WO2024009986A1 - Endurance-improving agent - Google Patents

Endurance-improving agent Download PDF

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Publication number
WO2024009986A1
WO2024009986A1 PCT/JP2023/024722 JP2023024722W WO2024009986A1 WO 2024009986 A1 WO2024009986 A1 WO 2024009986A1 JP 2023024722 W JP2023024722 W JP 2023024722W WO 2024009986 A1 WO2024009986 A1 WO 2024009986A1
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Prior art keywords
exercise
fatty acids
composition
endurance
day
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PCT/JP2023/024722
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French (fr)
Japanese (ja)
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英輔 越智
香里 横井
賢一 柳本
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株式会社ニッスイ
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Publication of WO2024009986A1 publication Critical patent/WO2024009986A1/en

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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115Fatty acids or derivatives thereof; Fats or oils
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/232Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/02Nutrients, e.g. vitamins, minerals

Definitions

  • the present invention relates to a composition for improving endurance, a method for improving endurance using the same, and the like.
  • Polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) contained in fish oil are known to have various physiological effects.
  • EPA eicosapentaenoic acid
  • DHA docosahexaenoic acid
  • these highly unsaturated fatty acids are widely used as medicines, health foods, food materials, and the like.
  • ethyl ester of highly unsaturated fatty acids is used, and when used as a health food, it is often used as a triglyceride such as purified fish oil.
  • Patent Document 1 states that, as constituent fatty acids, it contains 1 to 20% fatty acids with 20 to 22 carbon atoms, 30 to 50% fatty acids with 14 to 18 carbon atoms, and 40 to 60% fatty acids with 6 to 12 carbon atoms.
  • Compositions containing triglycerides, suitable for parenteral administration, and which can be used to treat or prevent arteriosclerosis, hyperlipidemia are described.
  • Patent Document 2 describes that triglyceride obtained by transesterifying fish oil and medium-chain fatty acid triglyceride is quickly absorbed and is therefore suitable as a nutritional substitute for patients with reduced infection resistance.
  • Patent Document 3 describes an oil and fat composition having a blood lipid regulating function, which is a triglyceride containing 5 to 55% of N-3 long chain polyunsaturated fatty acids and 2 to 40% of medium chain fatty acids. There is. Based on the knowledge that fatty acids bound to the 1st and 3rd positions of triglycerides are less susceptible to decomposition by lipase and difficult to absorb, Patent Documents 4 to 6 state that highly unsaturated fatty acids are bound to the 2nd position and medium-chain fatty acids are bound to the 1st and 3rd positions of triglycerides. It has been described that triglycerides with bound fatty acids are suitable as infusion fluids and enteral nutrition for patients with reduced absorption.
  • Patent Document 7 states that when triglycerides (EPA/MCT structured lipids) whose constituent fatty acids are fatty acids derived from fish oil containing EPA and medium-chain fatty acids are ingested, a mixture of refined fish oil and triglycerides whose constituent fatty acids are medium-chain fatty acids occurs. It has been described that compared to oil, EPA is absorbed faster and a higher blood EPA concentration can be maintained. However, what is shown in Patent Document 7 is that when EPA/MCT structured lipid is ingested once, the movement of EPA into the blood increases transiently, and it is unclear what kind of effect can be obtained by continuous administration. Not shown.
  • Patent Document 8 states that orally ingesting highly unsaturated fatty acids increases lymph fluid flow, and that ingesting triglycerides containing highly unsaturated fatty acids and medium-chain fatty acids in one molecule as constituent fatty acids increases the lymph flow rate more significantly. It is disclosed that lymph fluid flow is increased.
  • n-3 or omega-3) long-chain unsaturated fatty acids (PUFA) such as EPA and DHA. While some reports conclude that n-3 PUFA intake had a beneficial effect on exercise performance, others report that exercise performance did not improve.
  • PUFA long-chain unsaturated fatty acids
  • Non-Patent Document 1 healthy male cyclists were given 3.2 g/day of n-3 PUFA (0.8 g of EPA and 2.4 g of DHA) for 8 weeks, and were asked to exercise for at least 60 minutes on a bicycle ergometer. It is stated that although heart rate, RPP (Rate Pressure Product), and whole body O 2 consumption decreased, no significant difference was observed in exercise time until fatigue compared to a placebo.
  • Non-Patent Document 2 states that when male cyclists took 6 g/day of fish oil with or without vitamin E for 3 weeks and exercised on a bicycle ergometer for about 1 hour, there was no improvement in exercise performance compared to a placebo. It is stated that no significant difference was observed.
  • Non-Patent Document 3 describes a 14-day intake of fish oil (containing 1.1 g/day EPA and 0.7 g/day DHA) by healthy, sedentary male subjects in a human study using a bicycle ergometer. However, it was reported that there was no effect on maximum oxygen uptake (VO 2 max) or energy metabolism.
  • VO 2 max maximum oxygen uptake
  • Non-Patent Document 4 states that when elite cyclists took 2.6 g/day of n-3 PUFA for 3 weeks and performed a bicycle pedal exercise test, maximum oxygen uptake (VO 2 max) was significantly lower than that of a placebo. It is stated that there has been an increase in Non-Patent Document 5 describes that 8 weeks of n-3 PUFA intake and lifestyle modification significantly improved maximum oxygen uptake in overweight women compared to a control group. Non-Patent Document 6 describes that subjects were given 3.6 g/day of fish oil (29.6% EPA and 12.9% DHA to total fatty acids) for 8 weeks without engaging in strenuous exercise.
  • Non-Patent Documents 4 to 6 do not disclose any specific results showing that exercise performance is improved by ingesting fish oil or n-3 PUFA, but they do not disclose any specific results showing that exercise performance is improved by ingesting fish oil or n-3 PUFA, but they do not disclose any specific results showing that exercise performance is improved by ingesting fish oil or n-3 PUFA. There is no mention of results.
  • An object of the present invention is to provide a means for improving endurance.
  • triglycerides structured lipids
  • triglycerides that contain highly unsaturated fatty acids and medium-chain fatty acids in one molecule as constituent fatty acids
  • the present inventors unexpectedly found that intake of structured lipids increases the We found that the duration of exercise until fatigue when measuring intake (VO 2 peak) was significantly extended compared to before intake.
  • the amount of change in exercise duration before and after ingestion of the test substance was found in the group that ingested a mixture of triglycerides (physically mixed oil) with a similar fatty acid composition that does not contain polyunsaturated fatty acids or medium-chain fatty acids in one molecule. It was found that this was significantly greater in the group that ingested structured lipids.
  • anaerobic work threshold which is the point of transition from aerobic to anaerobic exercise, is also lowered by the intake of structured lipids compared to before intake or after intake of physical oil mixture. was found to be significantly higher than that of Furthermore, in the group that ingested structured lipids, subjects with low seafood intake tended to have larger changes in exercise duration before and after ingesting the test substance compared to subjects with high seafood intake. I found out. Based on this knowledge, the present inventors conducted further research and completed the present invention.
  • the present invention is as follows.
  • the composition according to [6], wherein the highly unsaturated fatty acid is eicosapentaenoic acid or docosahexaenoic acid.
  • the method described above includes imparting an endurance improving function by blending.
  • a method for improving endurance comprising causing a subject to ingest an effective amount of a composition containing as an active ingredient triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids.
  • a composition containing as an active ingredient triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids contains 10 to 70% by weight of highly unsaturated fatty acids and 20 to 70% by weight of medium chain fatty acids.
  • the method according to [12] or [13] which comprises causing the subject to ingest 19 mg/kg body weight/day or more and 30 mg/kg body weight/day or less of highly unsaturated fatty acids for 8 weeks or more.
  • [15] The method according to any one of [12] to [14], wherein the seafood intake in the subject is 1.1 kcal/kg body weight/day or less.
  • [16] The method according to any one of [12] to [15], wherein the maximum oxygen uptake in the subject is 60 mL/kg/min or less.
  • [17] The method according to any one of [12] to [16], wherein the highly unsaturated fatty acid is a fatty acid having 20 or more carbon atoms.
  • the highly unsaturated fatty acid is eicosapentaenoic acid or docosahexaenoic acid.
  • 19 mg/kg body weight/day or more and 30 mg/kg body weight/day or less of highly unsaturated fatty acids are used so as to be ingested by the subject for 8 weeks or more, [22] or The composition according to [23].
  • the composition according to [27], wherein the highly unsaturated fatty acid is eicosapentaenoic acid or docosahexaenoic acid.
  • Endurance can be improved by extending the duration of exercise, extending the duration of exercise during high-intensity exercise, extending the duration of exercise during aerobic exercise, extending the duration of exercise during progressively increasing load exercise, and promoting fat burning during exercise. , promoting fat burning during high-intensity exercise, promoting fat burning during aerobic exercise, promoting lipid burning during progressively increasing load exercise, improving anaerobic work threshold, reducing fatigue during exercise, and improving muscular endurance.
  • the composition according to any one of [22] to [30] which is in the form of a food composition or a food additive.
  • compositions containing a triglyceride containing a highly unsaturated fatty acid and a medium-chain fatty acid as an active ingredient for the production of a composition for improving endurance.
  • the fatty acid composition of the composition contains 10 to 70% by weight of highly unsaturated fatty acids and 20 to 70% by weight of medium chain fatty acids.
  • the endurance-improving composition is used so that the subject ingests polyunsaturated fatty acids of 19 mg/kg body weight/day or more and 30 mg/kg body weight/day or less for 8 weeks or more.
  • Endurance can be improved by orally ingesting the composition of the present invention.
  • STG group a group that ingested triglycerides
  • PM group a mixed oil
  • the duration of exercise at the time of measuring the maximum oxygen uptake before and after the intake in the intake group (PM group) is shown.
  • the amount of change in exercise duration when measuring the maximum oxygen uptake before and after intake in the STG group and the PM group is shown.
  • the anaerobic work threshold values (%VO 2 peak) before and after ingestion in the STG group and PM group are shown. **: p ⁇ 0.01 for the difference between the value before and after intake in the STG group. ⁇ : p ⁇ 0.05 for the difference between the post-intake value in the STG group and the post-intake value in the PM group.
  • the amount of change in the anaerobic work threshold value (%VO 2 peak) before and after intake in the STG group and the PM group is shown. *: p ⁇ 0.05 for the difference between the amount of change in the STG group and the amount of change in the PM group.
  • EPA Eicosapentaenoic acid
  • DHA Docosahexaenoic acid
  • MCFA Medium chain fatty acids
  • MCT Triglyceride whose constituent fatty acids are only medium-chain fatty acids
  • STG structured triglyceride, structured triacylglycerol, or structured lipid (STG is a structured lipid with a specific fatty acid composition in the examples)
  • PM physical mixture or physically mixed oil (in the examples, PM is a physically mixed oil with a specific fatty acid composition)
  • AT Anaerobic work threshold (also called anaerobic metabolic threshold)
  • the present invention provides a composition for improving endurance (hereinafter sometimes referred to as the composition of the present invention), which contains as an active ingredient a triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids.
  • “endurance” refers to the ability to continuously perform specific physical activities such as exercise (for example, walking, running, swimming, cycling, etc.). “Improving endurance” means that the duration of the physical activity is extended, or that the energy metabolism in the body is improved so that the duration of the physical activity can be extended.
  • Endurance improvement in the present invention can be evaluated by a multi-step load escalation method (Whipp BJ et al., J. Apple. Physiol.: Respirat. Environ. Exercise physiol. 50(1): 217-221, 1981).
  • a multi-step load escalation method For example, when using a bicycle ergometer, the pedal rotation speed during exercise is 60 rpm, and after 3 minutes of rest, a 3-minute warm-up exercise with a load of 20 watts is performed, and then the exercise is started with a load of 60 watts, and every 2 minutes. Increase the load by 30 watts and have them perform the exercise until they reach exhaustion.
  • the final exercise load is when the subject's pedal rotation speed falls below 50 rpm three times, and the exercise and measurement are terminated when the measurement of oxygen intake under that load is completed. If the duration of exercise is significantly longer in the group that ingested the test substance compared to before ingesting the test substance or compared to the group that did not ingest the test substance, the test substance is considered to have an endurance-enhancing effect. It is evaluated as having.
  • the anaerobic threshold (AT; also referred to as anaerobic metabolic threshold) was significantly higher than before ingestion of the test substance or compared to the group that did not ingest the test substance.
  • the test substance is also evaluated as having an endurance-enhancing effect if the In this specification, AT is the exercise intensity that is the change point from aerobic exercise to anaerobic exercise in the multi-step load increasing method (gradual load test) as described above, and is an exercise intensity that Identified by measurement. Therefore, in this specification, AT can also be referred to as ventilatory work threshold (VT).
  • VT ventilatory work threshold
  • AT is expressed as a value (%VO 2 peak) representing the ratio of oxygen uptake to maximum oxygen uptake at the exercise intensity when switching from aerobic exercise to anaerobic exercise.
  • %VO 2 peak can be calculated by measuring oxygen intake and identifying AT by measuring carbon dioxide output in the multi-step load escalation method described above.
  • the value of %VO 2 peak representing the anaerobic work threshold may be referred to as "AT value”.
  • the endurance improvement in the present invention can be an increase in exercise duration.
  • Exercise duration refers to the time from the start of exercise to the time when a person reaches exhaustion and becomes difficult to continue exercising in a specific physical activity.
  • the extension of the exercise duration can be, for example, an extension of the exercise duration during high-intensity exercise, an extension of the exercise duration during aerobic exercise, or an extension of the exercise duration during progressive load exercise.
  • High-intensity exercise is defined as 70% VO 2 max or higher, such as 75% VO 2 max or higher, 80% VO 2 max or higher, 85% VO 2 max or higher, 90% VO 2 max or higher, 95% VO 2 max or higher, or This refers to exercise that is intense enough to achieve 100% VO 2 max.
  • VO 2 max is the maximum oxygen uptake, which is the maximum amount of oxygen that can be taken in per minute (mL/kg/min or L/min).
  • %VO 2 max is a value expressed as a percentage of the subject's oxygen intake during exercise to VO 2 max.
  • Aerobic exercise is exercise performed using carbohydrates and lipids as energy sources through aerobic metabolism.
  • Gradual load exercise refers to exercise performed under conditions where the exercise load is increased by a certain amount at regular intervals.
  • the extension of exercise duration can be affected by various factors such as heart rate during exercise and improvement of muscle damage and muscle fatigue. This does not indicate that the duration of exercise actually increases.
  • improved endurance in the present invention may be an improvement in energy metabolism in the body so that the duration of exercise can be extended.
  • Such improvement of energy metabolism in the body may be the promotion of fat burning during exercise.
  • "Lipid burning” refers to using fat as an energy source.
  • the promotion of fat burning during exercise can be, for example, the promotion of fat burning during high-intensity exercise, the promotion of fat burning during aerobic exercise, or the promotion of fat burning during gradually increasing load exercise.
  • the effect of improving AT by the composition of the present invention means that fat burning during exercise is promoted. It has been known that medium-chain fatty acids are used more efficiently as an energy source during exercise than long-chain fatty acids such as EPA (Am J Clin Nutr. 36(5), 950-62. 1982)).
  • improving endurance in the present invention may be improving AT.
  • the improvement in AT can be, for example, an increase in AT during high-intensity exercise, an increase in AT during aerobic exercise, or an increase in AT during progressive resistance exercise.
  • improving endurance in the present invention may be reducing fatigue during exercise.
  • fatigue means physical fatigue resulting from exercise.
  • the extension of exercise duration due to the intake of the composition of the present invention can be attributed to the fact that fatigue becomes less likely to occur.
  • Reducing fatigue during exercise can be, for example, reducing fatigue during high-intensity exercise, reducing fatigue during aerobic exercise, or reducing fatigue during incremental load exercise.
  • improving endurance in the present invention may be improving muscular endurance.
  • Muscular endurance is the ability of a particular muscle to continue contracting repeatedly, or the ability to continue an exercise using one part of the body's muscles for an extended period of time.
  • the bicycle ergometer exercise used in the examples is known as training for improving muscular endurance.
  • Improving muscular endurance can be, for example, improving muscular endurance during high-intensity exercise, improving muscular endurance during aerobic exercise, or improving muscular endurance during progressive load exercise.
  • highly unsaturated fatty acids are fatty acids with 18 or more carbon atoms and 3 or more double bonds, such as fatty acids with 20 or more carbon atoms and 3 or more double bonds, fatty acids with 20 or more carbon atoms, and double bonds. It is a fatty acid with a number of 4 or more, or a fatty acid with a carbon number of 20 or more and a double bond number of 5 or more.
  • ⁇ -linolenic acid (18:3, n-3), ⁇ -linolenic acid (18:3, n-6), octadecatetraenoic acid (18:4, n-3), icosatetraenoic acid ( 20:4, n-3), arachidonic acid (20:4, n-6), dihomo- ⁇ -linolenic acid (20:3, n-6), icosapentaenoic acid (20:5, n-3), hemp Examples include icosapentaenoic acid (21:5, n-3), docosapentaenoic acid (22:5, n-6), and docosahexaenoic acid (22:6, n-3).
  • the highly unsaturated fatty acid is an n-3 highly unsaturated fatty acid, more preferably eicosapentaenoic acid and/or docosahexaenoic acid.
  • Glycerides containing highly unsaturated fatty acids as constituent fatty acids are known to be abundantly contained in certain types of microbial oils, vegetable oils, marine animal oils, and the like. Specifically, fish oils such as sardine oil, tuna oil, bonito oil, menhaden oil, cod liver oil, herring oil, capelin oil, and salmon oil and marine animal oils from crustaceans such as krill, perilla, flax, soybean, and rapeseed.
  • Examples include vegetable oils such as , oils and fats produced by microorganisms belonging to the genus Mortierella, Penicillium, Aspergillus, Rhodotorula, and Fusarium.
