Composition with effects in enhancing muscle strength and motor function

JP2025027248APending Publication Date: 2025-02-27OTSUKA PHARMACEUTICAL FACTORY INC
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Patent Information

Application Number
JP2023131893
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Filing Date
2023-08-14
Publication Date
2025-02-27

AI Technical Summary

Benefits of technology

【0013】 本発明の組成物によれば、ジオスゲニンを含む植物処理物および3-ヒドロキシイソ吉草酸もしくはその塩またはこれらの誘導体の対象者(特に、60歳未満の対象者)への投与により、対象者の筋力および運動機能を増強させることができる。

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Abstract

To provide a composition with effects in enhancing muscle strength and motor function.SOLUTION: A composition comprises a processed plant material comprising diosgenin and 3-hydroxyisovaleric acid or a salt thereof, or derivatives thereof.SELECTED DRAWING: Figure 2
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Description

[Technical field]

[0001] The present invention relates to a composition having the effect of enhancing muscle strength and motor function. [Background technology]

[0002] Aging-related declines in skeletal muscle mass and strength are called sarcopenia. Skeletal muscle characteristics in sarcopenia include selective atrophy of fast-twitch muscle fibers, a shift to slow-twitch muscle fiber composition, a decrease in the number of muscle fibers, and intramuscular fat and fibrosis. The causes of sarcopenia are diverse, including (1) a decrease in skeletal muscle protein synthesis due to attenuation of mammalian target of rapamysin (mTORC) signaling activity in response to exercise and amino acid intake and a decrease in muscle anabolic hormone concentrations, (2) an increase and dysfunction of the muscle protein degradation system, (3) a decrease in muscle regenerative capacity, and (4) an increase in inflammation and oxidative stress.

[0003] Blood levels of sex steroid hormones change significantly with age. However, the cellular mechanism by which testosterone increases skeletal muscle mass has not yet been fully studied, and the effects of testosterone on sarcopenia need to be further investigated in detail.

[0004] There are many kinds of yams, and in Japan, the main varieties cultivated for food are Daijo, Jinenjo, Nagaimo, and Togedokoro. Togedokoro is cultivated in Kyushu and south, and is said to have originated in the areas around Thailand and Vietnam.

[0005] Yams are known to contain the plant steroid diosgenin and its glycosides. Diosgenin is the aglycone portion of saponin and has a structure similar to that of dehydroepiandrosterone (DHEA) in its molecule.

[0006] Patent Document 1 reports that, among various types of yams, Togedokoro was found to be a yam with a particularly high content of diosgenin or its glycosides. Togedokoro is a type of yam known by the scientific name Dioscorea esculenta and is cultivated mainly in areas south of Kyushu.

[0007] Furthermore, Patent Document 2 reports that Acanthus or a processed product derived from Acanthus has anti-fatigue effects, endurance enhancing effects, nutritional tonic effects, and muscle building effects. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] Japanese Patent Application Publication No. 2007-274985 [Patent Document 2] International Publication No. 2008 / 123417 Summary of the Invention [Problem to be solved by the invention]

[0009] An object of the present invention is to provide a composition that has the effect of enhancing muscle strength and motor function. [Means for solving the problem]

[0010] As a result of extensive research to achieve the above-mentioned objective, the inventors have discovered that administering a plant treatment containing diosgenin and 3-hydroxyisovaleric acid to a subject can enhance the subject's muscle strength and motor function.

[0011] The present invention has been completed based on these findings and through further investigation, and provides the following composition.

[0012] Item 1. A composition comprising a plant treated product containing diosgenin and 3-hydroxyisovaleric acid or a salt thereof, or a derivative thereof. Item 2. The composition according to Item 1, wherein the plant treatment is a plant extract. Item 3. The composition according to Item 1, wherein the plant treated product is a yam treated product. Item 4. The composition according to Item 1, wherein the plant treatment is a yam extract. Item 5. The composition according to any one of Items 1 to 4, wherein the 3-hydroxyisovaleric acid or a salt thereof, or a derivative thereof is a calcium salt of 3-hydroxyisovaleric acid. Item 6. The composition according to any one of Items 1 to 5, wherein the mixing ratio of diosgenin to 3-hydroxyisovaleric acid or a salt thereof, or a derivative thereof is 1:1.5 or more by mass ratio. Item 7. The composition according to any one of Items 1 to 6, which is for enhancing muscle strength. Item 8. The composition according to any one of Items 1 to 7, which is used for enhancing motor function. Item 9. The composition according to item 7 or 8, for administration to a subject under 60 years of age. Item 10. The composition according to any one of Items 1 to 9, which is used for preventing and / or improving at least one condition selected from the group consisting of locomotive syndrome, sarcopenia and frailty. Item 11. The composition according to any one of Items 1 to 10, wherein the composition is a pharmaceutical composition, a food composition, or a supplement. Effect of the Invention

