WO2024190669A1 - Composition containing sesamin compound and ferulic acid or salt thereof - Google Patents
Composition containing sesamin compound and ferulic acid or salt thereof Download PDFInfo
- Publication number
- WO2024190669A1 WO2024190669A1 PCT/JP2024/009051 JP2024009051W WO2024190669A1 WO 2024190669 A1 WO2024190669 A1 WO 2024190669A1 JP 2024009051 W JP2024009051 W JP 2024009051W WO 2024190669 A1 WO2024190669 A1 WO 2024190669A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sesamin
- ferulic acid
- composition
- present
- salt
- Prior art date
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- KSEBMYQBYZTDHS-HWKANZROSA-M (E)-Ferulic acid Natural products COC1=CC(\C=C\C([O-])=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-M 0.000 title claims abstract description 139
- KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 title claims abstract description 139
- 229940114124 ferulic acid Drugs 0.000 title claims abstract description 139
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
- A23L2/52—Adding ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
- A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
Definitions
- the present invention relates to a composition containing a sesamin-class compound and ferulic acid or a salt thereof.
- NADH nicotinamide adenine dinucleotide
- ATP adenosine triphosphate
- Sesamin is one of the main lignan compounds found in sesame.
- Patent Document 1 describes that a composition containing sesamin and ⁇ -oryzanol has an anti-fatigue effect.
- Ferulic acid is a type of polyphenol and is known to have antioxidant properties.
- the present invention aims to provide a composition that can effectively improve, promote, inhibit the decline or maintain energy production.
- the present invention includes, but is not limited to, the following compositions and the like.
- a composition comprising (A) a sesamin-based compound and (B) ferulic acid or a salt thereof, wherein the ratio of the weight of (A) the sesamin-based compound to the weight of (B) ferulic acid or a salt thereof, in terms of ferulic acid, is 5 to 100.
- composition according to [1] or [2] above which is a cosmetic preparation.
- composition according to any one of [1] to [5] above which is a composition for improving, promoting, inhibiting a decrease in, or maintaining energy production.
- composition according to any one of [1] to [6] above which is an anti-aging composition.
- composition according to any one of [1] to [7] above which is a composition for extending lifespan and/or extending healthy lifespan.
- the present invention provides a composition that can effectively improve, promote, inhibit the decline of, or maintain energy production.
- FIG. 1 is a graph showing the effects of sesamin class compounds and ferulic acid on energy production.
- FIG. 1 is a graph showing the effects of sesamin class compounds and ferulic acid on energy production.
- FIG. 3 is a graph showing the results of investigating the effect
- the composition of the present invention contains (A) a sesamin-based compound and (B) ferulic acid or a salt thereof.
- the ratio of the weight of (A) the sesamin-based compound in terms of sesamin to the weight of (B) ferulic acid or a salt thereof in terms of ferulic acid is 5 to 100.
- sesamin compounds are a general term for compounds including sesamin and its analogues.
- the sesamin compounds one type of compound may be used alone, or two or more types of compounds may be used.
- Sesamin is one of the major lignan compounds contained in sesame.
- examples of sesamin analogues include dioxabicyclo[3.3.0]octane derivatives described in JP-A-4-9331.
- Specific examples of sesamin compounds include sesamin, episesamin, sesaminol, episesaminol, sesamol, and sesamolin, and these stereoisomers or racemates may be used alone or in mixture.
- Metabolites of sesamin compounds are also sesamin analogues contained in the sesamin compounds of the present invention, and can be used in the present invention, so long as they exhibit the effects of the present invention.
- Examples of metabolites that can be used as sesamin compounds include the compounds described in JP 2009-143884 A.
- metabolites of sesamin compounds include SC1 ((7 ⁇ ,7' ⁇ ,8 ⁇ ,8' ⁇ )-3',4'-methylenedioxy-7,9':7',9-diepoxylignane-3,4-diol) and SC2 ((7 ⁇ ,7' ⁇ ,8 ⁇ ,8' ⁇ )-7,9':7',9-diepoxylignane-3,3',4,4'-tetraol).
- SC1 ((7 ⁇ ,7' ⁇ ,8 ⁇ ,8' ⁇ )-3',4'-methylenedioxy-7,9':7',9-diepoxylignane-3,4-diol)
- SC2 ((7 ⁇ ,7' ⁇ ,8 ⁇ ,8' ⁇ )-7,9':7',9-diepoxylignane-3,3',4,4'-tetraol).
- SC1 is more preferred.
- the sesamin-class compound is preferably sesamin and/or episesamin, and more preferably sesamin and episesamin.
- the ratio is not particularly limited, but for example, the sesamin:episesamin (weight ratio) 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 form in which the weight ratio of sesamin:episesamin is 1:1 is one of the preferred embodiments of the present invention.
- sesamin compounds used in the present invention are not limited in any way by their form or production method.
- an extract containing sesamin (called a sesamin extract or purified product) extracted from sesame oil by a known method (for example, the method described in JP-A-4-9331) can be used.
- Sesamin compounds can also be obtained by synthesis.
- sesamin and episesamin can be synthesized by the method of Beroza et al. (J. Am. Chem. Soc., 78, 1242 (1956)).
- Ferulic acid is a type of polyphenol and is found in plants. Ferulic acid or its salts are not limited in any way by their form or production method. For example, ferulic acid can be obtained by extracting a plant containing ferulic acid or by chemical synthesis. Ferulic acid or its salts may be chemically synthesized or may be extracted and purified from natural products.
- Examples of plants that contain ferulic acid include corn, barley, wheat, rice, coffee, onion, radish, lemon, cnidium rhizome, angelica tree, pine, coptis japonica, and sweet potato.
- ferulic acid is abundant in rice bran.
- chemical synthesis of ferulic acid ferulic acid can be produced by condensation decarboxylation of vanillin and malonic acid.
- the method of extraction from raw materials of ferulic acid or its salts and the method of purification, and known methods can be used.
- the salt of ferulic acid is not particularly limited as long as it is a pharmacologically acceptable salt or a salt acceptable for use in foods and beverages, and examples of the salt include basic salts.
- Examples of basic salts include alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts and magnesium salts; and the like.
- 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 5 to 100.
- the composition of the present invention contains (A) sesamin-based compound and (B) ferulic acid or a salt thereof in the above weight ratio. As shown in the Examples below, when sesamin-class compounds and ferulic acid or its salts were used in combination at the above weight ratio, the decrease in ATP production caused by hydrogen peroxide ( H2O2 treatment ) was effectively suppressed.
- the effect of suppressing the decrease in ATP production when sesamin-class compounds and ferulic acid or its salts were used in combination at the above weight ratio was a synergistic effect that was significantly superior to the additive effect predicted when sesamin-class compounds were used alone and when ferulic acid or its salts were used alone.
- a composition containing a sesamin-class compound and ferulic acid or a salt thereof in the above weight ratio exhibits excellent effects in improving, promoting, decrease suppression or maintenance of energy production.
- the composition of the present invention when used as an active ingredient for improving, promoting, decrease suppression or maintenance of energy production, for example, the above effect can be exerted even with a low dose of the active ingredient, so that the intake amount of the active ingredient can be reduced.
- the reduced intake amount leads to ease of intake, and a composition for improving, promoting, decrease suppression or maintenance of energy production that is easier to take continuously can be obtained.
- the ratio of the weight of (B) ferulic acid or a salt thereof in ferulic acid equivalent to the weight of (A) sesamin-based compound in sesamin equivalent is preferably 10 or more, more preferably 11 or more, and preferably 70 or less, more preferably 55 or less.
- the above weight ratio ((B) in ferulic acid equivalent/(A) in sesamin equivalent) is preferably 10 to 100, more preferably 10 to 70, even more preferably 10 to 55, and particularly preferably 11 to 55.
- the weight in terms of sesamin or similar expressions means the weight when the sesamin-based compound is sesamin or episesamin, and when the sesamin-based compound is a compound other than sesamin and episesamin, means the value obtained by multiplying the number of moles of the compound by the molecular weight of sesamin.
- the weight in terms of ferulic acid or a similar expression means the weight of ferulic acid, and in the case of a salt of ferulic acid, means the value obtained by multiplying the number of moles of the salt by the molecular weight of ferulic acid.
- the composition of the present invention can be preferably used as a composition for improving, promoting, inhibiting or maintaining the decline of energy production.
- the composition of the present invention may be a composition for improving, promoting, inhibiting or maintaining the decline of energy production, containing a sesamin-class compound and ferulic acid or a salt thereof as active ingredients.
- Energy production function declines, for example, with aging.
- the decline in energy production leads to a decline in cell function, a decline in organ function, a decline in whole body function, etc.
- the improvement, promotion, inhibition of decline or maintenance of energy production will have the effect of inhibiting or maintaining the decline of cell function, inhibiting or maintaining the decline of organ function, inhibiting or maintaining the decline of whole body function, etc.
- the improvement, promotion, inhibition of decline or maintenance of energy production is effective, for example, for preventing or inhibiting aging (anti-aging), etc.
- Aging includes cellular aging and individual aging. The individual is preferably a human.
- the composition of the present invention can be used as an anti-aging composition.
- the composition of the present invention may be an anti-aging composition containing a sesamin-based compound and ferulic acid or a salt thereof as active ingredients.
- the composition of the present invention can be used to extend the lifespan of an individual.
- the composition of the present invention can be used as a composition for extending lifespan.
- the composition of the present invention is also useful for extending healthy lifespan. Healthy lifespan refers to the period during which one can live without daily life being restricted by health problems (Ministry of Health, Labour and Welfare, "2020 Edition, Ministry of Health, Labour and Welfare White Paper," p. 17).
- the composition of the present invention can be used as a composition for extending healthy lifespan.
- the composition of the present invention can be used as a composition for extending lifespan and/or healthy lifespan.
- the composition of the present invention can be used for preventing or improving the condition or disease associated with reduced energy production.
- the condition or disease associated with reduced energy production includes the condition or disease caused by reduced energy production, or the condition or disease associated with reduced energy production. These conditions or diseases include chronic fatigue syndrome, muscle diseases such as sarcopenia, and cognitive dysfunction such as dementia.
- prevention includes preventing onset, delaying onset, reducing the incidence, reducing the risk of onset, etc.
- Amelioration of a condition or disease includes recovering from a condition or disease, alleviating the symptoms of a condition or disease, ameliorating the symptoms of a condition or disease, delaying or preventing the progression of a condition or disease, etc.
- energy production may be evaluated based on common knowledge in the technical field to which the present invention pertains, and the method is not particularly limited.
- energy production can be evaluated by using an extracellular flux analyzer to continuously measure the oxygen consumption rate (OCR) used by mitochondria during ATP synthesis in the cells to be measured while adding an ATP synthase inhibitor (e.g., oligomycin).
- OCR oxygen consumption rate
- oligomycin an ATP synthase inhibitor
- Sesamin-based compounds and ferulic acid or its salts are compounds that are found in natural products and foods and beverages, and are consumed with the body. For this reason, from the standpoint of safety, it is believed that there are few problems with taking sesamin-based compounds and ferulic acid or its salts, for example, every day. According to the present invention, it is possible to provide a composition that contains a highly safe substance as an active ingredient and has excellent effects of improving, promoting, inhibiting the decrease of, or maintaining energy production.
- compositions of the present invention can be applied in either therapeutic (medical) or non-therapeutic (non-medical) applications, the latter being a concept that does not include medical procedures, i.e., surgery, treatment or diagnosis of humans.
- the composition of the present invention can be in the form of, but is not limited to, a food or drink, a cosmetic, a drug, a quasi-drug, a feed, etc.
- the composition of the present invention may be a food or drink, a cosmetic, a drug, a quasi-drug, a feed, etc., or may be a material or preparation to be mixed 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 be provided as a composition as it is, or as a composition containing the agent.
- the composition for improving, promoting, inhibiting a decrease, or maintaining energy production can also be referred to as an agent for improving, promoting, inhibiting a decrease, or maintaining energy production.
- the composition for anti-aging can also be referred to as an anti-aging agent.
- the composition for extending lifespan and/or extending healthy lifespan can also be referred to as an agent for extending lifespan and/or extending healthy lifespan.
- the composition of the present invention may be either an oral composition or a non-oral composition.
- the composition of the present invention is preferably an oral composition.
- the oral composition include food and drink, oral medicine, oral quasi-drug, and feed, and are preferably food and drink or oral medicine, and more preferably food and drink.
- the composition of the present invention can be used as an external preparation for the skin (external composition for the skin). External preparations for the skin include cosmetics, pharmaceuticals, quasi-drugs, etc., and are preferably cosmetics.
- the composition of the present invention may contain any additives and any components in addition to the sesamin-class compound and ferulic acid or a salt thereof, so long as the effects of the present invention are not impaired. These additives and components may be selected depending on the form of the composition, and those that can generally be used for foods and beverages, cosmetics, medicines, quasi-drugs, feed, etc. may be used. When the composition of the present invention is used as a food and beverage, cosmetics, medicines, quasi-drugs, feed, etc., there are no particular limitations on the method of production, and it may be produced by a general method. In one aspect, the composition of the present invention may consist of a sesamin-class compound and ferulic acid or a salt thereof.
- composition of the present invention when the composition of the present invention is made into a food or beverage, various foods and beverages can be made by blending the sesamin-class compounds and ferulic acid or a salt thereof with ingredients that can be used in foods and beverages (e.g., food ingredients, food additives used as necessary, etc.).
- the foods and beverages are not particularly limited, and examples include general foods and beverages, health foods, health supplements, health drinks, functional foods, foods for specified health uses, and foods and beverages for the sick.
- the above health foods, health supplements, functional foods, foods for specified health uses, and foods and beverages for the sick can be used in various formulation forms, such as fine granules, tablets, granules, powders, capsules, chewables, dry syrups, syrups, liquids, beverages, drinks, and liquid diets.
- composition of the present invention When the composition of the present invention is used as a cosmetic, various cosmetic preparations can be made by blending the sesamin-based compound and ferulic acid or its salt with ingredients that can be used in cosmetics (e.g., carriers, additives, etc. that are acceptable for cosmetics).
- the product form of the cosmetic preparation is not particularly limited, and examples include skin care cosmetics such as lotion, beauty serum, pack, milky lotion, cream, and sunscreen.
- composition of the present invention when used as a drug or quasi-drug, for example, a pharmacologically acceptable carrier and additives added as necessary can be mixed with sesamin-class compounds and ferulic acid or a salt thereof to produce a drug or quasi-drug in various dosage forms.
- Such carriers, additives, etc. may be any pharmacologically acceptable carriers that can be used in drugs or quasi-drugs, and examples of such carriers, additives, etc. include one or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants, etc.
- Examples of the administration (ingestion) form of a drug or quasi-drug include oral or non-oral (transdermal, transmucosal, enteral, injection, etc.) administration forms.
- the composition of the present invention when used as a drug or quasi-drug, it is preferable to use an oral drug or quasi-drug.
- dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewables, etc.
- the pharmaceutical or quasi-drug is preferably a skin topical preparation.
- the dosage form of the skin topical preparation is not particularly limited, and may be any form such as a solution, emulsion, cream, gel, powder, aerosol, mist, capsule, or sheet.
- the pharmaceutical agent may be a non-human animal drug.
- the sesamin-class compound and ferulic acid or a salt thereof 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.
- the content of the sesamin-family compounds contained in the composition of the present invention is not particularly limited and can be set according to the form, etc.
- the content of the sesamin-family compounds in the composition of the present invention is, for example, preferably 0.001% by weight or more in the composition, more preferably 0.01% by weight or more, even more preferably 0.05% by weight or more, and preferably 10% by weight or less, and more preferably 5% by weight or less, in terms of sesamin.
- the content of the sesamin-family compounds in the composition is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight, and even more preferably 0.05 to 5% by weight, in terms of sesamin.
- the above content is the total content of these.
- the content of the sesamin-family compounds in the composition can be measured by HPLC (high performance liquid chromatography).
- the content of ferulic acid or a salt thereof contained in the composition of the present invention is not particularly limited and can be set according to the form, etc.
- the content of ferulic acid or a salt thereof in the composition of the present invention is, for example, preferably 0.01% by weight or more in the composition, more preferably 0.1% by weight or more, even more preferably 1% by weight or more, and preferably 90% by weight or less, more preferably 55% by weight or less, in terms of the content of ferulic acid.
- the content of ferulic acid or a salt thereof in the composition of the present invention is preferably 0.01 to 90% by weight, more preferably 0.1 to 55% by weight, even more preferably 1 to 55% by weight, in terms of the content of ferulic acid.
- the content of ferulic acid or a salt thereof in the composition can be measured by HPLC.
- the composition of the present invention can be ingested or administered by various methods known per se according to its form or dosage form.
- the composition of the present invention is preferably ingested orally (administered orally).
- the dosage of the composition of the present invention (which may also be referred to as the intake amount) is not particularly limited.
- the dosage of the composition of the present invention may be an amount that can obtain, for example, an effect of improving, promoting, suppressing or maintaining the decrease of energy production, or an effect of anti-aging, and may be appropriately set depending on the dosage form, administration method, body weight of the subject, etc.
- the dosage of the sesamin-class compound when the composition of the present invention is ingested or administered to a human (adult), 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, in terms of sesamin per day. In one embodiment, the dosage of the sesamin-class compound is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg, in terms of sesamin per day, for a human (adult). When two or more types of sesamin-class compounds are used, the dosage is the total amount of these.
- sesamin and/or episesamin it is preferable to orally ingest or administer sesamin and/or episesamin to a human (adult) in an amount of preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg per day.
- the dosage of ferulic acid or a salt thereof is preferably 5 mg or more, more preferably 10 mg or more, even more preferably 35 mg or more, and preferably 2000 mg or less, more preferably 1200 mg or less, even more preferably 900 mg or less, per day, calculated as a dose of ferulic acid.
- the dosage of ferulic acid or a salt thereof is preferably 5 to 2000 mg, more preferably 10 to 1200 mg, even more preferably 35 to 900 mg, per day, calculated as a dose of ferulic acid.
- the above-mentioned amounts of sesamin-class compounds and ferulic acid or a salt thereof are preferably orally ingested or administered to a human per day.
- the above-mentioned amounts are preferably ingested or administered once or more times a day, for example, once a day or divided into several times (for example, 2 to 3 times a day).
- the above-mentioned dosages may be per 60 kg of body weight.
- the doses of the sesamin-class compound and ferulic acid or a salt thereof are preferably within the above-mentioned ranges.
