WO2017179225A1

WO2017179225A1 - Composition for suppressing or improving age-related physical hypofunction or physical dysfunction or age-related mental hypofunction or mental dysfunction

Info

Publication number: WO2017179225A1
Application number: PCT/JP2016/076355
Authority: WO
Inventors: 夏奈大山; 友範小泉
Original assignee: 味の素株式会社
Priority date: 2016-04-13
Filing date: 2016-09-07
Publication date: 2017-10-19
Also published as: JP6879297B2; JPWO2017179225A1

Abstract

Provided is a composition which can effectively suppress or improve physical hypofunction observed with age or physical dysfunction occurring with age, or mental hypofunction observed with age or mental dysfunction occurring with age, said composition comprising a capsinoid compound such as capsiate, dihydrocapsiate or nordihydrocapsiate.

Description

Composition for suppressing or improving physical function deterioration or physical impairment associated with aging, or mental function degradation or mental functional disorder associated with aging

The present invention relates to a decrease in physical function observed with aging, a physical dysfunction manifested with aging, a decrease in mental function observed with aging, or an expression with aging. The present invention relates to a composition for suppressing or improving mental dysfunction.

In recent years, Japan has become one of the world's leading longevity countries, and the proportion of elderly people in the population continues to increase.
However, with aging (aging), the immune system functions and the resistance to infection decreases, so in elderly people, it can often become serious due to influenza, pneumococcus, tuberculosis infection, etc. .
In addition, it is known that aging of vascular cells and adipose tissue accompanying aging causes chronic inflammation through production of inflammatory cytokines, and induces lifestyle-related diseases such as arteriosclerosis and type 2 diabetes. In the elderly, it is reported that the production amount of inflammatory cytokines is increased, and the increase in such inflammatory cytokines may be related to metabolic diseases such as type 2 diabetes, arteriosclerosis, Alzheimer-type dementia or aging-related diseases. It has been reported, and the concept of “inflammatory-aging” has been proposed (Non-patent Document 1). In particular, attention has been focused on the relationship between aging-related diseases such as cerebrovascular dementia and Alzheimer-type dementia and chronic inflammation in the brain.
In addition, it has been reported that the amount of physical activity in humans decreases with aging (Non-patent Document 2). The decrease in muscle mass and the decrease in muscle strength caused by aging, diseases, etc. Can reduce the quality of life (QOL) and cause severe sarcopenia.
Increasing infectious diseases and aging-related diseases associated with aging, and a decrease in the amount of physical activity have led to an increase in medical expenses and an increase in the burden of nursing care, which has become a major social problem as the elderly population increases.

Furthermore, decreased mental functions such as decreased motivation, cognitive function, and depression are observed with aging, and psychiatric disorders associated with aging such as senile depression and sleep disorders are often observed. It is done.

Therefore, a decrease in physical activity, a decrease in muscle mass, a decrease in muscle strength, etc., a decrease in physical function observed with aging, a physical dysfunction manifested with aging, or a decrease in motivation, cognitive function Suppresses mental dysfunction such as depression, psychiatric impairment associated with aging such as depression, senile depression, sleep dysfunction, etc., or aging related diseases, or Improvement is greatly demanded in order to improve the QOL of the elderly, thereby reducing medical expenses and reducing the burden of care.

Therefore, the present invention provides a decrease in physical function observed with aging, a physical dysfunction manifested with aging, a decrease in mental function observed with aging, or with aging. An object of the present invention is to provide a composition that can effectively suppress or ameliorate mental dysfunctions that are manifested.

As a result of diligent studies to solve the above-mentioned problems, the present inventors have shown that capsinoid compounds, which are capsaicin-like substances contained in capsicin varieties of capsicum such as “CH-19 sweet”, have reduced body functions due to aging. The present invention has been completed by finding an action for recovering and improving the physical dysfunction expressed by aging, and further studies.

That is, the present invention is as follows.
[1] A composition containing a capsinoid compound for suppressing or improving a decrease in physical function or impairment associated with aging, or a decrease in mental function or impairment associated with aging.
[2] The composition according to [1], wherein the capsinoid compound is at least one selected from the group consisting of capsiate, dihydrocapsiate and nordihydrocapsiate.
[3] The composition according to [1] or [2], wherein the capsinoid compound is at least one selected from the group consisting of a synthetic product and an extract of capsicum annuum L.
[4] The composition according to any one of [1] to [3], wherein the decrease in physical function is a decrease in the amount of physical activity.
[5] The composition according to any one of [1] to [3], wherein the decrease in physical function is a decrease in muscle mass or a decrease in muscle strength.
[6] The composition according to any one of [1] to [3], wherein the physical dysfunction is sarcopenia or locomotive syndrome.
[7] The composition according to any one of [1] to [3], wherein the decrease in mental function is decreased motivation, cognitive function or depression.
[8] The composition according to any one of [1] to [3], wherein the mental dysfunction is chronic inflammation in the brain.
[9] The composition according to any one of [1] to [3], wherein the mental dysfunction is an aging-related disease caused by chronic inflammation in the brain.
[10] The composition according to any one of [1] to [3], wherein the mental dysfunction is senile depression or sleep disorder.
[11] A pharmaceutical comprising the composition according to any one of [1] to [10].
[12] A food comprising the composition according to any one of [1] to [10].

