Exercise capacity improvement composition
Patent Information
- Application Number
- JP2024172091
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2019-03-29
- Filing Date
- 2024-10-01
- Publication Date
- 2025-01-07
- Estimated Expiration
- 2040-03-13
AI Technical Summary
【0010】 本発明は、運動能力の向上に寄与する、新規の組成物を提供することができる。
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Figure 2025000875000001_ABST
Abstract
Description
[Technical field]
[0001] The present invention relates to an orally ingestible composition for improving athletic performance, and an orally ingestible composition for growing Bacteroides uniformis, which may contribute to improving athletic performance. [Background technology]
[0002] Normally, when working or exercising, one needs at least enough physical strength to endure these activities. However, these activities cause fatigue to accumulate in the body, and the body's functions decline. In order to work, exercise, and other activities on a daily basis, it can be said that maintaining and improving physical strength and preventing and recovering from fatigue are essential. Physical fitness for activities such as work and exercise includes the physical abilities that form the basis of such actions, such as muscle strength, endurance, and flexibility.
[0003] Compositions for enhancing endurance, preventing or recovering from fatigue, or for strengthening the body have been developed. For example, Patent Document 1 describes a composition for enhancing endurance, preventing or recovering from fatigue, or for strengthening the body, which contains thioctic acids as an active ingredient. Patent Document 2 describes a basal metabolism enhancer that contains thioctic acids as an active ingredient and acts to prevent or quickly recover from fatigue and improve motivation to be active. It is also described that the compositions of Patent Documents 1 and 2 may contain cyclodextrin, which is generally used as an inclusion material, as an inclusion material for the active ingredient.
[0004] Cyclodextrin is also called cyclic oligosaccharide, and has a structure in which glucose is linked in a ring. A cyclodextrin with six glucose molecules bound is called α-cyclodextrin, a cyclodextrin with seven glucose molecules bound is called β-cyclodextrin, and a cyclodextrin with eight glucose molecules bound is called γ-cyclodextrin. α-cyclodextrin has a property of incorporating other molecules into the internal cavity (inclusion action), and this property is utilized to generally use it as a stabilizer or emulsifier in foods. And, regarding α-cyclodextrin, it has been recently announced in Non-Patent Document 1 that by feeding α-cyclodextrin to obese mice fed a high-fat diet, the decrease in the number of Bacteroides, Bifidobacterium, Lactobacillus, and total bacteria in the intestines of the mice is suppressed, the intestinal microflora is maintained, and as a result, fat accumulation can be reduced. However, Non-Patent Document 1 does not mention any species or strains that are lower than the taxonomic genera. [Prior art documents] [Patent documents]
[0005] [Patent Document 1] JP 2007-131609 A [Patent Document 2] JP 2007-308468 A [Non-patent literature]
[0006] [Non-Patent Document 1] BioFactors 2018,Volume44,Issue4,336-347 Summary of the Invention [Problem to be solved by the invention]
[0007] An object of the present invention is to provide a novel composition that can contribute to improving athletic performance. [Means for solving the problem]
[0008] The present inventors have found that the intake of Bacteroides uniformis has a sustained effect of improving physical strength and / or anti-fatigue (see International Publication No. 2019 / 069735 (PCT / JP2018 / 035295) (an international publication that was unpublished at the time of filing the basic application of this international application (Patent Application No. 2019-067,505)). Based on this knowledge, the present inventors thought that Bacteroides uniformis, known as a type of bacteria that constitutes the intestinal flora, might be one factor that brings about a physical strength improving effect and / or anti-fatigue effect. As a result of intensive research, it was unexpectedly confirmed that the number of Bacteroides uniformis in the intestine was increased in a test group of humans who had taken α-cyclodextrin, and that their athletic ability was improved. As a result of such research, the present invention was completed.
[0009] That is, the present invention is configured as follows: [1] to [8]. [1] A composition for improving athletic performance, comprising α-cyclodextrin as an active ingredient. [2] The composition described in [1] above, wherein the improvement of athletic ability includes at least one effect selected from improving physical strength, anti-fatigue, and reducing fatigue. [3] The composition described in [1] above, wherein the improvement of athletic ability includes suppressing an increase in heart rate during exercise. [4] A composition for the proliferation of intestinal Bacteroides uniformis, comprising α-cyclodextrin as an active ingredient. [5] The composition according to any one of [1] to [4] above, which is for oral intake. [6] The composition according to any one of the above [1] to [4], which is a food or drink additive, a pharmaceutical composition, a feed composition, or a feed additive. [7] The composition according to any one of [1] to [6] above, wherein α-cyclodextrin is administered in an amount of 0.01 mg / kg body weight to 200 mg / kg body weight per day. [8] The composition according to any one of [1] to [7] above, which is administered for at least 7 days. Effect of the Invention
[0010] The present invention can provide a novel composition that contributes to improving athletic performance. [Brief description of the drawings]
[0011] [Figure 1] FIG. 1 shows the change in the number of Bacteroides uniformis in the intestinal tract of subjects before and after 8 weeks of ingestion of the test food in Example 1. [Diagram 2] In Example 2, subjects were subjected to exercise load using an exercise bike (registered trademark) before, 4 weeks after, and 8 weeks after the intake of the test food, and a VAS (Visual Analogue Scale) questionnaire was administered regarding fatigue immediately after the exercise, 30 minutes after the exercise, and 60 minutes after the exercise, and the graph shows the change in general fatigue over time. A significant difference test for general fatigue between the placebo group and the α-cyclodextrin (αCD) intake group was performed using Student's t-test. [Diagram 3] In Example 3, the subjects were given a spin cycle before, 4 weeks after, and 8 weeks after the intake of the test food, and after the exercise of the fatigue reduction test and after a 60-minute rest, the time was measured when they pedaled 10 km. This is a diagram summarizing the