or the Brief Occupational Stress Questionnaire (BJSQ). In a VAS questionnaire, questions about stress are assessed using the VAS method. In the JPSS, responses to questions are obtained on a 5-point scale, which are converted into a score to calculate a total score, and stress levels are determined based on the result. In the BJSQ, a total score is calculated based on the answers to questions, and stress levels are determined based on the result.

[0060] The BJSQ's questions are divided into three groups: "physical and mental stress reactions," "work-related stress factors," and "support from those around you." The evaluation criteria are set so that "those with a high total score for the "physical and mental stress reactions" items" and "those with a total score above a certain level for the "physical and mental stress reactions" items and significantly high total scores for the "work-related stress factors" and "support from those around you" items are considered to be highly stressed."

[0061] In one embodiment, the stress response alleviated by the stress-reducing composition includes irritability, fatigue, anxiety, and / or somatic complaints, which can be assessed using questions in the "physical and mental stress response" group of the BJSQ.

[0062] There are no particular limitations on the person who takes the composition for stress reduction. In one embodiment, the person who takes the composition for stress reduction is preferably a person of a certain age or older, for example, 20 years or older, 30 years or older, 40 years or older, 50 years or older, 60 years or older, 70 years or older, or 80 years or older. There is no upper age limit, but the age can be, for example, 120 years or younger, 110 years or younger, or 100 years or younger.

[0063] In one embodiment, the user is preferably a person who is aware of their forgetfulness. In one embodiment, the user may include a person who is not suspected of brain function decline, a person who is suspected of brain function decline, and / or a person who has been determined to have brain function decline. In one embodiment, the user preferably has an MMSE score of 24 or more.

[0064] The stress-reducing composition preferably contains a diamine and / or a polyamine. The diamine and polyamine, the composition containing them, and the method for producing them are as described in Section A1 above.

[0065] Stress-reducing compositions can be used for both therapeutic (medical) and non-therapeutic (non-medical) purposes. Specifically, they can be used as compositions that explicitly or implicitly claim to prevent, reduce, or alleviate stress, regardless of whether they are classified as pharmaceuticals, quasi-drugs, cosmetics, foods, beverages, or the like. Furthermore, stress-reducing compositions can not only prevent or reduce stress-induced illnesses, but also prevent stress-induced declines in performance. Examples of such performance include, but are not limited to, desk work, physical labor, presentations, and calculations.

[0066] Examples of diseases caused by stress include, but are not limited to, respiratory diseases such as bronchial asthma and hyperarousal syndrome; cardiovascular diseases such as essential hypertension and coronary artery disease (angina pectoris, myocardial infarction); digestive diseases such as gastric and duodenal ulcers, irritable bowel syndrome, ulcerative colitis, and psychogenic vomiting; endocrine and metabolic diseases such as simple obesity and diabetes; neurological and muscular diseases such as muscle contraction headache, spasmodic torticollis, and writer's cramp; dermatological diseases such as chronic urticaria, atopic dermatitis, and alopecia areata; orthopedic diseases such as rheumatoid arthritis and lower back pain; urinary and reproductive diseases such as nocturnal enuresis and psychogenic impotence; ophthalmological diseases such as eye strain and essential blepharospasm; otorhinolaryngological diseases such as Meniere's disease; and dental and oral surgery diseases such as temporomandibular joint disorder. Other examples include anxiety, insomnia, mental fatigue, autonomic imbalance, menopausal disorder, nervous vomiting, etc. In the present invention, although not particularly limited, anxiety and insomnia are preferred as diseases caused by stress.

[0067] A stress-reducing composition can be labeled with a function that is achieved by reducing stress. Such a label is also called a functional label, and the content of the label is not particularly limited, but examples include "prevents stress," "reduces stress," "alleviates stress," "reduces mental fatigue," "enhances nervous function," "relieves anxiety," "calms the mind," "provides relaxation," "suppresses shortness of breath and palpitations," "relieves insomnia," and "relieves headaches," or functional labels that can be considered equivalent to these. In the present invention, the label may be attached to the composition itself, or to the container or packaging of the composition.

[0068] B2. Determination of the Effect of Ingestion of Diamine and / or Polyamine (Stress-Reducing Effect) In one embodiment, there is provided a method for determining the effect of ingestion of a diamine and / or polyamine (stress-reducing effect) in a subject who has ingested a diamine and / or polyamine (hereinafter referred to as the "determination method").

