WO2021065664A1 - 生活活動量の維持、低下予防、低下抑制又は改善用組成物 - Google Patents

生活活動量の維持、低下予防、低下抑制又は改善用組成物 Download PDF

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WO2021065664A1
WO2021065664A1 PCT/JP2020/035986 JP2020035986W WO2021065664A1 WO 2021065664 A1 WO2021065664 A1 WO 2021065664A1 JP 2020035986 W JP2020035986 W JP 2020035986W WO 2021065664 A1 WO2021065664 A1 WO 2021065664A1
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Prior art keywords
sesamin
amount
composition
activity
maintaining
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PCT/JP2020/035986
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English (en)
French (fr)
Japanese (ja)
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友紀 八木田
千絵 阿部
佳子 小野
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サントリーホールディングス株式会社
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Priority to JP2021551148A priority Critical patent/JPWO2021065664A1/ja
Priority to CN202080069358.3A priority patent/CN114514022A/zh
Publication of WO2021065664A1 publication Critical patent/WO2021065664A1/ja
Priority to JP2024062612A priority patent/JP2024098986A/ja

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/111—Aromatic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/116—Heterocyclic compounds
    • A23K20/121—Heterocyclic compounds containing oxygen or sulfur as hetero atom
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals

Definitions

  • the present invention relates to a composition for maintaining, preventing, suppressing or improving the amount of daily activity.
  • the present invention also relates to a method for maintaining, preventing, suppressing or improving the amount of daily activity, and using one or more sesamin for maintaining, preventing, suppressing or improving the amount of daily activity.
  • Non-Patent Document 1 discloses that daily activities decrease with aging.
  • Non-Patent Document 3 discloses that the higher the amount of physical activity, the longer the healthy life expectancy. In an aging society, it is required to maintain physical activity and extend healthy life expectancy by maintaining not only exercise but also daily activity.
  • the amount of human physical activity can be measured using the number of steps as a basic index.
  • the measurement of the number of movements by infrared rays and the measurement of the movement distance by telemetry are the mainstream.
  • low-intensity activity evaluation is also required to evaluate the amount of daily activity that does not include exercise.
  • a measurement method using an activity meter with a built-in triaxial accelerometer has been developed as a method for measuring the amount of daily living activity of humans. Since low-intensity activity can be accurately measured by using this measurement method, it can be an index for more accurately measuring the amount of daily activity. Using this measurement method, it was proved that the amount of daily activity in humans decreases with aging (Non-Patent Document 1).
  • Sesamin was subjected to an exercise stress test on rats fed a high-fat diet, and it has been proved in Non-Patent Document 2 that the decrease in endurance is suppressed.
  • sesamins prevent a decrease in the amount of daily activity, not exercise, and contribute to the maintenance of the amount of daily activity among physical activities. That is, it was not known that sesamin such as sesamin has an action of maintaining the amount of daily activity. In particular, it has not been reported whether sesamin such as sesamin contributes to the maintenance of activities of daily living with aging.
  • An object of the present invention is to provide a composition for maintaining, preventing, suppressing or improving the amount of daily activity. Another object of the present invention is to maintain, prevent a decrease in the amount of daily activity, suppress or improve the decrease, and use one or more sesamin for maintaining, preventing the decrease, suppressing or ameliorating the amount of daily activity. To do.
  • Non-Patent Document 1 The present inventors diligently studied to solve the above problems, and measured the activity amount of the rat without applying exercise by using the activity meter with a built-in triaxial accelerometer shown in Non-Patent Document 1. It was found that sesamines have the effect of maintaining the amount of physical activity excluding exercise, that is, the amount of living activity. In addition, the present inventors have found that sesamin are useful for preventing or maintaining a decrease in the amount of daily activity that decreases with age.
  • the present invention relates to the following compositions for maintaining, preventing, suppressing or improving the amount of daily activities.
  • a composition for maintaining, preventing, suppressing or improving the amount of daily activity containing one or more of sesamin.
  • Prevention or suppression of decrease in daily activity due to aging, improvement of decrease in daily activity with aging, prevention or suppression of increase in inactivity time with aging, increase in inactivity time with aging The composition according to any one of the above [1] to [3] for improving the above.
  • oral composition is a food or drink, a pharmaceutical product, a quasi drug, or a feed.
  • food or drink is a food for specified health use, a nutritionally functional food, or a food with functional claims.
