WO2021230146A1

WO2021230146A1 - Composition containing sesamin or like and nr and/or nmn

Info

Publication number: WO2021230146A1
Application number: PCT/JP2021/017472
Authority: WO
Inventors: 大輔竹本
Original assignee: サントリーホールディングス株式会社
Priority date: 2020-05-11
Filing date: 2021-05-07
Publication date: 2021-11-18
Also published as: KR20230010217A; JPWO2021230146A1; TW202200160A; AU2021271500A1; JP7594581B2; CN115867289A

Abstract

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

Description

Composition containing NR and / or NMN and sesamin

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

In recent years, extending healthy life expectancy has become an issue in countries with a high proportion of elderly people. One of the factors for shortening healthy life expectancy is a decrease in physical function due to a decrease in the production of ^{nicotinamide adenine dinucleotide (NAD +) in the body with aging.}

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 aging, causing defects in nuclear and mitochondrial function, and causing many age-related pathologies. For example, in Non-Patent Document 1, aging and aging-related diseases include ^{decreased intracellular nicotinamide adenine dinucleotide (NAD +} ) levels and enzymatic activity of the longevity gene sirtuin, which is a ^{NAD + -dependent deacetylase.} It has been suggested to be associated with decline. In recent years, ^{it has been reported that increasing NAD +} activates sirtuins and exhibits an anti-aging effect (Non-Patent Document 2). For this reason, vigorous research is being conducted on the search for ingredients that are effective in preventing or ameliorating the decline in ^{NAD +} associated with aging and that can be applied to pharmaceuticals, foods for specified health uses, functional foods, etc. ..

For example, in Non-Patent Document 3, the NAD precursor nicotinamide riboside (NR) induces mitochondrial expanded protein response and synthesis of prohibitin protein, thereby muscular stem cells (MuSC) in aged mice. Is disclosed to have been activated. It is also disclosed that NR prevented MuSC aging in a mouse model of muscular dystrophy, NR delayed aging of neural SC (stem cells), and melanocyte SC extended the lifespan of mice.

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

On the other hand, regarding sesamin and / or episesamin, no suggestion or disclosure has been made regarding the action of increasing nicotinamide adenine dinucleotide (NAD) in vivo.

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

As a result of diligent research to solve the above problems, the present inventor has an action of increasing nicotinamide adenine dinucleotide (NAD), and further, sesamines, nicotinamide riboside (NR), and nicotinamide mononucleotide. It has been found that a composition containing (NMN) and at least one selected from the group consisting of salts thereof effectively increases nicotinamide adenine dinucleotide (NAD).

The present invention relates to the following compositions.
[1] A composition containing at least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one sesamin as an active ingredient.
[2] The composition according to the above [1], wherein one or more of the sesamin species is sesamin and / or episesamin.
[3] The molar ratio of one or more selected from the group consisting of NR, NMN and their salts to sesamin (one or more selected from the group consisting of NR, NMN and their salts / sesamin) is The composition according to the above [1] or [2], which is 1 to 100.
[4] The composition according to any one of the above [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 the above [1] to [4], which improves, suppresses, maintains or improves the concentration of nicotinamide adenine dinucleotide (NAD).
[6] The composition according to any one of the above [1] to [5], which improves, suppresses, maintains or improves mitochondrial function.
[7] The composition according to any one of the above [1] to [6], which improves, suppresses, maintains or improves the energy production ability of mitochondria.
[8] The composition according to any one of the above [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 the above [1] to [8], which is a composition for anti-aging.
[10] The composition according to any one of the above [1] to [9], which is an oral composition.
[11] The composition according to any one of the above [1] to [10], which is a food or drink.
[12] The description in any of the above [1] to [11] with the indication of "suppression and / or delay of aging due to decrease in NAD concentration" and / or "suppression and / or delay of cell aging". Composition.
[13] Nicotinamide adenine dinucleotide to which one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more sesamines are administered. (NAD) Method for increasing concentration.
[14] Nicotinamide adenine dinucleotide to which one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more sesamines are administered. (NAD) A method for improving, suppressing, maintaining or improving a concentration.
[15] One or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof for increasing the concentration of nicotinamide adenine dinucleotide (NAD), and Use of one or more sesamin.
[16] Selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof for improving, suppressing, maintaining or improving the concentration of nicotinamide adenine dinucleotide (NAD). Use of one or more species and one or more sesamin species.