[0069] The assessment method includes obtaining a stress score for a subject at a first time point before or during the ingestion of diamines and / or polyamines, and obtaining a score for the same stress index for the same subject at a second time point after the first time point, during or after the ingestion of diamines and / or polyamines. In the assessment method, if the score at the second time point is less than or equal to the score at the first time point, it suggests that the ingestion of diamines and / or polyamines was effective. Furthermore, if the score at the second time point is equal to or greater than the score at the first time point, it suggests that the ingestion of diamines and / or polyamines was ineffective. However, this is the case when a lower score indicates a lower level of stress response. The stress index score can be obtained by a stress-related questionnaire using the VAS method described in 1. above, the Japanese Subjective Stress Questionnaire (JPSS), or the Brief Occupational Stress Questionnaire (BJSQ). The diamines and / or polyamines, etc., are as described in B1 above.

[0070] The present invention will be described in more detail below with reference to examples, but the present invention should not be construed as being limited to these examples.

[0071] A. Verification of effects on brain function A1. Subjects of study

[0072] In this study, subjects who met all of the following conditions were selected as subjects, and the effects of polyamine-containing capsules (hereinafter referred to as "the test food") on improving cognitive function when taken continuously for 12 weeks were evaluated: - Subjects who were fully informed of the purpose and content of the study, had the capacity to consent, fully understood the purpose, and volunteered voluntarily and agreed to participate in writing - Healthy Japanese people aged 40 years or older at the time of consent acquisition - Subjects who were aware of memory loss - MMSE score of 24 or higher at screening

[0073] A2. Study Methodology (1) Study Design a. Randomization: Randomized comparative study b. Blinding: Double-blind study c. Control: Placebo-controlled study d. Allocation: Parallel-group comparison In this study, 60 subjects were assigned to the following study groups, 30 subjects per group. Group I: Subjects took nine tablets of test food A daily for 12 weeks, three tablets after breakfast, lunch, and dinner. Group II: Subjects took nine tablets of test food B daily for 12 weeks, three tablets after breakfast, lunch, and dinner. (2) Overview of the Foods Used in This Study a. Test Foods Test foods A and B were either 2700 mg polyamine-containing capsules (9 tablets, containing 1.1 mg of polyamine as an active ingredient) or 2700 mg placebo (9 tablets). Each test food was blended with excipients and placed in a dark-colored capsule, making the contents of the capsule completely invisible from the outside. b. Ingredients / Raw Material Labeling - Polyamine-containing capsules: wheat germ extract 409 mg, starch hydrolysate 372 mg, sodium citrate 149 mg, dextrin 1734 mg, calcium stearate 36 mg - Placebo: sodium citrate 149 mg, dextrin 2515 mg, calcium stearate 36 mg (3) Evaluation Items The evaluation items were as follows: a. Primary endpoint - Cognitive function test (Cognitrax) b. Secondary endpoints - Mental Status Examination (MMSE) - VAS questionnaire regarding cognitive function - Urinary polyamines - Blood polyamines c. Safety evaluation items - Subjective findings (daily diary) - Objective findings (interview) (4) Allocation Method This study was conducted using a randomized comparative method to prevent differences in medical background between the study groups due to allocation. The person in charge of allocation assigned 30 people to each of Group I and Group II based on the MMSE score and median age at screening. (5) Study flow and schedule, and sample and information acquisition method a. Sample (information) and acquisition method Information was collected on each test day using the following methods.Consent of test subject: name of consenting person, date of consent acquisition Background of test subject: age (date of birth), gender, etc. Questionnaire at the time of the test (exercise and diet on the previous day, physical condition and diet on the day, etc.) Physical examination: height (pre-intake test only), weight, BMI Urine test: amount of polyamines in urine Blood test: amount of polyamines in blood Daily diary (daily test food intake and physical condition during the test period, etc.) b. Schedule The above tests were conducted according to the schedule below.

