Compositions containing nr and / or nmn in combination with sesaminoids

Abstract

The present application aims to provide a composition having an effect of increasing NAD concentration. The present application relates to a composition characterized by containing one or more selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof and one or more sesamin as an effective ingredient.

Description

Technical Field

[0001] This invention relates to a composition containing one or more selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and their salts, and sesamin. Background Technology

[0002] In recent years, extending healthy life expectancy has become a key issue in countries with high rates of aging. One contributing factor to the shortening of healthy life expectancy is the decline in nicotinamide adenine dinucleotide (NAD) levels in the body, which occurs with age. + Decreased productivity and decreased bodily functions, etc.

[0003] Here, nicotinamide adenine dinucleotide (NAD) + (Hereinafter referred to as NAD) is a coenzyme that mediates various redox reactions in the body. It is known that NAD levels decrease during aging, causing defects in cell nuclear and mitochondrial function, and leading to various age-related pathologies. For example, Non-Patent Literature 1 suggests that aging or age-related diseases are linked to intracellular nicotinamide adenine dinucleotide (NAD). + The decrease in NAD levels, and as a result of NAD + The activity of Sirtuin, a longevity gene and a long-lived enzyme dependent on deacetylation, is reduced. Furthermore, recent reports have indicated that it can be linked to NAD+ deacetylation. + Increased levels activate Sirtuin, resulting in anti-aging effects (Non-Patent Literature 2). Therefore, research is underway on the effects of NAD+ on aging-related NAD+. + It is effective in reducing, preventing or improving [the condition], and can be applied to the exploration of ingredients in pharmaceuticals, specific health foods, functional foods, etc.

[0004] For example, Non-Patent Literature 3 discloses that nicotinamide riboside (NR), as a precursor to NAD, induces a protein response in mitochondrial expansion and the synthesis of anti-proliferative proteins, thereby activating muscle stem cells (MuSCs) in aged mice. Furthermore, it discloses that NR prevents MuSC aging in a mouse model of muscular dystrophy, delays the aging of neural stem cells (SCs), and extends the lifespan of mice with melanocyte SCs.

[0005] Furthermore, Non-Patent Literature 4 shows nicotinamide ribose (NR) as NAD. + Pre-vitamins are widely used, and through a single oral administration of NR, human blood NAD+ levels are increased. + Increased concentration-dose dependence. Furthermore, Non-Patent Literature 5 shows that NMN activates Sirtuin, specifically demonstrating administration as the primary natural NAD in conventional wild-type mice. +Nicotinamide mononucleotide (NMN), an intermediate (also known as an intermediate metabolite), was administered for 12 months. NMN effectively alleviated the physiological decline associated with aging in mice without significant toxicity, demonstrating the great potential of NMN as an effective anti-aging intervention in humans.

[0006] On the other hand, there has been no indication or public statement regarding the effect of sesamin and / or episialin on increasing nicotinamide adenine dinucleotide (NAD) in the body.

[0007] Non-patent literature

[0008] Non-patent literature 1: Imai, S. & Guarente, L. (2014) Trends Cell Biol., 24, 464-471. "NAD+ and sirtuins in aging and disease"

[0009] Non-patent literature 2: Yoshida M, Satoh A, Lin JB, Mills KF, Sasaki Y, Rensing N, WongM, Apte RS, Imai SI., Cell Metab. (2019) 30(2): 329-342.e5. "Extracellular Vesicle-Contained eNAMPT Delays Aging and Extends Lifespan in Mice"

[0010] Non-patent literature 3: Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., D'Amico, D., Ropelle, ER, Lutolf, MP, A Ebersold, R., Schoonjans, K., Menzies, KJ, & Auwerx, J. (2016) Science, 352, 1436-1443. “NAD+repletion improves mitochondrial and stemcell function and enhances life span in mice”

[0011] Non-patent literature 4: Samuel AJ 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"

[0012] Non-patent literature 5: Mills, KF, Yoshida, S., Stein, LR, Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, ME, Apte, RS, Uchida, K., Yoshino, J., & Imai, SI (2016) Cell Metab., 24, 795-806. "Long-Term Administration of NicotinamideMononucleotide Mitigates Age-Associated Physiological Decline in Mice” Summary of the Invention

[0013] The purpose of this invention is to provide a composition that increases NAD concentration.

[0014] In order to solve the above-mentioned problems, the inventors conducted in-depth research and found that sesamin has the effect of increasing nicotinamide adenine dinucleotide (NAD). Furthermore, a composition containing sesamin and at least one of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and their salts can effectively increase nicotinamide adenine dinucleotide (NAD).

[0015] This invention relates to the following compositions.

[0016] [1] A composition characterized in that it contains one or more sesamins selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN) and their salts as active ingredients.

[0017] [2] The composition according to [1] above is characterized in that one or more sesamins are sesamin and / or episialin.

[0018] [3] The composition according to [1] or [2] above is characterized in that the molar ratio of one or more selected from NR, NMN and their salts to sesamin is 1 to 100.

[0019] [4] The composition according to any one of [1] to [3] above is characterized in that the total content of the one or more sesamins is 0.001 to 10% by weight.

[0020] [5] The composition according to any one of [1] to [4] above is characterized in that it increases the concentration of nicotinamide adenine dinucleotide, i.e., the NAD concentration, inhibits its decrease, maintains or improves the NAD concentration.

[0021] [6] The composition according to any one of [1] to [5] above is characterized in that it improves mitochondrial function, inhibits its decline, maintains or improves mitochondrial function.

[0022] [7] The composition according to any one of [1] to [6] above is characterized in that it can increase, inhibit, maintain or improve the energy production capacity of mitochondria.

[0023] [8] The composition according to any one of [1] to [7] above is characterized in that it is used to inhibit and / or delay aging accompanied by a decrease in NAD concentration.

[0024] [9] The composition according to any one of [1] to [8] above is characterized in that it is an anti-aging composition.

[0025]

[10] The composition according to any one of [1] to [9] above is characterized in that it is an oral composition.

[0026]

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

[10] above is characterized in that it is a food or beverage.

