WO2019208627A1 - Composition destinée à la prévention d'une diminution de la masse musculaire, à la prévention d'une diminution de la puissance musculaire, à l'augmentation de la masse musculaire ou à l'amélioration de la puissance musculaire - Google Patents

Composition destinée à la prévention d'une diminution de la masse musculaire, à la prévention d'une diminution de la puissance musculaire, à l'augmentation de la masse musculaire ou à l'amélioration de la puissance musculaire Download PDF

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WO2019208627A1
WO2019208627A1 PCT/JP2019/017413 JP2019017413W WO2019208627A1 WO 2019208627 A1 WO2019208627 A1 WO 2019208627A1 JP 2019017413 W JP2019017413 W JP 2019017413W WO 2019208627 A1 WO2019208627 A1 WO 2019208627A1
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muscle
muscle mass
soyasaponins
decrease
strength
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PCT/JP2019/017413
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English (en)
Japanese (ja)
Inventor
笠島　直樹
大将 吉田
寿栄 鈴木
優 小南
契吾 越前
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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 CN201980028698.9A priority Critical patent/CN112055544A/zh
Priority to JP2020515521A priority patent/JP7227962B2/ja
Publication of WO2019208627A1 publication Critical patent/WO2019208627A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/06—Anabolic agents

Definitions

  • the present invention relates to a composition for suppressing muscle mass decrease, for suppressing muscle strength decrease, for increasing muscle mass, or for increasing muscle strength.
  • the present invention also relates to a method for suppressing muscle mass decrease, suppressing muscle strength decrease, increasing muscle mass, or increasing muscle strength.
  • the present invention also relates to the use of one or more soyasapogenols and / or soyasaponins for inhibiting muscle mass reduction, inhibiting muscle strength reduction, increasing muscle mass or increasing muscle strength.
  • Patent Document 1 describes that when maslinic acid and oleanolic acid were ingested, skeletal muscle mass increased and resistance to grip increased after resistance training without using a training device, compared to the case of ingestion. .
  • maslinic acid and oleanolic acid described in Patent Document 1 are components contained in plants such as olives and are considered to be highly safe, they are substances having more excellent muscle mass reduction inhibitory activity, muscle strength reduction inhibitory effect, etc. Development is desired.
  • soyasapogenols and soyasaponins which are glycosides thereof, have excellent muscle mass reduction inhibitory activity, muscle strength reduction inhibitory effect, muscle mass increasing effect, or muscle strength increasing effect. Based on this finding, the present invention has been completed.
  • at least one soyasaponins is one or more of group A soyasaponins and / or group B soyasaponins.
  • a method for suppressing muscle mass reduction, suppressing muscle strength reduction, increasing muscle mass or increasing muscle strength comprising administering one or more soyasapogenols and / or soyasaponins.
  • at least one soyasapogenol is soyasapogenol A and / or soyasapogenol B.
  • ADVANTAGE OF THE INVENTION it has a muscle mass reduction inhibitory effect, a muscular strength reduction inhibitory effect, a muscular mass increase effect, or a muscular strength increase effect, and contains a highly safe substance as an active ingredient, for muscular mass reduction suppression, muscular strength reduction Compositions for suppression, muscle mass increase or muscle strength increase are provided.
  • a method for suppressing a decrease in muscle mass suppressing a decrease in muscle strength, increasing a muscle mass, or increasing a muscle strength.
  • a decrease in muscle mass or a decrease in muscle strength due to factors such as aging can be suppressed, or a muscle mass or muscle strength can be increased to maintain the muscle mass or muscle strength.
  • this invention can provide the new means which contributes to improvement of QOL, such as elderly people.
  • Soyasapogenols and soyasaponins used in the present invention for suppressing muscle mass decrease, muscle strength decrease, muscle mass increase or muscle strength increase are components that are also included in soybeans and other food plants, and continue to be highly safe. It is also advantageous in that it can be ingested.
  • FIG. 1 is a graph showing the results of examining changes in muscle strength with age for C57BL / 6J male mice.
  • FIG. 2 is a graph showing the grip strength change rate (grip strength at the end of the test / grip strength at the start of the test) of each of the control group, the soyasaponin group, and the soyasapogenol group.
  • FIG. 3 is a graph showing the ratio of both hindlimb muscle weights per body weight of the control group, soyasaponin group, and soyasapogenol group (both hindlimb muscle weight / body weight).
  • FIG. 4 is a graph showing the amount of protein synthesis in the gastrocnemius muscle of mice administered with the soyasapogenol crude fraction.