[0074]

[0075] Subjects undergoing the study were advised to pay attention to the following points:

[0076] - Do not make major changes to your current lifestyle habits, such as diet and exercise. Refrain from taking any new medicines or functional health foods (foods for specified health uses, foods with functional claims, and foods with nutrient functions) that may affect cognitive function. - During the test period, refrain from consuming polyamine-containing supplements other than the test foods, natto (more than one pack per day), or soy milk (more than one pack (about 200 mL) per day). - Refrain from strenuous exercise the day before the test, and finish eating by 9 p.m. Also, avoid overeating, excessive alcohol, smoking, and staying up late. - On the day of the test, avoid excessive exercise until the test is completed. - If you have an acute illness such as fever, diarrhea, or vomiting on the day of the test, the test will be canceled.

[0077] ・Do not disclose any information you learn about this exam to third parties. In particular, do not provide information via social media (Facebook, Twitter, Instagram, LINE, etc.).

[0078] (6) Exclusion criteria Subjects who met the following criteria were excluded from the study: 1) Subjects with a chronic disease receiving drug treatment or a history of serious illness 2) Subjects with cancer, familial adenomatous polyposis, or Helicobacter pylori infection 3) Subjects with allergies to the test food (especially those with allergies to wheat, as the test food contains wheat germ extract) 4) Subjects who regularly consume large amounts of polyamine-containing supplements 5) Subjects who consume one or more packs of natto daily 6) Subjects who consume one or more packs (approximately 200 mL) of soy milk daily 7) Subjects who regularly use medicines or health foods (specified health foods, functional foods, and nutrient-functional foods) that may affect cognitive function 8) Subjects who have participated in other studies within one month prior to the start of the study, or who plan to participate in other studies after agreeing to this study 9) Subjects who are deemed ineligible by the study physician and study representative 10) Subjects who are breastfeeding, pregnant, or who plan or hope to become pregnant during the study period

[0079] (7) Statistical analysis method

[0080] As a general rule, the Shapiro-Wilk test was used to examine the normality of the obtained evaluation results for continuous data. For paired data, a paired t-test was performed if normality was confirmed, and a Wilcoxon signed-rank test was used if it was not confirmed. For unpaired data, an F-test was used to test variance if normality was confirmed, followed by a Student's t-test (with homogeneity of variance) or an Aspin-Welch's t-test (without homogeneity of variance). If normality was not confirmed, a Mann-Whitney U-test was used. For ordinal data with many levels, a Wilcoxon signed-rank test was used for paired data, and a Mann-Whitney U-test was used for unpaired data. For ordinal data with few levels or nominal data, a McNemar test was used for paired data, and Fisher's exact test or χ test was used for unpaired data depending on the number of data. 2Tests were performed. When multiple comparisons were necessary, Bonferroni, Tukey, Dunnett, or other methods were used depending on the data format. Analysis of variance, correlation coefficient tests, and subgroup analyses were also performed as necessary. Regarding safety evaluation items, in principle, only intra-group comparisons of values ​​before and after intake and between-group comparisons of values ​​before and after intake were performed, and between-group comparisons of differences before and after intake were not performed. In two-sided tests, a significance level of less than 5% was considered to be "statistically significant," and a level between 5% and less than 10% was considered to be "tendency." Statistical analysis was primarily performed using R, but IBM SPSS Statistics (ver. 25) was also used when necessary.

[0081] A3. Study results A3-1. Efficacy evaluation (primary endpoint)

[0082] Of the 60 study participants, 11 dropped out for personal reasons and one was found to have deviated from the study protocol, and the remaining 48 were included in the efficacy analysis. Table 2 shows the background of the efficacy analysis subjects.

[0083]

[0084] The analysis results of the cognitive function tests are shown in Table 3.

[0085] The polyamine group showed significant improvements in overall memory, cognitive function speed, and motor speed compared to the placebo group. Additionally, the polyamine group showed a significant trend toward improvement in verbal memory and visual memory compared to the placebo group.

[0086]

[0087] A3-2. Efficacy evaluation (secondary endpoints)

[0088] As with the primary endpoint, of the 60 study participants, 11 dropped out for personal reasons and one was found to have deviated from the study protocol, and the remaining 48 were included in the efficacy analysis. The analysis results of the VAS questionnaire are shown in Table 4. Regarding the question regarding cognitive function speed, the polyamine intake group showed a significant improvement compared to the placebo intake group.

