WO2022131063A1 - 筋肉の柔軟性改善用組成物 - Google Patents
筋肉の柔軟性改善用組成物 Download PDFInfo
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- WO2022131063A1 WO2022131063A1 PCT/JP2021/044822 JP2021044822W WO2022131063A1 WO 2022131063 A1 WO2022131063 A1 WO 2022131063A1 JP 2021044822 W JP2021044822 W JP 2021044822W WO 2022131063 A1 WO2022131063 A1 WO 2022131063A1
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- muscle
- quercetin
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
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- A—HUMAN NECESSITIES
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
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- A—HUMAN NECESSITIES
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
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- A—HUMAN NECESSITIES
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
- A61K8/602—Glycosides, e.g. rutin
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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- A—HUMAN NECESSITIES
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- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/316—Foods, ingredients or supplements having a functional effect on health having an effect on regeneration or building of ligaments or muscles
Definitions
- the present invention relates to a composition for improving muscle flexibility.
- the present invention also relates to the use of quercetin and / or its glycosides for improving muscle flexibility and the like.
- Japan which is a super-aging society
- medical care is advancing and the proportion of the elderly in the late stages is increasing, while extending healthy life expectancy and improving the quality of life (QOL) are issues.
- QOL quality of life
- One of the factors for shortening healthy life expectancy is that there is a high risk of requiring nursing care due to a disorder of the locomotive organ, that is, locomotive syndrome. Pain due to musculoskeletal diseases associated with aging, muscle weakness, endurance, and decreased motor function occur, which together lead to a negative chain. As a result, it is thought that activities of daily living cannot be performed and the patient becomes in need of nursing care, and its prevention is important.
- motor function is not simply proportional to muscle mass, but that muscle flexibility and the like are also involved in motor function. Therefore, it is considered that it is important not only to increase the muscle mass but also to improve the flexibility of the muscle to suppress or improve the deterioration of the motor function.
- Quercetin is a type of flavonoid and is contained in many plants such as onions as it is or as a glycoside.
- PPAR ⁇ activating action and the like have been reported (for example, Patent Document 1).
- a component capable of improving muscle flexibility is effective, for example, in suppressing or improving motor function.
- An object of the present invention is to provide a composition for improving muscle flexibility.
- quercetin which is a kind of flavonol, and / or a glycoside thereof are effective in improving muscle flexibility.
- the present invention includes, but is not limited to, the following compositions for improving muscle flexibility and the like.
- FIG. 1 is a graph showing the amount of change in muscle shear wave velocity at 24 weeks of intervention compared to before the intervention of exercise and test food intake.
- composition for improving muscle flexibility of the present invention contains quercetin and / or a glycoside thereof.
- the composition for improving muscle flexibility of the present invention is hereinafter simply referred to as the composition of the present invention.
- the composition of the present invention usually contains quercetin and / or a glycoside thereof as an active ingredient.
- quercetin means quercetin, which is a compound belonging to flavonols, which is a kind of polyphenol.
- quercetin glycoside means the above-mentioned quercetin glycoside, and specifically, is a general term for a series of compounds in which one or more sugars are glycosidic bonded to the hydroxyl group at the 3-position of quercetin.
- Quercetin glycoside is a compound represented by the following general formula.
- (X) n in the following general formula represents a sugar chain.
- X represents a sugar (monosaccharide), and n is an integer of 1 or more.
- the quercetin glycoside may be one kind of compound or two or more kinds of compounds.
- the sugar constituting the sugar chain represented by X that glycosidically binds to quercetin is, for example, glucose, rhamnose, galactose, glucuronic acid, or the like, and preferably glucose or rhamnose.
- n is not particularly limited as long as it is 1 or more, but is preferably 1 to 16, and more preferably 1 to 8.
- the X portion may be composed of one kind of sugar or may be made of a plurality of kinds of sugars.
- (X) n may be a sugar chain composed of one kind of sugar or a sugar chain composed of a plurality of kinds of sugars.
- the quercetin glycoside in the present invention also includes a quercetin glycoside obtained by treating an existing quercetin glycoside with an enzyme or the like to transfer the sugar.
- the quercetin glycoside referred to in the present invention includes rutin, enzyme-treated rutin (enzyme-treated product of rutin), quercitrin, isoquercitrin and the like.
- enzyme-treated rutin it is particularly preferable to use enzyme-treated rutin as the quercetin glycoside.
- isoquercitrin obtained by enzymatically treating rutin to remove the rhamnose sugar chain portion isoquercitrin obtained by treating isoquercitrin with a glycosyltransferase, and a sugar consisting of 1 to 7 glucoses.
- examples thereof include those in which chains are bonded and those having a mixture thereof as a main component.
- quercetin glycoside a compound in which 1 to 8 glucoses are glycosidic bonded to the hydroxyl group at the 3-position of quercetin (for example, isoquercitrin, a glycoside in which 1 to 7 glucoses are bound to isoquercitrin). Body) and the like are preferable.
- quercetin glycoside is absorbed into the body after the sugar is cleaved in the intestinal tract to become aglycone (quercetin).