  • FIG. 5 is a graph showing the amount of phosphorylated p70S6K (T389) in gastrocnemius muscle of mice administered with the crude fraction of soyasapogenol.
  • FIG. 6 is a graph showing the amount of protein synthesis in the gastrocnemius muscle of mice administered with soyasapogenol A, soyasapogenol B, maslinic acid or oleanolic acid.
  • FIG. 7 is a graph showing the results of examining the myotube differentiation promoting effect of the soyasapogenol crude fraction using normal human skeletal myoblasts.
  • soyasapogenol compounds in the present invention include soyasapogenol A and soyasapogenol B.
  • the soyasapogenols in the present invention include one or more of these compounds.
  • the composition of the present invention preferably contains at least one soyasapogenol as an active ingredient.
  • Soyasapogenol A and / or soyasapogenol B is preferred as one or more of the soyasapogenols from the viewpoint of a muscle mass decrease inhibiting effect, a muscle strength decline inhibiting effect, a muscle mass increasing effect or a muscle strength increasing effect.
  • the soyasaponins are glycosides having the above-mentioned soyasapogenols as aglycones.
  • Examples of the soyasaponins compounds include group A soyasaponins, group B soyasaponins and the like.
  • Group A soyasaponins are glycosides having soyasapogenol A as an aglycon.
  • Group B soyasaponins are glycosides having soyasapogenol B as an aglycon.
  • Soyasapogenols contain one or more compounds.
  • the composition of the present invention may contain at least one soyasaponin as an active ingredient.
  • muscle mass decrease inhibitory effect muscle strength decrease inhibitory effect, muscle mass increasing effect or muscle strength increasing effect, one or more of the group A soyasaponins and / or the group B soyasaponins are preferred as one or more of the soyasaponins.
  • Group A Soyasaponins include Soyasaponin Aa (Soyasaponin A4), Soyasaponin Ab (Soyasaponin A1), Soyasaponin Ac, Soyasaponin Ad, Soyasaponin Ae (Soyasaponin A5), Soyasaponin A2 (Soyasaponin A2) Ah (Soyasaponin A3) is mentioned. Of these, Soyasaponin Aa and Soyasaponin Ab are preferable.
  • group B soyasaponins examples include soyasaponin Ba (soyasaponin V), soyasaponin Bb (soyasaponin I), soyasaponin Bc (soyasaponin II), soyasaponin Bb '(soyasaponin III), and soyasaponin Bc' (soyasaponin IV).
  • Soyasaponin Ba and Soyasaponin Bb are preferable.
  • soyasapogenols and / or soyasaponins are preferably soyasapogenols, and more preferably soyasapogenol A and / or soyasapogenol B.
  • Soybeans especially soybean seeds (soybeans)
  • red beans kudzu roots, and the like
  • Soyasapogenols and / or soyasaponins can be extracted and purified by a known method.
  • Soyasapogenols can also be obtained by hydrolyzing soyasaponins by a known method.
  • Commercially available products can be used as the soyasapogenols and soyasaponins.
  • a plant-derived raw material containing one or more kinds of soyasapogenols and / or soyasaponins may be contained in the composition of the present invention.
  • plant-derived materials rich in one or more of soyasapogenols and / or soyasaponins include, for example, soybean seeds that are raw or dried by freeze-drying, and soy seeds extracted with hot water or an organic solvent A solution (extract) obtained by concentrating or freeze-drying, or a product obtained by purifying a dried extract solution with a column or the like and purifying soyasapogenols and / or soyasaponins can be used.
  • the plant-derived raw material containing at least one kind of soyasapogenols and / or soyasaponins a commercially available one may be used, or it may be prepared from a plant such as soybean by a known method.
  • soy sapogenols or soy saponins were fed to an old mouse, the grip strength of the mouse increased.
  • the intake of soyasapogenols or soyasaponins increased the proportion of muscle weight per body weight of old mice.
  • protein synthesis amount decreased by fasting the amount of muscle protein synthesis significantly increased in mice fed with soyasapogenols compared to the fasted group.
  • phosphorylation of p70S6 kinase (p70S6K) was also promoted.
  • p70S6K is a major factor controlling muscle protein synthesis, and when phosphorylated, muscle protein synthesis is promoted.
  • promotion of phosphorylation of p70S6K promotes muscle protein synthesis, resulting in suppression or increase in muscle mass.
  • an effect of suppressing or increasing muscle strength can be obtained.
