Composition containing diamine and / or polyamine for preventing or improving frailty

Abstract

The present invention addresses the problem of providing a composition containing a diamine and / or a polyamine for preventing or improving frailty.　Provided is a composition containing a diamine and / or a polyamine for preventing or improving frailty.

Description

Composition containing diamine and / or polyamine for preventing or ameliorating frailty

[0001] Disclosed herein is a composition containing a diamine and / or a polyamine for preventing or ameliorating frailty.

[0002] Diamines are linear fatty acid hydrocarbon compounds with two amines. Polyamines are linear fatty acid hydrocarbon compounds with 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). Regarding spermidine, one of the polyamines, it has been reported that the amount of spermidine in urine samples corrected for creatinine concentration is elevated in some cases of kidney cancer and bladder cancer (Non-Patent Document 1).

[0003] Furthermore, Non-Patent Document 2 shows that polyamines decrease in aged muscles, suggesting a relationship between the decrease in polyamines in muscles and sarcopenia associated with aging. Furthermore, Patent Document 1 discloses a muscle-building agent containing polyamines and branched-chain amino acids as active ingredients.

[0004] International Publication No. 2021 / 200216

[0005] Sakai S, et al. Urological Bulletin (1986), 32(3): 343-350Uchitomi R, et al. Sci Rep. 2019 Jul 18;9(1):10425.

[0006] Japan has the world's highest aging rate, and it has been reported that medical expenses will continue to increase in the future, posing a major social issue. Therefore, measures to extend healthy lifespan are being promoted in order to optimize medical expenses. It has been suggested that one of the factors hindering the healthy lifespan of elderly people is the increasing importance of frailty with age. Frailty is a state of weakness observed in elderly people, and refers to a stage between a healthy state and a state requiring nursing care. Furthermore, frailty is believed to be primarily caused by physical, psychological, and social factors. Prevention and countermeasures for frailty are considered important for preventing future conditions requiring nursing care, such as becoming bedridden. The present invention aims to provide a composition containing a diamine and / or a polyamine for preventing or ameliorating frailty.

[0007] The present invention includes the following embodiments. Item 1. A composition comprising a diamine and / or a polyamine for preventing or ameliorating frailty. Item 2. The composition according to Item 1, wherein the subject is 40 years of age or older. Item 3. The composition according to Item 1, 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 homocaldohexamine spermidine. Item 4. The composition according to Item 1, wherein the composition is a food composition or a pharmaceutical oral composition. Item 5. Item 2. The composition according to Item 1, wherein the frailty is accompanied by at least one selected from the group consisting of decreased skeletal muscle mass, decreased right arm muscle mass, decreased left arm muscle mass, decreased trunk muscle mass, decreased right leg muscle mass, decreased left leg muscle mass, decreased grip strength, decreased back muscle strength, and decreased leg strength.

[0008] A composition containing a diamine and / or a polyamine for preventing or ameliorating frailty can be provided.

[0009] 1. Composition One embodiment of the present invention relates to a composition for preventing or ameliorating frailty, which comprises a diamine and / or a polyamine.

[0010] Frailty is a state of weakness seen in the elderly, and is said to be an intermediate stage between a healthy state and a state requiring nursing care. Furthermore, frailty is said to be primarily caused by physical, psychological, and social factors. Therefore, since frailty is not a medical "disease," the term "assessment" is used in place of "diagnosis." However, as frailty progresses, it can lead to a state requiring nursing care, such as difficulty walking, being forced to use a wheelchair, or becoming bedridden.

[0011] According to the evaluation criteria of Fried et al., the progression of frailty is assessed as follows: if three or more of the five items of weight loss, subjective fatigue, decreased daily activity, decreased physical ability (walking speed), and decreased muscle strength (grip strength) are present, the individual is considered frail; if one or two of these are present, the individual is considered pre-frail; and if none of these are present, the individual is considered healthy or robust.

[0012] Furthermore, there are no unified standards for judging each of the above items, but for example, according to the website of the Public Interest Foundation for Aging and Longevity (https: / / www.tyojyu.or.jp / net / byouki / frailty / shindan.html), the standards are as follows:

[0013] Regarding weight loss, participants were considered to have experienced weight loss if they answered "yes" to the question, "Have you experienced (unintentional) weight loss of 2-3 kg or more in the past 6 months?"; regarding subjective fatigue, participants were considered to have experienced fatigue if they answered "yes" to the question, "I feel tired for no apparent reason (in the past 2 weeks)."

[0014] Regarding a decrease in daily activity, if participants answered "I do not exercise or exercise" to either of the two questions, "How many days a week do you do light exercise or gymnastics (including farm work)?" and "How many days a week do you do regular exercise or sports (including farm work)?", they were determined to have a decrease in activity.

