JP7825569B2 - Composition for improving muscle flexibility - Google Patents

Description

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 to improve muscle flexibility.

Japan is an ultra-aging society, and while medical advances are making headway and the proportion of elderly people is increasing, extending healthy life expectancy and improving quality of life (QOL) are key challenges. One factor contributing to this shortened healthy life expectancy is a state in which people are at high risk of becoming dependent on care due to musculoskeletal disorders, known as locomotive syndrome. Age-related musculoskeletal disorders can cause pain and decline in motor function, including muscle weakness, endurance, and reduced speed, which can all combine to create a vicious cycle. As a result, people are unable to perform activities of daily living and are believed to become dependent on care, making prevention of this condition crucial.

Motor function is not simply proportional to muscle mass; it is known that muscle flexibility and other factors also play a role in motor function. Therefore, it is thought that not only increasing muscle mass but also improving muscle flexibility is important for preventing or improving the decline in motor function.

Quercetin is a type of flavonoid that is found in many plants, such as onions, either as is or as a glycoside. The physiological activities of quercetin or its glycosides have been reported to include PPARγ activation (see, for example, Patent Document 1).

Japanese Patent Application Laid-Open No. 2017-8117

For example, when muscle flexibility decreases, the muscles become less flexible. Ingredients that can improve muscle flexibility are effective, for example, in preventing or improving the decline in motor function.

The present invention aims to provide a composition for improving muscle flexibility.

The inventors have discovered that quercetin, a type of flavonol, and/or its glycosides are effective in improving muscle flexibility.

That is, the present invention includes, but is not limited to, the following compositions for improving muscle flexibility.
[1] A composition for improving muscle flexibility containing quercetin and/or its glycoside.
[2] The composition described in [1] above, which is used for one or more of the following purposes: reducing muscle stiffness, inhibiting an increase in muscle stiffness, improving muscle flexibility, and improving muscle elasticity.
[3] The composition described in [1] or [2] above, which is used in combination with exercise.
[4] The composition according to any one of [1] to [3] above, wherein the muscle is a thigh muscle.
[5] The composition according to any one of [1] to [4], which is a food or drink, a cosmetic, or a quasi-drug.
[6] Use of quercetin and/or its glycosides to improve muscle flexibility.

According to the present invention, a composition for improving muscle flexibility can be provided.

FIG. 1 is a graph showing the change in muscle shear wave velocity after 24 weeks of exercise and test food intake intervention compared to before the intervention.

The composition for improving muscle flexibility of the present invention contains quercetin and/or its glycoside. Hereinafter, the composition for improving muscle flexibility of the present invention will also be simply referred to as the composition of the present invention. The composition of the present invention typically contains quercetin and/or its glycoside as an active ingredient.

In this specification, "quercetin" refers to quercetin, a compound that belongs to the flavonol class, a type of polyphenol. In the present invention, "quercetin glycoside" refers to a glycoside of the above-mentioned quercetin, and specifically refers to a series of compounds in which one or more sugars are glycosidically bonded to the hydroxyl group at the 3-position of quercetin. Quercetin glycosides are compounds represented by the following general formula: In the following general formula, (X)n represents a sugar chain. X represents a sugar (monosaccharide), and n is an integer of 1 or greater. Quercetin glycosides may be one type of compound, or two or more types of compounds.

The sugars constituting the sugar chain represented by X that is glycosidically bonded to quercetin include, for example, glucose, rhamnose, galactose, glucuronic acid, etc., preferably glucose and rhamnose. Furthermore, n is not particularly limited as long as it is 1 or greater, but is preferably 1 to 16, more preferably 1 to 8. When n is 2 or greater, the X moiety may consist of a single type of sugar or multiple types of sugars. In other words, when n is 2 or greater, (X)n may be a sugar chain consisting of a single type of sugar or multiple types of sugars. The quercetin glycoside of the present invention also includes those obtained by transglycosylating existing quercetin glycosides by treatment with enzymes or the like. Specific examples of quercetin glycosides of the present invention include rutin, enzyme-treated rutin (enzyme-treated rutin), quercitrin, isoquercitrin, etc. In the present invention, enzyme-treated rutin is particularly preferred as the quercetin glycoside. Preferred examples of enzyme-treated rutin include isoquercitrin, which is obtained by enzymatically treating rutin to remove the rhamnose sugar chain portion, isoquercitrin obtained by treating isoquercitrin with a glycosyltransferase to which a sugar chain consisting of 1 to 7 glucose units is bound, and mixtures thereof as the main component. In one aspect, preferred quercetin glycosides include compounds in which 1 to 8 glucose units are glycosidically bound to the hydroxyl group at the 3-position of quercetin (e.g., isoquercitrin, glycosides in which 1 to 7 glucose units are bound to isoquercitrin).
When ingested, quercetin glycoside is broken down into its sugar in the intestinal tract, becoming the aglycone (quercetin), which is then absorbed into the body.