- quercetin and / or its glycoside there are no particular restrictions on the origin and production method for obtaining quercetin and / or its glycoside.
- buckwheat, enju, caper, apple, tea, onion, grape, broccoli, moroheiya, raspberry, bilberry, cranberry, opuntia, leafy vegetables, citrus and the like are known as plants rich in quercetin and / or its glycosides.
- buckwheat, enju, caper, apple, tea, onion, grape, broccoli, moroheiya, raspberry, bilberry, cranberry, opuntia, leafy vegetables, citrus and the like are known. Quercetin and / or glycosides thereof can be obtained from these plants.
- quercetin and / or glycosides thereof used in the present invention quercetin and / or quercetin and / or extracts derived from natural products such as the above-mentioned plants can be concentrated and purified as long as the effects of the present invention can be obtained.
- a concentrate or purified product having an increased content of the glycoside thereof for example, an extract containing quercetin and / or the glycoside thereof can be used.
- concentration method or the purification method a known method can be adopted.
- Purified or isolated quercetin and / or glycosides thereof may be used in the present invention.
- quercetin and / or its glycoside a chemically synthesized product can also be used.
- Quercetin and / or its glycosides are compounds contained in natural products and foods and drinks and have eating experience. Therefore, from the viewpoint of safety, quercetin and / or its glycoside is considered to have less problem in ingestion, for example, daily. According to the present invention, it is possible to provide a composition for improving muscle flexibility, which comprises a highly safe substance as an active ingredient.
- the flexibility of a muscle is the ease of expansion and contraction of the muscle.
- Muscle flexibility has been reported to decrease with age (eg, Muscle Nerve. 2017 Mar 55 (3) 305-315.). Improving muscle flexibility can also be said to be improving muscle hardness (muscle hardness).
- improvement of muscle flexibility includes suppression of decrease in muscle flexibility, maintenance of muscle flexibility, improvement of muscle flexibility (increase in flexibility), and the like.
- Improvement of muscle hardness includes suppression of increase in muscle hardness, maintenance of muscle hardness, decrease in muscle hardness, and the like.
- Muscle flexibility can be evaluated using the shear wave velocity of the muscle as an index, which is measured by the shear wave elastography method.
- Shear wave elastography is one of ultrasonic elastography, in which vibration is performed in the living body by acoustic radiation impulse, and the propagation velocity distribution of the shear wave generated by it is measured to evaluate the hardness of the tissue.
- the method (Makoto Yamakawa, Journal of the Society of Biomechanism, Vol. 40, No. 2 (2016), 73-78, especially page 74, right column, lines 10-12). It can be said that the smaller the shear wave velocity, the higher the flexibility of the muscle (the muscle is soft), and the larger the shear wave velocity, the lower the flexibility of the muscle (the muscle is hard).
- the muscle flexibility is increased by the test substance when the shear wave velocity of the muscle is reduced or the increase in the velocity is suppressed as compared with the case where the test substance is not ingested. It is evaluated that the improvement or the decrease in muscle flexibility was suppressed. Therefore, it can be said that the substance capable of reducing the shear wave velocity of the muscle or suppressing the increase of the velocity has an effect of improving the flexibility of the muscle.
- the flexibility of the muscle can be confirmed by the shear wave velocity of the muscle described above, and preferably by the shear wave velocity of the muscle in the state where the force is applied.
- the shear wave velocity of the thigh muscles in the fully flexed state increases with aging.
- ingestion of quercetin glycoside suppressed the increase in the shear wave velocity of the thigh muscle in the fully flexed state as compared with the case where it was not ingested. Therefore, quercetin and / or its glycosides have the effect of improving muscle flexibility.
- Quercetin and / or its glycosides can be used to improve muscle flexibility.
- quercetin and / or glycosides thereof can be used to suppress an increase in muscle shear wave velocity or reduce shear wave velocity.
- the composition of the present invention is one or more of reducing muscle hardness, suppressing an increase in muscle hardness, improving muscle suppleness and improving muscle elasticity.
- effects such as increase in muscle strength, increase in walking ability, improvement in balance ability, and improvement in agility can be obtained (for example, Ultrasound Med Biol. 2020 Nov; 46 (11): 2891). -2907.).
- the flexibility of the muscle is improved. As a result, the effect of improving the elasticity of the skin can be expected.
- the compositions of the invention are preferably used in combination with exercise.
- the compositions of the present invention can be suitably used to improve muscle flexibility in combination with exercise.
- the ingestion or administration of the composition of the present invention may be used in combination with exercise within a certain period of time, and the amount of exercise and the composition of the present invention may be ingested or administered.
- the timing and the like are not particularly limited. Ingestion or administration of quercetin and / or its glycosides in combination with exercise can further improve muscle flexibility.
- the effect of improving muscle flexibility can be further exerted.
- the type of exercise is not particularly limited, and examples thereof include daily exercise, aerobic exercise, strength training (for example, resistance exercise), and flexible exercise (stretching).
- One type of exercise may be performed, or two or more types may be combined.
