Components containing sesamin or similar substances and NR and / or NMN.

Abstract

The purpose of the present invention is to provide a composition having the effect of increasing NAD concentration. The present invention pertains to a composition containing, as active ingredients: at least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof; and at least one type of sesamin or the like.

Description

Composition containing NR and / or NMN and sesamin-class compounds

[0001] The present invention relates to a composition containing one or more members selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and sesamin-class compounds.

[0002] In recent years, extending healthy lifespan has become an issue in countries with a high elderly population. One of the factors that contribute to a shortened healthy lifespan is the decline in nicotinamide adenine dinucleotide (NAD) levels in the body with age. ＋ ) production, resulting in a decline in physical functions.

[0003] Here, nicotinamide adenine dinucleotide (NAD ＋ (hereinafter also referred to as NAD) is a coenzyme that mediates many redox reactions in the body. It is known that NAD levels decrease during the aging process, causing defects in nuclear and mitochondrial function and leading to many age-related pathologies. For example, Non-Patent Document 1 states that aging and age-related diseases are caused by the decrease in intracellular nicotinamide adenine dinucleotide (NAD ＋ ) levels, and NAD ＋ It has been suggested that this is related to the decreased activity of the longevity gene sirtuin, which is a NAD-dependent deacetylase. ＋ It has been reported that increasing NAD increases the activity of sirtuins and thus exerts anti-aging effects (Non-Patent Document 2). ＋ Intensive research is being conducted to find ingredients that are effective in preventing or improving the decline in blood cholesterol levels and that can be applied to pharmaceuticals, foods for specified health uses, functional foods, etc.

[0004] For example, Non-Patent Document 3 discloses that nicotinamide riboside (NR), a precursor of NAD, induces the mitochondrial unfolded protein response and the synthesis of prohibitin protein, thereby activating muscle stem cells (MuSCs) in aged mice. It also discloses that NR prevents MuSC aging in a mouse model of muscular dystrophy, delays the aging of neural SCs (stem cells), and extends the lifespan of melanocyte SCs in mice.

[0005] Furthermore, Non-Patent Document 4 states that nicotinamide riboside (NR) is a NAD ＋ It is widely used as a precursor vitamin, and a single oral administration of NR has been shown to increase blood NAD levels in humans. ＋ Furthermore, Non-Patent Document 5 discloses that NMN activates sirtuins, specifically, the major natural NAD ＋ We report that nicotinamide mononucleotide (NMN), an intermediate (also called an intermediate metabolite), was administered to normal wild-type mice for 12 months and that NMN effectively alleviated age-related physiological decline in the mice without any apparent toxicity, demonstrating the great potential of NMN as an effective anti-aging intervention in humans.

[0006] On the other hand, there has been no suggestion or disclosure whatsoever about the effect of sesamin and / or episesamin in increasing nicotinamide adenine dinucleotide (NAD) levels in the body.

[0007] Imai, S. & Guarente, L. (2014) Trends Cell Biol., 24, 464-471. “NAD+ and sirtuins in aging and disease”Yoshida M, Satoh A, Lin JB, Mills KF, Sasaki Y, Rensing N, Wong M, Apte RS, Imai SI., Cell Metab. (2019) 30(2):329-342.e5. “Extracellular Vesicle-Contained eNAMPT Delays Aging and Extends Lifespan in Mice”Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., D’Amico, D., Ropelle, E.R., Lutolf, M.P., Aebersold, R., Schoonjans, K., Menzies, K.J., & Auwerx, J. (2016) Science, 352, 1436-1443. “NAD+ repletion improvesmitochondrial and stem cell function and enhances life span in mice”Samuel A.J. Trammell, Mark S. Schmidt, Benjamin J. Weidemann, Philip Redpath, Frank Jaksch, Ryan W. Dellinger, Zhonggang Li, E Dale Abel, Marie E. Migaud & Charles Brenner, (2016) Nat. Commun. 7, 12948. “Nicotinamide riboside is uniquely and orally bioavailable in mice and humans”Mills, K.F., Yoshida, S., Stein, L.R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M.E., Apte, R.S., Uchida, K.,Yoshino, J. , & Imai, S. I. (2016) Cell Metab. , 24, 795-806. “Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice”,

[0008] An object of the present invention is to provide a composition that has the effect of increasing NAD concentration.

[0009] As a result of intensive research conducted by the inventors to solve the above-mentioned problems, they discovered that sesamin derivatives have the effect of increasing nicotinamide adenine dinucleotide (NAD), and further that a composition containing sesamin derivatives and at least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof effectively increases nicotinamide adenine dinucleotide (NAD).

[0010] The present invention relates to the following compositions: [1] A composition containing, as active ingredients, one or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamin compounds. [2] The composition according to [1] above, wherein the one or more sesamin compounds are sesamin and / or episesamin. [3] The composition according to [1] or [2] above, wherein the molar ratio of one or more compounds selected from the group consisting of NR, NMN, and salts thereof to sesamin compounds (one or more compounds selected from the group consisting of NR, NMN, and salts thereof / sesamins) is 1 to 100. [4] The composition according to any of [1] to [3] above, wherein the total content of one or more sesamins is 0.001 to 10% by weight. [5] The composition according to any of [1] to [4] above, which increases, inhibits a decrease in, maintains, or improves nicotinamide adenine dinucleotide (NAD) concentration. [6] The composition according to any one of [1] to [5] above, which improves, inhibits decline, maintains or improves mitochondrial function. [7] The composition according to any one of [1] to [6] above, which improves, inhibits decline, maintains or improves mitochondrial energy production capacity. [8] The composition according to any one of [1] to [7] above, which is used for inhibiting and / or delaying aging associated with a decrease in NAD concentration. [9] The composition according to any one of [1] to [8] above, which is an anti-aging composition.

[10] The composition according to any one of [1] to [9] above, which is an oral composition.

[11] The composition according to any one of [1] to

[10] above, which is a food or drink.

[12] The composition according to any one of [1] to

[11] above, which is labeled as "inhibiting and / or delaying aging associated with a decrease in NAD concentration" and / or "inhibiting and / or delaying cellular aging".