  • the highly unsaturated fatty acids that are constituent fatty acids of the triglyceride in the present invention may be derived from these fats and oils.
  • medium chain fatty acids refer to those having 8 to 12 carbon atoms, and may be either saturated fatty acids or unsaturated fatty acids. Specific examples include caprylic acid, pelargonic acid, capric acid, and lauric acid. The medium chain fatty acids may be used alone or in combination of two or more. In a preferred embodiment, the medium chain fatty acid is caprylic acid and/or capric acid. Glycerides whose constituent fatty acids are medium-chain fatty acids are known to be abundant in coconut oil, palm oil, and the like. In one embodiment, the medium chain fatty acids that are constituent fatty acids of the triglyceride in the present invention are derived from these fats and oils.
  • the active ingredient in the composition of the present invention is a triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids.
  • triglycerides containing highly unsaturated fatty acids and medium-chain fatty acids in one molecule as constituent fatty acids have a higher endurance-improving effect than mixed oils with the same fatty acid composition.
  • Such a triglyceride can be prepared, for example, by subjecting a triglyceride containing a highly unsaturated fatty acid as a constituent fatty acid and a triglyceride containing a medium chain fatty acid as a constituent fatty acid to a transesterification reaction, as described above.
  • the catalyst used for transesterification may be a chemical catalyst or an enzyme (lipase).
  • a chemical catalyst In transesterification using a chemical catalyst, the bonding positions of the constituent fatty acids are random. Note that triglycerides prepared by changing the bonding positions and fatty acid compositions of fatty acids in naturally occurring triglycerides are sometimes referred to as structured lipids.
  • a chemical catalyst for example, about 0.1 to 2% by weight of the catalyst is added to a mixed oil of a triglyceride containing a highly unsaturated fatty acid as a constituent fatty acid and a triglyceride containing a medium chain fatty acid as a constituent fatty acid, and the mixture is heated under normal pressure or reduced pressure.
  • the reaction is carried out with stirring at 50-270°C for 3-120 minutes.
  • the desired product can be obtained by performing usual purification such as washing with water, drying, decolorization, and deodorization.
  • the mixing ratio of triglycerides containing polyunsaturated fatty acids as constituent fatty acids and triglycerides containing medium-chain fatty acids as constituent fatty acids may be appropriately set so as to obtain an endurance improvement effect.
  • the proportions of highly unsaturated fatty acids and medium chain fatty acids in the composition are mixed as disclosed herein.
  • the chemical catalyst include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide, and alkali metal alkoxides such as lithium methoxide and sodium methoxide.
  • the highly unsaturated fatty acids are 10 to 70% by weight, such as 15 to 50%, 20 to 40% by weight, and the medium chain fatty acids are 20 to 70% by weight. It may be 70% by weight, such as 30-60%, 40-55% by weight.
  • highly unsaturated fatty acids may be 10 to 70% by weight and medium chain fatty acids may be 20 to 70% by weight.
  • the fatty acid composition of the composition of the present invention contains 5 to 65% by weight of highly unsaturated fatty acids.
  • medium chain fatty acids can be 20-70%, eg 30-60%, 40-55% by weight.
  • the highly unsaturated fatty acids are EPA and DHA
  • the medium chain fatty acids are caprylic acid and capric acid
  • the polyunsaturated fatty acids are 5-65% by weight in the fatty acid composition of the composition of the invention.
  • the medium chain fatty acids can be 20-70% by weight.
  • the proportion (wt%) of fatty acids to the total fatty acids in the composition is determined by gas chromatography after esterifying the components in the composition according to "AOCS official method Ce1b-89". Calculated based on the measured value.
  • the content of fatty acids also refers to the ratio (% by weight) of the fatty acids to the total fatty acids mentioned above.
  • the analysis conditions for gas chromatography are as follows.
  • compositions of the invention may be administered to a subject in need of increased endurance, particularly increased exercise duration.
  • the subjects to be administered are healthy people, such as professional athletes or athletes who regularly train, healthy people or casual athletes who actively exercise or play sports, and This includes healthy people who do not regularly engage in high-intensity exercise.
  • the subject to be administered has a GPAQ question item "number of days of moderate-intensity physical activity at work in a week" of 0 to 7 days, preferably 0 to 3 days, for example 0 days, 1 day. , 2 days, or 3 days.
  • “work” includes studies and part-time jobs.
  • “high-intensity physical activity” and “moderate-intensity physical activity” refer to physical activity of 8 METs and physical activity of 4 METs, respectively (Global Physical Activity Questionnaire (GPAQ) Analysis Guide, Surveillance and Population-Based Prevention, Prevention of Noncommunicable Diseases Department, World Health Organization).
  • GPAQ Global Physical Activity Questionnaire
  • the subject to be administered has a GPAQ question item of "number of days with travel of 10 minutes or more in a week" of 0 to 7 days, preferably 4 to 7 days, for example, 4 days, 5 days. It can be someone who is 1 day, 6 days, or 7 days old.
  • the subject is one whose maximum oxygen uptake is 60 mL/kg/min or less, such as 40-60 mL/kg/min, 40-50 mL/kg/min, or 50-60 mL/kg/min. It can be.
  • the composition of the present invention has a high effect of improving endurance in subjects who consume a small amount of seafood.
  • seafood refers to fish, shellfish, crustaceans, and cephalopods, but does not include small fish.
  • Seafood may be in any form, such as raw (for example, sashimi), filleted, surimi (for example, bamboo shoots, kamaboko, etc.), frozen, dried (for example, dried fish), or freeze-dried.
  • the intake of seafood by the subject is the average value for one week before the start of intake of the composition of the present invention.
  • the intake of seafood in the subject is determined by a survey method using a food frequency questionnaire (Takahashi et al., Journal of Nutrition, Vol.
  • the questionnaire includes questions equivalent to the following: "What kind of seafood and processed seafood do you eat? How many times a week do you eat it? Please enter small fish in a separate section. Normal The amount is 80g. 80g means 1 fillet, 1 medium fish, 5 sashimi, 1 dried fish, 1 medium chikuwa or kamaboko, 15 clams with shell, 3 to 4 medium shrimp. , 1/2 cup if you like.” In the answer column, select whether you eat breakfast, lunch, or dinner: none, a little (1/2 the usual amount), normal, or a lot (1.5 times the normal amount). The number of times shall be entered.
  • the subject to whom the composition of the present invention is administered has a seafood intake of 0 kcal/day or more and 71 kcal/day or less, for example, 60 kcal/day or less, 50 kcal/day or less, 40 kcal/day or less, It may be 30 kcal/day or less, 20 kcal/day or less, or 10 kcal/day or less.
  • the administration subject of the present invention may have a seafood intake of 0 kcal/kg body weight/day or more and 1.1 kcal/kg body weight/day or less, for example, 0.89 kcal/kg body weight/day or less, 0.75 kcal /kg body weight/day or less, 0.60 kcal/kg body weight/day or less, 0.45 kcal/kg body weight/day or less, 0.30 kcal/kg body weight/day or less, or 0.15 kcal/kg body weight/day or less It can be.
  • composition of the present invention can be used in forms suitable for pharmaceutical compositions, food compositions (e.g., functional foods, health foods, supplements, etc.), food additives, etc., such as granules (including dry syrup), capsules (soft capsules), etc.
  • granules including dry syrup
  • capsules soft capsules
  • Various solid preparations such as tablets (including chewable preparations), powders, and pills, and liquid preparations such as liquid preparations for internal use (including liquid preparations, suspensions, and syrups) It may also be prepared in the form of a preparation.
  • the composition of the present invention can be formulated as a soft capsule containing the active ingredient in a gelatin shell.
  • Additives for formulation include, for example, excipients, lubricants, binders, disintegrants, fluidizers, dispersants, wetting agents, preservatives, thickeners, pH adjusters, colorants, Examples include flavoring agents, surfactants, and solubilizing agents.
  • a thickener such as pectin, xanthan gum, guar gum, etc. can be added.
  • it can be made into a coated tablet using a coating agent or a paste-like glue.
  • conventional methods may be followed.
  • the composition of the present invention can take the form of a food composition or a food additive.
  • the food composition refers to foods in general including beverages, and includes general foods including health foods such as supplements, as well as foods for specified health uses and foods with nutritional function specified in the Food with Health Claims System of the Consumer Affairs Agency. Also includes.
  • functional foods labeled as having the effect of improving endurance are provided.
  • food products containing fish oil can be provided as is.
  • the food composition or food additive of the present invention also includes food materials that can be added to, mixed with, or applied to other foods to impart an endurance-improving effect. In addition to food, it can also be provided as animal feed.
  • the food composition or food additive of the present invention can be prepared by blending the composition of the present invention into the food composition or food additive, thereby imparting an endurance-improving function.
  • the food composition of the present invention may be a beverage, confectionery, bread, soup, etc., and includes, for example, general retort food, frozen food, instant food (noodles, etc.), canned food, sausage, cookies, biscuits, etc. Cereal bars, crackers, snacks (such as potato chips), pastries, cakes, pies, candies, chewing gum (including pellets and sticks), jellies, soups, ices, dressings, yogurts, etc., in the form of tablets, capsules, emulsions, etc. This includes supplements, soft drinks, etc.
  • the method for producing these foods is not particularly limited as long as it does not impair the effects of the present invention, and any method used by those skilled in the art for each food may be followed.
  • compositions of the present invention are packaged containers, product instructions, and pamphlets. It is also within the scope of the present invention to display the effects of the present invention on television, Internet websites, pamphlets, newspapers, magazines, etc. to advertise and sell the products according to the present invention.
  • the efficacy and effect of improving endurance may be indicated on the packaging container or the like.
  • the amount of the active ingredient ingested by the subject is not particularly limited, and for example, the amount of the active ingredient ingested by the subject is at least an effective amount to obtain the desired effect.
  • the effective amount for obtaining a desired effect refers to the amount necessary for improving endurance.
  • the active ingredient may be ingested at least 10 mg/kg body weight/day, such as at least 50 mg/kg body weight/day, or at least 100 mg/kg body weight/day.
  • the active ingredients of the composition of the present invention do not have strong side effects, there is no limit to the daily intake, but for example, up to 500 mg/kg body weight/day, 400 mg/kg body weight. /day, up to 200 mg/kg body weight/day, or up to 150 mg/kg body weight/day.
  • the period of intake of the composition of the present invention is not limited, but may be, for example, for 4 weeks or more, 5 weeks or more, 6 weeks or more, 7 weeks or more, or 8 weeks or more, and at least improves endurance. Intake may continue until confirmed.
  • the composition of the present invention comprises 2.0 g/day or less, such as 1.9 g/day or less, 1.8 g/day or less, 1.7 g/day or less, 1.6 g/day or less, 1. Up to .5 g/day, up to 1.4 g/day, or up to 1.3 g/day of highly unsaturated fatty acids can be used to be ingested by the subject for 8 weeks or more.
  • the composition of the present invention may be administered at a dose of 30 mg/kg body weight or less, such as 28 mg/kg body weight or less, 27 mg/kg body weight or less, 26 mg/kg body weight or less, 25 mg/kg body weight/day or less, Altitude below 24 mg/kg body weight/day, below 23 mg/kg body weight/day, below 22 mg/kg body weight/day, below 21 mg/kg body weight/day, below 20 mg/kg body weight/day, or below 19 mg/kg body weight/day
  • Unsaturated fatty acids can be used to be ingested by a subject for 8 weeks or more.
  • the composition of the invention may be administered at a dose of 19 mg/kg body weight or more and 30 mg/kg body weight/day or less, such as 28 mg/kg body weight or less, 27 mg/kg body weight/day or less, 26 mg/kg body weight/day or less. , 25 mg/kg body weight/day or less, 24 mg/kg body weight/day or less, 23 mg/kg body weight/day or less, 22 mg/kg body weight/day or less, 21 mg/kg body weight/day or less, or 20 mg/kg body weight/day or less Highly unsaturated fatty acids can be used to be ingested by a subject for 8 weeks or more.
  • the composition of the present invention may contain up to 1.0 g/day, such as up to 0.95 g/day, up to 0.90 g/day. , or 0.86 g/day or less of highly unsaturated fatty acids may be used to be ingested by the subject for 8 weeks or more.
  • the composition of the invention may contain up to 15 mg/kg body weight/day, such as up to 14 mg/kg body weight/day, or 13 mg/kg body weight/day.
  • the following highly unsaturated fatty acids may be used to be ingested by a subject for 8 weeks or more.
  • the composition of the invention may contain at least 13 mg/kg body weight/day and at most 15 mg/kg body weight/day, such as 14 mg/kg body weight/day.
  • the following highly unsaturated fatty acids may be used to be ingested by a subject for 8 weeks or more.
  • the intake amount of highly unsaturated fatty acids is the value obtained by converting the constituent fatty acids in triglyceride, which is an active ingredient of the composition of the present invention, into free fatty acids.
  • Patent Document 7 it has been known that when an EPA/MCT structured lipid is ingested once, the transfer of EPA into the blood is transiently increased. However, it is not known whether there is a relationship between blood EPA concentration and improved endurance.
  • the composition of the present invention is an endurance-improving composition containing as an active ingredient triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids,
  • highly unsaturated fatty acids are 10 to 70% by weight
  • medium chain fatty acids are 20 to 70% by weight
  • the highly unsaturated fatty acids are eicosapentaenoic acid and docosahexaenoic acid
  • medium chain fatty acids are caprylic acid and capric acid
  • 13 mg/kg body weight/day or more and 15 mg/kg body weight/day or less of highly unsaturated fatty acids are used so as to be ingested by the subject for 8 weeks or more
  • the target GPAQ question item ⁇ Number of days of high-intensity physical activity at work per week'' is 0 to 2 days
  • ⁇ Number of days of moderate-intensity physical activity at work per week'' is 0 to 2 days.
  • ⁇ the number of days in a week that involves movement for 10 minutes or more'' is 4 to 7 days
  • the improvement of endurance is due to prolonged exercise duration and high-intensity exercise.
  • Exercise duration during aerobic exercise increases exercise duration during progressively increasing load exercise, promotes fat burning during exercise, promotes fat burning during high-intensity exercise, increases fat during aerobic exercise
  • a composition that is at least one selected from the group consisting of promoting combustion, promoting fat burning during exercise with increasing load, improving anaerobic work threshold, reducing fatigue during exercise, and improving muscular endurance.
  • the composition of the present invention is a composition for extending exercise duration, which contains as an active ingredient triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids,
  • highly unsaturated fatty acids are 10 to 70% by weight
  • medium chain fatty acids are 20 to 70% by weight
  • the highly unsaturated fatty acids are eicosapentaenoic acid and docosahexaenoic acid
  • medium chain fatty acids are caprylic acid and capric acid
  • 13 mg/kg body weight/day or more and 15 mg/kg body weight/day or less of polyunsaturated fatty acids are used so as to be ingested by the subject for 8 weeks or more
  • the target GPAQ question item, ⁇ Number of days of high-intensity physical activity at work per week'' is 0 to 2 days
  • ⁇ Number of days of moderate-intensity physical activity at work per week'' is 0 to 2
  • the subject's seafood intake is 0 kcal/kg body weight/day. or more, and 1.1 kcal/kg body weight/day or less, 0.89 kcal/kg body weight/day or less, 0.75 kcal/kg body weight/day or less, 0.60 kcal/kg body weight/day or less, 0.45 kcal/kg body weight/day 0.30 kcal/kg body weight/day or less, or 0.15 kcal/kg body weight/day or less.
  • the present invention may provide a method for improving endurance, the method comprising causing a subject to ingest an effective amount of a composition of the present invention.
  • the method can be carried out according to the description herein regarding ingestion or administration of the compositions of the invention.
  • Example 1 Materials and methods (1) Preparation of test substance Refined fish oil (manufactured by Nippon Suisan Co., Ltd., standard values: EPA 28% by weight, DHA 12% by weight) and triglyceride (MCT; approximately 60% by weight caprylic acid) whose constituent fatty acids are only medium-chain fatty acids. %, about 40% by weight of capric acid). Refined fish oil and MCT were mixed at a weight ratio of 55:45, 0.2% by weight of sodium methoxide was added, and the mixture was stirred at 60 to 80°C for 60 minutes to perform transesterification.
  • MCT triglyceride
  • the product was washed with water, dried, bleached, and deodorized to prepare a triglyceride (hereinafter referred to as STG in the examples) whose constituent fatty acids were a fish oil-derived fatty acid containing EPA and a medium-chain fatty acid.
  • a mixed oil hereinafter referred to as PM in the Examples in which purified fish oil and MCT were mixed at a weight ratio of 50:50 was prepared as a control sample.
  • the fatty acid compositions of refined fish oil, MCT, STG, and PM are shown in Table 1.
  • Test participants Nineteen healthy young men with no regular training habits participated in the test. Data regarding the subjects (mean ⁇ SD) are shown below. Age, weight, average BMI, and VO 2 peak (peak oxygen uptake) are data at the start of the study. The number of days of physical activity is the average value for one week before the start of the study, and is calculated using the Global Physical Activity Questionnaire (GPAQ); Bull FC et al. Global physical activity questionnaire (GPAQ): nine country reliability and validity study. J Phys Act Health. 2009 Nov;6(6):790-804). Here, "work” includes studies and part-time jobs.
  • GPAQ Global Physical Activity Questionnaire
  • high-intensity physical activity and “moderate-intensity physical activity” refer to physical activity of 8 METs and physical activity of 4 METs, respectively (Global Physical Activity Questionnaire (GPAQ) Analysis Guide, Surveillance and Population-Based Prevention, Prevention of Noncommunicable Diseases Department, World Health Organization).
  • Seafood intake was the average value for one week before the start of the study, and was determined using a survey method using a food frequency questionnaire (Takahashi et al., Journal of Nutrition, Vol. 59, No. 5, p. 221 - 232 (2001). )).