  • the amount of muscle protein synthesis was higher in mice fed with one or more of the soyasapogenols than in mice fed with oleanolic acid and maslinic acid. This means that soyasapogenols exhibit a muscle mass decrease inhibitory effect, muscle strength reduction inhibitory effect, muscle mass increasing effect or muscle strength increasing effect superior to oleanolic acid and maslinic acid.
  • the fraction containing soyasapogenols promoted differentiation from myoblasts to myotubes.
  • Muscles are formed from muscle fibers in which myoblasts are differentiated into myotube cells and myotube cells are fused.
  • the promotion of differentiation from myoblasts to myotubes results in the suppression or increase in muscle mass and the suppression or increase in muscle strength.
  • soyasaponins ingested soyasaponins become soyasapogenols in the body due to the action of digestive enzymes or metabolic enzymes, and are considered to exhibit the same effects as soyasapogenols in the body.
  • soyasapogenols and / or soyasaponins have a muscle mass decrease inhibitory effect, a muscle strength decrease inhibitory effect, a muscle mass increase effect or a muscle strength increase effect, and to suppress muscle mass decrease, Can be used to increase muscle strength or muscle strength.
  • Soyasapogenols and / or soyasaponins can also be used to promote differentiation of myoblasts into myotubes in order to promote phosphorylation of p70S6 kinase.
  • the composition of the present invention exhibits an excellent muscle mass reduction inhibitory effect, muscle strength reduction inhibitory effect, muscle mass increase effect, or muscle strength increase effect by including one or more soyasapogenols and / or soyasaponins as active ingredients.
  • such effects can prevent, for example, the reduction of muscle mass, the maintenance of muscle mass, the prevention of muscle weakness, the maintenance of muscle strength, the improvement of a state in which the muscle mass is reduced or the muscle strength is reduced, and the like. Therefore, the composition of the present invention can prevent muscle loss, prevent muscle weakness, improve the state of reduced muscle mass, improve the state of reduced muscle strength, maintain muscle mass, Can be used for maintenance etc.
  • the composition of the present invention is suitably used for suppressing the decrease in muscle mass or suppressing the decrease in muscle strength, for example, for suppressing the decrease in muscle mass due to muscle atrophy due to aging, for suppressing the decrease in muscle strength, etc. It can be suitably used.
  • the muscle skeletal muscle is preferable, and muscles such as legs are exemplified.
  • the increase in muscle mass can be an increase in muscle weight per body weight.
  • the muscle mass of animals such as humans can be measured by, for example, microPET / CT (positron emission tomography / computed tomography, INVEON, Siemens, USA).
  • the composition of the present invention can be used for treatment of a condition or disease for which prevention or improvement can be expected by suppressing muscle mass decrease, suppressing muscle strength decrease, increasing muscle mass, or increasing muscle strength.
  • conditions or diseases include locomotive syndrome, cachexia (caused by debilitating diseases such as cancer and chronic diseases, severe skeletal muscle atrophy and organ dysfunction due to loss of appetite and metabolic regulation mechanisms.
  • Examples include a state or disease in which muscle mass is reduced or muscle strength is reduced, such as a state showing a disease state.
  • prevention of a condition or disease refers to preventing the onset of the condition or disease, delaying the onset of the condition or disease, reducing the incidence of the condition or disease, and risk of developing the condition or disease. Includes mitigation. Improvement of a condition or disease includes restoring the subject from the condition or disease, reducing the symptoms of the condition or disease, delaying or preventing the progression of the condition or disease.
  • composition of the present invention can be applied to either a therapeutic use (medical use) or a non-therapeutic use (non-medical use).
  • the composition of this invention can be provided with forms, such as food / beverage products, a pharmaceutical, a quasi-drug, and a feed, for example, it is not limited to these.
  • the composition of the present invention may itself be a food / beverage product, a pharmaceutical product, a quasi-drug, a feed or the like, or may be a preparation or a material such as an additive used in these.
  • the composition of this invention can be provided with the form of an agent as an example, it 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 can also be referred to as an agent for inhibiting muscle mass reduction, inhibiting muscle strength reduction, increasing muscle mass, or increasing muscle strength.
  • the composition of the present invention is preferably an oral composition.
  • ADVANTAGE OF THE INVENTION According to this invention, the composition for oral administration which has the outstanding muscle mass reduction
  • the oral composition include foods and drinks, pharmaceuticals, and quasi drugs, preferably foods and drinks.
