KR20230010217A - Compositions containing NR and/or NMN and sesamin - Google Patents

Abstract

An object of the present invention is to provide a composition having an effect of increasing the NAD concentration. The present invention relates to a composition containing at least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one member of sesamin as an active ingredient.

Description

Compositions containing NR and/or NMN and sesamin

The present invention relates to a composition containing sesamin and at least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof.

BACKGROUND OF THE INVENTION [0002] In recent years, in countries with a high proportion of the elderly, extension of a healthy lifespan has become an issue. As one of the factors for the shortening of a healthy lifespan, deterioration of body functions and the like due to a decrease in production of nicotinamide adenine dinucleotide (NAD ⁺ ) in the body according to age can be cited.

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 course of aging, leading to defects in nuclear and mitochondrial function and leading to many age-related pathologies. For example, in Non-Patent Document 1, aging and aging-related diseases include a decrease in intracellular nicotinamide adenine dinucleotide (NAD ⁺ ) level and enzymatic activity of longevity gene sirtuin, which is a NAD ⁺ dependent deacetylase. It is suggested that it is related to degradation. And recently, it has been reported that by increasing NAD ⁺ , sirtuin is activated and anti-aging action is exhibited (Non-Patent Document 2). For this reason, vigorous research is being conducted on the search for components that are effective in preventing or improving the decrease in NAD ⁺ due to aging and which can be applied to pharmaceuticals, foods for specified health uses, functional foods, and the like.

For example, in Non-Patent Document 3, nicotinamide riboside (NR), a NAD precursor, induces mitochondrial protein response and inhibitin protein synthesis, thereby activating old mouse muscle stem cells (MuSC). One has been disclosed. Further, it is disclosed that NR prevents MuSC aging in a mouse model of muscular dystrophy, that NR delays aging of neural SCs (stem cells), and that melanocyte SCs prolong the lifespan of mice.

Further, Non-Patent Document 4 shows that nicotinamide riboside (NR) is widely used as a NAD ⁺ precursor vitamin, and a single oral administration of NR increases the concentration of NAD ⁺ in human blood in a dose-dependent manner. In addition, Non-Patent Document 5 discloses that NMN activates sirtuins, and specifically, nicotinamide mononucleotide (NMN), a major natural NAD ⁺ intermediate (also referred to as an intermediate metabolite), was administered to normal wild-type mice. After administration for 12 months, it was disclosed that NMN effectively alleviated the age-related physiological decline of mice without significant toxicity, indicating the great potential of NMN as an effective anti-aging intervention in humans.

On the other hand, with respect to sesamin and/or episesamine, no suggestion or disclosure has been made about the effect of increasing nicotinamide adenine dinucleotide (NAD) in vivo.

Non-Patent Document 1: Imai, S. & Guarente, L. (2014) Trends Cell Biol., 24, 464-471. "NAD+ and sirtuins in aging and disease" Non-Patent Document 2: 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" Non-Patent Document 3: 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 improves mitochondrial and stem cell function and enhances life span in mice" Non-Patent Document 4: 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." Non-Patent Document 5: 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"

An object of the present invention is to provide a composition having an effect of increasing the NAD concentration.

As a result of intensive research to solve the above problems, the inventors of the present invention have found that sesamin has a synergistic effect with nicotinamide adenine dinucleotide (NAD), and also sesamin, nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) ) and salts thereof, it was found that a composition containing at least one selected from the group consisting of salts thereof effectively raises nicotinamide adenine dinucleotide (NAD).

The present invention relates to the following composition.

[1] A composition containing at least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one member of sesamin as active ingredients.

[2] The composition according to [1] above, wherein at least one of sesamin is sesamin and/or episesamine.

[3] a molar ratio of at least one selected from the group consisting of NR, NMN and salts thereof to sesamin (at least one selected from the group consisting of NR, NMN and salts thereof/sesamin) is 1 to 100 The composition according to [1] or [2] above.

[4] The composition according to any one of [1] to [3], wherein the total content of one or more of the sesamin is 0.001 to 10% by weight.

[5] The composition according to any one of [1] to [4] above, which improves, suppresses a decrease, maintains or improves the concentration of nicotinamide adenine dinucleotide (NAD).

[6] The composition according to any one of [1] to [5] above, which improves, suppresses decline, maintains or improves mitochondrial function.

[7] The composition according to any one of [1] to [6] above, which improves, suppresses a decrease in, maintains, or improves the energy production ability of mitochondria.

[8] The composition according to any one of [1] to [7], which is used for suppressing and/or delaying aging associated with a decrease in NAD concentration.

[9] The composition according to any one of [1] to [8], which is an anti-aging composition.

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

[11] The composition according to any one of [1] to [10], which is food or drink.

[12] The composition according to any one of the above [1] to [11], labeled with "inhibition and/or delay of senescence due to decrease in NAD concentration" and/or "inhibition and/or delay of cellular senescence".

[13] nicotinamide adenine dinucleotide (which is administered with at least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one of sesamin) NAD) Concentration Rising Method.

[14] nicotinamide adenine dinucleotide (which is administered with at least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one of sesamin) NAD) methods for enhancing, suppressing lowering, maintaining or improving concentrations.

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

[16] 1 selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof for improving, suppressing decrease, maintaining or improving the concentration of nicotinamide adenine dinucleotide (NAD) Use of more than one species and one or more of sesamin.