[0013] According to the composition of the present invention, by administering a plant treatment containing diosgenin and 3-hydroxyisovaleric acid or a salt thereof, or a derivative thereof to a subject (especially a subject under 60 years of age), the subject's muscle strength and motor function can be enhanced. [Brief description of the drawings]

[0014] [Figure 1] 1 is a graph showing the results of measuring grip strength in Test Example 1. Upper row: change in grip strength during the test period, lower row: grip strength at 12 weeks, left column: grip strength (N), right column: grip strength per body weight (N / kg), *p<0.05, CON: experimental feed 1, DH: experimental feed 2 [Diagram 2] FIG. 1 is a diagram showing a test schedule for Test Example 2. [Diagram 3] 1 is a graph showing the measurement results of the 5-times-rising test in Test Example 2. Left: actual measurements, upper right: amount of change, lower right: rate of change, test: group ingesting the test food, con: group ingesting a placebo [Figure 4] 1 is a graph showing the measurement results of the 5-times standing test (50s) in Test Example 2. Left: actual measurements, upper right: amount of change, lower right: rate of change, test: test food intake group, con: placebo intake group DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] Hereinafter, an embodiment of the present invention will be described.

[0016] The composition of the present invention is characterized by containing a plant treatment product containing diosgenin and 3-hydroxyisovaleric acid or a salt thereof, or a derivative of these.

[0017] Diosgenin is a plant steroid, a compound contained in plants. Diosgenin is the aglycone portion of saponin, and has a structure similar to DHEA in its molecule. In the present invention, diosgenin includes its salts, derivatives, solvates, crystal polymorphs, etc.

[0018] In this specification, a diosgenin derivative is an equivalent of diosgenin, which has the same effect as diosgenin. The diosgenin derivative may be, for example, an equivalent that can be achieved by chemical modification such as introducing a substituent into diosgenin or converting the substituent, or may be a diosgenin glycoside extracted from a natural product. There are various molecular species of diosgenin glycosides due to differences in sugar chains. The aglycone (non-sugar portion) of diostin (glycoside) is diosgenin.

[0019] Examples of diosgenin salts include salts with inorganic bases such as sodium salt, magnesium salt, potassium salt, calcium salt, and aluminum salt; salts with organic bases such as methylamine, ethylamine, and ethanolamine; salts with basic amino acids such as lysine, ornithine, and arginine, and ammonium salts. The salts may be acid addition salts, and specific examples of such salts include acid addition salts with mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid; organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, malic acid, tartaric acid, fumaric acid, succinic acid, lactic acid, maleic acid, citric acid, methanesulfonic acid, and ethanesulfonic acid; and acidic amino acids such as aspartic acid and glutamic acid.

[0020] The plant in the plant treatment containing diosgenin is not particularly limited as long as it contains diosgenin, and a plant with a high diosgenin content is preferably used. An example of the plant in the plant treatment is yam (a plant belonging to the Dioscoreaceae family). Such yam is preferably yam (a species of the Dioscoreaceae family, Dioscorea genus, whose tuberous root is edible). Examples of yams include Chinese yam, Chinese yam, Japanese yam, Japanese angelica, Japanese angelica, Japanese maple, Japanese maple, Japanese angelica, Japanese yam, Japanese water yam, yellow guinea yam, white guinea yam, Mexican yam, and wild yam. One type of yam may be used alone, or two or more types may be used in combination.

[0021] There is no particular limitation on the part of the yam to be used, and for example, the stem tuber, root, stem, leaf, or a mixture thereof can be used. Among them, it is preferable to use the stem tuber. In addition, since diosgenin is contained in large amounts in the outer skin of the stem tuber, it is preferable not to remove the outer skin of the stem tuber in order to obtain a plant treatment product with a high diosgenin content.

[0022] The plant processed product is not particularly limited as long as it is a product that has been processed in some way from a raw plant and has a high diosgenin content. Examples of the plant processed product include extracts, ground products, dried powders, crushed products, pulverized products, squeezed juice, chemically treated products, and enzyme-treated products. Among these, plant extracts are preferred.