The composition for suppressing or improving physical function deterioration or physical function disorder, or mental function decrease or mental function disorder according to the present invention is associated with aging, such as a decrease in physical activity, a decrease in muscle mass, a decrease in muscle strength, etc. Observed with aging, such as decreased physical function observed, sarcopenia, locomotive syndrome, etc., physical dysfunction manifested with aging, or reduced motivation, cognitive function, depression Good suppression or improvement of mental dysfunction that develops with aging, such as decreased mental function, senile depression, sleep disorders, chronic inflammation in the brain with aging, and aging-related diseases caused by it Show the effect.
Therefore, according to the present invention, the physical function or mental function of middle-aged persons that have decreased due to aging is recovered, and the physical function disorder or mental function disorder of middle-aged persons observed with aging is suppressed or improved. Can contribute to improving QOL of middle-aged and elderly people.

In Experiment 1, it is a figure which shows the measurement result of the self-issued amount of movement of each group. In Experiment 1, it is a figure which shows the measurement result of the gastrocnemius muscle weight and soleus muscle weight of each group. In Experiment 2, it is a figure which shows the expression level of the inflammation related gene in the cerebral cortex of each group. In Experiment 2, it is a figure which shows the expression level of the inflammation related gene in the hypothalamus of each group. FIG. 10 is a diagram showing the evaluation result by SF-36 in Test Example 3. In Test Example 3, it is a figure which shows the evaluation result by TMT.

A composition for suppressing or improving a decrease in physical function or dysfunction associated with aging according to the present invention, or a decrease or decrease in mental function associated with aging (hereinafter referred to as “the composition of the present invention”). ")" Contains a capsinoid compound as an active ingredient.

The “capsinoid compound” contained as an active ingredient in the composition of the present invention is a fatty acid ester of vanillyl alcohol, and representative compounds include capsiates represented by the following formula (1) and the following formula (2 ) And a nordihydrocapsiate represented by the following formula (3). It has been confirmed that these compounds are contained in non-paste varieties of pepper.

Capsinoid compounds are abundant in plants belonging to the Capsicum genus (hereinafter referred to as “Capsicum genus plants”). Therefore, the capsinoid compounds are extracted from the plants and / or fruits of the Capsicum plant, separated, and purified. Obtainable. There is no particular limitation on the Capsicum plant used as a supply material for the capsinoid compound as long as it is a Capsicum plant containing a capsinoid compound, and it is derived from varieties having a conventional pungent taste typified by “Nikko” and “Five Colors” Pepper (C. annuum L.) may be used, but a spicy variety (C. annuum L.) is preferred. Among them, spicy varieties such as “CH-19 Amane”, “Manganji”, “Fushimi Amaga”, C. annuum L., C. annuum L. var. Angulosum, green pepper (C. annuum L. var. grossum) and the like contain a large amount of capsinoid compounds and can be suitably used. In particular, “CH-19 sweet” which is a spicy taste varieties is more preferable because the content of the component is high. In this specification, the term “CH-19 sweet” means a group of varieties including “CH-19 sweet” varieties and progeny related varieties derived from “CH-19 sweet”.
In the present invention, a genetically modified plant in which production of capsinoids is increased can also be used as a supply material for capsinoid compounds. Examples of such genetically modified plants include capsicum plants with reduced expression or activity of enzymes that catalyze the transamination reaction from vanillin to vanillylamine, as described in WO2009 / 157376. Can be mentioned.
Separation and purification of capsinoid compounds can be carried out by solvent extraction, various types of chromatography such as silica gel chromatography, high-performance liquid chromatography for preparation, etc., which are well known to those skilled in the art, alone or in combination. For example, the method described in JP-A-11-246478 can be used.

The capsinoid compound can also be synthesized by a transesterification reaction using a corresponding fatty acid ester and vanillyl alcohol as starting materials, as described in, for example, JP-A No. 11-246478. Alternatively, it can be synthesized by other reaction methods well known to those skilled in the art based on the structural formula.
Furthermore, it can be easily prepared by a synthesis method using an enzyme. For example, a fatty acid ester corresponding to a desired capsinoid compound by a method described in JP 2000-31598 A, Kobata et al. (Biosci. Biotechnol. Biochem., 66 (2), 319-327, (2002)), and A desired capsinoid compound can be easily obtained by utilizing the reverse reaction of lipase using a compound such as triglyceride having the fatty acid and vanillyl alcohol as a substrate.

In the composition of the present invention, as the capsinoid compound, any of the above extracts and synthetic products may be used, and a crude product may be used. Moreover, a single capsinoid compound may be used, or a mixture of two or more kinds may be used.
From the viewpoint of simplicity, efficiency and cost of the method for obtaining capsinoid compounds, chemical synthesis methods such as the above-described transesterification reaction, synthetic products obtained by the synthesis methods using the above-mentioned enzymes, and spicy varieties of chili peppers ( C. annuum L.) is preferred, and one or more selected from the group consisting of these can be used.

In addition, from the viewpoint of the effect of suppressing or improving the decrease in physical function or dysfunction associated with aging, or the decrease or decrease in mental function associated with aging, preferred capsinoid compounds include capsiate, dihydrocapsiate and nordihydro. Capsicate is mentioned, and it is preferable to select and use one or more of these.
Alternatively, an extract from non-paste varieties of C. annuum L. such as “CH-19 sweet”, which is a mixture of capsiate, dihydrocapsiate and nordihydrocapsiate, eg 62.5% by weight of capsiate, A mixture containing 32.1% by weight of dihydrocapsiate and 5.5% by weight of nordihydrocapsiate can also be suitably used.

The content of the capsinoid compound in the composition of the present invention is usually 0.0001% by weight to 50% by weight, although it depends on the type of capsinoid compound used, the dosage form of the composition of the present invention, etc., preferably 0.001% to 30% by weight.