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

Figure 1 shows the synergistic effect of sesamin-epicesamin mixture (SE) (sesamin: episesamine (weight ratio = 1: 1)) and NR at a molar ratio of 1:100, SE or NR on intracellular NAD concentration It is a graph that represents
Figure 2 shows the synergistic effect of sesamin-episesamin mixture (SE) (sesamin: episesamine (weight ratio = 1: 1)) and NR in a molar ratio of 1: 1, SE or NR on intracellular NAD concentration It is a graph that represents
Figure 3 is a composition containing sesamin-epicesamin mixture (SE) (sesamin: episesamine (weight ratio = 1: 1)) and NR at a molar ratio of 1:3.3 or 1:10, or increase in intracellular NAD concentration of NR Here is a graph showing the effect.
Figure 4 is a composition containing sesamin-epicesamin mixture (SE) (sesamin: episesamine (weight ratio = 1: 1)) and NMN in a molar ratio of 1:3 or 1:10, intracellular NAD concentration of SE or NMN It is a graph showing the synergistic effect of

The composition of the present invention contains at least one type of sesamin.

Sesamin has an action of increasing the concentration of nicotinamide adenine dinucleotide (NAD), and has an action of increasing, suppressing a decrease, maintaining or improving the concentration of nicotinamide adenine dinucleotide (NAD) in cells, and for improving the concentration of NAD. , It is used for inhibiting a decrease in NAD concentration, for maintaining NAD concentration, or for improving NAD concentration. Raising the nicotinamide adenine dinucleotide (NAD) concentration means increasing the amount of nicotinamide adenine dinucleotide (NAD). In addition, NAD concentration means the NAD concentration in a cell.

Sesamin has an effect of increasing the concentration of nicotinamide adenine dinucleotide (NAD), and is expected to contribute to the prevention or improvement of aging associated with a decrease in the NAD concentration by the action of improving, inhibiting, maintaining or improving the concentration of NAD. Background Art Aging is understood as a phenomenon in which physical functions, physiological functions, and mental functions become weak. Physical changes due to aging begin around the age of 40 after reaching maturity, such as wrinkles on the skin, loss of hair and teeth, graying, accumulation of fatigue and deterioration in recovery, deterioration of vision and hearing, deterioration of motor function, Decreased muscle strength and activity, decreased quality of sleep, and decreased bone mass can be seen. Aging itself cannot be called a disease, but the decline in physical and physiological functions increases the risk of so-called geriatric diseases such as arteriosclerosis, abnormal sugar and lipid metabolism, degeneration of nerves, osteoporosis, and cataracts. In addition, aging of mental functions, such as memory and learning, accompanies the decline of physical functions. Raising the concentration of nicotinamide adenine dinucleotide (NAD) is effective for preventing or ameliorating aging associated with a decrease in NAD concentration.

(Sesamin)

In the present invention, sesamin is a general term for compounds containing sesamin and analogs thereof. Sesamin is a type of main lignan compound contained in sesame seeds. Examples of sesamin analogs include dioxabicyclo[3.3.0]octane derivatives described in Japanese Patent Laid-Open No. 4-9331, in addition to episesamine. As one or more types of sesamin, one type of these compounds may be used alone or two or more types may be used. Specific examples of sesamin include sesamin, episesamine, sesaminol, episesaminol, sesamol, sesamolin and the like, and stereoisomers or racemates thereof may be used alone or in combination. In addition, metabolites of sesamin (for example, described in Japanese Unexamined Patent Publication No. 2001-139579) are also sesamin analogs included in sesamin of the present invention, as long as they exhibit the effect of the present invention, and can be used in the present invention. . In the present invention, as at least one type of sesamin, sesamin and/or episesamine can be suitably used, and sesamin and episesamine can be used more suitably. When sesamin and episesamine are used, the ratio thereof is not particularly limited, but, for example, sesamin:epicesamin (weight ratio) is preferably 1:0.1 to 1:9, more preferably 1:0.3 to 1:3, 1:0.5 to 1:2 are more preferable.

Sesamin used in the present invention is not limited in any way by its form, manufacturing method, or the like. For example, in the case of sesamin, sesamin extracted from sesame oil by a known method (for example, the method described in Japanese Unexamined Patent Publication No. Heisei 4-9331) (referred to as a sesamin extract or purified product) can be used. Moreover, commercially available sesame oil (liquid form) can also be used as it is. However, when sesame oil is used, it is preferable to use a tasteless and odorless sesamin extract (or purified sesamin product) extracted from sesame oil because the flavor peculiar to sesame oil is evaluated as sensory undesirable in some cases. In addition, when sesame oil is used, since the sesamin content is low, when a desired amount of sesamin is blended, the volume per unit dose of the prescribed composition becomes excessively large, which may cause problems with intake. In particular, when formulated for oral administration, the preparation (tablet, capsule, etc.) becomes excessively large, causing difficulty in intake. Therefore, it is preferable to use the sesamin extract (or sesamin purified product) from sesame oil also from the viewpoint that the amount of intake is low. Sesamin can also be obtained by synthesis. As the method, for example, sesamin and episesamine can be synthesized by the method of Beroza et al. (J. Am. Chem. Soc., 78, 1242 (1956)). Metabolites of sesamin and episesamine can be synthesized by the method of Urata et al. (Chem. Pharm. Bull. (Tokyo), 56(11) 1611-2 (2008)).

Sesamin is a compound that is contained in natural products and foods and beverages, has abundant dietary experience, and is recognized to be highly stable. Sesamin, whose safety is guaranteed, is most suitable for continued intake and long-term intake.

(nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof)

The composition of the present invention includes at least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof.

NR and NMN are intermediate metabolites of NAD. It is known that NR is converted into NMN by nicotinamide riboside kinase (NRK) and NAD ⁺ is synthesized. NR, NMN and salts thereof are known compounds and can be produced by known production methods, and commercially available products can also be used.

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

As the salts of NR and/or NMN, salts usable in foods, beverages, pharmaceuticals, etc. are preferable, such as chlorides; alkali metal salts such as sodium salt and potassium salt; Alkaline-earth metal salts, such as a calcium salt and a magnesium salt, etc. are mentioned. As a salt of NR, nicotinamide riboside chloride (chloride) is preferable.

(A composition containing at least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one member of sesamin)

The composition of the present invention contains at least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one member of sesamin. The composition of the present invention contains at least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one member of the sesamin group as active ingredients. The composition of the present invention may be a composition for increasing the concentration of nicotinamide adenine dinucleotide (NAD).

