Composition containing sesamin compound and ferulic acid or salt thereof

Abstract

The purpose of the present invention is to provide a composition capable of effectively improving and promoting energy generation, inhibiting reduction of energy generation, or maintaining energy generation. The present invention relates to a composition characterized by containing (A) a sesamin-based compound and (B) ferulic acid or a salt thereof, the ratio of the weight of the ferulic acid (B) or the salt thereof in terms of ferulic acid to the weight of the sesamin-based compound (A) in terms of sesamin being 5-100.

Description

Technical Field

[0001] The present invention relates to a composition containing a sesamin-type compound and ferulic acid or a salt thereof. Background Art

[0002] Energy is essential for living things to function. Energy production primarily occurs within mitochondria, a small organelle within cells. Dietary nutrients such as sugars, lipids, and amino acids are metabolized and converted into NADH (nicotinamide adenine dinucleotide). The electrons from NADH are then transferred to proteins in the mitochondrial respiratory chain (electron transport system), generating energy in the form of ATP (adenosine triphosphate).

[0003] Energy production decreases due to aging, disease, etc. The decrease in energy production, for example, can lead to a decrease in cell function or a decrease in body function in humans. Therefore, a kind of ingredient that has the effect of improving, promoting, suppressing or maintaining energy production, without worrying about side effects and sustainable intake is sought. In addition, when the ingredient with such an effect is taken as a supplement, it is desired to be in a form that is easy for consumers to take continuously. Especially in the case of the elderly, due to the decline in swallowing function, oral preparations such as tablets and capsules are desired to be small. Especially when containing multiple ingredients, the volume often becomes larger, so in order to control the volume of the oral preparation, it is desired to use an ingredient or a combination of such ingredients that is highly effective even in a small amount.

[0004] Sesamin is one of the main lignan compounds contained in sesame. Patent Document 1 describes that a composition containing sesamin compounds and γ-oryzanol has anti-fatigue effects. Ferulic acid is a type of polyphenol and is known to have antioxidant effects.

[0005] Patent Literature Patent Document 1: Japanese Patent Application Laid-Open No. 2009-73749 Summary of the Invention

[0006] The object of the present invention is to provide a composition that can effectively increase or promote energy production, inhibit the decrease of energy production, or maintain energy production.

[0007] The present inventors conducted intensive studies to solve the above-mentioned problems and found that the combined use of sesamin-related compounds and ferulic acid or its salts at a specific ratio significantly increased the effects of enhancing or promoting energy production, inhibiting the decrease in energy production, or maintaining energy production, exceeding the range predicted by the effects of sesamin-related compounds when used alone or the effects of ferulic acid or its salts when used alone.

[0008] The present invention is not limited to the following, but includes the following compositions and the like. [1] A composition comprising (A) a sesamin-based compound and (B) ferulic acid or a salt thereof, The ratio of the ferulic acid-equivalent weight of ferulic acid or its salt (B) to the sesamin-equivalent weight of the sesamin-class compound (A) is 5 to 100. [2] The composition according to [1] above, characterized in that the sesamin-like compound is sesamin and / or episesamin. [3] The composition according to [1] or [2] above, which is a composition for oral administration. [4] The composition according to any one of [1] to [3] above, which is a food or drink. [5] The composition according to [1] or [2] above, which is a cosmetic. [6] The composition according to any one of [1] to [5] above, characterized in that it is a composition for increasing or promoting energy production, suppressing a decrease in energy production, or maintaining energy production. [7] The composition according to any one of [1] to [6] above, which is an anti-aging composition. [8] The composition according to any one of [1] to [7] above, characterized in that it is a composition for extending lifespan and / or healthy lifespan.

[0009] According to the present invention, a composition can be provided that can effectively increase or promote energy production, inhibit the decrease of energy production, or maintain energy production. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 This is a graph showing the effects of sesamin-based compounds and ferulic acid on energy production. Figure 2 This is a graph showing the results of a study on the effect of a combination of a sesamin-like compound and ferulic acid (weight ratio of ferulic acid / sesamin-like compound = 5) on extending the division lifespan in yeast. Figure 3 This is a graph showing the results of a study on the effect of a combination of sesamin-related compounds and ferulic acid (weight ratio of ferulic acid / sesamin-related compounds = 11) on extending the division lifespan in yeast. Figure 4 This is a graph showing the results of a study on the effect of a combination of sesamin-related compounds and ferulic acid (weight ratio of ferulic acid / sesamin-related compounds = 27) on extending the division lifespan in yeast. Figure 5 This is a graph showing the results of a study on the effect of a combination of sesamin-related compounds and ferulic acid (weight ratio of ferulic acid / sesamin-related compounds = 55) on extending the division lifespan in yeast. DETAILED DESCRIPTION

[0011] The composition of the present invention comprises (A) a sesamin-like compound and (B) ferulic acid or a salt thereof. In the composition of the present invention, the ratio of the ferulic acid-equivalent weight of (B) ferulic acid or a salt thereof to the sesamin-equivalent weight of (A) a sesamin-like compound is 5 to 100.