In addition to the capsinoid compound, the composition of the present invention can contain a nutritional component, an anti-fatigue component, an anti-inflammatory drug, and the like, and a preparation containing such a component is used in combination with the composition of the present invention. You can also
Examples of the components include sugars such as glucose and dextran, oils and fats such as refined soybean oil and refined egg yolk lecithin, proteins such as casein and whey protein, nutrients such as amino acids, vitamins and minerals; antioxidants such as polyphenols Ingredients; psychostimulants such as caffeine; anti-fatigue ingredients such as imidazole dipeptide; non-steroidal anti-inflammatory drugs such as aspirin and ibuprofen; anti-inflammatory drugs such as corticosteroids such as hydrocortisone and prednisolone; liver function improvement such as glycyrrhizin Examples include drugs.
The content of the above-described components in the composition of the present invention is an amount effective for imparting the expected effect to the composition of the present invention, depending on the type of the component contained, the pharmacological action, etc. Can be set as appropriate.

The composition of the present invention is a tablet, coated tablet, chewable tablet, pill, (micro) capsule, granule, fine granule, powder, elixir, limonase, syrup, suspension, emulsion, oral jelly Oral preparations such as pharmaceutical preparations; dosage forms such as injection preparations such as solution, suspension, emulsion, etc., solid injections that are dissolved or suspended at the time of use, infusion preparations, infusion preparations, etc. It can be.

The composition of the present invention in the above-mentioned dosage form is prepared by means of formulation well-known in the field of pharmaceutical preparations, for example, the 16th revised Japanese Pharmacopoeia Formulation General Rules [2] Formulation Articles, the 17th revised Japanese Pharmacopoeia Formulation General Rules [3] It can be prepared by the method described in each section of the preparation. At that time, various pharmacologically acceptable additives for pharmaceutical preparation can be blended as necessary. The additive can be appropriately selected depending on the dosage form of the composition of the present invention. For example, the excipient, binder, disintegrant, lubricant, coating agent, base, solvent, diluent , Solubilizer, solubilizer, emulsifier, dispersant, suspending agent, stabilizer, thickener, soothing agent, tonicity agent, pH adjuster, antioxidant, preservative, preservative, Examples include flavoring agents, flavoring agents, sweetening agents, flavoring agents, and coloring agents.

Specifically, for example, excipients such as magnesium carbonate, titanium dioxide, saccharides (eg, lactose, etc.), sugar alcohols (eg, mannitol, etc.), casein, etc., binders, such as gelatin, starch, cellulose, and derivatives thereof Crospovidone, crystalline cellulose, etc. as disintegrant, talc, magnesium stearate, etc. as lubricant, methacrylic acid / methyl methacrylate copolymer, methacrylic acid / ethyl acrylate copolymer, methacrylic acid as coating agent As a base, such as methyl / butyl methacrylate / dimethylaminoethyl methacrylate copolymer, ethyl acrylate / methyl methacrylate / methacrylated trimethylammonium ethyl copolymer, animal and vegetable oils (for example, olive oil, cocoa butter, Beef tallow, sesame oil, hydrogenated oil, Mashi oil, etc.), wax (carnauba wax, beeswax, etc.), polyethylene glycol, etc. As solvent, purified water, water for injection, monohydric alcohol (eg, ethanol, etc.), polyhydric alcohol (eg, glycerin, etc.), etc., as diluent , Purified water, physiological saline, Ringer's solution, etc., as a solubilizer, propylene glycol, medium chain fatty acid triglyceride, etc., solubilizer, emulsifier, dispersant or suspending agent, sorbitan fatty acid ester, glycerin fatty acid ester, polyoxy Surfactants such as ethylene sorbitan fatty acid esters (polysorbate 20, polysorbate 80, etc.), sucrose fatty acid esters, stabilizers, adipic acid, β-cyclodextrin, etc., thickeners, water-soluble polymers (eg polyacrylic) Sodium acid, carboxyvinyl polymer -), Polysaccharides (sodium alginate, xanthan gum, tragacanth, etc.), etc., as soothing agents, ethyl aminobenzoate, chlorobutanol, propylene glycol, benzyl alcohol, etc., as isotonic agents, potassium chloride, sodium chloride, sorbitol , Physiological saline, etc., pH adjusting agents such as hydrochloric acid, sulfuric acid, acetic acid, citric acid, lactic acid, sodium hydroxide, potassium hydroxide, etc. Antioxidants such as dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), α-tocopherol, erythorbic acid, etc., as preservatives or preservatives, parabens (eg, methylparaben, etc.), benzyl alcohol, sodium dehydroacetate, sorbic acid, etc. Um, etc., sweeteners such as aspartame, licorice extract, saccharin, etc., fragrances such as l-menthol, d-camphor, cineol, etc. ), Inorganic pigments (for example, iron sesquioxide, yellow iron oxide, black iron oxide, etc.), natural pigments (for example, Anato pigment, turmeric pigment, β-carotene, etc.) and the like.

The intake or dose of the composition of the present invention is the condition or symptom of the subject to which the composition of the present invention is applied (hereinafter also referred to as “application subject”), sex, age, composition of the present invention. The dosage form of the product, the administration method, etc. are appropriately determined. When the subject of application is a human adult, the total amount of capsinoid compound is usually 0.01 mg / kg body weight to 5.625 mg / kg body weight per day. It is preferably 0.01 mg / kg body weight to 2.5 mg / kg body weight, more preferably 0.03 mg / kg body weight to 1.25 mg / kg body weight, and particularly preferably 0.05 mg / kg body weight to 1 mg / kg body weight.
The daily intake or dose described above may be taken or administered once, or may be taken or administered divided into two or more (for example, 2 to 5 times).
The ingestion or administration period of the composition of the present invention is the degree of physical function deterioration or physical function disorder observed in the application subject, or the degree of mental function deterioration or mental functional disorder observed in the application subject. However, it is usually 1 day to 300 days, preferably 30 days to 180 days, more preferably 90 days to 150 days.
The composition of the present invention is highly safe and suitable for continuous ingestion or administration because it contains a capsinoid compound contained in a plant body such as a spicy variety of red pepper (C. annuum L.).