- the doses of the sesamin-class compound and ferulic acid or a salt thereof are preferably within the above-mentioned ranges.
- the composition of the present invention can be used to cause a human to ingest or administer the above-mentioned amounts of sesamin-class compounds and ferulic acid or a salt thereof per day.
- the content of sesamin-class compounds in the composition of the present invention is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg, of sesamin-equivalent compounds per daily intake for an adult.
- the content of ferulic acid or a salt thereof in the composition of the present invention is preferably 5 to 2000 mg, more preferably 10 to 1200 mg, and even more preferably 35 to 900 mg, of ferulic acid per daily intake for an adult.
- composition of the present invention is preferably taken or administered continuously.
- the composition of the present invention is preferably taken 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 twelve weeks.
- the subject to which the composition of the present invention is ingested or administered is not particularly limited, and is preferably a human or a non-human mammal, more preferably a human.
- the subject of administration includes a subject who needs or desires to improve, promote, inhibit decline, or maintain energy production, and a subject who needs or desires to prevent or improve aging symptoms. Examples of such subjects include middle-aged and elderly people.
- the composition of the present invention is suitably used as a composition for improving, promoting, inhibiting decline, or maintaining energy production for middle-aged and elderly people, or an anti-aging composition.
- Middle-aged and elderly people may be, for example, humans aged 40 years or older.
- elderly people are preferred as the subject.
- Elderly people may be, for example, humans aged 60 years or older or 65 years or older.
- the composition of the present invention can also be used for healthy people, for example, for the purpose of preventing conditions or diseases that can be expected to be prevented or improved by improving, promoting, inhibiting decline, or maintaining energy production.
- the composition of the present invention may be labeled with one or more functions, such as “aiding energy production or metabolism,””aiding cellular energy production or metabolism,””aiding energy production or metabolism in intracellular mitochondria,””maintaining and improving vitality and energy,””maintaining and improving physical strength and performance,””inhibiting cellular aging,””extending healthy lifespan,” and “healthy longevity.”
- the composition of the present invention is preferably a food or drink to which the above-mentioned label is attached.
- the above-mentioned label may be a label indicating that the composition is used to obtain the above-mentioned function.
- the above-mentioned label may be attached to the composition itself, or to a container or packaging of the composition.
- the present invention also encompasses the following methods.
- a method for improving, promoting, suppressing the decline or maintaining of energy production which comprises administering the above-mentioned composition of the present invention.
- the above method may be a therapeutic method or a non-therapeutic method.
- the preferred embodiment of the composition of the present invention is as described above.
- the present invention also encompasses the following uses: Use of the composition of the present invention described above for improving, promoting, suppressing the decline or maintaining energy production.
- the above-mentioned use may be therapeutic or non-therapeutic.
- the preferred embodiment of the composition of the present invention is as described above.
- the above-mentioned composition of the present invention may also be used for preventing or inhibiting aging.
- the above-mentioned composition of the present invention may also be used for extending lifespan and/or extending healthspan.
- the above-mentioned methods and uses it is preferable to administer (have the subject ingest) the above-mentioned composition at least once a day, for example, once to several times a day (for example, two to three times a day).
- Oral administration (ingestion) is a preferred method of administration.
- the above-mentioned uses are preferably in humans or non-human mammals, more preferably in humans.
- the composition of the present invention may be used in an amount that provides the desired effect (which may also be called an effective amount).
- the preferred dosages and subjects of administration of the sesamin-class compounds, ferulic acid or its salts are the same as those of the composition of the present invention described above.
- the present invention also includes the use of (A) a sesamin-class compound and (B) ferulic acid or a salt thereof to produce a composition for improving, promoting, inhibiting the decline or maintaining energy production.
- the present invention also includes the use of (A) a sesamin-class compound and (B) ferulic acid or a salt thereof to produce an anti-aging composition or a composition for extending lifespan and/or extending healthy lifespan.
- (A) a sesamin-class compound and (B) ferulic acid or a salt thereof are used so that the ratio of the weight of the (A) sesamin-class compound in terms of sesamin to the weight of ferulic acid in terms of sesamin in the composition is 5 to 100.
- the above compositions and their preferred aspects are the same as those of the composition of the present invention described above.
- a numerical range expressed by a lower limit and an upper limit includes the lower limit and the upper limit.
- a range expressed by "1 to 2" means 1 or more and 2 or less, including 1 and 2.
- the upper limit and the lower limit may be in any combination. All academic and patent literature cited herein is hereby incorporated by reference.
- sesamin-class compound a mixture of sesamin and episesamin (sesamin:episesamin (weight ratio) 1:1) was used as the sesamin-class compound.
- This mixture of sesamin and episesamin is hereinafter referred to as a sesamin-class mixture.
- Ferulic acid used was that manufactured by Oryza Oil & Fat Chemical Co., Ltd.
- TIG-3 cells fetal lung-derived cells
- the medium used was prepared by adding 10% Fetal Bovine Serum (Sigma-Aldrich, 500 mL) and 1% Antibiotic Antimycotic Mixed Stock Solution (100x) (Nacalai Tesque, Inc., product code: 02892-54) to DMEM high glucose (Nacalai Tesque, Inc., product code: 08458-45).
- the sesamin mixture and ferulic acid were added to the medium in the well at the concentrations shown in Table 1 below, and cultured for 24 hours (second culture).
- the medium containing the sesamin mixture and ferulic acid was removed, and the cells in the well were treated with H 2 O 2 (500 ⁇ M)-added medium for 2 hours (H 2 O 2 treatment).
- the medium was then replaced with an analysis medium, and the oxygen consumption rate (pmol/min) was analyzed using an analysis device (XF analyzer, Agilent Corporation). After the analysis was completed, the nuclei were stained with Hoechst, and the cells were photographed with a fluorescence microscope BZ-x (Keyence Corporation), and the number of cells was counted by image analysis.
- the amount of ATP production which indicates mitochondrial function, can be evaluated by measuring the decrease in oxygen consumption of live cells using the XF analyzer. Specifically, after measuring the oxygen consumption rate of basal respiration of living cells in the well, an ATP synthase inhibitor (oligomycin) was added to the well, and the amount of decrease in oxygen consumption rate due to the addition of oligomycin (pmol/min/cell) was measured and used as the amount of ATP production. Basal respiration indicates the cellular energy demand under baseline conditions, and a part of the basal respiration is used for ATP production. The amount of decrease in oxygen consumption rate due to the addition of oligomycin indicates the amount of ATP production. The results obtained are shown in Table 1.
- the weight ratio (FA/SE) of ferulic acid (FA) to sesamin-based compounds (SE) was 11, and the molar ratio (FA/SE) was 20.
- the weight ratio (FA/SE) of ferulic acid to sesamin-based compounds was 55, and the molar ratio (FA/SE) was 100.
- Example 1 ⁇ Reference Example 1>
- the second culture was carried out in a medium not containing a sesamin component mixture or ferulic acid, and no H 2 O 2 treatment was carried out. Specifically, the culture was carried out by the following method, and the amount of ATP produced was examined. TIG-3 cells were seeded on a dedicated plate at 5.5 x 103 cells/well and cultured for 24 hours at 37°C and CO2 (5%) (first culture). After 24 hours of culture, the cells were further cultured for 26 hours (second culture). The medium was then replaced with an analysis medium, and the cell count, oxygen consumption rate, and decrease in oxygen consumption rate were measured in the same manner as in Example 1. The results are shown in Table 1.
- Comparative Example 1 In Comparative Example 1, the second culture was carried out in a medium that did not contain a sesamin-component mixture or ferulic acid. Other than this, cell culture and H2O2 treatment were carried out in the same manner as in Example 1. Specifically, culture was carried out in the following manner, and the amount of ATP production was examined. TIG-3 cells were seeded on a dedicated plate at 5.5 x 103 cells/well and cultured at 37°C and CO2 (5%) for 24 hours (first culture) and then for another 24 hours (second culture). The medium was removed and the cells in the wells were treated with medium containing H2O2 (500 ⁇ M) for 2 hours ( H2O2 treatment ). The medium was then replaced with an analysis medium, and the cell count, oxygen consumption rate, and decrease in oxygen consumption rate were measured in the same manner as in Example 1. The results are shown in Table 1.
- Comparative Examples 2 to 4 the amount of ATP produced by cells treated with either the sesamin component mixture alone or ferulic acid alone was evaluated. Specifically, the cells were cultured in the following manner, and the amount of ATP produced was examined. TIG-3 cells were seeded on a dedicated plate at 5.5 x 10 3 cells/well and cultured for 24 hours under conditions of 37°C and CO 2 (5%) (first culture). After 24 hours of culture, a sesamin-based mixture (Comparative Example 2) or ferulic acid (Comparative Examples 3-4) was added to the medium in the well at the concentrations shown in Table 1 below, and cultured for 24 hours (second culture).
- the medium containing the sesamin-based mixture or ferulic acid was removed, and the cells in the well were treated with a medium containing H 2 O 2 (500 ⁇ M) for 2 hours (H 2 O 2 treatment).
- the medium was then replaced with an analysis medium, and the cell count, oxygen consumption rate, and amount of decrease in oxygen consumption rate were measured in the same manner as in Example 1. The results are shown in Table 1.
- SE represents sesamin-class compounds
- FA represents ferulic acid.
- SD standard deviation
- FIG. 1 shows a graph showing the effects of sesamin-class compounds and ferulic acid on energy production.
- the vertical axis (improvement rate) of the graph in Figure 1 is the improvement rate relative to the above Comparative Example 1.
- Figure 1 also shows the value obtained by adding up the improvement rates of Comparative Examples 2 and 3 (combined value), and the value obtained by adding up the improvement rates of Comparative Examples 2 and 4 (combined value).
- Comparative Example 2 sesamin-class compound concentration: 1 ⁇ M
- the improvement rate was 6.1%.
- the improvement rates in Examples 1 and 2 were greater than the combined improvement rate when treated with sesamin-based compounds alone and ferulic acid alone.
- the decrease in ATP production was not simply suppressed additively by the sesamin-based compounds and ferulic acid, but the combined use of sesamin-based compounds and ferulic acid synergistically suppressed the decrease in ATP production.
- a composition containing a sesamin-based compound and ferulic acid or a salt thereof exhibits a synergistic effect in improving, promoting, inhibiting the decrease, or maintaining energy production by containing both.
- Example 3 The effect of sesamin compounds and ferulic acid on extending the division life span was investigated. Since yeast K6001 does not divide into daughter yeasts, it is possible to measure the division life span of parent cells by counting the number of daughter cells budding from the parent cell. In this test, yeast K6001 was cultured in YPGalactose liquid medium (2% galactose, 1% yeast extract, 2% peptone) until stationary phase, and some yeast was collected and washed twice with water.
- YPGalactose liquid medium 2% galactose, 1% yeast extract, 2% peptone
- the washed yeast was inoculated on YPGlucose agar medium (2% galactose, 1% yeast extract, 2% peptone) containing a sesamin compound mixture and ferulic acid, and after culturing at 30°C for 2 days, the daughter cells were counted under a microscope.
- the concentration of the sesamin compound mixture in the medium was 1 ⁇ M.
- the concentration of ferulic acid in the medium was 10 ⁇ M, 20 ⁇ M, 50 ⁇ M, or 100 ⁇ M.
- the weight ratio (FA/SE) of ferulic acid (FA) to sesamin-based compounds (SE) contained in the medium was 5 in the medium containing 10 ⁇ M ferulic acid.
- the weight ratio (FA/SE) was 11 in the medium containing 20 ⁇ M ferulic acid, 27 in the medium containing 50 ⁇ M ferulic acid, and 55 in the medium containing 100 ⁇ M ferulic acid.
- yeast K6001 was cultured to stationary phase using the same method as above, washed with water, and inoculated onto YPGalactose liquid medium that did not contain the sesamin mixture or ferulic acid and cultured at 30°C for 2 days. Daughter cells were then counted under a microscope.
- Figures 2, 3, 4, and 5 are graphs showing the results of investigating the effect of combinations of sesamin-class compounds and ferulic acid on extending the replicative lifespan in yeast.
- the horizontal axis of the graphs in Figures 2, 3, 4, and 5 shows the generation (number) of daughter cells that budded from a single parent cell.
- the dividing cells (%) on the vertical axis show the proportion (%) of parent cells that budded off daughter cells of the generation shown on the horizontal axis to the total number of parent cells (100%) (Reference: Jarolim, et al. "A novel assay for replicative lifespan in Saccharomyces cerevisiae.” FEMS yeast research 5.2 (2004): 169-177).
- the weight ratio of ferulic acid to sesamin-based compounds (SE) and ferulic acid (FA) in the medium containing sesamin-based compounds (SE) and ferulic acid (FA) is 5 in Figure 2, 11 in Figure 3, 27 in Figure 4, and 55 in Figure 5.
- the sesamin-based compounds and ferulic acid increased the number of daughter yeasts.
- the combined use of sesamin-based compounds and ferulic acid showed an effect of extending the division lifespan of yeast.
- An extension of division lifespan can be considered as an extension of an individual's lifespan or an extension of healthy lifespan.
- An extension of division lifespan can also be considered as prevention or inhibition of aging.
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Abstract
The purpose of the present invention is to provide a composition capable of effectively increasing, promoting, suppressing a decrease in, or maintaining energy production. The present invention pertains to a composition containing (A) a sesamin compound and (B) ferulic acid or a salt thereof and the ratio of the weight of (B) the ferulic acid or ferulic acid equivalent to the salt thereof to the weight of sesamin equivalent to (A) sesamin compound is 5-100.
Description
本発明は、セサミン類化合物、及び、フェルラ酸又はその塩を含有する組成物等に関する。
The present invention relates to a composition containing a sesamin-class compound and ferulic acid or a salt thereof.
生物がその活動を維持するためには、エネルギーが必要不可欠である。エネルギー産生の大部分は、細胞内小器官の一つであるミトコンドリア内で行われる。食事から摂取された栄養源である糖、脂質、アミノ酸などが代謝され、ＮＡＤＨ（ニコチンアミドアデニンジヌクレオチド）に変換される。次いで、ＮＡＤＨの電子がミトコンドリア呼吸鎖タンパク質（電子伝達系）に受け渡され、ＡＴＰ（アデノシン三リン酸）の形でエネルギーが産生される。
Energy is essential for living organisms to maintain their activity. Most energy production takes place in mitochondria, a type of intracellular organelle. Nutrients ingested from food, such as sugars, lipids, and amino acids, are metabolized and converted into NADH (nicotinamide adenine dinucleotide). Next, electrons from NADH are transferred to mitochondrial respiratory chain proteins (electron transport chain), and energy is produced in the form of ATP (adenosine triphosphate).
加齢、疾患等によってエネルギー産生は低下する。エネルギー産生の低下は、例えばヒトでは、細胞の働きの低下や身体機能の低下等をもたらす。このため、エネルギー産生の向上、促進、低下抑制又は維持作用を有し、副作用の心配がなく継続摂取可能な成分が求められている。また、このような作用を有する成分をサプリメント等として摂取する場合、消費者が継続して摂取しやすい形態であることが望まれる。特に高齢者の場合、嚥下機能が衰えてくることから、例えば錠剤、カプセル剤等の経口用製剤は小型であることが望ましい。特に複数の成分を含む場合は体積が大きくなりがちであることから、経口用製剤の体積を抑えるため、少量でも効果の高い成分、又はこのような成分の組合せを用いることが望ましい。
Energy production declines due to aging, disease, etc. In humans, for example, a decline in energy production leads to a decline in cellular activity and a decline in physical function. For this reason, there is a demand for ingredients that have the effect of improving, promoting, inhibiting the decline, or maintaining energy production, and that can be taken continuously without worrying about side effects. Furthermore, when ingredients with such effects are taken as supplements, etc., it is desirable for them to be in a form that is easy for consumers to take continuously. In particular, for elderly people, as their swallowing function declines, it is desirable for oral preparations such as tablets and capsules to be small. In particular, when multiple ingredients are included, the volume tends to be large, so in order to reduce the volume of the oral preparation, it is desirable to use ingredients that are highly effective even in small amounts, or a combination of such ingredients.
セサミンは、ゴマに含まれる主要なリグナン化合物の一種である。特許文献１には、セサミン類と、γ－オリザノールとを含有する組成物が抗疲労作用を有することが記載されている。フェルラ酸は、ポリフェノールの一種であり、抗酸化作用を有することが知られている。
Sesamin is one of the main lignan compounds found in sesame. Patent Document 1 describes that a composition containing sesamin and γ-oryzanol has an anti-fatigue effect. Ferulic acid is a type of polyphenol and is known to have antioxidant properties.
本発明は、エネルギー産生を効果的に向上、促進、低下抑制又は維持することができる組成物を提供することを目的とする。
The present invention aims to provide a composition that can effectively improve, promote, inhibit the decline or maintain energy production.
本発明者らは上記課題を解決すべく鋭意研究した結果、セサミン類化合物と、フェルラ酸又はその塩とを特定の比率で併用すると、エネルギー産生を向上、促進、低下抑制又は維持する作用が、セサミン類化合物を単独使用した場合の作用、及びフェルラ酸又はその塩を単独使用した場合の作用から予測される範囲を超えて、顕著に高まることを見出した。
As a result of intensive research conducted by the inventors to solve the above problems, they discovered that when a sesamin-based compound is used in combination with ferulic acid or a salt thereof in a specific ratio, the effect of improving, promoting, inhibiting the decline of, or maintaining energy production is significantly enhanced beyond the range predicted from the effect of using a sesamin-based compound alone and the effect of using ferulic acid or a salt thereof alone.
本発明は、以下に限定されるものではないが、以下の組成物等を包含する。
〔１〕（Ａ）セサミン類化合物、及び、（Ｂ）フェルラ酸又はその塩を含有し、（Ａ）セサミン類化合物のセサミン換算の重量に対する、（Ｂ）フェルラ酸又はその塩のフェルラ酸換算の重量の比が、５～１００である、組成物。
〔２〕上記セサミン類化合物が、セサミン及び／又はエピセサミンである上記〔１〕に記載の組成物。
〔３〕経口用組成物である上記〔１〕又は〔２〕に記載の組成物。
〔４〕飲食品である上記〔１〕～〔３〕のいずれかに記載の組成物。
〔５〕化粧料である上記〔１〕又は〔２〕に記載の組成物。
〔６〕エネルギー産生の向上、促進、低下抑制又は維持用組成物である、上記〔１〕～〔５〕のいずれかに記載の組成物。
〔７〕抗老化用組成物である、上記〔１〕～〔６〕のいずれかに記載の組成物。
〔８〕寿命延長用及び／又は健康寿命延長用組成物である、上記〔１〕～〔７〕のいずれかに記載の組成物。 The present invention includes, but is not limited to, the following compositions and the like.