In the composition of the present invention, from the viewpoint of effectively increasing the synergistic action of nicotinamide adenine dinucleotide (NAD) concentration, that is, from the viewpoint of effectively increasing the action of enhancing, inhibiting the decrease, maintaining or improving the concentration of NAD, It is preferable that the molar ratio of at least one selected from the group consisting of NR, NMN and salts thereof (at least one selected from the group consisting of NR, NMN and salts thereof/sesamin) is 1 to 100. In addition, the molar ratio of at least one selected from the group consisting of NR, NMN and salts thereof to sesamin (at least one selected from the group consisting of NR, NMN and salts thereof / sesamin) is 3 to 80 It is more preferable, and it is more preferable that it is 5-50. Since the anti-aging effect is exhibited by increasing the synergistic action of nicotinamide adenine dinucleotide (NAD) concentration, that is, the action of enhancing, inhibiting the decrease, maintaining or improving the concentration of NAD, in the composition of the present invention, NR , NMN or salts thereof, and the molar ratio of sesamin within the above-specified range is also preferable from the viewpoint of anti-aging action.

In addition, in this specification, when expressing the amount of NR, NMN or these salts, the value converted into the amount of nicotinamide riboside (NR) is used. The weight in terms of NR of at least one selected from the group consisting of NR, NMN and salts thereof is a value in terms of NR of the total weight of NR, NMN and salts thereof.

The total content of one or more types of sesamin contained in the composition of the present invention is not particularly limited, and can be set depending on the form and the like.

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, still more preferably 0.05% by weight or more, and 10% by weight or less in the composition, for example. It is preferred, and 5% by weight or less is more preferred. In one aspect, the total content of sesamin in the composition is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight, still more preferably 0.05 to 5% by weight. The said total content is these total content, when 2 or more types of compounds of sesamin are contained.

The total content of at least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof included in the composition of the present invention is not particularly limited, and can be set depending on the form and the like. .

The total content of at least one 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 in the composition, 0.01 wt% or more is more preferable, 0.05 wt% or more is still more preferable, and 95 wt% or less is preferable, and 80 wt% or less is more preferable. In one embodiment, the total content of at least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof is preferably 0.001 to 95% by weight, and 0.01 to 95% by weight in the composition. 80% by weight is more preferred, and 0.05 to 70% by weight is still more preferred. The above total content is the total content of one or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof when two or more are contained.

The composition of the present invention is capable of increasing the concentration of nicotinamide adenine dinucleotide (NAD), and improves, suppresses a decrease in, maintains or improves the concentration of nicotinamide adenine dinucleotide (NAD), and is capable of increasing the concentration of nicotinamide adenine dinucleotide (NAD) reduced by aging Adenine dinucleotide (NAD) concentration can be increased, inhibited from decreased, maintained, or improved.

NAD in a living body plays an important role in promoting the expression and synthesis of molecules related to mitochondrial function and energy production by activating sirtuins and deacetylating downstream enzymes or transcription factors. For this reason, the effect of improving, suppressing a decrease, maintaining or improving mitochondrial function is obtained by increasing, suppressing a decrease, maintaining or improving the NAD concentration. The composition of the present invention can enhance, inhibit decline, maintain or improve mitochondrial function. In addition, the composition of the present invention can improve, suppress decrease, maintain or improve the energy production ability of mitochondria. In addition, the composition of the present invention thereby exhibits an anti-cell aging effect.

In the present specification, mitochondrial function and mitochondrial energy production ability may be evaluated based on common knowledge in the technical field to which the present invention belongs, and the method is not particularly limited. For example, using an extracellular flux analyzer, the rate of oxygen consumption used in mitochondria during ATP synthesis in the cell to be measured (hereinafter also referred to as "OCR") is measured by ATP synthase inhibitors (eg, oligomycin and rotene). rice), and by continuously measuring while adding a deconjugating agent (e.g., carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP)), mitochondrial function can be evaluated. As evaluation items, for example, mitochondrial function can be evaluated by analyzing basal respiratory rate, ATP production capacity, and maximal respiratory volume, which are major indicators in mitochondrial function evaluation.

The composition of the present invention can be used for suppression and/or delay of aging, and is preferably used for suppression and/or delay of aging due to a decrease in NAD concentration.

In one aspect, the composition of the present invention improves, suppresses a decrease, maintains or improves the NAD concentration, and is suitably used for improving, suppressing a decrease, maintaining or improving the NAD concentration decreased by aging.

In one aspect, it is suitably used for the improvement, reduction suppression, maintenance or improvement of the NAD concentration decreased with age in middle-aged and elderly people. Middle-aged and elderly people include elderly people. A middle-aged person may be, for example, a person of 40 years of age or older, and an elderly person may be a person of 60 years of age or older or 65 years of age or older.

The concentration of NAD in animals such as humans can be measured by a conventional method in the technical field to which the present invention belongs, for example, Amplite (registered trademark) Colorimetric NAD/NADH Ratio Assay Kit (AAT Bioquest) or NAD It can be measured by measuring intracellular NAD concentration using ⁺ /NADH Quantification Colorimetric Kit (Biovision).

The composition of the present invention can be used for the treatment of a condition or disease that can be expected to be prevented or improved by increasing, suppressing a decrease, maintaining or improving the concentration of NAD. As such a condition or disease, for example, decline in physical function, physiological function, mental function due to age, specifically, for example, occurrence of aging symptoms of the skin (occurrence of wrinkles, sagging, loss of elasticity of the skin, etc.), aging Dry skin (decreased skin moisturization), skin spots, freckles, skin roughness, hormones (growth hormone, thyroid hormone, adrenal cortex hormone, sex hormone, prolactin, antidiuretic hormone, parathyroid hormone, melatonin, etc.) Decreased or increased secretion, damage to cells (brain cells, cardiac muscle cells, etc.) by active oxygen, loss of hair or teeth, deterioration of eyesight or hearing, deterioration of motor function, deterioration of bone mass, deterioration of physical strength, deterioration of memory , decline in learning ability, decline in immune function, occurrence of geriatric diseases, etc.