[0023] A plant extract is obtained by performing an extraction operation on a raw plant using an extraction solvent. When performing the extraction process, a processed plant can be used, and examples of such processed products include ground products, crushed products, crushed products, and mixtures thereof. The extraction can be performed by a known extraction method. The extraction can be performed in a batch or continuous manner using a solvent. The extraction solvent used in the extraction is not particularly limited, and examples include alcohols such as water, chloroform, ethanol, methanol propanol, isopropyl alcohol, n-butyl alcohol, and 1,3-butylene glycol, ketones such as acetone and methyl ethyl ketone, methyl acetate, and ethyl acetate. The solvent can be used alone or as a mixture. Examples of the mixture can include various aqueous solutions. The amount of the extraction solvent, the extraction temperature, the extraction time, and the like can be appropriately determined taking into account the extraction efficiency, etc. The extraction operation can be performed, for example, by stirring or leaving the mixture to stand. In addition, the extraction can be repeated several times as necessary.

[0024] After extraction with a solvent, solid-liquid separation can be performed by filtration, centrifugation, etc., and the liquid portion can be collected as an extract. In addition, the extract can be concentrated and purified as necessary by processing such as filtration, centrifugation, ultrafiltration, molecular sieve chromatography (gel filtration), adsorption chromatography, ion exchange chromatography, affinity chromatography, high performance liquid chromatography (HPLC), dialysis, or a combination of these.

[0025] If desired, the extract can be subjected to removal of the solvent, and can be concentrated or dried (eg, freeze-drying, spray-drying, etc.).

[0026] Furthermore, the extract may be subjected to an acid treatment in order to convert diostin (a glycoside) contained in the plant into its aglycone (non-sugar portion), diosgenin. Examples of acids used for the acid treatment include hydrochloric acid, sulfuric acid, formic acid, and trifluoroacetic acid.

[0027] After the acid treatment, neutralization may be carried out with an alkali, such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, or ammonia.

[0028] After neutralization, the acid and alkali added for the neutralization are still present in the solution, and salts formed by these may be removed.

[0029] The plant treatment products containing diosgenin may be used alone or in combination of two or more kinds.

[0030] As plant treatments containing diosgenin, commercially available products are also available, such as Geopower 15 (Anti-Aging Pro Co., Ltd.).

[0031] The content of diosgenin in the diosgenin-containing plant treatment product is not particularly limited, and is, for example, 6 to 30% by mass, preferably 8 to 25% by mass, and most preferably 10 to 20% by mass. In the present specification, the content of diosgenin derivatives such as diosgenin glycosides can be calculated in terms of the amount of diosgenin.

[0032] The content of the plant treatment product containing diosgenin is not limited as long as the effects of the present invention are obtained, and the content of the plant treatment product in the composition of the present invention, converted into the amount of diosgenin, is, for example, 0.01 to 3 mass%, preferably 0.1 to 2.5 mass%, and most preferably 0.5 to 2 mass%.

[0033] 3-Hydroxyisovaleric acid (β-hydroxyisovaleric acid) is a metabolic product of the essential amino acid leucine and is also known as β-hydroxy-β-methylbutyric acid or HMB.

[0034] In the present invention, 3-hydroxyisovaleric acid or a salt thereof, or a derivative thereof includes a solvate, a crystal polymorph, and the like.

[0035] Examples of salts of 3-hydroxyisovaleric acid include salts with inorganic bases such as sodium salt, magnesium salt, potassium salt, calcium salt, aluminum salt, etc.; salts with organic bases such as methylamine, ethylamine, ethanolamine, etc.; salts with basic amino acids such as lysine, ornithine, arginine, etc., and ammonium salts. The salt may be an acid addition salt, and specific examples of such salts include acid addition salts with mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, malic acid, tartaric acid, fumaric acid, succinic acid, lactic acid, maleic acid, citric acid, methanesulfonic acid, ethanesulfonic acid, etc.; and acidic amino acids such as aspartic acid, glutamic acid, etc.

[0036] In the present specification, the derivative of 3-hydroxyisovaleric acid is an equivalent of 3-hydroxyisovaleric acid, which exhibits the effects of the present invention in the same manner as 3-hydroxyisovaleric acid. The derivative of 3-hydroxyisovaleric acid may be, for example, an equivalent that can be achieved by chemical modification such as introducing a substituent into 3-hydroxyisovaleric acid or converting the substituent.