  • the composition of this invention can contain arbitrary additives and arbitrary components other than the above-mentioned Soyasapogenols and / or Soyasaponins.
  • These additives and components can be selected according to the form of the composition and the like, and generally usable for foods and drinks, pharmaceuticals, quasi drugs, feeds and the like.
  • composition of the present invention When the composition of the present invention is used as a food or drink, one or more soyasapogenols and / or soyasaponins can be used in the food or drink (for example, food and drink materials, additives used as necessary).
  • Food / beverage products are not specifically limited, For example, general food / beverage products, health food, food additives, these raw materials, etc. are mentioned.
  • the form of the food or drink is not particularly limited, and examples thereof include a solid form, a semi-fluid form, and a fluid form.
  • Foods and beverages include tablets, coated tablets, fine granules, granules, powders, pills, capsules, dry syrups, chewables and other oral solid preparations; oral liquid preparations, syrups and other oral liquid preparations It can also be.
  • the administration form of a pharmaceutical product or quasi drug is preferably oral administration.
  • the dosage form may be a dosage form suitable for the dosage form.
  • Oral pharmaceutical dosage forms for example, oral solid preparations such as tablets, coated tablets, fine granules, granules, powders, pills, capsules, dry syrups, chewables; oral preparations such as oral liquids and syrups Liquid formulations are mentioned.
  • the medicament may be a non-human animal medicament.
  • a feed that can be used in the feed can be blended with one or more of the soyasapogenols and / or soyasaponins.
  • the feed include livestock feed used for cattle, pigs, chickens, sheep, horses, etc .; feed for small animals used for rabbits, guinea pigs, rats, mice, etc .; pet food used for dogs, cats, birds, etc. .
  • composition of the present invention When the composition of the present invention is used as a food / beverage product, pharmaceutical product, quasi-drug, feed, etc., its production method is not particularly limited, and at least one of soyasapogenols and / or soyasaponins used as an active ingredient is used. And can be produced by a general method.
  • a purified compound may be used as soyasapogenols and / or soyasaponins, and a plant-derived material rich in one or more of the above-mentioned soyasapogenols and / or soyasaponins May be used. Soyasapogenols and / or soyasaponins may be contained in the composition in the form of a plant-derived raw material containing the compound.
  • composition of the present invention one or more of the use, the type of active ingredient, the effects described above, the usage method (for example, the ingestion method, the administration method), etc. may be displayed on a package, container or instruction.
  • the composition of the present invention may have an indication that it has a muscle mass decrease inhibitory effect, a muscle strength decline inhibitory effect, a muscle mass increase effect or a muscle strength increase effect, or an action based on these effects.
  • composition of the present invention includes, for example, “inhibition of muscle loss”, “muscle maintenance”, “muscle increase”, “muscle improvement”, “muscle strength reduction inhibition”, “muscle strength maintenance”, “muscle strength increase”, “muscle strength improvement” ”,“ Support muscle building power ”,“ Improvement of walking function ”,“ Maintenance of walking function ”,“ Improvement of motor function ”,“ Maintenance of motor function ”,“ Maintenance of muscles that decline with aging ”and“ Aging ”
  • One or two or more indications such as “maintenance of muscular strength that weakens by” may be attached.
  • the content of soyasapogenols and / or soyasaponins in the composition of the present invention can be appropriately set according to the form of the composition.
  • the total content of soyasapogenols and soyasaponins may be 0.01-90% by weight in the composition.
  • the total content of soyasapogenols and soyasaponins is 0.01% by weight in the composition.
  • the above is preferable, 0.2% by weight or more is more preferable, 20% by weight or less is preferable, and 10% by weight or less is more preferable.
  • the total content of soyasapogenols and soyasaponins is preferably 0.01 to 20% by weight, more preferably 0.2 to 10% by weight in the composition of the present invention.
  • the total content is the total amount of soyasapogenols and / or soyasaponins when two or more compounds are contained.
  • the content of soyasapogenols and / or soyasaponins can be measured according to a known method, for example, HPLC method or the like can be used.
  • the composition of the present invention can be ingested or administered by an appropriate method according to its form.
  • the composition of the present invention is preferably administered orally or ingested.
  • the amount of intake (also referred to as a dose) of the composition of the present invention is not particularly limited, and is an amount (effective amount) that provides a muscle mass decrease inhibitory effect, muscle strength decrease inhibitory effect, muscle mass increase effect, or muscle strength increase effect. ) And may be set as appropriate according to the dosage form, administration method, and the like.