[0027]

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

[11] above is characterized by being labeled with “inhibition and / or delay of aging accompanied by a decrease in NAD concentration” and / or “inhibition and / or delay of cellular aging”.

[0028]

[13] A method for increasing the concentration of nicotinamide adenine dinucleotide, i.e., NAD concentration, characterized in that one or more of nicotinamide ribose (NR), nicotinamide mononucleotide (NMN) and their salts, and one or more sesamins are used.

[0029]

[14] A method for increasing, decreasing, inhibiting, maintaining or improving the concentration of nicotinamide adenine dinucleotide, i.e., NAD, characterized in that one or more of nicotinamide ribose, i.e. NR, nicotinamide mononucleotide, i.e. NMN and their salts, and one or more of sesamins are used.

[0030]

[15] An application characterized in that one or more of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and their salts, and one or more sesamins are used to increase the concentration of nicotinamide adenine dinucleotide (NAD).

[0031]

[16] An application characterized in that one or more of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and their salts, and one or more sesamins are used to increase, decrease, inhibit, maintain or improve the concentration of nicotinamide adenine dinucleotide (NAD).

[0032] According to the present invention, a composition having the effect of increasing the concentration of nicotinamide adenine dinucleotide (NAD) can be provided. Attached Figure Description

[0033] Figure 1 A graph showing the effect of a composition containing a mixture of sesamin and epissamin (SE) (sessamin: epissamin (weight ratio = 1:1)) and NR at a molar ratio of 1:100 on the increase of intracellular NAD concentration, SE or NR.

[0034] Figure 2 A graph showing the effect of a composition containing a mixture of sesamin and episialin (SE) (sessamin: episialin (weight ratio = 1:1)) and NR in a 1:1 molar ratio, on the increase in intracellular NAD concentration of SE or NR.

[0035] Figure 3 A graph showing the effect of a composition containing a mixture of sesamin and episialin (SE) (sessamin:episialin (weight ratio = 1:1)) and NR in a molar ratio of 1:3.3 or 1:10 on the increase of intracellular NAD concentration.

[0036] Figure 4 A graph showing the effect of increasing intracellular NAD concentration on compositions containing a mixture of sesamin and episagein (SE) (sessamin: episagein (weight ratio = 1:1)) and NMN in a molar ratio of 1:3 or 1:10, or on SE or NMN. Detailed Implementation

[0037] The composition of the present invention contains one or more sesamins.

[0038] Sesamin derivatives have the effect of increasing the concentration of nicotinamide adenine dinucleotide (NAD). They can increase, decrease, inhibit, maintain, or improve intracellular NAD concentration, thus increasing NAD concentration, inhibiting its decrease, maintaining it, or improving it. The increase in NAD concentration is due to the rise in the amount of NAD. Note that NAD concentration refers to the intracellular NAD concentration.

[0039] Sesamin derivatives have the effect of increasing nicotinamide adenine dinucleotide (NAD) concentration. By increasing, decreasing, inhibiting, maintaining, or improving NAD concentration, they are expected to help prevent or improve aging associated with declining NAD levels. Aging is understood as the decline of bodily, physiological, and mental functions. Based on the physical changes of aging reaching maturity, starting around age 40, we can see wrinkles, hair or tooth loss, graying hair, accumulated fatigue or decreased recovery ability, decreased vision or hearing, decreased motor function, decreased muscle strength or activity level, decreased sleep quality, and decreased bone mass. Although aging itself is not a disease, the decline in bodily and physiological functions increases the risk of so-called age-related diseases such as arteriosclerosis, abnormal glucose and lipid metabolism, nerve degeneration, osteoporosis, and cataracts. Furthermore, with the decline in bodily functions, mental functions such as memory and learning also decline. Increasing nicotinamide adenine dinucleotide (NAD) concentration is effective in preventing or improving aging associated with declining NAD levels.

[0040] (Sesanoin)

[0041] In this invention, sesaminoids are a general term encompassing compounds including sesamin and its analogues. Sesamin is one of the main lignan compounds contained in sesame. Examples of sesamin analogues, besides episialin, include, for example, the dioxabicyclo[3.3.0]octane derivative described in Japanese Patent Application Publication No. 4-9331. One or more sesaminoids may be used alone or in combination. Specific examples of sesaminoids include sesamin, episialin, sesaminol, episialinol, sesaminol, sesamolinin, etc., and these stereoisomers or racemates may be used alone or in combination. Furthermore, metabolites of sesaminoids (e.g., described in Japanese Patent Application Publication No. 2001-139579), as long as they exhibit the effects of this invention and are sesamin analogues included in the sesaminoids of this invention, may be used in this invention. In this invention, sesamin and / or episialin are preferably used as one or more sesaminoids, and sesamin and episialin are more preferably used. When using sesamin and episaflavin, their ratio is not particularly limited. For example, the ratio of sesamin to episaflavin (by weight) 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.

[0042] The sesamin used in this invention is not limited by its form or manufacturing method. For example, in the case of sesamin, sesamin extracted from sesame oil by a known method (e.g., the method described in Japanese Patent Application Publication No. 4-9331) can be used (referred to as sesamin extract or refined product). Alternatively, commercially available sesame oil (liquid) can be used directly. However, when using sesame oil, since the characteristic flavor of sesame oil is sometimes not sensorily satisfactory, it is preferable to use a tasteless and odorless sesamin extract (or sesamin refined product) extracted from sesame oil. Furthermore, when using sesame oil, due to its low sesamin content, if a preferred amount of sesamin is desired, the volume of each unit dosage of the formulation becomes too large, which can sometimes cause inconvenience during ingestion. In particular, when formulated for oral administration, the dosage form (tablets, capsules, etc.) becomes too large, creating obstacles during ingestion. Therefore, from the viewpoint that the intake amount can be small, it is preferable to use a sesamin extract (or sesamin refined product) from sesame oil. Sesamin can also be obtained through synthesis. As a method, for example, sesamin and episaflavin can be synthesized by the method of Beroza et al. (J. Am. Chem. Soc., 78, 1242 (1956)). Metabolites of sesamin and episaflavin can be synthesized by the method of Urata et al. (Chem. Pharm. Bull. (Tokyo), 56 (11) 1611-2 (2008)).