[1] A composition comprising (A) a sesamin-based compound and (B) ferulic acid or a salt thereof, wherein the ratio of the weight of (A) the sesamin-based compound to the weight of (B) ferulic acid or a salt thereof, in terms of ferulic acid, is 5 to 100.
[2] The composition according to [1] above, wherein the sesamin-class compound is sesamin and/or episesamin.
[3] The composition according to [1] or [2] above, which is an oral composition.
[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 preparation.
[6] The composition according to any one of [1] to [5] above, which is a composition for improving, promoting, inhibiting a decrease in, 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, which is a composition for extending lifespan and/or extending healthy lifespan.
〔１〕（Ａ）セサミン類化合物、及び、（Ｂ）フェルラ酸又はその塩を含有し、（Ａ）セサミン類化合物のセサミン換算の重量に対する、（Ｂ）フェルラ酸又はその塩のフェルラ酸換算の重量の比が、５～１００である、組成物。
〔２〕上記セサミン類化合物が、セサミン及び／又はエピセサミンである上記〔１〕に記載の組成物。
〔３〕経口用組成物である上記〔１〕又は〔２〕に記載の組成物。
〔４〕飲食品である上記〔１〕～〔３〕のいずれかに記載の組成物。
〔５〕化粧料である上記〔１〕又は〔２〕に記載の組成物。
〔６〕エネルギー産生の向上、促進、低下抑制又は維持用組成物である、上記〔１〕～〔５〕のいずれかに記載の組成物。
〔７〕抗老化用組成物である、上記〔１〕～〔６〕のいずれかに記載の組成物。
〔８〕寿命延長用及び／又は健康寿命延長用組成物である、上記〔１〕～〔７〕のいずれかに記載の組成物。 The present invention includes, but is not limited to, the following compositions and the like.
[1] A composition comprising (A) a sesamin-based compound and (B) ferulic acid or a salt thereof, wherein the ratio of the weight of (A) the sesamin-based compound to the weight of (B) ferulic acid or a salt thereof, in terms of ferulic acid, is 5 to 100.
[2] The composition according to [1] above, wherein the sesamin-class compound is sesamin and/or episesamin.
[3] The composition according to [1] or [2] above, which is an oral composition.
[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 preparation.
[6] The composition according to any one of [1] to [5] above, which is a composition for improving, promoting, inhibiting a decrease in, 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, which is a composition for extending lifespan and/or extending healthy lifespan.
本発明によれば、エネルギー産生を効果的に向上、促進、低下抑制又は維持することができる組成物を提供することができる。
The present invention provides a composition that can effectively improve, promote, inhibit the decline of, or maintain energy production.
本発明の組成物は、（Ａ）セサミン類化合物、及び、（Ｂ）フェルラ酸又はその塩を含有する。本発明の組成物においては、（Ａ）セサミン類化合物のセサミン換算の重量に対する、（Ｂ）フェルラ酸又はその塩のフェルラ酸換算の重量の比が、５～１００である。
The composition of the present invention contains (A) a sesamin-based compound and (B) ferulic acid or a salt thereof. In the composition of the present invention, the ratio of the weight of (A) the sesamin-based compound in terms of sesamin to the weight of (B) ferulic acid or a salt thereof in terms of ferulic acid is 5 to 100.
本発明において、セサミン類化合物とは、セサミン及びその類縁体を含む化合物の総称である。セサミン類化合物には、１種の化合物を単独で用いてもよく、２種以上の化合物を用いてもよい。セサミンは、ゴマに含まれる主要なリグナン化合物の一種である。セサミン類縁体としては、エピセサミンの他、例えば特開平４－９３３１号公報に記載されたジオキサビシクロ［３．３．０］オクタン誘導体が挙げられる。セサミン類化合物の具体例としては、セサミン、エピセサミン、セサミノール、エピセサミノール、セサモール、セサモリン等を例示でき、これらの立体異性体又はラセミ体を単独で、または混合して使用することができる。セサミン類の代謝物（例えば、特開２００１－１３９５７９号公報に記載）も、本発明の効果を示す限り、本発明におけるセサミン類化合物に含まれるセサミン類縁体であり、本発明に使用することができる。セサミン類化合物として使用できる代謝物として、例えば、特開２００９－１４３８８４号に記載の化合物が挙げられる。セサミン類の代謝物として、ＳＣ１（（７α，７’α，８α，８’α）－３’，４’－ｍｅｔｈｙｌｅｎｅｄｉｏｘｙ－７，９’：７’，９－ｄｉｅｐｏｘｙｌｉｇｎａｎｅ－３，４－ｄｉｏｌ）、ＳＣ２（（７α，７’α，８α，８’α）－７，９’：７’，９－ｄｉｅｐｏｘｙｌｉｇｎａｎｅ－３，３’，４，４’－ｔｅｔｒａｏｌ）が挙げられる。代謝物として、セサミンの代謝物が好ましく、ＳＣ１がより好ましい。
In the present invention, sesamin compounds are a general term for compounds including sesamin and its analogues. As the sesamin compounds, one type of compound may be used alone, or two or more types of compounds may be used. Sesamin is one of the major lignan compounds contained in sesame. In addition to episesamin, examples of sesamin analogues include dioxabicyclo[3.3.0]octane derivatives described in JP-A-4-9331. Specific examples of sesamin compounds include sesamin, episesamin, sesaminol, episesaminol, sesamol, and sesamolin, and these stereoisomers or racemates may be used alone or in mixture. Metabolites of sesamin compounds (for example, those described in JP-A-2001-139579) are also sesamin analogues contained in the sesamin compounds of the present invention, and can be used in the present invention, so long as they exhibit the effects of the present invention. Examples of metabolites that can be used as sesamin compounds include the compounds described in JP 2009-143884 A. Examples of metabolites of sesamin compounds 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). As metabolites, metabolites of sesamin are preferred, and SC1 is more preferred.
本発明においては、セサミン類化合物として、セサミン及び／又はエピセサミンが好ましく、セサミン及びエピセサミンがより好ましい。セサミン及びエピセサミンを用いる場合、これらの比率は特に限定されないが、例えば、セサミン：エピセサミン（重量比）が１：０．１～１：９が好ましく、１：０．３～１：３がより好ましく、１：０．５～１：２が更に好ましい。セサミン：エピセサミンの重量比が１：１である形態は、本発明の好適な実施形態の１つである。
In the present invention, the sesamin-class compound is preferably sesamin and/or episesamin, and more preferably sesamin and episesamin. When sesamin and episesamin are used, the ratio is not particularly limited, but for example, the sesamin:episesamin (weight ratio) 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 form in which the weight ratio of sesamin:episesamin is 1:1 is one of the preferred embodiments of the present invention.
本発明で使用されるセサミン類化合物は、その形態や製造方法等によって、何ら制限されるものではない。例えば、セサミンの場合は、ゴマ油から公知の方法（例えば、特開平４－９３３１号公報に記載された方法）によって抽出したセサミンを含有する抽出物（セサミン抽出物又は精製物という）を用いることができる。合成によりセサミン類を得ることもできる。その方法としては、例えば、セサミン、エピセサミンについては、Ｂｅｒｏｚａらの方法（Ｊ．Ａｍ．Ｃｈｅｍ．Ｓｏｃ．，７８，１２４２（１９５６））で合成することができる。
The sesamin compounds used in the present invention are not limited in any way by their form or production method. For example, in the case of sesamin, an extract containing sesamin (called a sesamin extract or purified product) extracted from sesame oil by a known method (for example, the method described in JP-A-4-9331) can be used. 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)).
フェルラ酸は、ポリフェノールの一種であり、植物に含まれている。フェルラ酸又はその塩は、その形態や製造方法等によって、何ら制限されるものではない。例えば、フェルラ酸は、フェルラ酸を含有する植物を抽出することによって、又は化学合成によって得ることができる。フェルラ酸又はその塩は、化学合成品を使用してもよく、天然物から抽出及び精製したものを使用してもよい。
Ferulic acid is a type of polyphenol and is found in plants. Ferulic acid or its salts are not limited in any way by their form or production method. For example, ferulic acid can be obtained by extracting a plant containing ferulic acid or by chemical synthesis. Ferulic acid or its salts may be chemically synthesized or may be extracted and purified from natural products.
フェルラ酸を含有する植物としては、例えば、トウモロコシ、大麦、小麦、米、コーヒー、タマネギ、ダイコン、レモン、センキュウ、トウキ、マツ、オウレン、アギ、カンショ等が挙げられる。米の場合には、フェルラ酸は米ぬかに豊富に含まれている。フェルラ酸の化学合成の例としては、バニリンとマロン酸の縮合脱炭酸によってフェルラ酸を製造することができる。フェルラ酸又はその塩の原料からの抽出方法、精製方法等は特に限定されず、公知の方法を使用することができる。
Examples of plants that contain ferulic acid include corn, barley, wheat, rice, coffee, onion, radish, lemon, cnidium rhizome, angelica tree, pine, coptis japonica, and sweet potato. In the case of rice, ferulic acid is abundant in rice bran. As an example of chemical synthesis of ferulic acid, ferulic acid can be produced by condensation decarboxylation of vanillin and malonic acid. There are no particular limitations on the method of extraction from raw materials of ferulic acid or its salts, and the method of purification, and known methods can be used.
フェルラ酸の塩としては、薬理学的に許容される塩又は飲食品に許容される塩であれば特に限定されず、例えば、塩基性塩を挙げることができる。塩基性塩として、例えば、ナトリウム塩、カリウム塩等のアルカリ金属塩；カルシウム塩、マグネシウム塩等のアルカリ土類金属塩等が挙げられる。
The salt of ferulic acid is not particularly limited as long as it is a pharmacologically acceptable salt or a salt acceptable for use in foods and beverages, and examples of the salt include basic salts. Examples of basic salts include alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts and magnesium salts; and the like.
本発明の組成物においては、（Ａ）セサミン類化合物のセサミン換算の重量に対する、（Ｂ）フェルラ酸又はその塩のフェルラ酸換算の重量の比（フェルラ酸換算の（Ｂ）／セサミン換算の（Ａ））が、５～１００である。本発明の組成物は（Ａ）セサミン類化合物、及び、（Ｂ）フェルラ酸又はその塩を、上記の重量比で含有するものである。
後記の実施例に示されるように、セサミン類化合物及びフェルラ酸又はその塩を上記の重量比で併用すると、過酸化水素（Ｈ２Ｏ２処理）によるＡＴＰ産生の減少が効果的に抑制された。セサミン類化合物及びフェルラ酸又はその塩を上記の重量比で併用した場合のＡＴＰ産生の低下抑制効果は、セサミン類化合物を単独使用した場合、及びフェルラ酸又はその塩を単独使用した場合から予測される相加効果よりも、顕著に優れる相乗効果であった。 In the composition of 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 5 to 100. The composition of the present invention contains (A) sesamin-based compound and (B) ferulic acid or a salt thereof in the above weight ratio.
As shown in the Examples below, when sesamin-class compounds and ferulic acid or its salts were used in combination at the above weight ratio, the decrease in ATP production caused by hydrogen peroxide ( H2O2 treatment ) was effectively suppressed. The effect of suppressing the decrease in ATP production when sesamin-class compounds and ferulic acid or its salts were used in combination at the above weight ratio was a synergistic effect that was significantly superior to the additive effect predicted when sesamin-class compounds were used alone and when ferulic acid or its salts were used alone.
後記の実施例に示されるように、セサミン類化合物及びフェルラ酸又はその塩を上記の重量比で併用すると、過酸化水素（Ｈ２Ｏ２処理）によるＡＴＰ産生の減少が効果的に抑制された。セサミン類化合物及びフェルラ酸又はその塩を上記の重量比で併用した場合のＡＴＰ産生の低下抑制効果は、セサミン類化合物を単独使用した場合、及びフェルラ酸又はその塩を単独使用した場合から予測される相加効果よりも、顕著に優れる相乗効果であった。 In the composition of 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 5 to 100. The composition of the present invention contains (A) sesamin-based compound and (B) ferulic acid or a salt thereof in the above weight ratio.
As shown in the Examples below, when sesamin-class compounds and ferulic acid or its salts were used in combination at the above weight ratio, the decrease in ATP production caused by hydrogen peroxide ( H2O2 treatment ) was effectively suppressed. The effect of suppressing the decrease in ATP production when sesamin-class compounds and ferulic acid or its salts were used in combination at the above weight ratio was a synergistic effect that was significantly superior to the additive effect predicted when sesamin-class compounds were used alone and when ferulic acid or its salts were used alone.
セサミン類化合物とフェルラ酸又はその塩とを上記重量比で併用することで、セサミン類化合物を単独使用した場合の効果、及びフェルラ酸又はその塩を単独使用した場合の効果から予測される範囲を超えた、顕著に高いエネルギー産生の向上、促進、低下抑制又は維持効果を得ることができる。セサミン類化合物及びフェルラ酸又はその塩を上記重量比で含む組成物は、エネルギー産生の向上、促進、低下抑制又は維持において優れた効果を示す。これにより、本発明の組成物を、例えば、エネルギー産生の向上、促進、低下抑制又は維持のための有効成分に用いると、有効成分が低用量であっても上記作用を発揮させることができることから、有効成分の摂取量を少量化することも可能となる。摂取量の少量化は摂取のしやすさに繋がり、より継続摂取しやすいエネルギー産生能の向上、促進、低下抑制又は維持のための組成物等を得ることができる。
By using a combination of a sesamin-class compound and ferulic acid or a salt thereof in the above weight ratio, a significantly high energy production improvement, promotion, decrease suppression or maintenance effect can be obtained that exceeds the range predicted from the effect of using a sesamin-class compound alone and the effect of using ferulic acid or a salt thereof alone. A composition containing a sesamin-class compound and ferulic acid or a salt thereof in the above weight ratio exhibits excellent effects in improving, promoting, decrease suppression or maintenance of energy production. As a result, when the composition of the present invention is used as an active ingredient for improving, promoting, decrease suppression or maintenance of energy production, for example, the above effect can be exerted even with a low dose of the active ingredient, so that the intake amount of the active ingredient can be reduced. The reduced intake amount leads to ease of intake, and a composition for improving, promoting, decrease suppression or maintenance of energy production that is easier to take continuously can be obtained.
本発明において、（Ａ）セサミン類化合物のセサミン換算の重量に対する、（Ｂ）フェルラ酸又はその塩のフェルラ酸換算の重量の比（フェルラ酸換算の（Ｂ）／セサミン換算の（Ａ））は、１０以上であることが好ましく、１１以上であることがより好ましく、また、７０以下であることが好ましく、５５以下であることがより好ましい。一態様において、上記の重量の比（フェルラ酸換算の（Ｂ）／セサミン換算の（Ａ））は、１０～１００であることが好ましく、１０～７０であることがより好ましく、１０～５５であることが更に好ましく、１１～５５であることが特に好ましい。
In the present invention, the ratio of the weight of (B) ferulic acid or a salt thereof in ferulic acid equivalent to the weight of (A) sesamin-based compound in sesamin equivalent ((B) in ferulic acid equivalent/(A) in sesamin equivalent) is preferably 10 or more, more preferably 11 or more, and preferably 70 or less, more preferably 55 or less. In one embodiment, the above weight ratio ((B) in ferulic acid equivalent/(A) in sesamin equivalent) is preferably 10 to 100, more preferably 10 to 70, even more preferably 10 to 55, and particularly preferably 11 to 55.
本明細書中、セサミン類化合物について、セサミン換算の重量又はこれに類する表現は、セサミン類化合物がセサミン又はエピセサミンである場合にはその重量を意味し、セサミン類化合物がセサミン及びエピセサミン以外の化合物である場合には、当該化合物のモル数に、セサミンの分子量を乗じて得られる値を意味する。
フェルラ酸又はその塩について、フェルラ酸換算の重量又はこれに類する表現は、フェルラ酸の場合にはその重量を意味し、フェルラ酸の塩の場合には、当該塩のモル数に、フェルラ酸の分子量を乗じて得られる値を意味する。 In this specification, with regard to sesamin-based compounds, the weight in terms of sesamin or similar expressions means the weight when the sesamin-based compound is sesamin or episesamin, and when the sesamin-based compound is a compound other than sesamin and episesamin, means the value obtained by multiplying the number of moles of the compound by the molecular weight of sesamin.
With respect to ferulic acid or a salt thereof, the weight in terms of ferulic acid or a similar expression means the weight of ferulic acid, and in the case of a salt of ferulic acid, means the value obtained by multiplying the number of moles of the salt by the molecular weight of ferulic acid.
フェルラ酸又はその塩について、フェルラ酸換算の重量又はこれに類する表現は、フェルラ酸の場合にはその重量を意味し、フェルラ酸の塩の場合には、当該塩のモル数に、フェルラ酸の分子量を乗じて得られる値を意味する。 In this specification, with regard to sesamin-based compounds, the weight in terms of sesamin or similar expressions means the weight when the sesamin-based compound is sesamin or episesamin, and when the sesamin-based compound is a compound other than sesamin and episesamin, means the value obtained by multiplying the number of moles of the compound by the molecular weight of sesamin.
With respect to ferulic acid or a salt thereof, the weight in terms of ferulic acid or a similar expression means the weight of ferulic acid, and in the case of a salt of ferulic acid, means the value obtained by multiplying the number of moles of the salt by the molecular weight of ferulic acid.