[13] A method for increasing nicotinamide adenine dinucleotide (NAD) levels, comprising administering one or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamin analogues.

[14] A method for increasing, inhibiting a decrease in, maintaining, or improving nicotinamide adenine dinucleotide (NAD) levels, comprising administering one or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamin analogues.

[15] Use of one or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamin analogues for increasing nicotinamide adenine dinucleotide (NAD) levels.

[16] Use of one or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamin analogues for increasing, inhibiting a decrease in, maintaining, or improving nicotinamide adenine dinucleotide (NAD) levels.

[0011] According to the present invention, a composition having the effect of increasing nicotinamide adenine dinucleotide (NAD) concentration can be provided.

[0012] Graph showing the effect of increasing intracellular NAD concentration of a composition containing a sesamin / episesamin mixture (SE) (sesamin:episesamin (weight ratio = 1:1)) and NR at a molar ratio of 1:100, SE, or NR. Graph showing the effect of increasing intracellular NAD concentration of a composition containing a sesamin / episesamin mixture (SE) (sesamin:episesamin (weight ratio = 1:1)) and NR at a molar ratio of 1:1, SE, or NR. Graph showing the effect of increasing intracellular NAD concentration of a composition containing a sesamin / episesamin mixture (SE) (sesamin:episesamin (weight ratio = 1:1)) and NR at a molar ratio of 1:3.3 or 1:10, or NR. This is a graph showing the effect of a composition containing a sesamin / episesamin mixture (SE) (sesamin:episesamin (weight ratio = 1:1)) and NMN in a molar ratio of 1:3 or 1:10, SE, or NMN on increasing intracellular NAD concentration.

[0013] The composition of the present invention contains one or more sesamin compounds. Sesamin compounds have the effect of increasing nicotinamide adenine dinucleotide (NAD) concentration, and have the effect of increasing, inhibiting a decrease, maintaining, or improving intracellular nicotinamide adenine dinucleotide (NAD) concentration, and are used for increasing NAD concentration, inhibiting a decrease in NAD concentration, maintaining NAD concentration, or improving NAD concentration. Increasing nicotinamide adenine dinucleotide (NAD) concentration means increasing the amount of nicotinamide adenine dinucleotide (NAD). Note that NAD concentration refers to intracellular NAD concentration.

[0014] Sesamin compounds have the effect of increasing nicotinamide adenine dinucleotide (NAD) levels, and are expected to contribute to the prevention or improvement of aging associated with a decline in NAD levels by increasing, inhibiting, maintaining, or improving NAD levels. Aging is understood to be a phenomenon in which physical, physiological, and mental functions decline. Physical changes due to aging begin around the age of 40 after reaching maturity, and include wrinkled skin, hair and tooth loss, graying, fatigue accumulation and reduced recovery, decreased vision and hearing, decreased motor function, decreased muscle strength and activity, decreased sleep quality, and decreased bone mass. While aging itself is not considered a disease, declines in physical and physiological functions increase the risk of so-called geriatric diseases such as arteriosclerosis, abnormal glucose and lipid metabolism, neurodegeneration, osteoporosis, and cataracts. Furthermore, the decline in physical functions can lead to aging of mental functions such as memory and learning. Increasing the nicotinamide adenine dinucleotide (NAD) concentration is effective in preventing or improving aging associated with a decrease in NAD concentration.

[0015] (Sesamin Compounds) In the present invention, "sesamins" refers to compounds including sesamin and its analogs. Sesamin is a major lignan compound found in sesame. Sesamin analogs include episesamin and, for example, the dioxabicyclo[3.3.0]octane derivatives described in Japanese Patent Application Laid-Open No. 4-9331. As one or more types of sesamins, one or more of these compounds may be used alone or in combination. Specific examples of sesamins include sesamin, episesamin, sesaminol, episesaminol, sesamol, and sesamolin. These stereoisomers or racemates may be used alone or in mixtures. Furthermore, metabolites of sesamin compounds (e.g., those described in Japanese Patent Application Laid-Open No. 2001-139579) are also sesamin analogs included in the sesamins of the present invention, and can be used in the present invention, so long as they exhibit the effects of the present invention. In the present invention, sesamin and / or episesamin can be preferably used as one or more of the sesamins, with sesamin and episesamin being more preferred. When sesamin and episesamin are used, their ratio is not particularly limited, but for example, a weight ratio of sesamin:episesamin of 1:0.1 to 1:9 is preferred, 1:0.3 to 1:3 is more preferred, and 1:0.5 to 1:2 is even more preferred.

[0016] The sesamin compounds used in the present invention are not limited by their form or production method. For example, in the case of sesamin, sesamin (referred to as sesamin extract or purified product) extracted from sesame oil by known methods (e.g., the method described in Japanese Patent Application Laid-Open No. 4-9331) can be used. Alternatively, commercially available sesame oil (liquid) can be used as is. However, when sesame oil is used, the characteristic flavor of sesame oil can be perceived as sensorily undesirable. Therefore, it is preferable to use a tasteless and odorless sesamin extract (or purified sesamin product) extracted from sesame oil. Furthermore, when sesame oil is used, the sesamin content is low, and if a desired amount of sesamin is to be incorporated, the volume per unit dose of the formulated composition becomes too large, which can cause ingestion problems. In particular, when formulated for oral administration, the formulation (e.g., tablet, capsule) becomes too large, hindering ingestion. Therefore, from the viewpoint of requiring a small intake amount, it is preferable to use a sesamin extract (or purified sesamin product) from sesame oil. Sesamin compounds can also be obtained by synthesis. For example, sesamin and episesamin can be synthesized by the method of Beroza et al. (J. Am. Chem. Soc., 78, 1242 (1956)). Metabolites of sesamin and episesamin can be synthesized by the method of Urata et al. (Chem. Pharm. Bull. (Tokyo), 56 (11) 1611-2 (2008)).

[0017] Sesamin compounds are found in natural products and foods, have a wide dietary history, and are recognized for their high safety. With their guaranteed safety, sesamin compounds are ideal for continuous and long-term intake.

[0018] (Nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof) The composition of the present invention comprises one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof. NR and NMN are intermediate metabolic products of NAD. NR is converted to NMN by nicotinamide riboside kinase (NRK), and NAD ＋NR, NMN, and salts thereof are known compounds and can be produced by known production methods, or commercially available products can also be used.