changes in exercise performance due to the intake of α-cyclodextrin (αCD). The significant difference between the placebo group and the α-cyclodextrin (αCD) intake group was tested using Student's t-test. In addition, the significant difference was examined by a paired t-test for comparisons between before the intake of α-cyclodextrin (αCD) and after 4 and 8 weeks of intake of α-cyclodextrin (αCD). [Figure 4]In Example 4, subjects were given an exercise load test (load intensity: 50 minutes at 55% of the maximum exercise load intensity for each subject) using an exercise bike (Konami Sports & Life Co., Ltd., model number AEROBIKE-75XLIII) before, 4 weeks after, and 8 weeks after taking the test food. The graph shows the changes in average heart rate in the 10 minutes immediately before the end of exercise compared to before taking the food, 4 weeks after and 8 weeks after taking the food. Analysis of covariance (ANCOVA) was used to test for significant differences between the placebo group and the α-cyclodextrin (αCD) group, with the value before taking the food as a covariate (*: p<0.05). [Diagram 5] In Example 5, subjects were subjected to exercise load using an exercise bike (registered trademark) before and 8 weeks after ingestion of the test food, and a VAS (Visual Analogue Scale) questionnaire was administered regarding fatigue immediately after the load, 30 minutes after the load, and 60 minutes after the load, and the graph shows the change in general fatigue over time. A significant difference test for general fatigue between the placebo group and the α-cyclodextrin (αCD) intake group was performed using Student's t-test. [Figure 6] In Example 6, the subjects were measured for their time when pedaling 10 km on a spin cycle before and after 8 weeks of ingestion of the test food, after the exercise in the fatigue reduction test in Example 5, and after a 60-minute rest, and this is a diagram summarizing the changes in exercise performance due to α-cyclodextrin (αCD) ingestion. Analysis of covariance (ANCOVA) was used to test for significant differences between the placebo group and the α-cyclodextrin (αCD) ingestion group, with the values before ingestion as covariates. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0012] <Composition for improving athletic performance> The present invention relates to a composition containing α-cyclodextrin (αCD) and having an athletic performance enhancing effect. In the present invention, the term "athletic performance enhancing effect" refers to at least one effect selected from "physical strength enhancing effect," "fatigue reduction," "anti-fatigue," "fatigue resistance enhancing effect," and "inhibition of an increase in heart rate during exercise." α-Cyclodextrin is a non-reducing oligosaccharide that has a cyclic structure and is used as a compound with an inclusion function that incorporates various substances, such as functional ingredients in foods, into its cavity. Specifically, the inclusion function of α-cyclodextrin is usually used to encapsulate hydrophobic molecules to increase their solubility in water, but it is also used to stabilize substances that are prone to react with volatile components, ultraviolet rays, heat, oxygen, etc., by inclusion. In the present invention, a composition using α-cyclodextrin alone as an active ingredient can significantly improve the athletic performance enhancing effect. The effects that α-cyclodextrin alone can bring about have not been very clear so far. The α-cyclodextrin in the present invention is not particularly limited, but can be obtained, for example, by allowing starch to undergo the action of a cyclodextrin-forming enzyme (cyclodextrin glucanotransferase). In addition, commercially available products can be used as appropriate.
[0013] In the present invention, "physical strength" refers to the physical ability that is the basis of actions that enable one to perform activities such as labor and exercise, and in particular refers to the bodily strength that enables one to endure activities such as labor and exercise and to continue performing them. More preferably, "physical strength" refers to one or more of whole body endurance and aerobic exercise endurance that enables one to continue performing aerobic exercise. "Whole body endurance" refers to the ability to move the body for a long period of time, which is generally called stamina.
[0014] In the present invention, "improving physical strength" means one or more of improving physical strength and promoting recovery, particularly means one or more of improving the physical strength that enables one to endure and continue activities such as labor and exercise, and promoting the recovery of said physical strength, and more preferably means one or more selected from the group consisting of improving one or more of whole body endurance and aerobic exercise endurance, and promoting the recovery of one or more of whole body endurance and aerobic exercise endurance. Indicators of whole body endurance and aerobic exercise endurance are not limited, but for example, maximum oxygen intake and the results of a time trial using a fitness bike can be used.
[0015] In the present invention, "fatigue" refers to a decrease in bodily function as a result of continued activity such as labor or exercise. In the present invention, "fatigue" refers to a subjective sensation of being fatigued, which is often accompanied by discomfort and a decreased will to be active. The general malaise, lethargy, and weakness experienced in various illnesses are used almost synonymously with "fatigue."
[0016] In the present invention, "anti-fatigue" and "improving fatigue resistance" are synonymous and mean one or more of reducing fatigue, promoting recovery from fatigue, and preventing fatigue, and preferably mean reducing the decline in physical function that occurs as a result of continued activities such as labor or exercise, promoting recovery from the decline in physical function, or preventing the decline in physical function to create a state in which the decline in physical function is less likely to occur. Although not limited thereto, "anti-fatigue" and "fatigue resistance improving effect" can be evaluated, for example, by a VAS questionnaire, a time trial using a fitness bike, maximum oxygen intake, etc. In the present invention, "reducing fatigue" means one or more of the following: reducing the sense of awareness of the presence of fatigue, reducing discomfort and / or decreased motivation to be active that occurs as a result of continued activity such as labor or exercise, promoting recovery from the discomfort and / or decreased motivation to be active, and preventing the discomfort and / or decreased motivation to be active. Although not limited thereto, the "fatigue reducing effect" can be evaluated, for example, by a VAS questionnaire.