一態様において、本発明の組成物は、エネルギー産生の向上、促進、低下抑制又は維持用組成物として好ましく使用することができる。本発明の組成物は、セサミン類化合物及びフェルラ酸又はその塩を有効成分として含有する、エネルギー産生の向上、促進、低下抑制又は維持用組成物であってよい。エネルギー産生機能は、例えば、加齢に伴って低下する。エネルギー産生の低下は、細胞の機能低下、臓器の機能低下、全身の機能低下等を招く。エネルギー産生の向上、促進、低下抑制又は維持によって、細胞の機能の低下抑制又は機能の維持、臓器の機能低下の抑制又は機能維持、全身の機能低下抑制又は機能維持等の効果が得られることが期待される。エネルギー産生の向上、促進、低下抑制又は維持は、例えば、老化の予防又は抑制（抗老化）等に有効である。老化には、細胞老化、個体の老化が含まれる。個体は、好ましくはヒトである。
In one aspect, the composition of the present invention can be preferably used as a composition for improving, promoting, inhibiting or maintaining the decline of energy production. The composition of the present invention may be a composition for improving, promoting, inhibiting or maintaining the decline of energy production, containing a sesamin-class compound and ferulic acid or a salt thereof as active ingredients. Energy production function declines, for example, with aging. The decline in energy production leads to a decline in cell function, a decline in organ function, a decline in whole body function, etc. It is expected that the improvement, promotion, inhibition of decline or maintenance of energy production will have the effect of inhibiting or maintaining the decline of cell function, inhibiting or maintaining the decline of organ function, inhibiting or maintaining the decline of whole body function, etc. The improvement, promotion, inhibition of decline or maintenance of energy production is effective, for example, for preventing or inhibiting aging (anti-aging), etc. Aging includes cellular aging and individual aging. The individual is preferably a human.
後記の実施例に示されるように、セサミン類化合物及びフェルラ酸を上記の重量比で併用すると、酵母において分裂寿命延長効果が得られた。分裂寿命の延長は、個体の寿命の延長又は健康寿命の延長と捉えることができる。また、分裂寿命の延長は、老化が予防又は抑制されたと捉えることもできる。一態様において、本発明の組成物は、抗老化用組成物として使用することができる。本発明の組成物は、セサミン類化合物及びフェルラ酸又はその塩を有効成分として含有する、抗老化用組成物であってよい。
As shown in the examples below, when sesamin-based compounds and ferulic acid were used in combination in the above weight ratio, an effect of extending the replicative lifespan was obtained in yeast. The extension of replicative lifespan can be considered as an extension of an individual's lifespan or an extension of healthy lifespan. The extension of replicative lifespan can also be considered as the prevention or inhibition of aging. In one aspect, the composition of the present invention can be used as an anti-aging composition. The composition of the present invention may be an anti-aging composition containing a sesamin-based compound and ferulic acid or a salt thereof as active ingredients.
一態様において、本発明の組成物は、個体の寿命延長のために使用することができる。本発明の組成物は、寿命延長用組成物として使用することができる。本発明の組成物は、健康寿命延長にも有用である。健康寿命とは、健康上の問題によって日常生活が制限されることなく生活できる期間のことをいう（厚生労働省「令和２年版 厚生労働白書」１７頁）。一態様において、本発明の組成物は、健康寿命延長用組成物として使用することができる。本発明の組成物は、寿命延長用及び／又は健康寿命延長用組成物として使用することができる。
In one aspect, the composition of the present invention can be used to extend the lifespan of an individual. The composition of the present invention can be used as a composition for extending lifespan. The composition of the present invention is also useful for extending healthy lifespan. Healthy lifespan refers to the period during which one can live without daily life being restricted by health problems (Ministry of Health, Labour and Welfare, "2020 Edition, Ministry of Health, Labour and Welfare White Paper," p. 17). In one aspect, the composition of the present invention can be used as a composition for extending healthy lifespan. The composition of the present invention can be used as a composition for extending lifespan and/or healthy lifespan.
一態様において、本発明の組成物は、エネルギー産生の低下に関連する状態又は疾患の予防又は改善のために使用することができる。エネルギー産生の低下に関連する状態又は疾患として、エネルギー産生の低下に起因する状態又は疾患、エネルギー産生の低下を伴う状態又は疾患が挙げられる。このような状態又は疾患として、慢性疲労症候群、サルコペニアなどの筋疾患、認知症などの認知機能障害が挙げられる。
本明細書で予防は、発症を防止すること、発症を遅延させること、発症率を低下させること、発症のリスクを軽減すること等を包含する。状態又は疾患の改善は、状態又は疾患から回復させること、状態又は疾患の症状を軽減すること、状態又は疾患の症状を好転させること、状態又は疾患の進行を遅延させること、防止すること等を包含する。 In one aspect, the composition of the present invention can be used for preventing or improving the condition or disease associated with reduced energy production.The condition or disease associated with reduced energy production includes the condition or disease caused by reduced energy production, or the condition or disease associated with reduced energy production.These conditions or diseases include chronic fatigue syndrome, muscle diseases such as sarcopenia, and cognitive dysfunction such as dementia.
As used herein, prevention includes preventing onset, delaying onset, reducing the incidence, reducing the risk of onset, etc. Amelioration of a condition or disease includes recovering from a condition or disease, alleviating the symptoms of a condition or disease, ameliorating the symptoms of a condition or disease, delaying or preventing the progression of a condition or disease, etc.
本明細書で予防は、発症を防止すること、発症を遅延させること、発症率を低下させること、発症のリスクを軽減すること等を包含する。状態又は疾患の改善は、状態又は疾患から回復させること、状態又は疾患の症状を軽減すること、状態又は疾患の症状を好転させること、状態又は疾患の進行を遅延させること、防止すること等を包含する。 In one aspect, the composition of the present invention can be used for preventing or improving the condition or disease associated with reduced energy production.The condition or disease associated with reduced energy production includes the condition or disease caused by reduced energy production, or the condition or disease associated with reduced energy production.These conditions or diseases include chronic fatigue syndrome, muscle diseases such as sarcopenia, and cognitive dysfunction such as dementia.
As used herein, prevention includes preventing onset, delaying onset, reducing the incidence, reducing the risk of onset, etc. Amelioration of a condition or disease includes recovering from a condition or disease, alleviating the symptoms of a condition or disease, ameliorating the symptoms of a condition or disease, delaying or preventing the progression of a condition or disease, etc.
本明細書において、エネルギー産生は、本発明の属する技術分野における通常の知識に基づき評価されればよく、その方法は特に限定されない。例えば、細胞外フラックスアナライザーを使用して、測定対象である細胞におけるＡＴＰ合成時にミトコンドリアで使用される酸素消費速度（ＯＣＲ）を、ＡＴＰ合成酵素阻害剤（例えば、オリゴマイシン）を添加しながら継続的に測定することで、エネルギー産生の評価をすることができる。評価項目は、例えば、エネルギー産生評価における主要な指標とされる、ＡＴＰ産生について解析することにより、エネルギー産生を評価することができる。
In this specification, energy production may be evaluated based on common knowledge in the technical field to which the present invention pertains, and the method is not particularly limited. For example, energy production can be evaluated by using an extracellular flux analyzer to continuously measure the oxygen consumption rate (OCR) used by mitochondria during ATP synthesis in the cells to be measured while adding an ATP synthase inhibitor (e.g., oligomycin). Energy production can be evaluated, for example, by analyzing ATP production, which is considered to be a major index in the evaluation of energy production.
セサミン類化合物及びフェルラ酸又はその塩は、天然物や飲食品に含まれ、食経験がある化合物である。このため安全性の観点から、セサミン類化合物及びフェルラ酸又はその塩は、例えば毎日摂取することにも問題が少ないと考えられる。本発明によれば、安全性が高い物質を有効成分として含み、優れたエネルギー産生の向上、促進、低下抑制又は維持作用を有する組成物を提供することができる。
Sesamin-based compounds and ferulic acid or its salts are compounds that are found in natural products and foods and beverages, and are consumed with the body. For this reason, from the standpoint of safety, it is believed that there are few problems with taking sesamin-based compounds and ferulic acid or its salts, for example, every day. According to the present invention, it is possible to provide a composition that contains a highly safe substance as an active ingredient and has excellent effects of improving, promoting, inhibiting the decrease of, or maintaining energy production.
本発明の組成物は、治療的用途（医療用途）又は非治療的用途（非医療用途）のいずれにも適用することができる。非治療的とは、医療行為、すなわち人間の手術、治療又は診断を含まない概念である。
本発明の組成物は、飲食品、化粧料、医薬品、医薬部外品、飼料等の形態とすることができるが、これらに限定されるものではない。本発明の組成物は、それ自体が飲食品、化粧料、医薬品、医薬部外品、飼料等であってもよく、これらに配合して使用される素材又は製剤等であってもよい。
本発明の組成物は、一例として、剤の形態で提供することができるが、本形態に限定されるものではない。当該剤をそのまま組成物として、又は、当該剤を含む組成物として提供することもできる。一態様において、エネルギー産生の向上、促進、低下抑制又は維持用組成物は、エネルギー産生の向上、促進、低下抑制又は維持のための剤ということもできる。抗老化用組成物は、抗老化剤ということもできる。寿命延長用及び／又は健康寿命延長用組成物は、寿命延長及び／又は健康寿命延長のための剤ということもできる。 The compositions of the present invention can be applied in either therapeutic (medical) or non-therapeutic (non-medical) applications, the latter being a concept that does not include medical procedures, i.e., surgery, treatment or diagnosis of humans.
The composition of the present invention can be in the form of, but is not limited to, a food or drink, a cosmetic, a drug, a quasi-drug, a feed, etc. The composition of the present invention may be a food or drink, a cosmetic, a drug, a quasi-drug, a feed, etc., or may be a material or preparation to be mixed 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 be provided as a composition as it is, or as a composition containing the agent. In one embodiment, the composition for improving, promoting, inhibiting a decrease, or maintaining energy production can also be referred to as an agent for improving, promoting, inhibiting a decrease, or maintaining energy production. The composition for anti-aging can also be referred to as an anti-aging agent. The composition for extending lifespan and/or extending healthy lifespan can also be referred to as an agent for extending lifespan and/or extending healthy lifespan.
本発明の組成物は、飲食品、化粧料、医薬品、医薬部外品、飼料等の形態とすることができるが、これらに限定されるものではない。本発明の組成物は、それ自体が飲食品、化粧料、医薬品、医薬部外品、飼料等であってもよく、これらに配合して使用される素材又は製剤等であってもよい。
本発明の組成物は、一例として、剤の形態で提供することができるが、本形態に限定されるものではない。当該剤をそのまま組成物として、又は、当該剤を含む組成物として提供することもできる。一態様において、エネルギー産生の向上、促進、低下抑制又は維持用組成物は、エネルギー産生の向上、促進、低下抑制又は維持のための剤ということもできる。抗老化用組成物は、抗老化剤ということもできる。寿命延長用及び／又は健康寿命延長用組成物は、寿命延長及び／又は健康寿命延長のための剤ということもできる。 The compositions of the present invention can be applied in either therapeutic (medical) or non-therapeutic (non-medical) applications, the latter being a concept that does not include medical procedures, i.e., surgery, treatment or diagnosis of humans.
The composition of the present invention can be in the form of, but is not limited to, a food or drink, a cosmetic, a drug, a quasi-drug, a feed, etc. The composition of the present invention may be a food or drink, a cosmetic, a drug, a quasi-drug, a feed, etc., or may be a material or preparation to be mixed 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 be provided as a composition as it is, or as a composition containing the agent. In one embodiment, the composition for improving, promoting, inhibiting a decrease, or maintaining energy production can also be referred to as an agent for improving, promoting, inhibiting a decrease, or maintaining energy production. The composition for anti-aging can also be referred to as an anti-aging agent. The composition for extending lifespan and/or extending healthy lifespan can also be referred to as an agent for extending lifespan and/or extending healthy lifespan.
本発明の組成物は、経口用組成物、非経口用組成物のいずれであってもよい。一態様において、本発明の組成物は、好ましくは経口用組成物である。経口用組成物としては、飲食品、経口用の医薬品、経口用の医薬部外品、飼料が挙げられ、好ましくは飲食品又は経口用医薬品であり、より好ましくは飲食品である。
別の一態様において、本発明の組成物は、皮膚外用剤（皮膚外用組成物）として使用することができる。皮膚外用剤は、化粧料、医薬品、医薬部外品等を含み、好ましくは化粧料である。 The composition of the present invention may be either an oral composition or a non-oral composition. In one embodiment, the composition of the present invention is preferably an oral composition. Examples of the oral composition include food and drink, oral medicine, oral quasi-drug, and feed, and are preferably food and drink or oral medicine, and more preferably food and drink.
In another embodiment, the composition of the present invention can be used as an external preparation for the skin (external composition for the skin). External preparations for the skin include cosmetics, pharmaceuticals, quasi-drugs, etc., and are preferably cosmetics.
別の一態様において、本発明の組成物は、皮膚外用剤（皮膚外用組成物）として使用することができる。皮膚外用剤は、化粧料、医薬品、医薬部外品等を含み、好ましくは化粧料である。 The composition of the present invention may be either an oral composition or a non-oral composition. In one embodiment, the composition of the present invention is preferably an oral composition. Examples of the oral composition include food and drink, oral medicine, oral quasi-drug, and feed, and are preferably food and drink or oral medicine, and more preferably food and drink.
In another embodiment, the composition of the present invention can be used as an external preparation for the skin (external composition for the skin). External preparations for the skin include cosmetics, pharmaceuticals, quasi-drugs, etc., and are preferably cosmetics.
本発明の組成物は、本発明の効果を損なわない限り、セサミン類化合物及びフェルラ酸又はその塩に加えて、任意の添加剤、任意の成分を含有することができる。これらの添加剤及び成分は、組成物の形態等に応じて選択することができ、一般的に飲食品、化粧料、医薬品、医薬部外品、飼料等に使用可能なものが使用できる。本発明の組成物を、飲食品、化粧料、医薬品、医薬部外品、飼料等とする場合、その製造方法は特に限定されず、一般的な方法により製造することができる。一態様において、本発明の組成物は、セサミン類化合物及びフェルラ酸又はその塩からなるものであってもよい。
The composition of the present invention may contain any additives and any components in addition to the sesamin-class compound and ferulic acid or a salt thereof, so long as the effects of the present invention are not impaired. These additives and components may be selected depending on the form of the composition, and those that can generally be used for foods and beverages, cosmetics, medicines, quasi-drugs, feed, etc. may be used. When the composition of the present invention is used as a food and beverage, cosmetics, medicines, quasi-drugs, feed, etc., there are no particular limitations on the method of production, and it may be produced by a general method. In one aspect, the composition of the present invention may consist of a sesamin-class compound and ferulic acid or a salt thereof.
例えば本発明の組成物を飲食品とする場合、セサミン類化合物及びフェルラ酸又はその塩に、飲食品に使用可能な成分（例えば、食品素材、必要に応じて使用される食品添加物等）を配合して、種々の飲食品とすることができる。飲食品は特に限定されず、例えば、一般的な飲食品、健康食品、健康補助食品、健康飲料、機能性表示食品、特定保健用食品、病者用飲食品等が挙げられる。上記健康食品、健康補助食品、機能性表示食品、特定保健用食品、病者用飲食品等は、例えば、細粒剤、錠剤、顆粒剤、散剤、カプセル剤、チュアブル剤、ドライシロップ剤、シロップ剤、液剤、飲料、ドリンク剤、流動食等の各種製剤形態として使用することができる。
For example, when the composition of the present invention is made into a food or beverage, various foods and beverages can be made by blending the sesamin-class compounds and ferulic acid or a salt thereof with ingredients that can be used in foods and beverages (e.g., food ingredients, food additives used as necessary, etc.). The foods and beverages are not particularly limited, and examples include general foods and beverages, health foods, health supplements, health drinks, functional foods, foods for specified health uses, and foods and beverages for the sick. The above health foods, health supplements, functional foods, foods for specified health uses, and foods and beverages for the sick can be used in various formulation forms, such as fine granules, tablets, granules, powders, capsules, chewables, dry syrups, syrups, liquids, beverages, drinks, and liquid diets.
本発明の組成物を化粧料とする場合、セサミン類化合物及びフェルラ酸又はその塩に、化粧料に使用可能な成分（例えば、化粧料に許容される担体、添加剤等）を配合して種々の化粧料とすることができる。化粧料の製品形態は特に限定されず、例えば、化粧水、美容液、パック、乳液、クリーム、日焼け止め等のスキンケア化粧料等が挙げられる。
When the composition of the present invention is used as a cosmetic, various cosmetic preparations can be made by blending the sesamin-based compound and ferulic acid or its salt with ingredients that can be used in cosmetics (e.g., carriers, additives, etc. that are acceptable for cosmetics). The product form of the cosmetic preparation is not particularly limited, and examples include skin care cosmetics such as lotion, beauty serum, pack, milky lotion, cream, and sunscreen.
本発明の組成物を医薬品又は医薬部外品とする場合、例えば、セサミン類化合物及びフェルラ酸又はその塩に、薬理学的に許容される担体、必要に応じて添加される添加剤等を配合して、各種剤形の医薬品又は医薬部外品とすることができる。そのような担体、添加剤等は、医薬品又は医薬部外品に使用可能な、薬理学的に許容されるものであればよく、例えば、賦形剤、結合剤、崩壊剤、滑沢剤、抗酸化剤、着色剤等の１又は２以上が挙げられる。医薬品又は医薬部外品の投与（摂取）形態としては、経口又は非経口（経皮、経粘膜、経腸、注射等）投与の形態が挙げられる。一態様において、本発明の組成物を医薬品又は医薬部外品とする場合、経口用の医薬品又は医薬部外品とすることが好ましい。経口投与のための剤形としては、液剤、錠剤、散剤、細粒剤、顆粒剤、糖衣錠、カプセル剤、懸濁液、乳剤、チュアブル剤等が挙げられる。
別の一態様において、医薬品又は医薬部外品は、皮膚外用剤とすることが好ましい。皮膚外用剤の剤形等は特に限定されず、例えば溶液、乳液、クリーム、ゲル、粉末、エアゾール、ミスト、カプセル及びシート等任意の形態とすることができる。
医薬品は、非ヒト動物用医薬であってもよい。 When the composition of the present invention is used as a drug or quasi-drug, for example, a pharmacologically acceptable carrier and additives added as necessary can be mixed with sesamin-class compounds and ferulic acid or a salt thereof to produce a drug or quasi-drug in various dosage forms. Such carriers, additives, etc. may be any pharmacologically acceptable carriers that can be used in drugs or quasi-drugs, and examples of such carriers, additives, etc. include one or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants, etc. Examples of the administration (ingestion) form of a drug or quasi-drug include oral or non-oral (transdermal, transmucosal, enteral, injection, etc.) administration forms. In one aspect, when the composition of the present invention is used as a drug or quasi-drug, it is preferable to use an oral drug or quasi-drug. Examples of dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewables, etc.
In another embodiment, the pharmaceutical or quasi-drug is preferably a skin topical preparation. The dosage form of the skin topical preparation is not particularly limited, and may be any form such as a solution, emulsion, cream, gel, powder, aerosol, mist, capsule, or sheet.