  • study participants were instructed not to change their dietary habits prior to intake.
  • the average calorie intake of study participants during the study period was 2235 kcal/day, and the average water intake
  • the mean protein intake was 90 g/day
  • the mean fat intake was 74 g/day
  • the mean carbohydrate intake was 289 g/day.
  • Figure 1 shows the duration of exercise when measuring the maximum oxygen uptake before and after intake in each group.
  • the exercise duration after STG intake was significantly increased compared to before STG intake (two-way analysis of variance, p ⁇ 0.05).
  • the PM group no significant change in exercise duration was observed before and after ingesting PM.
  • the amount of change in exercise duration before and after intake in the STG group 53 ⁇ 53 seconds
  • the amount of change in exercise duration before and after intake in the PM group (10 ⁇ 63 seconds)
  • Figure 2 shows that there was a significant A difference (p ⁇ 0.05) was observed (Figure 2). Therefore, it has been shown that triglycerides containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids have a function of improving endurance, particularly a function of extending exercise duration.
  • Figure 3 shows the anaerobic work threshold values (%VO 2 peak) before and after intake in each group.
  • the AT value after STG intake was significantly higher compared to before STG intake and compared to after PM intake (two-way analysis of variance, p ⁇ 0.05).
  • the PM group no significant change in AT value was observed before and after ingesting PM.
  • the amount of change in AT value before and after intake in the STG group (6 ⁇ 5) and the amount of change in AT value before and after intake in the PM group (0 ⁇ 6) were analyzed using a t-test, there was a significant difference (p ⁇ 0.05). ) was observed (Figure 4).
  • a higher AT value means that the time available for aerobic exercise is extended.
  • the main energy sources during aerobic exercise are carbohydrates and lipids
  • the main energy sources during anaerobic exercise are carbohydrates. It is thought that the AT value increases by promoting lipid utilization during exercise. Therefore, from the results of this example, the intake of triglycerides containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids is more effective as an energy source during exercise than the intake of physically mixed oils with similar fatty acid compositions. It was suggested that the utilization of lipids was promoted.
  • triglycerides containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids exhibit a particularly high ability to improve endurance in subjects who consume relatively little seafood.
  • the present invention provides pharmaceutical compositions, food compositions, food additives, etc. that improve endurance.

Abstract

The present invention provides: an endurance-improving composition that contains, as an active ingredient, triglycerides containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids; and an endurance-improving food composition, food additive, or the like that contains said composition.

Description

持久力向上剤endurance enhancer
 本発明は、持久力向上用組成物、それを用いた持久力を向上させる方法などに関する。 The present invention relates to a composition for improving endurance, a method for improving endurance using the same, and the like.
 魚油中に含まれる、エイコサペンタエン酸(EPA)、ドコサヘキサエン酸(DHA)等の高度不飽和脂肪酸は、様々な生理作用を持つことが知られている。例えば、EPAは、高トリグリセリド血症などの脂質異常症(高脂血症)等に対して改善効果を有することが知られている。そのため、これら高度不飽和脂肪酸は、医薬品、健康食品、食品素材等として広く利用されている。
 医薬品として用いられる場合、高度不飽和脂肪酸のエチルエステルが用いられ、健康食品等に用いられる場合は、精製魚油などトリグリセリドとして用いられることが多い。
Polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) contained in fish oil are known to have various physiological effects. For example, EPA is known to have an ameliorating effect on dyslipidemia (hyperlipidemia) such as hypertriglyceridemia. Therefore, these highly unsaturated fatty acids are widely used as medicines, health foods, food materials, and the like.
When used as a medicine, ethyl ester of highly unsaturated fatty acids is used, and when used as a health food, it is often used as a triglyceride such as purified fish oil.
 中鎖脂肪酸は吸収が良い脂肪酸であることから、高度不飽和脂肪酸と中鎖脂肪酸とを含有するトリグリセリドとすることにより高度不飽和脂肪酸の吸収を高めようという報告がある。 Since medium-chain fatty acids are easily absorbed, there are reports of attempts to increase the absorption of polyunsaturated fatty acids by creating triglycerides containing polyunsaturated fatty acids and medium-chain fatty acids.
 特許文献1には、構成脂肪酸として、炭素数20~22の脂肪酸を1~20%、炭素数14-18の脂肪酸を30~50%、炭素数6~12の脂肪酸を40~60%含有するトリグリセリドを含む、非経口的投与に適した、動脈硬化、高脂血症の治療または予防に用いることができる組成物が記載されている。
 特許文献2には、魚油と中鎖脂肪酸トリグリセリドをエステル交換したトリグリセリドの吸収が早いので、感染抵抗力が低下した患者等の栄養代替物として適することが記載されている。
 特許文献3には、n-3系長鎖多価不飽和脂肪酸を5~55%、中鎖脂肪酸を2~40%含有するトリグリセリドである血中脂質調整機能を有する油脂組成物が記載されている。
 特許文献4~6には、トリグリセリドの1および3位に結合した脂肪酸はリパーゼによる分解を受けにくく吸収されにくいという知見から、2位に高度不飽和脂肪酸が結合し、1および3位に中鎖脂肪酸が結合したトリグリセリドが、吸収の低下した患者用の輸液や経腸栄養剤として適していることが記載されている。
 特許文献7には、EPAを含む魚油由来の脂肪酸と中鎖脂肪酸とを構成脂肪酸とするトリグリセリド(EPA/MCT構造脂質)を摂取すると、精製魚油と中鎖脂肪酸を構成脂肪酸とするトリグリセリドとの混合油と比較して、EPAの吸収が早く、かつ高い血中EPA濃度を維持できることが記載されている。しかし、特許文献7に示されているのは、EPA/MCT構造脂質を単回摂取した際にEPAの血中移行が一過性に高まることであり、継続投与によっていかなる効果が得られるのかは示されていない。
 特許文献8には、高度不飽和脂肪酸を経口摂取することによりリンパ液流量が増加すること、また、構成脂肪酸として高度不飽和脂肪酸および中鎖脂肪酸を一分子中に含むトリグリセリドの摂取により、より顕著にリンパ液流量が増加することが開示されている。
Patent Document 1 states that, as constituent fatty acids, it contains 1 to 20% fatty acids with 20 to 22 carbon atoms, 30 to 50% fatty acids with 14 to 18 carbon atoms, and 40 to 60% fatty acids with 6 to 12 carbon atoms. Compositions containing triglycerides, suitable for parenteral administration, and which can be used to treat or prevent arteriosclerosis, hyperlipidemia are described.
Patent Document 2 describes that triglyceride obtained by transesterifying fish oil and medium-chain fatty acid triglyceride is quickly absorbed and is therefore suitable as a nutritional substitute for patients with reduced infection resistance.
Patent Document 3 describes an oil and fat composition having a blood lipid regulating function, which is a triglyceride containing 5 to 55% of N-3 long chain polyunsaturated fatty acids and 2 to 40% of medium chain fatty acids. There is.
Based on the knowledge that fatty acids bound to the 1st and 3rd positions of triglycerides are less susceptible to decomposition by lipase and difficult to absorb, Patent Documents 4 to 6 state that highly unsaturated fatty acids are bound to the 2nd position and medium-chain fatty acids are bound to the 1st and 3rd positions of triglycerides. It has been described that triglycerides with bound fatty acids are suitable as infusion fluids and enteral nutrition for patients with reduced absorption.
Patent Document 7 states that when triglycerides (EPA/MCT structured lipids) whose constituent fatty acids are fatty acids derived from fish oil containing EPA and medium-chain fatty acids are ingested, a mixture of refined fish oil and triglycerides whose constituent fatty acids are medium-chain fatty acids occurs. It has been described that compared to oil, EPA is absorbed faster and a higher blood EPA concentration can be maintained. However, what is shown in Patent Document 7 is that when EPA/MCT structured lipid is ingested once, the movement of EPA into the blood increases transiently, and it is unclear what kind of effect can be obtained by continuous administration. Not shown.
Patent Document 8 states that orally ingesting highly unsaturated fatty acids increases lymph fluid flow, and that ingesting triglycerides containing highly unsaturated fatty acids and medium-chain fatty acids in one molecule as constituent fatty acids increases the lymph flow rate more significantly. It is disclosed that lymph fluid flow is increased.
 魚油、またはEPAやDHAなどのn-3(またはオメガ3)長鎖不飽和脂肪酸(PUFA)の摂取による運動パフォーマンスへの影響については、いくつかの研究結果が報告されている。n-3 PUFAの摂取により運動パフォーマンスに有益な影響があったと結論づける報告がある一方、運動パフォーマンスは向上しなかったとの報告もある。 Several research results have been reported regarding the effects on exercise performance of ingesting fish oil or n-3 (or omega-3) long-chain unsaturated fatty acids (PUFA) such as EPA and DHA. While some reports conclude that n-3 PUFA intake had a beneficial effect on exercise performance, others report that exercise performance did not improve.
 非特許文献1には、健康な男性サイクリストに対し、3.2g/日のn-3 PUFA(EPA 0.8gおよびDHA 2.4g)を8週間摂取させ、最低60分間の自転車エルゴメータでの運動を行ったところ、心拍数、RPP(Rate Pressure Product)および全身O消費は低下したものの、疲労までの運動時間にはプラセボと比べて有意な差は見られなかったことが記載されている。
 非特許文献2には、男性サイクリストに対し、6g/日の魚油をビタミンEなしまたはありで3週間摂取させ、1時間程度の自転車エルゴメータでの運動を行ったところ、運動パフォーマンスにはプラセボと比べて有意な差は見られなかったことが記載されている。
 非特許文献3には、自転車エルゴメータによるヒト試験において、健康であまり運動しない(sedentary)男性被験者による魚油(1.1g/日のEPAおよび0.7g/日のDHAを含む)の14日間の摂取が、最大酸素摂取量(VO2max)およびエネルギー代謝に影響を及ぼさなかったことが報告されている。
In Non-Patent Document 1, healthy male cyclists were given 3.2 g/day of n-3 PUFA (0.8 g of EPA and 2.4 g of DHA) for 8 weeks, and were asked to exercise for at least 60 minutes on a bicycle ergometer. It is stated that although heart rate, RPP (Rate Pressure Product), and whole body O 2 consumption decreased, no significant difference was observed in exercise time until fatigue compared to a placebo.
Non-Patent Document 2 states that when male cyclists took 6 g/day of fish oil with or without vitamin E for 3 weeks and exercised on a bicycle ergometer for about 1 hour, there was no improvement in exercise performance compared to a placebo. It is stated that no significant difference was observed.
Non-Patent Document 3 describes a 14-day intake of fish oil (containing 1.1 g/day EPA and 0.7 g/day DHA) by healthy, sedentary male subjects in a human study using a bicycle ergometer. However, it was reported that there was no effect on maximum oxygen uptake (VO 2 max) or energy metabolism.
 非特許文献4には、エリートサイクリストに2.6g/日のn-3 PUFAを3週間摂取させ、自転車こぎ運動試験を行ったところ、プラセボと比べて最大酸素摂取量(VO2max)が有意に増加したことなどが記載されている。
 非特許文献5には、過体重の女性において、8週間のn-3 PUFAの摂取と生活様式の改変により、対照群と比べて最大酸素摂取量が有意に改善したことが記載されている。
 非特許文献6には、激しい運動を行うことなく3.6g/日の魚油(総脂肪酸に対してEPAが29.6%、DHAが12.9%)を8週間摂取させ、自転車エルゴメータでの運動を行ったところ、プラセボと比べて酸素摂取量が低減し、また自覚的運動強度の指標であるBorgスケールの数値も低下したことが記載されている。
 しかし、非特許文献4~6には、魚油またはn-3 PUFAの摂取により運動パフォーマンスが向上したことを示す具体的な結果は開示されておらず、運動継続時間延長などの持久力向上を示す結果の記載もない。
Non-Patent Document 4 states that when elite cyclists took 2.6 g/day of n-3 PUFA for 3 weeks and performed a bicycle pedal exercise test, maximum oxygen uptake (VO 2 max) was significantly lower than that of a placebo. It is stated that there has been an increase in
Non-Patent Document 5 describes that 8 weeks of n-3 PUFA intake and lifestyle modification significantly improved maximum oxygen uptake in overweight women compared to a control group.
Non-Patent Document 6 describes that subjects were given 3.6 g/day of fish oil (29.6% EPA and 12.9% DHA to total fatty acids) for 8 weeks without engaging in strenuous exercise. It is stated that when exercised, the amount of oxygen intake decreased compared to a placebo, and the value on the Borg scale, which is an index of perceived exercise intensity, also decreased.
However, Non-Patent Documents 4 to 6 do not disclose any specific results showing that exercise performance is improved by ingesting fish oil or n-3 PUFA, but they do not disclose any specific results showing that exercise performance is improved by ingesting fish oil or n-3 PUFA, but they do not disclose any specific results showing that exercise performance is improved by ingesting fish oil or n-3 PUFA. There is no mention of results.
特開昭63-154618号公報Japanese Unexamined Patent Publication No. 63-154618 特許2722229号公報Patent No. 2722229 特開2001-226693号公報Japanese Patent Application Publication No. 2001-226693 米国特許第4607052号公報US Patent No. 4,607,052 WO88/09325WO88/09325 WO90/04010WO90/04010 WO2015/050071WO2015/050071 WO2019/156210WO2019/156210
 本発明は、持久力を向上させるための手段を提供することを課題とする。 An object of the present invention is to provide a means for improving endurance.
 本発明者らは、構成脂肪酸として高度不飽和脂肪酸および中鎖脂肪酸を一分子中に含むトリグリセリド(構造脂質)の新規用途を開発する中で、予想外にも、構造脂質の摂取により、最高酸素摂取量(VO2peak)測定時の疲労までの運動継続時間が、摂取前と比較して有意に延長されることを見出した。また、被験物質の摂取前後の運動継続時間の変化量は、高度不飽和脂肪酸および中鎖脂肪酸を一分子中に含まない同様の脂肪酸組成を有するトリグリセリドの混合物(物理的混合油)を摂取した群と比較して、構造脂質を摂取した群において有意に大きいことを見出した。さらに、有酸素性運動から無酸素性運動に移行する変化点である無酸素性作業閾値(AT)も、構造脂質の摂取により、その摂取前と比較して、または物理的混合油の摂取後と比較して、有意に高くなることを見出した。さらに、構造脂質を摂取した群において、魚介類摂取量が少ない被験者においては、魚介類摂取量が多い被験者と比較して、被験物質の摂取前後の運動継続時間の変化量が大きい傾向があることを見出した。
 本発明者らは、かかる知見に基づきさらに研究を重ね、本発明を完成するに至った。
While developing new uses for triglycerides (structured lipids) that contain highly unsaturated fatty acids and medium-chain fatty acids in one molecule as constituent fatty acids, the present inventors unexpectedly found that intake of structured lipids increases the We found that the duration of exercise until fatigue when measuring intake (VO 2 peak) was significantly extended compared to before intake. In addition, the amount of change in exercise duration before and after ingestion of the test substance was found in the group that ingested a mixture of triglycerides (physically mixed oil) with a similar fatty acid composition that does not contain polyunsaturated fatty acids or medium-chain fatty acids in one molecule. It was found that this was significantly greater in the group that ingested structured lipids. In addition, the anaerobic work threshold (AT), which is the point of transition from aerobic to anaerobic exercise, is also lowered by the intake of structured lipids compared to before intake or after intake of physical oil mixture. was found to be significantly higher than that of Furthermore, in the group that ingested structured lipids, subjects with low seafood intake tended to have larger changes in exercise duration before and after ingesting the test substance compared to subjects with high seafood intake. I found out.
Based on this knowledge, the present inventors conducted further research and completed the present invention.
 即ち、本発明は以下の通りである。
[1]構成脂肪酸として高度不飽和脂肪酸と中鎖脂肪酸とを含むトリグリセリドを有効成分として含有する、持久力向上用組成物。
[2]当該組成物の脂肪酸組成において高度不飽和脂肪酸が10~70重量%であり、中鎖脂肪酸が20~70重量%である、[1]に記載の組成物。
[3]19mg/kg体重/日以上、かつ30mg/kg体重/日以下の高度不飽和脂肪酸が、8週間以上、対象に摂取されるように使用されることを特徴とする、[1]または[2]に記載の組成物。
[4]魚介類摂取量が1.1kcal/kg体重/日以下である対象に摂取されるように使用されることを特徴とする、[1]~[3]のいずれかに記載の組成物。
[5]最高酸素摂取量が60mL/kg/分以下である対象に摂取されるように使用されることを特徴とする、[1]~[4]のいずれかに記載の組成物。
[6]高度不飽和脂肪酸が、炭素数20以上の脂肪酸である、[1]~[5]のいずれかに記載の組成物。
[7]高度不飽和脂肪酸が、エイコサペンタエン酸またはドコサヘキサエン酸である、[6]に記載の組成物。
[8]中鎖脂肪酸が、炭素数8~12の脂肪酸である、[1]~[7]のいずれかに記載の組成物。
[9]持久力向上が、運動継続時間延長、高強度運動時の運動継続時間延長、有酸素性運動時の運動継続時間延長、漸増負荷運動時の運動継続時間延長、運動時の脂質燃焼促進、高強度運動時の脂質燃焼促進、有酸素性運動時の脂質燃焼促進、漸増負荷運動時の脂質燃焼促進、無酸素性作業閾値の向上、運動時の疲労の軽減、および筋持久力向上からなる群から選択される少なくとも1つである、[1]~[8]のいずれかに記載の組成物。
[10][1]~[9]のいずれかに記載の組成物を含む、持久力向上用食品組成物または食品添加剤。
[11]持久力向上に用いるための食品組成物または食品添加剤を製造する方法であって、食品組成物または食品添加剤中に、[1]~[9]のいずれかに記載の組成物を配合することにより持久力向上機能を付与することを含む、前記方法。
That is, the present invention is as follows.