[0012] In the present invention, the term "sesamin-like compounds" is a general term for compounds including sesamin and its analogs. Sesamin-like compounds may be used singly or in combination. Sesamin is a major lignan compound found in sesame. Sesamin analogs, in addition to episesamin, include dioxabicyclo[3.3.0]octane derivatives described in Japanese Patent Application Laid-Open No. 4-9331. Specific examples of sesamin-like compounds include sesamin, episesamin, sesaminol, episesaminol, sesamol, and sesamolin. These stereoisomers or racemates may be used singly or in combination. Metabolites of sesamin-like compounds (e.g., those described in Japanese Patent Application Laid-Open No. 2001-139579) that exhibit the effects of the present invention are sesamin analogs found in the sesamin-like compounds of the present invention and may be used in the present invention. Metabolites that can be used as sesamin-like compounds include, for example, compounds described in Japanese Patent Application Laid-Open No. 2009-143884. Examples of metabolites of sesamin include SC1 ((7α,7'α,8α,8'α)-3',4'-methylenedioxy-7,9':7',9-diepoxylignane-3,4-diol) and SC2 ((7α,7'α,8α,8'α)-7,9':7',9-diepoxylignane-3,3',4,4'-tetraol). Metabolites of sesamin are preferred, and SC1 is more preferred.

[0013] In the present invention, as sesamin-based compounds, sesamin and / or episesamin are preferred, with sesamin and episesamin being more preferred. When using sesamin and episesamin, their ratio is not particularly limited. For example, the weight ratio of sesamin:episesamin is preferably 1:0.1 to 1:9, more preferably 1:0.3 to 1:3, and even more preferably 1:0.5 to 1:2. A weight ratio of sesamin:episesamin of 1:1 is one of the preferred embodiments of the present invention.

[0014] The sesamin compounds used in the present invention are not subject to any restriction due to their form or manufacture method. For example, when it is sesamin, an extract (called sesamin extract or purified product) containing sesamin extracted from sesame oil by a known method (for example, the method of recording in Japanese Unexamined Patent Publication No. 4-9331) can be used. Sesamin can also be obtained by synthesis. As its method, for example, about sesamin and episesamin, it can be synthesized by the method of Beroza et al. (J.Am.Chem.Soc., 78,1242 (1956)).

[0015] Ferulic acid is a type of polyphenol found in plants. Ferulic acid or its salts are not subject to any limitation due to their form or production method. For example, ferulic acid can be obtained by extracting plants containing ferulic acid or by chemical synthesis. Ferulic acid or its salts can be chemically synthesized products or extracted and purified from natural products.

[0016] Plants containing ferulic acid include, for example, corn, barley, wheat, rice, coffee, onion, radish, lemon, Chuanxiong, Chinese angelica, pine, coptis root, ferula, and sweet potato. Rice is rich in ferulic acid in rice bran. As an example of the chemical synthesis of ferulic acid, it can be produced by the condensation decarboxylation reaction of vanillin and malonic acid. There are no particular limitations on the methods for extracting raw materials and purifying ferulic acid or its salts, and known methods can be used.

[0017] The salt of ferulic acid is not particularly limited as long as it is a pharmaceutically acceptable salt or a salt permitted for use in food and beverages, and examples thereof include basic salts. Examples of basic salts include alkali metal salts such as sodium salts and potassium salts; and alkaline earth metal salts such as calcium salts and magnesium salts.

[0018] In the composition of the present invention, the ratio of the ferulic acid-equivalent weight of (B) ferulic acid or its salt to the sesamin-equivalent weight of (A) sesamin-like compound (ferulic acid-equivalent (B) / sesamin-equivalent (A)) is 5 to 100. The composition of the present invention contains (A) sesamin-like compound and (B) ferulic acid or its salt in the above weight ratio. As shown in the Examples described below, the combined use of sesamin compounds and ferulic acid or its salts at the aforementioned weight ratio effectively inhibits the reduction in ATP production caused by hydrogen peroxide (H₂O₂ treatment). The inhibitory effect of the combined use of sesamin compounds and ferulic acid or its salts at the aforementioned weight ratio on the reduction in ATP production demonstrates a significantly superior synergistic effect compared to the additive effect predicted from the separate use of sesamin compounds and ferulic acid or its salts.

[0019] By combining sesamin-like compounds and ferulic acid or its salts in the aforementioned weight ratio, significantly higher effects can be achieved in increasing, promoting, inhibiting, or maintaining energy production, exceeding the range predicted by the effects of using sesamin-like compounds or ferulic acid or its salts alone. Compositions containing sesamin-like compounds and ferulic acid or its salts in the aforementioned weight ratio exhibit excellent effects in increasing, promoting, inhibiting, or maintaining energy production. Therefore, when the composition of the present invention is used as an active ingredient for, for example, increasing, promoting, inhibiting, or maintaining energy production, even at low dosages, the active ingredient can exert the aforementioned effects, thereby minimizing the amount of active ingredient intake. Minimizing the amount of intake improves ease of ingestion, resulting in a composition for increasing, promoting, inhibiting, or maintaining energy production that is easier to consume on a sustained basis.