Prevention in this specification includes preventing the onset, delaying the onset, reducing the onset rate, reducing the risk of onset, and the like. Amelioration of a condition or disease refers to recovering a subject from a condition or disease, alleviating the symptoms of a condition or disease, ameliorating the symptoms of a condition or disease, delaying or preventing the progression of a condition or disease. Include etc.

The composition of the present invention can be applied to either therapeutic use (medical use) or non-therapeutic use (non-medical use). Non-therapeutic is a concept that does not include medical practice, that is, surgery, treatment or diagnosis of humans.

The composition of the present invention can be in the form of food or drink, drug, quasi-drug, feed or the like. The composition of the present invention may itself be a food or drink, drug, quasi-drug, feed, etc. used to improve, suppress a decrease, maintain or improve the concentration of nicotinamide adenine dinucleotide (NAD), or be used in combination with these It may be a material or formulation.

In addition, the composition of the present invention itself is used for improving, inhibiting, maintaining, or improving mitochondrial function, or for improving, suppressing, reducing, maintaining or improving mitochondrial energy production ability, food and drink, pharmaceuticals, and pharmaceuticals. It may be a quasi-product, feed, etc., or may be a material or preparation used in combination with these.

As an example, the composition of the present invention can be provided in the form of a tablet, but is not limited to this form. The agent may be provided as a composition as it is or as a composition containing the agent.

The composition of the present invention may be either an oral composition or a parenteral composition, but is preferably an oral composition. As the composition for oral use, food or drink, oral pharmaceuticals, quasi-drugs, feeds, etc. themselves may be used, or they may be included in these. The composition of the present invention is preferably a food or drink or an oral drug, more preferably a food or drink.

The composition of the present invention, in addition to at least one selected from the group consisting of NR, NMN and salts thereof, and at least one of sesamin, any additives, any may contain ingredients. These additives and components can be selected according to the form of the composition, etc., and those that can be generally used for foods, drugs, quasi-drugs, feeds, and the like can be used. When the composition of the present invention is used as food or drink, drug, quasi-drug, or feed, the manufacturing method is not particularly limited, and can be produced by a general method.

For example, when the composition of the present invention is used as food or drink, in addition to at least one selected from the group consisting of NR, NMN, and salts thereof, and at least one of sesamin, components usable for food and drink (eg, food materials, food additives used as needed, etc.) can be blended to make various foods and beverages. The food or drink is not particularly limited, and examples thereof include general food and drink, health food, health drink, functional display food, specific health use food, and food and drink for the sick. The health food, food with functional indications, food for specific health use, etc., can be used in various formulations such as, for example, fine granules, tablets, granules, powders, capsules, chewables, dry syrups, syrups, liquids, beverages, and liquid formulas. there is.

When the composition of the present invention is used as a drug or quasi-drug, for example, at least one selected from the group consisting of NR, NMN, and salts thereof, and at least one sesamin, as well as a pharmacologically acceptable carrier, It can be made into a pharmaceutical or quasi-drug of various dosage forms by blending additives and the like added as needed. Such carriers, additives, etc. may be used as long as they are pharmacologically acceptable and usable for pharmaceuticals or quasi-drugs, and examples thereof include one or two or more of excipients, binders, disintegrants, lubricants, antioxidants, and coloring agents. there is. Examples of administration (intake) forms of pharmaceuticals or quasi-drugs include oral or parenteral (transdermal, transmucosal, enteral, injection, etc.) forms of administration. When the composition of the present invention is used as a drug or quasi-drug, it is preferably used as an oral drug or quasi-drug. Formulations for oral administration include solutions, tablets, powders, fine granules, granules, dragees, capsules, suspensions, emulsions, chewables and the like. The medicine may be a medicine for non-human animals.

When the composition of the present invention is used as a feed, at least one selected from the group consisting of NR, NMN and salts thereof and at least one sesamin may be mixed with the feed. Feed also includes feed additives. As the feed, for example, livestock feed used for cows, pigs, chickens, sheep, horses, etc.; feed for small animals used for rabbits, rats, mice, etc.; and pet food used for dogs, cats, small birds, and the like.

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

In one aspect, when the composition of the present invention is orally ingested or administered to humans (adults), the total dose of sesamin is preferably 0.5 mg or more, preferably 0.5 mg or more, at 60 kg body weight per day. It is preferably 1 mg or more, more preferably 3 mg or more, more preferably 200 mg or less, more preferably 100 mg or less, still more preferably 80 mg or less. In one aspect, the total dose of sesamin is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, still more preferably 3 to 80 mg per day for a human (adult) body weight of 60 kg. is mg. It is preferable to ingest or administer the above amount at least once a day, for example, once a day or divided into several times (eg, 2 to 3 times). In one aspect, it is preferable to orally ingest or administer the above amount of sesamin to humans. In one aspect, the composition of the present invention can be used for ingesting or administering the above amount of sesamin per 60 kg of body weight per day to a human. The said total dose is these total amount, when using 2 or more types of sesamin type compounds. In one embodiment, sesamin and/or episesamine are administered as a total dose of sesamin and episesamin in a body weight of 60 kg per day, preferably 0.5 to 200 mg, more preferably 1 to 100 mg, still more preferably 3 to 80 mg, preferably orally ingested or administered to humans (adults).