[0019] Salts of NR and / or NMN can be pharmacologically acceptable salts, such as acid addition salts and base addition salts. Specific examples include metal salts (e.g., alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts, magnesium salts and barium salts), ammonium salts, salts with inorganic acids (e.g., salts with inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid and phosphoric acid), and salts with organic acids (e.g., salts with organic acids such as acetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid and p-toluenesulfonic acid).

[0020] As the salt of NR and / or NMN, salts that can be used in foods, beverages, pharmaceuticals, etc. are preferred, and examples thereof include chlorides; alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts and magnesium salts, etc. As the salt of NR, nicotinamide riboside chloride (chloride) is preferred.

[0021] (Composition containing one or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamins) The composition of the present invention contains one or more compounds selected from the group consisting of the nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamins. The composition of the present invention contains, as active ingredients, one or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamins. The composition of the present invention may be a composition for increasing nicotinamide adenine dinucleotide (NAD) levels. In the composition of the present invention, from the viewpoint of effectively enhancing the effect of increasing nicotinamide adenine dinucleotide (NAD) concentration, i.e., from the viewpoint of effectively enhancing the effect of improving, inhibiting a decrease in, maintaining, or improving NAD concentration, the molar ratio of one or more selected from the group consisting of NR, NMN, and salts thereof to sesamin-class compounds (one or more selected from the group consisting of NR, NMN, and salts thereof / sesamins) is preferably 1 to 100. Furthermore, the molar ratio of one or more selected from the group consisting of NR, NMN, and salts thereof / sesamins to sesamin-class compounds (one or more selected from the group consisting of NR, NMN, and salts thereof / sesamins) is more preferably 3 to 80, and even more preferably 5 to 50. Since the anti-aging effect is achieved by increasing the nicotinamide adenine dinucleotide (NAD) concentration, i.e., by enhancing the NAD concentration increasing effect, inhibiting the decrease, maintaining or improving the NAD concentration, it is preferable from the viewpoint of the anti-aging effect to set the molar ratio of NR, NMN or their salts to sesamin-class compounds within the above-mentioned specific range in the composition of the present invention. Note that, in this specification, when indicating the amount of NR, NMN or their salts, the value converted into the amount of nicotinamide riboside (NR) is used. The NR-equivalent weight of one or more selected from the group consisting of NR, NMN and their salts is the NR-equivalent value of the total weight of NR, NMN and their salts.

[0022] The total content of one or more sesamin compounds contained in the composition of the present invention is not particularly limited and can be set depending on the form, etc. The total content of sesamin compounds in the composition of the present invention is, for example, preferably 0.001 wt% or more, more preferably 0.01 wt% or more, even more preferably 0.05 wt% or more, and preferably 10 wt% or less, more preferably 5 wt% or less. In one embodiment, the total content of sesamin compounds in the composition is preferably 0.001 to 10 wt%, more preferably 0.01 to 5 wt%, even more preferably 0.05 to 5 wt%. When two or more sesamin compounds are contained, the total content is the total content of these compounds.

[0023] The total content of one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof contained in the composition of the present invention is not particularly limited and can be set depending on the form, etc. The total content of one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof in the composition of the present invention is, for example, preferably 0.001% by weight or more, more preferably 0.01% by weight or more, even more preferably 0.05% by weight or more, and preferably 95% by weight or less, more preferably 80% by weight or less. In one embodiment, the total content of one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof in the composition is preferably 0.001 to 95% by weight, more preferably 0.01 to 80% by weight, and even more preferably 0.05 to 70% by weight. When two or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof are contained, the total content is the total content of these compounds.

[0024] The composition of the present invention is capable of increasing nicotinamide adenine dinucleotide (NAD) concentration, enhancing, inhibiting a decrease in, maintaining or improving nicotinamide adenine dinucleotide (NAD) concentration, and enhancing, inhibiting a decrease in, maintaining or improving nicotinamide adenine dinucleotide (NAD) concentration that has decreased with age.

[0025] NAD in the body plays an important role in activating sirtuins and deacetylating downstream enzymes or transcription factors, thereby promoting the expression and synthesis of molecules involved in mitochondrial function and energy production. Therefore, improving, inhibiting a decrease, maintaining, or improving NAD concentration can improve, inhibit a decrease, maintain, or improve mitochondrial function. The composition of the present invention can improve, inhibit a decrease, maintain, or improve mitochondrial function. Furthermore, the composition of the present invention can improve, inhibit a decrease, maintain, or improve mitochondrial energy production capacity. This also allows the composition of the present invention to exhibit an anti-cellular aging effect.

[0026] In this specification, mitochondrial function and mitochondrial energy production capacity may be evaluated based on common knowledge in the technical field to which the present invention pertains, and the method for doing so is not particularly limited. For example, mitochondrial function can be evaluated by using an extracellular flux analyzer to continuously measure the oxygen consumption rate (hereinafter also referred to as "OCR") used by mitochondria during ATP synthesis in the cells being measured while adding an ATP synthase inhibitor (e.g., oligomycin and rotenone) and an uncoupler (e.g., carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)). Mitochondrial function can be evaluated, for example, by analyzing basal respiration, ATP production capacity, and maximum respiration, which are considered to be major indicators in the evaluation of mitochondrial function.

[0027] The composition of the present invention can be used to inhibit and / or delay aging, and is preferably used to inhibit and / or delay aging associated with a decrease in NAD concentration.

[0028] In one aspect, the composition of the present invention improves, inhibits a decrease, maintains, or improves NAD concentration, and is suitable for use in improving, inhibiting a decrease, maintaining, or improving NAD concentration that has decreased with age. In one aspect, the composition of the present invention is suitable for use in improving, inhibiting a decrease, maintaining, or improving NAD concentration that has decreased with age in middle-aged and elderly people. Middle-aged and elderly people include elderly people. Middle-aged and elderly people may be, for example, humans aged 40 years or older, and elderly people may be, for example, humans aged 60 years or older or 65 years or older. The NAD concentration of animals such as humans can be measured by a conventional method in the technical field to which the present invention belongs, and for example, Amplite (registered trademark) Colorimetric NAD / NADH Ratio Assay Kit (AAT Bioquest) or NAD ＋ It can be measured by measuring the intracellular NAD concentration using an NADH Quantification Colorimetric Kit (Biovision).