[0015] Regarding physical ability (normal walking speed), if the speed is less than 1 m / s (a 1 m runway is set up before and after the measurement section, and the measurement is taken when the measurement section is 5 m long), it is determined that there is a decline in physical ability; regarding muscle strength (grip strength), if the measurement of the dominant hand is less than 26 kg for men and less than 18 kg for women, it is determined that there is a decline in muscle strength.

[0016] The subjects of administration may include those who are not suspected of frailty, those suspected of frailty, and those who have been determined to be frail. Those determined to be pre-frail according to the evaluation criteria of Fried et al. may correspond to those suspected of frailty. Those determined to be frail according to the evaluation criteria of Fried et al. may correspond to those determined to be frail. Furthermore, those determined to be healthy or robust according to the evaluation criteria of Fried et al. may correspond to those not suspected of frailty.

[0017] Since elderly people are at risk of frailty, the age of the subject to be administered is preferably 40 years or older, 50 years or older, 60 years or older, 70 years or older, or 80 years or older.

[0018] Preventing frailty may include preventing progression to pre-frailty or frailty, or inhibiting progression of pre-frailty or frailty. Preferably, preventing frailty may include inhibiting declines in regional muscle mass (right leg, left leg), grip strength, and back muscle strength. Improving frailty may include alleviating the pre-frailty or frailty state, or returning it to normal. Preferably, improving frailty may include increasing regional muscle mass (right leg, left leg), grip strength, and back muscle strength.

[0019] 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.

[0020] Diamines and / or polyamines may be added to the composition as synthesized compounds. Alternatively, diamines and / or polyamines may be added to the composition as plant-derived extracts, biomass, or purified products thereof containing these compounds. Plant-derived extracts, biomass, or purified products thereof (hereinafter also referred to as "diamine and / or polyamine compositions") may contain natural components other than diamines and / or polyamines, such as sugars (e.g., monosaccharides, oligosaccharides, and polysaccharides), peptides, and proteins. In the present invention, the term "diamine and / or polyamine composition" refers to both aqueous and powder forms of the diamine and / or polyamine composition. The "solid content" refers to the solute content excluding water in the aqueous diamine and / or polyamine composition (solution), including diamines and / or polyamines, sugars, peptides, and salts. When the diamine and / or polyamine composition is powder, the "solid content" refers to the entire powder diamine and / or polyamine composition.

[0021] In the present invention, the term "plant" refers to a plant body or plant tissue, and the term "processed plant product" refers to a product obtained by processing a plant or plant tissue. "And / or" means that both are included, or either one may be included.

[0022] 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, Leguminosae plants, Malvaceae plants, Asteraceae plants, Chenopodiaceae plants, Leguminosae 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, lily, orchid, carnation, rose, chrysanthemum, Examples include petunia, torenia, snapdragon, cyclamen, gypsophila, geranium, sunflower, lawn grass, cotton, enoki mushroom, shimeji mushroom, matsutake mushroom, shiitake mushroom, mushrooms, ginseng, agaricus, turmeric, ginseng, citrus fruits, banana, kiwi, fruit juice, rice, wheat, barley, soybean, corn, milo, sunflower, germ extract, germ extract, green tea, black tea, oolong tea, natto, soy milk, and okara. Preferably, grasses and legumes are used.

[0023] The plant body or plant tissue used for producing a 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 a diamine and / or polyamine composition. In particular, yeast contains high concentrations of polyamines, and a method for isolating and purifying a polyamine-containing fraction by extracting yeast cells or a culture solution with an acid solution has been described (Japanese Patent Laid-Open Publication No. 10-52291). The polyamine contents of yeasts reported in a patent publication (JP-A-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 dried cells.

[0024] In the present invention, 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.

[0025] 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.

[0026] 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.

[0027] 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.

[0028] 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.

[0029] 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.

[0030] 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 multiple times of adding an acid or acid solution and allowing it to stand or stir. Because the amount of acid or acid solution added varies depending on the type and amount of plant or processed plant product, adding the acid or acid solution in multiple batches while measuring the pH is recommended to ensure the minimum amount of acid or acid solution needed. Furthermore, when the acidic solution reacts with the plant or processed plant product, some neutralization occurs. However, adding the acid or acid solution in small amounts reduces the corrosiveness of the acidic solution to stainless steel due to the neutralization reaction, thereby reducing the strain on the stainless steel tank.

[0031] 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.

[0032] 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.

[0033] 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.

[0034] 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.

[0035] 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.

[0036] The composition may be prepared by combining a diamine and / or a polyamine with a carrier or an additive, and is preferably a food composition or a pharmaceutical composition for oral administration.