  • the total intake of soyasapogenols and soyasaponins is preferably 5 mg or more, more preferably 10 mg or more, still more preferably 20 mg or more, Moreover, 500 mg or less is preferable, 200 mg or less is more preferable, and 100 mg or less is further more preferable.
  • the intake of the composition of the present invention is preferably 5 to 500 mg per day as the total intake of soyasapogenols and soyasaponins. 10 to 200 mg is more preferable, and 20 to 100 mg is more preferable.
  • the above amount is preferably administered or taken orally once a day or divided into 2 to 3 times a day.
  • the composition of the present invention for the purpose of obtaining the effect of suppressing muscle mass decrease, the effect of suppressing muscle strength decrease, the effect of increasing muscle mass or the effect of increasing muscle strength in humans (adults), the total of soyasapogenols and soyasaponins It is preferred that the composition of the present invention be orally ingested or administered to a subject so that the intake amount falls within the above range.
  • the composition of the present invention takes into consideration the dosage form, administration method, and the like, in an amount that provides the desired effect of the present invention, that is, an effective amount of the above-mentioned soyasapogenols and / or soyasaponins. It is preferable to contain seeds or more.
  • the composition of the present invention is an oral composition such as foods and drinks and oral pharmaceuticals, the total content of soyasapogenols and soyasaponins in the daily intake per adult of the composition The amount is preferably 5 to 500 mg, more preferably 10 to 200 mg, and even more preferably 20 to 100 mg.
  • the composition of the present invention is to be taken continuously.
  • the composition of the present invention is preferably taken continuously for 1 week or longer, more preferably 4 weeks or longer, and even more preferably 8 weeks or longer.
  • the subject to be administered or ingested the composition of the present invention is preferably a mammal (human and non-human mammal), more preferably a human.
  • a subject to be administered in the present invention a subject requiring or desiring to suppress muscle mass decrease, muscle strength decrease, muscle mass increase or muscle strength increase is preferable.
  • a subject whose muscle mass has decreased, a subject whose muscle strength has declined, a subject whose muscle mass has been reduced or whose muscle strength has been reduced, or a subject who wishes to prevent or ameliorate a disease, etc. can be mentioned as suitable subjects.
  • the subject of administration of the composition of the present invention is preferably elderly.
  • Soyasapogenols and / or soyasaponins are suitably used, for example, for the suppression of muscle mass loss (reduction in muscle mass due to aging) and the suppression of muscle strength reduction (reduction in muscle strength due to aging) in the elderly.
  • the composition of the present invention is used for a subject in a healthy state for the purpose of preventing a decrease in muscle mass, suppressing a decrease in muscle strength, a state in which improvement can be expected by an increase in muscle mass or an increase in muscle strength, or a disease. be able to.
  • the present invention also includes the following methods for suppressing muscle mass decrease, suppressing muscle strength decrease, increasing muscle mass, or increasing muscle strength.
  • the method may be a therapeutic method or a non-therapeutic method. “Non-therapeutic” is a concept that does not include medical practice, ie surgery, treatment or diagnosis.
  • soyasapogenols and / or soyasaponins is not particularly limited as long as it is an amount that can provide a muscle mass decrease inhibitory effect, muscle strength decrease inhibitory effect, muscle mass increase effect, or muscle strength increase effect, that is, an effective amount. It is preferred to administer the amounts described above. Soyasapogenols and / or soyasaponins may be administered as they are, or may be administered as a composition containing one or more of soyasapogenols and / or soyasaponins. For example, the composition of the present invention described above can be administered.
  • Soyasapogenols and / or soyasaponins, administration subjects, administration methods, dosages and preferred embodiments thereof are the same as those in the composition of the present invention described above.
  • ADVANTAGE OF THE INVENTION According to this invention, the side effect is not produced, but the outstanding muscle mass reduction
  • the present invention also encompasses the use of one or more soyasapogenols and / or soyasaponins for inhibiting muscle mass loss, inhibiting muscle weakness, increasing muscle mass or increasing muscle strength.
  • the above use is usually used in a human or non-human animal, preferably a human or non-human mammal, more preferably a human.
  • the use may be therapeutic or non-therapeutic.
  • Preferred embodiments such as soyasapogenols and / or soyasaponins are the same as those of the composition of the present invention described above.
  • soyasapogenols and / or soyasaponins may be used, or two or more compounds may be used.
  • it is preferable to administer one or more soyasapogenols and / or soyasaponins preferably continuously for 1 week or more, more preferably 4 weeks or more, and even more preferably 8 weeks or more.