  • the present invention it is possible to provide a composition for maintaining, preventing, suppressing or improving the amount of daily activity. Further, according to the present invention, it is possible to provide a method for maintaining, preventing, suppressing or improving the amount of daily activity. Further, according to the present invention, it is possible to provide the use of one or more kinds of sesamin for maintaining, preventing, suppressing or improving the amount of daily activity. Ingestion of one or more of sesamin has the effect of maintaining, preventing, suppressing or improving the amount of daily activity. Ingestion of one or more sesamin species prevents or suppresses the decrease in daily activity due to aging, improves the decrease in daily activity due to aging, or prevents the increase in inactivity time due to aging. , Can be suppressed or improved.
  • the sesamin used in the present invention is a component that has been ingested as a food for a long time, and is also advantageous in that it is highly safe and can be continuously ingested.
  • the composition for maintaining, preventing, suppressing or improving the amount of daily activity of the present invention contains one or more sesamin.
  • Sesamin is one of the main lignan compounds of sesame, and is contained in sesame in an amount of about 0.5 to 1.0% by weight. While long-term ingestion of artificially synthesized compounds is not preferable from the viewpoint of unexpected side effects and the like, sesamins whose safety is guaranteed are most suitable for long-term ingestion.
  • physical activity, exercise, and living activity have the same meaning as the definitions of physical activity, exercise, and living activity in the "Exercise Guideline for Health Promotion 2006" issued by the Ministry of Health, Labor and Welfare. .. That is, physical activity is all activities that consume more energy than in a resting state, and living activities are physical activities other than exercise.
  • the exercise is carried out systematically and intentionally for the purpose of maintaining and improving physical fitness, for example.
  • the amount of daily activity can be measured using an activity meter with a built-in triaxial accelerometer (Actimarker manufactured by Panasonic Corporation). Animals can be measured using an activity meter with a built-in triaxial accelerometer (nanotag manufactured by Kissei Comtech Co., Ltd.) under conditions such as a treadmill that do not impose exercise.
  • the life activity in the present invention is not particularly limited, and examples thereof include household chores, work and / or childcare activities in humans. In animals, the amount of activity measured under the condition that no exercise is applied is considered to correspond to the amount of daily activity in humans.
  • the amount of daily activity can be measured as the amount of daily activity and / or the time of daily activity. That is, maintenance, prevention of decrease, suppression or improvement of decrease in the amount of daily activity means maintenance, prevention of decrease, suppression or improvement of decrease in amount of daily activity and / or living activity time. Since the inactivity time increases due to the decrease (decrease) in the living activity time, the prevention, suppression or improvement of the increase in the inactivity time is also used for maintaining, preventing the decrease, suppressing or improving the amount of living activity in the present invention. included.
  • the inactivity time means a time during which physical activity is not performed, that is, a time during rest such as sleeping or sitting behavior.
  • the above-mentioned maintenance, prevention of decrease, suppression or improvement of decrease in daily activity means prevention or suppression of decrease in daily activity, improvement of decreased daily activity, prevention or suppression of increase in inactivity time, or increased inactivity time. It is preferable that it is an improvement.
  • the maintenance, prevention of decrease, suppression or improvement of the above-mentioned amount of daily activity is the prevention or suppression of the decrease in the amount of daily activity associated with aging, the improvement of the amount of daily activity decreased with aging, and the inactivity time associated with aging. It is preferable to prevent or suppress the increase and improve the inactivity time that has increased with aging.
  • aging refers to a change associated with an increase in age after middle and old age, especially after about 40 years old.
  • sesamin is a general term for compounds containing sesamin and its analogs. Sesamin is one of the major lignan compounds contained in sesame seeds. Examples of sesamin analogs include episesamin and dioxabicyclo [3.3.0] octane derivatives described in JP-A-4-9331. As one or more kinds of sesamin, one kind of compound may be used alone, or two or more kinds may be used. Specific examples of sesamin include sesamin, episesamine, sesaminol, episesaminol, sesamol, sesamolin and the like, and these stereoisomers or racemates can be used alone or in combination.
  • sesamin and / or episesamin can be preferably used as one or more of the sesamin, sesamin and episesamin, or episesamin can be more preferably used, and episesamin can be further preferably used. ..
  • sesamin and episesamin are used, their ratios are not particularly limited, but for example, sesamin: episesamin (weight ratio) is preferably 1: 0.1 to 1: 9, and more preferably 1: 0.3 to 1: 3. , 1: 0.5 to 1: 2 is more preferable.
  • sesamin used in the present invention is not limited by its form, production method, or the like.
  • sesamin referred to as sesamin extract or purified product
  • a known method for example, the method described in JP-A-4-9331