[0020] In the present invention, the ratio of the weight of (B) ferulic acid or a salt thereof in terms of ferulic acid to the weight of (A) sesamin-based compound in terms of sesamin ((B) in terms of ferulic acid / (A) in terms of sesamin) is preferably 10 or greater, more preferably 11 or greater, and is preferably 70 or less, more preferably 55 or less. In one embodiment, the above-mentioned weight ratio ((B) in terms of ferulic acid / (A) in terms of sesamin) is preferably 10 to 100, more preferably 10 to 70, further preferably 10 to 55, and particularly preferably 11 to 55.

[0021] In this specification, with respect to sesamin-like compounds, sesamin-converted weight, or similar expressions, when the sesamin-like compound is sesamin or episesamin, refers to its weight; when the sesamin-like compound is a compound other than sesamin and episesamin, it refers to the value obtained by multiplying the number of moles of the compound by the molecular weight of sesamin. Regarding ferulic acid or a salt thereof, the ferulic acid-equivalent weight or similar expressions refers to the weight of ferulic acid, and refers to the value obtained by multiplying the number of moles of the salt by the molecular weight of ferulic acid, when referring to a salt of ferulic acid.

[0022] In one embodiment, the composition of the present invention can be preferably used as a composition for improving, promoting energy production, inhibiting the reduction of energy production or maintaining energy production. The composition of the present invention can be a composition for improving, promoting energy production, inhibiting the reduction of energy production or maintaining energy production, which contains a sesamin compound and ferulic acid or a salt thereof as an active ingredient. The energy production function, for example, decreases with age. The reduction in energy production can lead to a decrease in cell function, a decrease in organ function, a decrease in whole body function, etc. By improving, promoting energy production, inhibiting the reduction of energy production or maintaining energy production, it is expected to obtain the following effects: inhibiting the reduction of cell function or maintaining cell function, inhibiting the reduction of organ function or maintaining organ function, inhibiting the reduction of whole body function or maintaining whole body function, etc. Improving, promoting energy production, inhibiting the reduction of energy production or maintaining energy production is, for example, effective for the prevention or inhibition of aging (anti-aging). The aging includes cell aging and individual aging. The individual is preferably human.

[0023] As shown in the examples described below, the combined use of sesamin-related compounds and ferulic acid in the aforementioned weight ratio extended the mitotic lifespan in yeast. Extending mitotic lifespan can be understood as extending individual lifespan or healthspan. Furthermore, extending mitotic lifespan can also be understood as preventing or inhibiting aging. In one embodiment, the composition of the present invention can be used as an anti-aging composition. The composition of the present invention can be an anti-aging composition containing sesamin-related compounds and ferulic acid or a salt thereof as active ingredients.

[0024] In one embodiment, the composition of the present invention can be used to extend the life of an individual. The composition of the present invention can be used as a composition for extending life. The composition of the present invention is also useful for extending healthy life. The so-called healthy life span refers to the period during which one can live without being restricted in daily life due to health problems (page 17 of the Ministry of Health, Labor and Welfare of Japan's "White Book of Health and Labor, 2020 Edition"). In one embodiment, the composition of the present invention can be used as a composition for extending healthy life. The composition of the present invention can be used as a composition for extending life and / or extending healthy life.

[0025] In one embodiment, the composition of the present invention can be used to prevent or ameliorate conditions or diseases associated with reduced energy production. Examples of conditions or diseases associated with reduced energy production include conditions or diseases caused by reduced energy production, or conditions or diseases accompanied by reduced energy production. Examples of such conditions or diseases include muscle diseases such as chronic fatigue syndrome and sarcopenia, and cognitive impairments such as dementia. As used herein, prevention includes: preventing the onset of disease, delaying the onset of disease, reducing the incidence of disease, reducing the risk of disease, etc. Amelioration of a condition or disease includes: recovering from the condition or disease, alleviating the symptoms of the condition or disease, improving the symptoms of the condition or disease, delaying, or preventing the progression of the condition or disease, etc.

[0026] In this specification, energy production can be evaluated based on the common knowledge in the technical field to which the present invention belongs, and the method is not particularly limited. For example, by using an extracellular flux analyzer, while adding an ATP synthase inhibitor (such as oligomycin) while continuously measuring the oxygen consumption rate (OCR) used by mitochondria during ATP synthesis in the cell as the measurement object, energy production can be evaluated. In terms of evaluation items, for example, by analyzing ATP generation as the main indicator in energy production evaluation, energy production can be evaluated.

[0027] Sesamin compounds and ferulic acid or its salts are found in natural products or foods and beverages and are commonly consumed. Therefore, from a safety perspective, it is generally believed that daily ingestion of sesamin compounds and ferulic acid or its salts poses little risk. The present invention provides a composition containing a highly safe substance as an active ingredient that exhibits excellent effects in enhancing or promoting energy production, inhibiting the reduction of energy production, or maintaining energy production.

[0028] The composition of the present invention can be used for either therapeutic applications (medical applications) or non-therapeutic applications (non-medical applications). The term "non-therapeutic" refers to a concept that does not include medical procedures, i.e., human surgery, treatment, or diagnosis. Composition of the present invention, for example, can be made into forms such as food and drink, cosmetics, pharmaceuticals, quasi-drugs, feeds, but is not limited to these. With regard to composition of the present invention, itself can be food and drink, cosmetics, pharmaceuticals, quasi-drugs, feeds etc., also can be for being deployed in these and the material or preparation etc. that use. As an example, the composition of the present invention can be provided as an agent, but is not limited to this method. The agent can be provided directly as a composition or as a composition containing the agent. In one embodiment, a composition for increasing, promoting, inhibiting a decrease in energy production, or maintaining energy production can also be referred to as an agent for increasing, promoting, inhibiting a decrease in energy production, or maintaining energy production. An anti-aging composition can also be referred to as an anti-aging agent. A composition for extending lifespan and / or healthspan can also be referred to as an agent for extending lifespan and / or healthspan.