The pharmaceutical agent may be a non-human animal drug.
別の一態様において、医薬品又は医薬部外品は、皮膚外用剤とすることが好ましい。皮膚外用剤の剤形等は特に限定されず、例えば溶液、乳液、クリーム、ゲル、粉末、エアゾール、ミスト、カプセル及びシート等任意の形態とすることができる。
医薬品は、非ヒト動物用医薬であってもよい。 When the composition of the present invention is used as a drug or quasi-drug, for example, a pharmacologically acceptable carrier and additives added as necessary can be mixed with sesamin-class compounds and ferulic acid or a salt thereof to produce a drug or quasi-drug in various dosage forms. Such carriers, additives, etc. may be any pharmacologically acceptable carriers that can be used in drugs or quasi-drugs, and examples of such carriers, additives, etc. include one or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants, etc. Examples of the administration (ingestion) form of a drug or quasi-drug include oral or non-oral (transdermal, transmucosal, enteral, injection, etc.) administration forms. In one aspect, when the composition of the present invention is used as a drug or quasi-drug, it is preferable to use an oral drug or quasi-drug. Examples of dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewables, etc.
In another embodiment, the pharmaceutical or quasi-drug is preferably a skin topical preparation. The dosage form of the skin topical preparation is not particularly limited, and may be any form such as a solution, emulsion, cream, gel, powder, aerosol, mist, capsule, or sheet.
The pharmaceutical agent may be a non-human animal drug.
本発明の組成物を飼料とする場合には、セサミン類化合物及びフェルラ酸又はその塩を飼料に配合すればよい。飼料には飼料添加剤も含まれる。飼料としては、例えば、牛、豚、鶏、羊、馬等に用いる家畜用飼料；ウサギ、ラット、マウス等に用いる小動物用飼料；犬、猫、小鳥等に用いるペットフードなどが挙げられる。
When the composition of the present invention is used as feed, the sesamin-class compound and ferulic acid or a salt thereof 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.
本発明の組成物に含まれるセサミン類化合物の含有量は特に限定されず、その形態等に応じて設定することができる。本発明の組成物中のセサミン類化合物の含有量は、例えば、セサミン換算の含有量として、該組成物中に０．００１重量％以上が好ましく、０．０１重量％以上がより好ましく、０．０５重量％以上が更に好ましく、また、１０重量％以下が好ましく、５重量％以下がより好ましい。一態様において、セサミン類化合物の含有量は、セサミン換算の含有量として、組成物中に０．００１～１０重量％が好ましく、０．０１～５重量％がより好ましく、０．０５～５重量％が更に好ましい。上記含有量は、セサミン類化合物を２種以上含有する場合は、これらの合計含有量である。組成物中のセサミン類化合物の含有量は、ＨＰＬＣ（高速液体クロマトグラフ）法により測定することができる。
The content of the sesamin-family compounds contained in the composition of the present invention is not particularly limited and can be set according to the form, etc. The content of the sesamin-family compounds in the composition of the present invention is, for example, preferably 0.001% by weight or more in the composition, more preferably 0.01% by weight or more, even more preferably 0.05% by weight or more, and preferably 10% by weight or less, and more preferably 5% by weight or less, in terms of sesamin. In one embodiment, the content of the sesamin-family compounds in the composition is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight, and even more preferably 0.05 to 5% by weight, in terms of sesamin. When two or more types of sesamin-family compounds are contained, the above content is the total content of these. The content of the sesamin-family compounds in the composition can be measured by HPLC (high performance liquid chromatography).
本発明の組成物に含まれるフェルラ酸又はその塩の含有量は特に限定されず、その形態等に応じて設定することができる。本発明の組成物中のフェルラ酸又はその塩の含有量は、例えば、フェルラ酸換算の含有量として、該組成物中に０．０１重量％以上が好ましく、０．１重量％以上がより好ましく、１重量％以上が更に好ましく、また、９０重量％以下が好ましく、５５重量％以下がより好ましい。一態様において、本発明の組成物中のフェルラ酸又はその塩の含有量は、フェルラ酸換算の含有量として、０．０１～９０重量％が好ましく、０．１～５５重量％がより好ましく、１～５５重量％が更に好ましい。組成物中のフェルラ酸又はその塩の含有量は、ＨＰＬＣ法により測定することができる。
The content of ferulic acid or a salt thereof contained in the composition of the present invention is not particularly limited and can be set according to the form, etc. The content of ferulic acid or a salt thereof in the composition of the present invention is, for example, preferably 0.01% by weight or more in the composition, more preferably 0.1% by weight or more, even more preferably 1% by weight or more, and preferably 90% by weight or less, more preferably 55% by weight or less, in terms of the content of ferulic acid. In one embodiment, the content of ferulic acid or a salt thereof in the composition of the present invention is preferably 0.01 to 90% by weight, more preferably 0.1 to 55% by weight, even more preferably 1 to 55% by weight, in terms of the content of ferulic acid. The content of ferulic acid or a salt thereof in the composition can be measured by HPLC.
本発明の組成物は、その形態又は剤形に応じて自体公知の種々の方法で摂取又は投与することができる。一態様において、本発明の組成物は、経口で摂取（経口投与）されることが好ましい。別の一態様において、本発明の組成物を皮膚外用剤とする場合は、皮膚に適用することができる。
本発明の組成物の投与量（摂取量ということもできる）は特に限定されない。一態様において、本発明の組成物の投与量は、例えば、エネルギー産生の向上、促進、低下抑制又は維持効果又は抗老化効果が得られるような量であればよく、投与形態、投与方法、対象の体重等に応じて適宜設定すればよい。 The composition of the present invention can be ingested or administered by various methods known per se according to its form or dosage form. In one embodiment, the composition of the present invention is preferably ingested orally (administered orally). In another embodiment, when the composition of the present invention is used as a skin external preparation, it can be applied to the skin.
The dosage of the composition of the present invention (which may also be referred to as the intake amount) is not particularly limited. In one embodiment, the dosage of the composition of the present invention may be an amount that can obtain, for example, an effect of improving, promoting, suppressing or maintaining the decrease of energy production, or an effect of anti-aging, and may be appropriately set depending on the dosage form, administration method, body weight of the subject, etc.
本発明の組成物の投与量（摂取量ということもできる）は特に限定されない。一態様において、本発明の組成物の投与量は、例えば、エネルギー産生の向上、促進、低下抑制又は維持効果又は抗老化効果が得られるような量であればよく、投与形態、投与方法、対象の体重等に応じて適宜設定すればよい。 The composition of the present invention can be ingested or administered by various methods known per se according to its form or dosage form. In one embodiment, the composition of the present invention is preferably ingested orally (administered orally). In another embodiment, when the composition of the present invention is used as a skin external preparation, it can be applied to the skin.
The dosage of the composition of the present invention (which may also be referred to as the intake amount) is not particularly limited. In one embodiment, the dosage of the composition of the present invention may be an amount that can obtain, for example, an effect of improving, promoting, suppressing or maintaining the decrease of energy production, or an effect of anti-aging, and may be appropriately set depending on the dosage form, administration method, body weight of the subject, etc.
一態様において、本発明の組成物をヒト（成人）を対象に摂取させる又は投与する場合、セサミン類化合物の投与量は、１日当たり、セサミン換算の投与量として、好ましくは０．５ｍｇ以上、より好ましくは１ｍｇ以上、更に好ましくは３ｍｇ以上、また、好ましくは２００ｍｇ以下、より好ましくは１００ｍｇ以下、更に好ましくは８０ｍｇ以下である。一態様において、セサミン類化合物の投与量は、ヒト（成人）であれば、１日当たり、セサミン換算の投与量として、好ましくは０．５～２００ｍｇ、より好ましくは１～１００ｍｇ、更に好ましくは３～８０ｍｇである。上記投与量は、セサミン類化合物を２種以上使用する場合は、これらの合計量である。一態様においては、セサミン及び／又はエピセサミンを、１日当たりで、好ましくは０．５～２００ｍｇ、より好ましくは１～１００ｍｇ、更に好ましくは３～８０ｍｇ、ヒト（成人）に経口で摂取させる又は投与することが好ましい。
In one embodiment, when the composition of the present invention is ingested or administered to a human (adult), the dosage of the sesamin-class compound 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, in terms of sesamin per day. In one embodiment, the dosage of the sesamin-class compound is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg, in terms of sesamin per day, for a human (adult). When two or more types of sesamin-class compounds are used, the dosage is the total amount of these. In one embodiment, it is preferable to orally ingest or administer sesamin and/or episesamin to a human (adult) in an amount of preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg per day.
一態様において、本発明の組成物をヒト（成人）を対象に摂取させる又は投与する場合、フェルラ酸又はその塩の投与量は、１日当たり、フェルラ酸換算の投与量として、好ましくは５ｍｇ以上、より好ましくは１０ｍｇ以上、更に好ましくは３５ｍｇ以上、また、好ましくは２０００ｍｇ以下、より好ましくは１２００ｍｇ以下、更に好ましくは９００ｍｇ以下である。一態様において、ヒト（成人）を対象に摂取させる又は投与する場合、フェルラ酸又はその塩の投与量は、フェルラ酸換算の投与量として、１日当たり、好ましくは５～２０００ｍｇ、より好ましくは１０～１２００ｍｇ、更に好ましくは３５～９００ｍｇである。
一態様においては、１日当たり上記量のセサミン類化合物、及び、フェルラ酸又はその塩を、ヒトに経口で摂取させる又は投与することが好ましい。また、上記量を、１日１回以上、例えば、１日１回で又は数回（例えば２～３回）に分けて、摂取させる又は投与することが好ましい。上記の投与量は、体重６０ｋｇあたりの投与量であってよい。
ヒトにおいて、エネルギー産生の向上、促進、低下抑制又は維持効果を得ることを目的として本発明の組成物を使用する場合、セサミン類化合物及びフェルラ酸又はその塩の投与量を上記の範囲とすることが好ましい。ヒトにおいて、抗老化効果、寿命延長効果又は健康寿命延長効果を得ることを目的とする場合も、セサミン類化合物及びフェルラ酸又はその塩の投与量を上記の範囲とすることが好ましい。
一態様において、本発明の組成物は、ヒトに、１日あたり上記量のセサミン類化合物及びフェルラ酸又はその塩を摂取させる又は投与するために使用することができる。 In one embodiment, when the composition of the present invention is ingested or administered to a human (adult) subject, the dosage of ferulic acid or a salt thereof is preferably 5 mg or more, more preferably 10 mg or more, even more preferably 35 mg or more, and preferably 2000 mg or less, more preferably 1200 mg or less, even more preferably 900 mg or less, per day, calculated as a dose of ferulic acid. In one embodiment, when the composition of the present invention is ingested or administered to a human (adult) subject, the dosage of ferulic acid or a salt thereof is preferably 5 to 2000 mg, more preferably 10 to 1200 mg, even more preferably 35 to 900 mg, per day, calculated as a dose of ferulic acid.
In one embodiment, the above-mentioned amounts of sesamin-class compounds and ferulic acid or a salt thereof are preferably orally ingested or administered to a human per day. The above-mentioned amounts are preferably ingested or administered once or more times a day, for example, once a day or divided into several times (for example, 2 to 3 times a day). The above-mentioned dosages may be per 60 kg of body weight.
When the composition of the present invention is used for the purpose of improving, promoting, inhibiting the decline of, or maintaining energy production in humans, the doses of the sesamin-class compound and ferulic acid or a salt thereof are preferably within the above-mentioned ranges.When the composition of the present invention is used for the purpose of obtaining an anti-aging effect, a lifespan extension effect, or a healthy lifespan extension effect in humans, the doses of the sesamin-class compound and ferulic acid or a salt thereof are preferably within the above-mentioned ranges.
In one embodiment, the composition of the present invention can be used to cause a human to ingest or administer the above-mentioned amounts of sesamin-class compounds and ferulic acid or a salt thereof per day.
一態様においては、１日当たり上記量のセサミン類化合物、及び、フェルラ酸又はその塩を、ヒトに経口で摂取させる又は投与することが好ましい。また、上記量を、１日１回以上、例えば、１日１回で又は数回（例えば２～３回）に分けて、摂取させる又は投与することが好ましい。上記の投与量は、体重６０ｋｇあたりの投与量であってよい。
ヒトにおいて、エネルギー産生の向上、促進、低下抑制又は維持効果を得ることを目的として本発明の組成物を使用する場合、セサミン類化合物及びフェルラ酸又はその塩の投与量を上記の範囲とすることが好ましい。ヒトにおいて、抗老化効果、寿命延長効果又は健康寿命延長効果を得ることを目的とする場合も、セサミン類化合物及びフェルラ酸又はその塩の投与量を上記の範囲とすることが好ましい。
一態様において、本発明の組成物は、ヒトに、１日あたり上記量のセサミン類化合物及びフェルラ酸又はその塩を摂取させる又は投与するために使用することができる。 In one embodiment, when the composition of the present invention is ingested or administered to a human (adult) subject, the dosage of ferulic acid or a salt thereof is preferably 5 mg or more, more preferably 10 mg or more, even more preferably 35 mg or more, and preferably 2000 mg or less, more preferably 1200 mg or less, even more preferably 900 mg or less, per day, calculated as a dose of ferulic acid. In one embodiment, when the composition of the present invention is ingested or administered to a human (adult) subject, the dosage of ferulic acid or a salt thereof is preferably 5 to 2000 mg, more preferably 10 to 1200 mg, even more preferably 35 to 900 mg, per day, calculated as a dose of ferulic acid.
In one embodiment, the above-mentioned amounts of sesamin-class compounds and ferulic acid or a salt thereof are preferably orally ingested or administered to a human per day. The above-mentioned amounts are preferably ingested or administered once or more times a day, for example, once a day or divided into several times (for example, 2 to 3 times a day). The above-mentioned dosages may be per 60 kg of body weight.
When the composition of the present invention is used for the purpose of improving, promoting, inhibiting the decline of, or maintaining energy production in humans, the doses of the sesamin-class compound and ferulic acid or a salt thereof are preferably within the above-mentioned ranges.When the composition of the present invention is used for the purpose of obtaining an anti-aging effect, a lifespan extension effect, or a healthy lifespan extension effect in humans, the doses of the sesamin-class compound and ferulic acid or a salt thereof are preferably within the above-mentioned ranges.
In one embodiment, the composition of the present invention can be used to cause a human to ingest or administer the above-mentioned amounts of sesamin-class compounds and ferulic acid or a salt thereof per day.
本発明の組成物は、セサミン類化合物の含有量が、成人の１日摂取量当たり、セサミン換算の含有量で０．５～２００ｍｇであることが好ましく、１～１００ｍｇであることがより好ましく、３～８０ｍｇであることが更に好ましい。
本発明の組成物は、フェルラ酸又はその塩の含有量が、成人の１日摂取量当たり、フェルラ酸換算の含有量で５～２０００ｍｇであることが好ましく、１０～１２００ｍｇであることがより好ましく、３５～９００ｍｇであることが更に好ましい。 The content of sesamin-class compounds in the composition of the present invention is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg, of sesamin-equivalent compounds per daily intake for an adult.
The content of ferulic acid or a salt thereof in the composition of the present invention is preferably 5 to 2000 mg, more preferably 10 to 1200 mg, and even more preferably 35 to 900 mg, of ferulic acid per daily intake for an adult.
本発明の組成物は、フェルラ酸又はその塩の含有量が、成人の１日摂取量当たり、フェルラ酸換算の含有量で５～２０００ｍｇであることが好ましく、１０～１２００ｍｇであることがより好ましく、３５～９００ｍｇであることが更に好ましい。 The content of sesamin-class compounds in the composition of the present invention is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg, of sesamin-equivalent compounds per daily intake for an adult.
The content of ferulic acid or a salt thereof in the composition of the present invention is preferably 5 to 2000 mg, more preferably 10 to 1200 mg, and even more preferably 35 to 900 mg, of ferulic acid per daily intake for an adult.
本発明の組成物は、継続して摂取又は投与されるものであることが好ましい。一態様において、本発明の組成物は、好ましくは１週間以上、より好ましくは４週間以上、更に好ましくは８週間以上、特に好ましくは１２週間以上継続して摂取又は投与されることが好ましい。
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 at least one week, more preferably at least four weeks, even more preferably at least eight weeks, and particularly preferably at least twelve weeks.
本発明の組成物を摂取させる又は投与する対象（投与対象ということもできる）は、特に限定されない。好ましくはヒト又は非ヒト哺乳動物であり、より好ましくはヒトである。
一態様において、投与対象として、エネルギー産生の向上、促進、低下抑制又は維持を必要とする又は希望する対象、老化症状の予防又は改善を必要とする又は希望する対象等が挙げられる。このような対象として、例えば、中高年者等が挙げられる。一態様において、本発明の組成物は、中高年者用のエネルギー産生の向上、促進、低下抑制又は維持用組成物又は抗老化用組成物として好適に使用される。中高年者は、例えば、４０歳以上のヒトであってよい。一態様において中高年者の中でも、対象として高齢者が好ましい。高齢者は、例えば、６０歳以上又は６５歳以上のヒトであってよい。本発明の組成物は、例えば、エネルギー産生の向上、促進、低下抑制又は維持により予防又は改善が期待できる状態又は疾患の予防等を目的として、健常者に対して使用することもできる。 The subject to which the composition of the present invention is ingested or administered (also referred to as an administration subject) is not particularly limited, and is preferably a human or a non-human mammal, more preferably a human.
In one embodiment, the subject of administration includes a subject who needs or desires to improve, promote, inhibit decline, or maintain energy production, and a subject who needs or desires to prevent or improve aging symptoms. Examples of such subjects include middle-aged and elderly people. In one embodiment, the composition of the present invention is suitably used as a composition for improving, promoting, inhibiting decline, or maintaining energy production for middle-aged and elderly people, or an anti-aging composition. Middle-aged and elderly people may be, for example, humans aged 40 years or older. In one embodiment, among middle-aged and elderly people, elderly people are preferred as the subject. Elderly people may be, for example, humans aged 60 years or older or 65 years or older. The composition of the present invention can also be used for healthy people, for example, for the purpose of preventing conditions or diseases that can be expected to be prevented or improved by improving, promoting, inhibiting decline, or maintaining energy production.