- the above exercise is preferably a combination of strength training and flexible exercise, or strength training, more preferably a combination of resistance exercise and flexible exercise, or a resistance exercise, and even more preferably a resistance exercise.
- the flexible exercise may be performed either before or after the resistance exercise, or both before and after.
- the above-mentioned resistance exercise is an exercise performed by applying a constant load to the muscles.
- the method of applying the load is not particularly limited, and for example, a barbell, a machine, an appropriate heavy object, water, an expander, a rubber tube, or the like can be used.
- Resistance movements include, for example, leg extensions, leg presses, leg curls, chest presses, squats, bench presses, side raises, rowing, calf raises, sit-ups and the like.
- the resistance exercise can be performed by one type or a combination of two or more types. Examples of the aerobic exercise include jogging, walking, gymnastics, aerobics and the like. Quercetin and / or glycosides thereof can be used to promote or enhance the improvement of muscle flexibility by exercise.
- the compositions of the invention can be used to promote or enhance the improvement of muscle flexibility by exercise.
- the frequency and duration of the exercise can be, for example, one day or more per week, five minutes or more (preferably 30 minutes or more) once a day, and preferably two days or more per day. It is 5 minutes or more (preferably 30 minutes or more) once, more preferably 3 days or more per week, and 5 minutes or more (preferably 30 minutes or more) once per day.
- the frequency and / or exercise time of the exercise may be determined according to the subject, the type of exercise, and / or the combination of exercises. For example, in the case of aerobic exercise, it may be about 10 to 60 minutes once a day for 2 to 5 days a week.
- resistance exercise it may be about 1 to 3 days a week, about 10 to 60 minutes once a day, and in the case of flexible exercise, 1 to 7 days a week (for example, 1 to 3 days). It may be about 5 to 30 minutes once a day.
- the intensity of exercise combined with the composition of the present invention is preferably 2.0 METs (eg, walking / very slow / code 17151) or higher, preferably 2.3 METs (eg, stretch / loose / code 02101) or higher. More preferably, it is 3.5 METs (for example, resistance weight training / code 02054) or more. Further, the intensity of the resistance exercise is preferably 80% or less (preferably 30% or more) of the maximum lifting weight (1RM), and more preferably 60% or less (preferably 30% or more).
- the exercise load is preferably determined according to the subject. (For the intensity of exercise, refer to "Revised Mets Table of Physical Activity (National Institute of Health and Nutrition 2012)" and MedSci Sports Exerc. 2009 Mar; 41 (3): 687-708. "Code” is the code described in the "Revised Mets Table of Physical Activity (National Institute of Health and Nutrition 2012)".)
- skeletal muscle and cutaneous muscle are mentioned as the target muscle for improving the flexibility of the muscle, and skeletal muscle is preferable.
- the site for improving the flexibility of the muscle is not particularly limited, but the muscle of the thigh is preferable.
- the compositions of the invention are suitably used to improve the flexibility of the thigh muscles.
- compositions of the present invention can be applied to either therapeutic or non-therapeutic 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 foods and drinks, cosmetics, pharmaceuticals, quasi-drugs, feeds and the like.
- the composition of the present invention may be a food or drink, a cosmetic, a pharmaceutical product, a quasi-drug, a feed, etc., which is itself used for improving muscle flexibility, and is a material used by blending the composition. Alternatively, it may be a preparation or the like.
- the composition for improving muscle flexibility of the present invention can be provided in the form of an agent as an example, 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 for improving muscle flexibility of the present invention can also be said to be a muscle flexibility improving agent.
- the composition of the present invention may be either an oral composition or a parenteral composition.
- the oral composition include foods and drinks, oral medicines, quasi-drugs for oral use, and feeds, and foods and drinks or quasi-drugs for oral use are preferable.
- the parenteral composition include cosmetics, parenteral medicines, and parenteral quasi-drugs. It is preferably a cosmetic or a quasi-drug for parenteral use.
- composition of the present invention may contain any additive and any component in addition to quercetin and / or a glycoside thereof, 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, cosmetics, pharmaceuticals, quasi-drugs, feeds and the like can be used.
- the composition of the present invention is a food or drink, a cosmetic, 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, quercetin and / or its glycoside is mixed with ingredients that can be used in the food or drink (for example, food materials, food additives used as necessary, etc.). It can be made into various foods and drinks.
- the food and drink is not particularly limited, and examples thereof include general food and drink, health food, health drink, food with functional claims, food for specified health use, health supplement, food and drink for the sick, and the like.
- the above-mentioned health foods, foods with functional claims, foods for specified health use, dietary supplements, etc. are, 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 when used as a cosmetic, quercetin and / or a glycoside thereof can be mixed with a carrier, an additive or the like acceptable for the cosmetic.
- the product form of the cosmetic is not particularly limited.
- composition of the present invention is a drug or a quasi-drug, for example, quercetin and / or a glycoside thereof is mixed with a pharmacologically acceptable carrier, an additive added as necessary, and the like. It can be a drug or a quasi-drug in various dosage forms.