  • the present invention also includes the use of one or more soyasapogenols and / or soyasaponins for producing a composition for inhibiting muscle mass loss, for inhibiting muscle weakness, for increasing muscle mass, or for increasing muscle strength.
  • soyasapogenols and / or soyasaponins muscle mass reduction suppression, muscle strength reduction suppression, muscle mass increase or muscle strength increase composition and preferred embodiments thereof are the same as the above-described composition of the present invention and preferred embodiments thereof It is.
  • soyasaponin a commercially available soybean-derived saponin (saponin B-50 manufactured by J-Oil Mills Co., Ltd. (group B soybean saponin content is 60% by weight, A The group soybean saponin content was evaluated using 13 wt%)).
  • group B soybean saponins in saponin B-50 include soya saponin Ba and soya saponin Bb, and group A soybean saponins include soya saponin Aa and soya saponin Ab.
  • a fraction containing soybean-derived sapogenol was prepared by the following method.
  • Saponin B-50 was reacted in a 20-fold amount of 2N aqueous hydrochloric acid at 100 ° C. for 2 hours to cleave the saponin sugar chain. After completion of the reaction, the reaction solution was cooled to room temperature and neutralized with an aqueous sodium hydroxide solution. The reaction solution was subjected to suction filtration, the residue was washed with a large amount of distilled water, and suction filtration was repeated. After confirming that no sodium hydroxide remained, the residue was dried and soyasapogenol crude fraction (purity 50%: soyasapogenol A and B). Total).
  • the transition of the total limb grip strength as an index was examined.
  • the total grip strength of the limbs at 7 months of age (23 animals), 20 months of age (22 animals), 22 months of age (7 animals) and 24 months of age (7 animals) was measured using the grip strength measuring device (MK-380S, Muromachi Machine Co., Ltd.) Company) and measured the grip strength. Dunnett's multiple comparison test was used for the significant difference test.
  • the grip strength measurement results of each group of 7 months old (7M), 20 months old (20M), 22 months old (22M) and 24 months old (24M) are shown in FIG. 1 (*: P ⁇ 0.05, ** : P ⁇ 0.01, compared with 7 months old). The results are shown as the mean value ⁇ standard error of each group. As a result of statistical analysis, it can be seen that the grip strength of 20-month-old, 22-month-old, and 24-month-old mice is significantly lower than that of 7-month-old mice. From this result, it was confirmed that a decrease in muscle strength accompanying aging can be observed in mice of the above strain.
  • Soya saponin and soya sapogenol crude fraction decrease suppression or increase action and muscular strength decrease suppression or increase action Soya saponin and soya sapogenol crude fraction show muscular strength decrease suppression or increase effect on aging muscle weakness? It was evaluated by measuring the grip strength of the limbs of mice. At the same time, it was also examined whether or not there was an effect of suppressing or increasing the hind limb muscle weight. As the soyasapogenol crude fraction, the one prepared in Preparation Example 1 was used.
  • mice 70-week-old C57BL / 6J male mice (Nippon Charles River Co., Ltd.) were preliminarily raised for 8 weeks. Mice after pre-breeding (old mice) were divided into three groups: a control group, a soyasaponin group, and a soyasapogenol group. Each group was evaluated with 5 to 8 animals. In the control group, CE-2 feed (CLEA Japan, Inc.) was allowed to eat freely for 8 weeks (test period).
  • CE-2 feed CLEA Japan, Inc.
  • the soyasaponin group contains CE-2 feed containing 0.5% by weight of saponin B-50 (manufactured by J-Oil Mills Co., Ltd.), and the soyasapogenol group contains 0.5% by weight of the crude soyasapogenol fraction.
  • the formulated CE-2 feed was fed ad libitum for 8 weeks. After the test period, the mouse body weight, hind limb muscle weight and grip strength were measured. The grip strength was measured by using a grip strength measuring device (MK-380S, Muromachi Kikai Co., Ltd.) as the total grip strength of the mouse limbs.
  • the muscle weights of the hind limbs were collected from the gastrocnemius, soleus, plantar muscles, anterior tibial muscles, extensor extensors and quadriceps muscles, and weighed.
  • As an evaluation index of muscle weight the ratio of both hind limb muscle weights per body weight (total weight of gastrocnemius, soleus, plantar, anterior tibial, long extensor and quadriceps) was determined. Dunnett's multiple comparison test was used for the significant difference test. Significance level P ⁇ 0.05 was considered significant.