[0017] In the present invention, the "heart rate during exercise" refers to the average number of heart beats per minute (bpm) during a certain period of time during an activity such as labor or exercise of a certain intensity. The "heart rate during exercise" is also used to calculate the exercise intensity of humans. For example, it is common to set the "heart rate during exercise" at 50-80% of the maximum heart rate (the fastest heart rate for each individual) as a barometer for building a healthy body, and the heart rate during exercise is linked to the exercise load that each subject receives through exercise. For this reason, as the subject's heart rate during exercise increases, the exercise load that the subject receives increases, and the discomfort that the subject feels during exercise also increases. In the present invention, "suppression of increase in heart rate during exercise" means, for example, that the heart rate during exercise of a subject who has received an exercise load of a certain intensity does not increase compared to the heart rate during exercise of the same subject who has received the same exercise load in the past, that is, it is kept low. A subject whose heart rate increase during exercise is suppressed means that the physical strength of the subject has improved, and the same exercise intensity for the subject has substantially decreased compared to before, and therefore the discomfort felt during exercise is also reduced. Therefore, for example, when the increase in heart rate of a subject during exercise of a certain intensity is suppressed, the subject can perform the same intensity of exercise more lightly and refreshingly, and can easily continue activities such as labor and exercise. This makes it easier for the subject to make exercise a habit and improves the enjoyment of exercise. An indicator of "suppression of heart rate during exercise" is not limited, but for example, a record of the heart rate during an exercise load test of a certain intensity can be used.
[0018] The amount of α-cyclodextrin contained in the composition of the present invention may vary depending on the dosage form or shape of the composition, but can usually be selected from the range of 1 to 100% by mass, preferably 7 to 47% by mass, and more preferably 17 to 37% by mass relative to the composition. For example, when the composition of the present invention is molded into a tablet form with a total weight of 250 mg, the amount of α-cyclodextrin contained in one tablet can be selected from the range of 2.5 to 250 mg, preferably 17.5 to 117.5 mg, and more preferably 42.5 to 92.5 mg.
[0019] The subject (subject) to which the composition of the present invention is administered or ingested may be a mammal (e.g., human, primate (monkey, chimpanzee, etc.), livestock (cow, horse, pig, sheep, etc.), pet (dog, cat, etc.), laboratory animal (mouse, rat, etc.)), bird, reptile, etc. that requires one or more of the effects of improving physical strength, reducing fatigue, and anti-fatigue. However, preferred is a mammal, and particularly preferred is a human. In the present invention, the present invention can improve the athletic ability of not only subjects (e.g., humans) who do not have exercise habits, but also humans who have certain exercise habits. For example, the subject may be a human who exercises at an intensity of 5 METs or more for 30 minutes or more once a week or more. The athletic ability of such subjects who have moderate exercise habits can also be improved. In addition, the present invention can improve fatigue resistance during and / or after moderate to high intensity exercise such as walking, jogging, running, marathon, swimming, cycling, aerobics, tennis, soccer, skiing, and skating, and / or reduce fatigue, thereby suppressing fatigue accumulation. Note that METs (metabolic equivalent of task) is an index of exercise intensity, and 1 MET is equivalent to an oxygen intake of 3.5 ml / kg body weight / min, which is the oxygen demand required for the body to function at rest.
[0020] The dosage or intake of the composition of the present invention may vary depending on factors such as the age and body weight of the subject, the route of administration, the number of administrations or intakes, and one or more of the levels of physical strength and fatigue, and any dosage or intake may be adopted. For example, when administered or taken orally, the intake amount of α-cyclodextrin is 0.01 mg / kg body weight or more, preferably 0.1 mg / kg body weight or more, more preferably 1 mg / kg body weight or more per day, and may be administered or taken in an amount of 200 mg / kg body weight or less, preferably 50 mg / kg body weight or less, more preferably 20 mg / kg body weight or less, or 10 mg / kg body weight or less, once or in multiple doses (e.g., 2 to 5 times, preferably 2 to 3 times).
[0021] The composition of the present invention can be effective in a small amount and in a short period of time, but tends to be more effective when administered or taken for a long period of time.The composition of the present invention can be confirmed to have an athletic ability improving effect by administering or taking it for at least 7 days, but it is more preferable to continuously administer or take the composition of the present invention for 14 days or more, 1 month or more, 2 months or more, 6 months or more, 1 year or more, or more, according to the above-mentioned dosage and administration.
[0022] The composition of the present invention has an athletic ability improving effect. Specifically, the composition of the present invention can provide one or more of the following effects in a subject to which the composition is administered or ingested, compared to a case where the composition is not administered or ingested: improving and recovering physical strength, particularly improving the physical strength that allows the subject to endure and continue to perform labor or exercise, and promoting the recovery of the physical strength; more preferably, improving one or more of the endurance during aerobic exercise and promoting the recovery of one or more of the endurance during aerobic exercise. In addition, the composition of the present invention can provide one or more of the following effects in a subject to which the composition is administered or ingested, compared to a case where the composition is not administered or ingested: reducing fatigue, promoting the recovery of fatigue, and preventing fatigue; preferably reducing the decline in physical function resulting from continued activities such as labor or exercise, promoting the recovery of the decline in physical function, and preventing the decline in physical function to make the decline in physical function less likely to occur. Furthermore, the composition of the present invention can provide one or more of the following effects in a subject to which the composition is administered or ingested: reducing fatigue and reducing the sense of awareness of the presence of fatigue, preferably reducing discomfort and / or decreased motivation to do activities resulting from continued activities such as labor or exercise, promoting recovery from said discomfort and / or decreased motivation to do activities, and preventing said discomfort and / or decreased motivation to do activities. Furthermore, the composition of the present invention can provide one or more of the following effects in a subject to which the composition is administered or ingested: suppressing an increase in heart rate during exercise, exercising more lightly and refreshingly, easily continuing activities such as labor or exercise, making it easier for the subject to make exercise a habit, and / or improving the enjoyment of exercise, compared to a subject to which the composition is not administered or ingested. Based on these effects, the composition of the present invention has efficacy and effects in nutritional supplementation in cases of nourishment and strengthening, frail constitution, physical fatigue, etc.