In one aspect, when the composition of the present invention is orally ingested or administered to humans (adults), in the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof The total dosage of one or more selected species is preferably 0.5 mg or more, more preferably 1 mg or more, even more preferably 3 mg or more, and more preferably 20000 mg or less, more preferably 10000 mg or less, still more preferably 8000 mg or less. In one aspect, the total dose of one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof is, in terms of NR, per day for humans (adults) For a body weight of 60 kg, it is preferably 0.5 to 20000 mg, more preferably 1 to 10000 mg, still more preferably 3 to 8000 mg. It is preferable to ingest or administer the above amount at least once a day, for example, once a day or divided into several times (eg, 2 to 3 times). In one aspect, it is preferable to orally ingest or administer to humans at least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof in the above amount. . In one aspect, the composition of the present invention is administered to a human in the amount of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof per 60 kg of body weight per day. It can be used to ingest or administer more than one species. The total dose is the total amount of two or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof.

The composition of the present invention is preferably continuously ingested or administered. Sesamin is expected to enhance the above effect by continuously ingesting or administering sesamin. In addition, by continuously ingesting or administering compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, the aforementioned effects are expected to be enhanced. In one aspect, the composition of the present invention is preferably ingested or administered continuously for 1 week or longer, more preferably 4 weeks or longer, still more preferably 8 weeks or longer, particularly preferably continuously for 12 weeks or longer. desirable.

The composition of the present invention may be labeled with a function exhibited by increasing, suppressing a decrease, maintaining or improving the concentration of nicotinamide adenine dinucleotide (NAD). As such indications, for example, "improvement, suppression or maintenance of reduction in mitochondrial function", "improvement, suppression or maintenance of reduction in energy production ability by mitochondria", "inhibition and/or delay of aging due to reduction in NAD concentration", Displays of one or two or more functions selected from the group consisting of "inhibition and/or delay of cellular senescence" and "inhibition of senescence" may be attached.

1 aspect of this invention WHEREIN: It is preferable that the composition of this invention is food-drinks with the said mark. Further, the display may be a display to the effect that the function is used to obtain the function.

The subject to which the composition of the present invention is ingested or administered (can also be referred to as an administration subject) is not particularly limited, and can be ingested by humans and non-human animals. Examples of non-human animals include industrial animals, pets, and laboratory animals. Specifically, industrial animals include livestock such as cows, horses, pigs, goats and sheep, poultry such as chickens, ducks, quails, turkeys and ostriches, yellowtail, young yellowtail, red snapper, horse mackerel, carp, rainbow trout and eels, etc. We say animal which it is necessary to breed industrially including fish of this. Pets refer to so-called pets and companion animals such as dogs, cats, marmosets, small birds and hamsters, and laboratory animals include mice, rats, guinea pigs, beagle dogs, mini pigs, rhesus monkeys and crab monkeys, medicine, It refers to animals commonly used for research in fields such as biology, agriculture, and pharmacy.

The subject to which the composition of the present invention is ingested or administered (can also be referred to as an administration subject) is preferably a human or a non-human mammal, more preferably a human.

In one aspect, as the subject of administration, a subject requiring or desired to increase, suppress a decrease, maintain or improve the concentration of nicotine adenine dinucleotide (NAD) is exemplified. As such a subject, for example, middle-aged or elderly people, a subject who needs or desires to improve, suppress decline, maintain or improve mitochondrial function, who needs or desires to improve, suppress decline, maintain or improve mitochondrial energy production ability Targets, targets requiring or desired to suppress and/or delay aging by lowering the NAD concentration, and the like are exemplified. A middle-aged person may be, for example, a person of 40 years of age or older. In one aspect, among middle-aged and elderly people, the elderly are preferable as the target. An elderly person may be, for example, a human being 60 years old or older or 65 years old or older. The composition of the present invention, for example, for the purpose of preventing or preventing symptoms or diseases that can be expected to be prevented or improved by improving, suppressing a decrease, maintaining or improving the concentration of nicotinamide adenine dinucleotide (NAD), for healthy people can also be used

The present invention also includes the following methods.

At least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and at least one of sesamin, nicotinamide adenine dinucleotide (NAD) concentration way of rising.

At least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and at least one of sesamin, nicotinamide adenine dinucleotide (NAD) concentration A method of improving, suppressing degradation, maintaining or improving

At least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one member of sesamin are administered, for example, reduced nicotinamide adenine di A method of enhancing, suppressing a decrease, maintaining or improving nucleotide (NAD) concentration.

The present invention also includes the following uses.

At least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one member of sesamin for increasing the concentration of nicotinamide adenine dinucleotide (NAD) use of more than one.

At least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof for improving, suppressing decrease, maintaining or improving the concentration of nicotinamide adenine dinucleotide (NAD), and, the use of one or more of sesamin.

Selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof for improving, inhibiting, maintaining or improving the concentration of nicotinamide adenine dinucleotide (NAD) reduced by aging Use of one or more types and one or more types of sesamin. The methods and uses may be therapeutic or non-therapeutic methods or uses.

By administering at least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one sesamin, the concentration of nicotinamide adenine dinucleotide (NAD) Improvement, deterioration suppression, maintenance or improvement becomes possible. This makes it possible to improve, suppress, maintain, or improve mitochondrial function, improve, suppress, maintain, or improve mitochondrial energy-producing ability, and suppress and/or delay aging due to a decrease in NAD concentration.

In the method and use, compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, sesamin, and preferred embodiments thereof are the same as the above-described composition of the present invention Do. As one or more types of sesamin, one type of compound of sesamin may be used, and two or more types may be used. Further, as a compound selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, one or more of these compounds may be used, or two or more of them may be used. In the above method and use, at least once a day, for example, once to several times a day (eg, 2 to 3 times), nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof It is preferable to administer (or ingest) a composition containing at least one member selected from the group consisting of sesamin and at least one member of sesamin. In the above method and use, it is preferable to orally administer (ingest) the composition of the present invention. The use is preferably for humans or non-human mammals, more preferably for humans.

