Antifatigue composition and composition for improving, suppressing reduction of, and maintaining energy production performance

Abstract

The present invention aims to provide a composition which can improve or maintain mitochondrial function or reduce a decline in mitochondrial function, which is effective in improving or maintaining energy production capacity or reducing a decline in energy production capacity and effective in anti-fatigue, and which is highly safe and suitable for continuous ingestion. The present invention relates to an anti-fatigue composition containing at least one sesamin-class compound and lutein and / or a fatty acid ester thereof.

Description

Anti-fatigue composition and composition for improving, inhibiting decline in, or maintaining energy production capacity

[0001] The present invention relates to an anti-fatigue composition. The present invention also relates to a composition for improving, inhibiting a decline in, or maintaining energy production capacity. The present invention also relates to the use of one or more sesamin compounds and lutein and / or its fatty acid esters for inhibiting, alleviating, or ameliorating fatigue. The present invention further relates to the use of one or more sesamin compounds and lutein and / or its fatty acid esters for improving, inhibiting a decline in, or maintaining energy production capacity.

[0002] Energy production refers to the production of energy necessary for humans and non-human animals to maintain their activities. Most energy production occurs within mitochondria, a type of intracellular organelle. Sugars, lipids, amino acids, and other nutrients ingested from food are metabolized through glycolysis, the pentose phosphate pathway, and the citric acid cycle and converted into nicotinamide adenine dinucleotide (NADH). NADH electrons are then transferred to mitochondrial respiratory chain proteins (electron transport chain), producing energy in the form of adenosine triphosphate (ATP). Reduced ATP production is known to cause various problems in humans, including obesity due to decreased metabolic capacity, increased risk of diabetes, decreased muscle strength, increased fatigue, lethargy, decreased concentration, and depression.

[0003] Maintaining ATP production is important for reducing fatigue, maintaining concentration, exercising using muscles, and maintaining physical and mental vitality.

[0004] Various energy production enhancers containing carbohydrates, amino acids, and lipids, which are substrates necessary for ATP production, have been known so far. Patent Document 1 describes a composition for improving intracellular energy production metabolism from fatty acids, which contains xanthophyll as an active ingredient.

[0005] As mentioned above, the substrates necessary for ATP production are converted to ATP via the mitochondrial electron transport system, but even if the substrates increase, ATP cannot be produced if mitochondrial function is impaired. It is known that impaired mitochondrial function is caused by aging and oxidative stress, resulting in a decrease in ATP production (Non-Patent Documents 1 and 3).

[0006] When a component that suppresses mitochondrial dysfunction is taken as a supplement, it is desirable that the form be easy for consumers to take continuously. For elderly people in particular, as their swallowing function declines, it is desirable for tablets and capsules to be small. Since the volume of tablets and capsules tends to be large, especially when multiple components are included, it is desirable to use a component or combination of such components that is highly effective even in small amounts in order to reduce the volume of the tablets and capsules.

[0007] Sesamin is a lignan compound found in sesame and has been reported to have antioxidant properties. It has been reported that sesamin has an antioxidant effect that inhibits mitochondrial dysfunction in diabetic model mice (Non-Patent Document 4). Furthermore, sesamin is known to inhibit mitochondrial reactive oxygen production and mitochondrial membrane potential decline through its antioxidant properties (Non-Patent Document 2). It has also been reported that sesamin activates PGC1α, which is involved in mitochondrial biogenesis (Patent Document 2).

[0008] Lutein has also been reported to activate mitochondrial function in neuronal cell lines (Non-Patent Document 5). Ingestion of a mixture containing lutein has been reported to alleviate mental stress (Non-Patent Document 6) and eye fatigue (Non-Patent Documents 7 and 8).

[0009] JP 2009-215170 A International Publication No. 2018 / 079719

[0010] Conley, Kevin E., et al. “Oxidative capacity and ageing in human muscle.” The Journal of physiology 526.1 (2000): 203-210.Maharjan, Sunita, et al. “Mitochondrial impairment triggers cytosolic oxidative stress and cell death following proteasome inhibition.” Scientific reports 4 (2014): 5896.Kudryavtseva, Anna V., et al. “Mitochondrial dysfunction and oxidative stress in aging and cancer.” Oncotarget 7.29 (2016): 44879.Takada, Shingo, et al. “Sesamin prevents decline in exercise capacity and impairment of skeletal muscle mitochondrial function in mice with high-fat diet-induced diabetes.” Experimental physiology 100.11 (2015): 1319-1330.Xie K, et al. “Modulation of mitochondrial respiration underpins neuronal differentiation enhanced by lutein.” Neural Regen Res. 2019 Jan;14(1):87-99. Stringham NT, et al. “Supplementation with macular carotenoids reduces psychological stress, serum cortisol, and sub-optimal symptoms of ``Physical and emotional health in young adults.'' Nutr Neurosci. 2018 May; 21 (4): 286-296. Stringham JM, et al. “Macular Carotenoid Supplementation Improves Visual Performance, Sleep Quality, and Adverse Physical Symptoms in Those with High Screen Time Exposure. 2017 Jun 29;6(7). pii: E47. Kawabata F, et al. “Effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on objective Symptoms of asthenopia in humans.” Biomed Res. 2011 Dec; 32(6):387-93. ;

[0011] Since energy is constantly required to maintain activity in humans and other organisms, a highly safe method for promoting energy production using ingredients that can be taken continuously without the risk of side effects is desired. Conventionally, methods for increasing energy production by ingesting energy production substrates have been proposed, but the effects cannot be fully enjoyed when mitochondrial function is impaired. Furthermore, while food ingredients that have the effect of improving energy production are known, from the standpoint of ease of intake and safety when taken continuously, it is desirable to have an ingredient or combination of ingredients that is effective even in small amounts.