[0023] <Composition for the proliferation of intestinal Bacteroides uniformis> The present invention also relates to a composition for growing Bacteroides uniformis in the intestine, comprising α-cyclodextrin. A subject who has been ingested or administered α-cyclodextrin has a significant increase in the number of Bacteroides uniformis in the intestine compared to before the ingestion. In addition, a subject who has been ingested or administered α-cyclodextrin has improved athletic performance. Therefore, it is considered that one of the reasons why athletic performance can be improved is that the number of Bacteroides uniformis in the intestine is increased by the ingestion or administration of the composition of the present invention. Here, since the intestinal flora is extremely complex and consists of an exquisite balance of bacterial composition, even if a system capable of growing Bacteroides uniformis alone in vitro is established, it cannot be said that it can be simply applied to Bacteroides uniformis in the intestinal flora as it is. It has been confirmed that the composition according to the present invention can actually significantly increase the number of Bacteroides uniformis in the intestinal tract of a mammal when ingested or administered to the body of the mammal.
[0024] The "Bacteroides uniformis" in the present invention is known and can be characterized based on the known bacteriological properties described in, for example, Burgess Manual of Bacteriology Vol. 4 (1989). Bacteroides uniformis is an anaerobic gram-negative bacillus having a size of about 0.8 x 1.5 μm, which does not form spores and has no motility. Bacteroides uniformis is a eubacterium that is normally present in the intestines of many mammals, including humans. The "Bacteroides uniformis" that can be grown in the present invention is a strain found in the intestinal tract of mammals (e.g., humans, monkeys, chimpanzees, cows, horses, pigs, sheep, dogs, cats, mice, rats, etc.), preferably humans.
[0025] The composition of the present invention can increase any strain classified as Bacteroides uniformis. The Bacteroides uniformis to be increased may be a Bacteroides uniformis strain present in the intestinal tract of a subject who ingests the composition of the present invention, or may be a Bacteroides uniformis strain ingested from the outside by the subject. The Bacteroides uniformis strain to be ingested from the outside is not particularly limited as long as it is a Bacteroides uniformis strain, and examples thereof include the ATCC8492 strain, CCUG4942 strain, CIP103695 strain, DSM6597 strain, NCTC13054 strain, JCM5828 strain, CP3585 strain, and CP3586 strain. The JCM5828 strain, CP3585 strain, and CP3586 strain are preferred. The JCM5828 strain is a type strain registered and preserved at the Microbial Materials Development Division of the RIKEN BioResource Center (3-1-1 Takanodai, Tsukuba, Ibaraki, 305-0074, Japan). The CP3585 and CP3586 strains were internationally deposited on August 25, 2017 at the National Institute of Technology and Evaluation, Patent Microorganism Depositary (Room 122, 2-5-8 Kazusa Kamatari, Kisarazu, Chiba, 292-0818, Japan) under the accession numbers NITEBP-02536 and NITEBP-02537.
[0026] Intestinal Bacteroides uniformis can be isolated and confirmed according to known methods (Paola Gauffin Canoetal, PLoS One. July 2012, Volume 7, Issue 7, e41079). That is, feces, fecal matter, or faeces of a mammal are diluted in an appropriate solvent, plated on a plate medium, cultured under anaerobic conditions, and bacteria are picked from the colonies that appear on the medium. The medium can be one described in detail below, but it is preferable to use a selective isolation medium that can differentiate and select Bacteroides from the perspective of isolation efficiency (Jap. J. Vet. Sci., 36, 93-98 (1974)). After confirming that the obtained bacteria are gram-negative rods by gram staining and microscopy, Bacteroides uniformis can be identified and cloned by analyzing the selected bacteria based on the base sequence of the 16S rRNA gene. The nucleotide sequence of the 16S rRNA gene of Bacteroides uniformis is known and is disclosed in known databases such as GenBank, and is registered under the numbers NR_040866, AB050110, AB510711, and L16486. When analyzing the 16S rRNA gene, this sequence information can be used. Analysis and identification of the 16S rRNA gene can be performed based on known techniques such as quantitative PCR, DGGE / TGGE, FISH, 16S rDNA cloning library, T-RFLP, FISH-FCM, and base sequencing (Biochemistry. Vol. 80, No. 5, pp. 421-425, 2008; J Nutr. Feb. 2004; 134(2): 465-72; Appl. Environ. Microbiol. 64. 3336-3345. 1998; Appl. Environ. Microbiol., 65, 4799-4807, 1999; Appl. Environ. Microbiol., 62, 2273-2278, 1996; Appl. Environ. Microbiol., 64, 3854-3859, 1998).
[0027] For example, in the quantitative PCR method, primers specific to the bacterium are prepared based on the known base sequence information of the 16S rRNA gene of Bacteroides uniformis. A PCR reaction is performed using the primers and DNA extracted from the selected bacterium as a template, and it is possible to determine whether the bacterium is Bacteroides uniformis or not based on the presence or absence of a PCR amplification product of the intended size. The design of specific primers and the determination of PCR conditions can be performed according to standard methods (Bio Experiment Illustrated 3: Truly Increasing PCR: Cell Engineering Appendix, Experimental Notes Series Seen with the Eyes; Hiroki Nakayama, Shujunsha Co., Ltd.).