[1] An endurance-improving composition containing, as an active ingredient, triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids.
[2] The composition according to [1], wherein the fatty acid composition of the composition contains 10 to 70% by weight of highly unsaturated fatty acids and 20 to 70% by weight of medium chain fatty acids.
[3] 19 mg/kg body weight/day or more and 30 mg/kg body weight/day or less of highly unsaturated fatty acids are used so as to be ingested by the subject for 8 weeks or more, [1] or The composition according to [2].
[4] The composition according to any one of [1] to [3], which is used to be ingested by a subject whose seafood intake is 1.1 kcal/kg body weight/day or less. .
[5] The composition according to any one of [1] to [4], which is used to be ingested by a subject whose maximum oxygen uptake is 60 mL/kg/min or less.
[6] The composition according to any one of [1] to [5], wherein the highly unsaturated fatty acid is a fatty acid having 20 or more carbon atoms.
[7] The composition according to [6], wherein the highly unsaturated fatty acid is eicosapentaenoic acid or docosahexaenoic acid.
[8] The composition according to any one of [1] to [7], wherein the medium chain fatty acid is a fatty acid having 8 to 12 carbon atoms.
[9] Endurance can be improved by extending the duration of exercise, extending the duration of exercise during high-intensity exercise, extending the duration of exercise during aerobic exercise, extending the duration of exercise during progressively increasing load exercise, and promoting fat burning during exercise. , promoting fat burning during high-intensity exercise, promoting fat burning during aerobic exercise, promoting lipid burning during progressively increasing load exercise, improving anaerobic work threshold, reducing fatigue during exercise, and improving muscular endurance. The composition according to any one of [1] to [8], which is at least one selected from the group consisting of:
[10] A food composition or food additive for improving endurance, comprising the composition according to any one of [1] to [9].
[11] A method for producing a food composition or food additive for use in improving endurance, wherein the composition according to any one of [1] to [9] is added to the food composition or food additive. The method described above includes imparting an endurance improving function by blending.
[12]持久力を向上させる方法であって、構成脂肪酸として高度不飽和脂肪酸と中鎖脂肪酸とを含むトリグリセリドを有効成分として含有する組成物の有効量を対象に摂取させることを含む、方法。
[13]当該組成物の脂肪酸組成において高度不飽和脂肪酸が10~70重量%であり、中鎖脂肪酸が20~70重量%である、[12]に記載の方法。
[14]19mg/kg体重/日以上、かつ30mg/kg体重/日以下の高度不飽和脂肪酸を、8週間以上、対象に摂取させることを含む、[12]または[13]に記載の方法。
[15]対象における魚介類摂取量が1.1kcal/kg体重/日以下である、[12]~[14]のいずれかに記載の方法。
[16]対象における最高酸素摂取量が60mL/kg/分以下である、[12]~[15]のいずれかに記載の方法。
[17]高度不飽和脂肪酸が、炭素数20以上の脂肪酸である、[12]~[16]のいずれかに記載の方法。
[18]高度不飽和脂肪酸が、エイコサペンタエン酸またはドコサヘキサエン酸である、[17]に記載の方法。
[19]中鎖脂肪酸が、炭素数8~12の脂肪酸である、[12]~[18]のいずれかに記載の方法。
[20]持久力向上が、運動継続時間延長、高強度運動時の運動継続時間延長、有酸素性運動時の運動継続時間延長、漸増負荷運動時の運動継続時間延長、運動時の脂質燃焼促進、高強度運動時の脂質燃焼促進、有酸素性運動時の脂質燃焼促進、漸増負荷運動時の脂質燃焼促進、無酸素性作業閾値の向上、運動時の疲労の軽減、および筋持久力向上からなる群から選択される少なくとも1つである、[12]~[19]のいずれかに記載の方法。
[21]組成物が、食品組成物または食品添加剤の形態である、[12]~[20]のいずれかに記載の方法。
[12] A method for improving endurance, the method comprising causing a subject to ingest an effective amount of a composition containing as an active ingredient triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids.
[13] The method according to [12], wherein the fatty acid composition of the composition contains 10 to 70% by weight of highly unsaturated fatty acids and 20 to 70% by weight of medium chain fatty acids.
[14] The method according to [12] or [13], which comprises causing the subject to ingest 19 mg/kg body weight/day or more and 30 mg/kg body weight/day or less of highly unsaturated fatty acids for 8 weeks or more.
[15] The method according to any one of [12] to [14], wherein the seafood intake in the subject is 1.1 kcal/kg body weight/day or less.
[16] The method according to any one of [12] to [15], wherein the maximum oxygen uptake in the subject is 60 mL/kg/min or less.
[17] The method according to any one of [12] to [16], wherein the highly unsaturated fatty acid is a fatty acid having 20 or more carbon atoms.
[18] The method according to [17], wherein the highly unsaturated fatty acid is eicosapentaenoic acid or docosahexaenoic acid.
[19] The method according to any one of [12] to [18], wherein the medium chain fatty acid is a fatty acid having 8 to 12 carbon atoms.
[20] Endurance can be improved by extending the duration of exercise, extending the duration of exercise during high-intensity exercise, extending the duration of exercise during aerobic exercise, extending the duration of exercise during progressively increasing load exercise, and promoting fat burning during exercise. , promoting fat burning during high-intensity exercise, promoting fat burning during aerobic exercise, promoting lipid burning during progressively increasing load exercise, improving anaerobic work threshold, reducing fatigue during exercise, and improving muscular endurance. The method according to any one of [12] to [19], which is at least one selected from the group consisting of:
[21] The method according to any one of [12] to [20], wherein the composition is in the form of a food composition or a food additive.
[22]持久力向上における使用のための、構成脂肪酸として高度不飽和脂肪酸と中鎖脂肪酸とを含むトリグリセリドを有効成分として含有する、組成物。
[23]当該組成物の脂肪酸組成において高度不飽和脂肪酸が10~70重量%であり、中鎖脂肪酸が20~70重量%である、[22]に記載の組成物。
[24]19mg/kg体重/日以上、かつ30mg/kg体重/日以下の高度不飽和脂肪酸が、8週間以上、対象に摂取されるように使用されることを特徴とする、[22]または[23]に記載の組成物。
[25]魚介類摂取量が1.1kcal/kg体重/日以下である対象に摂取されるように使用されることを特徴とする、[22]~[24]のいずれかに記載の組成物。
[26]最高酸素摂取量が60mL/kg/分以下である対象に摂取されるように使用されることを特徴とする、[22]~[25]のいずれかに記載の組成物。
[27]高度不飽和脂肪酸が、炭素数20以上の脂肪酸である、[22]~[26]のいずれかに記載の組成物。
[28]高度不飽和脂肪酸が、エイコサペンタエン酸またはドコサヘキサエン酸である、[27]に記載の組成物。
[29]中鎖脂肪酸が、炭素数8~12の脂肪酸である、[22]~[28]のいずれかに記載の組成物。
[30]持久力向上が、運動継続時間延長、高強度運動時の運動継続時間延長、有酸素性運動時の運動継続時間延長、漸増負荷運動時の運動継続時間延長、運動時の脂質燃焼促進、高強度運動時の脂質燃焼促進、有酸素性運動時の脂質燃焼促進、漸増負荷運動時の脂質燃焼促進、無酸素性作業閾値の向上、運動時の疲労の軽減、および筋持久力向上からなる群から選択される少なくとも1つである、[22]~[29]のいずれかに記載の組成物。
[31]食品組成物または食品添加剤の形態である、[22]~[30]のいずれかに記載の組成物。
[22] A composition containing as an active ingredient a triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids, for use in improving endurance.
[23] The composition according to [22], wherein the fatty acid composition of the composition contains 10 to 70% by weight of highly unsaturated fatty acids and 20 to 70% by weight of medium chain fatty acids.
[24] 19 mg/kg body weight/day or more and 30 mg/kg body weight/day or less of highly unsaturated fatty acids are used so as to be ingested by the subject for 8 weeks or more, [22] or The composition according to [23].
[25] The composition according to any one of [22] to [24], which is used to be ingested by a subject whose seafood intake is 1.1 kcal/kg body weight/day or less. .
[26] The composition according to any one of [22] to [25], which is used to be ingested by a subject whose maximum oxygen uptake is 60 mL/kg/min or less.
[27] The composition according to any one of [22] to [26], wherein the highly unsaturated fatty acid is a fatty acid having 20 or more carbon atoms.
[28] The composition according to [27], wherein the highly unsaturated fatty acid is eicosapentaenoic acid or docosahexaenoic acid.
[29] The composition according to any one of [22] to [28], wherein the medium chain fatty acid is a fatty acid having 8 to 12 carbon atoms.
[30] Endurance can be improved by extending the duration of exercise, extending the duration of exercise during high-intensity exercise, extending the duration of exercise during aerobic exercise, extending the duration of exercise during progressively increasing load exercise, and promoting fat burning during exercise. , promoting fat burning during high-intensity exercise, promoting fat burning during aerobic exercise, promoting lipid burning during progressively increasing load exercise, improving anaerobic work threshold, reducing fatigue during exercise, and improving muscular endurance. The composition according to any one of [22] to [29], which is at least one selected from the group consisting of:
[31] The composition according to any one of [22] to [30], which is in the form of a food composition or a food additive.
[32]持久力向上用組成物の製造のための、構成脂肪酸として高度不飽和脂肪酸と中鎖脂肪酸とを含むトリグリセリドを有効成分として含有する組成物の使用。
[33]当該組成物の脂肪酸組成において高度不飽和脂肪酸が10~70重量%であり、中鎖脂肪酸が20~70重量%である、[32]に記載の使用。
[34]持久力向上用組成物が、19mg/kg体重/日以上、かつ30mg/kg体重/日以下の高度不飽和脂肪酸が、8週間以上、対象に摂取されるように使用されることを特徴とする、[32]または[33]に記載の使用。
[35]持久力向上用組成物が、魚介類摂取量が1.1kcal/kg体重/日以下である対象に摂取されるように使用されることを特徴とする、[32]~[34]のいずれかに記載の使用。
[36]持久力向上用組成物が、最高酸素摂取量が60mL/kg/分以下である対象に摂取されるように使用されることを特徴とする、[32]~[35]のいずれかに記載の使用。
[37]高度不飽和脂肪酸が、炭素数20以上の脂肪酸である、[32]~[36]のいずれかに記載の使用。
[38]高度不飽和脂肪酸が、エイコサペンタエン酸またはドコサヘキサエン酸である、[37]に記載の使用。
[39]中鎖脂肪酸が、炭素数8~12の脂肪酸である、[32]~[38]のいずれかに記載の使用。
[40]持久力向上が、運動継続時間延長、高強度運動時の運動継続時間延長、有酸素性運動時の運動継続時間延長、漸増負荷運動時の運動継続時間延長、運動時の脂質燃焼促進、高強度運動時の脂質燃焼促進、有酸素性運動時の脂質燃焼促進、漸増負荷運動時の脂質燃焼促進、無酸素性作業閾値の向上、運動時の疲労の軽減、および筋持久力向上からなる群から選択される少なくとも1つである、[32]~[39]のいずれかに記載の使用。
[41]持久力向上用組成物が、食品組成物または食品添加剤の形態である、[32]~[40]のいずれかに記載の使用。
[32] Use of a composition containing a triglyceride containing a highly unsaturated fatty acid and a medium-chain fatty acid as an active ingredient for the production of a composition for improving endurance.
[33] The use according to [32], wherein the fatty acid composition of the composition contains 10 to 70% by weight of highly unsaturated fatty acids and 20 to 70% by weight of medium chain fatty acids.
[34] The endurance-improving composition is used so that the subject ingests polyunsaturated fatty acids of 19 mg/kg body weight/day or more and 30 mg/kg body weight/day or less for 8 weeks or more. The use according to [32] or [33], characterized in that:
[35] The composition for improving endurance is used so as to be ingested by a subject whose seafood intake is 1.1 kcal/kg body weight/day or less, [32] to [34] Use as described in any of the above.
[36] Any one of [32] to [35], wherein the composition for improving endurance is used to be ingested by a subject whose maximum oxygen uptake is 60 mL/kg/min or less. Uses as described in.
[37] The use according to any one of [32] to [36], wherein the highly unsaturated fatty acid is a fatty acid having 20 or more carbon atoms.
[38] The use according to [37], wherein the highly unsaturated fatty acid is eicosapentaenoic acid or docosahexaenoic acid.
[39] The use according to any one of [32] to [38], wherein the medium chain fatty acid is a fatty acid having 8 to 12 carbon atoms.
[40] Endurance can be improved by extending the duration of exercise, extending the duration of exercise during high-intensity exercise, extending the duration of exercise during aerobic exercise, extending the duration of exercise during progressively increasing load exercise, and promoting fat burning during exercise. , promoting fat burning during high-intensity exercise, promoting fat burning during aerobic exercise, promoting fat burning during progressively increasing load exercise, improving anaerobic work threshold, reducing fatigue during exercise, and improving muscular endurance. The use according to any one of [32] to [39], which is at least one selected from the group consisting of:
[41] The use according to any one of [32] to [40], wherein the endurance improving composition is in the form of a food composition or a food additive.
 本発明の組成物を経口摂取することにより、持久力を向上させることができる。 Endurance can be improved by orally ingesting the composition of the present invention.
EPAを含む魚油由来の脂肪酸と中鎖脂肪酸を構成脂肪酸とするトリグリセリド(STG)を摂取した群(STG群)および精製魚油とMCTとを重量比50:50にて混合した混合油(PM)を摂取した群(PM群)における、摂取前後の最高酸素摂取量測定時の運動継続時間を示す。*:STG群における摂取前の値と摂取後の値との差についてp<0.05。A group that ingested triglycerides (STG) whose constituent fatty acids were fatty acids derived from fish oil containing EPA and medium-chain fatty acids (STG group), and a mixed oil (PM) in which refined fish oil and MCT were mixed at a weight ratio of 50:50. The duration of exercise at the time of measuring the maximum oxygen uptake before and after the intake in the intake group (PM group) is shown. *: p<0.05 for the difference between the value before and after intake in the STG group. STG群およびPM群における摂取前後の最高酸素摂取量測定時の運動継続時間の変化量を示す。*:STG群の変化量とPM群の変化量との差についてp<0.05。The amount of change in exercise duration when measuring the maximum oxygen uptake before and after intake in the STG group and the PM group is shown. *: p<0.05 for the difference between the amount of change in the STG group and the amount of change in the PM group. STG群およびPM群における摂取前後の無酸素性作業閾値の値(%VO2peak)を示す。**:STG群における摂取前の値と摂取後の値との差についてp<0.01。†:STG群の摂取後の値とPM群の摂取後の値との差についてp<0.05。The anaerobic work threshold values (%VO 2 peak) before and after ingestion in the STG group and PM group are shown. **: p<0.01 for the difference between the value before and after intake in the STG group. †: p<0.05 for the difference between the post-intake value in the STG group and the post-intake value in the PM group. STG群およびPM群における摂取前後の無酸素性作業閾値の値(%VO2peak)の変化量を示す。*:STG群の変化量とPM群の変化量との差についてp<0.05。The amount of change in the anaerobic work threshold value (%VO 2 peak) before and after intake in the STG group and the PM group is shown. *: p<0.05 for the difference between the amount of change in the STG group and the amount of change in the PM group.
 以下、本発明をより具体的に説明する。
 なお本明細書中、以下の略号を使用する場合がある。
EPA:エイコサペンタエン酸
DHA:ドコサヘキサエン酸
MCFA:中鎖脂肪酸
MCT:中鎖脂肪酸のみを構成脂肪酸とするトリグリセリド
STG:structured triglyceride、structured triacylglycerol、または構造脂質(実施例では特定の脂肪酸組成を有する構造脂質をSTGとしている)
PM:physical mixtureまたは物理的混合油(実施例では特定の脂肪酸組成を有する物理的混合油をPMとしている)
AT:無酸素性作業閾値(嫌気性代謝閾値ともいう)
The present invention will be explained in more detail below.
Note that the following abbreviations may be used in this specification.
EPA: Eicosapentaenoic acid
DHA: Docosahexaenoic acid
MCFA: Medium chain fatty acids
MCT: Triglyceride whose constituent fatty acids are only medium-chain fatty acids
STG: structured triglyceride, structured triacylglycerol, or structured lipid (STG is a structured lipid with a specific fatty acid composition in the examples)
PM: physical mixture or physically mixed oil (in the examples, PM is a physically mixed oil with a specific fatty acid composition)
AT: Anaerobic work threshold (also called anaerobic metabolic threshold)
 本発明は、構成脂肪酸として高度不飽和脂肪酸と中鎖脂肪酸とを含むトリグリセリドを有効成分として含有する、持久力向上用組成物(以下、本発明の組成物という場合がある)を提供する。 The present invention provides a composition for improving endurance (hereinafter sometimes referred to as the composition of the present invention), which contains as an active ingredient a triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids.
 本発明において「持久力」とは、運動などの特定の身体活動(例えば、歩く、走る、泳ぐ、自転車をこぐなど)を継続的に行う能力をいう。「持久力向上」とは、当該身体活動の継続時間が延長されること、または、当該身体活動の継続時間の延長が可能となるように体内のエネルギー代謝が改善されることをいう。 In the present invention, "endurance" refers to the ability to continuously perform specific physical activities such as exercise (for example, walking, running, swimming, cycling, etc.). "Improving endurance" means that the duration of the physical activity is extended, or that the energy metabolism in the body is improved so that the duration of the physical activity can be extended.