[0029] The compositions of the present invention can be used to treat conditions or diseases that can be prevented or improved by increasing, inhibiting a decrease, maintaining, or improving NAD concentration. Examples of such conditions or diseases include age-related declines in physical, physiological, and mental functions, specifically, the occurrence of skin aging symptoms (wrinkles, sagging, loss of skin firmness, etc.), dry skin due to aging (decreased skin moisture retention), skin spots, freckles, rough skin, decreased or increased secretion of hormones (growth hormone, thyroid hormone, adrenocortical hormone, sex hormones, prolactin, antidiuretic hormone, parathyroid hormone, melatonin, etc.), cell damage (brain cells, cardiac muscle cells, etc.) caused by reactive oxygen species, hair and tooth loss, decreased eyesight and hearing, decreased motor function, decreased bone mass, decreased physical strength, decreased memory, decreased learning ability, decreased immune function, and the occurrence of geriatric diseases. As used herein, "prevention" encompasses preventing the onset of a disease, delaying the onset of a disease, reducing the incidence, reducing the risk of onset, etc. Amelioration of a condition or disease includes causing a subject to recover from the condition or disease, alleviating the symptoms of the condition or disease, reversing the symptoms of the condition or disease, slowing or preventing the progression of the condition or disease, and the like.

[0030] The composition of the present invention can be used for both therapeutic (medical) and non-therapeutic (non-medical) purposes. Non-therapeutic does not include medical procedures, i.e., surgery, treatment, or diagnosis in humans. The composition of the present invention can be in the form of a food or beverage, a drug, a quasi-drug, a feed, or the like. The composition of the present invention may be a food or beverage, a drug, a quasi-drug, a feed, or the like that is used to increase, inhibit a decline, maintain, or improve nicotinamide adenine dinucleotide (NAD) concentration, or may be a material or preparation that is incorporated therein. The composition of the present invention may be a food or beverage, a drug, a quasi-drug, a feed, or the like that is used to increase, inhibit a decline, maintain, or improve mitochondrial function, or to increase, inhibit a decline, maintain, or improve mitochondrial energy production capacity, or may be a material or preparation that is incorporated therein. The composition of the present invention can be provided in the form of a preparation, for example, but is not limited to this form. The preparation can also be provided as a composition itself, or as a composition containing the preparation. The composition of the present invention may be either an oral composition or a parenteral composition, but is preferably an oral composition. The oral composition may be or may be contained in a food or drink, an oral drug, a quasi-drug, a feed, etc. The composition of the present invention is preferably a food or drink or an oral drug, more preferably a food or drink.

[0031] The composition of the present invention can contain at least one selected from the group consisting of NR, NMN, and their salts, and at least one sesamin-class compound, as well as any additives and ingredients, as long as the effects of the present invention are not impaired. These additives and ingredients can be selected depending on the form of the composition, and those that can generally be used in foods and beverages, pharmaceuticals, quasi-drugs, feed, etc. can be used. When the composition of the present invention is used as a food and beverage, pharmaceutical, quasi-drug, feed, etc., the manufacturing method thereof is not particularly limited, and it can be manufactured by a general method.

[0032] For example, when the composition of the present invention is used as a food or beverage, various foods and beverages can be prepared by blending at least one selected from the group consisting of NR, NMN, and their salts with at least one sesamin-class compound, as well as ingredients that can be used in foods and beverages (e.g., food ingredients, food additives used as needed, etc.). The foods and beverages are not particularly limited, and examples include general foods and beverages, health foods, health drinks, functional foods, foods for specified health uses, and foods and beverages for patients. The health foods, functional foods, foods for specified health uses, etc. can be used in various dosage forms, such as fine granules, tablets, granules, powders, capsules, chewable tablets, dry syrups, syrups, liquids, beverages, and liquid diets.

[0033] When the composition of the present invention is used as a pharmaceutical or quasi-drug, it can be formulated into various dosage forms by combining at least one selected from the group consisting of NR, NMN, and their salts with one or more sesamin-class compounds, as well as a pharmacologically acceptable carrier and additives as needed. Such carriers, additives, etc. may be any pharmacologically acceptable carriers that can be used in pharmaceuticals or quasi-drugs, and may include, for example, one or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants, etc. Pharmaceuticals or quasi-drugs can be administered orally or parenterally (e.g., transdermal, transmucosal, enteral, or by injection). When the composition of the present invention is used as a pharmaceutical or quasi-drug, it is preferably an oral pharmaceutical or quasi-drug. Dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewable tablets, etc. Pharmaceuticals may also be used for non-human animals.

[0034] When the composition of the present invention is used as a feed, at least one selected from the group consisting of NR, NMN, and their salts and one or more sesamin-class compounds may be blended into the feed. The feed also includes feed additives. Examples of the feed include livestock feed for cattle, pigs, chickens, sheep, horses, etc.; small animal feed for rabbits, rats, mice, etc.; and pet food for dogs, cats, small birds, etc.

[0035] The composition of the present invention is preferably an oral composition (a composition to be taken orally (administered orally)). The dosage (which can also be referred to as the intake amount) of the composition of the present invention is not particularly limited. The dosage of the composition of the present invention may be an amount that can achieve the effect of increasing, inhibiting a decrease in, maintaining, or improving nicotinamide adenine dinucleotide (NAD) concentration, and may be appropriately set depending on the dosage form, administration method, body weight of the subject, etc.