In the above method and use, the desired action (synergism of nicotinamide adenine dinucleotide (NAD) concentration, that is, an action to increase, suppress a decrease, maintain or improve the concentration of NAD, thereby improving, suppressing a decrease, or maintaining mitochondrial function) Alternatively, the amount (which can also be referred to as an effective amount) can achieve an improvement action, an improvement in mitochondrial energy production ability, suppression of decrease, maintenance or improvement action, and/or suppression and/or delay action of aging due to a decrease in NAD concentration. At least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one member of sesamin may be used. At least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and a preferred dose or subject for administration of at least one member of the sesamin group of the present invention described above. the same as the composition. At least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one member of sesamin may be administered as they are, and as a composition containing them may be administered. For example, the composition of the present invention described above may be used.

In the above use, a composition containing at least one type of sesamin and a composition containing at least one type selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof If they are individually prepared and taken almost simultaneously, or after taking one composition, then taking the other composition while the effect is maintained, nicotinamide riboside (NR) and nicotinamide mononucleotide intended by the present invention (NMN) and at least one selected from the group consisting of salts thereof and at least one sesamin (synergism of NAD concentration, that is, improvement of NAD concentration, suppression of decrease, maintenance or improvement of NAD concentration, Improvement, suppression of decrease, maintenance or improvement of mitochondrial function, improvement of mitochondrial energy production ability, suppression of decrease, maintenance or improvement of mitochondrial function, and/or suppression and/or delay of aging due to decrease in NAD concentration) The enhancing action of is obtained. Therefore, a kit including a composition containing at least one type of sesamin and a composition containing at least one type selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof is also available. Included within the scope of the composition of the present invention.

The present invention relates to the use of at least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one member of sesamin for preparing the composition of the present invention. include

Example

Hereinafter, the present invention will be described in more detail based on examples. In addition, this invention is not limited to these Examples.

In Examples and Comparative Examples, as the sesamin/epicesamin mixture (SE), a mixture of sesamin and episesamine (sesamin:epicesamin (weight ratio) = 1:1) was used.

<Comparative Examples 1 to 3, Example 1: Evaluation test of intracellular NAD ⁺ concentration (intracellular NAD concentration) by sesamin/epicesamine mixture (SE) and nicotinamide riboside (NR)>

In order to investigate the effect on the intracellular NAD ⁺ concentration, 0.5×10 ⁴ cells/well _of Hepa1-6 cells were seeded in a 96-well plate, and DMEM medium (Nacalai Tesk Co., Ltd., containing 10% FBS) for 96 hours. After 96 hours of culture, DMEM medium (containing 1% albumin, no FBS (Comparative Example 1)) without sesamin/epicesamine mixture (SE) and nicotinamide riboside (using NR chloride (manufactured by 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 SE A DMEM medium containing 0.3 µM and 30 µM of NR (containing 1% albumin, no FBS (Example 1)) was exchanged with the medium in each well, and further cultured for 24 hours. Thereafter, the addition medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque Co., Ltd.), followed by addition of Lysis Buffer (Amplite (registered trademark) Colorimetric NAD/NADH Ratio Assay Kit, AAT Bioquest) Thus, the cell extract was recovered. Then, according to the kit's manual, intracellular NAD ⁺ concentration was analyzed. The intracellular NAD ⁺ concentration was calculated as a value per protein concentration by measuring the protein concentration of the cell extract (Pierce (registered trademark) BCA Protein Assay Kit, Thermo Scientific). Significant difference test was performed by unpaired t test (significance level: p<0.05, relative to control group).

The obtained result (average of N=3) is shown in FIG. 1 (*: p<0.05).

From Figure 1, the intracellular NAD ⁺ concentration was 2.3% in the SE 0.3 µM group of Comparative Example 2 and 3.1% in the NR 30 µM group of Comparative Example 3, with respect to Comparative Example 1 (medium containing no SE and NR). increase was recognized. On the other hand, an increase of 14.6% was recognized in the combination group of SE 0.3 μM and NR 30 μM in Example 1, which is the increase rate by SE 0.3 μM treatment in Comparative Example 2 and the increase by NR 30 μM treatment in Comparative Example 3 It was significantly greater than the value simply adding the ratio (5.4%). From the above, it was confirmed that the synergistic increase effect of intracellular NAD ⁺ concentration was confirmed by the combination treatment of SE and NR at a molar ratio (SE:NR) of 1:100.

<Comparative Examples 4 to 6, Example 2: Evaluation test of intracellular NAD ⁺ concentration (intracellular NAD concentration) by sesamin/epicesamine mixture (SE) and nicotinamide riboside (NR)>

In order to investigate the effect on the intracellular NAD ⁺ concentration, 1.0 × 10 ⁴ cells/well _of Hepa1-6 cells were seeded in a 96-well plate, and DMEM medium (Nacalai Tesk Co., Ltd., containing 10% FBS) for 48 hours. After 48 hours of culture, DMEM medium (containing 1% albumin, no FBS (Comparative Example 4)) without sesamin/epicesamine mixture (SE) and nicotinamide riboside (NR, using chloride), SE at 10 µM DMEM medium containing 1% albumin (containing 1% albumin, no FBS (Comparative Example 5)), DMEM medium containing 10 μM NR (containing 1% albumin, no FBS (Comparative Example 6)), or 10 μM SE and NR A DMEM medium containing 10 µM (containing 1% albumin, no FBS (Example 2)) was exchanged with the medium in each well, and further cultured for 24 hours. Thereafter, the addition medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque Co., Ltd.), followed by addition of Lysis Buffer (Amplite (registered trademark) Colorimetric NAD/NADH Ratio Assay Kit, AAT Bioquest) Thus, the cell extract was recovered. Then, according to the kit's manual, intracellular NAD ⁺ concentration was analyzed. The intracellular NAD ⁺ concentration was calculated as a value per protein concentration by measuring the protein concentration of the cell extract (Pierce (registered trademark) BCA Protein Assay Kit, Thermo Scientific). The obtained result (average of N=3) is shown in FIG. 2 (*: p<0.05).