In the present invention, there are no particular limitations on the origin or production method for obtaining quercetin and/or its glycosides. For example, plants that are known to contain large amounts of quercetin and/or its glycosides include buckwheat, Sophora japonica, capers, apples, tea, onions, grapes, broccoli, mulukhiyah, raspberries, cowberries, cranberries, opuntia, leafy vegetables, and citrus fruits, and quercetin and/or its glycosides can be obtained from these plants.
The quercetin and/or glycosides thereof used in the present invention can be any extract derived from a natural product such as the above-mentioned plants, which has been concentrated, purified, or otherwise processed to increase the quercetin and/or glycoside content, as long as the effects of the present invention are achieved. For example, a concentrate or purified product of an extract containing quercetin and/or glycosides thereof can be used. Known methods can be used for concentration or purification. Purified or isolated quercetin and/or glycosides thereof may also be used in the present invention. Chemically synthesized quercetin and/or glycosides may also be used.

Quercetin and/or its glycosides are compounds found in natural products and foods and beverages, and are commonly consumed as food. Therefore, from a safety standpoint, it is believed that quercetin and/or its glycosides pose few problems, even when ingested daily. According to the present invention, a composition for improving muscle flexibility can be provided that contains a highly safe substance as an active ingredient.

In the present invention, muscle flexibility refers to the ease with which a muscle can stretch and contract. It has been reported that muscle flexibility decreases with age (e.g., Muscle Nerve. 2017 Mar 55(3) 305-315.).
Improvement of muscle flexibility can also be referred to as improvement of muscle hardness (muscle hardness). In the present invention, improvement of muscle flexibility includes suppressing a decrease in muscle flexibility, maintaining muscle flexibility, improving muscle flexibility (increasing flexibility), etc. Improvement of muscle hardness (muscle hardness) includes suppressing an increase in muscle hardness, maintaining muscle hardness, decreasing muscle hardness, etc.
Muscle flexibility can be evaluated using the shear wave velocity of the muscle as an index, as measured by shear wave elastography. Shear wave elastography is a type of ultrasound elastography that involves applying vibrations in vivo using an acoustic radiation impulse, measuring the propagation velocity distribution of the resulting shear waves, and evaluating tissue stiffness (Yamakawa Makoto, Journal of the Society of Biomechanisms, Vol. 40, No. 2 (2016), 73-78, particularly lines 10-12 in the right column on page 74). The lower the shear wave velocity, the higher the muscle flexibility (softer the muscle), and the higher the shear wave velocity, the lower the muscle flexibility (harder the muscle). For example, if the shear wave velocity of the muscle decreases or the increase in the velocity is suppressed when a test substance is ingested compared to when the test substance is not ingested, it is evaluated that the test substance has improved muscle flexibility or suppressed the decrease in muscle flexibility. Therefore, a substance that can reduce the shear wave velocity of the muscle or suppress an increase in the velocity can be said to have the effect of improving muscle flexibility. In the present invention, muscle flexibility can be confirmed by the shear wave velocity of the muscle, preferably by the shear wave velocity of the muscle when strained.

For example, the shear wave velocity of thigh muscles in a fully flexed position (seiza (knee-sitting) position) increases with age. As shown in the examples described below, when quercetin glycoside is taken, the increase in shear wave velocity of thigh muscles in a fully flexed position is suppressed compared to when quercetin glycoside is not taken. Therefore, quercetin and/or its glycoside has the effect of improving muscle flexibility. Quercetin and/or its glycoside can be used to improve muscle flexibility. In one aspect, quercetin and/or its glycoside can be used to suppress the increase in shear wave velocity of muscles or to reduce shear wave velocity.