[0029] The composition of the present invention may be any of an oral composition or a non-oral composition. In one embodiment, the composition of the present invention is preferably an oral composition. As the oral composition, food and drink, oral pharmaceuticals, oral quasi-drugs, and feeds may be listed, preferably food and drink or oral pharmaceuticals, more preferably food and drink. In another embodiment, the composition of the present invention can be used as a skin external preparation (skin external composition). Skin external preparations include cosmetics, pharmaceuticals, quasi-drugs, etc., and cosmetics are preferred.

[0030] The composition of the present invention may contain any additives or ingredients other than sesamin compounds and ferulic acid or its salts, as long as they do not impair the effects of the present invention. These additives and ingredients can be selected based on the form of the composition, and general additives and ingredients that can be used in foods, cosmetics, pharmaceuticals, quasi-drugs, feeds, etc. can be used. When the composition of the present invention is prepared into foods, cosmetics, pharmaceuticals, quasi-drugs, feeds, etc., its production method is not particularly limited and can be produced by general methods. In one embodiment, the composition of the present invention can be composed of sesamin compounds and ferulic acid or its salts.

[0031] When for example compositions of the present invention are made into food and drink, various food and drink can be made by allocating spendable composition (for example, food material, the food additive used as required etc.) in sesamin compounds and ferulic acid or its salt. Food and drink are not particularly limited, for example, general food and drink, health food, health supplement food, health drink, functional label food, specific health food, patient food and drink etc. can be enumerated. Above-mentioned health food, health supplement food, functional label food, specific health food, patient food and drink etc. can be used in the various preparation modes of for example fine granules, tablets, granules, powders, capsules, chewables, dry syrups, syrups, liquids, beverages, drinkables, liquid food etc.

[0032] When the composition of the present invention is formulated into a cosmetic, various cosmetics can be prepared by blending sesamin-based compounds and ferulic acid or its salts with ingredients suitable for cosmetics (e.g., cosmetically acceptable carriers, additives, etc.). The cosmetic product form is not particularly limited, and examples thereof include skin care cosmetics such as lotions, serums, facial masks, emulsions, creams, and sunscreens.

[0033] When the composition of the present invention is made into pharmaceuticals or quasi-pharmaceuticals, for example, a pharmacologically permitted carrier can be prepared in sesamin-type compounds and ferulic acid or its salt, and the additives added as needed, etc., to prepare pharmaceuticals or quasi-pharmaceuticals of various dosage forms. Such carriers, additives, etc., can be substances that can be used for the pharmacology of pharmaceuticals or quasi-pharmaceuticals. For example, one or more of excipients, binding agents, disintegrants, lubricants, antioxidants, colorants, etc. can be listed. As the mode of administration (intake) of pharmaceuticals or quasi-pharmaceuticals, oral or parenteral (dermal, mucosal, enteral, injection, etc.) administration can be listed. In one embodiment, when the composition of the present invention is made into pharmaceuticals or quasi-pharmaceuticals, it is preferably made into oral pharmaceuticals or quasi-pharmaceuticals. As the dosage form for oral administration, liquid, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewable tablets, etc. can be listed. In another embodiment, the pharmaceutical or quasi-drug is preferably a topical preparation for skin application. The dosage form of the topical preparation for skin application is not particularly limited and may be in any form, such as a solution, emulsion, cream, gel, powder, aerosol, spray, capsule, or sheet. Pharmaceuticals may also be medicines for non-human animals.

[0034] When the composition of the present invention is formulated into feed, the sesamin-based compounds and ferulic acid or its salts can be mixed into the feed. Feed also includes feed additives. Examples of feed include livestock feed for cattle, pigs, chickens, sheep, horses, etc.; feed for small animals such as rabbits, rats, and mice; and pet food for dogs, cats, birds, etc.

[0035] The content of the sesamin-like compounds contained in the composition of the present invention is not particularly limited and can be set according to its form, etc. The content of the sesamin-like compounds in the composition of the present invention, for example, as the content converted as sesamin, is preferably 0.001% by weight or more in the composition, more preferably 0.01% by weight or more, further preferably 0.05% by weight or more, and further preferably 10% by weight or less, more preferably 5% by weight or less. In one embodiment, the content of the sesamin-like compounds, as the content converted as sesamin, is preferably 0.001 to 10% by weight in the composition, more preferably 0.01 to 5% by weight, and further preferably 0.05 to 5% by weight. When containing two or more sesamin-like compounds, the above content is their total content. The content of the sesamin-like compounds in the composition can be measured using HPLC (high performance liquid chromatography) method.