[0012] The present invention aims to provide a composition that can improve, inhibit the decline of, or maintain mitochondrial function, is effective in improving, inhibiting the decline of, or maintaining energy production capacity, and is effective against fatigue, is highly safe, and can be taken continuously.

[0013] The present inventors conducted extensive research to solve the above problems and investigated components that can be used to improve, inhibit the decline of, or maintain mitochondrial function. They found that by combining sesamin-class compounds, which are components that maintain or activate mitochondrial function, with lutein and / or its fatty acid esters, which are components that activate mitochondrial function, it is possible to improve, inhibit the decline of, or maintain mitochondrial function and energy production capacity more effectively (synergistically) than by using sesamin-class compounds alone or lutein and / or its fatty acid esters alone.

[0014] That is, the present invention encompasses, but is not limited to, the following anti-fatigue compositions, compositions for improving, inhibiting decline, or maintaining energy production capacity, uses, etc.: [1] An anti-fatigue composition containing one or more sesamin compounds and lutein and / or its fatty acid esters. [2] The composition described in [1] above, which inhibits, alleviates, or improves fatigue by improving, inhibiting decline, or maintaining energy production capacity. [3] The composition described in [2] above, in which the improvement, inhibiting decline, or maintenance of energy production capacity is mediated by improvement, inhibiting decline, or maintenance of mitochondrial function. [4] A composition for improving, inhibiting decline, or maintaining energy production capacity, which contains one or more sesamin compounds and lutein and / or its fatty acid esters. [5] The composition described in [4] above, in which the improvement, inhibiting decline, or maintenance of energy production capacity is mediated by improvement, inhibiting decline, or maintenance of mitochondrial function. [6] The composition described in any of [1] to [5] above, in which one or more sesamin compounds are sesamin and / or episesamin. [7] The composition according to any one of [1] to [6] above, wherein the molar ratio of lutein and / or its fatty acid ester to sesamin-class compounds is 0.003 to 125. [8] The composition according to any one of [1] to [7] above, which is an oral composition. [9] The composition according to any one of [1] to [8] above, which is a food or drink.

[10] The composition according to any one of [1] to [9] above, which is labeled with one or more indications selected from the group consisting of "relief of fatigue," "relief of fatigue sensation," "relief of discomfort," "suppression of decline in motivation to be active," "aids energy production," and "maintains and improves vitality."

[11] Use of one or more sesamin-class compounds and lutein and / or its fatty acid ester for suppressing, alleviating, or ameliorating fatigue.

[12] Use of one or more sesamin-class compounds and lutein and / or its fatty acid ester for improving, suppressing decline, or maintaining energy production capacity.

[13] A method for suppressing, alleviating, or ameliorating fatigue, comprising administering one or more sesamin compounds and lutein and / or its fatty acid esters.

[14] A method for improving, suppressing a decline in, or maintaining energy production capacity, comprising administering one or more sesamin compounds and lutein and / or its fatty acid esters.

[0015] According to the present invention, it is possible to provide a composition that can improve, inhibit the decline of, or maintain mitochondrial function, is effective in improving, inhibiting the decline of, or maintaining energy production capacity, and is effective in anti-fatigue, is highly safe, and can be taken continuously.

[0016] FIG. 1 is a graph showing the effects of sesamin / episesamin mixture (SE) and lutein on ATP production.

[0017] The anti-fatigue composition of the present invention contains one or more sesamin compounds and lutein and / or their fatty acid esters. The anti-fatigue composition of the present invention contains one or more sesamin compounds and lutein and / or their fatty acid esters as active ingredients. The composition of the present invention for improving, inhibiting a decline in, or maintaining energy production capacity contains one or more sesamin compounds and lutein and / or their fatty acid esters. The composition of the present invention for improving, inhibiting a decline in, or maintaining energy production capacity contains one or more sesamin compounds and lutein and / or their fatty acid esters as active ingredients. Energy production refers to the production of energy necessary for humans or non-human animals to maintain their activity. The anti-fatigue composition of the present invention and the composition for improving, inhibiting a decline in, or maintaining energy production capacity will hereinafter be collectively referred to as the composition of the present invention.

[0018] (Sesamin Compounds) In the present invention, "sesamins" refers to compounds including sesamin and its analogs. Sesamin is a major lignan compound found in sesame. Sesamin analogs include episesamin and, for example, the dioxabicyclo[3.3.0]octane derivatives described in JP 4-9331 A. As one or more types of sesamins, one of these compounds may be used alone, or two or more may be used. Specific examples of sesamins include sesamin, episesamin, sesaminol, episesaminol, sesamol, and sesamolin. These stereoisomers or racemates may be used alone or in mixtures. Furthermore, metabolites of sesamin compounds (e.g., those described in JP 2001-139579 A) are also sesamin analogs included in the sesamins of the present invention, and can be used in the present invention, so long as they exhibit the effects of the present invention. In the present invention, sesamin and / or episesamin can be preferably used as one or more of the sesamins, with sesamin and episesamin being more preferred. When sesamin and episesamin are used, their ratio is not particularly limited, but for example, a weight ratio of sesamin:episesamin of 1:0.1 to 1:9 is preferred, 1:0.3 to 1:3 is more preferred, and 1:0.5 to 1:2 is even more preferred.

[0019] The sesamin compounds used in the present invention are not limited by their form or production method. Sesamin compounds are one of the major lignan compounds found in sesame, and are present in sesame seeds at approximately 0.5 to 1.0% by weight. For example, in the case of sesamin, sesamin (referred to as sesamin extract or purified product) extracted from sesame oil by known methods (e.g., the method described in Japanese Patent Application Laid-Open No. 4-9331) can be used. Commercially available sesame oil (liquid) can also be used as is. However, when using sesame oil, the characteristic flavor of sesame oil can be evaluated as sensory undesirable. Therefore, it is preferable to use a tasteless and odorless sesamin extract (or sesamin purified product) extracted from sesame oil. Furthermore, when using sesame oil, the sesamin content is low, and if a desired amount of sesamin is to be incorporated, the volume per unit dose of the formulated composition may become too large, resulting in ingestion problems. In particular, when formulated for oral administration, the formulation (e.g., tablets, capsules) may become too large, hindering ingestion. Therefore, from the viewpoint of requiring a small intake amount, it is preferable to use a sesamin extract (or purified sesamin) from sesame oil. Sesamin compounds can also be obtained by synthesis. For example, sesamin and episesamin can be synthesized by the method of Beroza et al. (J. Am. Chem. Soc., 78, 1242 (1956)). Sesamin and episesamin metabolites can be synthesized by the method of Urata et al. (Chem. Pharm. Bull. (Tokyo), 56 (11) 1611-2 (2008)).