- a pharmacologically acceptable carrier for example, quercetin and / or a glycoside thereof
- Such carriers, additives and the like may be pharmacologically acceptable as long as they can be used in pharmaceutical products or quasi-drugs, for example, excipients, binders, disintegrants, lubricants, etc. 1 or 2 or more of 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, enteral, injection, etc.) administration.
- oral or parenteral transdermal, transmucosal, enteral, injection, etc.
- the composition of the present invention is a drug or a quasi-drug, it is preferably an oral (orally administered) 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.
- Dosage forms for parenteral administration include injections, infusions, external skin preparations (patches, creams, ointments, etc.) and the like.
- the drug may be a non-human animal drug.
- composition of the present invention When the composition of the present invention is used as a feed, quercetin and / or a glycoside thereof 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 quercetin and / or its glycoside contained in the composition of the present invention is not particularly limited and can be set according to its form and the like.
- the content of quercetin and / or its glycoside in the composition of the present invention is preferably 0.01% by weight or more, more preferably 0.1% by weight or more in the composition in terms of quercetin, for example. Further, 80% by weight or less is preferable, and 50% by weight or less is more preferable.
- the content of quercetin and / or its glycoside is preferably 0.01 to 80% by weight, more preferably 0.1 to 50% by weight in the composition of the present invention in terms of quercetin.
- the content of quercetin and / or its glycoside can be measured according to a known method, and for example, HPLC (high performance liquid chromatography) method can be used.
- compositions of the present invention are usually ingested or administered to a subject.
- the route of administration of the composition of the present invention is not particularly limited, and the composition can be ingested or administered by an appropriate method according to the form thereof.
- the composition of the present invention is preferably taken orally (orally administered).
- the dose (also referred to as ingestion amount) of the composition of the present invention is not particularly limited as long as it is an amount (also referred to as an effective amount) that can obtain an effect of improving muscle flexibility, and is an administration form and an administration method. It may be set appropriately according to the above.
- the dose of quercetin and / or its glycoside is defined as a quercetin equivalent value per 60 kg of body weight per day, preferably 0. It is 3 mg or more, more preferably 1.0 mg or more, still more preferably 10 mg or more, preferably 4000 mg or less, more preferably 2000 mg or less, still more preferably 1000 mg or less.
- the dose of quercetin and / or its glycoside is, in terms of quercetin equivalent, for a human (adult), per 60 kg of body weight per day, preferably 0.3 to 4000 mg, more preferably 1.0.
- compositions of the invention can be used to ingest or administer the above amounts of quercetin and / or glycosides thereof per day to a human body weight of 60 kg.
- the composition of the present invention is preferably continuously ingested or administered. It is expected that a high muscle flexibility improving effect can be obtained by continuously ingesting or administering quercetin and / or its glycoside. In one embodiment, it is preferable to continuously ingest or administer the composition of the present invention for preferably 1 week or longer, more preferably 4 weeks or longer, still more preferably 8 weeks or longer.
- composition of the present invention can be used for the prevention or improvement of a condition or disease that can be prevented or expected to be improved by improving the flexibility of muscles.
- a state or disease include a state or disease caused by a decrease in muscle flexibility, a state or disease in which muscle flexibility is reduced, and the like.
- myogenic diseases including sarcopenia and muscular dystrophy, neurological disorders including cerebral palsy, Parkinson's disease, stroke and the like (Ultrasound Med Biol. 2020 Nov; 46 (11) :. 2891-2907.).
- the composition of the present invention comprises a myogenic disorder including sarcopenia, muscular dystrophy, etc., a neurological disorder including cerebral palsy, Parkinson's disease, a state such as stroke, or a muscle abnormality due to a disease (eg, muscle hardening).
- a myogenic disorder including sarcopenia, muscular dystrophy, etc.
- a neurological disorder including cerebral palsy, Parkinson's disease, a state such as stroke, or a muscle abnormality due to a disease (eg, muscle hardening).
- a myogenic disorder including sarcopenia, muscular dystrophy, etc.
- a neurological disorder including cerebral palsy, Parkinson's disease, a state such as stroke, or a muscle abnormality due to a disease (eg, muscle hardening).
- prevention of a condition or disease includes preventing the onset of the condition or disease, delaying the onset, reducing the incidence, reducing the risk of developing the condition, and
- the subject to ingest or administer the composition of the present invention (which may also be the subject of administration) is not particularly limited. It is preferably a human or non-human mammal, more preferably a human.
- the administration target includes a subject who needs or desires improvement of muscle flexibility, a subject who needs or desires prevention or improvement of a condition or a disease caused by a decrease in muscle flexibility, and the like. Be done.
- the decrease in muscle flexibility may be a decrease in muscle flexibility due to aging, or may be a decrease in muscle flexibility due to aging in middle-aged and elderly people.
- the subject of administration in the present invention includes middle-aged and elderly people. Middle-aged and elderly people include the elderly. Among middle-aged and elderly people, elderly people are preferable as targets.
- the middle-aged person may be, for example, a human being 40 years or older.
- the elderly person may be, for example, a human aged 60 years or older or 65 years or older.