[0028] <Optional Additives> The composition of the present invention may contain, together with α-cyclodextrin, additives commonly used in the manufacture of pharmaceuticals, foods and beverages, such as excipients, lubricants, binders, disintegrants, etc., and may be manufactured into a dosage form or shape suitable for the intended administration route or ingestion method.
[0029] Examples of excipients include lactose, sucrose, D-mannitol, D-sorbitol, starch, pregelatinized starch, dextrin, glucose, corn starch, crystalline cellulose, low-substituted hydroxypropyl cellulose, sodium carboxymethylcellulose, gum arabic, pullulan, light anhydrous silicic acid, synthetic aluminum silicate, and magnesium aluminometasilicate.
[0030] Examples of lubricants include sugar esters such as sucrose fatty acid esters and glycerin fatty acid esters, calcium stearate, magnesium stearate, stearic acid, stearyl alcohol, hardened oils such as powdered vegetable oils and fats, waxes such as white beeswax, talc, silicic acid, silicon, and the like.
[0031] Examples of binders include pregelatinized starch, sucrose, gelatin, gum arabic, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, crystalline cellulose, sucrose, D-mannitol, trehalose, dextrin, pullulan, hydroxypropylcellulose, hydroxypropylmethylcellulose, and polyvinylpyrrolidone.
[0032] Disintegrants that can be used include lactose, sucrose, starch, carboxymethylcellulose, filtration, salting out, solvent precipitation, solvent extraction, distillation, immunoprecipitation, polyacrylamide gel electrophoresis, isoelectric focusing, dialysis, recrystallization, and the like, which may be appropriately selected and combined.
[0033] Examples of additives that can be used in the composition of the present invention and are commonly used in the manufacture of medicines, foods, and beverages include various oils and fats (e.g., vegetable oils such as soybean oil, corn oil, safflower oil, and olive oil, and animal oils and fats such as beef tallow and sardine oil), herbal medicines (e.g., royal jelly, ginseng, etc.), amino acids (e.g., glutamine, cysteine, leucine, arginine, etc.), polyhydric alcohols (e.g., ethylene glycol, polyethylene glycol, propylene glycol, glycerin, sugar alcohols such as sorbitol, erythritol, xylitol, maltitol, mannitol, etc.), natural polymers (e.g., gum arabic, agar, water-soluble corn fiber, gelatin, etc.), and the like. Examples of suitable surfactants include glycerin, xanthan gum, casein, gluten or gluten hydrolysate, lecithin, starch, dextrin, etc.), vitamins (e.g. vitamin C, B vitamins, etc.), minerals (e.g. calcium, magnesium, zinc, iron, etc.), dietary fiber (e.g. mannan, pectin, hemicellulose, etc.), surfactants (e.g. glycerin fatty acid ester, sorbitan fatty acid ester, etc.), purified water, molding aids (tricalcium phosphate, etc.), flow improvers (tricalcium phosphate, etc.), diluents, stabilizers, isotonicity agents, pH adjusters, buffers, wetting agents, solubilizing agents, suspending agents, colorants, flavorings, odorants, fragrances, antioxidants, sweeteners, taste-providing components, and acidulants.
[0034] <Optional other active ingredients> The composition of the present invention may contain, in addition to the active ingredient α-cyclodextrin, other ingredients known to have one or more of the following effects: improving physical strength, anti-fatigue, and reducing fatigue. Examples of such other ingredients include, but are not limited to, taurine, glutathione, carnitine, creatine, coenzyme Q10, glucuronic acid, glucuronolactone, guarana extract, theanine, γ-aminobutyric acid (GABA), capsaicin, capsiate, allicin, vitamins (vitamins B1, B2, B6, B12, C, E, etc.), various organic acids (citric acid, etc.), flavonoids, polyphenols, catechins, caffeine, etc.
[0035] The composition of the present invention is used for growing Bacteroides uniformis, and may contain Bacteroides uniformis or a processed product thereof as another active ingredient. Bacteroides uniformis usable in the present invention can be cultured and harvested using a normal culture medium and culture conditions that can culture the bacterium.
[0036] The culture medium may be any medium capable of culturing Bacteroides uniformis, and is not particularly limited. For example, the carbon source may include glucose, fructose, galactose, maltose, lactose, cellobiose, sucrose, rhamnose, amygdalin, esculin, salicin, melibiose, trehalose, L-arabinose, ribose, D-xylose, inulin, raffinose, starch, molasses, etc., the nitrogen source may include inorganic ammonium salts such as ammonium sulfate and ammonium nitrate, organic nitrogen-containing substances such as urea, amino acids, meat extract, yeast extract, polypeptone, protein hydrolysates, etc., and the inorganic salts may include magnesium sulfate, potassium dihydrogen phosphate, potassium tartrate, zinc sulfate, magnesium sulfate, copper sulfate, calcium chloride, iron chloride, manganese chloride, etc. Any known culture medium suitable for culturing Bacteroides uniformis (e.g., NBGT medium, BL medium, GAM medium, etc.) may be used. The culture medium is preferably a liquid medium, but agar or gelatin may be added as necessary to form a solid medium or a semi-liquid medium. The culture can be performed under anaerobic conditions at a temperature of 20°C to 50°C, preferably 25°C to 45°C, and more preferably 35°C to 37°C. The "anaerobic conditions" may be a low-oxygen environment that allows Bacteroides uniformis to grow, and the anaerobic conditions can be achieved, for example, by using an anaerobic chamber, an anaerobic box, a sealed container or a culture container containing an oxygen scavenger, or the like.