  • FIG. 3 shows the ratio of both hind limb muscle weights per body weight of the control group, soyasaponin group, and soyasapogenol group.
  • the results shown in FIG. 3 are shown as the mean value ⁇ standard error of each group.
  • soyasaponins and soyasapogenols have an effect of maintaining muscle strength by suppressing or increasing muscle strength associated with aging. Moreover, the effect of increasing the proportion of hindlimb muscle weight per body weight was confirmed for soyasaponins and soyasapogenols.
  • Example 2 Evaluation of muscle protein synthesis and muscle synthesis signal (soyasapogenol crude fraction) (Test method) (reagent) Ponceau S solution was purchased from Sigma-Aldrich. Sodium carboxymethylcellulose (CMC-Na), Extra PAGE One Precast Gel, and Blocking one were purchased from Nacalai Tesque. The Tissue Protein Extraction Reagent, the Protease Inhibitor Cocktail Kit, and the Pierce BCA protein assay kit were purchased from Thermo Fisher Scientific. Puromycin was purchased from InvivoGen, and Anti-puromycin was purchased from Millipore.
  • mice Male 7-week-old C57BL6J mice were purchased from Clea Japan, Inc. and subjected to experiments after a 1-week acclimatization period. The animals were raised in a breeding room with air conditioning (temperature 23.5 ⁇ 1.0 ° C., humidity 55 ⁇ 10%, ventilation rate 12-15 times / hour, lighting 7: 00-19: 00 / day). During the acclimation period, commercial feed (CE-2, Nippon Claire Co., Ltd.) and tap water were freely consumed.
  • mice were divided into the following 3 groups.
  • the amount of protein synthesis was measured by the following method.
  • the amount of p70S6K (phosphorylated p70S6K (T389)) in which the 389th threonine (T389) was phosphorylated was measured for p70S6 kinase (p70S6K) in gastrocnemius muscle.
  • the amount of protein synthesis in the gastrocnemius muscle was measured using the surface sensing of translation (SUNSET) method (Nat Methods. 2009 Apr; 6 (4): 275-7).
  • the mouse gastrocnemius muscle was homogenized with ice-cooled Protease Inhibitor Cocktail and Tissue protein extraction reagent containing EDTA, and then centrifuged at 10,000 rpm, 10 min, 4 ° C., and the supernatant was collected. The supernatant was subjected to protein concentration quantification using Pierce BCA protein assay kit and subjected to SDS for Western blotting.
  • the obtained sample was adjusted to a protein concentration of 10 ⁇ g / 10 ⁇ L, 10 ⁇ L was applied to Extra PAGE One Precast Gel, and electrophoresis was performed using an electrophoresis apparatus (Atto Corporation). After completion of electrophoresis, transfer was performed on a PVDF membrane using a blotting apparatus. After confirming that there was no difference in the amount of protein transferred by staining with the Ponceau S solution, Anti-puromycin (1: 3000) and Anti- ⁇ -actin (1: 2000) were added in the presence of Blocking one, and 4 Incubation was performed at 0 ° C. for 18 hours.
  • Anti-rabbit IgG and HRP-linked Antibody (1: 10000) were added at room temperature, and after incubation for 2 hours, ECL Western Blotting Detection Reagents were added, and detection and analysis of bands were performed using FUSIONSOLO. The results were expressed as relative values with the fasting group (Fast.) As 100.
  • FIG. 4 is a graph showing the amount of protein synthesis in the gastrocnemius muscle of mice administered with the crude fraction of soyasapogenol (*: P ⁇ 0.05, compared with fasting group).
  • FIG. 5 is a graph showing the amount of phosphorylated p70S6K (T389) in the gastrocnemius muscle of mice administered with the crude fraction of soyasapogenol (*: P ⁇ 0.05, comparison with fasting group).
  • FIG. 6 is a graph showing the amount of protein synthesis in the gastrocnemius muscle of mice administered with soyasapogenol A, soyasapogenol B, maslinic acid or oleanolic acid (*: P ⁇ 0.05, comparison with each group).
  • Fast. fasting + Soyasapogenol A group
  • Fast. + SSB fasting + Soyasapogenol B group
  • Example 4 Using normal human skeletal myoblasts (HSMM) (LONZA), the myotube differentiation promoting effect of the test substance was examined.
  • the soyasapogenol crude fraction produced in Preparation Example 1 was used as the test substance.