 本発明における持久力向上は、多段階負荷漸増法(Whipp BJ et al., J. Apple. Physiol.: Respirat. Environ. Exercise physiol. 50(1): 217-221, 1981)により評価され得る。例えば、自転車エルゴメータを用いる場合、運動時のペダル回転速度は60rpmとし、3分間の安静後、20wattの負荷で3分間のウォーミングアップ運動を行った後、60wattの負荷から運動を開始し、2分毎に30wattずつ負荷を上げ、疲労困憊に至るまで運動を行わせる。被験者のペダル回転速度が50rpmを3回下回った時を最終の運動負荷とし、その負荷での酸素摂取量の測定が完了した時点を以て、運動及び測定を終了する。被験物質を摂取した群において、被験物質を摂取する前と比較して、または被験物質を摂取しない群と比較して、運動継続時間が有意に延長した場合、当該被験物質は持久力向上効果を有すると評価される。 Endurance improvement in the present invention can be evaluated by a multi-step load escalation method (Whipp BJ et al., J. Apple. Physiol.: Respirat. Environ. Exercise physiol. 50(1): 217-221, 1981). For example, when using a bicycle ergometer, the pedal rotation speed during exercise is 60 rpm, and after 3 minutes of rest, a 3-minute warm-up exercise with a load of 20 watts is performed, and then the exercise is started with a load of 60 watts, and every 2 minutes. Increase the load by 30 watts and have them perform the exercise until they reach exhaustion. The final exercise load is when the subject's pedal rotation speed falls below 50 rpm three times, and the exercise and measurement are terminated when the measurement of oxygen intake under that load is completed. If the duration of exercise is significantly longer in the group that ingested the test substance compared to before ingesting the test substance or compared to the group that did not ingest the test substance, the test substance is considered to have an endurance-enhancing effect. It is evaluated as having.
 また、被験物質を摂取した群において、被験物質を摂取する前と比較して、または被験物質を摂取しない群と比較して、無酸素性作業閾値(AT;嫌気性代謝閾値ともいう)が有意に高くなった場合も、当該被験物質は持久力向上効果を有すると評価される。本明細書中、ATとは、上記のような多段階負荷漸増法(漸増負荷試験)において有酸素性運動から無酸素性運動に移行する変化点となる運動強度であり、二酸化炭素排出量を測定することにより特定される。したがって、本明細書中、ATは、換気性作業閾値(VT)と言い換えることもできる。本明細書中、ATは、有酸素性運動から無酸素性運動に切り替わる運動強度における酸素摂取量の最高酸素摂取量に対する割合を百分率で表した値(%VO2peak)によって表される。%VO2peakは、上述の多段階負荷漸増法において、酸素摂取量を測定するとともに、二酸化炭素排出量の測定によりATを特定することにより、算出することができる。本明細書中、無酸素性作業閾値を表す%VO2peakの値を「AT値」という場合がある。 In addition, in the group that ingested the test substance, the anaerobic threshold (AT; also referred to as anaerobic metabolic threshold) was significantly higher than before ingestion of the test substance or compared to the group that did not ingest the test substance. The test substance is also evaluated as having an endurance-enhancing effect if the In this specification, AT is the exercise intensity that is the change point from aerobic exercise to anaerobic exercise in the multi-step load increasing method (gradual load test) as described above, and is an exercise intensity that Identified by measurement. Therefore, in this specification, AT can also be referred to as ventilatory work threshold (VT). In this specification, AT is expressed as a value (%VO 2 peak) representing the ratio of oxygen uptake to maximum oxygen uptake at the exercise intensity when switching from aerobic exercise to anaerobic exercise. %VO 2 peak can be calculated by measuring oxygen intake and identifying AT by measuring carbon dioxide output in the multi-step load escalation method described above. In this specification, the value of %VO 2 peak representing the anaerobic work threshold may be referred to as "AT value".
 一実施形態において、本発明における持久力向上は、運動継続時間延長であり得る。運動継続時間は、特定の身体活動において、運動開始から、疲労困憊に至り運動継続が困難になるまでの時間をいう。運動継続時間の延長は、例えば、高強度運動時の運動継続時間延長、有酸素性運動時の運動継続時間延長、または漸増負荷運動時の運動継続時間延長であり得る。高強度運動とは、70%VO2max以上、例えば75%VO2max以上、80%VO2max以上、85%VO2max以上、90%VO2max以上、95%VO2max以上、または100%VO2maxとなる強度の運動をいう。VO2maxは、最大酸素摂取量であり、1分間に摂取できる酸素量の最大値(mL/kg/minまたはL/min)である。%VO2maxは、運動中の対象の酸素摂取量のVO2maxに対する割合を百分率で表した値である。有酸素性運動とは、好気的代謝により糖質および脂質をエネルギー源として行う運動である。漸増負荷運動とは、一定時間ごとに運動負荷を一定量上げる条件下で行う運動をいう。
 なお、運動継続時間の延長は、運動時の心拍数や筋損傷・筋疲労改善などの種々の要素が影響し得るため、例えば最大酸素摂取量(VO2max)の上昇のような結果は、実際に運動継続時間が延長することを示すものではない。
In one embodiment, the endurance improvement in the present invention can be an increase in exercise duration. Exercise duration refers to the time from the start of exercise to the time when a person reaches exhaustion and becomes difficult to continue exercising in a specific physical activity. The extension of the exercise duration can be, for example, an extension of the exercise duration during high-intensity exercise, an extension of the exercise duration during aerobic exercise, or an extension of the exercise duration during progressive load exercise. High-intensity exercise is defined as 70% VO 2 max or higher, such as 75% VO 2 max or higher, 80% VO 2 max or higher, 85% VO 2 max or higher, 90% VO 2 max or higher, 95% VO 2 max or higher, or This refers to exercise that is intense enough to achieve 100% VO 2 max. VO 2 max is the maximum oxygen uptake, which is the maximum amount of oxygen that can be taken in per minute (mL/kg/min or L/min). %VO 2 max is a value expressed as a percentage of the subject's oxygen intake during exercise to VO 2 max. Aerobic exercise is exercise performed using carbohydrates and lipids as energy sources through aerobic metabolism. Gradual load exercise refers to exercise performed under conditions where the exercise load is increased by a certain amount at regular intervals.
In addition, the extension of exercise duration can be affected by various factors such as heart rate during exercise and improvement of muscle damage and muscle fatigue. This does not indicate that the duration of exercise actually increases.
 一実施形態において、本発明における持久力向上は、運動継続時間延長が可能となるように体内のエネルギー代謝が改善されることであり得る。そのような体内のエネルギー代謝の改善は、運動時の脂質燃焼促進であり得る。「脂質燃焼」とは、脂質をエネルギー源として使用することをいう。運動時の脂質燃焼促進は、例えば、高強度運動時の脂質燃焼促進、有酸素性運動時の脂質燃焼促進、または漸増負荷運動時の脂質燃焼促進であり得る。本発明の組成物によるATを向上させる効果は、運動時の脂質燃焼が促進されることを意味する。従来、中鎖脂肪酸は、EPAのような長鎖脂肪酸に比べて、運動時にエネルギー源として効率よく使用されることが知られていた(Am J Clin Nutr.36(5),950-62.(1982))。一方、構造脂質の形態ではない長鎖脂肪酸を摂取するのみで運動時の脂質燃焼が促進されることは知られていない。実際、後述の実施例において示されているとおり、構成脂肪酸としてEPAを含むトリグリセリドを含む物理的混合油では、ATは向上しなかった。構成脂肪酸として高度不飽和脂肪酸と中鎖脂肪酸とを含むトリグリセリドを摂取した場合には、体内のエネルギー代謝が改善され、運動時の脂質燃焼が促進されると考えられる。このことは、当該技術分野においてこれまで知られていなかった。 In one embodiment, improved endurance in the present invention may be an improvement in energy metabolism in the body so that the duration of exercise can be extended. Such improvement of energy metabolism in the body may be the promotion of fat burning during exercise. "Lipid burning" refers to using fat as an energy source. The promotion of fat burning during exercise can be, for example, the promotion of fat burning during high-intensity exercise, the promotion of fat burning during aerobic exercise, or the promotion of fat burning during gradually increasing load exercise. The effect of improving AT by the composition of the present invention means that fat burning during exercise is promoted. It has been known that medium-chain fatty acids are used more efficiently as an energy source during exercise than long-chain fatty acids such as EPA (Am J Clin Nutr. 36(5), 950-62. 1982)). On the other hand, it is not known that simply ingesting long-chain fatty acids that are not in the form of structured lipids promotes fat burning during exercise. In fact, as shown in the Examples below, AT was not improved in a physically mixed oil containing a triglyceride containing EPA as a constituent fatty acid. Ingestion of triglycerides containing polyunsaturated fatty acids and medium-chain fatty acids as constituent fatty acids is thought to improve energy metabolism in the body and promote fat burning during exercise. This was previously unknown in the art.
 一実施形態において、本発明における持久力向上は、ATの向上であり得る。ATの向上は、例えば、高強度運動時のATの向上、有酸素性運動時のATの向上、または漸増負荷運動時のATの向上であり得る。 In one embodiment, improving endurance in the present invention may be improving AT. The improvement in AT can be, for example, an increase in AT during high-intensity exercise, an increase in AT during aerobic exercise, or an increase in AT during progressive resistance exercise.
 一実施形態において、本発明における持久力向上は、運動時の疲労の軽減であり得る。本明細書中、疲労とは、運動に由来する身体的疲労を意味する。本発明の組成物の摂取による運動継続時間延長は、疲労が生じにくくなったことによるものということができる。運動時の疲労の軽減は、例えば、高強度運動時の疲労の軽減、有酸素性運動時の疲労の軽減、または漸増負荷運動時の疲労の軽減であり得る。 In one embodiment, improving endurance in the present invention may be reducing fatigue during exercise. As used herein, fatigue means physical fatigue resulting from exercise. The extension of exercise duration due to the intake of the composition of the present invention can be attributed to the fact that fatigue becomes less likely to occur. Reducing fatigue during exercise can be, for example, reducing fatigue during high-intensity exercise, reducing fatigue during aerobic exercise, or reducing fatigue during incremental load exercise.
 一実施形態において、本発明における持久力向上は、筋持久力向上であり得る。筋持久力は、特定の筋肉が繰り返し収縮し続ける能力、または体の一部の筋肉を使った運動を長く続ける能力である。実施例において用いられている自転車エルゴメータによる運動は、筋持久力の向上を図るトレーニングとして知られている。筋持久力向上は、例えば、高強度運動時の筋持久力向上、有酸素性運動時の筋持久力向上、または漸増負荷運動時の筋持久力向上であり得る。 In one embodiment, improving endurance in the present invention may be improving muscular endurance. Muscular endurance is the ability of a particular muscle to continue contracting repeatedly, or the ability to continue an exercise using one part of the body's muscles for an extended period of time. The bicycle ergometer exercise used in the examples is known as training for improving muscular endurance. Improving muscular endurance can be, for example, improving muscular endurance during high-intensity exercise, improving muscular endurance during aerobic exercise, or improving muscular endurance during progressive load exercise.
 本発明において高度不飽和脂肪酸とは、炭素数18以上、二重結合数3以上の脂肪酸であり、例えば、炭素数20以上、二重結合数3以上の脂肪酸、炭素数20以上、二重結合数4以上の脂肪酸、または炭素数20以上、二重結合数5以上の脂肪酸である。具体的にはα-リノレン酸(18:3,n-3)、γ-リノレン酸(18:3,n-6)、オクタデカテトラエン酸(18:4,n-3)、イコサテトラエン酸(20:4,n-3)、アラキドン酸(20:4,n-6)、ジホモ-γ-リノレン酸(20:3,n-6)、イコサペンタエン酸(20:5,n-3)、ヘンイコサペンタエン酸(21:5,n-3)、ドコサペンタエン酸(22:5,n-6)、ドコサヘキサエン酸(22:6,n-3)などが例示される。好ましい態様において、高度不飽和脂肪酸は、n-3系高度不飽和脂肪酸であり、より好ましくはエイコサペンタエン酸および/またはドコサヘキサエン酸である。
 高度不飽和脂肪酸を構成脂肪酸として含有するグリセリドは、ある種の微生物油、植物油や海産動物油などに多く含まれることが知られている。具体的には、イワシ油、マグロ油、カツオ油、メンヘイデン油、タラ肝油、ニシン油、カペリン油、およびサーモン油などの魚油やオキアミなどの甲殻類の海産動物油、エゴマ、アマ、大豆、菜種などの植物油、モルティエレラ(Mortierella)属、ペニシリューム(Penicillium)属、アスペルギルス(Aspergillus)属、ロードトルラ(Rhodotorula)属、フザリューム(Fusarium)属に属する微生物が産生する油脂などが例示される。一実施形態において、本発明におけるトリグリセリドの構成脂肪酸である高度不飽和脂肪酸は、これらの油脂に由来するものであり得る。
In the present invention, highly unsaturated fatty acids are fatty acids with 18 or more carbon atoms and 3 or more double bonds, such as fatty acids with 20 or more carbon atoms and 3 or more double bonds, fatty acids with 20 or more carbon atoms, and double bonds. It is a fatty acid with a number of 4 or more, or a fatty acid with a carbon number of 20 or more and a double bond number of 5 or more. Specifically, α-linolenic acid (18:3, n-3), γ-linolenic acid (18:3, n-6), octadecatetraenoic acid (18:4, n-3), icosatetraenoic acid ( 20:4, n-3), arachidonic acid (20:4, n-6), dihomo-γ-linolenic acid (20:3, n-6), icosapentaenoic acid (20:5, n-3), hemp Examples include icosapentaenoic acid (21:5, n-3), docosapentaenoic acid (22:5, n-6), and docosahexaenoic acid (22:6, n-3). In a preferred embodiment, the highly unsaturated fatty acid is an n-3 highly unsaturated fatty acid, more preferably eicosapentaenoic acid and/or docosahexaenoic acid.
Glycerides containing highly unsaturated fatty acids as constituent fatty acids are known to be abundantly contained in certain types of microbial oils, vegetable oils, marine animal oils, and the like. Specifically, fish oils such as sardine oil, tuna oil, bonito oil, menhaden oil, cod liver oil, herring oil, capelin oil, and salmon oil and marine animal oils from crustaceans such as krill, perilla, flax, soybean, and rapeseed. Examples include vegetable oils such as , oils and fats produced by microorganisms belonging to the genus Mortierella, Penicillium, Aspergillus, Rhodotorula, and Fusarium. In one embodiment, the highly unsaturated fatty acids that are constituent fatty acids of the triglyceride in the present invention may be derived from these fats and oils.
 本発明において中鎖脂肪酸とは、炭素数が8~12のものをいい、飽和脂肪酸または不飽和脂肪酸のいずれであってもよい。具体的には、カプリル酸、ペラルゴン酸、カプリン酸、ラウリン酸などが挙げられる。中鎖脂肪酸は1種でも2種以上の組み合わせでもよい。好ましい態様において、中鎖脂肪酸は、カプリル酸および/またはカプリン酸である。中鎖脂肪酸を構成脂肪酸とするグリセリドは、ヤシ油、パーム油などに多く含まれることが知られている。一実施形態において、本発明におけるトリグリセリドの構成脂肪酸である中鎖脂肪酸は、これらの油脂に由来するものである。 In the present invention, medium chain fatty acids refer to those having 8 to 12 carbon atoms, and may be either saturated fatty acids or unsaturated fatty acids. Specific examples include caprylic acid, pelargonic acid, capric acid, and lauric acid. The medium chain fatty acids may be used alone or in combination of two or more. In a preferred embodiment, the medium chain fatty acid is caprylic acid and/or capric acid. Glycerides whose constituent fatty acids are medium-chain fatty acids are known to be abundant in coconut oil, palm oil, and the like. In one embodiment, the medium chain fatty acids that are constituent fatty acids of the triglyceride in the present invention are derived from these fats and oils.
 本発明の組成物における有効成分は、構成脂肪酸として高度不飽和脂肪酸と中鎖脂肪酸とを含むトリグリセリドである。下記実施例に示すとおり、構成脂肪酸として高度不飽和脂肪酸と中鎖脂肪酸とを一分子中に含むトリグリセリドは、同等の脂肪酸組成の混合油と比較して、高い持久力向上効果を有する。
 このようなトリグリセリドは、例えば、上述のような、構成脂肪酸として高度不飽和脂肪酸を含むトリグリセリドと構成脂肪酸として中鎖脂肪酸を含むトリグリセリドとを、エステル交換反応に供することによって調製することができる。エステル交換に使用される触媒は、化学触媒であっても酵素(リパーゼ)であってもよい。化学触媒を用いたエステル交換では、構成脂肪酸の結合位置はランダムとなる。なお、このような、天然に存在するトリグリセリド中の脂肪酸の結合位置および脂肪酸組成を変更することにより調製したトリグリセリドを、構造脂質と呼ぶことがある。
 化学触媒を用いる場合、例えば、構成脂肪酸として高度不飽和脂肪酸を含むトリグリセリドと構成脂肪酸として中鎖脂肪酸を含むトリグリセリドとの混合油に、触媒を約0.1~2重量%添加し、常圧又は減圧下、50~270℃で3~120分間、撹拌して反応を行う。水洗、乾燥、脱色、脱臭などの通常の精製を行うことにより目的物を得ることができる。構成脂肪酸として高度不飽和脂肪酸を含むトリグリセリドと構成脂肪酸として中鎖脂肪酸を含むトリグリセリドとの混合比は、持久力向上効果が得られるように適宜設定すればよく、例えば、本発明の組成物の脂肪酸組成における高度不飽和脂肪酸と中鎖脂肪酸の割合が、本明細書中に開示された割合となるように混合される。
 化学触媒としては、例えば、水酸化リチウム、水酸化ナトリウム、水酸化カリウムなどのアルカリ金属水酸化物、リチウムメトキシド、ナトリウムメトキシドなどのアルカリ金属アルコキシドなどが挙げられる。
The active ingredient in the composition of the present invention is a triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids. As shown in the examples below, triglycerides containing highly unsaturated fatty acids and medium-chain fatty acids in one molecule as constituent fatty acids have a higher endurance-improving effect than mixed oils with the same fatty acid composition.