[0043] Sesaminoids are found in natural substances and food products, and are compounds with extensive experience in consumption and proven high safety. Given their guaranteed safety, sesaminoids are suitable for continuous and long-term consumption.

[0044] (Nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and their salts)

[0045] The compositions of the present invention contain one or more selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts.

[0046] NR and NMN are intermediate metabolites of NAD. It is known that NR is converted to NMN via nicotinamide ribokinase (NRK), which is then used to synthesize NAD. + NR, NMN, and their salts are known compounds that can be manufactured using known methods, or commercially available products can be used.

[0047] As salts of NR and / or NMN, pharmacologically permissible salts may be used, such as acid-added salts and base-added salts. Specifically, examples include metal salts (e.g., alkali metal salts such as sodium and potassium salts; alkaline earth metal salts such as calcium, magnesium, and barium salts), ammonium salts, salts with inorganic acids (e.g., salts with inorganic acids such as hydrochloric acid, hydrogen bromide, 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).

[0048] As a salt for NR and / or NMN, salts that can be used in food, beverages, pharmaceuticals, etc. are preferred, for example, chlorides; alkali metal salts such as sodium and potassium salts; alkaline earth metal salts such as calcium and magnesium salts, etc. As a salt for NR, nicotinamide ribocyanate (chloride) is preferred.

[0049] (A composition containing one or more sesamin derivatives selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts)

[0050] The compositions of the present invention contain one or more selected from the above-mentioned nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts, and one or more of the above-mentioned sesamin derivatives as active ingredients. The compositions of the present invention can also be compositions for increasing the concentration of nicotinamide adenine dinucleotide (NAD).

[0051] In the compositions of the present invention, from the viewpoint of effectively increasing the concentration of nicotinamide adenine dinucleotide (NAD), that is, from the viewpoint of effectively increasing the concentration of NAD, reducing the inhibitory effect, maintaining the effect, or improving the effect, the molar ratio of one or more selected from NR, NMN, and their salts to sesamin (one or more selected from NR, NMN, and their salts / sesamin) is preferably 1 to 100. Furthermore, the molar ratio of one or more selected from NR, NMN, and their salts to sesamin (one or more selected from NR, NMN, and their salts / sesamin) is more preferably 3 to 80, and even more preferably 5 to 50. Since an anti-aging effect is achieved by increasing the concentration of nicotinamide adenine dinucleotide (NAD), that is, by increasing the concentration of NAD, reducing the inhibitory effect, maintaining the effect, or improving the effect, the composition of the present invention, from the viewpoint of anti-aging effect, also preferably has the molar ratio of NR, NMN, or their salts to sesamin set to the above-mentioned specific range.

[0052] Furthermore, in this specification, when indicating the amount of NR, NMN, or their salts, values ​​converted to nicotinamide ribose (NR) are used. The weight of NR selected from one or more of NR, NMN, and their salts is the NR conversion value of the total weight of NR, NMN, and their salts.

[0053] The total content of one or more sesamins contained in the composition of the present invention is not particularly limited, and can be set according to their morphology, etc.

[0054] The total content of sesamin in the composition of the present invention is 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 10% by weight or less, even more preferably 5% by weight or less. In one embodiment, the total content of sesamin in the composition is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight, even more preferably 0.05 to 5% by weight. Regarding the above-mentioned total content, when two or more sesamin compounds are contained, it is their combined content.

[0055] The total content of one or more of nicotinamide ribose (NR), nicotinamide mononucleotide (NMN) and their salts contained in the composition of the present invention is not particularly limited, and can be set according to their form, etc.

[0056] The total content of one or more compounds selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts in the composition of the present invention is preferably 0.001% by weight or more, more preferably 0.01% by weight or more, further 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 compounds selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts in the composition is preferably 0.001 to 95% by weight, more preferably 0.01 to 80% by weight, and further preferably 0.05 to 70% by weight. Regarding the above-mentioned total content, when the composition contains two or more compounds selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts, the total content of these compounds is considered.

[0057] The compositions of the present invention are compositions that can increase the concentration of nicotinamide adenine dinucleotide (NAD), compositions that can increase the concentration of nicotinamide adenine dinucleotide (NAD), inhibit its decrease, maintain or improve the concentration of nicotinamide adenine dinucleotide (NAD), and compositions that can increase the concentration of nicotinamide adenine dinucleotide (NAD) that decreases due to aging, inhibit its decrease, maintain or improve the concentration of nicotinamide adenine dinucleotide (NAD) that decreases due to aging.

[0058] NAD+ in vivo plays a crucial role in promoting mitochondrial function and the expression and synthesis of molecules related to mitochondrial energy production by activating Sirtuin and deacetyling downstream enzymes or transcription factors. Therefore, by increasing, decreasing, maintaining, or improving NAD+ concentration, mitochondrial function can be enhanced, reduced, maintained, or improved. The compositions of this invention can enhance mitochondrial function, inhibit its reduction, maintain, or improve mitochondrial function. Furthermore, the compositions of this invention can enhance, inhibit its reduction, maintain, or improve mitochondrial energy production. In addition, the compositions of this invention thus exert an anti-cellular aging effect.

[0059] Furthermore, in this specification, mitochondrial function and mitochondrial energy production can be evaluated based on common knowledge in the technical field to which this invention pertains, and the method is not particularly limited. For example, mitochondrial function can be evaluated by using an extracellular flow analyzer to continuously measure the rate of oxygen consumption (hereinafter also referred to as "OCR") used by mitochondria during ATP synthesis in the cell being tested, while adding ATP synthase inhibitors (e.g., oligomycin and rotenone) and uncoupling agents (e.g., trifluoromethoxyphenylhydrazone carbonyl cyanide (FCCP)). Evaluation items can be used to assess mitochondrial function by analyzing, for example, basal respiration, ATP production energy, and maximum respiration, which are key indicators in mitochondrial function evaluation.

[0060] The compositions of the present invention can be used to inhibit and / or delay aging, preferably to inhibit and / or delay aging accompanied by a decrease in NAD concentration.

[0061] In one embodiment, the composition of the present invention is a substance that increases NAD concentration, inhibits its decrease, maintains or improves NAD concentration, preferably for increasing, inhibiting, maintaining or improving NAD concentration that decreases due to aging.