[0020] (Lutein and / or fatty acid ester of lutein) The composition of the present invention contains lutein and / or its fatty acid ester. Lutein is a type of carotenoid. Lutein and / or its fatty acid ester are contained in plants and can be prepared, for example, by extraction from plants. Lutein fatty acid esters are contained in, for example, green and yellow vegetables such as spinach, kale, broccoli, pumpkin, carrot, and pepper; fruits such as oranges, peaches, papayas, prunes, mangoes, avocados, raspberries, and rosehips; and marigold petals. In the present invention, plant-derived materials rich in lutein and / or its fatty acid esters may be contained in the composition of the present invention as long as the effects of the present invention are achieved. Commercially available lutein and / or its fatty acid esters can also be used.

[0021] The fatty acid ester of lutein is a fatty acid ester in which a fatty acid is bonded to one or two hydroxyl groups of lutein. Examples of the fatty acid in the fatty acid ester of lutein include fatty acids having 4 to 20 carbon atoms, and preferably fatty acids having 8 to 18 carbon atoms. The fatty acid ester of lutein may be one type or two or more types. Lutein is produced by hydrolysis of the fatty acid ester of lutein.

[0022] Sesamin derivatives, lutein, and / or their fatty acid esters are compounds found in natural products and foods, have a long history of consumption, and are recognized as being highly safe. Therefore, sesamin derivatives, lutein, and / or their fatty acid esters are suitable for continuous and long-term intake.

[0023] The composition of the present invention contains one or more of the above-mentioned sesamin compounds and lutein and / or its fatty acid esters as active ingredients. Combining sesamin compounds with lutein and / or its fatty acid esters provides significantly superior effects in improving, inhibiting decline, or maintaining mitochondrial function. The improvement, inhibition of decline, or maintenance of mitochondrial function can provide an effect of improving, inhibiting decline, or maintaining energy production capacity. The improvement, inhibition of decline, or maintenance effect of mitochondrial function and the improvement, inhibition of decline, or maintenance effect of energy production capacity obtained by combining sesamin compounds with lutein and / or its fatty acid esters are synergistic effects superior to the additive effects expected from the effects obtained by using sesamin compounds, or lutein and / or its fatty acid esters alone.

[0024] In the composition of the present invention, from the viewpoint of synergistically enhancing the effects of improving, inhibiting or maintaining mitochondrial function, and improving, inhibiting or maintaining energy production capacity, the weight ratio of the total content of lutein and / or its fatty acid esters to the total content of sesamin compounds, expressed in lutein equivalents ((lutein equivalent value of the total content of lutein and / or its fatty acid esters) / total content of sesamin compounds), is preferably 0.005 to 200, more preferably 0.01 to 40, and even more preferably 0.4 to 16. In the present invention, the molar ratio of lutein and / or its fatty acid esters to sesamin compounds is preferably 0.003 to 125, more preferably 0.006 to 25, even more preferably 0.25 to 10, and particularly preferably 0.3 to 10. The above molar ratio is the ratio of the total number of moles of lutein and / or its fatty acid esters to the total number of moles of sesamin compounds ((total number of moles of lutein and / or its fatty acid esters) / total number of moles of sesamin compounds). By enhancing the effect of improving, inhibiting the decline of, or maintaining mitochondrial function, it is possible to enhance the effect of improving, inhibiting the decline of, or maintaining energy production capacity. Improving, inhibiting the decline of, or maintaining mitochondrial function and / or energy production capacity is effective in inhibiting, alleviating, or improving fatigue. In the composition of the present invention, it is preferable from the viewpoint of anti-fatigue effect to have the ratio of sesamin-class compounds to lutein and / or its fatty acid esters within the above range.

[0025] The composition of the present invention for improving, inhibiting a decline, or maintaining energy production capacity can be used, for example, to improve, inhibit a decline, or maintain energy production capacity through improvement, inhibiting a decline, or maintenance of mitochondrial function. The composition of the present invention can be used as a composition for improving, inhibiting a decline, or maintaining energy production capacity through improvement, inhibiting a decline, or maintenance of mitochondrial function. Furthermore, the anti-fatigue composition of the present invention can inhibit, alleviate, or ameliorate fatigue by improving, inhibiting a decline, or maintaining energy production capacity, and can be used for such purposes. The anti-fatigue composition of the present invention can be used to inhibit, alleviate, or ameliorate fatigue by improving, inhibiting a decline, or maintaining energy production capacity through improvement, inhibiting a decline, or maintenance of mitochondrial function.

[0026] The use of one or more sesamin compounds with lutein and / or its fatty acid esters can synergistically enhance the effects of improving, inhibiting, or maintaining mitochondrial function, and improving, inhibiting, or maintaining energy production capacity. Therefore, when sesamin compounds and lutein and / or their fatty acid esters are used as active ingredients for improving, inhibiting, or maintaining energy production capacity, or as active ingredients for anti-fatigue, the above effects can be achieved even with low doses of the active ingredients, making it possible to reduce the intake amount of the active ingredients. Reducing the intake amount leads to easier intake, and it is possible to obtain anti-fatigue compositions, compositions for improving, inhibiting, or maintaining energy production capacity, and the like that are easier to take continuously.