The composition of the present invention can be in a unit packaging form. In this specification, “unit packaging form” refers to a specific amount (for example, intake or dose per administration) as one unit, and one unit or two or more units are filled in one container or package. Or the packaged form is said, for example, the unit packaging form which makes the intake amount per time 1 unit is called "the packaging form of the intake amount unit per time". The container or package used in the unit packaging form can be appropriately selected according to the dosage form of the composition of the present invention. For example, a paper container or bag, a plastic container or bag, a pouch, Examples include aluminum cans, steel cans, glass bottles, PET bottles, PTP (press-through-pack) packaging sheets.

Examples of animals to which the composition of the present invention is applied (hereinafter also referred to as “target animals”) include mammals (eg, humans, mice, rats, hamsters, rabbits, cats, dogs, cows, horses, Donkey, pig, sheep, monkey, etc.) and birds (eg, chicken, duck, goose, etc.). When the composition of the present invention is applied to a target animal other than a human, the intake or dose of the composition of the present invention may be appropriately set according to the type, sex, weight, etc. of the target animal.

The composition of the present invention can satisfactorily suppress or improve the decrease in physical function observed with aging.
“Physical function” refers to the ability to perform movement by moving the body, and “decrease in physical function” refers to decreased ability to perform movement by moving the body. Examples of the decrease in physical function include a decrease in physical activity, a decrease in muscle mass, and a decrease in muscle strength.
“Physical activity” is defined as “various physical movements that cause energy consumption through skeletal muscle” and includes all activities such as sports, work, and housework. “Physical activity” is an index that indicates the amount of energy consumed by physical activity, including the time study method based on a 24-hour action record table, SF-36 (MOS 36-Item Short-Form Health Survey). Can be evaluated by the questionnaire method.
Therefore, “decrease in the amount of physical activity” means that the amount of the physical movement is reduced. The suppression or improvement of the decrease in the amount of physical activity includes an increase in the frequency or time of exercise such as sports, an increase in the frequency or time of going out, an increase in the frequency or time of work or housework.
The muscle mass can be measured by a known measurement method such as the DXA method (Dual-energy X-ray absorptiometry method) or the bioelectrical impedance analysis (Bioelectrical impedance analysis (BIA method)).
“Muscle strength” is classified into static muscular strength that is exhibited when the muscle is fixed at a certain angle, instantaneous muscular strength that is exhibited when the muscle is contracted instantaneously, and muscle endurance that continuously contracts the muscle. Static muscle strength can be evaluated by measuring grip strength, leg strength (knee extension strength), back strength, or the like. Instantaneous muscle strength can be evaluated by vertical jumping, ball / cannon throwing, leg extension force measurement, and the like. Muscle endurance can be evaluated by hanging, raising the body, and the like.

Furthermore, the composition of the present invention can satisfactorily suppress or improve the onset of physical dysfunction caused by the progress of the decrease in physical function, such as sarcopenia and locomotive syndrome.
Here, “Sarcopenia” is a syndrome characterized by progressive and generalized skeletal muscle mass and decreased skeletal muscle strength, and “locomotive syndrome” refers to the risk of needing care due to motor organ deterioration and disability. This is a state of increasing.

Therefore, the composition of the present invention is a composition for suppressing or improving a decrease in physical activity associated with aging, or a composition for suppressing or improving a decrease in muscle mass or muscular strength associated with aging, or aging. It is suitably used as a composition for suppressing or improving physical dysfunctions such as sarcopenia and locomotive syndrome.

Moreover, the composition of this invention can suppress well the fall of the mental function accompanying aging, or can improve it.
Mental function decline includes both general mental function declines such as consciousness, vitality and drive, and individual mental function declines such as memory, language, and computation. In particular, for example, decreased motivation, reduced cognitive function, and depression can be mentioned.
Decreased motivation is observed as a state in which the feeling of going out, work, housework, etc. is reduced or the desire to participate in activities such as hobbies is reduced. The “depressed state” is a state of feeling depressed, sad, sad, etc., and can be evaluated using, for example, a GDS (Geriatric Depression Scale) described later. The decrease in cognitive function can be evaluated by, for example, a trail making test (TMT) as a decrease in attention function or performance function.

Furthermore, the composition of the present invention can suppress or improve mental dysfunction that develops with aging. Mental dysfunction that develops with aging can include senile depression and sleep disorders.
Senile depression is a phenomenon of depression in the elderly, psychosomatic heads that are not refreshing, unconcerned, mentally motivated to do anything, unwilling to do anything, tiredness, stiff shoulders, head It is a disease in which physical symptoms such as insomnia, loss of appetite, and constipation are observed, and the degree thereof can be evaluated using, for example, the Geriatric Depression Scale (GDS).
As for sleep disorders associated with aging, especially in the early morning when you wake up early in the morning and you cannot sleep after that, you wake up in the middle of the night and you cannot sleep well. Inability to sleep well, for example, can be assessed using the Pittsburgh Sleep Questionnaire.