[0062] In one approach, it is preferably used to increase, reduce, maintain, or improve age-related decreases in NAD concentrations in middle-aged and elderly individuals. Middle-aged and elderly individuals include the very old. For example, middle-aged and elderly individuals may be humans aged 40 years or older, and very old individuals may be humans aged 60 years or older or 65 years or older.

[0063] The NAD concentration in humans and other animals can be determined using conventional methods within the technical field to which this invention pertains, such as the Amplite (registered trademark) Colorimetric NAD / NADH Ratio Assay Kit (AAT Bioquest) or NAD... + The NADH Quantification Colorimetric Kit (Biovision) is used to measure intracellular NAD concentration.

[0064] The compositions of the present invention, by increasing, decreasing, maintaining, or improving NAD concentration, can be used to treat states or diseases that can be prevented or improved. Such states or diseases include, for example, the decline in physical, physiological, and mental functions associated with aging; specifically, examples include the occurrence of aging symptoms of the skin (wrinkles, sagging, loss of skin firmness, etc.), age-related dry skin (decreased skin hydration), age 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.), damage to cells (brain cells, myocardial cells, etc.) based on reactive oxygen species, hair or tooth loss, decreased vision or hearing, decreased motor function, decreased bone mass, decreased physical strength, decreased memory, decreased learning ability, decreased immune function, and the occurrence of age-related diseases.

[0065] In this instruction manual, prevention includes: preventing complications, delaying complications, reducing the incidence of complications, and mitigating the risk of complications. Improvement of a condition or disease includes: helping the subject recover from the condition or disease, alleviating the symptoms of the condition or disease, improving the symptoms of the condition or disease, and delaying or preventing the progression of the condition or disease.

[0066] The compositions of the present invention are suitable for either therapeutic (medical) or non-therapeutic (non-medical) uses. Non-therapeutic uses are defined as those that do not involve medical procedures, i.e., human surgery, treatment, or diagnosis.

[0067] The compositions of the present invention can be formulated into food products, pharmaceuticals, quasi-drugs, feeds, etc. The compositions of the present invention can themselves be food products, pharmaceuticals, quasi-drugs, feeds, etc., used to increase, decrease, inhibit, maintain, or improve nicotinamide adenine dinucleotide (NAD) concentration, or they can be materials or preparations formulated therein.

[0068] Furthermore, the compositions of the present invention may themselves be food, medicine, quasi-drug, feed, etc., used to improve mitochondrial function, inhibit its decline, maintain or improve mitochondrial function, or used to improve mitochondrial energy production, inhibit its decline, maintain or improve mitochondrial energy production, or may be materials or preparations formulated therein.

[0069] The compositions of the present invention, as an example, may be provided directly as a formulation, but are not limited to this manner. The formulation may also be provided directly as a composition, or as a composition containing the formulation.

[0070] The composition of the present invention may be either an oral composition or a non-oral composition, preferably an oral composition. As an oral composition, it may be a food product, an oral pharmaceutical product, a quasi-drug, feed, etc., or may be contained therein. The composition of the present invention is preferably a food product or an oral pharmaceutical product, more preferably a food product.

[0071] The compositions of the present invention, provided that the effects of the present invention are not impaired, may contain any additives and any ingredients other than one or more sesamin derivatives selected from NR, NMN and their salts. These additives and ingredients may be selected according to the form of the composition, and may be substances commonly used in food products, pharmaceuticals, quasi-drugs, and animal feed. When the compositions of the present invention are made into food products, pharmaceuticals, quasi-drugs, animal feed, etc., the manufacturing method is not particularly limited and can be manufactured by conventional methods.

[0072] For example, when the composition of the present invention is formulated into a food or beverage, various food or beverage products can be formulated by adding one or more sesamin derivatives selected from NR, NMN, and their salts, including ingredients that can be used in the food or beverage product (e.g., food materials, food additives, etc., as needed). There are no particular limitations on the food or beverage product; examples include general food and beverage products, health foods, health drinks, functionally labeled foods, foods for specific health purposes, and food and beverage products for patients. The aforementioned health foods, functionally labeled foods, and foods for specific health purposes can be used in various formulations such as granules, tablets, pellets, powders, capsules, chewable tablets, dry syrups, syrups, liquids, beverages, and liquid foods.

[0073] When the compositions of the present invention are formulated into pharmaceuticals or quasi-drugs, for example, a pharmacologically permissible carrier can be formulated into one or more sesamin derivatives selected from NR, NMN and their salts, and additives can be added as needed to prepare pharmaceuticals or quasi-drugs in various dosage forms. Such carriers, additives, etc., can be pharmacologically permissible substances that can be used in pharmaceuticals or quasi-drugs; for example, one or more excipients, binders, disintegrants, lubricants, antioxidants, colorants, etc., can be listed. As for the administration (ingestion) of the pharmaceuticals or quasi-drugs, oral or non-oral (dermal, mucosal, enteric, injection, etc.) administration methods can be listed. When the compositions of the present invention are formulated into pharmaceuticals or quasi-drugs, oral pharmaceuticals or quasi-drugs are preferred. As for dosage forms for oral administration, liquids, tablets, powders, granules, pellets, sugar-coated tablets, capsules, suspensions, emulsions, chewable tablets, etc., can be listed. Pharmaceuticals can also be for non-human animal use.

[0074] When the composition of the present invention is made into feed, one or more sesamin derivatives selected from NR, NMN and their salts are added to the feed. The feed also includes feed additives. Examples of feeds include livestock feeds for cattle, pigs, chickens, sheep, horses, etc.; small animal feeds for rabbits, rats, mice, etc.; and pet food for dogs, cats, birds, etc.

[0075] The compositions of the present invention are preferably oral compositions (composed by oral intake). The dosage (also referred to as intake) of the compositions of the present invention is not particularly limited. The dosage of the compositions of the present invention is only required to achieve an effect of increasing, decreasing, maintaining, or improving the concentration of nicotinamide adenine dinucleotide (NAD), and can be appropriately set according to the form of administration, method of administration, and the weight of the subject.