[0037] As 3-hydroxyisovaleric acid or a salt thereof, or a derivative thereof, a salt of 3-hydroxyisovaleric acid is preferred, and a calcium salt of 3-hydroxyisovaleric acid is more preferred.

[0038] 3-Hydroxyisovaleric acid or a salt thereof, or a derivative thereof may be used alone or in combination of two or more kinds.

[0039] The content of 3-hydroxyisovaleric acid or a salt thereof, or a derivative thereof is not limited as long as the effects of the present invention are obtained, and the content of 3-hydroxyisovaleric acid or a salt thereof, or a derivative thereof in the composition of the present invention is, for example, 0.1 to 50 mass%, preferably 10 to 45 mass%, and most preferably 15 to 40 mass%.

[0040] The blending ratio of diosgenin and 3-hydroxyisovaleric acid or a salt thereof or a derivative thereof is not limited as long as the effects of the present invention can be obtained, and the blending ratio in the composition of the present invention is, for example, 1:1.5 or more by mass ratio, for example, in the range of 1:1.5-100, preferably 1:5-70, and most preferably 1:10-50.

[0041] In addition to the above-mentioned components, the composition of the present invention may contain any component as necessary within a range that does not impair the effects of the present invention, and the optional components may include, for example, edible or pharma- ceutically acceptable carriers, additives, etc. Examples of edible or pharma- ceutically acceptable carriers and additives include aqueous media, excipients, binders, disintegrants, lubricants, thickeners, surfactants, pH adjusters, sweeteners, flavors, colorants, etc. These are known to those skilled in the art and may be appropriately selected and used. Specific examples of these include aqueous media such as water, physiological saline, and fruit juice; excipients such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid, potassium phosphate, corn starch, and dextrin; binders such as water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, hydroxypropylcellulose, methylcellulose, and polyvinylpyrrolidone; sodium carboxymethylcellulose, calcium carboxymethylcellulose, low-substituted hydroxypropylcellulose, dry starch, and sodium alginate. Examples of suitable disintegrants include gum, agar powder, laminaran powder, sodium bicarbonate, and calcium carbonate; lubricants such as purified talc, stearates, powdered boric acid, and polyethylene glycol; thickeners such as gelatin, gum arabic, dextrin, methylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl cellulose, xanthan gum, pectin, tragacanth gum, casein, and alginic acid; surfactants such as polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, and monoglyceride stearate; and sweeteners such as stevia, saccharin, acesulfame K, aspartame, and sucralose.

[0042] Those skilled in the art can appropriately select the components to be used as needed, and the amounts of the components may be appropriately adjusted to suit the desired form, preferences, etc., within a range that does not interfere with the effects of the present invention.

[0043] The form of the composition of the present invention is not particularly limited, and examples thereof include solid forms such as powders, granules, tablets, pills, and troches; semi-solid forms such as jelly, mousse, yogurt, pudding, and cream; and liquid forms such as liquids, suspensions, emulsions, and syrups. These forms can also be filled into microcapsules, soft capsules, hard capsules, and the like to form capsules. The composition of the present invention can also be in the form of an effervescent preparation. The manufacturing method of these forms can be carried out according to methods known in the art.

[0044] The composition of the present invention may be applied to any animal, as long as it is an animal intended to enhance muscle strength and motor function. For example, the animal may be a mammal such as a human, and may also be a variety of animals, including pets and livestock other than mammals. The present invention is not limited to any age or sex of the subject. It is preferable to administer the composition to subjects under 60 years of age, more preferable to administer the composition to subjects between 40 and 60 years of age, and even more preferable to administer the composition to subjects between 50 and 60 years of age. In this specification, "administer" and "ingest" are synonymous terms, and "administer" and "ingest" can be used interchangeably.

[0045] The composition of the present invention can be applied to a food composition. That is, the composition of the present invention can be used as a food composition as it is. It can also be used as an additive to a food composition. Such a food composition containing the composition of the present invention can provide the above-mentioned effects attributable to the composition of the present invention. The composition of the present invention can be used as a pharmaceutical composition as it is. It can also be used as an additive to a pharmaceutical composition. Such a pharmaceutical composition containing the composition of the present invention can provide the above-mentioned effects attributable to the composition of the present invention. When the composition of the present invention is applied to a pharmaceutical composition, it can be used as an oral preparation.