[0036] In one embodiment, when the composition of the present invention is orally administered to a human (adult), the total dosage of sesamin compounds is preferably 0.5 mg or more, more preferably 1 mg or more, even more preferably 3 mg or more, and preferably 200 mg or less, more preferably 100 mg or less, and even more preferably 80 mg or less per day per 60 kg body weight. In one embodiment, the total dosage of sesamin compounds is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg per day per 60 kg body weight to a human (adult). It is preferable to ingest or administer the above amount once or more times per day, for example, once or several times (e.g., 2 to 3 times) per day. In one embodiment, it is preferable to orally ingest or administer the above amount of sesamin compounds to a human. In one embodiment, the composition of the present invention can be used to ingest or administer the above amount of sesamin compounds per day per 60 kg body weight to a human. When two or more sesamin compounds are used, the above total dosage is the combined amount of these compounds. In one aspect, it is preferable that sesamin and / or episesamin be orally ingested or administered to a human (adult) at a total dosage of sesamin and episesamin of preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg per day per 60 kg body weight.

[0037] In one embodiment, when the composition of the present invention is orally ingested or administered to a human (adult), the total dose of one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, in NR equivalents per day per 60 kg body weight, is preferably 0.5 mg or more, more preferably 1 mg or more, even more preferably 3 mg or more, and preferably 20,000 mg or less, more preferably 10,000 mg or less, and even more preferably 8,000 mg or less. In one embodiment, the total dose of one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, in NR equivalents per day per 60 kg body weight, for a human (adult), is preferably 0.5 to 20,000 mg, more preferably 1 to 10,000 mg, and even more preferably 3 to 8,000 mg. It is preferable to ingest or administer the above amount once or more times a day, for example, once or divided into several times (e.g., 2 to 3 times) a day. In one embodiment, it is preferable to orally ingest or administer to a human the above-mentioned amount of one or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof. In one embodiment, the composition of the present invention can be used to orally ingest or administer to a human the above-mentioned amount of one or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof per 60 kg of body weight per day. When two or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof are used, the above-mentioned total dosage is the sum of these amounts.

[0038] The composition of the present invention is preferably one that is ingested or administered continuously. It is expected that the above-mentioned effects of sesamin-class compounds will be enhanced by their continuous ingestion or administration. Furthermore, it is expected that the above-mentioned effects of compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof will be enhanced by their continuous ingestion or administration. In one embodiment, the composition of the present invention is preferably ingested or administered continuously for at least one week, more preferably at least four weeks, even more preferably at least eight weeks, and particularly preferably at least 12 weeks.

[0039] The composition of the present invention may be labeled with a function exhibited by improving, inhibiting a decrease, maintaining, or improving nicotinamide adenine dinucleotide (NAD) concentration. Such a label may be labeled with one or more functions selected from the group consisting of "improving, inhibiting a decrease, or maintaining mitochondrial function," "improving, inhibiting a decrease, or maintaining mitochondrial energy production capacity," "inhibiting and / or delaying aging due to a decrease in NAD concentration," "inhibiting and / or delaying cellular aging," and "inhibiting aging." In one aspect of the present invention, the composition of the present invention is preferably a food or beverage labeled with the above-mentioned label. The above-mentioned label may also be a label indicating that the composition is used to obtain the above-mentioned function.

[0040] The subject (which can also be referred to as the administration subject) to which the composition of the present invention is ingested or administered is not particularly limited, and can be humans or non-human animals. Examples of non-human animals include industrial animals, pets, and laboratory animals. Specifically, industrial animals refer to animals that need to be raised industrially, such as livestock such as cows, horses, pigs, goats, and sheep, poultry such as chickens, ducks, quails, turkeys, and ostriches, and fish such as yellowtail, yellowtail, red sea bream, horse mackerel, carp, rainbow trout, and eels. Pets refer to so-called pets and companion animals such as dogs, cats, marmosets, small birds, and hamsters, while laboratory animals refer to animals used in research in fields such as medicine, biology, agriculture, and pharmacy, such as mice, rats, guinea pigs, beagles, minipigs, rhesus monkeys, and cynomolgus monkeys.

[0041] The subject (which can also be referred to as the administration subject) to whom the composition of the present invention is ingested or administered is preferably a human or non-human mammal, more preferably a human. In one embodiment, the administration subject includes a subject who requires or desires to improve, inhibit decline, maintain, or improve nicotine adenine dinucleotide (NAD) levels. Examples of such subjects include middle-aged and elderly subjects, subjects who require or desire to improve, inhibit decline, maintain, or improve mitochondrial function, subjects who require or desire to improve, inhibit decline, maintain, or improve mitochondrial energy production capacity, and subjects who require or desire to inhibit and / or delay aging due to a decrease in NAD levels. Middle-aged and elderly subjects may be, for example, humans aged 40 years or older. In one embodiment, among middle-aged and elderly subjects, elderly subjects are preferred. Elderly subjects 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 in healthy individuals, for example, for the prevention of symptoms or diseases that can be prevented or improved by improving, inhibiting decline, maintaining, or improving nicotinamide adenine dinucleotide (NAD) levels.

[0042] The present invention also encompasses the following methods: A method for increasing nicotinamide adenine dinucleotide (NAD) levels by administering one or more members selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamins; A method for increasing, inhibiting a decrease, maintaining, or improving nicotinamide adenine dinucleotide (NAD) levels by administering one or more members selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamins; A method for increasing, inhibiting a decrease, maintaining, or improving nicotinamide adenine dinucleotide (NAD) levels that have decreased with age by administering one or more members selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamins.

[0043] The present invention also encompasses the following uses: Use of one or more members selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamins to increase nicotinamide adenine dinucleotide (NAD) levels; Use of one or more members selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamins to increase, inhibit decline, maintain, or improve nicotinamide adenine dinucleotide (NAD) levels; Use of one or more members selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamins to increase, inhibit decline, maintain, or improve nicotinamide adenine dinucleotide (NAD) levels that have declined with age. The above methods and uses may be therapeutic or non-therapeutic. Administration of one or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, together with one or more sesamin-class compounds, enables the enhancement, suppression of decline, maintenance, or improvement of nicotinamide adenine dinucleotide (NAD) levels, thereby enabling the enhancement, suppression of decline, maintenance, or improvement of mitochondrial function, the enhancement, suppression of decline, maintenance, or improvement of mitochondrial energy production capacity, and the suppression and / or delay of aging due to a decrease in NAD levels.