Such a triglyceride can be prepared, for example, by subjecting a triglyceride containing a highly unsaturated fatty acid as a constituent fatty acid and a triglyceride containing a medium chain fatty acid as a constituent fatty acid to a transesterification reaction, as described above. The catalyst used for transesterification may be a chemical catalyst or an enzyme (lipase). In transesterification using a chemical catalyst, the bonding positions of the constituent fatty acids are random. Note that triglycerides prepared by changing the bonding positions and fatty acid compositions of fatty acids in naturally occurring triglycerides are sometimes referred to as structured lipids.
When using a chemical catalyst, for example, about 0.1 to 2% by weight of the catalyst is added to a mixed oil of a triglyceride containing a highly unsaturated fatty acid as a constituent fatty acid and a triglyceride containing a medium chain fatty acid as a constituent fatty acid, and the mixture is heated under normal pressure or reduced pressure. The reaction is carried out with stirring at 50-270°C for 3-120 minutes. The desired product can be obtained by performing usual purification such as washing with water, drying, decolorization, and deodorization. The mixing ratio of triglycerides containing polyunsaturated fatty acids as constituent fatty acids and triglycerides containing medium-chain fatty acids as constituent fatty acids may be appropriately set so as to obtain an endurance improvement effect. The proportions of highly unsaturated fatty acids and medium chain fatty acids in the composition are mixed as disclosed herein.
Examples of the chemical catalyst include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide, and alkali metal alkoxides such as lithium methoxide and sodium methoxide.
 一実施形態において、本発明の組成物の脂肪酸組成において、高度不飽和脂肪酸は、10~70重量%、例えば15~50重量%、20~40重量%であり、かつ中鎖脂肪酸は、20~70重量%、例えば30~60重量%、40~55重量%であり得る。好ましい実施形態において、本発明の組成物の脂肪酸組成において、高度不飽和脂肪酸は10~70重量%であり、かつ中鎖脂肪酸は20~70重量%であり得る。また一実施形態において、高度不飽和脂肪酸がEPAおよびDHAであり、かつ中鎖脂肪酸がカプリル酸およびカプリン酸である場合、本発明の組成物の脂肪酸組成において高度不飽和脂肪酸は5~65重量%、例えば10~45重量%、15~35重量%であり、かつ中鎖脂肪酸は20~70重量%、例えば30~60重量%、40~55重量%であり得る。好ましい実施形態において、高度不飽和脂肪酸はEPAおよびDHAであり、かつ中鎖脂肪酸がカプリル酸およびカプリン酸であり、本発明の組成物の脂肪酸組成において高度不飽和脂肪酸は5~65重量%であり、かつ中鎖脂肪酸は20~70重量%であり得る。 In one embodiment, in the fatty acid composition of the composition of the invention, the highly unsaturated fatty acids are 10 to 70% by weight, such as 15 to 50%, 20 to 40% by weight, and the medium chain fatty acids are 20 to 70% by weight. It may be 70% by weight, such as 30-60%, 40-55% by weight. In a preferred embodiment, in the fatty acid composition of the composition of the invention, highly unsaturated fatty acids may be 10 to 70% by weight and medium chain fatty acids may be 20 to 70% by weight. Further, in one embodiment, when the highly unsaturated fatty acids are EPA and DHA and the medium chain fatty acids are caprylic acid and capric acid, the fatty acid composition of the composition of the present invention contains 5 to 65% by weight of highly unsaturated fatty acids. , for example 10-45%, 15-35% by weight, and medium chain fatty acids can be 20-70%, eg 30-60%, 40-55% by weight. In a preferred embodiment, the highly unsaturated fatty acids are EPA and DHA, and the medium chain fatty acids are caprylic acid and capric acid, and the polyunsaturated fatty acids are 5-65% by weight in the fatty acid composition of the composition of the invention. , and the medium chain fatty acids can be 20-70% by weight.
 本明細書中、組成物中の総脂肪酸に対する脂肪酸の割合(重量%)は、特に明記しない限り、「AOCS official method Ce1b-89」に従い、組成物中の成分をエステル化した後、ガスクロマトグラフィーにより測定した値に基づいて算出される。脂肪酸の含有量という場合も、上記の総脂肪酸に対する当該脂肪酸の割合(重量%)を意味する。ガスクロマトグラフィーの分析条件は以下の通りである。
 装置:Agilent6890N GC system(Agilent社)
 カラム:DB-WAX(Agilent Technologies, 30m x 0.25mm ID, 0.25μm film thickness)
 キャリアガス:ヘリウム(1.0mL/min, コンスタントフロー)
 注入口温度:250℃
 注入量:1μL
 注入法:スプリット
 スプリット比:20:1
 カラムオーブン:180℃ - 3℃/min - 230℃
 検出器:FID
 検出器温度:250℃
In this specification, unless otherwise specified, the proportion (wt%) of fatty acids to the total fatty acids in the composition is determined by gas chromatography after esterifying the components in the composition according to "AOCS official method Ce1b-89". Calculated based on the measured value. The content of fatty acids also refers to the ratio (% by weight) of the fatty acids to the total fatty acids mentioned above. The analysis conditions for gas chromatography are as follows.
Equipment: Agilent 6890N GC system (Agilent)
Column: DB-WAX (Agilent Technologies, 30m x 0.25mm ID, 0.25μm film thickness)
Carrier gas: Helium (1.0mL/min, constant flow)
Inlet temperature: 250℃
Injection volume: 1μL
Injection method: Split Split ratio: 20:1
Column oven: 180℃ - 3℃/min - 230℃
Detector: FID
Detector temperature: 250℃
 本発明の組成物の投与対象は、哺乳動物であり、好ましくはヒトである。一実施形態において、本発明の組成物は、持久力向上、特に運動継続時間延長を必要とする対象に投与され得る。本発明の組成物を非治療用途で用いる場合、投与対象は健常者であり、トレーニングを日常的に行っているプロスポーツ選手またはアスリート、運動やスポーツを積極的に行う健常者またはカジュアルアスリート、日常的に高強度の運動を行わない健常者などが含まれる。 The subject to whom the composition of the present invention is administered is a mammal, preferably a human. In one embodiment, the compositions of the invention may be administered to a subject in need of increased endurance, particularly increased exercise duration. When the composition of the present invention is used for non-therapeutic purposes, the subjects to be administered are healthy people, such as professional athletes or athletes who regularly train, healthy people or casual athletes who actively exercise or play sports, and This includes healthy people who do not regularly engage in high-intensity exercise.
 一実施形態において、投与対象は、世界標準化身体活動質問票(Global Physical Activity Questionnaire(GPAQ);Bull FC et al. Global physical activity questionnaire (GPAQ): nine country reliability and validity study. J Phys Act Health. 2009 Nov;6(6):790-804)の質問項目である「1週間の中で、仕事での高強度身体活動日数」が0~7日、好ましくは0~2日、例えば0日、1日、または2日である者であり得る。
 一実施形態において、投与対象は、GPAQの質問項目である「1週間の中で、仕事での中強度身体活動日数」が0~7日、好ましくは0~3日、例えば0日、1日、2日、または3日である者であり得る。
 ここで、「仕事」には、学業およびアルバイトも含まれる。また、「高強度身体活動」および「中強度身体活動」とは、それぞれ8メッツの身体活動および4メッツの身体活動をいう(Global Physical Activity Questionnaire (GPAQ) Analysis Guide, Surveillance and Population-Based Prevention, Prevention of Noncommunicable Diseases Department, World Health Organization)。
In one embodiment, the subject administered the Global Physical Activity Questionnaire (GPAQ); Bull FC et al. Global physical activity questionnaire (GPAQ): nine country reliability and validity study. J Phys Act Health. 2009 Nov;6(6):790-804) question item "Number of days of high-intensity physical activity at work per week" is 0 to 7 days, preferably 0 to 2 days, for example 0 days, 1 It can be someone who is a day or two days old.
In one embodiment, the subject to be administered has a GPAQ question item "number of days of moderate-intensity physical activity at work in a week" of 0 to 7 days, preferably 0 to 3 days, for example 0 days, 1 day. , 2 days, or 3 days.
Here, "work" includes studies and part-time jobs. In addition, "high-intensity physical activity" and "moderate-intensity physical activity" refer to physical activity of 8 METs and physical activity of 4 METs, respectively (Global Physical Activity Questionnaire (GPAQ) Analysis Guide, Surveillance and Population-Based Prevention, Prevention of Noncommunicable Diseases Department, World Health Organization).
 一実施形態において、投与対象は、GPAQの質問項目である「1週間の中で、10分以上の移動を伴う日数」が0~7日、好ましくは4~7日、例えば、4日、5日、6日、または7日である者であり得る。 In one embodiment, the subject to be administered has a GPAQ question item of "number of days with travel of 10 minutes or more in a week" of 0 to 7 days, preferably 4 to 7 days, for example, 4 days, 5 days. It can be someone who is 1 day, 6 days, or 7 days old.
 一実施形態において、投与対象は、最高酸素摂取量が60mL/kg/分以下、例えば、40~60mL/kg/分、40~50mL/kg/分、または50~60mL/kg/分である者であり得る。 In one embodiment, the subject is one whose maximum oxygen uptake is 60 mL/kg/min or less, such as 40-60 mL/kg/min, 40-50 mL/kg/min, or 50-60 mL/kg/min. It can be.
 後述の実施例に示されているとおり、本発明の組成物は、魚介類の摂取量が少ない投与対象に対して、持久力向上効果が高い。本発明において、魚介類とは、魚類、貝類、甲殻類、および頭足類をいうが、小魚は含まない。魚介類は、生(例えば刺身など)、切り身、スリミ(例えば竹輪、蒲鉾など)、凍結物、乾燥物(例えば干物)、凍結乾燥物などのいずれの形態であってもよい。投与対象における魚介類の摂取量は、本発明の組成物の摂取開始前1週間の平均値である。好ましい実施形態において、投与対象における魚介類の摂取量は、食物摂取頻度調査票を用いた調査法(高橋ら、栄養学雑誌、Vol. 59、No. 5、p. 221 - 232(2001))により決定され得る。調査票には、以下と同等の質問が記載される:「魚介類・その加工品は何をどのくらいの量、一週間に何回食べますか?小魚は別項目に記入して下さい。普通量は80gです。80gとは、切り身1切れ、魚なら中1尾、さしみなら5切れ、干物なら1枚、竹輪やかまぼこなら中1本、あさり殻付15個、エビなら中3~4尾、いかなら1/2杯。」。回答欄においては、朝食、昼食、および夕食のそれぞれについて、食べない、少し(普通量の1/2)、普通、およびたっぷり(普通量の1.5倍)のいずれかを選択し、その1週間の回数を記入するものとする。 As shown in the Examples below, the composition of the present invention has a high effect of improving endurance in subjects who consume a small amount of seafood. In the present invention, seafood refers to fish, shellfish, crustaceans, and cephalopods, but does not include small fish. Seafood may be in any form, such as raw (for example, sashimi), filleted, surimi (for example, bamboo shoots, kamaboko, etc.), frozen, dried (for example, dried fish), or freeze-dried. The intake of seafood by the subject is the average value for one week before the start of intake of the composition of the present invention. In a preferred embodiment, the intake of seafood in the subject is determined by a survey method using a food frequency questionnaire (Takahashi et al., Journal of Nutrition, Vol. 59, No. 5, p. 221-232 (2001)). can be determined by The questionnaire includes questions equivalent to the following: "What kind of seafood and processed seafood do you eat? How many times a week do you eat it? Please enter small fish in a separate section. Normal The amount is 80g. 80g means 1 fillet, 1 medium fish, 5 sashimi, 1 dried fish, 1 medium chikuwa or kamaboko, 15 clams with shell, 3 to 4 medium shrimp. , 1/2 cup if you like.” In the answer column, select whether you eat breakfast, lunch, or dinner: none, a little (1/2 the usual amount), normal, or a lot (1.5 times the normal amount). The number of times shall be entered.
 一実施形態において、本発明の組成物の投与対象は、魚介類の摂取量が、0kcal/日以上、かつ71kcal/日以下、例えば、60kcal/日以下、50kcal/日以下、40kcal/日以下、30kcal/日以下、20kcal/日以下、または10kcal/日以下である者であり得る。あるいは、本発明の投与対象は、魚介類の摂取量が、0kcal/kg体重/日以上、かつ1.1kcal/kg体重/日以下、例えば、0.89kcal/kg体重/日以下、0.75kcal/kg体重/日以下、0.60kcal/kg体重/日以下、0.45kcal/kg体重/日以下、0.30kcal/kg体重/日以下、または0.15kcal/kg体重/日以下である者であり得る。 In one embodiment, the subject to whom the composition of the present invention is administered has a seafood intake of 0 kcal/day or more and 71 kcal/day or less, for example, 60 kcal/day or less, 50 kcal/day or less, 40 kcal/day or less, It may be 30 kcal/day or less, 20 kcal/day or less, or 10 kcal/day or less. Alternatively, the administration subject of the present invention may have a seafood intake of 0 kcal/kg body weight/day or more and 1.1 kcal/kg body weight/day or less, for example, 0.89 kcal/kg body weight/day or less, 0.75 kcal /kg body weight/day or less, 0.60 kcal/kg body weight/day or less, 0.45 kcal/kg body weight/day or less, 0.30 kcal/kg body weight/day or less, or 0.15 kcal/kg body weight/day or less It can be.
 本発明の組成物は、医薬組成物、食品組成物(例えば機能性食品、健康食品、サプリメントなど)、食品添加剤などに適した形態、例えば顆粒剤(ドライシロップを含む)、カプセル剤(軟カプセル剤、硬カプセル剤)、錠剤(チュアブル剤などを含む)、散剤(粉末剤)、丸剤などの各種の固形製剤、又は内服用液剤(液剤、懸濁剤、シロップ剤を含む)などの液状製剤などの形態で調製してもよい。例えば本発明の組成物は、有効成分をゼラチン皮膜に充填したソフトカプセルとして製剤化することができる。 The composition of the present invention can be used in forms suitable for pharmaceutical compositions, food compositions (e.g., functional foods, health foods, supplements, etc.), food additives, etc., such as granules (including dry syrup), capsules (soft capsules), etc. Various solid preparations such as tablets (including chewable preparations), powders, and pills, and liquid preparations such as liquid preparations for internal use (including liquid preparations, suspensions, and syrups) It may also be prepared in the form of a preparation. For example, the composition of the present invention can be formulated as a soft capsule containing the active ingredient in a gelatin shell.
 製剤化のための添加物としては、例えば、賦形剤、滑沢剤、結合剤、崩壊剤、流動化剤、分散剤、湿潤剤、防腐剤、粘稠剤、pH調整剤、着色剤、矯味矯臭剤、界面活性剤、溶解補助剤が挙げられる。また、液剤の形態にする場合は、ペクチン、キサンタンガム、グアガムなどの増粘剤を配合することができる。また、コーティング剤を用いてコーティング錠剤にしたり、ペースト状の膠剤とすることもできる。さらに、他の形態に調製する場合であっても、従来の方法に従えばよい。 Additives for formulation include, for example, excipients, lubricants, binders, disintegrants, fluidizers, dispersants, wetting agents, preservatives, thickeners, pH adjusters, colorants, Examples include flavoring agents, surfactants, and solubilizing agents. In addition, when it is in the form of a liquid agent, a thickener such as pectin, xanthan gum, guar gum, etc. can be added. Moreover, it can be made into a coated tablet using a coating agent or a paste-like glue. Furthermore, even when preparing other forms, conventional methods may be followed.
 本発明の組成物は、食品組成物または食品添加剤の形態をとることができる。本発明において、食品組成物は、飲料を含む食品全般を意味し、サプリメントなどの健康食品を含む一般食品の他、消費者庁の保健機能食品制度に規定される特定保健用食品や栄養機能食品をも含む。例えば、持久力向上効果を有する旨の表示を付した機能性食品が提供される。例えば、魚油を含有する食品をそのまま提供することができる。また、本発明の食品組成物または食品添加剤は、他の食品に添加し、混合し、または塗布することなどにより持久力向上効果を付与するための、食品素材も含む。食品の他に、動物用の餌料などとして提供することもできる。 The composition of the present invention can take the form of a food composition or a food additive. In the present invention, the food composition refers to foods in general including beverages, and includes general foods including health foods such as supplements, as well as foods for specified health uses and foods with nutritional function specified in the Food with Health Claims System of the Consumer Affairs Agency. Also includes. For example, functional foods labeled as having the effect of improving endurance are provided. For example, food products containing fish oil can be provided as is. The food composition or food additive of the present invention also includes food materials that can be added to, mixed with, or applied to other foods to impart an endurance-improving effect. In addition to food, it can also be provided as animal feed.
 本発明の食品組成物または食品添加剤は、食品組成物または食品添加剤中に、本発明の組成物を配合することにより、調製することができ、それにより持久力向上機能が付与される。 The food composition or food additive of the present invention can be prepared by blending the composition of the present invention into the food composition or food additive, thereby imparting an endurance-improving function.
 本発明の食品組成物は、飲料、菓子類、パン類、スープ類などであってよく、例えば、一般的なレトルト食品、冷凍食品、インスタント食品(ヌードルなど)、缶詰、ソーセージ、クッキー、ビスケット、シリアルバー、クラッカー、スナック(ポテトチップなど)、ペストリー、ケーキ、パイ、キャンデー、チューインガム(ペレットおよびスティックを含む)、ゼリー、スープ、アイス、ドレッシング、ヨーグルトなど、錠剤、カプセル剤、エマルションなどの形態のサプリメント、清涼飲料などが含まれる。これらの食品の製造方法は、本発明の効果を損なわないものであれば特に限定されず、各食品について当業者によって使用されている方法に従えばよい。 The food composition of the present invention may be a beverage, confectionery, bread, soup, etc., and includes, for example, general retort food, frozen food, instant food (noodles, etc.), canned food, sausage, cookies, biscuits, etc. Cereal bars, crackers, snacks (such as potato chips), pastries, cakes, pies, candies, chewing gum (including pellets and sticks), jellies, soups, ices, dressings, yogurts, etc., in the form of tablets, capsules, emulsions, etc. This includes supplements, soft drinks, etc. The method for producing these foods is not particularly limited as long as it does not impair the effects of the present invention, and any method used by those skilled in the art for each food may be followed.