Improving muscle flexibility can improve muscle flexibility, elasticity, etc. In one aspect, the composition of the present invention can be used for one or more of reducing muscle stiffness, inhibiting an increase in muscle stiffness, improving muscle flexibility, and improving muscle elasticity.
Improving muscle flexibility can result in increased muscle strength, walking ability, balance ability, and agility (eg, Ultrasound Med Biol. 2020 Nov; 46 (11): 2891-2907).
Furthermore, improving muscle flexibility improves the flexibility of cutaneous muscles (for example, facial muscles), which can be expected to improve skin elasticity.

In one embodiment, the composition of the present invention is preferably used in combination with exercise. The composition of the present invention can be suitably used in combination with exercise to improve muscle flexibility. When the composition of the present invention is used in combination with exercise, the ingestion or administration of the composition of the present invention and exercise may be performed in combination within a certain period of time, and the amount of exercise, the timing of ingestion or administration of the composition of the present invention, etc. are not particularly limited. Ingestion or administration of quercetin and/or its glycoside in combination with exercise can further enhance the muscle flexibility improving effect. When used in combination with exercise, the composition of the present invention can further exert the muscle flexibility improving effect.
The type of exercise is not particularly limited, and examples include daily exercise, aerobic exercise, strength training (e.g., resistance exercise), flexibility exercise (stretching), etc. One type of exercise may be performed, or two or more types may be combined. In one embodiment, the exercise is preferably a combination of strength training and flexibility exercise, or strength training, more preferably a combination of resistance exercise and flexibility exercise, or resistance exercise, and even more preferably a combination of resistance exercise and flexibility exercise. In this case, flexibility exercise may be performed either before or after resistance exercise, or both before and after.
The resistance exercise is an exercise performed by applying a certain load to the muscles. The method of applying the load is not particularly limited, and examples thereof include a barbell, a machine, a suitable weight, water, an expander, a rubber tube, etc. Examples of resistance exercise include leg extensions, leg presses, leg curls, chest presses, squats, bench presses, side raises, rowing, calf raises, and sit-ups. Resistance exercises can be performed alone or in combination of two or more types. Examples of aerobic exercise include jogging, walking, gymnastics, aerobics, etc.
Quercetin and/or its glycosides can be used to promote or enhance exercise-induced improvement in muscle flexibility. In one aspect, the composition of the present invention can be used to promote or enhance exercise-induced improvement in muscle flexibility.

The frequency and duration of the exercise can be, for example, at least one day per week, once per day for at least 5 minutes (preferably at least 30 minutes), preferably at least two days per week, once per day for at least 5 minutes (preferably at least 30 minutes), and more preferably at least three days per week, once per day for at least 5 minutes (preferably at least 30 minutes). The frequency and/or duration of the exercise can also be determined depending on the subject, the type of exercise, and/or the combination of exercises. For example, aerobic exercise can be performed 2-5 days per week, once per day for approximately 10-60 minutes. Resistance exercise can be performed 1-3 days per week, once per day for approximately 10-60 minutes, and flexibility exercise can be performed 1-7 days per week (e.g., 1-3 days), once per day for approximately 5-30 minutes.

The intensity of exercise to be combined with the composition of the present invention is preferably 2.0 METs or more (e.g., walking/very slowly/code 17151), more preferably 2.3 METs or more (e.g., stretching/relaxed/code 02101), and even more preferably 3.5 METs or more (e.g., resistance weight training/code 02054). Furthermore, the intensity of resistance exercise is preferably 80% or less (preferably 30% or more) of the maximum lifting weight (1 RM), more preferably 60% or less (preferably 30% or more). It is preferable that the exercise load be determined according to the subject. (For information on exercise intensity, see the "Revised Physical Activity METs Table (National Institute of Health and Nutrition 2012)" and MedSci Sports Exerc. 2009 Mar; 41(3): 687-708. The "codes" above are those listed in the "Revised Physical Activity METs Table (National Institute of Health and Nutrition 2012).")