From FIG. 2, the intracellular NAD ⁺ concentration was 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, with respect to Comparative Example 4 (medium containing no SE and NR). increase was recognized. On the other hand, an increase of 15.7% was recognized in the combination group of SE 10 μM and NR 10 μM in Example 2, which is the increase rate by SE 10 μM treatment in Comparative Example 5 and the increase by NR 10 μM treatment in Comparative Example 6 It was clearly greater than simply adding the percentage (13.1%). From the above, it was confirmed that the synergistic increase effect of intracellular NAD ⁺ concentration was confirmed by the combination treatment of SE and NR at a molar ratio (SE:NR) of 1:1.

<Comparative Examples 7 to 9, Examples 3 and 4: Evaluation test of intracellular NAD ⁺ concentration (intracellular NAD concentration) by sesamin/epicesamine mixture (SE) and nicotinamide riboside (NR)>

In order to investigate the effect on the intracellular NAD ⁺ concentration, 1.0 × 10 ⁴ cells/well _of Hepa1-6 cells were seeded in a 96-well plate, and DMEM medium (Nacalai Tesk Co., Ltd., containing 10% FBS) for 48 hours. After 48 hours of culture, a DMEM medium (containing 1% albumin and no FBS (Comparative Example 7)) containing no sesamin/epicesamine mixture (SE) and nicotinamide riboside (NR, using chloride), 10 μM NR DMEM medium containing 1% albumin (containing 1% albumin, no FBS (Comparative Example 8)), DMEM medium containing 30 μM NR (containing 1% albumin, no FBS (Comparative Example 9)), 3 μM SE and 10 μM NR DMEM medium containing 1% albumin (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)), in each well The culture medium was exchanged and further cultured for 24 hours. Thereafter, the addition medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque Co., Ltd.), followed by addition of Lysis Buffer (Amplite (registered trademark) Colorimetric NAD/NADH Ratio Assay Kit, AAT Bioquest) Thus, the cell extract was recovered. Then, according to the kit's manual, intracellular NAD ⁺ concentration was analyzed. The intracellular NAD ⁺ concentration was calculated as a value per protein concentration by measuring the protein concentration of the cell extract (Pierce (registered trademark) BCA Protein Assay Kit, Thermo Scientific). The obtained result (average of N=3) is shown in FIG. 3 (*: p<0.05).

From Figure 3, the intracellular NAD ⁺ concentration was 11.6% in the NR 10 µM group of Comparative Example 8 and 15.5% in the NR 30 µM group of Comparative Example 9, with respect to Comparative Example 7 (a medium containing no SE and NR). increase was recognized. On the other hand, an increase of 17.5% in the combination group of 3 μM SE and 10 μM NR in Example 3 and 21.8% in the combination group of 3 μM SE and 30 μM NR in Example 4 was recognized. Here, although there is no test example treated with DEME medium containing 3 μM of SE, an increase in NAD concentration of 2.3% was recognized in the 0.3 μM SE group of Comparative Example 2, and also in the 10 μM SE group of Comparative Example 5. Since an increase in the NAD concentration of 1.5% was observed, it is inferred that the NAD concentration increased at an equal rate to these in the SE 3 µM group. If so, the increase rate of NAD concentration in Comparative Example 8 or Comparative Example 9, the value obtained by simply adding the increase rate (2.3 to 1.5%) of NAD concentration thought to be obtained by SE 3 μM, and the value obtained in Example 3 and Comparing the increase rate of the NAD concentration in Example 4, it was found that the increase rate in Example 3 and Example 4 was clearly large. From the above, it was confirmed that the synergistic increase effect of intracellular NAD ⁺ concentration was confirmed by the combination treatment of SE and NR at a molar ratio (SE:NR) of 1:3.3 or 1:10.

<Comparative Examples 10 to 12, Example 5: Evaluation test of intracellular NAD ⁺ concentration (intracellular NAD concentration) by sesamin/epicesamine mixture (SE) and nicotinamide riboside (NR)>

In order to investigate the effect on intracellular NAD ⁺ concentration, 1.5 × 10 ⁴ cells/well of HepG2 cells were seeded in a 96-well plate, and DMEM medium (Nakarai Tesque approved) was seeded in a 96-well plate at 37° C. under CO ₂ (5%) conditions. Shikigaisha, containing 10% FBS) for 96 hours. After 96 hours of culture, DMEM medium (containing 1% albumin, no FBS (Comparative Example 10)) that does not contain sesamin/epicesamin mixture (SE) and nicotinamide riboside (NR, using chloride), SE at 0.3 μM DMEM medium containing 1% albumin (containing 1% albumin, no FBS (Comparative Example 11)), DMEM medium containing 10 µM NR (containing 1% albumin, no FBS (Comparative Example 12)), or 0.3 µM SE and NR The DMEM medium (containing 1% albumin, no FBS (Example 5)) containing 10 µM was exchanged with the medium in each well, and further cultured for 24 hours. Thereafter, the addition medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque Co., Ltd.), followed by addition of Lysis Buffer (Amplite (registered trademark) Colorimetric NAD/NADH Ratio Assay Kit, AAT Bioquest) Thus, the cell extract was recovered. Then, according to the kit's manual, intracellular NAD ⁺ concentration was analyzed. The intracellular NAD ⁺ concentration was calculated as a value per protein concentration by measuring the protein concentration of the cell extract (Pierce (registered trademark) BCA Protein Assay Kit, Thermo Scientific).

As for the intracellular NAD ⁺ concentration, an increase of 5.0% was observed in the SE 0.3 μM group of Comparative Example 11 with respect to Comparative Example 10 (a medium containing no Cont, SE, and NR), and the NR 10 μM group of Comparative Example 12 increase was not recognized. On the other hand, an increase of 8.0% was recognized in the combination group of SE 0.3 μM and NR 10 μM in Example 5, which is simply the sum of the increase rate by SE 0.3 μM treatment and the increase rate by NR 10 μM treatment (5.0% ) was obviously greater than From the above, it was confirmed that the synergistic increase effect of intracellular NAD ⁺ concentration was confirmed by the combination treatment of SE and NR at a molar ratio (SE:NR) of 1:33.