 本発明の組成物の奏する効果を、包装容器、製品の説明書、パンフレットに表示して本発明の係る製品を販売することは本発明の範囲に含まれる。またテレビ、インターネットのウェブサイト、パンフレット、新聞、雑誌などに本発明の効果を表示して、本発明に係る製品を宣伝・販売することも本発明の範囲に含まれる。本発明の組成物を医薬品や医薬部外品とする場合には、持久力向上の効能・効果を包装容器等に表示してもよい。 It is within the scope of the present invention to sell the products of the present invention by displaying the effects of the compositions of the present invention on packaging containers, product instructions, and pamphlets. It is also within the scope of the present invention to display the effects of the present invention on television, Internet websites, pamphlets, newspapers, magazines, etc. to advertise and sell the products according to the present invention. When the composition of the present invention is used as a drug or quasi-drug, the efficacy and effect of improving endurance may be indicated on the packaging container or the like.
 本発明において対象が摂取する有効成分の量は特に限定されず、例えば、所望の効果を得るための有効量以上の量で摂取される。ここで所望の効果を得るための有効量とは、持久力向上のために必要な量をいう。例えば、成人の場合、対象の年齢、体重および健康状態などの条件に応じて、有効成分を10mg/kg体重/日以上、例えば50mg/kg体重/日以上、100mg/kg体重/日以上、摂取させることができ、また、本発明の組成物の有効成分は、強い副作用を有するものではないので、1日の摂取量に制限はないが、例えば500mg/kg体重/日以下、400mg/kg体重/日以下、200mg/kg体重/日以下、または150mg/kg体重/日以下であり得る。同様に、本発明の組成物の摂取期間に制限はないが、例えば、4週間以上、5週間以上、6週間以上、7週間以上、または8週間以上であり得、また、少なくとも持久力向上が確認されるまで摂取を継続し得る。 In the present invention, the amount of the active ingredient ingested by the subject is not particularly limited, and for example, the amount of the active ingredient ingested by the subject is at least an effective amount to obtain the desired effect. Here, the effective amount for obtaining a desired effect refers to the amount necessary for improving endurance. For example, in the case of adults, depending on the subject's age, weight, health condition, etc., the active ingredient may be ingested at least 10 mg/kg body weight/day, such as at least 50 mg/kg body weight/day, or at least 100 mg/kg body weight/day. Furthermore, since the active ingredients of the composition of the present invention do not have strong side effects, there is no limit to the daily intake, but for example, up to 500 mg/kg body weight/day, 400 mg/kg body weight. /day, up to 200 mg/kg body weight/day, or up to 150 mg/kg body weight/day. Similarly, the period of intake of the composition of the present invention is not limited, but may be, for example, for 4 weeks or more, 5 weeks or more, 6 weeks or more, 7 weeks or more, or 8 weeks or more, and at least improves endurance. Intake may continue until confirmed.
 一実施形態において、本発明の組成物は、2.0g/日以下、例えば、1.9g/日以下、1.8g/日以下、1.7g/日以下、1.6g/日以下、1.5g/日以下、1.4g/日以下、または1.3g/日以下の高度不飽和脂肪酸が、8週間以上、対象に摂取されるように使用され得る。あるいは、本発明の組成物は、30mg/kg体重/日以下、例えば28mg/kg体重/日以下、27mg/kg体重/日以下、26mg/kg体重/日以下、25mg/kg体重/日以下、24mg/kg体重/日以下、23mg/kg体重/日以下、22mg/kg体重/日以下、21mg/kg体重/日以下、20mg/kg体重/日以下、または19mg/kg体重/日以下の高度不飽和脂肪酸が、8週間以上、対象に摂取されるように使用され得る。あるいは、本発明の組成物は、19mg/kg体重/日以上、かつ30mg/kg体重/日以下、例えば28mg/kg体重/日以下、27mg/kg体重/日以下、26mg/kg体重/日以下、25mg/kg体重/日以下、24mg/kg体重/日以下、23mg/kg体重/日以下、22mg/kg体重/日以下、21mg/kg体重/日以下、または20mg/kg体重/日以下の高度不飽和脂肪酸が、8週間以上、対象に摂取されるように使用され得る。 In one embodiment, the composition of the present invention comprises 2.0 g/day or less, such as 1.9 g/day or less, 1.8 g/day or less, 1.7 g/day or less, 1.6 g/day or less, 1. Up to .5 g/day, up to 1.4 g/day, or up to 1.3 g/day of highly unsaturated fatty acids can be used to be ingested by the subject for 8 weeks or more. Alternatively, the composition of the present invention may be administered at a dose of 30 mg/kg body weight or less, such as 28 mg/kg body weight or less, 27 mg/kg body weight or less, 26 mg/kg body weight or less, 25 mg/kg body weight/day or less, Altitude below 24 mg/kg body weight/day, below 23 mg/kg body weight/day, below 22 mg/kg body weight/day, below 21 mg/kg body weight/day, below 20 mg/kg body weight/day, or below 19 mg/kg body weight/day Unsaturated fatty acids can be used to be ingested by a subject for 8 weeks or more. Alternatively, the composition of the invention may be administered at a dose of 19 mg/kg body weight or more and 30 mg/kg body weight/day or less, such as 28 mg/kg body weight or less, 27 mg/kg body weight/day or less, 26 mg/kg body weight/day or less. , 25 mg/kg body weight/day or less, 24 mg/kg body weight/day or less, 23 mg/kg body weight/day or less, 22 mg/kg body weight/day or less, 21 mg/kg body weight/day or less, or 20 mg/kg body weight/day or less Highly unsaturated fatty acids can be used to be ingested by a subject for 8 weeks or more.
 一実施形態において、高度不飽和脂肪酸がエイコサペンタエン酸および/またはドコサヘキサエン酸である場合、本発明の組成物は、1.0g/日以下、例えば0.95g/日以下、0.90g/日以下、または0.86g/日以下の高度不飽和脂肪酸が、8週間以上、対象に摂取されるように使用され得る。あるいは、高度不飽和脂肪酸がエイコサペンタエン酸および/またはドコサヘキサエン酸である場合、本発明の組成物は、15mg/kg体重/日以下、例えば14mg/kg体重/日以下、または13mg/kg体重/日以下の高度不飽和脂肪酸が、8週間以上、対象に摂取されるように使用され得る。あるいは、高度不飽和脂肪酸がエイコサペンタエン酸および/またはドコサヘキサエン酸である場合、本発明の組成物は、13mg/kg体重/日以上、かつ15mg/kg体重/日以下、例えば14mg/kg体重/日以下の高度不飽和脂肪酸が、8週間以上、対象に摂取されるように使用され得る。ここで、高度不飽和脂肪酸の摂取量は、本発明の組成物の有効成分であるトリグリセリド中の構成脂肪酸を遊離脂肪酸に変換した値である。特許文献7などに示されているように、EPA/MCT構造脂質を単回摂取した際にEPAの血中移行が一過性に高まることが知られていた。しかし、血中EPA濃度と持久力向上との間に関連性があるか否かは知られていない。 In one embodiment, when the highly unsaturated fatty acid is eicosapentaenoic acid and/or docosahexaenoic acid, the composition of the present invention may contain up to 1.0 g/day, such as up to 0.95 g/day, up to 0.90 g/day. , or 0.86 g/day or less of highly unsaturated fatty acids may be used to be ingested by the subject for 8 weeks or more. Alternatively, if the highly unsaturated fatty acid is eicosapentaenoic acid and/or docosahexaenoic acid, the composition of the invention may contain up to 15 mg/kg body weight/day, such as up to 14 mg/kg body weight/day, or 13 mg/kg body weight/day. The following highly unsaturated fatty acids may be used to be ingested by a subject for 8 weeks or more. Alternatively, when the highly unsaturated fatty acid is eicosapentaenoic acid and/or docosahexaenoic acid, the composition of the invention may contain at least 13 mg/kg body weight/day and at most 15 mg/kg body weight/day, such as 14 mg/kg body weight/day. The following highly unsaturated fatty acids may be used to be ingested by a subject for 8 weeks or more. Here, the intake amount of highly unsaturated fatty acids is the value obtained by converting the constituent fatty acids in triglyceride, which is an active ingredient of the composition of the present invention, into free fatty acids. As shown in Patent Document 7 and the like, it has been known that when an EPA/MCT structured lipid is ingested once, the transfer of EPA into the blood is transiently increased. However, it is not known whether there is a relationship between blood EPA concentration and improved endurance.
 好ましい実施形態において、本発明の組成物は、構成脂肪酸として高度不飽和脂肪酸と中鎖脂肪酸とを含むトリグリセリドを有効成分として含有する、持久力向上用組成物であって、
当該組成物の脂肪酸組成において高度不飽和脂肪酸が10~70重量%であり、中鎖脂肪酸が20~70重量%であり、
高度不飽和脂肪酸がエイコサペンタエン酸およびドコサヘキサエン酸であり、
中鎖脂肪酸がカプリル酸およびカプリン酸であり、
13mg/kg体重/日以上、かつ15mg/kg体重/日以下の高度不飽和脂肪酸が、8週間以上、対象に摂取されるように使用され、
対象が、GPAQの質問項目である「1週間の中で、仕事での高強度身体活動日数」が0~2日であり、「1週間の中で、仕事での中強度身体活動日数」が0~3日であり、かつ「1週間の中で、10分以上の移動を伴う日数」が4~7日である者であり、かつ
持久力向上が、運動継続時間延長、高強度運動時の運動継続時間延長、有酸素性運動時の運動継続時間延長、漸増負荷運動時の運動継続時間延長、運動時の脂質燃焼促進、高強度運動時の脂質燃焼促進、有酸素性運動時の脂質燃焼促進、漸増負荷運動時の脂質燃焼促進、無酸素性作業閾値の向上、運動時の疲労の軽減、および筋持久力向上からなる群から選択される少なくとも1つである、組成物を提供する。
In a preferred embodiment, the composition of the present invention is an endurance-improving composition containing as an active ingredient triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids,
In the fatty acid composition of the composition, highly unsaturated fatty acids are 10 to 70% by weight, medium chain fatty acids are 20 to 70% by weight,
The highly unsaturated fatty acids are eicosapentaenoic acid and docosahexaenoic acid,
medium chain fatty acids are caprylic acid and capric acid;
13 mg/kg body weight/day or more and 15 mg/kg body weight/day or less of highly unsaturated fatty acids are used so as to be ingested by the subject for 8 weeks or more,
The target GPAQ question item, ``Number of days of high-intensity physical activity at work per week'' is 0 to 2 days, and ``Number of days of moderate-intensity physical activity at work per week'' is 0 to 2 days. 0 to 3 days, and ``the number of days in a week that involves movement for 10 minutes or more'' is 4 to 7 days, and the improvement of endurance is due to prolonged exercise duration and high-intensity exercise. Extends exercise duration during aerobic exercise, increases exercise duration during progressively increasing load exercise, promotes fat burning during exercise, promotes fat burning during high-intensity exercise, increases fat during aerobic exercise Provided is a composition that is at least one selected from the group consisting of promoting combustion, promoting fat burning during exercise with increasing load, improving anaerobic work threshold, reducing fatigue during exercise, and improving muscular endurance. .
 好ましい実施形態において、本発明の組成物は、構成脂肪酸として高度不飽和脂肪酸と中鎖脂肪酸とを含むトリグリセリドを有効成分として含有する、運動継続時間延長用組成物であって、
当該組成物の脂肪酸組成において高度不飽和脂肪酸が10~70重量%であり、中鎖脂肪酸が20~70重量%であり、
高度不飽和脂肪酸がエイコサペンタエン酸およびドコサヘキサエン酸であり、
中鎖脂肪酸がカプリル酸およびカプリン酸であり、
13mg/kg体重/日以上、かつ15mg/kg体重/日以下の高度不飽和脂肪酸が、8週間以上、対象に摂取されるように使用され、
対象が、GPAQの質問項目である「1週間の中で、仕事での高強度身体活動日数」が0~2日であり、「1週間の中で、仕事での中強度身体活動日数」が0~3日であり、かつ「1週間の中で、10分以上の移動を伴う日数」が4~7日である者であり、かつ
対象の魚介類摂取量が、0kcal/kg体重/日以上、かつ1.1kcal/kg体重/日以下、0.89kcal/kg体重/日以下、0.75kcal/kg体重/日以下、0.60kcal/kg体重/日以下、0.45kcal/kg体重/日以下、0.30kcal/kg体重/日以下、または0.15kcal/kg体重/日以下である、組成物を提供する。
In a preferred embodiment, the composition of the present invention is a composition for extending exercise duration, which contains as an active ingredient triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids,
In the fatty acid composition of the composition, highly unsaturated fatty acids are 10 to 70% by weight, medium chain fatty acids are 20 to 70% by weight,
The highly unsaturated fatty acids are eicosapentaenoic acid and docosahexaenoic acid,
medium chain fatty acids are caprylic acid and capric acid;
13 mg/kg body weight/day or more and 15 mg/kg body weight/day or less of polyunsaturated fatty acids are used so as to be ingested by the subject for 8 weeks or more,
The target GPAQ question item, ``Number of days of high-intensity physical activity at work per week'' is 0 to 2 days, and ``Number of days of moderate-intensity physical activity at work per week'' is 0 to 2 days. 0 to 3 days, and the number of days in a week that involves traveling for 10 minutes or more is 4 to 7 days, and the subject's seafood intake is 0 kcal/kg body weight/day. or more, and 1.1 kcal/kg body weight/day or less, 0.89 kcal/kg body weight/day or less, 0.75 kcal/kg body weight/day or less, 0.60 kcal/kg body weight/day or less, 0.45 kcal/kg body weight/day 0.30 kcal/kg body weight/day or less, or 0.15 kcal/kg body weight/day or less.
 一態様において、本発明は、持久力を向上させる方法であって、対象に有効量の本発明の組成物を摂取させることを含む、前記方法を提供し得る。当該方法は、本発明の組成物の摂取または投与に関する本明細書中の記載にしたがって実施することができる。 In one aspect, the present invention may provide a method for improving endurance, the method comprising causing a subject to ingest an effective amount of a composition of the present invention. The method can be carried out according to the description herein regarding ingestion or administration of the compositions of the invention.
 次に実施例を挙げて本発明を更に説明するが、本発明はこれらに限定されるものではない。 Next, the present invention will be further explained with reference to Examples, but the present invention is not limited thereto.
 実施例1
 1.材料および方法
 (1)被験物質の調製
 精製魚油(日本水産株式会社製、規格値としてEPA28重量%、DHA12重量%)と、中鎖脂肪酸のみを構成脂肪酸とするトリグリセリド(MCT;カプリル酸約60重量%、カプリン酸約40重量%)を用いた。精製魚油とMCTとを重量比55:45にて混合し、ナトリウムメトキシドを0.2重量%添加し、60~80℃で60分間撹拌しエステル交換を行った。生成物を、水洗、乾燥、脱色、脱臭して、EPAを含む魚油由来の脂肪酸と中鎖脂肪酸を構成脂肪酸とするトリグリセリド(実施例中、以下、STG)を調製した。
 精製魚油とMCTとを重量比50:50にて混合した混合油(実施例中、以下、PM)を対照サンプルとして調製した。
 精製魚油、MCT、STG、およびPMの脂肪酸組成を表1に示す。
Example 1
1. Materials and methods (1) Preparation of test substance Refined fish oil (manufactured by Nippon Suisan Co., Ltd., standard values: EPA 28% by weight, DHA 12% by weight) and triglyceride (MCT; approximately 60% by weight caprylic acid) whose constituent fatty acids are only medium-chain fatty acids. %, about 40% by weight of capric acid). Refined fish oil and MCT were mixed at a weight ratio of 55:45, 0.2% by weight of sodium methoxide was added, and the mixture was stirred at 60 to 80°C for 60 minutes to perform transesterification. The product was washed with water, dried, bleached, and deodorized to prepare a triglyceride (hereinafter referred to as STG in the examples) whose constituent fatty acids were a fish oil-derived fatty acid containing EPA and a medium-chain fatty acid.
A mixed oil (hereinafter referred to as PM in the Examples) in which purified fish oil and MCT were mixed at a weight ratio of 50:50 was prepared as a control sample.
The fatty acid compositions of refined fish oil, MCT, STG, and PM are shown in Table 1.