[0089]

[0090] A3-3. Safety Evaluation Items The results of the safety evaluation analysis are shown in Table 5. Significant decreases in weight and BMI were observed in both the polyamine intake group and the placebo intake group, but no significant differences were observed between the groups.

[0091]

[0092] B. Verification of stress reduction effects B1. Subjects In this study, subjects who met all of the following conditions were selected as subjects, and the stress-reducing effects of ingesting polyamine-containing capsules (hereinafter referred to as "the test food") for 12 consecutive weeks were evaluated. - Subjects who were fully informed about the purpose and contents of the study, had the capacity to consent, fully understood the content, and volunteered of their own free will and agreed to participate in writing - Healthy Japanese people aged 40 years or older at the time of consent acquisition - Subjects who were aware of memory loss - MMSE score of 24 or higher at screening

[0093] B2. Study Methodology (1) Study Design a. Randomization: Randomized comparative study b. Blinding: Double-blind study c. Control: Placebo-controlled study d. Allocation: Parallel-group comparison In this study, 60 subjects were assigned to the following study groups, 30 subjects per group. Group I: Subjects took nine tablets of test food A daily for 12 weeks, three tablets after breakfast, lunch, and dinner. Group II: Subjects took nine tablets of test food B daily for 12 weeks, three tablets after breakfast, lunch, and dinner. (2) Overview of Foods Used in This Study a. Test Foods Test food A was a 2700 mg polyamine-containing capsule (9 tablets, containing 1.1 mg of polyamine as an active ingredient). Test food B was a 2700 mg placebo. Each test food was blended with excipients and placed in a dark-colored capsule so that the contents of the capsule were completely invisible from the outside. b. Ingredients / raw materials - Polyamine-containing capsule: wheat germ extract 409 mg, starch hydrolysate 372 mg, sodium citrate 149 mg, dextrin 1734 mg, calcium stearate 36 mg (Note: The wheat germ extract was prepared using the method described in Patent Document 1, and contains at least putrescine and spermine in addition to spermidine. Wheat germ extract also contains asparagine, maleic acid, glycolic acid, gluconic acid, and succinic acid, but these substances have not been reported to have a stress-reducing effect.) - Placebo: sodium citrate 149 mg, dextrin 2515 mg, calcium stearate 36 mg (3) Evaluation items The evaluation items were as follows.・VAS questionnaire regarding stress ・Japanese Subjective Stress Questionnaire (JPSS) ・Brief Occupational Stress Questionnaire (BJSQ) ・Urinary polyamines ・Blood polyamines ・Subjective findings (daily diary) ・Objective findings (interview) (4) Allocation method This study was conducted using a randomized comparison to ensure that allocation did not result in differences in medical background between the study groups. The person in charge of allocation allocated 30 people to Group I and 30 people to Group II based on the MMSE score and median age at screening. (5) Study flow and schedule, and sample / information acquisition method a. Samples (information) and acquisition method Information was collected on each test day using the following methods.Consent of test subject: name of consenting person, date of consent acquisition Background of test subject: age (date of birth), gender, etc. Questionnaire at the time of the test (exercise and diet on the previous day, physical condition and diet on the day, etc.) Physical examination: height (pre-intake test only), weight, BMI Urine test: amount of polyamines in urine Blood test: amount of polyamines in blood Daily diary (daily test food intake and physical condition during the test period, etc.) b. Schedule The above tests were conducted according to the schedule below.

[0094]

[0095] During the test, subjects were urged to pay attention to the following points: - Do not make major changes to their lifestyle habits, such as their current diet or exercise. - During the test period, refrain from consuming polyamine-containing supplements other than the test foods, natto (more than one pack per day), or soy milk (more than one pack (about 200 mL) per day). - Refrain from strenuous exercise the day before the test and finish eating by 9 p.m. Also, avoid overeating, excessive alcohol, smoking, and staying up late. - On the day of the test, avoid excessive exercise until the test is completed. - If you experience acute illness such as fever, diarrhea, or vomiting on the day of the test, the test will be discontinued. - Do not leak any information you learn about this test to third parties. In particular, do not provide information via social media (Facebook, Twitter, Instagram, LINE, etc.).