[0076] In one embodiment, when the composition of the present invention is orally ingested or administered to a human (adult), the total dosage of sesamin is preferably 0.5 mg or more per 60 kg of body weight per day, more preferably 1 mg or more, further preferably 3 mg or more, and preferably 200 mg or less, more preferably 100 mg or less, and further preferably 80 mg or less. In another embodiment, the total dosage of sesamin, for a human (adult), is preferably 0.5 to 200 mg per 60 kg of body weight per day, more preferably 1 to 100 mg, and further preferably 3 to 80 mg. It is preferable to divide the above amount into one or more doses per day, for example, once or several times a day (e.g., 2 to 3 times). In another embodiment, it is preferable to administer orally the above amount of sesamin to a human. In another embodiment, the composition of the present invention can be used to administer orally the above amount of sesamin to a human per 60 kg of body weight per day. Regarding the above total dosage, when two or more sesamin compounds are used, it is the combined dosage of both. In one manner, the total dosage of sesamin and episialin is preferably 0.5 to 200 mg per day for a human (adult) weighing 60 kg, administered orally or by oral administration. More preferably, it is 1 to 100 mg, and even more preferably, it is 3 to 80 mg of sesamin and / or episialin.

[0077] In one embodiment, when the composition of the present invention is taken orally by a human (adult), the total dosage of one or more selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts, converted to NR, is preferably 0.5 mg or more per day for a body weight of 60 kg, more preferably 1 mg or more, further preferably 3 mg or more, and preferably 20,000 mg or less, more preferably 10,000 mg or less, and further preferably 8,000 mg or less for a human (adult). In another embodiment, the total dosage of one or more selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts, converted to NR, is preferably 0.5 to 20,000 mg per day for a body weight of 60 kg, more preferably 1 to 10,000 mg, and further preferably 3 to 8,000 mg. It is preferable that the above dosage is divided into one or more doses per day, for example, once or more times per day (e.g., 2 to 3 times). In one embodiment, it is preferable to administer orally to a human the aforementioned amount of one or more selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts. In one embodiment, the composition of the present invention can be used to administer orally to a human at a dose of 60 kg per day the aforementioned amount of one or more selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts. Regarding the aforementioned total dosage, when two or more compounds selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts are used, this constitutes the total dosage.

[0078] The compositions of the present invention are preferably ingested or administered continuously. Sesamin derivatives, through continuous ingestion or administration, are expected to enhance the aforementioned effects. Furthermore, compounds selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts, through continuous ingestion or administration, are expected to enhance the aforementioned effects. In one embodiment, the compositions of the present invention are preferably ingested or administered continuously for at least one week, more preferably for at least four weeks, further preferably for at least eight weeks, and particularly preferably for at least twelve weeks.

[0079] The compositions of the present invention may also be labeled with a function exerted by increasing, decreasing, inhibiting, maintaining, or improving the concentration of nicotinamide adenine dinucleotide (NAD). Such labeling may include, for example, one or more functions selected from "increasing, decreasing, inhibiting, or maintaining mitochondrial function," "increasing, decreasing, inhibiting, or maintaining mitochondrial energy production," "inhibition and / or delay of aging due to decreased NAD concentration," "inhibition and / or delay of cellular aging," and "inhibition of aging."

[0080] In one embodiment of the invention, the composition of the invention is preferably a food or beverage bearing the above-described label. Furthermore, the above-described label may also be a label indicating that the above-described function is achieved.

[0081] The object of ingestion or administration of the compositions of the present invention (also referred to as the object of administration) is not particularly limited and can be humans or animals other than humans. Animals other than humans include, for example, industrial animals, pets, and laboratory animals. Specifically, industrial animals refer to livestock such as cattle, horses, pigs, goats, and sheep; poultry such as chickens, ducks, quails, turkeys, and ostriches; and fish such as yellowtail, juvenile yellowtail, red sea bream, horse mackerel, carp, rainbow trout, and eels, which are animals that need to be raised industrially. Pets refer to so-called ornamental or companion animals such as dogs, cats, marmosets, small birds, and hamsters. Laboratory animals refer to animals used for research in the fields of medicine, biology, agriculture, and pharmacy, such as mice, rats, guinea pigs, beagles, miniature pigs, macaques, and crab-eating macaques.

[0082] The object that ingests or administers the composition of the present invention (also referred to as the object of administration) is preferably a human or a non-human mammal, more preferably a human.

[0083] In one embodiment, the intended recipients may include individuals who require or desire an increase, reduction, maintenance, or improvement in nicotinamide adenine dinucleotide (NAD) concentration. Examples of such recipients include middle-aged and elderly individuals, individuals who require or desire an increase in mitochondrial function, an inhibition of its decline, a maintenance or improvement of mitochondrial function, individuals who require or desire an increase in mitochondrial energy production, an inhibition of its decline, a maintenance or improvement of mitochondrial energy production, and individuals who require or desire to inhibit and / or delay aging caused by a decrease in NAD concentration. Middle-aged and elderly individuals may be, for example, humans aged 40 years or older. In one embodiment, among middle-aged and elderly individuals, the very elderly are preferred. The very elderly may be, for example, humans aged 60 years or older or 65 years or older. The compositions of the present invention can be used in healthy individuals for the purpose of preventing or improving symptoms or diseases, for example, by increasing, reducing, maintaining, or improving the concentration of nicotinamide adenine dinucleotide (NAD).

[0084] The present invention also includes the following methods.

[0085] A method for increasing the concentration of nicotinamide adenine dinucleotide (NAD), characterized by the use of one or more selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN) and their salts, and one or more sesamin derivatives.

[0086] A method for increasing, decreasing, inhibiting, maintaining, or improving the concentration of nicotinamide adenine dinucleotide (NAD), characterized by the use of one or more selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts, as well as one or more sesamin derivatives.

[0087] A method for increasing, decreasing, inhibiting, maintaining, or improving the concentration of nicotinamide adenine dinucleotide (NAD) that decreases with age, characterized by the use of one or more selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts, as well as one or more sesamin derivatives.

[0088] The present invention also includes the following applications.