- the composition of the present invention is suitably used as a composition for improving muscle flexibility for middle-aged and elderly people.
- the subject of administration of the composition of the present invention may be a healthy person, for example, a healthy middle-aged person.
- the composition of the present invention can also be used for a healthy person, for example, for the purpose of prevention or prevention of a condition or disease that can be prevented or expected to be improved by improving muscle flexibility.
- the composition of the present invention may be labeled with a function exerted by improving muscle flexibility.
- the composition for improving muscle flexibility of the present invention includes, for example, “softening muscles”, “making muscles supple”, “improving muscle elasticity", “softening body”, etc.
- display of two or more functions may be attached.
- the composition of the present invention has one or more functions such as “skin elasticity”, “skin firmness”, “bouncy feeling”, “moist feeling”, and “pull-pull feeling”. May be attached.
- the display of the above function may describe that the above function is a function obtained by improving the flexibility of the muscle.
- 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 label may be affixed to the composition itself or to the container or packaging of the composition.
- the present invention also includes the following methods and uses.
- the methods and uses may be therapeutic or non-therapeutic methods or uses.
- Administration (ingestion) of quercetin and / or its glycosides can improve muscle flexibility.
- Quercetin and / or its glycosides can improve muscle suppleness and / or muscle elasticity by improving muscle flexibility.
- quercetin and / or its glycoside is one or more selected from the group consisting of a decrease in muscle hardness, suppression of increase in muscle hardness, improvement in muscle suppleness and improvement in muscle elasticity.
- Quercetin and / or its glycosides can be used, for example, for the prevention or amelioration of conditions or diseases that can be prevented or expected to improve by improving muscle flexibility.
- Quercetin and / or glycosides thereof are preferably used in combination with exercise to improve muscle flexibility.
- the muscles are the same as above, with the thigh muscles being preferred.
- Exercise, preferred embodiments thereof, etc. are the same as described above.
- quercetin and / or its glycoside may be administered (ingested) to the subject at least once a day, for example, once to several times a day (for example, 2 to 3 times).
- Quercetin and / or its glycosides are as described above.
- quercetin and / or a glycoside thereof may be used in an amount (effective amount) that can improve muscle flexibility.
- the preferable dose, administration target, administration method and the like of quercetin and / or its glycoside are the same as those of the above-mentioned composition for improving muscle flexibility of the present invention.
- the above use is preferably in humans or non-human mammals, more preferably in humans.
- Quercetin and / or its glycoside may be administered as it is, or may be administered as a composition containing the same.
- the composition of the present invention described above may be used.
- Quercetin and / or its glycosides are preferably orally administered (ingested).
- Quercetin and / or glycosides thereof can be used for the production of foods and drinks, cosmetics, pharmaceuticals, quasi-drugs, feeds and the like used to improve muscle flexibility.
- the invention also includes the use of quercetin and / or glycosides thereof to produce compositions for improving muscle flexibility.
- the composition for improving muscle flexibility and preferred embodiments thereof are the same as the above-mentioned composition of the present invention. All academic and patent documents described herein are incorporated herein by reference.
- Example 1 Example 2 and Comparative Example 1
- Hard capsules were manufactured using quercetin glycosides (San Emic P30, Saneigen FFI Co., Ltd.) and excipients (1 capsule size: major axis 19.54 mm x minor axis 6.94 mm), 6 Quercetin glycoside-containing foods containing 200 mg or 500 mg of quercetin glycosides per grain (referred to as 200 mg quercetin glycoside-containing foods and 500 mg quercetin glycoside-containing foods, respectively) were prepared.
- San-Emic P30 is a mixture of two or more quercetin glycosides in which 1 to 7 glucoses are added to quercetin.
- ⁇ Clinical trial> A placebo-controlled, single-blind, parallel-group comparative study was conducted in healthy middle-aged and elderly people (without exercise habits) aged 50 to 74 years who gave their consent to participate in the study.
- the subjects were a group ingesting a control food with exercise (Comparative Example 1: control food group), a group ingesting a food containing 200 mg kelcetin glycoside with exercise (Example 1: 200 mg kelcetin glycoside group), and a group. They were assigned to three groups: a group that ingested a food containing 500 mg kelcetin glycoside with exercise (Example 2: 500 mg kelcetin glycoside group). Exercise and test food intake interventions were performed in each group for 24 weeks.
- the shear wave velocity was measured and quantified using the shear wave elastography mode of Aixplorer (manufactured by Konica Minolta). It can be said that the smaller the shear wave velocity, the higher the flexibility of the muscle (softer), and the larger the shear wave velocity, the lower the flexibility of the muscle (hard).
- the vastus lateralis muscle of the right thigh in the fully flexed state was used as the analysis site. In this fully flexed state, the vastus lateralis muscle of the right thigh is in a state of exertion (a state in which the muscle is stretched).