[0037] The culture can be carried out in any form, such as stationary culture, shaking culture, or tank culture, and the culture time is not particularly limited, but can be, for example, 3 hours to 7 days.
[0038] After the culture, the obtained culture may be used as it is, or Bacteroides uniformis may be purified or roughly purified from the culture and then used.
[0039] Purification or crude purification of the cells from the culture can be carried out by any means, for example, centrifugation, filtration, or the like.
[0040] The Bacteroides uniformis used in the present invention may be in the form of wet or dry cells.
[0041] In the present invention, a processed product of Bacteroides uniformis can also be used. In the present invention, the "processed product" can be, for example, a bacterial cell complex of Bacteroides uniformis. The bacterial cell complex can be obtained by coating Bacteroides uniformis with a coating agent, and can be obtained by a known process. Examples of the coating agent include polysaccharides such as starch, amylose, cellulose, hemilose, mannan, and chitosan, thickening polysaccharides such as gelatin, gellan gum, locust bean gum, carrageenan, furcellan, tamarind, and pectin, and proteins such as casein and skim milk powder.
[0042] The Bacteroides uniformis or a processed product thereof used in the present invention can be used in any form, such as a dried product, a frozen product, a water dispersion, an emulsion, etc. The dried product can be obtained by any drying means, such as spray drying, drum drying, vacuum drying, freeze drying, etc., and can be in the form of a powder, granules, etc.
[0043] <Embodiments of the composition> The dosage form or form of the composition of the present invention is not particularly limited. The pharmaceutical preparation may be in the form of, for example, tablets, capsules, granules, powders, powders, syrups, dry syrups, liquids, suspensions, inhalants, suppositories, etc., but is preferably an oral preparation. Liquid preparations such as liquids and suspensions may be provided in a freeze-dried and storable state, and may be dissolved in a buffer solution containing water or saline solution, etc., and adjusted to an appropriate concentration before use. In addition, those having a solid dosage form such as tablets may be coated as necessary (for example, sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, etc.), or may be prepared into a preparation with controlled release such as a sustained release preparation, delayed release preparation, or immediate release preparation using known techniques.
[0044] Examples of foods and beverages include health foods and beverages (supplements, nutritional supplements, health supplements, nutritionally adjusted foods, etc.) in the form of tablets, chewable tablets, powders, capsules, granules, drinks, etc., soft drinks, tea drinks, jelly drinks, sports drinks, coffee drinks, carbonated drinks, vegetable drinks, fruit juice drinks, fermented vegetable drinks, fermented fruit juice drinks, fermented milk drinks (yogurt, etc.), lactic acid bacteria drinks, milk drinks, powdered drinks, cocoa drinks, sweets (e.g., biscuits, cookies, chocolate, candy, chewing gum, tablets), jellies, etc. (but are not limited to these).
[0045] The food and drink may be a health functional food (specified health food (including conditional specified health food), nutrient functional food, functional food, health food, beauty food, etc.) that contains ingredients that have the effect of improving athletic performance.
[0046] Furthermore, the composition of the present invention can be in the form of not only food and drink for humans, but also feed or feed additives for livestock, racehorses, pets, and the like.
[0047] The following examples are merely illustrative of the subject matter disclosed herein, and they should not be construed in any way as limiting the scope of the disclosed subject matter. EXAMPLES
[0048] The subjects and selection criteria, the composition of the test foods, the test period, and the evaluation items in Examples 1 to 3 were as follows. 1. Subjects and Selection Criteria The subjects were 21 healthy men aged 20 to 49 years who had the habit of exercising for at least 30 minutes at an intensity of 5 METs or more once or twice a week and who were able to continue their exercise habit during the study period. Of the 21 participants, 10 were assigned to the α-cyclodextrin (αCD) group and the remaining 11 to the placebo group. The subjects were not informed of which group they were in. 2. Test Food The test food (tablet) used had the composition shown in Table 1 below. Each tablet of the test food was approximately 250 mg.
[0049] [Table 1] 3. Study period and evaluation items Subjects in the αCD group and placebo group were asked to take three tablets of the above test food once a day at any time of their choice. In other words, subjects in the α-cyclodextrin group were asked to take approximately 200 mg of α-cyclodextrin per day. The test food intake period was 9 weeks, and changes in intestinal flora were evaluated before the start of intake, after 4 weeks, and after 8 weeks of intake, a fatigue questionnaire was administered, and changes in running time were evaluated. During the test period, the subjects were asked to live the same lifestyle as before the test. In addition, foods and beverages that claim to support sports or training, medicines and quasi-drugs whose efficacy includes recovery, prevention, or improvement of "fatigue," "tiredness," "physical strength," and / or "languor," and supplements in general (including functional foods and foods for specified health uses) were prohibited from intake for one week prior to the date of consent to participate in the study and during the test period.