According to the present invention, it is possible to provide a composition having an action of increasing the concentration of nicotinamide adenine dinucleotide (NAD).

A composition containing a sesamin / episesamin mixture (SE) (sesamin: episesamin (weight ratio = 1: 1)) and NR at a molar ratio of 1: 100, showing an effect of increasing the intracellular NAD concentration of SE or NR. It is a graph. A composition containing a sesamin / episesamin mixture (SE) (sesamin: episesamin (weight ratio = 1: 1)) and NR in a molar ratio of 1: 1 showing the effect of increasing the intracellular NAD concentration of SE or NR. It is a graph. A composition containing a sesamin / episesamin mixture (SE) (sesamin: episesamin (weight ratio = 1: 1)) and NR in a molar ratio of 1: 3.3 or 1:10, or the intracellular NAD concentration of NR. It is a graph which shows the increase effect. A composition containing a sesamin / episesamin mixture (SE) (sesamin: episesamin (weight ratio = 1: 1)) and NMN in a molar ratio of 1: 3 or 1:10, the intracellular NAD concentration of SE or NMN. It is a graph which shows the increase effect.

The composition of the present invention contains one or more of sesamin.
Sesamines have the effect of increasing the concentration of nicotinamide adenine dinucleotide (NAD), and have the effect of improving, suppressing, maintaining or improving the concentration of nicotinamide adenine dinucleotide (NAD) in cells, and the concentration of NAD. It is used for improvement, suppression of decrease in NAD concentration, maintenance of NAD concentration, or improvement of NAD concentration. Increasing the concentration of nicotinamide adenine dinucleotide (NAD) means increasing the amount of nicotinamide adenine dinucleotide (NAD). The NAD concentration means the intracellular NAD concentration.

Sesamins have an action of increasing the concentration of nicotinamide adenine dinucleotide (NAD), and are expected to contribute to the prevention or improvement of aging associated with the decrease of the NAD concentration by improving, suppressing, maintaining or improving the NAD concentration. .. Aging is understood to be a phenomenon in which physical, physiological and mental functions decline. Physical changes due to aging begin around the age of 40 after reaching maturity, wrinkles on the skin, hair and teeth loss, whitening, deterioration of accumulation and recovery of fatigue, deterioration of eyesight and hearing, deterioration of motor function. , Decreased muscle strength and activity, decreased sleep quality, decreased bone mass, etc. Although aging is not a disease in itself, deterioration of physical and physiological functions increases the risk of so-called senile diseases such as arteriosclerosis, abnormal glucose / lipid metabolism, nerve loss degeneration, osteoporosis, and cataract. And, with the decline of physical function, aging of mental function such as memory and learning will occur. Increasing the nicotinamide adenine dinucleotide (NAD) concentration is effective in preventing or ameliorating aging associated with the decrease in NAD concentration.

(Sesamin)
In the present invention, sesamin is a general term for compounds containing sesamin and its analogs. Sesamin is one of the major lignan compounds contained in sesame seeds. Examples of sesamin analogs include episesamin and dioxabicyclo [3.3.0] octane derivatives described in JP-A-4-9331. As one or more kinds of sesamin, one kind of these compounds may be used alone, or two or more kinds may be used. Specific examples of sesamin include sesamin, episesamin, sesaminol, episesaminol, sesamol, sesamolin and the like, and these stereoisomers or racemates can be used alone or in combination. Further, a metabolite of sesamin (for example, described in JP-A-2001-139579) is also a sesamin analog contained in the sesamin of the present invention as long as the effect of the present invention is shown, and is used in the present invention. Can be done. In the present invention, sesamin and / or episesamin can be preferably used as one or more of the sesamin, and sesamin and episesamin can be more preferably used. When sesamin and episesamin are used, their ratios are not particularly limited, but for example, sesamin: episesamin (weight ratio) is preferably 1: 0.1 to 1: 9, and more preferably 1: 0.3 to 1: 3. , 1: 0.5 to 1: 2 are more preferable.