  • commercially available sesame oil (liquid) can be used as it is.
  • sesame oil liquid
  • the flavor peculiar to sesame oil may be evaluated as sensually unfavorable. Therefore, a tasteless and odorless sesamin extract (or refined sesamin product) extracted from sesame oil is used. Is preferable.
  • sesame oil when sesame oil is used, the sesamin content is low, and if a preferable amount of sesamin is to be added, the volume of the prescribed composition per unit dose becomes too large, which may cause inconvenience in intake. ..
  • the formulation tablettes, etc.
  • one or more of purified or isolated sesamin may be used. Sesamin can also be obtained by synthesis.
  • sesamin and episesamin can be synthesized by the method of Beroza et al. (J. Am. Chem. Soc., 78, 1242 (1956)).
  • the metabolites of sesamin and episesamin can be synthesized by the method of Urata et al. (Chem. Pharm. Bull. (Tokyo), 56 (11) 1611-2 (2008)).
  • Sesamin is a compound that is contained in natural products and foods and drinks and has eating experience. Therefore, from the viewpoint of safety, sesamin is considered to have few problems in ingestion every day, for example. According to the present invention, it is possible to provide a composition for maintaining, preventing, suppressing or improving the amount of daily activity containing a highly safe substance as an active ingredient.
  • the composition of the present invention can be applied to either therapeutic use (medical use) or non-therapeutic use (non-medical use).
  • Non-therapeutic is a concept that does not include medical practice, ie human surgery, treatment or diagnosis.
  • the composition of the present invention can be in the form of food and drink, pharmaceuticals, quasi-drugs, feed and the like.
  • the composition of the present invention may itself be a food or drink, a drug, a quasi-drug, a feed, etc. for maintaining, preventing, suppressing or improving the amount of daily activity, and is used in combination with these. It may be a material or a preparation to be used.
  • the composition of the present invention can be provided, for example, in the form of an agent, but is not limited to this form.
  • the agent can be provided as it is as a composition or as a composition containing the agent.
  • the composition of the present invention may be either an oral composition or a parenteral composition, but is preferably an oral composition.
  • examples of the oral composition include foods and drinks, oral medicines, quasi-drugs, and feeds, preferably foods and drinks or oral medicines, and more preferably foods and drinks.
  • composition of the present invention may contain any additive and any component in addition to one or more sesamins as long as the effects of the present invention are not impaired.
  • additives and ingredients can be selected according to the form of the composition and the like, and generally those that can be used for foods and drinks, pharmaceuticals, quasi-drugs, feeds and the like can be used.
  • the composition of the present invention is a food or drink, a pharmaceutical product, a quasi-drug, a feed or the like
  • the production method thereof is not particularly limited and can be produced by a general method.
  • composition of the present invention when used as a food or drink, one or more kinds of sesamin are mixed with ingredients that can be used in the food or drink (for example, food materials, food additives used as needed, etc.).
  • Various foods and drinks can be used.
  • Foods and drinks are not particularly limited, and examples thereof include general foods and drinks, health foods, dietary supplements, health drinks, foods with functional claims, foods for specified health use, foods and drinks for the sick, and the like.
  • the above-mentioned health foods, health supplements, foods with functional claims, foods for specified health use, etc. include, for example, fine granules, tablets, granules, powders, capsules, chewables, dry syrups, syrups, liquids, beverages, fluids. It can be used as various formulations such as food.
  • composition of the present invention is a pharmaceutical product or a quasi-drug
  • a pharmacologically acceptable carrier for example, an additive added as necessary, or the like is blended with one or more of sesamin. It can be a drug of various dosage forms or a quasi-drug.
  • Such carriers, additives and the like may be pharmacologically acceptable as long as they can be used in pharmaceutical products or quasi-drugs, and for example, excipients, binders, disintegrants, lubricants, etc.
  • antioxidants, colorants and the like can be mentioned.
  • Examples of the administration (ingestion) form of the drug or quasi-drug include oral or parenteral (transdermal, transmucosal, intestinal, injection, etc.) administration forms.
  • composition of the present invention is a drug or a quasi-drug
  • it is preferably an oral drug or a quasi-drug.
  • Dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewables and the like.
  • the drug may be a non-human veterinary drug.
  • composition of the present invention When the composition of the present invention is used as a feed, one or more of sesamin may be added to the feed.
  • the feed also contains feed additives. Examples of the feed include livestock feed used for cattle, pigs, chickens, sheep, horses and the like; small animal feed used for rabbits, rats, mice and the like; pet food used for dogs, cats, small birds and the like.
  • the content of sesamin contained in the composition of the present invention is not particularly limited and can be set according to the form and the like.