一態様において、投与対象として、エネルギー産生の向上、促進、低下抑制又は維持を必要とする又は希望する対象、老化症状の予防又は改善を必要とする又は希望する対象等が挙げられる。このような対象として、例えば、中高年者等が挙げられる。一態様において、本発明の組成物は、中高年者用のエネルギー産生の向上、促進、低下抑制又は維持用組成物又は抗老化用組成物として好適に使用される。中高年者は、例えば、４０歳以上のヒトであってよい。一態様において中高年者の中でも、対象として高齢者が好ましい。高齢者は、例えば、６０歳以上又は６５歳以上のヒトであってよい。本発明の組成物は、例えば、エネルギー産生の向上、促進、低下抑制又は維持により予防又は改善が期待できる状態又は疾患の予防等を目的として、健常者に対して使用することもできる。 The subject to which the composition of the present invention is ingested or administered (also referred to as an administration subject) is not particularly limited, and is preferably a human or a non-human mammal, more preferably a human.
In one embodiment, the subject of administration includes a subject who needs or desires to improve, promote, inhibit decline, or maintain energy production, and a subject who needs or desires to prevent or improve aging symptoms. Examples of such subjects include middle-aged and elderly people. In one embodiment, the composition of the present invention is suitably used as a composition for improving, promoting, inhibiting decline, or maintaining energy production for middle-aged and elderly people, or an anti-aging composition. Middle-aged and elderly people may be, for example, humans aged 40 years or older. In one embodiment, among middle-aged and elderly people, elderly people are preferred as the subject. Elderly people may be, for example, humans aged 60 years or older or 65 years or older. The composition of the present invention can also be used for healthy people, for example, for the purpose of preventing conditions or diseases that can be expected to be prevented or improved by improving, promoting, inhibiting decline, or maintaining energy production.
本発明の組成物には、例えば、「エネルギー産生又は代謝を助ける」、「細胞のエネルギー産生又は代謝を助ける」、「細胞内のミトコンドリアにおけるエネルギー産生又は代謝を助ける」、「活気、活力の維持向上」、「体力、パフォーマンスの維持向上」、「細胞老化抑制」、「健康寿命延長」、「健康長寿」等の１又は２以上の機能の表示等が付されていてもよい。
一態様において、本発明の組成物は、上記の表示が付された飲食品であることが好ましい。また上記の表示は、上記の機能を得るために用いる旨の表示であってもよい。上記の表示は、組成物自体に付されてもよいし、組成物の容器又は包装に付されていてもよい。 The composition of the present invention may be labeled with one or more functions, such as "aiding energy production or metabolism,""aiding cellular energy production or metabolism,""aiding energy production or metabolism in intracellular mitochondria,""maintaining and improving vitality and energy,""maintaining and improving physical strength and performance,""inhibiting cellular aging,""extending healthy lifespan," and "healthy longevity."
In one embodiment, the composition of the present invention is preferably a food or drink to which the above-mentioned label is attached. The above-mentioned label may be a label indicating that the composition is used to obtain the above-mentioned function. The above-mentioned label may be attached to the composition itself, or to a container or packaging of the composition.
一態様において、本発明の組成物は、上記の表示が付された飲食品であることが好ましい。また上記の表示は、上記の機能を得るために用いる旨の表示であってもよい。上記の表示は、組成物自体に付されてもよいし、組成物の容器又は包装に付されていてもよい。 The composition of the present invention may be labeled with one or more functions, such as "aiding energy production or metabolism,""aiding cellular energy production or metabolism,""aiding energy production or metabolism in intracellular mitochondria,""maintaining and improving vitality and energy,""maintaining and improving physical strength and performance,""inhibiting cellular aging,""extending healthy lifespan," and "healthy longevity."
In one embodiment, the composition of the present invention is preferably a food or drink to which the above-mentioned label is attached. The above-mentioned label may be a label indicating that the composition is used to obtain the above-mentioned function. The above-mentioned label may be attached to the composition itself, or to a container or packaging of the composition.
本発明は、以下の方法も包含する。
上述した本発明の組成物を投与することを含む、エネルギー産生の向上、促進、低下抑制又は維持のための方法。
本発明の組成物を対象に投与することにより、対象においてエネルギー産生を効果的に向上、促進、低下抑制又は維持することが可能となる。上記方法は、治療的な方法であってもよく、非治療的な方法であってもよい。本発明の組成物の好ましい態様は、上述した通りである。 The present invention also encompasses the following methods.
A method for improving, promoting, suppressing the decline or maintaining of energy production, which comprises administering the above-mentioned composition of the present invention.
By administering the composition of the present invention to a subject, it is possible to effectively improve, promote, inhibit or maintain energy production in the subject. The above method may be a therapeutic method or a non-therapeutic method. The preferred embodiment of the composition of the present invention is as described above.
上述した本発明の組成物を投与することを含む、エネルギー産生の向上、促進、低下抑制又は維持のための方法。
本発明の組成物を対象に投与することにより、対象においてエネルギー産生を効果的に向上、促進、低下抑制又は維持することが可能となる。上記方法は、治療的な方法であってもよく、非治療的な方法であってもよい。本発明の組成物の好ましい態様は、上述した通りである。 The present invention also encompasses the following methods.
A method for improving, promoting, suppressing the decline or maintaining of energy production, which comprises administering the above-mentioned composition of the present invention.
By administering the composition of the present invention to a subject, it is possible to effectively improve, promote, inhibit or maintain energy production in the subject. The above method may be a therapeutic method or a non-therapeutic method. The preferred embodiment of the composition of the present invention is as described above.
本発明は、以下の使用も包含する。
エネルギー産生の向上、促進、低下抑制又は維持のための、上述した本発明の組成物の使用。
上記使用は、治療的な使用であってもよく、非治療的な使用であってもよい。本発明の組成物の好ましい態様は、上述した通りである。上述した本発明の組成物は、老化の予防又は抑制のために使用することもできる。上述した本発明の組成物は、寿命延長のため及び／又は健康寿命延長のために使用することもできる。 The present invention also encompasses the following uses:
Use of the composition of the present invention described above for improving, promoting, suppressing the decline or maintaining energy production.
The above-mentioned use may be therapeutic or non-therapeutic. The preferred embodiment of the composition of the present invention is as described above. The above-mentioned composition of the present invention may also be used for preventing or inhibiting aging. The above-mentioned composition of the present invention may also be used for extending lifespan and/or extending healthspan.
エネルギー産生の向上、促進、低下抑制又は維持のための、上述した本発明の組成物の使用。
上記使用は、治療的な使用であってもよく、非治療的な使用であってもよい。本発明の組成物の好ましい態様は、上述した通りである。上述した本発明の組成物は、老化の予防又は抑制のために使用することもできる。上述した本発明の組成物は、寿命延長のため及び／又は健康寿命延長のために使用することもできる。 The present invention also encompasses the following uses:
Use of the composition of the present invention described above for improving, promoting, suppressing the decline or maintaining energy production.
The above-mentioned use may be therapeutic or non-therapeutic. The preferred embodiment of the composition of the present invention is as described above. The above-mentioned composition of the present invention may also be used for preventing or inhibiting aging. The above-mentioned composition of the present invention may also be used for extending lifespan and/or extending healthspan.
上記の方法及び使用においては、１日に１回以上、例えば、１日１回～数回（例えば２～３回）、上述した組成物を対象に投与する（摂取させる）ことが好ましい。投与方法としては、経口投与（摂取）が好ましい。上記の使用は、好ましくはヒト又は非ヒト哺乳動物、より好ましくはヒトにおける使用である。
In the above-mentioned methods and uses, it is preferable to administer (have the subject ingest) the above-mentioned composition at least once a day, for example, once to several times a day (for example, two to three times a day). Oral administration (ingestion) is a preferred method of administration. The above-mentioned uses are preferably in humans or non-human mammals, more preferably in humans.
上記方法及び使用においては、所望の作用が得られる量（有効量ということもできる）の本発明の組成物を使用すればよい。セサミン類化合物、フェルラ酸又はその塩の好ましい投与量や投与対象等は上述した本発明の組成物と同じである。
In the above-mentioned methods and uses, the composition of the present invention may be used in an amount that provides the desired effect (which may also be called an effective amount). The preferred dosages and subjects of administration of the sesamin-class compounds, ferulic acid or its salts are the same as those of the composition of the present invention described above.
本発明は、エネルギー産生の向上、促進、低下抑制又は維持用組成物を製造するための、（Ａ）セサミン類化合物及び（Ｂ）フェルラ酸又はその塩の使用も包含する。本発明は、抗老化用組成物、又は、寿命延長用及び／又は健康寿命延長用組成物を製造するための、（Ａ）セサミン類化合物及び（Ｂ）フェルラ酸又はその塩の使用も包含する。上記使用においては、組成物における（Ａ）セサミン類化合物のセサミン換算の重量に対する、フェルラ酸換算の重量の比が、５～１００となるように、（Ａ）セサミン類化合物及び（Ｂ）フェルラ酸又はその塩を使用する。上記の組成物及びそれらの好ましい態様等は、上述した本発明の組成物と同じである。
The present invention also includes the use of (A) a sesamin-class compound and (B) ferulic acid or a salt thereof to produce a composition for improving, promoting, inhibiting the decline or maintaining energy production. The present invention also includes the use of (A) a sesamin-class compound and (B) ferulic acid or a salt thereof to produce an anti-aging composition or a composition for extending lifespan and/or extending healthy lifespan. In the above use, (A) a sesamin-class compound and (B) ferulic acid or a salt thereof are used so that the ratio of the weight of the (A) sesamin-class compound in terms of sesamin to the weight of ferulic acid in terms of sesamin in the composition is 5 to 100. The above compositions and their preferred aspects are the same as those of the composition of the present invention described above.
本明細書において下限値と上限値によって表されている数値範囲、即ち「下限値～上限値」は、それら下限値及び上限値を含む。例えば、「１～２」により表される範囲は、１以上２以下を意味し、１及び２を含む。本明細書において、上限及び下限は、いずれの組み合わせによる範囲としてもよい。
なお、本明細書中に記載された学術文献及び特許文献の全ては、参照として本明細書に組み入れられる。 In this specification, a numerical range expressed by a lower limit and an upper limit, i.e., "lower limit to upper limit," includes the lower limit and the upper limit. For example, a range expressed by "1 to 2" means 1 or more and 2 or less, including 1 and 2. In this specification, the upper limit and the lower limit may be in any combination.
All academic and patent literature cited herein is hereby incorporated by reference.
なお、本明細書中に記載された学術文献及び特許文献の全ては、参照として本明細書に組み入れられる。 In this specification, a numerical range expressed by a lower limit and an upper limit, i.e., "lower limit to upper limit," includes the lower limit and the upper limit. For example, a range expressed by "1 to 2" means 1 or more and 2 or less, including 1 and 2. In this specification, the upper limit and the lower limit may be in any combination.
All academic and patent literature cited herein is hereby incorporated by reference.
以下、本発明を実施例に基づいてより具体的に説明する。尚、本発明はこれらの実施例に限定されるものではない。
The present invention will be described in more detail below with reference to examples. Note that the present invention is not limited to these examples.
実施例においては、セサミン類化合物として、セサミン及びエピセサミンの混合物（セサミン：エピセサミン（重量比）が１：１）を使用した。このセサミン及びエピセサミンの混合物を、以下ではセサミン類混合物と記載する。
フェルラ酸には、オリザ油化（株）製のフェルラ酸を使用した。 In the examples, a mixture of sesamin and episesamin (sesamin:episesamin (weight ratio) 1:1) was used as the sesamin-class compound. This mixture of sesamin and episesamin is hereinafter referred to as a sesamin-class mixture.
Ferulic acid used was that manufactured by Oryza Oil & Fat Chemical Co., Ltd.
フェルラ酸には、オリザ油化（株）製のフェルラ酸を使用した。 In the examples, a mixture of sesamin and episesamin (sesamin:episesamin (weight ratio) 1:1) was used as the sesamin-class compound. This mixture of sesamin and episesamin is hereinafter referred to as a sesamin-class mixture.
Ferulic acid used was that manufactured by Oryza Oil & Fat Chemical Co., Ltd.
＜実施例１及び２＞
５．５×１０３ｃｅｌｌｓ／ｗｅｌｌのＴＩＧ－３細胞（胎児肺由来細胞）を専用プレートに播き、３７℃、ＣＯ２（５％）の条件で２４時間培養した（第一の培養）。培地には、ＤＭＥＭ ｈｉｇｈ Ｇｌｕｃｏｓｅ（ナカライテスク（株）、商品コード：０８４５８－４５）に、１０％ Ｆｅｔａｌ Ｂｏｖｉｎｅ Ｓｅｒｕｍ（Ｓｉｇｍａ－Ａｌｄｒｉｃｈ、５００ｍＬ）、１％ Ａｎｔｉｂｉｏｔｉｃ Ａｎｔｉｍｙｃｏｔｉｃ Ｍｉｘｅｄ Ｓｔｏｃｋ Ｓｏｌｕｔｉｏｎ（１００×）（ナカライテスク（株）、商品コード：０２８９２－５４）を添加して調製したものを使用した。培養２４時間後に、セサミン類混合物及びフェルラ酸を、下記表１に記載の濃度でウェル中の培地に添加し、２４時間培養した（第二の培養）。セサミン類混合物及びフェルラ酸を添加した培地を取り除き、ウェル中の細胞を、Ｈ２Ｏ２（５００μＭ）添加培地で２時間処理した（Ｈ２Ｏ２処理）。その後、解析培地に交換し、分析機器（ＸＦ ａｎａｌｙｚｅｒ、Ａｇｉｌｅｎｔ株式会社）にて酸素消費速度（ｐｍｏｌ／ｍｉｎ）を分析した。分析終了後、ヘキストで核を染色し、細胞を蛍光顕微鏡ＢＺ－ｘ（株式会社キーエンス）で撮影し、画像解析にて細胞数のカウントを行った。ＸＦ ａｎａｌｙｚｅｒで生細胞の酸素消費の減少量を測定することにより、ミトコンドリア機能を示すＡＴＰ産生量を評価することができる。具体的には、ウェル中の生細胞の基礎呼吸の酸素消費速度を測定後に、ウェルにＡＴＰシンターゼ阻害剤（オリゴマイシン）を添加し、オリゴマイシン添加による酸素消費速度減少量（ｐｍｏｌ／ｍｉｎ／ｃｅｌｌ）を測定し、ＡＴＰ産生量とした。基礎呼吸は、ベースライン条件下での細胞エネルギー需要を示し、基礎呼吸の一部がＡＴＰ生産のために使用される。オリゴマイシンの添加による酸素消費速度減少量はＡＴＰ産生量を示す。得られた結果を表１に示す。 <Examples 1 and 2>
TIG-3 cells (fetal lung-derived cells) were seeded on a dedicated plate at 5.5 x 103 cells/well and cultured for 24 hours under conditions of 37°C and CO2 (5%) (first culture). The medium used was prepared by adding 10% Fetal Bovine Serum (Sigma-Aldrich, 500 mL) and 1% Antibiotic Antimycotic Mixed Stock Solution (100x) (Nacalai Tesque, Inc., product code: 02892-54) to DMEM high glucose (Nacalai Tesque, Inc., product code: 08458-45). After 24 hours of culture, the sesamin mixture and ferulic acid were added to the medium in the well at the concentrations shown in Table 1 below, and cultured for 24 hours (second culture). The medium containing the sesamin mixture and ferulic acid was removed, and the cells in the well were treated with H 2 O 2 (500 μM)-added medium for 2 hours (H 2 O 2 treatment). The medium was then replaced with an analysis medium, and the oxygen consumption rate (pmol/min) was analyzed using an analysis device (XF analyzer, Agilent Corporation). After the analysis was completed, the nuclei were stained with Hoechst, and the cells were photographed with a fluorescence microscope BZ-x (Keyence Corporation), and the number of cells was counted by image analysis. The amount of ATP production, which indicates mitochondrial function, can be evaluated by measuring the decrease in oxygen consumption of live cells using the XF analyzer. Specifically, after measuring the oxygen consumption rate of basal respiration of living cells in the well, an ATP synthase inhibitor (oligomycin) was added to the well, and the amount of decrease in oxygen consumption rate due to the addition of oligomycin (pmol/min/cell) was measured and used as the amount of ATP production. Basal respiration indicates the cellular energy demand under baseline conditions, and a part of the basal respiration is used for ATP production. The amount of decrease in oxygen consumption rate due to the addition of oligomycin indicates the amount of ATP production. The results obtained are shown in Table 1.