[0027] As used herein, fatigue refers to a decrease in physical activity capacity and / or a decrease in mental vitality caused by physical or mental factors. Fatigue is usually accompanied by a feeling of tiredness (e.g., discomfort, decreased motivation to be active, etc.). Anti-fatigue refers to suppressing, alleviating, or ameliorating fatigue. Suppressing fatigue includes increasing resistance to fatigue and preventing fatigue (including reducing the risk in subjects at risk of fatigue), etc. Reducing fatigue includes alleviating symptoms of fatigue (e.g., fatigue, etc.). Improving fatigue includes recovering from fatigue and ameliorating symptoms of fatigue, etc. The anti-fatigue composition of the present invention can be used to suppress, alleviate, or ameliorate physical fatigue and / or mental fatigue, and is particularly preferably used to suppress, alleviate, or ameliorate physical fatigue and physical fatigue. The anti-fatigue composition of the present invention can be used, for example, to prevent or ameliorate conditions or diseases accompanied by fatigue. Conditions or diseases accompanied by fatigue include chronic fatigue syndrome. Prevention of a condition or disease includes preventing the onset, delaying the onset, reducing the incidence, reducing the risk of onset, etc. Amelioration of a condition or disease includes recovering a subject from a condition or disease, alleviating the symptoms of a condition or disease, improving the symptoms of a condition or disease, delaying or preventing the progression of a condition or disease, etc. The compositions of the present invention can be applied for both therapeutic and non-therapeutic uses. Non-therapeutic is a concept that does not include medical procedures, i.e., surgery, treatment, or diagnosis of humans.

[0028] In this specification, mitochondrial function may be evaluated based on common knowledge in the technical field to which the present invention pertains, and the method for evaluating it is not particularly limited. For example, mitochondrial function can be evaluated by continuously measuring the oxygen consumption rate (OCR) used by mitochondria during ATP synthesis in the cells being measured using an extracellular flux analyzer while adding an ATP synthase inhibitor (e.g., oligomycin and rotenone) and an uncoupler (e.g., carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)). Mitochondrial function can be evaluated, for example, by analyzing basal respiration, ATP production capacity, or maximum respiration, which are considered to be major indicators in the evaluation of mitochondrial function.

[0029] The composition of the present invention can be in the form of a food or beverage, a pharmaceutical product, a quasi-drug, a feed, etc. The composition of the present invention may be a food or beverage, a pharmaceutical product, a quasi-drug, a feed, etc., for anti-fatigue purposes, or for improving, inhibiting a decline in, or maintaining energy production capacity, or may be a material or preparation to be used in combination with these. The composition of the present invention can be provided in the form of an agent, for example, but is not limited to this form. The agent can also be provided as a composition as is, or as a composition containing the agent. In one embodiment of the present invention, the anti-fatigue composition of the present invention can also be referred to as an anti-fatigue agent. The composition of the present invention may be either an oral composition or a parenteral composition, but is preferably an oral composition. Oral compositions include food or beverages, oral pharmaceutical products, quasi-drugs, and feed, preferably food or beverages or oral pharmaceutical products, and more preferably food or beverages.

[0030] The composition of the present invention may contain any additives and ingredients in addition to one or more sesamin-class compounds and lutein and / or its fatty acid esters, as long as the effects of the present invention are not impaired. These additives and ingredients can be selected depending on the form of the composition, and those that can generally be used in foods and beverages, pharmaceuticals, quasi-drugs, feed, etc. can be used. When the composition of the present invention is used as a food and beverage, pharmaceutical, quasi-drug, feed, etc., the manufacturing method thereof is not particularly limited, and it can be manufactured by a general method.

[0031] For example, when the composition of the present invention is used as a food or beverage, various foods and beverages can be prepared by blending one or more sesamin compounds and lutein and / or its fatty acid esters with ingredients that can be used in foods and beverages (e.g., food ingredients, food additives used as needed, etc.). The foods and beverages are not particularly limited, and examples include general foods and beverages, health foods, health drinks, functional foods, foods for specified health uses, and foods and beverages for patients. The health foods, functional foods, foods for specified health uses, etc. can be used in various dosage forms, such as fine granules, tablets, granules, powders, capsules, chewable tablets, dry syrups, syrups, liquids, beverages, and liquid diets.

[0032] When the composition of the present invention is used as a pharmaceutical or quasi-drug, for example, one or more sesamin compounds and lutein and / or its fatty acid esters can be combined with a pharmacologically acceptable carrier and, if necessary, additives to produce a pharmaceutical or quasi-drug in various dosage forms. Such carriers, additives, etc. may be any pharmacologically acceptable carriers that can be used in pharmaceuticals or quasi-drugs, and may include, for example, one or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants, etc. The pharmaceutical or quasi-drug may be administered orally or parenterally (e.g., transdermal, transmucosal, enteral, or by injection). When the composition of the present invention is used as a pharmaceutical or quasi-drug, it is preferably an oral pharmaceutical or quasi-drug. Dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewable tablets, etc. The pharmaceutical may also be a non-human animal drug.

[0033] When the composition of the present invention is used as feed, one or more sesamin compounds and lutein and / or its fatty acid esters may be blended into the feed. Feed also includes feed additives. Examples of feed include livestock feed for cows, pigs, chickens, sheep, horses, etc.; small animal feed for rabbits, rats, mice, etc.; and pet food for dogs, cats, small birds, etc.

[0034] The content of sesamin-class compounds in the composition of the present invention is not particularly limited and can be set depending on the form, etc. The total content of sesamin-class compounds in the composition of the present invention is, for example, preferably 0.001 wt% or more, more preferably 0.01 wt% or more, even more preferably 0.05 wt% or more, and preferably 10 wt% or less, more preferably 5 wt% or less. In one embodiment, the total content of sesamin-class compounds in the composition is preferably 0.001 to 10 wt%, more preferably 0.01 to 10 wt%, even more preferably 0.05 to 5 wt%.