Therefore, the composition of the present invention is a composition for reducing motivation associated with aging, cognitive function, suppressing or improving depression, or senile depression, sleep disorders, etc. that develop with aging. It is suitably used as a composition for suppressing or improving.

Furthermore, the composition of the present invention is a gene encoding cytokines, chemokines and the like that are associated with inflammation in the brain with age, such as Icam1 (Intercellular adhesion molecule-1), Il1β (Interleukin-1β), Il6 ( Interleukin-6), Ccl3 (Chemokine (CC motif) ligand 3), Ccl5 (Chemokine (CC motif) ligand 5), Cxcl1 (Chemokine (CXC motif) ligand 1), Cxcl10 (Chemokine (CXC motif) ligand 10), Tgfβ1 (Transforming growth factor-β1), Tnfα (Tumor necrosis factor α), Pml (Promyelocytic leukemia), etc. are suppressed from increasing in expression, and triggered by an increase in inflammatory cytokines encoded by these inflammation-related genes Can suppress or ameliorate chronic inflammation in the brain.
As a result, the composition of the present invention suppresses aging-related mental dysfunction such as aging-related diseases (Alzheimer type dementia, cerebrovascular dementia, Parkinson's disease, etc.) caused by the above chronic inflammation in the brain, or Can be improved.
Therefore, the composition of the present invention is suitable as a composition for suppressing or improving chronic inflammation in the brain accompanying aging, or a composition for suppressing or improving aging-related diseases caused by chronic inflammation in the brain. Used for.

Deterioration of physical functions associated with aging, physical dysfunction associated with aging, mental function impairment associated with aging, and mental dysfunction associated with aging are individual differences depending on lifestyle and exercise habits, The tendency gradually begins to be seen around 40 years old, and the tendency often becomes stronger with aging. Therefore, in this specification, the “middle-aged person” can refer to a human who is 40 years old or older.

In the present specification, “decrease” of a decrease in physical function or dysfunction associated with aging, or a decrease in mental function or dysfunction associated with aging refers to the suppression of the onset or progression of the decrease or disorder. Alternatively, it is referred to as stopping, and “improvement” means that the state or degree of the decrease or failure is alleviated and a better state is achieved.

In addition, the composition of the present invention can be used in various dosage forms such as liquid, emulsion, gel, solid, capsule, etc. as it is or with further addition of excipients, solvents, diluents and the like as described above. It can be a pharmaceutical (hereinafter also referred to as “the pharmaceutical of the present invention”).

The pharmaceutical agent of the present invention is effective in suppressing or improving a decrease in physical function or dysfunction associated with aging, or a decrease in mental function or dysfunction associated with aging.
Therefore, the pharmaceutical product of the present invention develops or develops physical dysfunction such as middle-aged people, sarcopenia, locomotive syndrome, etc. in which physical function decreases, particularly physical activity, muscle mass, and muscle strength. Middle-aged and elderly people who are likely to suffer, especially those who are mentally impaired, particularly motivated, cognitively impaired, middle-aged people who are depressed, and who are or may be experiencing mental dysfunction, especially Middle-aged and elderly with or may be affected by senile depression, middle-aged or older with sleep disorders, or with or may develop chronic inflammation in the brain For elderly people, middle-aged people who are highly likely to suffer from aging-related diseases caused by inflammation in the brain, such as Alzheimer-type dementia, or middle-aged people who have the aging-related diseases And it can be suitably administered.

The content of the capsinoid compound in the pharmaceutical product of the present invention is appropriately determined according to the type and form of the pharmaceutical product, and is usually about 0.0001% by weight to 50% by weight with respect to the total weight of the pharmaceutical product, preferably Is about 0.001 wt% to 30 wt%.

In addition, the daily dose of the pharmaceutical product of the present invention can be set as an amount capable of administering the above-mentioned daily dose of the capsinoid compound in the composition of the present invention.
The administration period of the pharmaceutical product of the present invention is also appropriately determined according to the degree of physical function deterioration or physical function disorder observed in the patient, or the degree of mental function deterioration or mental functional disorder observed in the subject of application. However, the composition of the present invention can be administered for a period of time comparable to that described above.
In addition, since the pharmaceutical of this invention uses a highly safe capsinoid compound as an active ingredient, it is suitable for long-term continuous administration.

Furthermore, the composition of the present invention can be prepared by using a production agent (such as kansui and binder), a thickening stabilizer (such as xanthan gum and sodium carboxymethylcellulose), and a gelling agent (such as gelatin, agar, and carrageenan). , Gum base (vinyl acetate resin, gelton, chicle, etc.), emulsifier (glycerin fatty acid ester, sucrose fatty acid ester, saponin, lecithin, etc.), preservative (benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, ε-polylysine) Etc.), antioxidants (ascorbic acid, erythorbic acid, catechin, etc.), brighteners (shellac, paraffin wax, beeswax, etc.), pH adjusters, sweeteners (aspartame, acesulfame potassium, licorice extract, etc.), bitters ( Caffeine, naringin, sagebrush extract, etc.), acidulant (quee Acid, tartaric acid, lactic acid, etc.), seasonings (sodium L-glutamate, disodium 5′-inosinate, etc.), coloring agents (anato dye, turmeric dye, gardenia dye, etc.), flavors (ethyl acetoacetate, anisaldehyde, etc.) A food additive such as a synthetic fragrance, a natural fragrance such as orange or lavender) can be added and provided as a food, or can be added to various existing foods.
The food to which the composition of the present invention is added is not particularly limited, and may be any food as long as it is generally used for meals and desserts. For example, the composition of the present invention can be added to a beverage, and an appropriate flavor can be added as desired to form a drink (for example, a soft drink). More specifically, the composition of the present invention can be added to, for example, soft drinks such as juices and sports drinks; dairy products such as milk and yogurt; confectionery such as jelly and strawberries.