[0050] [Example 1] Test of the effect of α-cyclodextrin on the proliferation of Bacteroides uniformis in the intestinal tract Changes in Bacteroides uniformis in the intestines of the subjects were confirmed. Feces were collected from each subject before and 8 weeks after ingestion of the test food and used for evaluation. DNA was extracted from the collected feces by standard methods, and quantitative PCR (probe method) was performed by standard methods using forward primers, reverse primers, and probes targeting specific sequences in the 16S rDNA sequence region of Bacteroides uniformis, with reference to the descriptions in Anaerobe (2011), 17, 64-68, and Jia Tong et al., to evaluate the absolute number of Bacteroides uniformis in the intestinal tract. Forward primer sequence: 5'-TCTTCCGCATGGTAGAACTATTA-3' (SEQ ID NO: 1) Reverse primer sequence: 5'-ACCGTGTCTCAGTTCCAATGTG-3' (SEQ ID NO: 2) Probe sequence: 5'-CGTTCCATTAGGTTGTTGGCGGGG-3' (SEQ ID NO: 3) The results are shown in Figure 1. In the α-cyclodextrin intake group, the number of Bacteroides uniformis bacteria in the intestine increased by about 2.5 times 8 weeks after intake (8 weeks) compared to before intake (0w). On the other hand, in the placebo group, no statistically significant change was observed in the number of Bacteroides uniformis bacteria before intake and after 8 weeks of intake. Statistical analysis of the number of bacteria before intake and after 8 weeks of intake was performed using Wilcoxon signed-rank test (*: p<0.05).
[0051] [Example 2] Test to reduce fatigue with α-cyclodextrin Before, 4 weeks after, and 8 weeks after the intake of the test food, the subjects were subjected to exercise load (load intensity: 45% of the maximum exercise load intensity for each subject for 50 minutes) using an aero bike (registered trademark) (manufactured by Konami Sports & Life Co., Ltd., model number AEROBIKE-75XLIII). In this embodiment, the maximum exercise load intensity refers to the pedal weight (W) just before exhaustion in a progressive load test conducted in advance, in which the load was increased by 15W per minute. A VAS (Visual Analogue Scale) questionnaire was conducted based on the fatigue VAS test method established by the Japan Society for Fatigue Science to examine the change in fatigue over time regarding fatigue immediately after the load, 30 minutes after the load, and 60 minutes after the load. The items in the questionnaire were "general fatigue," "leg fatigue," "leg stiffness," "general malaise," and "shortness of breath," and the "best condition (0mm)" and "worst condition (100mm)" of each item were based on the criteria shown in Table 2. In each intake group, the changes in the measurements after 4 and 8 weeks of intake were evaluated based on the measurements before intake. The α-cyclodextrin intake group showed a significant decrease in general fatigue after exercise during each intake period compared to the placebo group. The significance test for the general fatigue between the placebo group and the α-cyclodextrin (αCD) intake group was performed using Student's t-test, and the results are summarized in Figure 2 (*: p<0.05). The results for the items "feeling of fatigue in the legs," "leg stiffness," "general malaise," and "shortness of breath" are summarized in Table 3. In Table 3, the significant difference between the values before intake of αCD was examined using a paired t-test, and the significance test for the placebo group and the α-cyclodextrin (αCD) intake group was performed using Student's t-test. As can be seen from Table 3, in the α-cyclodextrin intake group, the scores were significantly lower (i.e., fatigue sensation was reduced) compared to before intake, especially after 8 weeks of intake. It was also suggested that fatigue resistance was improved in the α-cyclodextrin intake group, especially after 8 weeks of intake, compared to before intake.
[0052] [Table 2]
[0053] [Table 3]
[0054] [Example 3] Examination of the improvement of athletic ability by α-cyclodextrin (exercise performance test) In order to evaluate the change in exercise performance due to α-cyclodextrin (αCD) intake, the subjects were measured for their running time when pedaling 10 km using a spin cycle (manufactured by Fujimori Co., Ltd., model number FBS-101) before, 4 weeks after, and 8 weeks after intake of the test food, after the exercise of the fatigue reduction test described in Example 2, and after a 60-minute rest. The load intensity was set to a value that could be set on the spin cycle close to 45% of the maximum exercise load intensity for each subject. After 4 weeks of αCD intake, the time was significantly shorter than the time before intake of the same group, and after 8 weeks of αCD intake, the time was significantly shorter than the time before intake of the same group and the time after 8 weeks of intake of the placebo group. The results are summarized in a graph in Figure 3. Comparisons with before αCD intake were performed using paired t-tests to determine significant differences, and student's t-tests were used to determine significant differences between the placebo group and the α-cyclodextrin (αCD) intake group (*: p<0.05, **p<0.01). The results in Figure 3 show that taking α-cyclodextrin not only reduces fatigue, but also contributes to improving physical strength, particularly overall endurance and endurance during aerobic exercise. The results in Figure 3 also show that taking α-cyclodextrin contributes to improving fatigue resistance. The data from Examples 1 to 3 support the idea that ingestion of α-cyclodextrin contributes to the improvement of athletic ability.
[0055] Next, the subjects and selection criteria, the composition of the test foods, the test period, and the evaluation items in Examples 4 to 6 were as follows. 1. Subjects and Selection Criteria The subjects were 86 healthy men aged 20 to 49 years who had the habit of exercising for at least 30 minutes at an intensity of 5 METs or more once or twice a week and who were able to continue their exercise habit during the study period. Of the 86 participants, 43 were assigned to the α-cyclodextrin (αCD) group and the remaining 43 to the placebo group. The subjects were not informed of which group they were in. 2. Test Food A test food (tablet) having the composition shown in the following Table 4 was used. Each tablet of the test food was about 600 mg.
[0056] [Table 4]
[0057] 3. Study period and evaluation items Subjects in the αCD group and placebo group were asked to take the above test food, four tablets once a day, at any time of their choice. In other words, subjects in the α-cyclodextrin group were asked to take about 1000 mg of α-cyclodextrin per day. The test food intake period was 8 weeks, and heart rate during exercise was measured before intake, 4 weeks after intake, and 8 weeks after intake to evaluate changes in heart rate. In addition, a fatigue questionnaire was administered before intake of the test food and 8 weeks after intake, and changes in running time were evaluated. During the test period, the subjects were asked to live the same lifestyle as before the test. In addition, foods and beverages that claim to support sports and training, medicines and quasi-drugs whose efficacy includes recovery, prevention, and improvement of "fatigue," "tiredness," "physical strength," and / or "languor," and supplements in general (including functional foods and foods for specified health uses) were prohibited from intake for one week prior to the date of consent to participate in the study and during the test period.