[0036] The content of ferulic acid or its salt contained in the composition of the present invention is not particularly limited and can be set according to its form, etc. The content of ferulic acid or its salt in the composition of the present invention, for example, as a content converted to ferulic acid, is preferably 0.01% by weight or more, more preferably 0.1% by weight or more, and further preferably 1% by weight or more in the composition. In addition, it is preferably 90% by weight or less, and more preferably 55% by weight or less. In one embodiment, the content of ferulic acid or its salt in the composition of the present invention, as a content converted to ferulic acid, is preferably 0.01 to 90% by weight, more preferably 0.1 to 55% by weight, and further preferably 1 to 55% by weight. The content of ferulic acid or its salt in the composition can be measured using HPLC.

[0037] The composition of the present invention can be taken or administered in various ways known to the user according to its form or dosage form. In one embodiment, the composition of the present invention is preferably taken orally (orally administered). In another embodiment, the composition of the present invention can be applied to the skin as a topical preparation. The dosage (also referred to as intake) of the composition of the present invention is not particularly limited. In one embodiment, the dosage of the composition of the present invention is an amount that can achieve, for example, an effect of increasing or promoting energy production, inhibiting a decrease in energy production, or maintaining energy production, or an anti-aging effect, and can be appropriately determined based on the dosage form, method of administration, and the subject's weight.

[0038] In one embodiment, when a human (adult) is used as the subject to ingest or administer the composition of the present invention, the dosage of the sesamin compound is preferably 0.5 mg or more, more preferably 1 mg or more, further preferably 3 mg or more, and preferably 200 mg or less, more preferably 100 mg or less, and further preferably 80 mg or less per day, as a dosage converted to sesamin. In one embodiment, the dosage of the sesamin compound is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and further preferably 3 to 80 mg per day, as a dosage converted to sesamin, for a human (adult). The above dosage is their total amount when two or more sesamin compounds are used. In one embodiment, a human (adult) is preferably orally ingested or administered 0.5 to 200 mg of sesamin and / or episesamin per day, more preferably 1 to 100 mg, and further preferably 3 to 80 mg.

[0039] In one embodiment, when the composition of the present invention is ingested or administered to humans (adults), the dosage of ferulic acid or its salt is preferably 5 mg or more per day, more preferably 10 mg or more, and even more preferably 35 mg or more, and is preferably 2000 mg or less, more preferably 1200 mg or less, and even more preferably 900 mg or less. In one embodiment, when the composition of the present invention is ingested or administered to humans (adults), the dosage of ferulic acid or its salt is preferably 5 to 2000 mg per day, more preferably 10 to 1200 mg, and even more preferably 35 to 900 mg per day, as a dosage converted to ferulic acid. In one embodiment, the above-mentioned amount of sesamin-based compounds and ferulic acid or its salt is preferably orally ingested or administered to a human daily. Furthermore, the above-mentioned amount is preferably ingested or administered once a day or more, for example, once a day or in divided doses (e.g., 2-3 times). The above-mentioned dosage can be per 60 kg body weight. When the composition of the present invention is used in humans to achieve an effect of increasing or promoting energy production, inhibiting a decrease in energy production, or maintaining energy production, the dosage of the sesamin-like compound and ferulic acid or a salt thereof is preferably within the above-mentioned range. When the composition of the present invention is used in humans to achieve an anti-aging effect, a lifespan-extending effect, or a healthy lifespan-extending effect, the dosage of the sesamin-like compound and ferulic acid or a salt thereof is also preferably within the above-mentioned range. In one embodiment, the composition of the present invention can be used to allow humans to ingest or administer the above-mentioned amount of sesamin-based compounds and ferulic acid or a salt thereof per day.

[0040] The composition of the present invention preferably contains sesamin-based compounds in an amount of 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg per day for an adult in terms of sesamin content. The composition of the present invention preferably contains ferulic acid or a salt thereof in an amount of 5 to 2000 mg, more preferably 10 to 1200 mg, and even more preferably 35 to 900 mg per day for an adult in terms of ferulic acid.

[0041] The composition of the present invention is preferably taken or administered continuously. In one embodiment, the composition of the present invention is preferably taken or administered continuously for 1 week or more, more preferably for 4 weeks or more, further preferably for 8 weeks or more, and particularly preferably for 12 weeks or more.

[0042] The subject to whom the composition of the present invention is taken or administered (also referred to as the subject of administration) is not particularly limited, but is preferably a human or a non-human mammal, and more preferably a human. In one embodiment, the subjects for administration include subjects who need or wish to increase or promote energy production, suppress the reduction of energy production, or maintain energy production, and subjects who need or wish to prevent or improve symptoms of aging. As such subjects, for example, middle-aged and elderly people can be listed. In one embodiment, the composition of the present invention is suitable for use as a composition for increasing or promoting energy production, suppressing the reduction of energy production, or maintaining energy production, or as an anti-aging composition for middle-aged and elderly people. Middle-aged and elderly people can be, for example, humans over 40 years old. In one embodiment, among middle-aged and elderly people, the elderly are preferably the subjects. The elderly can be, for example, humans over 60 years old or over 65 years old. The composition of the present invention can also be used on healthy people for the purpose of preventing or improving a condition or disease that can be expected to be prevented or improved by increasing or promoting energy production, suppressing the reduction of energy production, or maintaining energy production.