- ⁇ Analysis result> The analysis subjects who completed the intervention were 16 subjects in the control food group, 16 subjects in the 200 mg quercetin glycoside group, and 16 subjects in the 500 mg quercetin glycoside group, respectively. In the 500 mg quercetin glycoside group, 1 person was missing data, so 15 people were analyzed for the shear wave velocity at 12 weeks. Table 1 shows the results of the average value of the shear wave velocity (m / s) (standard error in parentheses). In Table 1, * indicates that there is a significant difference compared to the control food group (* p ⁇ 0.05, Dunnett's test). The results shown in Table 1 are rounded to the first decimal place. The shear wave velocities before the intervention were not significantly different between the three groups.
- FIG. 1 shows a graph of the amount of change in shear wave velocity at 24 weeks of intervention compared to before the intervention of exercise and test food intake.
- the shear wave velocity of fully flexed muscles increases with age, i.e., muscle flexibility decreases. Only in the group that ingested the quercetin glycoside, a decrease in the shear wave velocity in the fully flexed state was observed, confirming the usefulness of ingesting quercetin and / or its glycoside for muscle flexibility.
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Abstract
Description
〔1〕ケルセチン及び/又はその配糖体を含有する筋肉の柔軟性改善用組成物。
〔2〕筋肉の硬さを低下させる、筋肉の硬さの増加を抑制する、筋肉のしなやかさを改善する及び筋肉の弾力性を改善する、のうちの1以上のために使用される上記〔1〕に記載の組成物。
〔3〕運動と組み合わせて使用される、上記〔1〕又は〔2〕に記載の組成物。
〔4〕筋肉が、大腿部の筋肉である上記〔1〕~〔3〕のいずれかに記載の組成物。
〔5〕飲食品、化粧料又は医薬部外品である〔1〕~〔4〕のいずれかに記載の組成物。
〔6〕筋肉の柔軟性を改善するための、ケルセチン及び/又はその配糖体の使用。
摂取されたケルセチン配糖体は、腸管内で糖が切断されてアグリコン(ケルセチン)になってから体内へ吸収される。
本発明に用いられるケルセチン及び/又はその配糖体には、本発明の効果を奏することになる限り、上記の植物等の天然物由来の抽出物を、濃縮、精製等の操作によってケルセチン及び/又はその配糖体の含量を高めたもの、例えば、ケルセチン及び/又はその配糖体を含有する抽出物の、濃縮物又は精製物を用いることができる。濃縮方法又は精製方法は、既知の方法を採用することができる。本発明においては、精製又は単離されたケルセチン及び/又はその配糖体を使用してもよい。ケルセチン及び/又はその配糖体は、化学合成品を使用することもできる。
筋肉の柔軟性の改善は、筋肉の硬さ(筋硬度)の改善ということもできる。本発明において、筋肉の柔軟性の改善は、筋肉の柔軟性の低下抑制、筋肉の柔軟性維持、筋肉の柔軟性の向上(柔軟性の増加)等を含む。筋肉の硬さ(筋硬度)の改善は、筋肉の硬さの増加抑制、筋肉の硬さの維持、筋肉の硬さの低下等を含む。
筋肉の柔軟性は、シアウェーブエラストグラフィ法(shear wave elastography)で測定される、筋肉のせん断波速度を指標として評価することができる。シアウェーブエラストグラフィ法は、超音波エラストグラフィーの一つであり、音響放射インパルスによって生体内で加振を行い、それによって生じたせん断波の伝搬速度分布を計測し、組織の硬さを評価する方法である(山川誠、バイオメカニズム学会誌,Vol.40, No. 2(2016),73-78、特に74頁の右欄10-12行)。上記せん断波速度が小さいほど、筋肉の柔軟性が高く(筋肉が柔らかく)、せん断波速度が大きいほど、筋肉の柔軟性が低い(筋肉が硬い)といえる。例えば、被験物質を摂取した場合に、当該被験物質を摂取しない場合と比較して、筋肉のせん断波速度が低下する又は当該速度の増加が抑制されると、当該被験物質によって筋肉の柔軟性が向上した又は筋肉の柔軟性の低下が抑制されたと評価される。従って上記筋肉のせん断波速度を低下させる又は当該速度の増加を抑制することができる物質は、筋肉の柔軟性改善作用を有するといえる。本発明において、筋肉の柔軟性は、上記の筋肉のせん断波速度により確認することができ、好ましくは、力を入れた状態における筋肉のせん断波速度により確認することができる。