[0044] In the above-described methods and uses, the compound selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts, the sesamins, and their preferred embodiments are the same as those in the composition of the present invention described above. As the one or more sesamins, one or more sesamin compounds may be used. Furthermore, as the compound selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts, one or more such compounds may be used. In the above-described methods and uses, it is preferable to administer (ingest) to a subject a composition containing one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts, and one or more sesamins, at least once a day, for example, once to several times a day (e.g., 2-3 times a day). In the above-described methods and uses, it is preferable to orally administer (ingest) the composition of the present invention. The above-described uses are preferably used in humans or non-human mammals, more preferably in humans.

[0045] In the above-mentioned methods and uses, one or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamin compounds may be used in an amount (which may also be referred to as an effective amount) sufficient to achieve the desired effect (i.e., increasing nicotinamide adenine dinucleotide (NAD) concentration, i.e., increasing, inhibiting, maintaining, or improving NAD concentration, thereby improving, inhibiting, maintaining, or improving mitochondrial function, improving, inhibiting, maintaining, or improving mitochondrial energy production capacity, and / or inhibiting and / or delaying aging due to a decrease in NAD concentration). The preferred dosage and administration targets of one or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and one or more sesamin compounds are the same as those for the composition of the present invention described above. One or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more sesamin-class compounds may be administered as they are, or may be administered as a composition containing them. For example, the composition of the present invention described above may be used.

[0046] In the above-mentioned use, a composition containing one or more types of sesamin compounds and a composition containing one or more types selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and their salts are prepared separately, and the two are taken at approximately the same time, or after taking one composition while the effect of the other composition is still sustained, thereby achieving the enhanced effect of the combined use of one or more types selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and their salts with one or more types of sesamin compounds intended by the present invention (elevating NAD concentration, i.e., improving, inhibiting a decline, maintaining, or improving NAD concentration, thereby improving, inhibiting a decline, maintaining, or improving mitochondrial function, improving, inhibiting a decline, maintaining, or improving mitochondrial energy production capacity, and / or inhibiting and / or delaying aging due to a decrease in NAD concentration). Therefore, kits containing a composition containing one or more types of sesamin compounds and a composition containing one or more types selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof are also included in the scope of the compositions of the present invention.

[0047] The present invention also encompasses the use of one or more members selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more sesamin derivatives, for the manufacture of the composition of the present invention.

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

[0049] In the examples and comparative examples, a mixture of sesamin and episesamin (sesamin:episesamin (weight ratio) = 1:1) was used as the sesamin / episesamin mixture (SE).

[0050] Comparative Examples 1 to 3, Example 1: Intracellular NAD by Sesamin / Episesamin Mixture (SE) and Nicotinamide Riboside (NR) ＋ Concentration (intracellular NAD concentration) evaluation test > Intracellular NAD ＋ To examine the effect on concentration, 0.5 × 10 ４Hepa1-6 cells were seeded in a 96-well plate at 1000 cells / well and incubated at 37°C under CO ２ The cells were cultured for 96 hours in DMEM medium (Nacalai Tesque, Inc., containing 10% FBS) under conditions of 5% FBS. After 96 hours of culture, the medium in each well was replaced with DMEM medium (containing 1% albumin and no FBS (Comparative Example 1)) containing no sesamin-episesamin mixture (SE) or nicotinamide riboside (NR chloride (Carbosynth Limited)), DMEM medium (containing 1% albumin and no FBS (Comparative Example 2)) containing 0.3 μM SE, DMEM medium (containing 1% albumin and no FBS (Comparative Example 3)) containing 30 μM NR, or DMEM medium (containing 1% albumin and no FBS (Example 1)) containing 0.3 μM SE and 30 μM NR, and the cells were cultured for an additional 24 hours. Thereafter, the supplemented medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque, Inc.). Lysis Buffer (Amplite (registered trademark) Colorimetric NAD / NADH Ratio Assay Kit, AAT Bioquest) was added to recover the cell extract. Then, according to the kit manual, the intracellular NAD ＋ The concentration of intracellular NAD ＋ The protein concentration of the cell extract was measured (Pierce® BCA Protein Assay Kit, Thermo Scientific) and the concentration was calculated as a value per protein concentration. Significance testing was performed using an unpaired t-test (significance level: p<0.05, relative to the control group). The results (average of N=3) are shown in Figure 1 (*: p<0.05).

[0051] As shown in Figure 1, intracellular NAD ＋The concentration increased by 2.3% in the SE 0.3 μM group in Comparative Example 2 and 3.1% in the NR 30 μM group in Comparative Example 3 compared to Comparative Example 1 (medium not containing SE and NR). On the other hand, an increase of 14.6% was observed in the combination group of SE 0.3 μM and NR 30 μM in Example 1, which was significantly greater than the simple sum (5.4%) of the increase rate due to the SE 0.3 μM treatment in Comparative Example 2 and the increase rate due to the NR 30 μM treatment in Comparative Example 3. From the above, it was found that intracellular NAD ＋ A synergistic effect of increasing the concentration was confirmed.

[0052] Comparative Examples 4 to 6, Example 2: Intracellular NAD by Sesamin / Episesamin Mixture (SE) and Nicotinamide Riboside (NR) ＋ Concentration (intracellular NAD concentration) evaluation test > Intracellular NAD ＋ To examine the effect on concentration, 1.0 × 10 ４ Hepa1-6 cells were seeded in a 96-well plate at 1000 cells / well and incubated at 37°C under CO ２ The cells were cultured for 48 hours in DMEM medium (Nacalai Tesque, Inc., containing 10% FBS) under conditions of 5% (5%). After 48 hours of culture, the medium in each well was replaced with DMEM medium (containing 1% albumin and no FBS (Comparative Example 4)) containing no sesamin-episesamin mixture (SE) or nicotinamide riboside (NR, chloride), DMEM medium containing 10 μM SE (containing 1% albumin and no FBS (Comparative Example 5)), DMEM medium containing 10 μM NR (containing 1% albumin and no FBS (Comparative Example 6)), or DMEM medium containing 10 μM SE and 10 μM NR (containing 1% albumin and no FBS (Example 2)), and the cells were cultured for an additional 24 hours. Thereafter, the supplemented medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque, Inc.). Lysis Buffer (Amplite (registered trademark) Colorimetric NAD / NADH Ratio Assay Kit, AAT Bioquest) was added to recover the cell extract. Then, according to the kit manual, the intracellular NAD ＋ The concentration of intracellular NAD ＋The protein concentration of the cell extract was measured (Pierce (registered trademark) BCA Protein Assay Kit, Thermo Scientific) and the concentration was calculated as a value per protein concentration. The results (average of N = 3) are shown in Figure 2 (*: p < 0.05).