  • the total content of sesamin in the composition of the present invention is, for example, preferably 0.001% by weight or more, more preferably 0.01% by weight or more, still more preferably 0.05% by weight or more in the composition. , 10% by weight or less is preferable, and 5% by weight or less is more preferable.
  • the total content of sesamin is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight, still more preferably 0.05 to 5% by weight in the composition.
  • the total content is the total content of two or more sesamin compounds when they are contained.
  • the composition of the present invention is preferably taken orally (orally administered).
  • the dose (which can also be referred to as ingestion) of the composition of the present invention is not particularly limited.
  • the dose of the composition of the present invention may be any amount as long as it can maintain, prevent, suppress or improve the amount of daily activity, and is appropriately set according to the administration form, administration method, body weight of the subject, and the like. do it.
  • the total dose of sesamin is 60 kg body weight per day, preferably 0.5 mg or more, more preferably. It is 1 mg or more, more preferably 3 mg or more, preferably 200 mg or less, more preferably 100 mg or less, still more preferably 80 mg or less. In one embodiment, the total dose of sesamin is 60 kg body weight per day for humans (adults), preferably 0.5 to 200 mg, more preferably 1 to 100 mg, still more preferably 3 to 80 mg. It is preferable to ingest or administer the above amount once or more a day, for example, once a day or several times (for example, 2 to 3 times).
  • the above amounts of sesamin be orally ingested or administered to humans.
  • the compositions of the present invention can be used to allow humans to ingest or administer the above amounts of sesamin per 60 kg of body weight per day.
  • the total dose is the total amount when two or more sesamin compounds are used.
  • sesamin and / or episesamin is used as the total dose of sesamin and episesamin at a body weight of 60 kg per day, preferably 0.5 to 200 mg, more preferably 1 to 100 mg, still more preferably 3 to 80 mg, human ( It is preferable to ingest or administer it orally to an adult).
  • composition of the present invention is preferably continuously ingested or administered. It is expected that the above effects will be enhanced by continuously ingesting or administering sesamin.
  • the composition of the present invention is preferably ingested or administered continuously for 1 week or longer, more preferably 4 weeks or longer, further preferably 8 weeks or longer, and particularly preferably 12 weeks or longer. preferable.
  • the subject to ingest or administer the composition of the present invention is not particularly limited, and can be ingested by humans and non-human animals.
  • non-human animals include industrial animals, pets, laboratory animals and the like.
  • industrial animals include livestock such as cattle, horses, pigs, goats and sheep, poultry such as chickens, ducks, quail, turkeys and ostriches, as well as yellowtail, hamachi, madai, maji, koi, nigga and eel.
  • Pets are so-called companion animals such as dogs, cats, marmosets, small birds and hamsters, and companion animals. And represents animals used for research in fields such as pharmacy.
  • the administration target of the composition of the present invention is preferably a human or a non-human mammal, and more preferably a human.
  • the administration target includes a subject who needs or desires to maintain, prevent a decrease in the amount of daily activity, suppress or suppress the decrease, or abide.
  • targets include, for example, middle-aged and elderly people, subjects who need or desire to maintain, prevent decline, suppress decline or improve living activity amount and / or daily activity time, and decrease vitality or energy to perform daily activities.
  • the middle-aged person may be, for example, a person aged 40 years or older.
  • Middle-aged and elderly people are a concept that includes elderly people. Among the middle-aged and elderly people in one aspect, the elderly are preferable as the target.
  • the elderly person may be, for example, a person aged 60 years or older or a person aged 65 years or older.
  • the composition of the present invention is used, for example, for a healthy person for the purpose of maintaining, preventing, suppressing or improving the amount of daily activity and / or the time of daily living, for the purpose of preventing or preventing a symptom or disease that can be expected to be prevented or improved. It can also be used.
  • composition of the present invention may be labeled with a function exerted by maintaining, preventing, suppressing or improving the amount of daily activity and / or the time of daily living.
  • Such indications include, for example, "maintaining or improving the amount of daily activity that decreases with age”, “maintaining or extending the time of daily living that decreases with age”, and “maintaining or extending the amount of inactivity that increases with age”.
  • the composition of the present invention is preferably a food or drink with the above indication. Further, the above display may be a display to the effect that it is used to obtain the above function.
  • the present invention also includes the following methods.
  • the present invention also includes the following uses.
  • the methods and uses may be therapeutic or non-therapeutic methods or uses.