[0035] The total content of lutein and / or its fatty acid esters in the composition of the present invention is not particularly limited and can be set depending on the form, etc. The total content of lutein and / or its fatty acid esters in the composition of the present invention is, for example, preferably 0.001 wt % or more, more preferably 0.01 wt % or more, even more preferably 0.05 wt % or more, and preferably 10 wt % or less, more preferably 5 wt % or less, in terms of lutein. In one embodiment, the total content of lutein and / or its fatty acid esters in the composition is preferably 0.001 to 10 wt %, more preferably 0.01 to 10 wt %, even more preferably 0.05 to 5 wt %, in terms of lutein.

[0036] The composition of the present invention is preferably taken orally (administered orally). The dosage (which can also be referred to as intake amount) of the composition of the present invention is not particularly limited. The dosage of the composition of the present invention may be an amount that can achieve the effect of improving, suppressing or maintaining the decline of mitochondrial function, the effect of improving, suppressing or maintaining the decline of energy production capacity, and / or the effect of anti-fatigue, and may be appropriately determined depending on the dosage form, administration method, body weight of the subject, etc.

[0037] In one embodiment, when the composition of the present invention is orally ingested or administered to a human (adult), the total dosage of sesamin-class compounds is preferably 0.5 mg or more, more preferably 1 mg or more, even more preferably 3 mg or more, and preferably 200 mg or less, more preferably 100 mg or less, and even more preferably 80 mg or less per 60 kg of body weight per day. Furthermore, the total dosage of lutein and / or its fatty acid esters is preferably 0.5 mg or more, more preferably 1 mg or more, even more preferably 3 mg or more, and preferably 200 mg or less, more preferably 100 mg or less, and even more preferably 80 mg or less per 60 kg of body weight per day, calculated as lutein. In one embodiment, the total dosage of sesamin-class compounds is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg per 60 kg of body weight per day for a human (adult). Furthermore, the total dosage of lutein and / or its fatty acid esters, in terms of lutein equivalent, for humans (adults) is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg per 60 kg of body weight per day. It is preferable to ingest or administer the above amount at least once per day, for example, once or several times (e.g., 2 to 3 times) per day. In one embodiment, the above amounts of sesamin-class compounds and lutein and / or their fatty acid esters are preferably orally ingested or administered to humans. In one embodiment, the composition of the present invention can be used to ingest or administer the above amounts of sesamin-class compounds and lutein and / or their fatty acid esters per 60 kg of body weight per day to humans. When two or more sesamin-class compounds are used, the total dosage of sesamin-class compounds refers to the combined amount. The total dosage of lutein and / or its fatty acid esters refers to the combined amount of lutein and its fatty acid esters. In one aspect, it is preferable that sesamin and / or episesamin be orally ingested or administered to a human (adult) at a total dosage of sesamin and / or episesamin per day per 60 kg body weight, preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg.

[0038] The composition of the present invention is preferably ingested or administered continuously. It is expected that greater effects will be obtained by continuously ingesting or administering sesamin-class compounds and lutein and / or its fatty acid esters. In one embodiment, the composition of the present invention is preferably ingested or administered continuously for at least one week, more preferably at least four weeks, even more preferably at least eight weeks, and particularly preferably at least 12 weeks.

[0039] The subject (which may also be referred to as the administration subject) to which the composition of the present invention is administered or ingested is not particularly limited, and includes humans and non-human animals. Examples of non-human animals include industrial animals, pets, and laboratory animals. Specifically, industrial animals refer to animals that need to be raised industrially, such as livestock such as cows, horses, pigs, goats, and sheep, poultry such as chickens, ducks, quail, turkeys, and ostriches, and fish such as yellowtail, yellowtail, red sea bream, horse mackerel, carp, rainbow trout, and eels. Pets refer to so-called pets and companion animals such as dogs, cats, marmosets, small birds, and hamsters, while laboratory animals refer to animals used in research in fields such as medicine, biology, agriculture, and pharmacy, such as mice, rats, guinea pigs, beagles, minipigs, rhesus monkeys, and cynomolgus monkeys.

[0040] The subject to which the composition of the present invention is administered is preferably a human or a non-human mammal, more preferably a human. In one embodiment, the subject to which the composition of the present invention is administered includes subjects who need or desire to improve, inhibit decline, or maintain mitochondrial function, subjects who need or desire to improve, inhibit decline, or maintain energy production capacity, and subjects who need or desire to inhibit, alleviate, or improve fatigue. As described above, it is known that mitochondrial function and energy production capacity decline with age. In one embodiment, the subject to which the composition of the present invention is administered is preferably middle-aged or elderly people. The composition of the present invention may be an anti-fatigue composition for middle-aged or elderly people (preferably elderly people), or a composition for improving, inhibiting decline, or maintaining energy production capacity. Middle-aged or elderly people may be, for example, humans aged 40 years or older. Middle-aged or elderly people include elderly people. The composition of the present invention can also be used in healthy individuals, for example, to improve, inhibit decline, or maintain mitochondrial function, improve, inhibit decline, or maintain energy production capacity, or achieve anti-fatigue effects.

[0041] The composition of the present invention may be labeled with one or more of the following: "relief of fatigue," "relief of fatigue," "relief of discomfort," "suppression of decline in motivation," "aids energy production," "maintains and improves vitality," "less likely to feel fatigue," "maintains vitality," and "full of energy." In one aspect, the composition of the present invention may be labeled with one or more of the following: "relief of fatigue," "relief of fatigue," "relief of discomfort," "suppression of decline in motivation," "aids energy production," and "maintains and improves vitality." For example, fatigue may be something that is more easily felt with age. Energy production may be produced in cells or mitochondria. In one aspect of the present invention, the composition of the present invention is preferably a food or beverage labeled with the above-mentioned label. The above-mentioned label may also indicate that the composition is used to obtain the above-mentioned function.