[0053] As shown in Figure 2, intracellular NAD ＋ The concentration increased by 1.5% in the SE 10 μM group of Comparative Example 5 and 11.6% in the NR 10 μM group of Comparative Example 6 compared to Comparative Example 4 (medium not containing SE and NR). On the other hand, an increase of 15.7% was observed in the combination group of SE 10 μM and NR 10 μM in Example 2, which was clearly greater than the simple sum (13.1%) of the increase rate due to the SE 10 μM treatment of Comparative Example 5 and the increase rate due to the NR 10 μM treatment of Comparative Example 6. From the above, it can be seen that intracellular NAD ＋ A synergistic effect of increasing the concentration was confirmed.

[0054] Comparative Examples 7 to 9, Examples 3 and 4: Intracellular NAD by Sesamin / Episesamin Mixture (SE) and Nicotinamide Riboside (NR) ＋ Concentration (intracellular NAD concentration) evaluation test > Intracellular NAD ＋ To examine the effect on concentration, 1.0 × 10 ４ Hepa1-6 cells were seeded in a 96-well plate at 1000 cells / well and incubated at 37°C under CO ２The cells were cultured for 48 hours in DMEM medium (Nacalai Tesque, Inc., containing 10% FBS) under conditions of 5% (5%). After 48 hours of culture, the medium in each well was replaced with DMEM medium (containing 1% albumin and no FBS (Comparative Example 7)) containing no sesamin-episesamin mixture (SE) or nicotinamide riboside (NR, chloride), DMEM medium (containing 1% albumin and no FBS (Comparative Example 8)) containing 10 μM NR, DMEM medium (containing 1% albumin and no FBS (Comparative Example 9)) containing 3 μM SE and 10 μM NR, DMEM medium (containing 1% albumin and no FBS (Example 3)), or DMEM medium (containing 1% albumin and no FBS (Example 4)) containing 3 μM SE and 30 μM NR, and the cells were cultured for an additional 24 hours. Thereafter, the supplemented medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque, Inc.). Lysis Buffer (Amplite (registered trademark) Colorimetric NAD / NADH Ratio Assay Kit, AAT Bioquest) was added to recover the cell extract. Then, according to the kit manual, the intracellular NAD ＋ The concentration of intracellular NAD ＋ The protein concentration of the cell extract was measured (Pierce (registered trademark) BCA Protein Assay Kit, Thermo Scientific) and the concentration was calculated as a value per protein concentration. The results (average of N = 3) are shown in Figure 3 (*: p < 0.05).

[0055] As shown in Figure 3, intracellular NAD ＋In terms of concentration, an increase of 11.6% was observed in the NR 10 μM group of Comparative Example 8 and a 15.5% increase was observed in the NR 30 μM group of Comparative Example 9 compared to Comparative Example 7 (medium not containing SE and NR). On the other hand, an increase of 17.5% was observed in the combination group of SE 3 μM and NR 10 μM in Example 3, and an increase of 21.8% was observed in the combination group of SE 3 μM and NR 30 μM in Example 4. Here, although there are no test examples treated with DEME medium containing SE 3 μM, an increase in NAD concentration of 2.3% was observed in the SE 0.3 μM group of Comparative Example 2, and an increase in NAD concentration of 1.5% was observed in the SE 10 μM group of Comparative Example 5. Therefore, it is inferred that the NAD concentration will increase at a rate equivalent to these in the SE 3 μM group. Thus, when the value obtained by simply adding the increase in NAD concentration (2.3 to 1.5%) that is thought to be obtained by 3 μM SE to the increase in NAD concentration in Comparative Example 8 or Comparative Example 9 is compared with the increase in NAD concentration in Examples 3 and 4, it is found that the increase in NAD concentration in Examples 3 and 4 is clearly greater. From the above, it can be seen that the increase in intracellular NAD concentration by treatment with a combination of SE and NR at a molar ratio (SE:NR) of 1:3.3 or 1:10 is ＋ A synergistic effect of increasing the concentration was confirmed.

[0056] Comparative Examples 10 to 12, Example 5: Intracellular NAD by Sesamin / Episesamin Mixture (SE) and Nicotinamide Riboside (NR) ＋ Concentration (intracellular NAD concentration) evaluation test > Intracellular NAD ＋ To examine the effect on concentration, 1.5 × 10 ４ HepG2 cells were seeded in a 96-well plate at 1000 cells / well and incubated at 37°C under CO ２The cells were cultured for 96 hours in DMEM medium (Nacalai Tesque, Inc., containing 10% FBS) under conditions of 5% (5%). After 96 hours of culture, the medium in each well was replaced with DMEM medium (containing 1% albumin and no FBS (Comparative Example 10)) containing no sesamin-episesamin mixture (SE) or nicotinamide riboside (NR, chloride), DMEM medium (containing 1% albumin and no FBS (Comparative Example 11)) containing 0.3 μM SE, DMEM medium (containing 1% albumin and no FBS (Comparative Example 12)) containing 10 μM NR, or DMEM medium (containing 1% albumin and no FBS (Example 5)) containing 0.3 μM SE and 10 μM NR, and the cells were cultured for an additional 24 hours. Thereafter, the supplemented medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque, Inc.). Lysis Buffer (Amplite (registered trademark) Colorimetric NAD / NADH Ratio Assay Kit, AAT Bioquest) was added to recover the cell extract. Then, according to the kit manual, the intracellular NAD ＋ The concentration of intracellular NAD ＋ The protein concentration of the cell extract was measured (Pierce (registered trademark) BCA Protein Assay Kit, Thermo Scientific) and the concentration was calculated as a value per protein concentration.