[0089] An application characterized in that one or more of nicotinamide ribose (NR), nicotinamide mononucleotide (NMN) and their salts, and one or more sesamin derivatives are used to increase the concentration of nicotinamide adenine dinucleotide (NAD).

[0090] An application characterized in that one or more of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and their salts, and one or more sesamin derivatives are used to increase, decrease, inhibit, maintain or improve the concentration of nicotinamide adenine dinucleotide (NAD).

[0091] An application characterized by using one or more selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and their salts, as well as one or more sesamin derivatives, to increase, decrease, inhibit, maintain, or improve the concentration of nicotinamide adenine dinucleotide (NAD) that decreases due to aging. The above method and application can be therapeutic or non-therapeutic.

[0092] By administering one or more sesamin derivatives selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts, the concentration of nicotinamide adenine dinucleotide (NAD) can be increased, its decrease inhibited, or its concentration maintained or improved. This can thereby enhance mitochondrial function, inhibit its decrease, maintain or improve mitochondrial function, increase mitochondrial energy production capacity, inhibit its decrease, maintain or improve mitochondrial energy production capacity, and inhibit and / or delay aging caused by a decrease in NAD concentration.

[0093] In the above methods and applications, compounds selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts, sesamin derivatives, and their preferred methods are the same as those used in the compositions of the present invention. As one or more sesamin derivatives, one or more sesamin derivative compounds may be used, or two or more may be used. Furthermore, as compounds selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts, one or more of these compounds may be used, or two or more may be used. In the above methods and applications, it is preferable to administer (ensure ingestion) one or more sesamin derivatives selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts to a subject once or more times daily, for example, once or more times daily (e.g., 2 to 3 times). In the above methods and applications, it is preferable to administer (ensure ingestion) the compositions of the present invention orally. The above applications are preferably in humans or non-human mammals, and more preferably in humans.

[0094] In the above methods and applications, any one or more sesamin derivatives selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts may be used in an amount (also referred to as an effective amount) that yields the desired effect (an increase in nicotinamide adenine dinucleotide (NAD) concentration, i.e., an increase, decrease, reduction, maintenance, or improvement in NAD concentration, an increase, decrease, maintenance, or improvement in mitochondrial function based thereon, an increase, decrease, maintenance, or improvement in mitochondrial energy production, and / or an inhibition and / or delay in aging due to a decrease in NAD concentration). The preferred dosage or target of one or more sesamin derivatives selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts is the same as in the compositions of the present invention described above. One or more sesamin derivatives selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts may be used directly or as a composition containing them. For example, the compositions of the present invention described above may also be used.

[0095] In the above applications, compositions containing one or more sesamin derivatives and compositions containing one or more derivatives selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts are prepared respectively. These are taken substantially simultaneously, or one composition is taken after the other during its duration of effect. This allows for the enhancement of the effects of the combined use of one or more derivatives selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts, as intended by the present invention (the effect of increasing NAD concentration, i.e., increasing, decreasing, maintaining, or improving NAD concentration; based on this, improving, decreasing, maintaining, or improving mitochondrial function; increasing, decreasing, maintaining, or improving mitochondrial energy production capacity; and / or inhibiting and / or delaying aging due to decreased NAD concentration). Therefore, kits containing compositions containing one or more sesamin derivatives and compositions containing one or more derivatives selected from nicotinamide ribose (NR), nicotinamide mononucleotide (NMN), and their salts, etc., fall within the scope of the compositions of the present invention.

[0096] The present invention also includes an application of using one or more sesamins selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and their salts to manufacture the composition of the present invention.

[0097] Example

[0098] The present invention will now be described in more detail with reference to specific embodiments. However, the present invention is not limited to these embodiments.

[0099] In the examples and comparative examples, a mixture of sesamin and episialin (SE) was used as a mixture of sesamin and episialin (sessamin: episialin (weight ratio) = 1:1).

[0100] <Comparative Examples 1-3, Example 1: Intracellular NAD based on sesamin and epissamin mixture (SE) and nicotinamide riboside (NR)> + Evaluation assays of concentration (intracellular NAD concentration) >

[0101] To investigate intracellular NAD + The effect of concentration, 0.5×10 4Hepa1-6 cells / well were seeded into 96-well plates and cultured for 96 hours at 37°C and CO2 (5%) in DMEM medium (Nacalai Tesque Co., Ltd., containing 10% FBS). After 96 hours of culture, the medium in each well was exchanged with the following: DMEM medium (containing 1% albumin, no FBS (Comparative Example 1)) without sesamin and epissamin mixture (SE) and nicotinamide ribose (using NR chloride (Carbosynth Limited)); DMEM medium containing 0.3 μM SE (containing 1% albumin, no FBS (Comparative Example 2)); DMEM medium containing 30 μM NR (containing 1% albumin, no FBS (Comparative Example 3)); or DMEM medium containing 0.3 μM SE and 30 μM NR (containing 1% albumin, no FBS (Example 1)); and cultured for another 24 hours. Then, the added culture medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque Co., Ltd.). Lysis Buffer (Amplite Colorimetric NAD / NADH Ratio Assay Kit, AATBioquest) was added, and the cell extract was recovered. Intracellular NAD was then analyzed according to the kit manual. + Concentration. Regarding intracellular NAD... + In terms of concentration, the protein concentration of the cell extract was determined (Pierce BCA Protein Assay Kit, Thermo Scientific), and calculated as a value relative to the protein concentration. Significance differences were tested using a t-test without a corresponding value (significance level: p < 0.05 relative to the control group).

[0102] The results (average of N=3) are shown in Figure 1 (*: p < 0.05).

[0103] Depend on Figure 1 Confirmed regarding intracellular NAD + In terms of concentration, compared to Comparative Example 1 (medium without SE and NR), the SE 0.3 μM group in Comparative Example 2 showed an increase of 2.3%, and the NR 30 μM group in Comparative Example 3 showed an increase of 3.1%. On the other hand, the combination of SE 0.3 μM and NR 30 μM in Example 1 showed an increase of 14.6%, which is significantly greater than the sum of the increases in Comparative Example 2 based on SE 0.3 μM treatment and Comparative Example 3 based on NR 30 μM treatment (5.4%). Therefore, it is confirmed that treatment with a combination of SE and NR at a molar ratio (SE:NR) of 1:100 results in a significant increase in intracellular NAD+. +The concentration showed a synergistic increasing effect.