In the present invention, the muscles targeted for improvement in muscle flexibility include skeletal muscle and cutaneous muscle, and preferably skeletal muscle. In the present invention, the site targeted for improvement in muscle flexibility is not particularly limited, but thigh muscles are preferred. In one aspect, the composition of the present invention is suitably used to improve thigh muscle flexibility.

The compositions of the present invention may be applied in either therapeutic or non-therapeutic applications, the latter being a concept that does not include medical procedures, i.e., human surgery, treatment, or diagnosis.
The composition of the present invention can be in the form of a food or drink, a cosmetic, a pharmaceutical, a quasi-drug, a feed, etc. The composition of the present invention may be a food or drink, a cosmetic, a pharmaceutical, a quasi-drug, a feed, etc. that is used by itself for improving muscle flexibility, or may be a material or preparation that is blended with these.
The muscle flexibility improving composition of the present invention can be provided in the form of an agent, for example, but is not limited to this form. The agent can be provided as a composition as is, or as a composition containing the agent. In one aspect, the muscle flexibility improving composition of the present invention can also be referred to as a muscle flexibility improving agent.
The composition of the present invention may be either an oral composition or a parenteral composition. By orally ingesting or administering the composition of the present invention to a subject, or by parenterally administering it, muscle flexibility in the subject can be improved. Oral compositions include foods and beverages, oral pharmaceuticals, oral quasi-drugs, and feeds, and are preferably foods and beverages or oral quasi-drugs. Parenteral compositions include cosmetics, parenteral pharmaceuticals, and parenteral quasi-drugs. Cosmetics or parenteral quasi-drugs are preferred.

The composition of the present invention may contain any additives and ingredients in addition to quercetin and/or its glycosides, as long as the effects of the present invention are not impaired. These additives and ingredients can be selected depending on the form of the composition, and those that can generally be used in foods and beverages, cosmetics, pharmaceuticals, quasi-drugs, feed, etc. can be used. When the composition of the present invention is used as a food and beverage, cosmetic, pharmaceutical, quasi-drug, feed, etc., there are no particular limitations on the manufacturing method, and it can be manufactured by a general method.

For example, when the composition of the present invention is made into a food or beverage, various foods and beverages can be prepared by blending quercetin and/or its glycosides with ingredients that can be used in foods and beverages (e.g., food ingredients, food additives used as needed, etc.). The foods and beverages are not particularly limited, and examples include general foods and beverages, health foods, health drinks, functional foods, foods for specified health uses, health supplements, and foods and beverages for patients. The health foods, functional foods, foods for specified health uses, health supplements, etc. can be used in various formulations, such as fine granules, tablets, granules, powders, capsules, chewable tablets, dry syrups, syrups, liquids, beverages, and liquid diets.

When the composition of the present invention is used as a cosmetic, quercetin and/or its glycosides can be blended with carriers, additives, etc. that are acceptable for cosmetics. There are no particular limitations on the product form of the cosmetic.

When the composition of the present invention is used as a pharmaceutical or quasi-drug, it can be formulated into various dosage forms, for example, by blending quercetin and/or its glycoside with a pharmacologically acceptable carrier and, if necessary, additives. Such carriers, additives, etc. may be any pharmacologically acceptable agent that can be used in pharmaceuticals or quasi-drugs, and may include, for example, one or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants, etc. Pharmaceuticals or quasi-drugs can be administered (ingested) orally or parenterally (transdermally, transmucosally, enterally, by injection, etc.). When the composition of the present invention is used as a pharmaceutical or quasi-drug, it is preferably an oral (oral administration) pharmaceutical or quasi-drug. Dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewable tablets, etc. Dosage forms for parenteral administration include injections, infusions, topical skin preparations (patches, creams, ointments, etc.), etc. The pharmaceutical product may be a pharmaceutical product for non-human animals.

When the composition of the present invention is used as feed, quercetin and/or its glycosides can be blended into the feed. Feed also includes feed additives. Examples of feed include livestock feed for cows, pigs, chickens, sheep, horses, etc.; small animal feed for rabbits, rats, mice, etc.; and pet food for dogs, cats, small birds, etc.