[0046] When the composition of the present invention is applied to pharmaceutical compositions and food compositions in this manner, the type of pharmaceutical composition and food composition is not limited, and it is sufficient that the plant processed product containing diosgenin and 3-hydroxyisovaleric acid or a salt thereof, or a derivative thereof, are blended into the pharmaceutical composition and food composition, and any optional components, such as edible or pharma- ceutical acceptable carriers and additives, can be further included as necessary.

[0047] In addition, when the composition of the present invention is applied to a pharmaceutical composition and a food composition, the pharmaceutical composition and the food composition are not particularly limited as long as they exhibit the effects of the present invention. For example, the food composition includes, but is not limited to, confectionery (gum, candy, cookies, gummies, rice crackers, biscuits, jellies, mousses, cream caramel, Ramune candy, edible sheets, edible films, troches, etc.), mouth fresheners (gum, candy, gummies, edible films, troches, etc.), beverages (carbonated beverages, soft drinks, milk beverages, alcoholic beverages, fruit juice beverages, teas, nutritional beverages, etc.), powdered beverages (powdered juice, powdered soup, etc.), dairy products (cheese, yogurt, etc.), bread, noodles, cereals, etc. In addition to the above-mentioned components, the food composition may contain any components such as oil, sugar, salt, soy sauce, miso, dashi soy sauce, various extracts, various spices, acidulants, amino acids, minerals, vitamins, flavors, colorants, antioxidants, and nutritional enhancers, if necessary. These may be appropriately selected according to the purpose, such as imparting taste, aroma, color, or desired function to the food composition, and the amount of each component may be appropriately set according to the purpose. Examples of food compositions include foods for specified health uses, nutritional supplements, supplements, functional foods, and foods for sick people. The form of the food composition is not particularly limited, and may be any of a beverage form, a semi-liquid or gel form, and a solid form. The pharmaceutical composition is also not limited, and may be a solid, semi-solid, or liquid form formulation, a capsule, or an effervescent formulation, as described above. The manufacturing method of these may be performed according to a method known in the art.

[0048] The dosage of the composition of the present invention is adjusted appropriately depending on age, sex, symptoms, etc., but the dosage per 1 kg of body weight per day for adults is preferably 0.1 to 4.0 mg, more preferably 0.5 to 2.0 mg, and even more preferably 0.7 to 1.3 mg for diosgenin, and preferably 3 to 150 mg, more preferably 18 to 76 mg, and even more preferably 26 to 50 mg for 3-hydroxyisovaleric acid or a salt thereof, or a derivative thereof. This can be administered once a day or in several divided doses.

[0049] The composition of the present invention can be provided as a composition comprising a plant treatment containing diosgenin and 3-hydroxyisovaleric acid or a salt thereof or a derivative thereof in a daily dose as exemplified above. In this case, the composition of the present invention may be packaged so that an effective daily intake can be ingested, and the package form may be a single package or multiple packages as long as an effective daily intake can be ingested.

[0050] In order to more effectively exert the effects of the composition of the present invention, it can be administered continuously for 4 weeks or more, and the administration period is more preferably 4 to 12 weeks, and particularly preferably 4 to 8 weeks. Here, "continuously" means that the composition is administered every day.

[0051] As shown in the examples described below, plant processed products containing diosgenin and 3-hydroxyisovaleric acid or its salts, or derivatives thereof, have the effect of enhancing muscle strength and motor function (e.g., muscle-storing effect), and therefore the composition of the present invention can be used as a composition for enhancing muscle strength and / or motor function (particularly for enhancing lower limb muscle strength and / or motor function of the lower limbs).

[0052] The increase in muscle strength can be confirmed, for example, by an increase in the muscle strength of a subject after taking the composition of the present invention by 0.1% or more, preferably 0.2% or more, and most preferably 1% or more, compared to before taking the composition of the present invention. The increase in muscle strength can be measured, for example, using a dynamometer (e.g., μTas F2 (manufactured by OG Engineering Co., Ltd.)). The increase in muscle strength may be achieved by increasing at least one type of muscle strength.

[0053] The enhancement of motor function can be confirmed, for example, by an improvement of 1% or more, preferably 2% or more, and most preferably 5% or more in the motor function score of a subject after taking the composition of the present invention compared to before taking the composition of the present invention. Motor function can be measured, for example, by the 5-times rearing test described below.