[0058] [Example 4] Test to suppress the increase in heart rate during exercise by α-cyclodextrin Before, 4 weeks after, and 8 weeks after the intake of the test food, the subjects were subjected to an exercise stress test (load intensity: 50 minutes at 55% of the estimated maximum exercise stress intensity for each subject) using an aero bike (registered trademark, manufactured by Konami Sports & Life Co., Ltd., model number AEROBIKE-75XLIII). The estimated maximum exercise stress intensity in this embodiment refers to the maximum exercise stress intensity (pedal weight (W)) calculated by the program built into the aero bike from the heart rate during exercise. The estimated maximum exercise stress intensity was measured in advance for each subject. The heart rate during the exercise stress test was recorded every minute using an ear sensor. The average heart rate for the 10 minutes immediately before the end of exercise (i.e., from 40 minutes after the start of exercise to the end of exercise) was evaluated for changes (Δ values) at 4 weeks and 8 weeks of intake based on the value before intake. The heart rate after 8 weeks of intake was significantly lower in the α-cyclodextrin (αCD) group than in the placebo group (Figure 4). Furthermore, after four weeks of intake, the heart rate in the α-cyclodextrin (αCD) group tended to be significantly lower than that in the placebo group (Figure 4). Analysis of covariance (ANCOVA) was used to test for significant differences between the placebo group and the α-cyclodextrin (αCD) intake group, with the baseline being before intake (*: p<0.05). Heart rate during exercise refers to the average heart rate for a certain period of time during exercise, and is also used to calculate exercise intensity, and is linked to the exercise load imposed by exercise. The fact that the subject's heart rate during exercise was reduced by taking α-cyclodextrin means that the exercise load on the subject was reduced. In other words, the results of this example suggest that the intake of α-cyclodextrin improved athletic ability, inhibited the increase in heart rate during exercise, and further reduced the discomfort felt during exercise.
[0059] [Example 5] Test for reducing fatigue with α-cyclodextrin Before and 8 weeks after the intake of the test food, the subjects were subjected to exercise load (load intensity: 50 minutes at 55% of the estimated maximum exercise load intensity for each subject) using an aero bike (registered trademark) (manufactured by Konami Sports & Life Co., Ltd., model number AEROBIKE-75XLIII). In this embodiment, the estimated maximum exercise load intensity refers to the maximum exercise load intensity (pedal weight (W)) calculated by the program built into the aero bike from the heart rate during exercise. The estimated maximum exercise load intensity was measured in advance for each subject. A VAS (Visual Analogue Scale) questionnaire was conducted based on the fatigue VAS test method established by the Japan Society for Fatigue Science to examine the change in fatigue over time regarding fatigue immediately after the load, 30 minutes after the load, and 60 minutes after the load. The questionnaire included one item, "general fatigue," and the criteria for "best condition (0 mm)" and "worst condition (100 mm)" were as shown in Table 5. In each intake group, the change in the measurement value (Δ value) after 8 weeks of intake was evaluated based on the measurement value before intake. The α-cyclodextrin intake group showed a significant decrease in general fatigue immediately after exercise after 8 weeks of intake compared to the placebo group (Figure 5). The significance of the difference in general fatigue between the placebo group and the α-cyclodextrin (αCD) intake group was tested using Student's t-test (*: p<0.05).
[0060] [Table 5]
[0061] [Example 6] Examination of the improvement of athletic ability by α-cyclodextrin (exercise performance test) In order to evaluate the change in exercise performance due to α-cyclodextrin (αCD) intake, the subjects were subjected to the exercise load test described in Example 5 before and after 8 weeks of intake of the test food, and then after a 60-minute rest, the running time was measured when pedaling 10 km using a spin cycle (Fujimori Co., Ltd., model number FBS-101). The load intensity was set to a value that could be set on the spin cycle close to 45% of the estimated maximum exercise load intensity for each subject. When the change in time (Δ value) after 8 weeks of intake was evaluated based on the time before intake of α-cyclodextrin (αCD), the time after 8 weeks of intake was significantly lower in the α-cyclodextrin (αCD) intake group than in the placebo group (Figure 6). The significant difference test between the placebo group and the α-cyclodextrin (αCD) intake group was performed using analysis of covariance (ANCOVA) with the measured value before intake as a covariate (*: p<0.05). The data from Examples 4 to 6 support the idea that ingestion of α-cyclodextrin contributes to improved athletic performance.
Claims
1. A composition for improving athletic performance, comprising α-cyclodextrin as an active ingredient.
2. The composition according to claim 1 , wherein the improvement of athletic performance includes at least one effect selected from the group consisting of improving physical strength, anti-fatigue, and reducing fatigue.
3. The composition according to claim 1 , wherein the improvement in athletic performance includes suppression of an increase in heart rate during exercise.
4. A composition for growing Bacteroides uniformis in the intestinal tract, comprising α-cyclodextrin as an active ingredient.
5. The composition according to any one of claims 1 to 4, which is for oral intake.
6. The composition according to any one of claims 1 to 4, which is a food or drink additive, a pharmaceutical composition, a feed composition, or a feed additive.
7. The composition according to any one of claims 1 to 6, wherein the α-cyclodextrin is administered in an amount of 0.01 mg / kg to 200 mg / kg of body weight per day.
8. The composition of any one of claims 1 to 7, wherein the composition is administered for at least 7 days.
Citation Information
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