５．５×１０３ｃｅｌｌｓ／ｗｅｌｌのＴＩＧ－３細胞（胎児肺由来細胞）を専用プレートに播き、３７℃、ＣＯ２（５％）の条件で２４時間培養した（第一の培養）。培地には、ＤＭＥＭ ｈｉｇｈ Ｇｌｕｃｏｓｅ（ナカライテスク（株）、商品コード：０８４５８－４５）に、１０％ Ｆｅｔａｌ Ｂｏｖｉｎｅ Ｓｅｒｕｍ（Ｓｉｇｍａ－Ａｌｄｒｉｃｈ、５００ｍＬ）、１％ Ａｎｔｉｂｉｏｔｉｃ Ａｎｔｉｍｙｃｏｔｉｃ Ｍｉｘｅｄ Ｓｔｏｃｋ Ｓｏｌｕｔｉｏｎ（１００×）（ナカライテスク（株）、商品コード：０２８９２－５４）を添加して調製したものを使用した。培養２４時間後に、セサミン類混合物及びフェルラ酸を、下記表１に記載の濃度でウェル中の培地に添加し、２４時間培養した（第二の培養）。セサミン類混合物及びフェルラ酸を添加した培地を取り除き、ウェル中の細胞を、Ｈ２Ｏ２（５００μＭ）添加培地で２時間処理した（Ｈ２Ｏ２処理）。その後、解析培地に交換し、分析機器（ＸＦ ａｎａｌｙｚｅｒ、Ａｇｉｌｅｎｔ株式会社）にて酸素消費速度（ｐｍｏｌ／ｍｉｎ）を分析した。分析終了後、ヘキストで核を染色し、細胞を蛍光顕微鏡ＢＺ－ｘ（株式会社キーエンス）で撮影し、画像解析にて細胞数のカウントを行った。ＸＦ ａｎａｌｙｚｅｒで生細胞の酸素消費の減少量を測定することにより、ミトコンドリア機能を示すＡＴＰ産生量を評価することができる。具体的には、ウェル中の生細胞の基礎呼吸の酸素消費速度を測定後に、ウェルにＡＴＰシンターゼ阻害剤（オリゴマイシン）を添加し、オリゴマイシン添加による酸素消費速度減少量（ｐｍｏｌ／ｍｉｎ／ｃｅｌｌ）を測定し、ＡＴＰ産生量とした。基礎呼吸は、ベースライン条件下での細胞エネルギー需要を示し、基礎呼吸の一部がＡＴＰ生産のために使用される。オリゴマイシンの添加による酸素消費速度減少量はＡＴＰ産生量を示す。得られた結果を表１に示す。 <Examples 1 and 2>
TIG-3 cells (fetal lung-derived cells) were seeded on a dedicated plate at 5.5 x 103 cells/well and cultured for 24 hours under conditions of 37°C and CO2 (5%) (first culture). The medium used was prepared by adding 10% Fetal Bovine Serum (Sigma-Aldrich, 500 mL) and 1% Antibiotic Antimycotic Mixed Stock Solution (100x) (Nacalai Tesque, Inc., product code: 02892-54) to DMEM high glucose (Nacalai Tesque, Inc., product code: 08458-45). After 24 hours of culture, the sesamin mixture and ferulic acid were added to the medium in the well at the concentrations shown in Table 1 below, and cultured for 24 hours (second culture). The medium containing the sesamin mixture and ferulic acid was removed, and the cells in the well were treated with H 2 O 2 (500 μM)-added medium for 2 hours (H 2 O 2 treatment). The medium was then replaced with an analysis medium, and the oxygen consumption rate (pmol/min) was analyzed using an analysis device (XF analyzer, Agilent Corporation). After the analysis was completed, the nuclei were stained with Hoechst, and the cells were photographed with a fluorescence microscope BZ-x (Keyence Corporation), and the number of cells was counted by image analysis. The amount of ATP production, which indicates mitochondrial function, can be evaluated by measuring the decrease in oxygen consumption of live cells using the XF analyzer. Specifically, after measuring the oxygen consumption rate of basal respiration of living cells in the well, an ATP synthase inhibitor (oligomycin) was added to the well, and the amount of decrease in oxygen consumption rate due to the addition of oligomycin (pmol/min/cell) was measured and used as the amount of ATP production. Basal respiration indicates the cellular energy demand under baseline conditions, and a part of the basal respiration is used for ATP production. The amount of decrease in oxygen consumption rate due to the addition of oligomycin indicates the amount of ATP production. The results obtained are shown in Table 1.
実施例１で第二の培養に使用した培地中の、セサミン類化合物（ＳＥ）に対するフェルラ酸（ＦＡ）の重量比（ＦＡ／ＳＥ）は、１１であり、モル比（ＦＡ／ＳＥ）は２０であった。実施例２で第二の培養に使用した培地中の、セサミン類化合物に対するフェルラ酸の重量比（ＦＡ／ＳＥ）は、５５であり、モル比（ＦＡ／ＳＥ）は１００であった。
In the medium used for the second culture in Example 1, the weight ratio (FA/SE) of ferulic acid (FA) to sesamin-based compounds (SE) was 11, and the molar ratio (FA/SE) was 20. In the medium used for the second culture in Example 2, the weight ratio (FA/SE) of ferulic acid to sesamin-based compounds was 55, and the molar ratio (FA/SE) was 100.
＜参考例１＞
参考例１では、セサミン類混合物及びフェルラ酸を含まない培地で第二の培養を行い、Ｈ２Ｏ２処理を行わなかった。具体的には、下記の方法で培養を行い、ＡＴＰ産生量を調べた。
５．５×１０３ｃｅｌｌｓ／ｗｅｌｌのＴＩＧ－３細胞を専用プレートに播き、３７℃、ＣＯ２（５％）の条件で２４時間培養した（第一の培養）。培養２４時間後に、さらに、２６時間培養した（第二の培養）。その後、解析培地に交換し、実施例１と同じ方法で、細胞数のカウント、並びに酸素消費速度及び酸素消費速度減少量の測定を行った。結果を表１に示す。 <Reference Example 1>
In Reference Example 1, the second culture was carried out in a medium not containing a sesamin component mixture or ferulic acid, and no H 2 O 2 treatment was carried out. Specifically, the culture was carried out by the following method, and the amount of ATP produced was examined.
TIG-3 cells were seeded on a dedicated plate at 5.5 x 103 cells/well and cultured for 24 hours at 37°C and CO2 (5%) (first culture). After 24 hours of culture, the cells were further cultured for 26 hours (second culture). The medium was then replaced with an analysis medium, and the cell count, oxygen consumption rate, and decrease in oxygen consumption rate were measured in the same manner as in Example 1. The results are shown in Table 1.
参考例１では、セサミン類混合物及びフェルラ酸を含まない培地で第二の培養を行い、Ｈ２Ｏ２処理を行わなかった。具体的には、下記の方法で培養を行い、ＡＴＰ産生量を調べた。
５．５×１０３ｃｅｌｌｓ／ｗｅｌｌのＴＩＧ－３細胞を専用プレートに播き、３７℃、ＣＯ２（５％）の条件で２４時間培養した（第一の培養）。培養２４時間後に、さらに、２６時間培養した（第二の培養）。その後、解析培地に交換し、実施例１と同じ方法で、細胞数のカウント、並びに酸素消費速度及び酸素消費速度減少量の測定を行った。結果を表１に示す。 <Reference Example 1>
In Reference Example 1, the second culture was carried out in a medium not containing a sesamin component mixture or ferulic acid, and no H 2 O 2 treatment was carried out. Specifically, the culture was carried out by the following method, and the amount of ATP produced was examined.
TIG-3 cells were seeded on a dedicated plate at 5.5 x 103 cells/well and cultured for 24 hours at 37°C and CO2 (5%) (first culture). After 24 hours of culture, the cells were further cultured for 26 hours (second culture). The medium was then replaced with an analysis medium, and the cell count, oxygen consumption rate, and decrease in oxygen consumption rate were measured in the same manner as in Example 1. The results are shown in Table 1.
＜比較例１＞
比較例１では、セサミン類混合物及びフェルラ酸を含まない培地で第二の培養を行った。これ以外は、実施例１と同じ方法で細胞培養及びＨ２Ｏ２処理を行った。具体的には、下記の方法で培養を行い、ＡＴＰ産生量を調べた。
５．５×１０３ｃｅｌｌｓ／ｗｅｌｌのＴＩＧ－３細胞を専用プレートに播き、３７℃、ＣＯ２（５％）の条件で２４時間培養し（第一の培養）、さらに２４時間培養した（第二の培養）。培地を取り除き、ウェル中の細胞を、Ｈ２Ｏ２（５００μＭ）添加培地で２時間処理した（Ｈ２Ｏ２処理）。その後、解析培地に交換し、実施例１と同じ方法で、細胞数のカウント、並びに酸素消費速度及び酸素消費速度減少量の測定を行った。結果を表１に示す。 <Comparative Example 1>
In Comparative Example 1, the second culture was carried out in a medium that did not contain a sesamin-component mixture or ferulic acid. Other than this, cell culture and H2O2 treatment were carried out in the same manner as in Example 1. Specifically, culture was carried out in the following manner, and the amount of ATP production was examined.
TIG-3 cells were seeded on a dedicated plate at 5.5 x 103 cells/well and cultured at 37°C and CO2 (5%) for 24 hours (first culture) and then for another 24 hours (second culture). The medium was removed and the cells in the wells were treated with medium containing H2O2 (500 μM) for 2 hours ( H2O2 treatment ). The medium was then replaced with an analysis medium, and the cell count, oxygen consumption rate, and decrease in oxygen consumption rate were measured in the same manner as in Example 1. The results are shown in Table 1.
比較例１では、セサミン類混合物及びフェルラ酸を含まない培地で第二の培養を行った。これ以外は、実施例１と同じ方法で細胞培養及びＨ２Ｏ２処理を行った。具体的には、下記の方法で培養を行い、ＡＴＰ産生量を調べた。
５．５×１０３ｃｅｌｌｓ／ｗｅｌｌのＴＩＧ－３細胞を専用プレートに播き、３７℃、ＣＯ２（５％）の条件で２４時間培養し（第一の培養）、さらに２４時間培養した（第二の培養）。培地を取り除き、ウェル中の細胞を、Ｈ２Ｏ２（５００μＭ）添加培地で２時間処理した（Ｈ２Ｏ２処理）。その後、解析培地に交換し、実施例１と同じ方法で、細胞数のカウント、並びに酸素消費速度及び酸素消費速度減少量の測定を行った。結果を表１に示す。 <Comparative Example 1>
In Comparative Example 1, the second culture was carried out in a medium that did not contain a sesamin-component mixture or ferulic acid. Other than this, cell culture and H2O2 treatment were carried out in the same manner as in Example 1. Specifically, culture was carried out in the following manner, and the amount of ATP production was examined.
TIG-3 cells were seeded on a dedicated plate at 5.5 x 103 cells/well and cultured at 37°C and CO2 (5%) for 24 hours (first culture) and then for another 24 hours (second culture). The medium was removed and the cells in the wells were treated with medium containing H2O2 (500 μM) for 2 hours ( H2O2 treatment ). The medium was then replaced with an analysis medium, and the cell count, oxygen consumption rate, and decrease in oxygen consumption rate were measured in the same manner as in Example 1. The results are shown in Table 1.
＜比較例２～４＞
比較例２～４では、セサミン類混合物単独又はフェルラ酸単独で処理した細胞のＡＴＰ産生量を評価した。具体的には、下記の方法で培養を行い、ＡＴＰ産生量を調べた。
５．５×１０３ｃｅｌｌｓ／ｗｅｌｌのＴＩＧ－３細胞を専用プレートに播き、３７℃、ＣＯ２（５％）の条件で２４時間培養した（第一の培養）。培養２４時間後に、セサミン類混合物（比較例２）又はフェルラ酸（比較例３～４）をそれぞれ下記表１に記載の濃度でウェル中の培地に添加し、２４時間培養した（第二の培養）。セサミン類混合物又はフェルラ酸を添加した培地を取り除き、ウェル中の細胞を、Ｈ２Ｏ２（５００μＭ）添加培地で２時間処理した（Ｈ２Ｏ２処理）。その後、解析培地に交換し、実施例１と同じ方法で、細胞数のカウント、並びに酸素消費速度及び酸素消費速度減少量の測定を行った。結果を表１に示す。 <Comparative Examples 2 to 4>
In Comparative Examples 2 to 4, the amount of ATP produced by cells treated with either the sesamin component mixture alone or ferulic acid alone was evaluated. Specifically, the cells were cultured in the following manner, and the amount of ATP produced was examined.
TIG-3 cells were seeded on a dedicated plate at 5.5 x 10 3 cells/well and cultured for 24 hours under conditions of 37°C and CO 2 (5%) (first culture). After 24 hours of culture, a sesamin-based mixture (Comparative Example 2) or ferulic acid (Comparative Examples 3-4) was added to the medium in the well at the concentrations shown in Table 1 below, and cultured for 24 hours (second culture). The medium containing the sesamin-based mixture or ferulic acid was removed, and the cells in the well were treated with a medium containing H 2 O 2 (500 μM) for 2 hours (H 2 O 2 treatment). The medium was then replaced with an analysis medium, and the cell count, oxygen consumption rate, and amount of decrease in oxygen consumption rate were measured in the same manner as in Example 1. The results are shown in Table 1.
比較例２～４では、セサミン類混合物単独又はフェルラ酸単独で処理した細胞のＡＴＰ産生量を評価した。具体的には、下記の方法で培養を行い、ＡＴＰ産生量を調べた。
５．５×１０３ｃｅｌｌｓ／ｗｅｌｌのＴＩＧ－３細胞を専用プレートに播き、３７℃、ＣＯ２（５％）の条件で２４時間培養した（第一の培養）。培養２４時間後に、セサミン類混合物（比較例２）又はフェルラ酸（比較例３～４）をそれぞれ下記表１に記載の濃度でウェル中の培地に添加し、２４時間培養した（第二の培養）。セサミン類混合物又はフェルラ酸を添加した培地を取り除き、ウェル中の細胞を、Ｈ２Ｏ２（５００μＭ）添加培地で２時間処理した（Ｈ２Ｏ２処理）。その後、解析培地に交換し、実施例１と同じ方法で、細胞数のカウント、並びに酸素消費速度及び酸素消費速度減少量の測定を行った。結果を表１に示す。 <Comparative Examples 2 to 4>
In Comparative Examples 2 to 4, the amount of ATP produced by cells treated with either the sesamin component mixture alone or ferulic acid alone was evaluated. Specifically, the cells were cultured in the following manner, and the amount of ATP produced was examined.
TIG-3 cells were seeded on a dedicated plate at 5.5 x 10 3 cells/well and cultured for 24 hours under conditions of 37°C and CO 2 (5%) (first culture). After 24 hours of culture, a sesamin-based mixture (Comparative Example 2) or ferulic acid (Comparative Examples 3-4) was added to the medium in the well at the concentrations shown in Table 1 below, and cultured for 24 hours (second culture). The medium containing the sesamin-based mixture or ferulic acid was removed, and the cells in the well were treated with a medium containing H 2 O 2 (500 μM) for 2 hours (H 2 O 2 treatment). The medium was then replaced with an analysis medium, and the cell count, oxygen consumption rate, and amount of decrease in oxygen consumption rate were measured in the same manner as in Example 1. The results are shown in Table 1.
表１中、ＳＥはセサミン類化合物を、ＦＡはフェルラ酸を、それぞれ示す。
「ＡＴＰ産生（１０－２ｐｍｏｌ／ｍｉｎ／ｃｅｌｌ）」に、上記で求めたＡＴＰ産生量（ＡＴＰシンターゼ阻害による酸素消費速度減少量）の平均及び標準偏差（ＳＤ）（ｎ＝４）を示した。「比較例１に対する改善率」は、表１に示すＡＴＰ産生量（１０－２ｐｍｏｌ／ｍｉｎ／ｃｅｌｌ）から、下記の方法で求めた。
比較例１に対する改善率（％）＝１００×（（実施例又は比較例のＡＴＰ産生量）－（比較例１のＡＴＰ産生量））／（比較例１のＡＴＰ産生量） In Table 1, SE represents sesamin-class compounds, and FA represents ferulic acid.
The average and standard deviation (SD) (n=4) of the amount of ATP production (amount of decrease in oxygen consumption rate due to ATP synthase inhibition) obtained above are shown in "ATP production (10 -2 pmol/min/cell)". The "improvement rate relative to Comparative Example 1" was calculated from the amount of ATP production (10 -2 pmol/min/cell) shown in Table 1 by the following method.
Improvement rate (%) relative to Comparative Example 1=100×((ATP production amount of Example or Comparative Example)−(ATP production amount of Comparative Example 1))/(ATP production amount of Comparative Example 1)
「ＡＴＰ産生（１０－２ｐｍｏｌ／ｍｉｎ／ｃｅｌｌ）」に、上記で求めたＡＴＰ産生量（ＡＴＰシンターゼ阻害による酸素消費速度減少量）の平均及び標準偏差（ＳＤ）（ｎ＝４）を示した。「比較例１に対する改善率」は、表１に示すＡＴＰ産生量（１０－２ｐｍｏｌ／ｍｉｎ／ｃｅｌｌ）から、下記の方法で求めた。
比較例１に対する改善率（％）＝１００×（（実施例又は比較例のＡＴＰ産生量）－（比較例１のＡＴＰ産生量））／（比較例１のＡＴＰ産生量） In Table 1, SE represents sesamin-class compounds, and FA represents ferulic acid.
The average and standard deviation (SD) (n=4) of the amount of ATP production (amount of decrease in oxygen consumption rate due to ATP synthase inhibition) obtained above are shown in "ATP production (10 -2 pmol/min/cell)". The "improvement rate relative to Comparative Example 1" was calculated from the amount of ATP production (10 -2 pmol/min/cell) shown in Table 1 by the following method.
Improvement rate (%) relative to Comparative Example 1=100×((ATP production amount of Example or Comparative Example)−(ATP production amount of Comparative Example 1))/(ATP production amount of Comparative Example 1)
参考例１と比較例１との比較から、過酸化水素処理によってＡＴＰ産生量が減少した。比較例１に対する改善率（以下、単に改善率という）が大きいほど、ＡＴＰ産生量の減少が抑制されたことを意味する。図１に、セサミン類化合物及びフェルラ酸のエネルギー産生への効果を示すグラフを示す。図１のグラフの縦軸（改善率）は、上記の比較例１に対する改善率である。図１に、比較例２及び３の改善率を加算した値（合算値）、比較例２及び４の改善率を加算した値（合算値）も示した。
比較例２（セサミン類化合物濃度が１μＭ）では、改善率は６．１％であった。比較例３（フェルラ酸濃度が２０μＭ）では、改善率は－０．７％であった。
実施例１（セサミン類化合物濃度が１μＭ、フェルラ酸濃度が２０μＭ）では、改善率は１５．２であった。この実施例１の改善率は、セサミン類化合物濃度が同じである比較例２の改善率（６．１％）、及びフェルラ酸濃度が同じである比較例３の改善率（－０．７％）を加算した値（５．４％）よりも顕著に高かった。
実施例２についても、上記改善率は、比較例２及び４の改善率を加算した値（６．１＋４．８＝１０．９％）よりも高かった。 A comparison between Reference Example 1 and Comparative Example 1 shows that hydrogen peroxide treatment reduced ATP production. A larger improvement rate relative to Comparative Example 1 (hereinafter simply referred to as improvement rate) means that the decrease in ATP production was more suppressed. Figure 1 shows a graph showing the effects of sesamin-class compounds and ferulic acid on energy production. The vertical axis (improvement rate) of the graph in Figure 1 is the improvement rate relative to the above Comparative Example 1. Figure 1 also shows the value obtained by adding up the improvement rates of Comparative Examples 2 and 3 (combined value), and the value obtained by adding up the improvement rates of Comparative Examples 2 and 4 (combined value).
In Comparative Example 2 (sesamin-class compound concentration: 1 μM), the improvement rate was 6.1%. In Comparative Example 3 (ferulic acid concentration: 20 μM), the improvement rate was −0.7%.
In Example 1 (sesamin-family compound concentration: 1 μM, ferulic acid concentration: 20 μM), the improvement rate was 15.2. This improvement rate in Example 1 was significantly higher (5.4%) than the sum of the improvement rates (6.1%) in Comparative Example 2, which had the same sesamin-family compound concentration, and Comparative Example 3, which had the same ferulic acid concentration (-0.7%).