[0054] Furthermore, the muscle strength and motor function enhancing effect of the composition of the present invention is particularly effective for subjects under 60 years of age (e.g., middle-aged and elderly people (particularly middle-aged and elderly people whose muscle synthesis has decreased compared to their younger years)), and therefore the composition of the present invention can be used as a composition for preventing and / or improving at least one condition selected from the group consisting of locomotive syndrome, sarcopenia, and frailty. In particular, the composition of the present invention is preferably used as a composition for preventing and / or improving sarcopenia.

[0055] The composition of the present invention can be used for middle-aged and elderly people who feel the decline of the lower body. Furthermore, the composition of the present invention contains a plant processed product containing diosgenin that can be used as a food, and 3-hydroxyisovaleric acid or its salt or a derivative thereof as active ingredients, and has no or very few side effects.

[0056] The disclosures of all patent and non-patent publications cited herein are hereby incorporated by reference in their entirety.

[0057] In addition, in this specification, the term "comprising" includes "consisting essentially of" and "consisting of." In addition, the present invention includes all arbitrary combinations of the constituent elements described in this specification.

[0058] Furthermore, the various characteristics (properties, structures, functions, etc.) described in each embodiment of the present invention above may be combined in any way to specify the subject matter included in the present invention. In other words, the present invention includes all subject matter consisting of all combinations of the combinable characteristics described in this specification.

[0059] In addition, in each of the above-mentioned embodiments of the present invention, the composition of the present invention is described as a composition containing a plant treatment product containing diosgenin and 3-hydroxyisovaleric acid or a salt thereof, or a derivative thereof, but the composition of the present invention may also be a composition containing diosgenin and 3-hydroxyisovaleric acid or a salt thereof, or a derivative thereof. EXAMPLES

[0060] The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

[0061] Test Example 1 <Test Method> Animals used: Mouse, C57BL / 6J, male (Charles River Biosciences Japan) Young (3 months old), middle-aged (10 months old), elderly (22 months old) (at time of delivery: 11-12 weeks old, 41-42 weeks old, 93-94 weeks old) Experimental diet The test substances were mixed in the following proportions with the AIN-93M standard sample for mice and rats (Oriental Yeast Co., Ltd.) as the basic composition. The amount of cornstarch was reduced from the AIN-93M when mixing. The composition is shown in Table 1. The test substances in Table 1 are as follows: HMB-Ca:TSI Inc. Geopower 15 (registered trademark): Anti-Aging Pro Co., Ltd. (Contains approximately 15% by mass of diosgenin.)

[0062] [Table 1]

[0063] ·Group composition

[0064] [Table 2]

[0065] Testing Method During the breeding period, the animals were individually housed with free access to food and water. After acclimation, the animals were divided into groups based on their body weight and muscle strength. The animals were fed the specified diet for 12 weeks. Muscle strength was measured at 0, 4, 8, and 12 weeks.

[0066] Grip strength measurement Muscle strength was measured using a small animal grip strength device (Nidec Drive Technology Co., Ltd., Nidec SHIMPO FGP-5) at 0, 4, 8, and 12 weeks. The mouse's tail was held in the hand, and the forelimbs were grabbed and pulled by the measuring bar of the device to measure maximum grip strength. In principle, measurements were taken five times in a row, and the average of the measured values ​​was regarded as muscle strength.

[0067] ·Statistical analysis The values ​​of each measurement item were expressed as the mean (Mean) ± standard deviation (SD). For each evaluation item, the difference between the CON group and the DH group at each time point for each age was analyzed by unpaired t-test. The young mouse group was treated as a reference value. The significance level was set at 5%. Data was collected using Microsoft Excel (registered trademark) 2010 (Microsoft Japan Co., Ltd.). EXSUS 10.0 (CAC Exicare Co., Ltd.) was used as the statistical analysis software.

[0068] <Test Results> The results of grip strength measurements during the test period are shown in Figure 1.

[0069] In middle-aged and aged mice, compared to the control group, administration of diet containing diosgenin and HMB significantly increased muscle strength at 12 weeks (p<0.05), and muscle strength per body weight tended to increase (p=0.06). No difference was observed between the groups in aged mice.

[0070] Test Example 2 <Test Method> ·subject When recruiting subjects, a telephone interview survey was conducted for registered volunteers, and a pre-test (SCR) was conducted on 139 people who met the inclusion criteria, did not violate the exclusion criteria, and were judged by the principal investigator to be appropriate for participation in the study. From these, 40 people were selected in accordance with the subject selection criteria to become subjects for this study. Informed consent was obtained for each subject before the pre-test.