[0043] The composition of the present invention may also be accompanied by labels of one or more functions selected from, for example, "helps energy production or metabolism", "helps energy production or metabolism in cells", "helps energy production or metabolism in mitochondria within cells", "maintains and improves vigor and vitality", "maintains and improves physical strength and performance", "inhibits cell aging", "extends healthy life span", and "healthy longevity". In one embodiment, the composition of the present invention is preferably a food or beverage with the above-mentioned label. In addition, the above-mentioned label can also be a label with the meaning used to obtain the above-mentioned function. The above-mentioned label can be attached to the composition itself, or it can be attached to the container or packaging of the composition.

[0044] The present invention also includes the following method. A method for increasing, promoting, inhibiting the decrease of energy production or maintaining energy production, characterized by comprising administering the composition of the present invention. By administering the composition of the present invention to a subject, energy production can be effectively increased, promoted, inhibited, or maintained in the subject. The above method can be a therapeutic method or a non-therapeutic method. Preferred embodiments of the composition of the present invention are as described above.

[0045] The present invention also includes the following applications. An application characterized in that the combination of the present invention is used to increase, promote, inhibit the decrease of energy production or maintain energy production. The above applications may be therapeutic or non-therapeutic. Preferred embodiments of the compositions of the present invention are as described above. The compositions of the present invention may be used to prevent or inhibit aging. The compositions of the present invention may be used to extend lifespan and / or healthspan.

[0046] In the above methods and uses, the composition is preferably administered to (or ingested by) a subject once or more per day, for example, once to several times per day (e.g., 2 to 3 times). Oral administration (ingestion) is preferred as the method of administration. The above uses are preferably in humans or non-human mammals, more preferably in humans.

[0047] In the above methods and applications, the composition of the present invention can be used in an amount that can achieve the desired effect (also called an effective amount). The preferred dosage and subject matter of sesamin-like compounds, ferulic acid or its salts are the same as those of the composition of the present invention.

[0048] The present invention also includes the use of (A) sesamin-like compounds and (B) ferulic acid or its salts for producing a composition for increasing or promoting energy production, inhibiting a decrease in energy production, or maintaining energy production. The present invention also includes the use of (A) sesamin-like compounds and (B) ferulic acid or its salts for producing an anti-aging composition or a composition for extending lifespan and / or healthy lifespan. In the above-mentioned use, (A) sesamin-like compounds and (B) ferulic acid or its salts are used in such a manner that the ratio of the weight of the ferulic acid in the composition to the weight of the sesamin-converted sesamin in the (A) sesamin-like compounds is 5 to 100. The above-mentioned compositions and their preferred embodiments are the same as those of the above-mentioned compositions of the present invention.

[0049] In this specification, numerical ranges expressed with lower and upper limits, i.e., "lower limit to upper limit," include both lower and upper limits. For example, a range expressed as "1 to 2" means from 1 to 2, inclusive. In this specification, upper and lower limits may be used in any combination. In addition, all academic documents and patent documents described in this specification are incorporated into this specification by reference. Example

[0050] Hereinafter, the present invention will be described in more detail based on Examples. However, the present invention is not limited to these Examples.

[0051] In the examples, a mixture of sesamin and episesamin (sesamin:episesamin (weight ratio) of 1:1) was used as a sesamin-related compound. This mixture of sesamin and episesamin is hereinafter referred to as a sesamin-related mixture. Ferulic acid produced by Auri Oil Chemical Co., Ltd. was used.

[0052] <Examples 1 and 2> 5.5×10 3TIG-3 cells (fetal lung-derived cells) at a concentration of cells / well were seeded onto a dedicated plate and cultured for 24 hours at 37°C and CO2 (5%) (first culture). The culture medium was prepared by adding 10% Fetal Bovine Serum (Sigma-Aldrich, 500 mL) and 1% Antibiotic Antimycotic Mixed Stock Solution (100×) (Nacalai Tesque Co., Ltd., product number: 02892-54) to DMEM high Glucose (Nacalai Tesque Co., Ltd., product number: 08458-45). After culturing for 24 hours, the sesamin mixture and ferulic acid were added to the culture medium in the wells at the concentrations listed in Table 1 below and cultured for 24 hours (second culture). The culture medium to which the sesamin mixture and ferulic acid were added was removed, and the cells in the wells were treated with a culture medium containing H2O2 (500 μM) for 2 hours (H2O2 treatment). Then, it was exchanged for the analysis medium and the oxygen consumption rate (pmol / min) was analyzed by an analytical instrument (XF analyzer, Agilent Co., Ltd.). After the analysis, the nucleus was stained with Hoechst, the cells were photographed with a fluorescence microscope BZ-x (Keyence Co., Ltd.), and the cell number was counted by image analysis. By measuring the reduction in oxygen consumption of living cells with an XF analyzer, the ATP production representing mitochondrial function can be evaluated. Specifically, after measuring the oxygen consumption rate of the basal respiration of the living cells in the wells, an ATP synthase inhibitor (oligomycin) was added to the wells, and the reduction in oxygen consumption rate (pmol / min / cell) caused by the addition of oligomycin was measured as ATP production. Basal respiration represents the cellular energy requirement under baseline conditions, and a part of the basal respiration is used for ATP production. The reduction in oxygen consumption rate caused by the addition of oligomycin represents ATP production. The results are shown in Table 1.