The improvement rate of Example 2 was also higher than the sum of the improvement rates of Comparative Examples 2 and 4 (6.1+4.8=10.9%).
比較例２（セサミン類化合物濃度が１μＭ）では、改善率は６．１％であった。比較例３（フェルラ酸濃度が２０μＭ）では、改善率は－０．７％であった。
実施例１（セサミン類化合物濃度が１μＭ、フェルラ酸濃度が２０μＭ）では、改善率は１５．２であった。この実施例１の改善率は、セサミン類化合物濃度が同じである比較例２の改善率（６．１％）、及びフェルラ酸濃度が同じである比較例３の改善率（－０．７％）を加算した値（５．４％）よりも顕著に高かった。
実施例２についても、上記改善率は、比較例２及び４の改善率を加算した値（６．１＋４．８＝１０．９％）よりも高かった。 A comparison between Reference Example 1 and Comparative Example 1 shows that hydrogen peroxide treatment reduced ATP production. A larger improvement rate relative to Comparative Example 1 (hereinafter simply referred to as improvement rate) means that the decrease in ATP production was more suppressed. Figure 1 shows a graph showing the effects of sesamin-class compounds and ferulic acid on energy production. The vertical axis (improvement rate) of the graph in Figure 1 is the improvement rate relative to the above Comparative Example 1. Figure 1 also shows the value obtained by adding up the improvement rates of Comparative Examples 2 and 3 (combined value), and the value obtained by adding up the improvement rates of Comparative Examples 2 and 4 (combined value).
In Comparative Example 2 (sesamin-class compound concentration: 1 μM), the improvement rate was 6.1%. In Comparative Example 3 (ferulic acid concentration: 20 μM), the improvement rate was −0.7%.
In Example 1 (sesamin-family compound concentration: 1 μM, ferulic acid concentration: 20 μM), the improvement rate was 15.2. This improvement rate in Example 1 was significantly higher (5.4%) than the sum of the improvement rates (6.1%) in Comparative Example 2, which had the same sesamin-family compound concentration, and Comparative Example 3, which had the same ferulic acid concentration (-0.7%).
The improvement rate of Example 2 was also higher than the sum of the improvement rates of Comparative Examples 2 and 4 (6.1+4.8=10.9%).
図１にも示されるように、実施例１及び２における改善率は、セサミン類化合物単独で処理した場合の改善率及びフェルラ酸単独で処理した場合の改善率の合算値よりも大きい値であった。つまり、単に、セサミン類化合物及びフェルラ酸に対し相加的にＡＴＰ産生量の減少が抑制されたのではなく、セサミン類化合物とフェルラ酸との併用により、相乗的にＡＴＰ産生量の減少が抑制された。セサミン類化合物とフェルラ酸又はその塩とを含む組成物は、両者を含むことによってエネルギー産生の向上、促進、低下抑制又は維持において相乗的な効果を示すことを確認した。
As shown in Figure 1, the improvement rates in Examples 1 and 2 were greater than the combined improvement rate when treated with sesamin-based compounds alone and ferulic acid alone. In other words, the decrease in ATP production was not simply suppressed additively by the sesamin-based compounds and ferulic acid, but the combined use of sesamin-based compounds and ferulic acid synergistically suppressed the decrease in ATP production. It was confirmed that a composition containing a sesamin-based compound and ferulic acid or a salt thereof exhibits a synergistic effect in improving, promoting, inhibiting the decrease, or maintaining energy production by containing both.
＜実施例３＞
セサミン類化合物及びフェルラ酸の分裂寿命延長効果を調べた。酵母Ｋ６００１は娘酵母が分裂しないため、親細胞から出芽した娘細胞数をカウントすることで、親細胞の分裂寿命を測定することが可能である。本試験では酵母Ｋ６００１をＹＰＧａｌａｃｔｏｓｅ液体培地（２％ガラクトース、１％酵母エキス、２％ペプトン）で定常期まで培養し、一部酵母を回収し、水で２回洗浄した。洗浄した酵母を、セサミン類混合物及びフェルラ酸を含むＹＰＧｌｕｃｏｓｅ寒天培地（２％ガラクトース、１％酵母エキス、２％ペプトン）に播種し、３０℃で２日間培養後、顕微鏡で娘細胞をカウントした。培地中のセサミン類混合物の濃度は、１μＭとした。培地中のフェルラ酸の濃度は、１０μＭ、２０μＭ、５０μＭ又は１００μＭとした。培地に含まれるセサミン類化合物（ＳＥ）に対するフェルラ酸（ＦＡ）の重量比（ＦＡ／ＳＥ）は、フェルラ酸１０μＭの培地では、５であった。上記重量比（ＦＡ／ＳＥ）は、フェルラ酸２０μＭの培地では、１１、フェルラ酸５０μＭの培地では、２７、フェルラ酸１００μＭの培地では、５５であった。 Example 3
The effect of sesamin compounds and ferulic acid on extending the division life span was investigated. Since yeast K6001 does not divide into daughter yeasts, it is possible to measure the division life span of parent cells by counting the number of daughter cells budding from the parent cell. In this test, yeast K6001 was cultured in YPGalactose liquid medium (2% galactose, 1% yeast extract, 2% peptone) until stationary phase, and some yeast was collected and washed twice with water. The washed yeast was inoculated on YPGlucose agar medium (2% galactose, 1% yeast extract, 2% peptone) containing a sesamin compound mixture and ferulic acid, and after culturing at 30°C for 2 days, the daughter cells were counted under a microscope. The concentration of the sesamin compound mixture in the medium was 1 μM. The concentration of ferulic acid in the medium was 10 μM, 20 μM, 50 μM, or 100 μM. The weight ratio (FA/SE) of ferulic acid (FA) to sesamin-based compounds (SE) contained in the medium was 5 in the medium containing 10 μM ferulic acid. The weight ratio (FA/SE) was 11 in the medium containing 20 μM ferulic acid, 27 in the medium containing 50 μM ferulic acid, and 55 in the medium containing 100 μM ferulic acid.
セサミン類化合物及びフェルラ酸の分裂寿命延長効果を調べた。酵母Ｋ６００１は娘酵母が分裂しないため、親細胞から出芽した娘細胞数をカウントすることで、親細胞の分裂寿命を測定することが可能である。本試験では酵母Ｋ６００１をＹＰＧａｌａｃｔｏｓｅ液体培地（２％ガラクトース、１％酵母エキス、２％ペプトン）で定常期まで培養し、一部酵母を回収し、水で２回洗浄した。洗浄した酵母を、セサミン類混合物及びフェルラ酸を含むＹＰＧｌｕｃｏｓｅ寒天培地（２％ガラクトース、１％酵母エキス、２％ペプトン）に播種し、３０℃で２日間培養後、顕微鏡で娘細胞をカウントした。培地中のセサミン類混合物の濃度は、１μＭとした。培地中のフェルラ酸の濃度は、１０μＭ、２０μＭ、５０μＭ又は１００μＭとした。培地に含まれるセサミン類化合物（ＳＥ）に対するフェルラ酸（ＦＡ）の重量比（ＦＡ／ＳＥ）は、フェルラ酸１０μＭの培地では、５であった。上記重量比（ＦＡ／ＳＥ）は、フェルラ酸２０μＭの培地では、１１、フェルラ酸５０μＭの培地では、２７、フェルラ酸１００μＭの培地では、５５であった。 Example 3
The effect of sesamin compounds and ferulic acid on extending the division life span was investigated. Since yeast K6001 does not divide into daughter yeasts, it is possible to measure the division life span of parent cells by counting the number of daughter cells budding from the parent cell. In this test, yeast K6001 was cultured in YPGalactose liquid medium (2% galactose, 1% yeast extract, 2% peptone) until stationary phase, and some yeast was collected and washed twice with water. The washed yeast was inoculated on YPGlucose agar medium (2% galactose, 1% yeast extract, 2% peptone) containing a sesamin compound mixture and ferulic acid, and after culturing at 30°C for 2 days, the daughter cells were counted under a microscope. The concentration of the sesamin compound mixture in the medium was 1 μM. The concentration of ferulic acid in the medium was 10 μM, 20 μM, 50 μM, or 100 μM. The weight ratio (FA/SE) of ferulic acid (FA) to sesamin-based compounds (SE) contained in the medium was 5 in the medium containing 10 μM ferulic acid. The weight ratio (FA/SE) was 11 in the medium containing 20 μM ferulic acid, 27 in the medium containing 50 μM ferulic acid, and 55 in the medium containing 100 μM ferulic acid.
コントロールにおいては、上記と同じ方法で定常期まで培養し、水で洗浄した酵母Ｋ６００１を、セサミン類混合物及びフェルラ酸を含まないＹＰＧａｌａｃｔｏｓｅ液体培地に播種して３０℃で２日間培養を行った。その後、顕微鏡で娘細胞をカウントした。
For the control, yeast K6001 was cultured to stationary phase using the same method as above, washed with water, and inoculated onto YPGalactose liquid medium that did not contain the sesamin mixture or ferulic acid and cultured at 30°C for 2 days. Daughter cells were then counted under a microscope.
＜結果＞
図２、図３、図４及び図５は、セサミン類化合物及びフェルラ酸の組合せの酵母における分裂寿命延長効果を調べた結果を示すグラフである。図２、図３、図４及び図５のグラフの横軸は、１つの親細胞から出芽した娘細胞の世代（数）を示す。縦軸の分裂細胞（％）は、親細胞の総数（１００％）に対する、横軸に示す世代の娘細胞を出芽した親細胞の割合（％）を示す（参考文献：Ｊａｒｏｌｉｍ， ｅｔ ａｌ． “Ａ ｎｏｖｅｌ ａｓｓａｙ ｆｏｒ ｒｅｐｌｉｃａｔｉｖｅ ｌｉｆｅｓｐａｎ ｉｎ Ｓａｃｃｈａｒｏｍｙｃｅｓ ｃｅｒｅｖｉｓｉａｅ．” ＦＥＭＳ ｙｅａｓｔ ｒｅｓｅａｒｃｈ ５．２ （２００４）： １６９－１７７）。例えば、親細胞から５つの娘細胞（世代１～５）が出芽した場合、当該親細胞（分裂細胞）は、世代１～５にそれぞれカウントされる。図２、図３、図４及び図５中、白丸（〇）がコントロール（ＣＴＬ）、黒丸（●）がセサミン類化合物（ＳＥ）及びフェルラ酸（ＦＡ）を含有する培地で培養した酵母である。図２、図３、図４及び図５において、培地中のセサミン類混合物の濃度は１μＭであり、フェルラ酸の濃度は、図２では１０μＭ、図３では２０μＭ、図４では５０μＭ、図５では１００μＭである。 <Results>
Figures 2, 3, 4, and 5 are graphs showing the results of investigating the effect of combinations of sesamin-class compounds and ferulic acid on extending the replicative lifespan in yeast. The horizontal axis of the graphs in Figures 2, 3, 4, and 5 shows the generation (number) of daughter cells that budded from a single parent cell. The dividing cells (%) on the vertical axis show the proportion (%) of parent cells that budded off daughter cells of the generation shown on the horizontal axis to the total number of parent cells (100%) (Reference: Jarolim, et al. "A novel assay for replicative lifespan in Saccharomyces cerevisiae." FEMS yeast research 5.2 (2004): 169-177). For example, when five daughter cells (generations 1 to 5) bud from a parent cell, the parent cells (dividing cells) are counted in generations 1 to 5, respectively. In Figures 2, 3, 4 and 5, open circles (◯) represent the control (CTL), and closed circles (●) represent yeast cultured in a medium containing a sesamin-class compound (SE) and ferulic acid (FA). In Figures 2, 3, 4 and 5, the concentration of the sesamin-class mixture in the medium is 1 μM, and the concentration of ferulic acid is 10 μM in Figure 2, 20 μM in Figure 3, 50 μM in Figure 4 and 100 μM in Figure 5.
図２、図３、図４及び図５は、セサミン類化合物及びフェルラ酸の組合せの酵母における分裂寿命延長効果を調べた結果を示すグラフである。図２、図３、図４及び図５のグラフの横軸は、１つの親細胞から出芽した娘細胞の世代（数）を示す。縦軸の分裂細胞（％）は、親細胞の総数（１００％）に対する、横軸に示す世代の娘細胞を出芽した親細胞の割合（％）を示す（参考文献：Ｊａｒｏｌｉｍ， ｅｔ ａｌ． “Ａ ｎｏｖｅｌ ａｓｓａｙ ｆｏｒ ｒｅｐｌｉｃａｔｉｖｅ ｌｉｆｅｓｐａｎ ｉｎ Ｓａｃｃｈａｒｏｍｙｃｅｓ ｃｅｒｅｖｉｓｉａｅ．” ＦＥＭＳ ｙｅａｓｔ ｒｅｓｅａｒｃｈ ５．２ （２００４）： １６９－１７７）。例えば、親細胞から５つの娘細胞（世代１～５）が出芽した場合、当該親細胞（分裂細胞）は、世代１～５にそれぞれカウントされる。図２、図３、図４及び図５中、白丸（〇）がコントロール（ＣＴＬ）、黒丸（●）がセサミン類化合物（ＳＥ）及びフェルラ酸（ＦＡ）を含有する培地で培養した酵母である。図２、図３、図４及び図５において、培地中のセサミン類混合物の濃度は１μＭであり、フェルラ酸の濃度は、図２では１０μＭ、図３では２０μＭ、図４では５０μＭ、図５では１００μＭである。 <Results>
Figures 2, 3, 4, and 5 are graphs showing the results of investigating the effect of combinations of sesamin-class compounds and ferulic acid on extending the replicative lifespan in yeast. The horizontal axis of the graphs in Figures 2, 3, 4, and 5 shows the generation (number) of daughter cells that budded from a single parent cell. The dividing cells (%) on the vertical axis show the proportion (%) of parent cells that budded off daughter cells of the generation shown on the horizontal axis to the total number of parent cells (100%) (Reference: Jarolim, et al. "A novel assay for replicative lifespan in Saccharomyces cerevisiae." FEMS yeast research 5.2 (2004): 169-177). For example, when five daughter cells (generations 1 to 5) bud from a parent cell, the parent cells (dividing cells) are counted in generations 1 to 5, respectively. In Figures 2, 3, 4 and 5, open circles (◯) represent the control (CTL), and closed circles (●) represent yeast cultured in a medium containing a sesamin-class compound (SE) and ferulic acid (FA). In Figures 2, 3, 4 and 5, the concentration of the sesamin-class mixture in the medium is 1 μM, and the concentration of ferulic acid is 10 μM in Figure 2, 20 μM in Figure 3, 50 μM in Figure 4 and 100 μM in Figure 5.
セサミン類化合物（ＳＥ）及びフェルラ酸（ＦＡ）を含む培地中のセサミン類化合物に対するフェルラ酸の重量比（ＦＡ／ＳＥ）は、図２では５、図３では１１、図４では２７、図５では５５である。図２、図３、図４及び図５に示されるように、コントロールと比較すると、セサミン類化合物及びフェルラ酸によって、娘酵母の数が増えた。セサミン類化合物及びフェルラ酸の併用は、酵母に分裂寿命延長効果を示した。分裂寿命の延長は、個体の寿命の延長又は健康寿命の延長と捉えることができる。また、分裂寿命の延長は、老化が予防又は抑制されたと捉えることもできる。（Ａ）セサミン類化合物と（Ｂ）フェルラ酸又はその塩とを、（Ａ）のセサミン換算の重量に対する（Ｂ）のフェルラ酸換算の重量の比（フェルラ酸換算の（Ｂ）／セサミン換算の（Ａ））５～１００で含むことによって、寿命延長効果等を発揮することを確認した。
The weight ratio of ferulic acid to sesamin-based compounds (SE) and ferulic acid (FA) in the medium containing sesamin-based compounds (SE) and ferulic acid (FA) (FA/SE) is 5 in Figure 2, 11 in Figure 3, 27 in Figure 4, and 55 in Figure 5. As shown in Figures 2, 3, 4, and 5, compared to the control, the sesamin-based compounds and ferulic acid increased the number of daughter yeasts. The combined use of sesamin-based compounds and ferulic acid showed an effect of extending the division lifespan of yeast. An extension of division lifespan can be considered as an extension of an individual's lifespan or an extension of healthy lifespan. An extension of division lifespan can also be considered as prevention or inhibition of aging. It was confirmed that by containing (A) a sesamin compound and (B) ferulic acid or a salt thereof in a ratio of the weight of (A) converted into sesamin to the weight of (B) converted into ferulic acid ((B) converted into ferulic acid / (A) converted into sesamin) of 5 to 100, a life extension effect can be achieved.
Claims (8)
- （Ａ）セサミン類化合物、及び、（Ｂ）フェルラ酸又はその塩を含有し、
（Ａ）セサミン類化合物のセサミン換算の重量に対する、（Ｂ）フェルラ酸又はその塩のフェルラ酸換算の重量の比が、５～１００である、組成物。 (A) a sesamin-class compound and (B) ferulic acid or a salt thereof;
A composition, in which the ratio of the weight of (A) sesamin-based compound to the weight of (B) ferulic acid or a salt thereof, in terms of ferulic acid, is 5 to 100. - 前記セサミン類化合物が、セサミン及び／又はエピセサミンである請求項１に記載の組成物。 The composition according to claim 1, wherein the sesamin-class compound is sesamin and/or episesamin.
- 経口用組成物である請求項１又は２に記載の組成物。 The composition according to claim 1 or 2, which is an oral composition.
- 飲食品である請求項１又は２に記載の組成物。 The composition according to claim 1 or 2, which is a food or drink.
- 化粧料である請求項１又は２に記載の組成物。 The composition according to claim 1 or 2, which is a cosmetic.
- エネルギー産生の向上、促進、低下抑制又は維持用組成物である、請求項１又は２に記載の組成物。 The composition according to claim 1 or 2, which is a composition for improving, promoting, inhibiting a decrease in, or maintaining energy production.
- 抗老化用組成物である、請求項１又は２に記載の組成物。 The composition according to claim 1 or 2, which is an anti-aging composition.
- 寿命延長用及び／又は健康寿命延長用組成物である、請求項１又は２に記載の組成物。
The composition according to claim 1 or 2, which is a composition for extending lifespan and/or extending healthspan.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2023038692 | 2023-03-13 | ||
| JP2023-038692 | 2023-03-13 |
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