[0071] The inclusion criteria were as follows: 1) Men and women aged 50 to 65 years at the time of obtaining consent to participate in the study; 2) Healthy individuals with no chronic physical illnesses; 3) Individuals who do not have an exercise habit on a daily basis and who feel that their motor functions are declining; 4) Individuals who have been fully informed of the purpose and content of the study, who have the capacity to consent, who have a good understanding of the study and who voluntarily volunteer to participate, and who can give written consent to participate in the study; 5) Individuals who are able to come to the facility on the designated examination date and undergo the examination; 6) Individuals who the principal investigator deems appropriate to participate in the study.

[0072] The exclusion criteria were as follows: 1) individuals who may have an allergic reaction to yam; 2) individuals who have difficulty performing the designated exercises at home during the study period; 3) individuals who are undergoing drug treatment for any disease; 4) individuals with a history or current illness of mental illness, sleep disorder, hypertension, diabetes, dyslipidemia, or other serious illness; 5) individuals with a history or current illness of serious illness involving the liver, kidneys, heart, lungs, blood, etc.; 6) individuals with a history or current illness of serious comorbidities in the digestive organs; 7) individuals with a history or current illness related to heart disease, or individuals with abnormalities in electrocardiograms; 8) individuals who have taken medication for the purpose of treating illness in the past month (excluding those who have taken medication for headaches, menstrual pain, colds, etc.); 9) individuals who may have a serious allergic reaction to food or medicine; 10) individuals with a BMI of 30 kg / m 2 11) Individuals who have donated more than 200 ml of blood in the past month, or more than 400 ml in the past three months; 12) Individuals who have a habit of continuously consuming functional foods, health foods, supplements, or beverages (however, this does not apply to individuals who are able to suspend consumption during the study period at the time of obtaining consent), or individuals who plan to consume such foods during the study period; 13) Individuals who exercise regularly, work in sales, or work outside the home a lot; 14) Individuals whose daily alcohol intake exceeds 60 g / day in pure alcohol equivalent; 15) Individuals who may undergo significant changes in their lifestyle during the study period, such as long-term business trips or travel; 16) Individuals who are pregnant, breastfeeding, or may be pregnant; 17) Individuals who are currently participating in other human clinical research, or who have participated in other human clinical research within the past three months; 18) Individuals who, or whose family members, work for a company that develops, manufactures, or sells health or functional foods; 19) Other individuals who the principal investigator deems inappropriate to be subjects of this study

[0073] Testing process The study was designed as a randomized, double-blind, placebo-controlled, parallel-group comparative study. A telephone interview survey was conducted on registered volunteers for the clinical trial at the time of subject recruitment, and 139 people were subjected to a pre-test (SCR). From among those who met the inclusion criteria, did not violate the exclusion criteria, and were deemed appropriate for study participation by the principal investigator, 40 people were selected for this study according to the selection criteria. After that, they were randomly assigned to two groups, 20 people per group, using a stratified block randomization method. The subjects were instructed to consume the test food and perform mild exercise once every two days for 12 weeks, and tests were conducted five times at the facility, including a pre-test, before intake, 4 weeks after intake, 8 weeks after intake, and 12 weeks after intake (Figure 2).

[0074] Test Food The ingredients and amounts of the test food (food containing yam extract + HMB-Ca) and placebo food (food not containing yam extract + HMB-Ca) are shown in Table 3. Subjects were asked to take one packet (3g) as is, or dissolve it in water or lukewarm water, three times a day.

[0075] [Table 3]

[0076] Exercise load at home From the pre-intake test (Visit-1) to the 12-week post-intake test (Visit-4), the following exercise routine was performed once every two days for the specified amount of exercise. -From before intake (Visit-1) to 4 weeks after intake (Visit-2) 1. Air chair: 5 sets of 30 seconds 2. Leg raises: 5 sets of 5 repetitions (10 seconds each) 3. Squats: 5 sets of 10 -From 4 weeks after intake (Visit-2) to 8 weeks after intake (Visit-3) 1. Air chair: 5 sets of 45 seconds 2. Leg raises: 7 repetitions (10 seconds per repetition) for 5 sets 3. Squats: 5 sets of 15 -From 8 weeks after intake (Visit-3) to 12 weeks after intake (Visit-4) 1. Air chair: 5 sets of 60 seconds 2. Leg raises: 10 repetitions (10 seconds per repetition) for 5 sets 3. Squats: 5 sets of 20

[0077] Evaluation items -Five-time standing test The chair was 42cm high, and the subject was asked to sit on the chair with both legs spread to shoulder width and both arms folded in front of the chest. After the command "Ready," the subject stood in a standing position with the trunk and both knees fully extended at the command "Go," and quickly returned to a sitting position. The time it took to complete the fifth standing attempt was measured. Measurements were taken twice as actual measurements after one or two practice sessions. The measured value was the measurement time (seconds), and the average of the two measurements was used.