The content of quercetin and/or its glycosides in the composition of the present invention is not particularly limited and can be set depending on the form, etc. The content of quercetin and/or its glycosides in the composition of the present invention is, for example, preferably 0.01 wt % or more, more preferably 0.1 wt % or more, and preferably 80 wt % or less, more preferably 50 wt % or less, in terms of quercetin. In one aspect, the content of quercetin and/or its glycosides in the composition of the present invention is preferably 0.01 to 80 wt %, more preferably 0.1 to 50 wt %, in terms of quercetin.
The content of quercetin and/or its glycosides can be measured by known methods, such as HPLC (high performance liquid chromatography).

The composition of the present invention is typically ingested or administered to a subject. The route of administration of the composition of the present invention is not particularly limited, and it can be ingested or administered by an appropriate method depending on its form. In one aspect, the composition of the present invention is preferably ingested orally (administered orally). The dosage (which can also be referred to as intake amount) of the composition of the present invention is not particularly limited, and may be an amount that provides the effect of improving muscle flexibility (also referred to as effective amount), and may be set appropriately depending on the dosage form, administration method, etc.

In one aspect, when the composition of the present invention is ingested or administered to a human (adult), the dosage of quercetin and/or its glycosides is preferably 0.3 mg or more, more preferably 1.0 mg or more, even more preferably 10 mg or more, and preferably 4000 mg or less, more preferably 2000 mg or less, and even more preferably 1000 mg or less, in quercetin equivalent values per 60 kg of body weight per day. In one aspect, the dosage of quercetin and/or its glycosides is preferably 0.3 to 4000 mg, more preferably 1.0 to 2000 mg, even more preferably 1.0 to 1000 mg, and particularly preferably 10 to 1000 mg, in quercetin equivalent values per 60 kg of body weight per day for a human (adult). It is preferable to ingest or administer the above amount once or more times a day, for example, once to several times a day (e.g., 2 to 3 times a day). In one aspect, it is preferable to orally ingest or administer the above amount of quercetin and/or its glycosides to a human. In one embodiment of the present invention, the composition of the present invention can be used to cause or administer the above-mentioned amount of quercetin and/or its glycosides per 60 kg body weight per day to a human.

It is preferable that the composition of the present invention be ingested or administered continuously. It is expected that continuous ingestion or administration of quercetin and/or its glycosides will have a significant effect on improving muscle flexibility. In one aspect, it is preferable that the composition of the present invention be ingested or administered continuously, preferably for one week or more, more preferably four weeks or more, and even more preferably eight weeks or more.

The composition of the present invention can be used to prevent or improve conditions or diseases that can be expected to be prevented or improved by improving muscle flexibility. Such conditions or diseases include conditions or diseases caused by decreased muscle flexibility and conditions or diseases in which muscle flexibility is decreased. Examples of such conditions or diseases include myopathic diseases including sarcopenia and muscular dystrophy, neurological disorders including cerebral palsy, Parkinson's disease, and stroke (Ultrasound Med Biol. 2020 Nov; 46(11):2891-2907.). In one aspect, the composition of the present invention can be used to prevent or improve muscle abnormalities (e.g., muscle stiffness) caused by conditions or diseases such as myopathic diseases including sarcopenia and muscular dystrophy, neurological disorders including cerebral palsy, Parkinson's disease, and stroke. As used herein, prevention of a condition or disease includes preventing the onset of a condition or disease, delaying the onset, reducing the incidence, and reducing the risk of onset. Amelioration of a condition or disease includes causing a subject to recover from the condition or disease, alleviating the symptoms of the condition or disease, reversing the symptoms of the condition or disease, slowing or preventing the progression of the condition or disease, and the like.

The subject to which the composition of the present invention is ingested or administered (also referred to as the administration subject) is not particularly limited, and is preferably a human or a non-human mammal, more preferably a human.
In one aspect, subjects for administration include subjects who need or desire improvement in muscle flexibility, subjects who need or desire prevention or improvement of conditions or diseases caused by decreased muscle flexibility, etc. The decreased muscle flexibility may be an age-related decrease in muscle flexibility, or an age-related decrease in muscle flexibility in middle-aged or elderly people.
In one aspect, the subject of administration in the present invention includes middle-aged and elderly people. Middle-aged and elderly people include elderly people. Among middle-aged and elderly people, elderly people are preferred as the subject. In the present invention, middle-aged and elderly people may be, for example, people aged 40 or older. Elderly people may be, for example, people aged 60 or older or 65 or older. In one aspect, the composition of the present invention is suitably used as a composition for improving muscle flexibility for middle-aged and elderly people.
The subject to which the composition of the present invention is administered may be a healthy individual, for example, a healthy middle-aged or elderly individual. The composition of the present invention can also be used in healthy individuals for the purpose of preventing or ameliorating conditions or diseases that can be expected to be prevented or ameliorated by improving muscle flexibility.