[0053] The weight ratio (FA / SE) of ferulic acid (FA) to sesamin-like compounds (SE) in the medium used in the second culture of Example 1 was 11, and the molar ratio (FA / SE) was 20. The weight ratio (FA / SE) of ferulic acid to sesamin-like compounds in the medium used in the second culture of Example 2 was 55, and the molar ratio (FA / SE) was 100.

[0054] Reference Example 1 In Reference Example 1, the second culture was performed in a medium not containing the sesamin-derivative mixture and ferulic acid, and no H 2 O 2 treatment was performed. Specifically, the culture was performed in the following manner to examine the amount of ATP produced. 5.5×10 3TIG-3 cells were seeded at 10 cells / well onto a dedicated plate and cultured at 37°C, CO2 (5%) for 24 hours (first culture). Following 24 hours of culture, the cells were cultured for a further 26 hours (second culture). The culture medium was then exchanged for analysis medium, and the cell count, oxygen consumption rate, and reduction in oxygen consumption rate were measured using the same methods as in Example 1. The results are shown in Table 1.

[0055] <Comparative Example 1> In Comparative Example 1, the second culture was performed in a medium that did not contain the sesamin-derivative mixture and ferulic acid. Otherwise, cell culture and H2O2 treatment were performed in the same manner as in Example 1. Specifically, ATP production was assessed by the following method. 5.5×10 3 TIG-3 cells were seeded at 100 cells / well on a dedicated plate and cultured at 37°C and CO2 (5%) for 24 hours (first culture) and further cultured for 24 hours (second culture). The culture medium was removed and the cells in the wells were treated with a culture medium supplemented with H2O2 (500 μM) for 2 hours (H2O2 treatment). The culture medium was then exchanged for the analysis medium, and the cell number was counted, and the oxygen consumption rate and the amount of reduction in oxygen consumption rate were measured using the same method as in Example 1. The results are shown in Table 1.

[0056] Comparative Examples 2 to 4 The ATP production of cells treated with the sesamin-class mixture alone or ferulic acid alone was evaluated in Comparative Examples 2 to 4. Specifically, the cells were cultured by the following method to examine the ATP production. 5.5×10 3 TIG-3 cells of cells / well were inoculated into a special plate and cultured for 24 hours (first culture) at 37°C and CO2 (5%). After 24 hours, the sesamin mixture (Comparative Example 2) or ferulic acid (Comparative Examples 3-4) were added to the culture medium in the hole at a concentration as described in Table 1 below and cultured for 24 hours (second culture). The culture medium to which the sesamin mixture or ferulic acid was added was removed and the cells in the hole were treated for 2 hours (H2O2) with the culture medium adding H2O2 (500 μM). The culture medium was then exchanged for analysis and the cell number was counted, and the oxygen consumption rate and the oxygen consumption rate reduction were measured using the same method as in Example 1. The results are shown in Table 1.

[0057] [Table 1]

[0058] In Table 1, SE represents sesamin-based compounds, and FA represents ferulic acid. “ATP production (10 -2pmol / min / cell)” represents the mean and standard deviation (SD) of the ATP production (reduction in oxygen consumption rate due to ATP synthase inhibition) obtained above (n=4). “Improvement rate relative to Comparative Example 1” is the ATP production (10 -2 pmol / min / cell) was determined by the following method. Improvement rate (%) relative to Comparative Example 1 = 100 × ((ATP production amount of the Example or Comparative Example) - (ATP production amount of Comparative Example 1)) / (ATP production amount of Comparative Example 1)

[0059] Comparison between Reference Example 1 and Comparative Example 1 reveals that ATP production is reduced by hydrogen peroxide treatment. A greater improvement rate relative to Comparative Example 1 (hereinafter simply referred to as improvement rate) indicates that the reduction in ATP production is more suppressed. Figure 1 A graph showing the effects of sesamin-based compounds and ferulic acid on energy production is shown. Figure 1 The vertical axis (improvement rate) of the graph is the improvement rate relative to the above-mentioned Comparative Example 1. Figure 1 The total value (total value) of the improvement rate of Comparative Examples 2 and 3 and the total value (total value) of the improvement rate of Comparative Examples 2 and 4 are shown. In Comparative Example 2 (sesamin-related compound concentration: 1 μM), the improvement rate was 6.1%, and in Comparative Example 3 (ferulic acid concentration: 20 μM), the improvement rate was -0.7%. In Example 1 (sesamin-related compound concentration of 1 μM, ferulic acid concentration of 20 μM), the improvement rate was 15.2%. This improvement rate in Example 1 was significantly higher than the combined improvement rate (6.1%) of Comparative Example 2 (with the same sesamin-related compound concentration) and the improvement rate (-0.7%) of Comparative Example 3 (with the same ferulic acid concentration) (5.4%). Regarding Example 2, the above-mentioned improvement rate is higher than the total improvement rate of Comparative Examples 2 and 4 (6.1+4.8=10.9%).