[0096] (6) Exclusion criteria Subjects who met any of the following criteria were excluded from the study: 1) Those with a chronic disease undergoing drug treatment or those with a history of serious illness 2) Those suffering from cancer, familial adenomatous polyposis, or Helicobacter pylori infection 3) Those with allergies to the test food (particularly those with allergies to wheat, as the test food contains wheat germ extract) 4) Those who regularly consume large amounts of polyamine-containing supplements 5) Those who consume one or more packs of natto every day 6) Those who consume one or more packs (approximately 200 mL) of soy milk every day 7) Those who have participated in other studies within one month prior to the start of the study, or those who plan to participate in other studies after giving consent for this study 8) Those who are deemed ineligible by the study physician and study representative 9) Those who are breastfeeding, pregnant, or those who plan or hope to become pregnant during the study period

[0097] (7) Statistical analysis method As a general rule, for the evaluation results obtained, the Shapiro-Wilk test was used to examine normality for continuous data. For paired data, if normality was demonstrated, a paired t-test was performed; if not, a Wilcoxon signed-rank test was used. For unpaired data, if normality was demonstrated, an F-test was used to test variance, followed by a Student's t-test (with homogeneity of variance) or an Aspin-Welch's t-test (without homogeneity of variance). If normality was not demonstrated, a Mann-Whitney U-test was used. For ordinal data with many levels, a Wilcoxon signed-rank test was used for paired data, and a Mann-Whitney U-test was used for unpaired data. For ordinal data with few levels or nominal data, a McNemar test was used for paired data, and Fisher's exact test or χ test was used for unpaired data depending on the number of data. 2 Tests were performed. When multiple comparisons were required, Bonferroni, Tukey, Dunnett, or other methods were used depending on the data format. Analysis of variance, correlation coefficient tests, and subgroup analyses were also performed as necessary. Regarding safety evaluation items, in principle, only intra-group comparisons of values ​​before and after intake and between-group comparisons of values ​​before and after intake were performed, and between-group comparisons of differences before and after intake were not performed. In two-sided tests, a significance level of less than 5% was considered to be "statistically significant," and a level of 5% to less than 10% was considered to be "tendency." Statistical analysis was primarily performed using R, but IBM SPSS Statistics (ver. 25) was also used when necessary.

[0098] B3. Study results B3-1. Efficacy evaluation: VAS questionnaire Of the 60 study participants, 11 dropped out for personal reasons and one person was found to have deviated from compliance with the study plan, and the remaining 48 people were included in the efficacy analysis. Table 7 shows the background of the efficacy analysis subjects.

[0099]

[0100] The analysis results of the VAS questionnaire are shown in Table 8. The questionnaire asked, "How much stress have you felt over the past month?" The scores in the polyamine intake group were significantly lower than those in the placebo intake group, indicating a significant reduction in stress.

[0101]

[0102] B3-2. Efficacy Evaluation: Japanese Self-Perceived Stress Questionnaire (JPSS) Analysis results of the Japanese Self-Perceived Stress Questionnaire (JPSS) are shown in Table 9. The polyamine intake group had a significantly lower total score than the placebo intake group, demonstrating a significant reduction in stress. Regarding individual survey items, the numerical response to the question, "Over the past month, to what extent have you had control over how you spent your time?" was significantly lower in Group I compared to Group II. Furthermore, the numerical response to the questions, "Over the past month, how often have you felt that you were unable to control important things in your life?" and "Over the past month, how often have you felt that you were adapting well to major changes in your life?" also significantly lower in Group I compared to Group II.

[0103]

[0104] The analysis results of the Brief Occupational Stress Questionnaire (BJSQ) are shown in Table 10. Of the individual question items, significant reductions in the scores for three items, "feeling irritated," "feeling restless," and "feeling sad," were observed with polyamine intake.

[0105]

[0106] B3-3. Safety Evaluation The analysis results of the safety evaluation are shown in Table 11. Significant decreases in weight and BMI were observed in both the polyamine intake group and the placebo intake group, but no significant differences were observed between the groups.

[0107]

Claims

1. A composition for reducing mental stress, which contains spermidine and is ingested in an amount of 0.4 mg / day to 1.1 mg / day in terms of spermidine amount.

2. The composition according to claim 1 for reducing stress in persons aged 40 or over.

3. The composition according to claim 1 or 2, which is a food composition or a pharmaceutical composition.

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