A food containing the composition of the present invention (hereinafter also referred to as “the food of the present invention”) is preferably used as a food for suppressing or improving physical function deterioration or dysfunction associated with aging. It can be provided as a food for suppressing or improving the decrease in physical activity, the decrease in muscle mass, and the decrease in muscle strength.
In addition, the food of the present invention is preferably used as a food for suppressing or improving a decrease in mental function or mental dysfunction associated with aging, preferably a decrease in motivation associated with aging, a decrease in cognitive function, a depression state or Foods for improvement, foods for suppressing or improving senile depression and sleep disorders that develop with aging, chronic inflammation in the brain that develops with aging, and aging-related diseases caused by the inflammation It can be provided as a food for inhibition or improvement.

The food of the present invention can be in various forms such as liquid, milk, powder, granule, sheet, capsule, tablet, and jelly.
Also, for example, beverages such as juices, soft drinks, tea, coffee; dairy products such as butter, cheese, yogurt, milk, processed milk, skim milk, lactic acid bacteria beverages, fermented milk; and livestock meat products such as ham, sausage, hamburger; Fish paste products such as salmon, bamboo rings, and fried fish cakes; egg products such as sushi rolls and egg tofu; confectionery such as cookies, jelly, chewing gum, candy, snack confectionery, frozen confectionery; breads; noodles; salmon products; dried fish; It can be provided in various forms such as a food, and may be a bottled food, a canned food, or a retort pouch food.

The food of the present invention can develop middle-aged and elderly people who have a tendency to decrease physical activity, muscle mass or strength, middle-aged and elderly people who have a tendency to decrease motivation, cognitive function or depression, and senile depression Highly prone middle-aged people, middle-aged people with a tendency to sleep disorders, middle-aged and elderly people who develop or are likely to develop chronic inflammation in the brain, suffer from aging-related diseases caused by the inflammation Or can be suitably ingested by middle-aged and elderly people who are highly likely to be affected.

Therefore, the food of the present invention can suppress or improve physical activity, muscle mass, muscle weakness, or reduce motivation, cognitive function, depression or suppress depression, senile depression, sleep disorder, etc. Specific health foods, nutritional functional foods, functional labeling foods, etc., functional foods for the prevention or improvement of chronic inflammation in the brain accompanying improvement or aging, or aging-related diseases caused thereby, It can also be provided as special-purpose foods such as foods for the elderly, health supplements, and the like.

Furthermore, the composition of the present invention can be used by adding to a concentrated liquid food or a food supplement.
“Concentrated liquid food” is adjusted to a concentration of about 1 kcal / mL, and even if it is ingested only for a long time, the qualitative composition of each nutrient is sufficient so that there is no significant excess or deficiency of nutrients Is a comprehensive nutritional food (liquid food) designed based on daily nutritional requirements.
The “food supplement” in the present invention refers to those ingested for the purpose of supplementing nutrition in addition to those ingested as food, and also includes nutritional supplements and supplements. When adding the composition of the present invention to food supplements, other nutritional components and additives are added as desired, for example, in the form of tablets, capsules, powders, granules, suspensions, chewables, syrups, etc. Can be prepared.

The above-described food of the present invention may be prepared by adding a food additive as necessary to the composition of the present invention, or by adding the composition of the present invention to food or food ingredients. By using it, it can be manufactured or processed.

The content of the capsinoid compound in the food of the present invention is the kind and form of the food, the degree of suppression or improvement of physical function deterioration or physical function disorder expected by ingesting the food, or the decrease in mental function or mental function. The amount is appropriately determined according to the degree of the suppression or improvement effect on the obstacle, but is usually about 0.0001% to 50% by weight, preferably 0.001% to 30% by weight with respect to the total weight of the food. %.

In addition, the daily intake of the food of the present invention can be set as an amount capable of taking the daily intake of the capsinoid compound described above for the composition of the present invention.
Regarding the ingestion period of the food of the present invention, the degree of the suppression or improvement effect on the decrease in physical function or physical dysfunction expected by the intake of the food of the present invention, or the suppression or improvement effect on mental function decrease or mental dysfunction However, it is preferable to take it continuously for a long period of time from the viewpoint of preventing a decrease in physical function or mental function accompanying aging, physical function disorder or mental function disorder.

Furthermore, the present invention relates to a method for suppressing or improving a decrease in physical function or impairment of physical function associated with aging, or a decrease in mental function or expression of mental impairment associated with aging in a target animal (hereinafter, (Also referred to herein as “the method of the invention”).

The method of the present invention is a subject animal in which a decrease in physical activity such as a decrease in physical activity, a decrease in muscle mass, a decrease in muscular strength, and the like, and an appearance of physical dysfunction with age, Aging, deterioration of mental function such as reduced motivation, cognitive function, depression, senile depression, sleep disorder, age-related chronic inflammation in the brain, or aging caused by the inflammation In order to suppress or improve a decrease in physical function or physical function disorder, or a decrease in mental function or mental function disorder in a target animal in which a mental function disorder that appears with aging such as a related disease is observed Ingesting or administering an effective amount of a capsinoid compound.