[0042] The present invention also encompasses the use of one or more sesamin-class compounds and lutein and / or its fatty acid esters for producing an anti-fatigue composition. The present invention also encompasses the use of one or more sesamin-class compounds and lutein or its fatty acid esters for producing a composition for improving, suppressing a decline in, or maintaining energy production capacity.

[0043] The present invention also encompasses the following methods: A method for suppressing, alleviating, or ameliorating fatigue by administering one or more sesamin compounds and lutein and / or its fatty acid esters; A method for improving, suppressing a decline in, or maintaining energy production capacity by administering one or more sesamin compounds and lutein and / or its fatty acid esters.

[0044] The present invention also encompasses the following uses: Use of one or more sesamin compounds and lutein and / or their fatty acid esters for the prevention, alleviation, or amelioration of fatigue; Use of one or more sesamin compounds and lutein and / or their fatty acid esters for the improvement, prevention of decline, or maintenance of energy production capacity. The above methods or uses may be therapeutic or non-therapeutic. By administering one or more sesamin compounds and lutein and / or their fatty acid esters to a subject, it is possible to improve, prevent decline, or maintain mitochondrial function, thereby achieving the effects of improving, preventing decline, or maintaining energy production capacity and anti-fatigue effects. The fatigue is preferably physical fatigue. One or more sesamin compounds and lutein and / or their fatty acid esters may be administered simultaneously or separately, but are preferably administered simultaneously.

[0045] In the above-mentioned uses and methods, preferred embodiments of sesamin compounds, lutein and / or their fatty acid esters, and the ratios thereof are the same as those of the composition of the present invention described above. In one embodiment, the weight ratio of the total amount of lutein and / or its fatty acid esters administered relative to the total amount of sesamin compounds administered, expressed in lutein equivalents ((lutein equivalent value of the total amount of lutein and / or its fatty acid esters administered) / total amount of sesamin compounds administered) is preferably 0.005 to 200, more preferably 0.01 to 40, and even more preferably 0.4 to 16. As the one or more types of sesamins, one or more types of sesamin compounds may be used. Lutein and its fatty acid esters may also be used. In the above-mentioned uses, it is preferable to administer (have the subject ingest) one or more types of sesamins and lutein and / or its fatty acid esters once or more per day, for example, once to several times (e.g., 2 to 3 times) per day. In the above-mentioned use, it is preferable to orally administer (ingest) one or more sesamin-class compounds and lutein and / or its fatty acid esters. The above-mentioned use is preferably in humans or non-human mammals, more preferably in humans.

[0046] In the above-mentioned use, one or more sesamin compounds, and lutein and / or their fatty acid esters may be used in an amount (which may be referred to as an effective amount) that achieves the desired effect. The preferred dosages and administration targets of the sesamin compounds, lutein and / or their fatty acid esters are the same as those of the composition of the present invention described above. The sesamin compounds, lutein and / or their fatty acid esters may be administered directly or as a composition containing them. For example, the composition of the present invention described above may be used.

[0047] In the above-mentioned uses and methods, one or more sesamin compounds (or a composition containing them) and lutein and / or its fatty acid esters (or a composition containing them) are prepared separately, and then ingested or administered at approximately the same time, or after one has been ingested or administered and while the other is still effective, the intended effects of the present invention (improvement of mitochondrial function, inhibition of or maintenance of decline, improvement of energy production capacity, inhibition of or maintenance of decline, and / or anti-fatigue effect) can be enhanced. Therefore, kits and the like comprising one or more sesamin compounds (or a composition containing them) and lutein and / or its fatty acid esters (or a composition containing them) are also included within the scope of the present invention.

[0048] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to these examples.

[0049] In the examples and comparative examples, the sesamin / episesamin mixture used was a mixture of sesamin and episesamin in a sesamin:episesamin weight ratio of 1:1. Hereinafter, the sesamin / episesamin mixture may also be referred to as SE.

[0050] Examples 1 to 3: Evaluation test of mitochondrial function in cells treated with sesamin / episesamin mixture (SE) and lutein. ３ TIG-3 cells (cells derived from fetal lung) were plated on a dedicated plate at 100 cells / well and incubated at 37°C, CO ２ (5%) for 24 hours. After 24 hours of culture, the sesamin / episesamin mixture and lutein were added to the medium in the wells at the concentrations shown in Table 1 below, and culture was continued for 24 hours. The molar ratio of lutein to sesamin compounds in the medium (lutein / sesamins) was 0.3 in Example 1, 3 in Example 2, and 10 in Example 3. The medium containing the sesamin / episesamin mixture and lutein was then removed, and the cells in the wells were incubated in H ２ O ２The cells were treated with medium containing ATP (800 μM) for 2 hours. The medium was then replaced with analysis medium, and the oxygen consumption rate (pmol / min) was analyzed using an analytical instrument (XF analyzer, Agilent Corporation). After the analysis was completed, the nuclei were stained with Hoechst He, and the cells were photographed using a fluorescence microscope BZ-x (Keyence Corporation), and the cell number was counted using image analysis. By measuring the decrease in oxygen consumption of live cells using the XF analyzer, the amount of ATP production, which indicates mitochondrial function, can be evaluated. Specifically, after measuring the oxygen consumption rate of basal respiration of live cells in the wells, an ATP synthase inhibitor (oligomycin) was added to the wells, and the decrease in oxygen consumption rate (pmol / min / 10 ) due to the addition of oligomycin was calculated. ３ The basal respiration rate (basal respiration rate) was measured and used as the ATP production rate. Basal respiration indicates the cellular energy demand under baseline conditions, and a portion of the basal respiration rate is used for ATP production. The decrease in oxygen consumption rate due to the addition of oligomycin indicates the ATP production rate. The results are shown in Table 1.