  • By administering one or more kinds of sesamin to a subject it is possible to maintain, prevent, suppress or improve the amount of daily activity and / or the time of daily activity.
  • sesamins and preferred embodiments thereof are the same as the compositions of the present invention described above.
  • one or more kinds of sesamin one kind of compound of sesamin may be used, and two or more kinds may be used.
  • the above use is preferably in humans or non-human mammals, more preferably in humans.
  • sesamin in an amount (which can be said to be an effective amount) that can obtain a desired action may be used.
  • the preferred dose of sesamin, the subject of administration, and the like are the same as those of the composition of the present invention described above.
  • the sesamin may be administered as it is, or may be administered as a composition containing the sesamin.
  • the composition of the present invention described above may be used.
  • the present invention also includes the use of one or more sesamins for producing the compositions of the present invention. All academic and patent documents described herein are incorporated herein by reference.
  • Example 1 Sesamin / episesamin mixture (1: 1) Effect of suppressing decrease in activities of daily living (in vivo test)> Since this experiment is performed under the condition that no exercise load is applied, it is considered that all the measured activity amounts correspond to the daily activity amount in humans.
  • the normal feed group and the sesamin / episesamin-containing feed group were divided into groups so that the amount of daily activities was equal.
  • An acceleration measuring instrument nanotag manufactured by Kissei Comtec Co., Ltd. was used to measure the amount of daily activities.
  • the amount of activity during the active period was measured for 3 days.
  • the number of vibrations above a certain intensity was continuously measured, and the total number of frequencies was taken as the amount of daily activity.
  • the group fed with the normal feed was the old-age normal feed group (normal feed group), and the group fed with the feed containing 0.1% by weight sesamin and episesamin was the old-age sesamin / episesamin-containing feed group (sesamin / episesamin-containing feed).
  • sesamin: episesamin (weight ratio) 1:
  • Rats that were determined to be difficult to continue the study by regularly measuring food intake and body weight to understand the health of the animals were subjected to appropriate euthanasia and excluded from the analysis.
  • the final analysis subjects were 4 animals in the old-age normal feed group and 6 animals in the old-age sesamin / episesamin-containing feed group.
  • FIG. 1 shows the change in the relative activity of daily living when the activity of daily living before the start of the test meal is 1.
  • ⁇ is an old-age normal feed group
  • ⁇ is an old-age sesamin / episesamin-containing feed group (*: p ⁇ 0.05, repeated measures two-way ANOVA for the old-age normal feed group). The lower the value, the lower the activity.
  • the amount of daily activity decreased with aging.
  • Example 2 Sesamin or episesamin alone administration has an effect of suppressing a decrease in activities of daily living (in vivo test)>
  • Example 2 is a test for examining whether sesamin or episesamin contributes more to the suppression of decrease in activities of daily living. The basic operation was carried out according to Example 1. A group in which 14-month-old Slc: SD male rats were fed a normal diet (CE-2, manufactured by Nippon Claire Co., Ltd.) or a diet containing 0.1% sesamin or episesamin so that the amount of activity was equal. The animals were divided into groups (3 animals / group), and each feed (test meal) was ingested for 1 month.
  • the amount of daily activity during the active period was measured.
  • the final analysis targets were 2 animals in the normal feed group, 3 animals in each of the sesamin-containing feed group and the episesamin-containing feed group.
  • Table 1 shows the amount of daily activity of each group one month after ingestion of the test meal, assuming that the amount of daily activity before the start of the test meal is 1. The lower the value, the lower the amount of daily activity. As shown in Table 1, the amount of daily activity decreased in the normal feed group.
  • the sesamin-containing feed group and the episesamin-containing feed group the decrease in the amount of daily activity due to aging was suppressed as compared with the normal feed group. In the episesamine-containing diet group, no decrease in daily activity due to aging was observed.
  • sesamin and episesamin suppressed the decrease in the amount of daily activity due to aging, and maintained, prevented the decrease, suppressed or improved the amount of daily activity. It was also revealed that the effect was stronger with episesamine.

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PCT/JP2020/035986 2019-10-04 2020-09-24 生活活動量の維持、低下予防、低下抑制又は改善用組成物 WO2021065664A1 (ja)

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JP2021551148A JPWO2021065664A1 (enrdf_load_stackoverflow) 2019-10-04 2020-09-24
CN202080069358.3A CN114514022A (zh) 2019-10-04 2020-09-24 维持生活活动量、预防其降低、抑制或改善其降低用组合物
JP2024062612A JP2024098986A (ja) 2019-10-04 2024-04-09 生活活動量の維持、低下予防、低下抑制又は改善用組成物

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015096072A (ja) * 2014-12-09 2015-05-21 国立大学法人北海道大学 身体活動促進剤
JP2018141014A (ja) * 2007-03-15 2018-09-13 サントリーホールディングス株式会社 抗疲労剤
JP2019001798A (ja) * 2015-08-07 2019-01-10 国立大学法人 筑波大学 活動意欲向上剤

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