[0037] 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.

[0038] 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.

[0039] 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.

[0040] 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.

[0041] 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.

[0042] 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.

[0043] 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, and 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 two to three times a 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 every day.

[0044] 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, and more preferably 0.4 mg / day to 2.4 mg / day, calculated as the amount of spermidine per adult. The composition is preferably taken two to three times a 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 every day.

[0045] 2. Determining the Effect of Intake of Diamine and / or Polyamine One embodiment of the present invention relates to a method for determining the effect of ingestion of diamine and / or polyamine in a subject who has taken diamine and / or polyamine (hereinafter referred to as the "determination method").

[0046] The determination method includes obtaining a measurement value of a frailty index of a subject at a first time point before or during the ingestion of a diamine and / or polyamine, and obtaining a measurement value of the same frailty index for the same subject at a second time point after the first time point during or after the ingestion of a diamine and / or polyamine. In the determination method, if the measurement value at the second time point is equal to or greater than the measurement value at the first time point, it suggests that the ingestion of diamine and / or polyamine was effective. Furthermore, if the measurement value at the second time point is lower than the measurement value at the first time point, it suggests that the ingestion of diamine and / or polyamine was ineffective.

[0047] The frailty index is, for example, at least one selected from the group consisting of decreased skeletal muscle mass, decreased right arm muscle mass, decreased left arm muscle mass, decreased trunk muscle mass, decreased right leg muscle mass, decreased left leg muscle mass, decreased grip strength, decreased back muscle strength, and decreased leg strength. Skeletal muscle mass and muscle mass by region (right arm, left arm, trunk, right leg, left leg) can be measured, for example, using Inbody570 (Inbody Japan Co., Ltd.). Grip strength can be measured, for example, using a digital grip strength meter (Takei Machine Industry Co., Ltd.). Back strength can be measured, for example, using a digital back strength meter (Takei Machine Industry Co., Ltd.). Leg strength can be evaluated, for example, using a five-time chair stand test.

[0048] The phrase "the measured value at the second time point is equal to or greater than the measured value at the first time point" means that when each measurement value is obtained multiple times at one time point, the measured value at the second time point is equal to or greater than the value of [mean value] - [2SD (standard deviation)] of the first measurement value, preferably equal to or greater than the value of [mean value] - [1SD (standard deviation)] (in the above formula, "-" indicates subtraction). "Multiple times" means, for example, three, four, or five times. The phrase "the measured value at the second time point is lower than the measured value at the first time point" means that when each measurement value is obtained multiple times at one time point, the measured value at the second time point is lower than the value of [mean value] - [2SD (standard deviation)] of the first measurement value, preferably lower than the value of [mean value] - [1SD (standard deviation)] (in the above formula, "-" indicates subtraction). "Multiple times" means, for example, three, four, or five times.

[0049] 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.

[0050] 1. Subjects of study The frailty prevention effect of a food containing polyamines (hereinafter referred to as the "test food") was evaluated when adult men aged 50 to 65 years took it for 12 consecutive weeks.

[0051] 2. Study Method (1) Study Design a. Randomization: Randomized comparison b. Blinding: Double-blind c. Control: Placebo control 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 six tablets of test food A daily for 12 weeks, two tablets after breakfast, lunch, and dinner. Group II: Subjects took six tablets of test food B daily for 12 weeks, two tablets after breakfast, lunch, and dinner.

[0052] (2) Overview of the foods used in this study a. Test foods Test foods A and B were either 1800 mg polyamine-containing capsules (6 tablets) or 1800 mg placebo (6 tablets). Each test food was mixed with excipients and placed in a dark-colored capsule so that the contents of the capsule were completely invisible from the outside.

[0053] b. Ingredients / raw material information: Polyamine-containing capsules: wheat germ extract 264 mg (0.9 mg as polyamine, 0.7 mg as spermidine), starch hydrolysate 240 mg, sodium citrate 96 mg, dextrin 1176 mg, calcium stearate 24 mg; Placebo: sodium citrate 96 mg, dextrin 1680 mg, calcium stearate 24 mg

[0054] (3) Evaluation items The evaluation items were as follows: Muscle mass by body part (right leg, left leg), grip strength, back strength

[0055] (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 Group I and 30 people to Group II based on skeletal muscle mass and age.

[0056] (5) Test flow and schedule, and sample / information collection method a. Sample (information) and collection 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 test (exercise / meal on the previous day, physical condition / meal on the day, etc.)