Examples of target animals in the method of the present invention include mammals such as humans, mice, rats, hamsters, rabbits, cats, dogs, cows, horses, donkeys, pigs, sheep, monkeys, and birds such as chickens, ducks, and geese. Is mentioned.
In the case of humans, the method of the present invention develops physical dysfunction such as middle-aged, sarcopenia, locomotive syndrome, etc. in which physical function tends to decrease, such as decreased physical activity, decreased muscle mass, and decreased muscle strength. Middle-aged and elderly people who are likely to develop, middle-aged and elderly people with a tendency to decrease mental functions such as reduced motivation, cognitive function, and depression, senile depression, sleep disorders, etc. Applicable to middle-aged people who are suspected, middle-aged people who may suffer from aging-related diseases caused by chronic inflammation in the brain such as Alzheimer-type dementia, middle-aged people who have the aging-related diseases .

The intake or dose of the capsinoid compound in the method of the present invention is determined according to the type, age, symptom or condition of the target animal, but for the composition of the present invention, the daily dose for human and non-human target animals. An amount similar to the amount described above as the per intake or dose can be ingested or administered in the above-mentioned number and period.
Furthermore, the ingestion or administration method of the capsinoid compound in the method of the present invention includes oral administration, enteral tube administration, administration by infusion, etc., but does not need to be performed under the supervision of a doctor at a medical institution, Oral administration is preferred because it can be taken easily.

The present invention will be described in detail by the following test examples.

[Test Example 1] Effect of dihydrocapsiate on physical activity and muscle mass decline with age Young male (57 weeks old) male C57BL6J mice (Nippon Charles River Co., Ltd.), 1 group, and elderly (1 age) For male C57BL6J mice (Nippon Charles River Co., Ltd.) 2 groups (each group n = 6-8), one group of young mice and old mice received a normal diet (AIN-93G composition), and the other group Mice were allowed to freely eat a normal diet (AIN-93G composition) containing 0.3% by weight of dihydrocapsiate and reared for 3 months.
In the first and second months of breeding, the spontaneous movement amount of the mouse was measured as an index of the amount of physical activity, and in the third month of breeding, dissection was performed to measure the weight of the gastrocnemius and soleus.
Spontaneous movement amount was continuously monitored for 60 hours with “Spontaneous Momentum Simple Measurement Sensor NS-AS01” (manufactured by Neuroscience Co., Ltd.), and average values for 2 light periods and 3 dark periods were obtained. Calculated.
The weights of the gastrocnemius and soleus were measured by “Analytical Balance AUX220” (manufactured by Shimadzu Corporation) and expressed as the weight per weight of each group of mice.
The measurement results of the self-issued movement amount and the muscle mass are shown in FIGS. 1 and 2 in the mean value ± standard error of the mean value (SEM), respectively. Each measurement result is subjected to Dunnett's test. In each figure, “*” is significant when P <0.05, and “**” is significant when P <0.01.

From FIG. 1, it was confirmed from the measurement results of the first month of breeding that the spontaneous activity in the dark period corresponding to the active period of the mouse was significantly decreased in the old mouse (P <0.01). In the aged mice fed with a diet containing capsiate (DCT), a recovery tendency of the self-issued amount decreased with aging was observed (P = 0.13). In the second month of breeding, significant recovery of the spontaneous movement amount in the dark period was observed in the aged mice fed the DCT-containing diet (P <0.05).

In addition, as shown in FIG. 2, the weight of both gastrocnemius and soleus muscles decreased in old mice as compared to young mice, and the decreased muscle weight tended to recover by ingestion of a DCT-containing food. It was.

[Test Example 2] Effect of dihydrocapsiate on increase in inflammation-related gene expression with aging For each group of mice dissected in Test Example 1, the expression level of inflammation-related genes in each tissue of the cerebral cortex and hypothalamus was measured. .
As inflammation-related genes, expression levels of Icam1, Ccl3, Cxcl1, I6, Pml, Tgfβ1, Tnfα in the cerebral cortex, and Icam1, Cxcl10, Ccl5, Il6, Pml, Tgfβ1, Tnfα in the hypothalamus (American et al. Physiology-Endocrinology and Metabolism 308 (4), E315-E323, 2015). Briefly, mRNA is extracted using “RNeasy Mini Kit” (QIAGEN) and “iScript ^™ Reverse Transcript Supermix for RT-qPCR” (Bio-Rad) is used. cDNA was synthesized. Subsequently, the gene expression level was measured by a real-time PCR method using “Quant Studio ^™ 12K Flex Real-Time PCR System” (Thermo Fisher Scientific).
The measurement results of the expression level of inflammation-related genes are shown in FIGS. 3 and 4 in terms of mean value ± standard error of mean value (SEM). The measurement results are subjected to Dunnet's test. In each figure, “*” is significant when P <0.05, and “**” is significant when P <0.01.

As shown in FIG. 3, in the cerebral cortex, the expression of each gene of Icam1, Ccl3, Cxcl1, I6, Pml, Tgfβ1, and Tnfα increases with aging, and the increase in the expression is suppressed by ingestion of a DCT-containing food. It was recognized that For Icam1 and I16, the expression level increased with aging was significantly reduced (P <0.05 and P <0.01, respectively).
In addition, as shown in FIG. 4, in the hypothalamus, the expression of Cxcl10, Ccl5, and Il6 increased with aging tended to decrease with the intake of DCT-containing food.
When the expression level of genes encoding inflammatory cytokines increases in the brain and other brain cortex, the production of inflammatory cytokines encoded by those genes increases, resulting in cerebrovascular dementia, Alzheimer-type dementia, etc. It is likely to be associated with the onset and progression of aging-related diseases.
Therefore, the result of Test Example 2 suggests that the composition of the present invention containing a capsinoid compound such as DCT is useful for the suppression or improvement of the aging-related disease that develops with aging.