From the above, it became clear that the composition containing the sesamin/epicesamine mixture and nicotinamide riboside (NR) exhibits a synergistic effect of increasing the intracellular NAD ⁺ concentration.

<Comparative Examples 13 to 16, Examples 6 and 7: Evaluation test of intracellular NAD ⁺ concentration (intracellular NAD concentration) by sesamin/epicesamine mixture (SE) and nicotinamide mononucleotide (NMN)>

In order to investigate the effect on the intracellular NAD ⁺ concentration, 2.5 × 10 ⁴ cells/well of HepG2 cells were seeded in a 96-well plate, and DMEM medium (Nakarai Tesque approved) was seeded in a 96-well plate at 37° C. under CO ₂ (5%) conditions. Shikigaisha, containing 10% FBS) for 48 hours. After 48 hours of culture, a DMEM medium containing no sesamin/epicesamine mixture (SE) and nicotinamide mononucleotide (NMN) (containing 1% albumin, no FBS (Comparative Example 13)), a DMEM medium containing 10 µM SE (Contains 1% albumin, no FBS (Comparative Example 14)), DMEM medium containing 30 μM NMN (containing 1% albumin, no FBS (Comparative Example 15)), DMEM medium containing 100 μM NMN (1% albumin containing, no FBS (Comparative Example 16)), DMEM medium containing 10 μM SE and 30 μM NMN (containing 1% albumin, no FBS (Example 6)) or DMEM medium containing 10 μM SE and 100 μM NMN (Containing 1% albumin, no FBS (Example 7)) was exchanged with the medium in each well, and further cultured for 24 hours. Thereafter, the addition medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque Co., Ltd.), followed by addition of Lysis Buffer (Amplite (registered trademark) Colorimetric NAD/NADH Ratio Assay Kit, AAT Bioquest) Thus, the cell extract was recovered. Then, according to the kit's manual, intracellular NAD ⁺ concentration was analyzed. The intracellular NAD ⁺ concentration was calculated as a value per protein concentration by measuring the protein concentration of the cell extract (Pierce (registered trademark) BCA Protein Assay Kit, Thermo Scientific). The obtained result (average of N=3) is shown in FIG. 4 (*: p<0.05).

From Figure 4, the intracellular NAD ⁺ concentration was 14.2% in the SE 10 µM group of Comparative Example 14 and 18.9% in the NMN 30 µM group of Comparative Example 15, with respect to Comparative Example 13 (a medium containing no SE and NR). , An increase of 21.3% was recognized in the NMN 100 µM group of Comparative Example 16. On the other hand, an increase of 38.0% was recognized in the combination group of SE 10 μM and NMN 30 μM in Example 6, which is the increase rate by SE 10 μM treatment in Comparative Example 14 and the increase by NMN 30 μM treatment in Comparative Example 15 It was clearly greater than simply adding the percentage (33.1%).

In addition, an increase of 74.6% was recognized in the combination group of SE 10 μM and NMN 100 μM in Example 7, which is the increase rate by SE 10 μM treatment in Comparative Example 14 and the increase by NMN 100 μM treatment in Comparative Example 16 It was clearly greater than simply adding the percentage (35.5%).

From the above, it was confirmed that the synergistic increase effect of intracellular NAD ⁺ concentration was confirmed by the combination treatment of SE and NMN at a molar ratio (SE:NMN) of 1:3 or 1:10.

From the above, also for a composition containing a combination of NMN and/or salts thereof known as NAD intermediate metabolites and at least one type of sesamin (preferably, a sesamin/epicesamin mixture), a sesamin/epicesamin mixture and NR, it was clarified that synergistic effect of increasing the intracellular NAD ⁺ concentration was exhibited.

Claims (16)

A composition comprising at least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one member of sesamin as active ingredients. The composition according to claim 1, wherein at least one of sesamin is sesamin and/or episesamine. The method of claim 1 or 2, wherein the molar ratio of at least one selected from the group consisting of NR, NMN and salts thereof to sesamin (at least one selected from the group consisting of NR, NMN and salts thereof / sesamin Ryu) is a composition of 1 to 100. The composition according to any one of claims 1 to 3, wherein the total content of one or more of the sesamin is 0.001 to 10% by weight. 5. The composition according to any one of claims 1 to 4, which enhances, inhibits a decrease, maintains or improves nicotinamide adenine dinucleotide (NAD) concentrations. 6. The composition according to any one of claims 1 to 5, which enhances, inhibits decline, maintains or improves mitochondrial function. The composition according to any one of claims 1 to 6, which improves, suppresses decrease, maintains or improves the energy production ability of mitochondria. The composition according to any one of claims 1 to 7, which is used for suppression and/or delay of aging caused by a decrease in NAD concentration. The composition according to any one of claims 1 to 8, which is an anti-aging composition. The composition according to any one of claims 1 to 9, which is an oral composition. The composition according to any one of claims 1 to 10, which is food or drink. The composition according to any one of claims 1 to 11, labeled with "inhibition and/or delay of senescence due to decrease in NAD concentration" and/or "inhibition and/or delay of cellular senescence". At least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and at least one of sesamin, nicotinamide adenine dinucleotide (NAD) concentration way of rising. At least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and salts thereof, and at least one of sesamin, nicotinamide adenine dinucleotide (NAD) concentration Methods of improving, suppressing degradation, maintaining or improving At least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one member of sesamin for increasing the concentration of nicotinamide adenine dinucleotide (NAD) more uses. At least one member selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof for improving, suppressing decrease, maintaining or improving the concentration of nicotinamide adenine dinucleotide (NAD), and, the use of one or more of sesamin.

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