[0057] Physical examination: height (only at the pre-intake test), weight, BMI, skeletal muscle mass (Inbody570, Inbody Japan Co., Ltd.), muscle mass by region (right leg, left leg) (Inbody570, Inbody Japan Co., Ltd.), grip strength (digital grip strength meter, Takei Machinery Co., Ltd.), back strength (digital back strength meter, Takei Machinery Co., Ltd.), medical interview by doctor, daily diary (daily test food intake and physical condition during the test period, etc.)

[0058] b. Schedule The above tests were carried out according to the following schedule.

[0059] During the study, subjects were advised to pay attention to the following points:

[0060] - Do not make major changes to your current lifestyle habits, such as diet and exercise. Refrain from taking any new medications or health foods (foods for specified health uses, foods with functional claims, and foods with nutrient functions) that may affect skeletal muscle mass, such as protein preparations. - During the test period, refrain from consuming polyamine-containing supplements or soy foods (natto: one or more packs per day, soy milk: one or more packs per day, tofu: one-third of a block 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 an acute illness such as fever, diarrhea, or vomiting on the day of the test, the test will be discontinued. - Do not disclose any information you learn about this test to third parties. In particular, do not provide information via social media (Facebook, Twitter, Instagram, LINE, etc.).

[0061] (6) Exclusion criteria Subjects who met 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 with allergies to the test food (particularly those with allergies to wheat, as the test food contains wheat germ extract) 3) Those who regularly consume large amounts of polyamine-containing supplements 4) Those who regularly consume soy foods (natto: one pack or more per day, soy milk: one pack or more per day, tofu: one-third of a block per day) 5) Those who regularly use pharmaceuticals that may affect skeletal muscle mass, such as protein preparations, or health foods (foods for specified health uses, foods with functional claims, and foods with nutrient claims) 6) 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 their consent for this study 7) Those who are deemed ineligible by the study director and study representative

[0062] (7) Statistical analysis methods 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 demonstrated, and a Wilcoxon signed-rank test was used if it was not. For unpaired data, if normality was demonstrated, an F-test was used to test the 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. 2Tests were performed. If 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 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.

[0063] 3. Study results 3-1. Efficacy evaluation (overall) Of the 60 study participants, 2 dropped out for personal reasons and 1 person whose intake rate was below 70% were excluded, and the remaining 57 people were included in the efficacy analysis. Table 2 shows the background of the subjects in the efficacy analysis.

[0064]

[0065] Grip strength and back strength In the group that took 1800 mg of polyamines per day for 12 weeks (hereafter referred to as the "polyamine intake group") (n=30), grip strength and back strength increased significantly before and after the polyamine intake group (p=0.004, p=0.0050, respectively). The results are shown in Tables 3 and 4.

[0066]

[0067]

[0068] 3-3. Muscle mass of the left leg As shown in Table 5, in the polyamine intake group (n=30), muscle mass of the left leg tended to increase before and after the polyamine injection group (p=0.066).

[0069]

[0070] 3-4. Muscle mass by region (right leg, left leg) The mean mean values ​​and errors of muscle mass by region when a subgroup analysis was conducted on people whose age was above the median age (57 years) are shown in Tables 6 and 7.

[0071] The muscle mass of the right leg (Table 6) tended to increase after ingestion compared to before ingestion in the polyamine intake group (p=0.074). The muscle mass of the left leg (Table 7) showed a significant increase after ingestion compared to before ingestion in the polyamine intake group (p=0.036).

[0072]

[0073]

[0074] The mean values ​​and error for grip strength when a subgroup analysis was conducted on subjects above the median age are shown in Table 8. A significant increase was observed after ingestion compared to before ingestion in the polyamine intake group (p=0.048).

[0075]

[0076] Regarding muscle mass by region, polyamine intake showed a tendency for an increase in muscle mass in the left leg. Furthermore, a subgroup analysis of elderly people showed a significant increase in muscle mass in the left leg and a significant trend for an increase in muscle mass in the right leg, suggesting that the leg muscle strengthening effect is stronger in elderly people. Furthermore, although the regions differed, polyamine intake showed a tendency for an increase in back muscle strength, and a subgroup analysis of elderly people showed a significant increase in grip strength, suggesting the possibility of an effect on strengthening muscles other than the legs.

Claims

1. A composition containing a diamine and / or a polyamine for preventing or ameliorating frailty.

2. The composition according to claim 1, wherein the subject is 40 years of age or older.

3. The composition according to claim 1, 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 homocaldohexamine spermidine.

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

5. The composition of claim 1, wherein the frailty is accompanied by at least one selected from the group consisting of decreased skeletal muscle mass, decreased right arm muscle mass, decreased left arm muscle mass, decreased trunk muscle mass, decreased right leg muscle mass, or decreased left leg muscle mass, decreased grip strength, decreased back muscle strength, and decreased leg strength.

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