[0051] Reference Example 1: Evaluation test of mitochondrial function in untreated group To examine mitochondrial function, 5.5 × 10 ３ TIG-3 cells were seeded onto a dedicated plate at 1000 cells / well and incubated at 37°C, CO ２ After 24 hours of culture, the sesamin / episesamin mixture and lutein were added to the medium, and the cells in the wells were cultured under the conditions of 5% HCl (5%) for 24 hours. ２ O ２ The oxygen consumption rate was analyzed and the cell number was counted in the same manner as in Example 1, except that the 2-hour treatment with the medium containing 800 μM of ATP was omitted and the cells were cultured for an additional 26 hours. The ATP production was also measured. The results are shown in Table 1.

[0052] <Comparative example 1: H ２ O ２ Evaluation test of mitochondrial function in treatment groups> To examine mitochondrial function, 5.5 x 10 ３ TIG-3 cells were seeded onto a dedicated plate at 1000 cells / well and incubated at 37°C, CO ２The cells were cultured for 24 hours under conditions of 0.1% CO₂ (5%). After 24 hours of culture, the cells were cultured for an additional 24 hours without adding the sesamin / episesamin mixture or lutein to the medium. The oxygen consumption rate was analyzed and the cell number was counted in the same manner as in Example 1. ATP production was also measured. The results are shown in Table 1.

[0053] Comparative Examples 2 to 5: Evaluation test of mitochondrial function of cells treated with sesamin / episesamin mixture or lutein. ３ TIG-3 cells were seeded onto a dedicated plate at 1000 cells / well and incubated at 37°C, CO ２ (5%) for 24 hours. After 24 hours of culture, a sesamin / episesamin mixture (Comparative Example 2) or lutein (Comparative Examples 3 to 5) was added to the medium in the wells at the concentrations shown in Table 1 below, and the culture was continued for 24 hours. Except for this, the oxygen consumption rate was analyzed and the cell number was counted in Comparative Examples 2 to 5 in the same manner as in Example 1 above. ATP production was also measured. The results are shown in Table 1.

[0054]

[0055] In Table 1, "measured value" (pmol / min / 10 ３The ATP production amount (amount of decrease in oxygen consumption rate due to ATP synthase inhibition) determined above is shown in Table 1 (cells). The "measured value" of Examples 1 to 3 and Comparative Examples 1 to 5 shown in Table 1 was divided by the "measured value" of Comparative Example 1, and the result was multiplied by 100 (100 × (measured value of Example or Comparative Example) / (measured value of Comparative Example 1)). The resulting value is shown in Table 1 as the "relative value (%)" (relative to Comparative Example 1). Furthermore, the value obtained by subtracting 100 (%) (Comparative Example 1) from the "relative value (%)" of Examples 1 to 3 and Comparative Examples 2 to 5 shown in Table 1 was used to determine the "recovery rate (%)" relative to Comparative Example 1. A higher recovery rate indicates a greater amount of ATP production. Figure 1 shows the recovery rates (%) (recovery rate relative to Comparative Example 1) determined for the Examples and Comparative Examples. In Figure 1, SE represents a sesamin / episesamin mixture. In Figure 1, "Comparative Example 4 + Comparative Example 2" is the sum of the recovery rates of Comparative Example 2 and Comparative Example 4, and "Comparative Example 5 + Comparative Example 2" is the sum of the recovery rates of Comparative Example 2 and Comparative Example 5. "Comparative Example 4 + Comparative Example 2" and "Comparative Example 5 + Comparative Example 2" show the recovery rates when sesamin-class compounds and lutein are combined (Examples 2 and 3), predicted from the recovery rates for sesamin-class compounds alone (Comparative Example 2) and lutein alone (Comparative Example 4 or 5).

[0056] As shown in Table 1, the amount of ATP produced was significantly higher in the control group (Reference Example 1) than in the control group (Reference Example 1) when 800 μM H ２ O ２ The treatment with lutein (300 nM or 1000 nM) according to Comparative Examples 4 and 5 reduced the H ２ O ２ The ATP production was 5.4% and 1.3% higher in the sesamin / episesamin mixture (100 nM) treatment group in Comparative Example 2 than in the H treatment group in Comparative Example 1. ２ O ２ The ATP production was 2.8% higher than that of the treatment group. From the above, it was confirmed that treatment with the sesamin / episesamin mixture increases, inhibits a decrease, or maintains ATP production. Next, the groups treated with the sesamin / episesamin mixture (100 nM) and lutein (30 nM, 300 nM, or 1000 nM) in Examples 1 to 3, and the H group in Comparative Example 1 were compared. ２ O ２Compared to the treatment group, ATP production was 17.7% higher in Example 1, 14.3% higher in Example 2, and 13.4% higher in Example 3. As shown in Figure 1, this value is greater than the combined value of the ATP production recovery rate when treated with the sesamin / episesamin mixture alone and the ATP production recovery rate when treated with lutein alone, confirming that ATP production did not simply increase additively with treatment with lutein and the sesamin / episesamin mixture, but rather that the combination of the sesamin / episesamin mixture and lutein increased ATP production synergistically. In other words, it was confirmed that a composition containing the sesamin / episesamin mixture and lutein exhibits a synergistic effect of increasing, inhibiting a decrease in, or maintaining ATP production due to the inclusion of both, and therefore exhibits this effect even at low doses.

[0057] From the above, it has become clear that the combination of sesamin / episesamin mixture and lutein exhibits a synergistic effect of increasing ATP production and suppressing or maintaining its decline. This confirms that a composition containing one or more sesamin compounds and lutein and / or its fatty acid esters can effectively improve, suppress or maintain mitochondrial function. Furthermore, the use of a combination of one or more sesamin compounds and lutein and / or its fatty acid esters can improve, suppress or maintain energy production capacity. This in turn provides an anti-fatigue effect.