筋肉の柔軟性を改善することによって、筋力の増加、歩行能力の増加、バランス能力の向上、俊敏性の向上等の効果が得られる(例えば、Ultrasound Med Biol. 2020 Nov;46(11):2891-2907.)。
また、筋肉の柔軟性を改善することによって、皮筋(例えば、表情筋等)の柔軟性が改善される。その結果、皮膚の弾力改善効果が期待できる。
運動の種類は特に限定されず、例えば日常的な運動、有酸素運動、筋力トレーニング(例えば、レジスタンス運動など)、柔軟運動(ストレッチ)等が挙げられる。運動は、1種を行ってもよく、2種以上を組み合わせて行ってもよい。一態様において、上記の運動は、好ましくは、筋力トレーニングと柔軟運動の組合せ、又は、筋力トレーニングであり、より好ましくはレジスタンス運動と柔軟運動の組合せ、又は、レジスタンス運動であり、さらに好ましくはレジスタンス運動と柔軟運動の組合せである。この場合、柔軟運動は、レジスタンス運動の前若しくは後のいずれか、又は前後の両方で実施されればよい。
上記レジスタンス運動とは、筋肉に一定の負荷をかけて行われる運動のことである。負荷をかける方法としては特に限定されないが、例えば、バーベル、マシン、適当な重量物、水、エキスパンダー、ゴムチューブ等を利用することができる。レジスタンス運動として、例えば、レッグエクステンション、レッグプレス、レッグカール、チェストプレス、スクワット、ベンチプレス、サイドレイズ、ローイング、カーフレイズ、シットアップ等が挙げられる。レジスタンス運動は、1種又は2種以上を組合わせて行うことができる。上記有酸素運動としては、例えば、ジョギング、ウォーキング、体操、エアロビックス等が挙げられる。
ケルセチン及び/又はその配糖体は、運動による筋肉の柔軟性改善を促進又は増強するために使用することができる。一態様において、本発明の組成物は、運動による筋肉の柔軟性改善を促進又は増強するために使用することができる。
本発明の組成物は、飲食品、化粧料、医薬品、医薬部外品、飼料等の形態とすることができる。本発明の組成物は、それ自体が筋肉の柔軟性改善のために用いられる飲食品、化粧料、医薬品、医薬部外品、飼料等であってもよく、これらに配合して使用される素材又は製剤等であってもよい。
本発明の筋肉の柔軟性改善用組成物は、一例として、剤の形態で提供することができるが、本形態に限定されるものではない。当該剤をそのまま組成物として、又は、当該剤を含む組成物として提供することもできる。一態様において、本発明の筋肉の柔軟性改善用組成物は、筋肉の柔軟性改善剤ということもできる。
本発明の組成物は、経口用組成物、非経口用組成物のいずれであってもよい。本発明の組成物を対象に経口で摂取させる又は投与することにより、又は、非経口投与することにより、対象において筋肉の柔軟性を改善することができる。経口用組成物としては、飲食品、経口用医薬品、経口用医薬部外品、飼料が挙げられ、好ましくは飲食品又は経口用医薬部外品である。非経口用組成物として、化粧料、非経口用医薬品、非経口用医薬部外品が挙げられる。好ましくは化粧料又は非経口用医薬部外品である。
ケルセチン及び/又はその配糖体の含有量は、公知の方法に従って測定することができ、例えば、HPLC(高速液体クロマトグラフィー)法などを用いることができる。
一態様において、投与対象として、筋肉の柔軟性の改善を必要とする又は希望する対象、筋肉の柔軟性の低下に起因する状態又は疾患の予防又は改善を必要とする又は希望する対象等が挙げられる。筋肉の柔軟性の低下は、加齢による筋肉の柔軟性の低下であってよく、中高年者における加齢による筋肉の柔軟性の低下であってよい。
一態様において、本発明における投与対象として、中高年者が挙げられる。中高年者は、高齢者を含む。中高年者の中でも、対象として高齢者が好ましい。本発明において、中高年者は、例えば、40歳以上のヒトであってよい。高齢者は、例えば、60歳以上又は65歳以上のヒトであってよい。一態様において、本発明の組成物は、中高年者用の筋肉の柔軟性改善用組成物として好適に使用される。
本発明の組成物の投与対象は、健常者であってよく、例えば健常な中高年者であってよい。本発明の組成物は、例えば、筋肉の柔軟性改善により予防又は改善が期待できる状態又は疾患の予防等を目的として、健常者に対して使用することもできる。
また、別の一態様においては、本発明の組成物には、「肌の弾力」、「肌のハリ」「弾む感じ」、「モチモチ感」、「プルプル感」等の1又は2以上の機能の表示が付されていてもよい。上記機能の表示には、上記機能が筋肉の柔軟性改善により得られる機能であることが記載されていてもよい。
一態様において、本発明の組成物は、上記の表示が付された飲食品であることが好ましい。また上記の表示は、上記の機能を得るために用いる旨の表示であってもよい。当該表示は、組成物自体に付されてもよいし、組成物の容器又は包装に付されていてもよい。
ケルセチン及び/又はその配糖体を投与する、筋肉の柔軟性を改善する方法。
筋肉の柔軟性を改善するための、ケルセチン及び/又はその配糖体の使用。