The sesamin used in the present invention is not limited by its form, production method, or the like. For example, in the case of sesamin, sesamin (referred to as sesamin extract or purified product) extracted from sesame oil by a known method (for example, the method described in JP-A-4-9331) can be used. Alternatively, commercially available sesame oil (liquid) can be used as it is. However, when sesame oil is used, the flavor peculiar to sesame oil may be evaluated as sensually unfavorable. Therefore, a tasteless and odorless sesamin extract (or refined sesamin) extracted from sesame oil is used. Is preferable. In addition, when sesame oil is used, the content of sesamin is low, and if a preferable amount of sesamin is to be added, the volume of the prescribed composition per unit dose becomes too large, which may cause inconvenience in intake. .. In particular, when the product is formulated for oral administration, the product (tablets, capsules, etc.) becomes too large and the intake is hindered. Therefore, it is preferable to use a sesamin extract (or a purified sesamin) from sesame oil from the viewpoint that the intake may be small. Sesamin can also be obtained by synthesis. As the method, for example, sesamin and episesamin can be synthesized by the method of Beroza et al. (J. Am. Chem. Soc., 78, 1242 (1956)). Metabolites of sesamin and episesamin can be synthesized by the method of Urata et al. (Chem. Pharma. Bull. (Tokyo), 56 (11) 1611-2 (2008)).

Sesamin is a compound contained in natural products and foods and drinks, which has abundant eating experience and is recognized for its high safety. Safety-guaranteed sesamin are optimal for continuous and long-term ingestion.

(Nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof)
The composition of the present invention comprises one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof.
NR and NMN are intermediate metabolites of NAD. It is known that NR is converted to NMN by nicotinamide riboside kinase (NRK) and NAD ^{+ is synthesized.} NR, NMN and salts thereof are known compounds and can be produced by a known production method, or commercially available products can also be used.

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

As the salt of NR and / or NMN, a salt that can be used for foods and drinks, pharmaceuticals and the like is preferable, and for example, chloride; alkali metal salt such as sodium salt and potassium salt; alkaline earth metal salt such as calcium salt and magnesium salt. And so on. As the salt of NR, nicotinamide riboside chloride (chloride) is preferable.

(Composition containing one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more sesamins)
The composition of the present invention contains one or more selected from the group consisting of the above nicotinamide riboside (NR), the above nicotinamide mononucleotide (NMN) and salts thereof, and one or more of the above sesamin. do. The composition of the present invention contains at least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more of the above sesamin as active ingredients. contains. 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 enhancing the effect of increasing the nicotinamide adenine dinucleotide (NAD) concentration, that is, from the viewpoint of effectively enhancing the effect of improving the NAD concentration, the effect of suppressing the decrease, the effect of maintaining or improving the concentration. , The molar ratio of one or more selected from the group consisting of NR, NMN and salts thereof to sesamines (one or more selected from the group consisting of NR, NMN and salts thereof / sesamines) is 1 to 1. It is preferably 100. In addition, the molar ratio of one or more selected from the group consisting of NR, NMN and their salts to sesamin (one or more selected from the group consisting of NR, NMN and their salts / sesamin) is 3 It is more preferably to 80, and even more preferably 5 to 50. In the composition of the present invention, NR is exhibited because it exerts an anti-aging effect by enhancing the action of increasing the nicotinamide adenine dinucleotide (NAD) concentration, that is, the effect of improving the NAD concentration, the effect of suppressing the decrease, the effect of maintaining or improving the concentration. , NMN or salts thereof and sesamines in the above-mentioned specific range is preferable from the viewpoint of anti-aging action.
In addition, in this specification, when the amount of NR, NMN or these salts is shown, the value converted into the amount of nicotinamide riboside (NR) is used. The NR-equivalent weight of one or more selected from the group consisting of NR, NMN and salts thereof is the NR-equivalent value of the total weight of NR, NMN and their salts.

The total content of one or more kinds of sesamin contained in the composition of the present invention is not particularly limited and can be set according to the form and the like.
The total content of sesamin in the composition of the present invention is, for example, preferably 0.001% by weight or more, more preferably 0.01% by weight or more, still more preferably 0.05% by weight or more in the composition. Further, 10% by weight or less is preferable, and 5% by weight or less is more preferable. In one embodiment, the total content of sesamin 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 in the composition. When two or more kinds of sesamin compounds are contained, the total content is the total content thereof.