The composition of the present invention may be labeled with a function to be exerted by improving muscle flexibility. The composition for improving muscle flexibility of the present invention may be labeled with one or more functions, such as "softening muscles,""making muscles supple,""improving muscle elasticity," or "making the body flexible."
In another embodiment, the composition of the present invention may be labeled with one or more functions such as "skin elasticity,""skinfirmness,""bouncyfeeling,""soft and chewy feeling,""soft and supple feeling," etc. The labeling of the functions may state that the functions are obtained by improving muscle flexibility.
In one embodiment, the composition of the present invention is preferably a food or drink labeled with the above-mentioned label. The above-mentioned label may also be a label indicating that the composition is used to obtain the above-mentioned function. The label may be attached to the composition itself, or to a container or packaging of the composition.

The present invention also encompasses the following methods and uses.
A method for improving muscle flexibility by administering quercetin and/or its glycosides.
Use of quercetin and/or its glycosides for improving muscle flexibility.
The above-mentioned methods and uses may be therapeutic or non-therapeutic. Administration (ingestion) of quercetin and/or its glycosides can improve muscle flexibility. By improving muscle flexibility, quercetin and/or its glycosides can improve muscle flexibility and/or muscle elasticity. In one aspect, quercetin and/or its glycosides can be used for one or more purposes selected from the group consisting of reducing muscle stiffness, inhibiting an increase in muscle stiffness, improving muscle flexibility, and improving muscle elasticity. Quercetin and/or its glycosides can be used, for example, to prevent or improve conditions or diseases that can be prevented or improved by improving muscle flexibility.

Quercetin and/or its glycosides are preferably used in combination with exercise to improve muscle flexibility. In the present invention, quercetin and/or its glycosides are preferably ingested or administered in combination with exercise. The muscles are the same as above, and thigh muscles are preferred. Exercise, its preferred aspects, etc. are the same as above.

In the above-mentioned methods and uses, it is preferable to administer (ingest) quercetin and/or its glycosides to the subject at least once a day, for example, once to several times a day (e.g., two to three times a day). The quercetin and/or its glycosides are as described above.

In the above-mentioned methods and uses, quercetin and/or its glycosides may be used in an amount (effective amount) that achieves the effect of improving muscle flexibility. The preferred dosage, administration target, administration method, etc. of quercetin and/or its glycosides are the same as those of the muscle flexibility improving composition of the present invention described above. The above-mentioned use is preferably in humans or non-human mammals, more preferably in humans. Quercetin and/or its glycosides may be administered directly or as a composition containing them. For example, the composition of the present invention described above may be used. Quercetin and/or its glycosides are preferably administered orally (ingested).

Quercetin and/or its glycosides can be used to produce foods and beverages, cosmetics, pharmaceuticals, quasi-drugs, feed, etc. that are used to improve muscle flexibility. In one aspect, the present invention also encompasses the use of quercetin and/or its glycosides to produce a composition for improving muscle flexibility. The composition for improving muscle flexibility and its preferred aspects are the same as those of the composition of the present invention described above.
All scientific and patent literature cited herein is hereby incorporated by reference.

The present invention will now be described in more detail with reference to examples, which are not intended to limit the scope of the present invention.

(Example 1, Example 2 and Comparative Example 1)
<Preparation of test foods>
Quercetin glycoside (Sanemic P30, San-Ei Gen F.F.I. Co., Ltd.) and excipients were used to prepare hard capsules (capsule size: major axis 19.54 mm x minor axis 6.94 mm), and quercetin glycoside-containing foods containing 200 mg or 500 mg of quercetin glycoside per six capsules (referred to as 200 mg quercetin glycoside-containing foods and 500 mg quercetin glycoside-containing foods, respectively). San-Emic P30 is a mixture of two or more quercetin glycosides, each consisting of one to seven glucose units attached to quercetin. Hard capsules containing only excipients were prepared as control foods for the clinical trials. To prevent deterioration such as oxidation, the quercetin glycoside-containing foods and control foods were individually packaged in aluminum pouches in groups of six, and the number required for the clinical trials was prepared.