[0078] ·Statistical analysis method The test results were compiled in a cumulative table using Microsoft Office Excel (registered trademark) 2016 (Microsoft Japan Co., Ltd.), and the average, standard deviation, standard error, maximum value, and minimum value were calculated as basic statistics. The values ​​used in the analysis were the actual measured values ​​and the changes from before intake. Statistical analysis was performed using appropriate statistical analysis software such as SAS (registered trademark) (SAS 9.4) or SPSS (registered trademark) (Statistics26), and the significance level for all tests was set at 5% on both sides, with a trend of 10%. p values ​​were rounded off to the fifth decimal place and displayed to the fourth decimal place. When the calculated data was listed in a table or graphed, it was shown as the average ± standard error.

[0079] The data was statistically analyzed using unpaired t-tests to compare the test food intake group and the placebo food intake group at each examination. For unpaired t-tests, p-values ​​assuming equal variance were used.

[0080] <Test Results> Figure 3 shows the measurement results of the 5-times-standing test throughout the entire test period. Figure 4 shows the measurement results of subjects in their 50s when stratified analysis was performed for subjects in their 50s and 60s. The actual values ​​in Figures 3 and 4 represent the time (seconds) required to complete the 5-times-standing test. The amount of change represents the difference between the actual value (seconds) after ingestion and the actual value (seconds) before ingestion (at the start). The rate of change represents the ratio of the actual value (seconds) after ingestion to the actual value (seconds) before ingestion (at the start). For all of the actual values, amount of change, and rate of change, the lower the value, the more enhanced motor function is.

[0081] As a result, the overall analysis (Figure 3) showed no significant differences between the groups in the 5-stand test. However, the actual measured values, changes, and rates of change were all lower in the test food group than in the placebo food group.

[0082] Additionally, in the results of stratified analysis of subjects in their 50s (17 subjects in each group) (Figure 4), the test food group showed significantly lower values ​​(enhanced motor function) in the amount of change in the 5-stand test compared to the placebo food group after 4 weeks of ingestion. Furthermore, a trend toward lower values ​​(enhanced motor function) was observed after 8 and 12 weeks of ingestion. The test food group showed significantly lower values ​​(enhanced motor function) in the rate of change in the 5-stand test compared to the placebo food group after 4 and 12 weeks of ingestion. Furthermore, a trend toward lower values ​​(enhanced motor function) was observed after 8 weeks of ingestion.

[0083] The number of subjects in their 60s was small, at three in each group, and was not sufficient for analysis. The reason for the small number of subjects in their 60s is that, due to the nature of the age group, there are few eligible subjects (healthy people who do not have exercise habits), and it is difficult to recruit them as study participants, due to limitations in the study design.

[0084] From the above, it was found that the motor function of subjects (especially those under 60 years of age) could be enhanced by taking diosgenin and 3-hydroxyisovaleric acid.

Claims

1. A composition comprising a plant treatment containing diosgenin and 3-hydroxyisovaleric acid or a salt thereof or a derivative thereof.

2. The composition of claim 1 , wherein the plant treatment is a yam extract.

3. 3. The composition according to claim 1, wherein the 3-hydroxyisovaleric acid or a salt thereof or a derivative thereof is a calcium salt of 3-hydroxyisovaleric acid.

4. 3. The composition according to claim 1, wherein the mixing ratio of diosgenin to 3-hydroxyisovaleric acid or a salt thereof or a derivative thereof is 1:1.5 or more by mass.

5. The composition according to claim 1, which is for increasing muscle strength.

6. The composition according to claim 1, which is for enhancing motor function.

7. 7. The composition of claim 5 or 6, for administration to a subject under 60 years of age.

8. The composition according to claim 1 or 2, which is for preventing and / or improving at least one selected from the group consisting of locomotive syndrome, sarcopenia and frailty.

9. The composition according to claim 1 or 2, wherein the composition is a pharmaceutical composition, a food composition or a supplement.

Citation Information

Patent Citations

  • Food containing treated product derived from dioscorea esculenta

    JP2007274985A

  • Anti-fatigue agent

    WO2008123417A1