上記方法及び使用は、治療的な方法又は使用であってもよく、非治療的な方法又は使用であってもよい。ケルセチン及び/又はその配糖体を投与する(摂取させる)と、筋肉の柔軟性を改善することができる。ケルセチン及び/又はその配糖体は、筋肉の柔軟性を改善することによって、筋肉のしなやかさ及び/又は筋肉の弾力性を改善することができる。一態様において、ケルセチン及び/又はその配糖体は、筋肉の硬さの低下、筋肉の硬さの増加抑制、筋肉のしなやかさ改善及び筋肉の弾力性改善からなる群より選択される1以上のために使用することができる。ケルセチン及び/又はその配糖体は、例えば、筋肉の柔軟性を改善することにより予防又は改善が期待できる状態又は疾患の予防又は改善のために使用することができる。
なお、本明細書中に記載された学術文献及び特許文献の全ては、参照として本明細書に組み入れられる。
<試験食品の作製>
ケルセチン配糖体(サンエミックP30、三栄源エフ・エフ・アイ(株))及び賦形剤を用いてハードカプセルを製造し(1カプセルの大きさ:長径19.54mm×短径6.94mm)、6粒あたり200mg又は500mgのケルセチン配糖体を含有するケルセチン配糖体含有食品(それぞれ200mgケルセチン配糖体含有食品、500mgケルセチン配糖体含有食品という)を作製した。サンエミックP30は、ケルセチンに1~7個のグルコースが付加した2種以上のケルセチン配糖体の混合物である。臨床試験用の対照食品として、賦形剤のみを含有するハードカプセルを製造した。酸化等の劣化を防ぐため、ケルセチン配糖体含有食品と対照食品はそれぞれ6粒ずつアルミニウムパウチで個包装され、臨床試験に必要な数が用意された。
試験参加同意の説明を行い、同意を得られた50-74歳の健康な中高年者(運動習慣のない)を対象にプラセボ対照単盲検並行群間比較試験を実施した。被験者は運動ありで対照食品を摂取する群(比較例1:対照食品群)、運動ありで200mgケルセチン配糖体含有食品を摂取する群(実施例1:200mgケルセチン配糖体群)、及び、運動ありで500mgケルセチン配糖体含有食品を摂取する群(実施例2:500mgケルセチン配糖体群)の3群に割り付けられた。それぞれの群で運動及び試験食品摂取の介入を24週間実施した。
運動は、トレーナーの管理下で、下肢を中心とした4種類のレジスタンス運動(レッグエクステンション、レッグプレス、レッグカール、チェストプレスをそれぞれ最大挙上重量(1RM)の40%の負荷で14回を1セットとして、1日3セット)を週3日間実施した。いずれの運動も主運動の前後にウォーミングアップとクールダウンの柔軟運動(ストレッチ)を実施した。また4週間に1回、1RMの測定を行い、被験者ごとに負荷重量を調整した。試験食品(対照食品又はケルセチン配糖体含有食品)は、1日6カプセルを、充分な量の水又はぬるま湯と共に摂取させた。
筋肉の柔軟性の評価には、Aixplorer(コニカミノルタ社製)のshear wave elastographyモードを用いて、せん断波速度の測定及び定量を行った。せん断波速度が小さいほど筋肉の柔軟性が高く(柔らかく)、せん断波速度が大きいほど、筋肉の柔軟性が低い(硬い)といえる。完全屈曲状態(正座(屈膝座法)の状態)における、右大腿部の外側広筋を解析部位とした。この完全屈曲状態では、右大腿部の外側広筋の状態は、力を入れた状態(筋肉が伸ばされている状態)である。
介入が完了した解析対象者はそれぞれ対照食品群:16名、200mgケルセチン配糖体群:16名、500mgケルセチン配糖体群:16名であった。500mgケルセチン配糖体群は、1名データ欠損のため、12週目のせん断波速度の解析対象者は15名であった。せん断波速度(m/s)の平均値(括弧内は標準誤差)の結果を表1に示す。表1中、*は、対照食品群と比較して有意差があることを示す(*p<0.05、Dunnett’s test)。表1に示す結果は、小数第三位を四捨五入した値である。
介入前のせん断波速度は、3群間に有意差はなかった。介入前後の変化に関しては、対照食品群との群間比較において、介入24週目のせん断波速度変化量は、200mgケルセチン配糖体群及び500mgケルセチン配糖体群において有意に低値を示した。図1に、運動及び試験食品摂取の介入前と比較した、介入24週目のせん断波速度の変化量のグラフを示す。
Claims (6)
- ケルセチン及び/又はその配糖体を含有する筋肉の柔軟性改善用組成物。
- 筋肉の硬さを低下させる、筋肉の硬さの増加を抑制する、筋肉のしなやかさを改善する及び筋肉の弾力性を改善する、のうちの1以上のために使用される請求項1に記載の組成物。
- 運動と組み合わせて使用される、請求項1又は2に記載の組成物。
- 筋肉が、大腿部の筋肉である請求項1~3のいずれか一項に記載の組成物。
- 飲食品、化粧料又は医薬部外品である請求項1~4のいずれか一項に記載の組成物。
- 筋肉の柔軟性を改善するための、ケルセチン及び/又はその配糖体の使用。
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- 2021-12-07 JP JP2022569885A patent/JPWO2022131063A1/ja active Pending
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JPWO2022131063A1 (ja) | 2022-06-23 |
AU2021398645A1 (en) | 2023-06-29 |
CN116648145A (zh) | 2023-08-25 |
TW202236976A (zh) | 2022-10-01 |
KR20230121866A (ko) | 2023-08-21 |
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