[Example 1] Soft capsule CH-19 sweet extract was diluted with rapeseed oil so that the content of capsinoid compound would be 0.765 wt%, and then the CH-19 sweet extract was added to 125 mg of plant film. Each 200 mg of the diluted product was encapsulated to prepare soft capsules containing 1.5 mg of capsinoid compound per capsule.

[Test Example 3] Examination of effects of capsinoid compound intake on physical and mental functions (1) Subjects Men and women aged 52 to 88 years who participate in exercise classes once a week (average 70.6 years) A total of 52 people were divided into two groups so that the gender ratio was equal in each group.
(2) Sample ingestion Each subject of one group (capsinoid compound group) was divided into two times, from getting up to breakfast, and from dinner to before bedtime. Ingested 6 capsules for 3 months.
Each subject in the other group (control group) received a soft capsule containing the same amount of rapeseed oil for 3 months.
(3) Evaluation by SF-36 (MOS 36-Item Short-Form Health Survey) One week before the start of sample intake and after the end of the sample intake period, each subject is asked to answer each item of SF-36. Subscales and three summary scales that combine the subscales (physical aspect QOL summary score, mental aspect QOL summary score, and role / social aspect QOL summary score) The score difference before intake of the sample and after the end of the sample intake period was calculated.
(4) Evaluation by Trail Making Test (TMT) One week before the start of sample intake, one month and two months after the start of intake, and after the end of the intake period, TMT is given to each subject. It was carried out.
Regarding TMT, TMT part A and TMT part B were conducted, and the time required for each subject to complete each test was measured. The time required to complete TMT part A and TMT part B The difference (ΔTMT) from the time required to complete the process was calculated.

The evaluation results by SF-36 are the evaluation results for 47 subjects who received answers. Regarding the evaluation results, there was a clear difference between the capsinoid compound group and the control group in the difference in scores before and after the intake of the QOL summary score of the mental aspect and the score of vitality. The difference in scores before and after the intake of each score is shown in FIG. 5 as an average value ± standard error of the average value.
As shown in FIG. 5, in the capsinoid compound group, improvement in the QOL summary score of the mental aspect was recognized, and among them, the score of the item related to vitality was observed to be improved in the capsinoid compound group. On the other hand, such an improvement was not observed in the control group, and it was suggested that taking the soft capsule of Example 1 for 3 months may suppress or improve a decrease in mental function such as an improvement in vitality.

The evaluation result by TMT is an evaluation result for 39 subjects who completed two types of TMT. Regarding the evaluation results, the difference between the time required to end each of the two types of TMT and the time required to end the two types of TMT is represented by the average value ± standard error of the average value. This is shown in FIG.
As shown in FIG. 6, for TMT part A, there was no difference in the time taken to complete the test between the capsinoid compound group and the control group. However, for TMT part B, which is more complicated and reflects the willingness to tackle the task, the time required to complete the test in the capsinoid compound group was shortened compared to the control group. In the capsinoid compound group, ΔTMT was significantly shortened (t test, P <0.05) compared to the control group.
TMT is known as a method for evaluating cognitive function, and ΔTMT has been reported to be associated with intellectual ability and the severity of cognitive dysfunction and is an index that expresses higher-order functions more sensitively.
Therefore, from the above evaluation results of TMT, it was suggested that the ingestion of the soft capsule of Example 1 may suppress or improve cognitive decline or cognitive impairment.

As described above in detail, according to the present invention, it is possible to provide a composition for suppressing or improving physical function deterioration or physical function disorder associated with aging, or mental function decrease or mental function disorder associated with aging. .
The composition of the present invention is a decrease in physical activity, a decrease in muscle mass, a decrease in muscle strength, etc., a decrease in physical function observed with aging, and sarcopenia, locomotive syndrome, etc. It is useful for suppressing or improving physical dysfunction.
In addition, the composition of the present invention is a decrease in motivation, cognitive function, depression, and other mental functions observed with aging, senile depression, sleep disorders, It is useful for suppression or improvement of mental dysfunction such as chronic inflammation in aging and aging-related diseases caused by the inflammation.

This application is based on Japanese Patent Application No. 2016-80675 filed in Japan, the contents of which are incorporated in full herein.

Claims

A composition for suppressing or improving a decrease in physical function or dysfunction associated with aging, or a decrease in mental function or dysfunction associated with aging, comprising a capsinoid compound.
The composition according to claim 1, wherein the capsinoid compound is at least one selected from the group consisting of capsiate, dihydrocapsiate and nordihydrocapsiate.
3. The composition according to claim 1 or 2, wherein the capsinoid compound is at least one selected from the group consisting of an extract of a synthetic product and an unpastey variety of capsicum annuum L.
The composition according to any one of claims 1 to 3, wherein the decrease in physical function is a decrease in the amount of physical activity.
The composition according to any one of claims 1 to 3, wherein the decrease in physical function is a decrease in muscle mass or a decrease in muscle strength.
The composition according to any one of claims 1 to 3, wherein the physical dysfunction is sarcopenia or locomotive syndrome.
The composition according to any one of claims 1 to 3, wherein the lowering of mental function is reduced motivation, cognitive function or depression.
The composition according to any one of claims 1 to 3, wherein the mental dysfunction is chronic inflammation in the brain.
The composition according to any one of claims 1 to 3, wherein the mental dysfunction is an aging-related disease caused by chronic inflammation in the brain.
The composition according to any one of claims 1 to 3, wherein the mental dysfunction is senile depression or sleep disorder.