  • the obtained cells were subjected to myotube staining with MHC staining and nuclear staining with Hoechst 33342 staining to quantify myotube differentiation rate.
  • DMSO dimethyl sulfoxide
  • DMEM F-12 medium (Lonza) supplemented with 2% HORSE SERUM (Thermo Fisher Scientific) was used.
  • a differentiation medium containing 0.1% DMSO supplemented with 0.5 ⁇ M LDN-193189 was used.
  • GFR Matrigel Matrix coat When inducing myotube differentiation, a 96-well plate was coated with GFR Matrigel Matrix (Corning). Thaw GFR FR Matrigel Matrix overnight at 4 ° C, dilute 100-fold with DMEM: F-12 medium (4 ° C), dispense 0.1 mL into each well of a 96-well plate on ice, and add 1 mL at room temperature. Incubated for hours. The solution was aspirated and rinsed with DMEM: F-12 medium (0.1 mL) and used for cell seeding.
  • DMEM F-12 medium
  • the primary antibody solution (prepared by adding 1/150 amount of primary antibody to 3% BSA / DPBS) was changed to 0.05 mL and incubated overnight at 4 ° C. After washing 3 times with 0.1 mL of 3% BSA / DPBS solution, secondary antibody solution (prepared by adding 1/500 volume of secondary antibody and 1/1000 volume of Hoechst 33342 to 3% BSA / DPBS) The volume was changed to 05 mL and incubated at room temperature for 2 hours. After washing with 0.1 mL of DPBS three times, 0.1 mL of DPBS was added, and image capturing and quantitative analysis were performed with Operatta CLS (registered trademark) (Perkin Elmer).
  • Operatta CLS registered trademark
  • the primary antibody is Anti-Myosin-Heavy Chain Purified (anti-MHC antibody) (Affymetrix), and the secondary antibody is Goast anti-Mouse IgG2b Secondary Antibody, Alexa Fluor Fisher 550, respectively. used.
  • FIG. 7 is a graph showing the results of examining the myotube differentiation promoting effect of soyasapogenol crude fraction using normal human skeletal muscle myoblasts (*: P ⁇ 0.05, comparison with control).
  • the soyasapogenol of FIG. 7 is a soyasapogenol crude fraction addition group.
  • the fusion index (% of MHC positive nuclei) was larger and the myotube differentiation rate was higher than the control.
  • the soyasapogenol crude fraction promoted the differentiation of normal human skeletal myoblasts into myotubes.

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Abstract

La présente invention concerne la fourniture d'une composition, qui comprend en tant que principe actif une substance présentant un effet de prévention d'une diminution de la masse musculaire, de prévention d'une diminution de la puissance musculaire, l'augmentation de la masse musculaire ou l'amélioration de la puissance musculaire ainsi qu'une sécurité élevée et qui doit être utilisée dans la prévention d'une diminution de la masse musculaire, la prévention d'une diminution de la puissance musculaire, l'augmentation de la masse musculaire ou l'amélioration de la puissance musculaire et un procédé destiné à la prévention d'une diminution de la masse musculaire, la prévention d'une diminution de la puissance musculaire, l'augmentation de la masse musculaire ou l'amélioration de la puissance musculaire. La composition selon la présente invention destinée à la prévention d'une diminution de la masse musculaire, à la prévention d'une diminution de la puissance musculaire, l'augmentation de la masse musculaire ou l'amélioration de la puissance musculaire comprend, en tant que principe actif, un ou plusieurs éléments de sapogénols de soja et/ou de saponines de soja.
PCT/JP2019/017413 2018-04-27 2019-04-24 Composition destinée à la prévention d'une diminution de la masse musculaire, à la prévention d'une diminution de la puissance musculaire, à l'augmentation de la masse musculaire ou à l'amélioration de la puissance musculaire WO2019208627A1 (fr)

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JP2020515521A JP7227962B2 (ja) 2018-04-27 2019-04-24 筋肉量減少抑制用、筋力低下抑制用、筋肉量増加用又は筋力増加用の組成物

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KR20140037107A (ko) * 2011-06-28 2014-03-26 제이-오일 밀스, 인코포레이티드 소야 사포게놀 조성물
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US20180104269A1 (en) * 2015-04-27 2018-04-19 Suntory Holdings Limited Composition for suppressing muscular fatty change
KR20170054115A (ko) * 2015-11-09 2017-05-17 대한민국(농촌진흥청장) 콩 발아배아 추출물을 포함하는 골다공증의 예방 또는 치료용 약학 조성물

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