[0057] Intracellular NAD ＋ In comparison with Comparative Example 10 (Cont, medium not containing SE and NR), a 5.0% increase was observed in the SE 0.3 μM group of Comparative Example 11, and no increase was observed in the NR 10 μM group of Comparative Example 12. On the other hand, an 8.0% increase was observed in the combination group of SE 0.3 μM and NR 10 μM in Example 5, which was clearly greater than the simple sum of the increase rate due to SE 0.3 μM treatment and the increase rate due to NR 10 μM treatment (5.0%). From the above, it can be seen that intracellular NAD ＋ A synergistic effect of increasing the concentration was confirmed.

[0058] From the above, it is believed that a composition containing a mixture of sesamin and episesamin and nicotinamide riboside (NR) can reduce intracellular NAD＋ It became clear that the concentration-increasing action exhibited a synergistic effect.

[0059] Comparative Examples 13 to 16, Examples 6 and 7: Intracellular NAD by Sesamin / Episesamin Mixture (SE) and Nicotinamide Mononucleotide (NMN) ＋ Concentration (intracellular NAD concentration) evaluation test > Intracellular NAD ＋ To examine the effect on concentration, 2.5 × 10 ４ HepG2 cells were seeded in a 96-well plate at 1000 cells / well and incubated at 37°C under CO ２ The cells were cultured for 48 hours in DMEM medium (Nacalai Tesque, Inc., containing 10% FBS) under the condition of (5%). After 48 hours of culture, the medium in each well was replaced with DMEM medium (containing 1% albumin and no FBS (Comparative Example 13)) containing no sesamin-episesamin mixture (SE) or nicotinamide mononucleotide (NMN), DMEM medium containing 10 μM SE (containing 1% albumin and no FBS (Comparative Example 14)), DMEM medium containing 30 μM NMN (containing 1% albumin and no FBS (Comparative Example 15)), DMEM medium containing 100 μM NMN (containing 1% albumin and no FBS (Comparative Example 16)), DMEM medium containing 10 μM SE and 30 μM NMN (containing 1% albumin and no FBS (Example 6)), or DMEM medium containing 10 μM SE and 100 μM NMN (containing 1% albumin and no FBS (Example 7)), and the cells were cultured for a further 24 hours. Thereafter, the supplemented medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque, Inc.). Lysis Buffer (Amplite (registered trademark) Colorimetric NAD / NADH Ratio Assay Kit, AAT Bioquest) was added to recover the cell extract. Then, according to the kit manual, the intracellular NAD ＋ The concentration of intracellular NAD ＋ The protein concentration of the cell extract was measured (Pierce (registered trademark) BCA Protein Assay Kit, Thermo Scientific) and the concentration was calculated as a value per protein concentration. The results (average of N = 3) are shown in Figure 4 (*: p < 0.05).

[0060] As shown in Figure 4, intracellular NAD ＋ The concentration was 14.2% in the SE 10 μM group of Comparative Example 14, 18.9% in the NMN 30 μM group of Comparative Example 15, and 21.3% in the NMN 100 μM group of Comparative Example 16, compared to Comparative Example 13 (medium not containing SE and NR). On the other hand, a 38.0% increase was observed in the combination group of SE 10 μM and NMN 30 μM in Example 6, which was clearly greater than the simple sum of the increase rate due to SE 10 μM treatment in Comparative Example 14 and the increase rate due to NMN 30 μM treatment in Comparative Example 15 (33.1%). In addition, a 74.6% increase was observed in the combination group of SE 10 μM and NMN 100 μM in Example 7, which was clearly greater than the simple sum of the increase rate due to SE 10 μM treatment in Comparative Example 14 and the increase rate due to NMN 100 μM treatment in Comparative Example 16 (35.5%). From the above, it was found that intracellular NAD by treatment with a combination of SE and NMN at a molar ratio (SE:NMN) of 1:3 or 1:10 ＋ A synergistic effect of increasing the concentration was confirmed.

[0061] From the above, it is believed that a composition containing a combination of NMN and / or salts thereof, which are known as NAD intermediate metabolites, and one or more types of sesamins (preferably a sesamin / episesamin mixture) can increase intracellular NAD, just like a composition containing a sesamin / episesamin mixture and NR. ＋ It became clear that the concentration-increasing action exhibited a synergistic effect.

Claims

DEPCT661. The composition which contains, as the active ingredient: at least one of the groups containing nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts; and at least one sesamin compound.

2. The composition according to claim 1, in which at least one sesamin compound includes at least one of sesamin or episesamin.

3. The composition according to claim 1 or 2, in which the molar ratio of at least one of the groups containing NR, NMN, and their salts.

1. The composition under any of the claims 1-3, in which at least one sesamin compound is present in a total amount of 0.001-10% by weight.

5. The composition under any of the claims 1-4, in which the composition improves, maintains, or enhances the nicotinamide adenine dinucleotide (NAD) concentration or reduces the degradation of the NAD concentration. 6.

7. Any one of Claims 1 through 5, where the component improves, maintains, or enhances mitochondrial function or reduces deterioration in mitochondrial function.

8. Any one of Claims 1 through 6, where the component improves, maintains, or enhances mitochondrial energy production or reduces deterioration in mitochondrial energy production.

9. Any one of Claims 1 through 7, where the component is used to inhibit and / or delay aging associated with decreased NAD concentrations.

10. Any one of Claims 1 through 8, where the component is an anti-aging component.

11. Any one of Claims 1 through 9, where the component is an orally administered component.

12. Any one of Claims 1 through 10, where the component is a food or beverage.

13. A method of increasing the concentration of nicotinamide adenine dinucleotide (NAD), which includes action of at least one of the following: "inhibition and / or delay of aging associated with a decrease in NAD concentration" or "inhibition and / or delay of cellular aging processes".

14. A method of improving, maintaining, or enhancing the concentration of nicotinamide adenine dinucleotide (NAD), or decreasing the concentration of NAD, which includes action of at least one of the following: "inhibition and / or delay of cellular aging processes".The use of at least one selected group of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts, and at least one sesamin compound, for increasing the concentration of nicotinamide adenine dinucleotide (NAD).

16. The use of at least one selected group of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts, and at least one sesamin compound, for improving, maintaining, or enhancing the concentration of nicotinamide adenine dinucleotide (NAD) or reducing the degradation of NAD concentration.

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