[0104] Comparative Examples 4-6, Example 2: Intracellular NAD based on sesamin and epissamin mixture (SE) and nicotinamide riboside (NR) + Evaluation assays of concentration (intracellular NAD concentration) >

[0105] To investigate intracellular NAD + The effect of concentration, 1.0 × 10 4 Hepa1-6 cells / well were seeded into 96-well plates and cultured for 48 hours in DMEM medium (Nacalai Tesque Co., Ltd., containing 10% FBS) at 37°C and CO2 (5%). After 48 hours of culture, the medium in each well was exchanged with the following: DMEM medium (containing 1% albumin, no FBS (Comparative Example 4)) without sesamin and epissamin mixture (SE) and nicotinamide ribose (using NR chloride); DMEM medium containing 10 μM SE (containing 1% albumin, no FBS (Comparative Example 5)); DMEM medium containing 10 μM NR (containing 1% albumin, no FBS (Comparative Example 6)); or DMEM medium containing 10 μM SE and 10 μM NR (containing 1% albumin, no FBS (Example 2)); and cultured for another 24 hours. Then, the added culture medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque Co., Ltd.). Lysis Buffer (Amplite Colorimetric NAD / NADH Ratio Assay Kit, AAT Bioquest) was added, and the cell extract was recovered. Intracellular NAD was then analyzed according to the kit manual. + Concentration. Regarding intracellular NAD... + In terms of concentration, the protein concentration of the cell extract (Pierce BCA Protein Assay Kit, Thermo Scientific) was determined and calculated as a value relative to the protein concentration. The results (average of N=3) are shown in... Figure 2 (*: p < 0.05).

[0106] Depend on Figure 2 Confirmed regarding intracellular NAD +In terms of concentration, compared to Comparative Example 4 (medium without SE and NR), the SE 10 μM group in Comparative Example 5 showed an increase of 1.5%, and the NR 10 μM group in Comparative Example 6 showed an increase of 11.6%. On the other hand, it was confirmed that the combination of SE 10 μM and NR 10 μM in Example 2 showed an increase of 15.7%, which is significantly greater than the sum of the increases in Comparative Example 5 (based on SE 10 μM treatment) and Comparative Example 6 (based on NR 10 μM treatment) (13.1%). Therefore, it is confirmed that by treating cells with a combination of SE and NR at a molar ratio (SE:NR) of 1:1, intracellular NAD+ is significantly reduced. + The concentration showed a synergistic increasing effect.

[0107] Comparative Examples 7-9, Examples 3 and 4: Intracellular NAD based on sesamin and episialin mixture (SE) and nicotinamide riboside (NR) + Evaluation assays of concentration (intracellular NAD concentration) >

[0108] To investigate intracellular NAD + The effect of concentration, 1.0 × 10 4 Hepa1-6 cells / well were seeded into 96-well plates and cultured for 48 hours in DMEM medium (Nacalai Tesque Co., Ltd., containing 10% FBS) at 37°C and CO2 (5%). After 48 hours of culture, the medium in each well was exchanged with the following: DMEM medium (containing 1% albumin, no FBS (Comparative Example 7)) without sesamin and epissamin mixture (SE) and nicotinamide ribose (using NR chloride); DMEM medium containing 10 μM NR (containing 1% albumin, no FBS (Comparative Example 8)); DMEM medium containing 30 μM NR (containing 1% albumin, no FBS (Comparative Example 9)); DMEM medium containing 3 μM SE and 10 μM NR (containing 1% albumin, no FBS (Example 3)); or DMEM medium containing 3 μM SE and 30 μM NR (containing 1% albumin, no FBS (Example 4)); and cultured for another 24 hours. Next, the added culture medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque Co., Ltd.). Lysis Buffer (Amplite Colorimetric NAD / NADH Ratio Assay Kit, AAT Bioquest) was then added, and the cell extract was recovered. Intracellular NAD was then analyzed according to the kit's instructions. + Concentration. Regarding intracellular NAD... +In terms of concentration, the protein concentration of the cell extract (Pierce BCA Protein Assay Kit, Thermo Scientific) was determined and calculated as a value relative to the protein concentration. The results (average of N=3) are shown in... Figure 3 (*: p < 0.05).

[0109] Depend on Figure 3 Confirmed regarding intracellular NAD + In terms of concentration, compared to Comparative Example 7 (medium without SE and NR), the NAD concentration increased by 11.6% in the NR 10 μM group of Comparative Example 8 and by 15.5% in the NR 30 μM group of Comparative Example 9. On the other hand, the NAD concentration increased by 17.5% in the combination of SE 3 μM and NR 10 μM in Example 3 and by 21.8% in the combination of SE 3 μM and NR 30 μM in Example 4. Although there are no test examples here treated with DEME medium containing 3 μM SE, the NAD concentration increased by 2.3% in the SE 0.3 μM group of Comparative Example 2 and by 1.5% in the SE 10 μM group of Comparative Example 5. Therefore, it is inferred that the NAD concentration in the SE 3 μM group also increased by the same proportion. Therefore, the value obtained by simply adding the perceived increase in NAD concentration (2.3-1.5%) from SE 3 μM to the increase in NAD concentration in Comparative Examples 8 or 9 is significantly larger than the increase in NAD concentration in Examples 3 and 4. Based on the above, it is confirmed that treating cells with a molar ratio (SE:NR) of 1:3.3 or 1:10 for SE and NR results in a higher intracellular NAD concentration. + The concentration showed a synergistic increasing effect.