 (2)試験参加者
 日頃からトレーニング習慣のない健康な若年男性19名が試験に参加した。
 被験者に関するデータ(平均±SD)を以下に示す。年齢、体重、平均BMI、およびVO2peak(最高酸素摂取量)は、試験開始時のデータである。身体活動日数は、試験開始前1週間の平均値であり、世界標準化身体活動質問票(Global Physical Activity Questionnaire(GPAQ);Bull FC et al. Global physical activity questionnaire (GPAQ): nine country reliability and validity study. J Phys Act Health. 2009 Nov;6(6):790-804)に対する回答に基づく。ここで、「仕事」には、学業およびアルバイトも含まれる。また、「高強度身体活動」および「中強度身体活動」とは、それぞれ8メッツの身体活動および4メッツの身体活動をいう(Global Physical Activity Questionnaire (GPAQ) Analysis Guide, Surveillance and Population-Based Prevention, Prevention of Noncommunicable Diseases Department, World Health Organization)。魚介類摂取量は、試験開始前1週間の平均値であり、食物摂取頻度調査票を用いた調査法(高橋ら、栄養学雑誌、Vol. 59、No. 5、p. 221 - 232(2001))により決定した。調査票には、以下の質問が記載された:「魚介類・その加工品は何をどのくらいの量、一週間に何回食べますか?小魚は別項目に記入して下さい。普通量は80gです。80gとは、切り身1切れ、魚なら中1尾、さしみなら5切れ、干物なら1枚、竹輪やかまぼこなら中1本、あさり殻付15個、エビなら中3~4尾、いかなら1/2杯。」。回答欄においては、朝食、昼食、および夕食のそれぞれについて、食べない、少し(普通量の1/2)、普通、およびたっぷり(普通量の1.5倍)のいずれかを選択し、その1週間の回数を記入するものとした。
 年齢:20±2歳
 体重:67.1±8.9 kg
 平均BMI:22.8±3.1 kg/m2
 VO2peak(最高酸素摂取量):43.4±6.1 mL/kg/min
 「1週間の中で、仕事での高強度身体活動日数」:0.4±0.9日
 「1週間の中で、仕事での中強度身体活動日数」:1.1±1.7日
 「1週間の中で、10分以上の移動を伴う日数」:5.3±1.0日
*:本実施例において測定されたVO2peakは、VO2max(最大酸素摂取量)とほぼ同じ値として扱うことができる。
(2) Test participants Nineteen healthy young men with no regular training habits participated in the test.
Data regarding the subjects (mean ± SD) are shown below. Age, weight, average BMI, and VO 2 peak (peak oxygen uptake) are data at the start of the study. The number of days of physical activity is the average value for one week before the start of the study, and is calculated using the Global Physical Activity Questionnaire (GPAQ); Bull FC et al. Global physical activity questionnaire (GPAQ): nine country reliability and validity study. J Phys Act Health. 2009 Nov;6(6):790-804). Here, "work" includes studies and part-time jobs. In addition, "high-intensity physical activity" and "moderate-intensity physical activity" refer to physical activity of 8 METs and physical activity of 4 METs, respectively (Global Physical Activity Questionnaire (GPAQ) Analysis Guide, Surveillance and Population-Based Prevention, Prevention of Noncommunicable Diseases Department, World Health Organization). Seafood intake was the average value for one week before the start of the study, and was determined using a survey method using a food frequency questionnaire (Takahashi et al., Journal of Nutrition, Vol. 59, No. 5, p. 221 - 232 (2001). )). The following questions were included in the questionnaire: ``What kind of seafood and processed seafood do you eat, how much of it, and how many times a week do you eat?Please write in a separate section for small fish. 80g. 80g means 1 fillet, 1 medium fish, 5 sashimi pieces, 1 dried fish, 1 medium chikuwa or kamaboko, 15 clams with shells, 3 to 4 medium shrimp, and squid. Then 1/2 cup." In the answer column, select whether you eat breakfast, lunch, or dinner: none, a little (1/2 the usual amount), normal, or a lot (1.5 times the normal amount). The number of times was recorded.
Age: 20±2 years Weight: 67.1±8.9 kg
Average BMI: 22.8±3.1 kg/ m2
VO 2 peak (maximum oxygen uptake) * : 43.4±6.1 mL/kg/min
“Number of days of high-intensity physical activity at work per week”: 0.4±0.9 days “Number of days of moderate-intensity physical activity at work per week”: 1.1±1.7 days “Number of days of moderate-intensity physical activity at work per week”: 10 days per week "Number of days involving travel of more than 1 minute": 5.3±1.0 days*: VO 2 peak measured in this example can be treated as approximately the same value as VO 2 max (maximum oxygen uptake).
 (3)試験概要
 試験参加者を、無作為に、STGを摂取する群(STG群;n=9)とPMを摂取する群(PM群;n=10)とに分けた。STG群およびPM群は、それぞれ4.38g/日のSTGおよびPMを、8週間摂取した。いずれも、遊離脂肪酸に換算して600mg/日のEPAおよび260mg/日のDHAを摂取することになる。
 試験参加者は、被験物質の摂取前および8週間の摂取後に、最高酸素摂取量(VO2peak)試験を受けた。試験期間中、試験参加者は、摂取前からの食生活を変えないように指導を受け、試験参加者の試験期間中の摂取カロリーの平均値は2235 kcal/日であり、水分摂取量の平均値は1085 g/日、たんぱく質摂取量の平均値は90 g/日、脂質摂取量の平均値は74 g/日、炭水化物摂取量の平均値は289 g/日であった。
(3) Study outline Test participants were randomly divided into a group that ingested STG (STG group; n = 9) and a group that ingested PM (PM group; n = 10). The STG and PM groups ingested 4.38 g/day of STG and PM, respectively, for 8 weeks. In either case, the intake amount is 600 mg/day of EPA and 260 mg/day of DHA in terms of free fatty acids.
Study participants underwent a peak oxygen uptake (VO 2 peak) test before and after 8 weeks of ingestion of the test substance. During the study period, study participants were instructed not to change their dietary habits prior to intake.The average calorie intake of study participants during the study period was 2235 kcal/day, and the average water intake The mean protein intake was 90 g/day, the mean fat intake was 74 g/day, and the mean carbohydrate intake was 289 g/day.
 (4)最高酸素摂取量(VO2peak)測定方法
 自転車エルゴメータを用いた多段階負荷漸増法(運動時のペダル回転速度は60rpmとした)により測定を行った。3分間の安静後、20wattの負荷で3分間のウォーミングアップ運動を行った。ウォーミングアップ運動終了後、60wattの負荷から運動を開始し、2分毎に30wattずつ負荷を上げ、疲労困憊に至るまで運動を行わせた。試験参加者のペダル回転速度が50rpmを3回下回った時を最終の運動負荷とし、その負荷での酸素摂取量の測定が完了した時点を以て、運動及び測定を終了した。運動終了時の運動継続時間を記録した。
 また、本試験において二酸化炭素排出量を測定した。酸素摂取量は運動負荷に比例して増加するが、二酸化炭素排出量はある運動負荷から急激に増加することが知られている。二酸化炭素排出量が急激に増加した点を、無酸素性作業閾値(換気性作業閾値)とした。無酸素性作業閾値の変化は、(無酸素性作業閾値における酸素摂取量/最高酸素摂取量)×100(%VO2peak;AT値)を算出して評価した。
(4) Maximum oxygen uptake (VO 2 peak) measurement method Measurement was performed by a multi-step load increasing method using a bicycle ergometer (pedal rotation speed during exercise was 60 rpm). After 3 minutes of rest, the subjects performed a 3-minute warm-up exercise with a load of 20 watts. After the warm-up exercise was completed, exercise was started with a load of 60 watts, and the load was increased by 30 watts every 2 minutes until exhaustion was reached. The final exercise load was defined as the time when the test participant's pedal rotation speed fell below 50 rpm three times, and the exercise and measurements were terminated when the measurement of oxygen intake under that load was completed. The duration of exercise at the end of exercise was recorded.
In addition, carbon dioxide emissions were measured in this test. It is known that oxygen intake increases in proportion to exercise load, but carbon dioxide output rapidly increases after a certain exercise load. The point at which carbon dioxide emissions suddenly increased was defined as the anaerobic work threshold (ventilatory work threshold). Changes in the anaerobic work threshold were evaluated by calculating (oxygen uptake at anaerobic work threshold/maximum oxygen uptake) x 100 (%VO 2 peak; AT value).
 (5)統計解析
 運動継続時間およびAT値の分析は、二元配置分散解析により行った。運動継続時間の変化量、AT値の変化量、およびVO2peakの変化量の分析は、対応のあるt検定により行った。
(5) Statistical analysis Analysis of exercise duration and AT value was performed by two-way analysis of variance. Analysis of the amount of change in exercise duration, the amount of change in AT value, and the amount of change in VO 2 peak was performed using a paired t-test.
 [結果]
 各群における摂取前後の最高酸素摂取量測定時の運動継続時間を図1に示す。STG群では、STG摂取後の運動継続時間は、STG摂取前と比較して有意に増加した(二元配置分散解析、p<0.05)。一方、PM群では、PMの摂取前後で運動継続時間の有意な変化は見られなかった。また、STG群の摂取前後の運動継続時間の変化量(53±53秒)とPM群の摂取前後の運動継続時間の変化量(-10±63秒)とをt検定により分析したところ、有意差(p<0.05)が見られた(図2)。したがって、構成脂肪酸として高度不飽和脂肪酸および中鎖脂肪酸を含むトリグリセリドが持久力を向上させる機能、特に運動継続時間を延長させる機能を有することが示された。
[result]
Figure 1 shows the duration of exercise when measuring the maximum oxygen uptake before and after intake in each group. In the STG group, the exercise duration after STG intake was significantly increased compared to before STG intake (two-way analysis of variance, p<0.05). On the other hand, in the PM group, no significant change in exercise duration was observed before and after ingesting PM. In addition, when we analyzed the amount of change in exercise duration before and after intake in the STG group (53 ± 53 seconds) and the amount of change in exercise duration before and after intake in the PM group (-10 ± 63 seconds), it was found that there was a significant A difference (p<0.05) was observed (Figure 2). Therefore, it has been shown that triglycerides containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids have a function of improving endurance, particularly a function of extending exercise duration.
 各群における摂取前後の無酸素性作業閾値の値(%VO2peak)を図3に示す。STG群では、STG摂取後のAT値は、STG摂取前と比較して、またPM摂取後と比較して、有意に高くなった(二元配置分散解析、p<0.05)。一方、PM群では、PMの摂取前後でAT値の有意な変化は見られなかった。また、STG群の摂取前後のAT値の変化量(6±5)とPM群の摂取前後のAT値の変化量(0±6)とをt検定により分析したところ、有意差(p<0.05)が見られた(図4)。AT値が高くなることは、有酸素性運動が可能な時間が延長することを意味する。有酸素性運動時の主なエネルギー源は糖質および脂質であり、無酸素性運動時の主なエネルギー源は糖質である。運動時の脂質利用が促進されることにより、AT値は高くなると考えられる。したがって、本実施例における結果から、構成脂肪酸として高度不飽和脂肪酸および中鎖脂肪酸を含むトリグリセリドの摂取により、同様の脂肪酸組成を有する物理的混合油を摂取した場合よりも、運動時のエネルギー源としての脂質の利用が促進されることが示唆された。 Figure 3 shows the anaerobic work threshold values (%VO 2 peak) before and after intake in each group. In the STG group, the AT value after STG intake was significantly higher compared to before STG intake and compared to after PM intake (two-way analysis of variance, p<0.05). On the other hand, in the PM group, no significant change in AT value was observed before and after ingesting PM. In addition, when the amount of change in AT value before and after intake in the STG group (6±5) and the amount of change in AT value before and after intake in the PM group (0±6) were analyzed using a t-test, there was a significant difference (p<0.05). ) was observed (Figure 4). A higher AT value means that the time available for aerobic exercise is extended. The main energy sources during aerobic exercise are carbohydrates and lipids, and the main energy sources during anaerobic exercise are carbohydrates. It is thought that the AT value increases by promoting lipid utilization during exercise. Therefore, from the results of this example, the intake of triglycerides containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids is more effective as an energy source during exercise than the intake of physically mixed oils with similar fatty acid compositions. It was suggested that the utilization of lipids was promoted.
 また、STG群の運動継続時間について、魚介類摂取量がSTG群の試験参加者の平均値(71 kcal/日、あるいは1.1 kcal/kg 体重/日)よりも少ない群(n=5)と多い群(n=3)に分けて層別解析を行った(表2)。その結果、魚介類摂取量が少ない群は、魚介類摂取量が多い群に比べて、STG摂取前後の運動継続時間の変化量が大きい傾向があることが見出された。
In addition, regarding the duration of exercise in the STG group, the intake of seafood was lower (n = 5) than the average value of test participants in the STG group (71 kcal/day, or 1.1 kcal/kg body weight/day). Stratified analysis was performed by dividing into groups (n=3) (Table 2). As a result, it was found that the group with a low seafood intake tended to have a larger change in exercise duration before and after STG intake than the group with a high seafood intake.
 したがって、構成脂肪酸として高度不飽和脂肪酸および中鎖脂肪酸を含むトリグリセリドは、魚介類の摂取量が比較的少ない対象に対して、特に高い持久力向上機能を発揮することが示された。 Therefore, it has been shown that triglycerides containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids exhibit a particularly high ability to improve endurance in subjects who consume relatively little seafood.
 本発明により、持久力を向上させる医薬組成物、食品組成物、食品添加剤などが提供される。 The present invention provides pharmaceutical compositions, food compositions, food additives, etc. that improve endurance.

Claims (11)

  1.  構成脂肪酸として高度不飽和脂肪酸と中鎖脂肪酸とを含むトリグリセリドを有効成分として含有する、持久力向上用組成物。 An endurance-improving composition containing as an active ingredient triglyceride containing highly unsaturated fatty acids and medium-chain fatty acids as constituent fatty acids.
  2.  当該組成物の脂肪酸組成において高度不飽和脂肪酸が10~70重量%であり、中鎖脂肪酸が20~70重量%である、請求項1に記載の組成物。 The composition according to claim 1, wherein the fatty acid composition of the composition contains 10 to 70% by weight of highly unsaturated fatty acids and 20 to 70% by weight of medium chain fatty acids.
  3.  19mg/kg体重/日以上、かつ30mg/kg体重/日以下の高度不飽和脂肪酸が、8週間以上、対象に摂取されるように使用されることを特徴とする、請求項1または2に記載の組成物。 3. According to claim 1 or 2, the highly unsaturated fatty acid is used so as to be ingested by the subject for 8 weeks or more. Composition of.
  4.  魚介類摂取量が1.1kcal/kg体重/日以下である対象に摂取されるように使用されることを特徴とする、請求項1~3のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 3, which is used to be ingested by a subject whose seafood intake is 1.1 kcal/kg body weight/day or less.
  5.  最高酸素摂取量が60mL/kg/分以下である対象に摂取されるように使用されることを特徴とする、請求項1~4のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 4, which is used to be ingested by a subject whose maximum oxygen uptake is 60 mL/kg/min or less.
  6.  高度不飽和脂肪酸が、炭素数20以上の脂肪酸である、請求項1~5のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 5, wherein the highly unsaturated fatty acid is a fatty acid having 20 or more carbon atoms.
  7.  高度不飽和脂肪酸が、エイコサペンタエン酸またはドコサヘキサエン酸である、請求項6に記載の組成物。 The composition according to claim 6, wherein the highly unsaturated fatty acid is eicosapentaenoic acid or docosahexaenoic acid.
  8.  中鎖脂肪酸が、炭素数8~12の脂肪酸である、請求項1~7のいずれか一項に記載の組成物。 The composition according to any one of claims 1 to 7, wherein the medium chain fatty acid is a fatty acid having 8 to 12 carbon atoms.
  9.  持久力向上が、運動継続時間延長、高強度運動時の運動継続時間延長、有酸素性運動時の運動継続時間延長、漸増負荷運動時の運動継続時間延長、運動時の脂質燃焼促進、高強度運動時の脂質燃焼促進、有酸素性運動時の脂質燃焼促進、漸増負荷運動時の脂質燃焼促進、無酸素性作業閾値の向上、運動時の疲労の軽減、および筋持久力向上からなる群から選択される少なくとも1つである、請求項1~8のいずれか一項に記載の組成物。 Improved endurance can be achieved by extending the duration of exercise, extending the duration of exercise during high-intensity exercise, extending the duration of exercise during aerobic exercise, extending the duration of exercise during progressively increasing load exercise, promoting fat burning during exercise, and increasing the intensity of exercise. From the group consisting of promoting fat burning during exercise, promoting fat burning during aerobic exercise, promoting fat burning during progressively increasing load exercise, improving anaerobic work threshold, reducing fatigue during exercise, and improving muscular endurance. The composition according to any one of claims 1 to 8, which is at least one selected from the group consisting of:
  10.  請求項1~9のいずれか一項に記載の組成物を含む、持久力向上用食品組成物または食品添加剤。 A food composition or food additive for improving endurance, comprising the composition according to any one of claims 1 to 9.
  11.  持久力向上に用いるための食品組成物または食品添加剤を製造する方法であって、食品組成物または食品添加剤中に、請求項1~9のいずれか一項に記載の組成物を配合することにより持久力向上機能を付与することを含む、前記方法。 A method for producing a food composition or food additive for use in improving endurance, the method comprising incorporating the composition according to any one of claims 1 to 9 into the food composition or food additive. said method comprising imparting an endurance-enhancing function.
PCT/JP2023/024722 2022-07-04 2023-07-04 Endurance-improving agent WO2024009986A1 (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11239465A (en) * 1997-06-16 1999-09-07 Nippon Suisan Kaisha Ltd Food product for healthy persons to increase their moving ability
JP2002180082A (en) * 2000-12-11 2002-06-26 Maruha Corp Intake material
WO2015050071A1 (en) * 2013-10-01 2015-04-09 日本水産株式会社 Nutritional supplement and agent for improving cardiovascular diseases
JP2019517470A (en) * 2016-05-27 2019-06-24 スマートフィッシュ・アーエス Use of a composition comprising marine oil and juice to improve muscle performance

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11239465A (en) * 1997-06-16 1999-09-07 Nippon Suisan Kaisha Ltd Food product for healthy persons to increase their moving ability
JP2002180082A (en) * 2000-12-11 2002-06-26 Maruha Corp Intake material
WO2015050071A1 (en) * 2013-10-01 2015-04-09 日本水産株式会社 Nutritional supplement and agent for improving cardiovascular diseases
JP2019517470A (en) * 2016-05-27 2019-06-24 スマートフィッシュ・アーエス Use of a composition comprising marine oil and juice to improve muscle performance

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