[0060] like Figure 1 As shown, the improvement rates in Examples 1 and 2 are greater than the combined improvement rates for treatment with sesamin-related compounds alone and ferulic acid alone. This indicates that the sesamin-related compounds and ferulic acid do not merely additively inhibit the reduction in ATP production, but rather, the combined use of sesamin-related compounds and ferulic acid synergistically inhibits the reduction in ATP production. This confirms that compositions containing sesamin-related compounds and ferulic acid or its salts exhibit a synergistic effect in enhancing or promoting energy production, inhibiting a decrease in energy production, or maintaining energy production.

[0061] <Example 3> The effect of sesamin compounds and ferulic acid on extending the lifespan of cells was investigated. Because yeast K6001 does not divide into daughter yeast, the lifespan of parent cells can be measured by counting the number of daughter cells produced by budding from parent cells. In this experiment, yeast K6001 was cultured in YPGalactose liquid medium (containing 2% galactose, 1% yeast extract, and 2% peptone) until the stationary phase. A portion of the yeast was recovered and washed twice with water. The washed yeast was inoculated into YPGlucose agar medium (containing 2% galactose, 1% yeast extract, and 2% peptone) containing a sesamin compound and ferulic acid. After incubation at 30°C for two days, the daughter cells were counted under a microscope. The concentration of the sesamin compound in the culture medium was set to 1 μM. The concentration of ferulic acid in the culture medium was set to 10 μM, 20 μM, 50 μM, or 100 μM. The weight ratio (FA / SE) of ferulic acid (FA) to sesamin-like compounds (SE) in the culture medium containing 10 μM ferulic acid was 5. The weight ratio (FA / SE) was 11 in the culture medium containing 20 μM ferulic acid, 27 in the culture medium containing 50 μM ferulic acid, and 55 in the culture medium containing 100 μM ferulic acid.

[0062] In a control, yeast K6001 was cultured to the stationary phase using the same method as above. After washing with water, it was inoculated into YPGalactose liquid medium without the sesamin-derived compound and ferulic acid and cultured at 30°C for 2 days. The daughter cells were then counted using a microscope.

[0063] Results Figure 2 、 Figure 3 、 Figure 4 and Figure 5 This is a graph showing the results of a study on the effect of a combination of sesamin-based compounds and ferulic acid on extending the lifespan of yeast cells. Figure 2 、 Figure 3 、 Figure 4 and Figure 5 The horizontal axis of the graph represents the number of daughter cells produced by budding from one parent cell. The vertical axis, divided cells (%), represents the ratio (%) of parent cells of the daughter cells of the generation shown on the horizontal axis that budded relative to the total number of parent cells (100%) (Reference: Jarolim, et al. "A novel assay for replicative lifespan in Saccharomyces cerevisiae." FEMS yeastresearch 5.2 (2004): 169-177). For example, if five daughter cells (generations 1 to 5) bud from a parent cell, the parent cell (divided cell) will be counted in generations 1 to 5 respectively. Figure 2 、 Figure 3 、 Figure 4 and Figure 5 In the figure, white circles (◯) represent the control (CTL), and black circles (●) represent yeast cultured in a medium containing sesamin-like compounds (SE) and ferulic acid (FA). Figure 2 、 Figure 3 、 Figure 4 and Figure 5 The concentration of the sesaminoid mixture in the culture medium was 1 μM, and the concentration of ferulic acid was Figure 2 10 μM, Figure 3 20 μM, Figure 4 50 μM, Figure 5 The concentration of 100 μM.

[0064] Regarding the weight ratio of ferulic acid to sesamin-like compounds (FA / SE) in the culture medium containing sesamin-like compounds (SE) and ferulic acid (FA), Figure 2 The middle is 5, Figure 3 The middle is 11, Figure 4 The middle is 27, Figure 5 The value is 55. Figure 2 、 Figure 3 、 Figure 4 and Figure 5 As shown, when compared with the control, the number of progeny yeast increased due to sesamin compounds and ferulic acid. The combined use of sesamin compounds and ferulic acid showed an effect of extending the division lifespan of yeast. The extension of division lifespan can be understood as the extension of individual lifespan or healthspan. In addition, the extension of division lifespan can be understood as the prevention or inhibition of aging. By containing (A) sesamin compounds and (B) ferulic acid or its salt at a ratio of the weight of (B) converted to ferulic acid to the weight of (A) converted to sesamin ((B) converted to ferulic acid / (A) converted to sesamin) of 5 to 100, it was confirmed that the lifespan extension effect was exerted.

Claims

1. A composition, characterized in that Containing (A) a sesamin-like compound and (B) ferulic acid or a salt thereof, The ratio of the ferulic acid-equivalent weight of ferulic acid or its salt (B) to the sesamin-equivalent weight of the sesamin-class compound (A) is 5 to 100.

2. The composition according to claim 1, characterized in that The sesamin-like compound is sesamin and / or episesamin.

3. The composition according to claim 1 or 2, characterized in that It is a composition for oral use.

4. The composition according to claim 1 or 2, characterized in that For food and drink.

5. The composition according to claim 1 or 2, characterized in that For cosmetics.

6. The composition according to claim 1 or 2, characterized in that A composition for increasing or promoting energy production, suppressing a decrease in energy production, or maintaining energy production.

7. The composition according to claim 1 or 2, characterized in that The invention is an anti-aging composition.

8. The composition according to claim 1 or 2, characterized in that The present invention is a composition for prolonging life span and / or healthy life span.

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