[0110] Comparative Examples 10-12, Example 5: Intracellular NAD based on sesamin and episaflavin mixture (SE) and nicotinamide riboside (NR) + Evaluation assays for concentration (intracellular NAD concentration) >

[0111] To investigate intracellular NAD + The effect of concentration, 1.5 × 10 4HepG2 cells / well were seeded into 96-well plates and cultured for 96 hours at 37°C and CO2 (5%) in DMEM medium (Nacalai Tesque Co., Ltd., containing 10% FBS). After 96 hours of culture, the medium in each well was exchanged with the following: DMEM medium (containing 1% albumin, no FBS (Comparative Example 10)) without sesamin and epissamin mixture (SE) and nicotinamide ribose (using NR chloride); DMEM medium (containing 1% albumin, no FBS (Comparative Example 11)) containing 0.3 μM SE; DMEM medium (containing 1% albumin, no FBS (Comparative Example 12)) containing 10 μM NR; or DMEM medium (containing 1% albumin, no FBS (Example 5)) containing 0.3 μM SE and 10 μM NR. The cells were then cultured for another 24 hours. Then, the added culture medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque Co., Ltd.). Lysis Buffer (Amplite Colorimetric NAD / NADH Ratio Assay Kit, AAT Bioquest) was added, and the cell extract was recovered. Intracellular NAD was then analyzed according to the kit manual. + Concentration. Regarding intracellular NAD... + In terms of concentration, the protein concentration of the cell extract (Pierce BCA Protein Assay Kit, Thermo Scientific) is determined and calculated as a value relative to the protein concentration.

[0112] Regarding intracellular NAD + Regarding concentration, compared to Comparative Example 10 (Cont, medium without SE and NR), a 5.0% increase was confirmed in the SE 0.3 μM group of Comparative Example 11, while no increase was confirmed in the NR 10 μM group of Comparative Example 12. On the other hand, an 8.0% increase was confirmed in the combination of SE 0.3 μM and NR 10 μM in Example 5, which is significantly greater than the sum of the increase based on SE 0.3 μM treatment and the increase based on NR 10 μM treatment (5.0%). Therefore, it is confirmed that treatment with a molar ratio (SE:NR) of 1:33 for combined SE and NR significantly increases intracellular NAD50 levels. + The concentration showed a synergistic increasing effect.

[0113] The above content clearly demonstrates that compositions containing sesamin, epissamin mixture, and nicotinamide ribose (NR) exhibit intracellular NAD+ expression. + Synergistic effect of increased concentration.

[0114] Comparative Examples 13-16, Examples 6 and 7: Intracellular NAD based on sesamin and episialin mixture (SE) and nicotinamide mononucleotide (NMN) + Evaluation assays of concentration (intracellular NAD concentration) >

[0115] To investigate intracellular NAD + The effect of concentration, 2.5 × 10 4 HepG2 cells / well were seeded into 96-well plates and cultured for 48 hours in DMEM medium (Nacalai Tesque Co., Ltd., containing 10% FBS) at 37°C and CO2 (5%). After 48 hours of incubation, the following media were exchanged with the culture media in each well: DMEM medium containing 1% albumin and no FBS (Comparative Example 13) without sesamin and epissamin mixture (SE) and nicotinamide mononucleotide (NMN); DMEM medium containing 10 μM SE (1% albumin and no FBS (Comparative Example 14)); DMEM medium containing 30 μM NMN (1% albumin and no FBS (Comparative Example 15)); DMEM medium containing 100 μM NMN (1% albumin and no FBS (Comparative Example 16)); DMEM medium containing 10 μM SE and 30 μM NMN (1% albumin and no FBS (Example 6)); or DMEM medium containing 10 μM SE and 100 μM NMN (1% albumin and no FBS (Example 7)); and incubated for another 24 hours. Then, the added culture medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque Co., Ltd.). Lysis Buffer (Amplite Colorimetric NAD / NADH Ratio Assay Kit, AAT Bioquest) was added, and the cell extract was recovered. Intracellular NAD was then analyzed according to the kit manual. + Concentration. Regarding intracellular NAD... + In terms of concentration, the protein concentration of the cell extract (Pierce BCA Protein Assay Kit, Thermo Scientific) was determined and calculated as a value relative to the protein concentration. The results (average of N=3) are shown in... Figure 4 (*: p < 0.05).

[0116] Depend on Figure 4 Confirmed regarding intracellular NAD +In terms of concentration, compared to Comparative Example 13 (culture medium without SE and NMN), the SE 10 μM group in Comparative Example 14 showed an increase of 14.2%, the NMN 30 μM group in Comparative Example 15 showed an increase of 18.9%, and the NMN 100 μM group in Comparative Example 16 showed an increase of 21.3%. On the other hand, the combination of SE 10 μM and NMN 30 μM in Example 6 showed an increase of 38.0%, which is significantly greater than the sum of the increase rates of Comparative Example 14 based on SE 10 μM treatment and Comparative Example 15 based on NMN 30 μM treatment (33.1%).

[0117] Furthermore, the combination of SE10μM and NMN100μM in Example 7 showed an increase of 74.6%, which is significantly greater than the sum of the increase rates of SE10μM-based treatment in Comparative Example 14 and NMN100μM-based treatment in Comparative Example 16 (35.5%).

[0118] Based on the above, it is confirmed that combining SE and NMN in a molar ratio (SE:NMN) of 1:3 or 1:10 will reduce intracellular NAD. + The concentration showed a synergistic increasing effect.

[0119] As clarified above, compositions containing NMN and / or their salts, known as intermediate metabolites of NAD, combined with one or more sesamin derivatives (preferably a mixture of sesamin and episialin), are similar to compositions containing a mixture of sesamin and episialin, as well as NR, in terms of intracellular NAD... + Concentration exhibits a synergistic effect of increasing concentration.

Claims

1. A composition, characterized in that, It contains one or more sesamin derivatives selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts as active ingredients. Sesamin and episialin are two or more types of sesamin. Sesamin: The weight ratio of sesamin to episesamin is 1:0.5~1:

2. The total content of one or more selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts is 0.001-95% by weight. The total content of one or more sesamin species is 0.001 to 10% by weight. The molar ratio of one or more selected from NR, NMN and their salts to sesamin is 1 to 100.

2. The composition according to claim 1, characterized in that, The total content of one or more selected from nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and their salts is 0.05 to 70% by weight.

3. The composition according to claim 1 or 2, characterized in that, The total content of one or more sesamins is 0.05 to 5% by weight.

4. The composition according to claim 1 or 2, characterized in that, This is an oral composition.

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

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