[0058] Example 4: Human Testing (Evaluation Sample) A food product was produced as the test food, containing 10 mg of a sesamin / episesamin mixture and 10 mg of lutein dispersed in edible vegetable oil with a glycerin fatty acid ester per three tablets, and then encapsulated in a film containing gelatin and glycerin. The control food was produced using the same ingredients as the test food, except that the sesamin / episesamin mixture and lutein were not used. The test food and control food had the same amounts of calories, protein, lipids, and carbohydrates per three tablets, and were indistinguishable from each other based on appearance, etc.

[0059] (Evaluation Method) Men and women aged 40 to under 65 years (30 per group) who became more susceptible to fatigue with age were given either the control food (3 tablets per day) or the test food (3 tablets per day) for 8 weeks. Test days were set before the start of the test and after 8 weeks of test intake. On the test day, fatigue (fatigue (1)) was measured after visiting the clinic. Then, a Kraepelin test (2 x 15-minute sessions with a 5-minute break) was performed as a mental fatigue load (mental load), and fatigue (fatigue (2)) was measured after completion. Then, as a physical fatigue load (physical load), 30 minutes of exercise was performed using an ergometer (EZ101 Aero Bike (registered trademark), Konami Sports & Life), and fatigue (fatigue (3)) was measured after completion. The exercise intensity was set to 3.5 to 6.8 METs, which is within the range of daily life. The exercise intensity was adjusted to eliminate individual differences. After the exercise, a 60-minute rest period was given, and fatigue (fatigue (4)) was measured. Furthermore, fatigue sensation the next morning (fatigue sensation (5)) was measured.

[0060] A visual analogue scale (VAS) was used to evaluate fatigue. Specifically, subjects were asked to mark their level of fatigue on a 10 cm line, with the left end (0 cm) representing "the best feeling of not feeling tired at all" and the right end (10 cm) representing "the worst feeling of being so exhausted that they could do nothing." The distance (cm) from the left end of the 10 cm line to the marked position was measured and used as a measurement value for fatigue. The change in fatigue at each time point during the 8th week was calculated from the measurements of fatigue (1) to (5) using the following formulas (i) to (iv).

[0061] Change in fatigue at visit = (fatigue at visit at week 8 (1)) - (fatigue at visit at week 0 (1)) Formula (i)

[0062] Change in fatigue sensation due to physical stress={(Fatigue sensation (3) immediately after exercise stress at week 8)−(Fatigue sensation (2) after Kraepelin test at week 8)}−{(Fatigue sensation (3) immediately after exercise stress at week 0)−(Fatigue sensation (2) after Kraepelin test at week 0)} Formula (ii)

[0063] Change in fatigue after rest = (fatigue after 60 minutes of exercise at week 8 (4)) - (fatigue after 60 minutes of exercise at week 0 (4)) Formula (iii)

[0064] Change in next morning fatigue feeling=(next morning fatigue feeling at week 8 (5))−(next morning fatigue feeling at week 0 (5)) Formula (iv)

[0065] (Analysis 1: Analysis of subjects analyzed for efficacy) The results of the analysis of the change in fatigue at the time of visit, excluding subjects who met the exclusion criteria (6 subjects in the test food group, 4 subjects in the control food group), are shown in Table 2. A paired t-test was used to test for significance (before and after difference (relative to fatigue at week 0): p<0.10). Only in the test food group was there a tendency for fatigue at the time of visit to improve. This confirmed that a composition containing sesamin-containing compounds and lutein improves fatigue in daily life.

[0066]

[0067] (Analysis 2: Subgroup analysis) Using subjects who were judged to have had an appropriate load applied to their entire bodies (8 subjects per group), the results (change in fatigue level) analyzed using formulas (ii) to (iv) are shown in Table 3. Significance tests were performed using a paired t-test to compare before and after the test, and an unpaired t-test to compare between groups (difference before and after (relative to fatigue level at week 0) #: p<0.10, †: p<0.05, difference between groups §: p<0.10).

[0068]

[0069] Compared to the control food group, the test food group showed a greater improvement in fatigue caused by physical stress. This indicates that a composition containing a combination of sesamin-class compounds and lutein improves fatigue when subjected to physical fatigue. Intake of the test food significantly improved fatigue after rest and the next morning. This suggests that a composition containing sesamin-class compounds and lutein acts to recover from fatigue after physical and / or mental fatigue.

Claims

1. A composition for anti-fatigue containing one or more sesaminoids, and lutein and / or its fatty acid ester.

2. The composition according to claim 1, which suppresses, reduces or improves fatigue by enhancing, suppressing the decline of, or maintaining energy production ability.

3. The composition according to claim 2, wherein the enhancement, suppression of decline, or maintenance of energy production ability is achieved through the enhancement, suppression of decline, or maintenance of mitochondrial function.

4. A composition for enhancing, suppressing the decline of, or maintaining energy production ability, containing one or more sesaminoids, and lutein and / or its fatty acid ester.

5. The composition according to claim 4, wherein the enhancement, suppression of decline, or maintenance of energy production ability is achieved through the enhancement, suppression of decline, or maintenance of mitochondrial function.

6. The composition according to any one of claims 1 to 5, wherein one or more sesaminoids are sesamin and / or episesamin.

7. The composition according to any one of claims 1 to 6, wherein the molar ratio of lutein and / or its fatty acid ester to sesaminoids is 0.003 to 125.

8. The composition according to any one of claims 1 to 7, which is an oral composition.

9. The composition according to any one of claims 1 to 8, which is a food or drink.

10. The composition according to any one of claims 1 to 9, which is labeled with one or more selected from the group consisting of "reduction of fatigue", "reduction of fatigue feeling", "reduction of discomfort", "suppression of decline in activity desire", "assisting energy production", and "maintaining and enhancing vitality".

11. Use of one or more sesaminoids, and lutein and / or its fatty acid ester for suppressing, reducing or improving fatigue.

12. Use of one or more sesaminoids, and lutein and / or its fatty acid ester for enhancing, suppressing the decline of, or maintaining energy production ability.