<Clinical Trials>
A placebo-controlled, single-blind, parallel-group comparative study was conducted on healthy middle-aged and elderly people aged 50-74 years (without regular exercise) who provided informed consent for participation in the study. The subjects were assigned to three groups: a group that exercised and consumed a control food (Comparative Example 1: control food group), a group that exercised and consumed a food containing 200 mg of quercetin glycoside (Example 1: 200 mg quercetin glycoside group), and a group that exercised and consumed a food containing 500 mg of quercetin glycoside (Example 2: 500 mg quercetin glycoside group). Each group underwent a 24-week exercise and test food intervention.
Under the supervision of a trainer, subjects performed four types of resistance exercises focusing on the lower limbs (leg extension, leg press, leg curl, and chest press, each performed with a load of 40% of the maximum lifting weight (1RM), with 14 repetitions per set, three sets per day) three days per week. For each exercise, warm-up and cool-down flexibility exercises (stretching) were performed before and after the main exercise. In addition, 1RM was measured once every four weeks, and the load weight was adjusted for each subject. Subjects were instructed to take six capsules of the test food (control food or quercetin glycoside-containing food) daily with a sufficient amount of water or lukewarm water.
To evaluate muscle flexibility, shear wave velocity was measured and quantified using the shear wave elastography mode of an Aixplore (Konica Minolta). The lower the shear wave velocity, the higher the muscle flexibility (softer), and the higher the shear wave velocity, the lower the muscle flexibility (harder). The vastus lateralis of the right thigh in a fully flexed position (sitting upright (knee-bent) position) was used as the analysis site. In this fully flexed position, the vastus lateralis of the right thigh is in a tense state (stretched).

<Analysis results>
The analysis subjects who completed the intervention were 16 in the control food group, 16 in the 200 mg quercetin glycoside group, and 16 in the 500 mg quercetin glycoside group. Due to missing data for one subject in the 500 mg quercetin glycoside group, 15 subjects were analyzed for shear wave velocity at 12 weeks. The mean shear wave velocity (m/s) (standard error in parentheses) is shown in Table 1. In Table 1, * indicates a significant difference compared to the control food group (*p<0.05, Dunnett's test). The results shown in Table 1 are rounded to two decimal places.
There was no significant difference in shear wave velocity before the intervention among the three groups. Regarding the changes before and after the intervention, the change in shear wave velocity at 24 weeks after the intervention was significantly lower in the 200 mg quercetin glycoside group and the 500 mg quercetin glycoside group when compared with the control food group. Figure 1 shows a graph of the change in shear wave velocity at 24 weeks after the intervention, compared with the values before the exercise and test food intake intervention.

The shear wave velocity of muscles in a fully flexed state increases with age, i.e., muscle flexibility decreases. A decrease in shear wave velocity in a fully flexed state was observed only in the group that ingested quercetin glycoside, confirming the usefulness of quercetin and/or its glycoside intake for improving muscle flexibility.

Claims (4)

A composition for improving thigh muscle flexibility, comprising quercetin and/or its glycoside,
The quercetin glycoside has the following general formula:
(In the above general formula, (X)n represents a sugar chain. X represents at least one monosaccharide selected from the group consisting of glucose, rhamnose, galactose, and glucuronic acid, and n is an integer from 1 to 16. When n is 2 or more, (X)n may be a sugar chain consisting of one type of sugar, or may be a sugar chain consisting of multiple types of sugars.)
is a compound represented by
The composition , wherein the thigh muscle is a human thigh muscle . The composition of claim 1 is used for one or more of the following: reducing muscle stiffness, inhibiting an increase in muscle stiffness, improving muscle flexibility, and improving muscle elasticity. The composition described in claim 1 or 2, used in combination with exercise. The composition according to any one of claims 1 to 3 , which is a food or drink, a cosmetic, or a quasi-drug.