The total content of one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof contained in the composition of the present invention is not particularly limited, and the form thereof and the like. Can be set according to.
The total content of one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof in the composition of the present invention is, for example, 0 in the composition. 001% by weight or more is preferable, 0.01% by weight or more is more preferable, 0.05% by weight or more is further preferable, 95% by weight or less is preferable, and 80% by weight or less is more preferable. In one embodiment, the total content of one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof is 0.001 to 95% by weight in the composition. Is preferable, 0.01 to 80% by weight is more preferable, and 0.05 to 70% by weight is further preferable. The total content is the total content of two or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof. The quantity.

The composition of the present invention is capable of increasing the concentration of nicotinamide adenine dinucleotide (NAD), and is intended to improve, suppress, maintain or improve the concentration of nicotinamide adenine dinucleotide (NAD). It is capable of improving, suppressing, maintaining, or improving the concentration of nicotinamide adenine dinucleotide (NAD) that has decreased with age.

In vivo NAD plays an important role in promoting the expression and synthesis of molecules involved in mitochondrial function and energy production by activating sirtuins and deacetylating downstream enzymes or transcription factors. Therefore, by improving, suppressing, maintaining or improving the NAD concentration, an improvement, suppression, maintenance or improvement effect of mitochondrial function can be obtained. The composition of the present invention can improve, suppress, maintain or improve mitochondrial function. In addition, the composition of the present invention can improve, suppress, maintain or improve the energy producing ability of mitochondria. In addition, the composition of the present invention thus exerts an anti-cell senescence effect.

In the present specification, the mitochondrial function and the energy producing ability of mitochondria may be evaluated based on ordinary knowledge in the technical field to which the present invention belongs, and the method thereof is not particularly limited. For example, using an extracellular flux analyzer, the rate of oxygen consumption used by mitochondria during ATP synthesis in the cells to be measured (hereinafter, also referred to as “OCR”) can be determined by using an ATP synthase inhibitor (eg, oligomycin). And rotenone) and a decoupler (eg, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)) can be continuously measured with the addition of an assessment of mitochondrial function. The evaluation items can evaluate mitochondrial function, for example, by analyzing the basal respiratory volume, ATP production ability, and maximum respiratory volume, which are the main indicators in the evaluation of mitochondrial function.

The composition of the present invention can be used for suppressing and / or delaying aging, and is preferably used for suppressing and / or delaying aging associated with a decrease in NAD concentration.

In one embodiment, the composition of the present invention improves, suppresses, maintains or improves the NAD concentration, and is suitably used for improving, suppressing, maintaining or improving the NAD concentration that has decreased with age. Will be done.
In one embodiment, it is suitably used for improving, suppressing, maintaining or improving the NAD concentration that has decreased due to aging in middle-aged and elderly people. Middle-aged and elderly people include the elderly. The middle-aged person may be, for example, a human being 40 years old or older, and the elderly person may be, for example, a human being 60 years old or older or 65 years old or older.
NAD concentration of animals such as human, can be determined by conventional methods in the art of the present invention, for example, Amplite (TM) Colorimetric NAD / NADH Ratio Assay Kit (AAT Bioquest Co.) and, ^NAD + / It can be measured by measuring the intracellular NAD concentration using a NADH Assay Corollimetric Kit (Biovision).

The composition of the present invention can be used for the treatment of a condition or disease in which prevention or improvement can be expected by improving, suppressing, maintaining or improving the NAD concentration. Such conditions or diseases include, for example, deterioration of physical function, physiological function, and mental function with aging, specifically, for example, aging symptoms of skin (wrinkles, occurrence of sagging, skin tension). (Loss of loss, etc.), dry skin due to aging (decrease in moisturizing skin), skin stains, freckles, rough skin, 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, myocardial cells, etc.) due to active oxygen, loss of hair and teeth, decreased eyesight and hearing, decreased motor function, decreased bone mass , Decreased physical strength, decreased memory, decreased learning ability, decreased immune function, outbreak of senile disease, etc.
As used herein, prevention includes preventing the onset, delaying the onset, reducing the incidence, reducing the risk of onset, and the like. Improvement of a condition or disease is to recover the subject from the condition or disease, alleviate the symptoms of the condition or disease, improve the symptoms of the condition or disease, delay the progression of the condition or disease, or prevent it. Etc. are included.

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, ie human surgery, treatment or diagnosis.
The composition of the present invention can be in the form of foods and drinks, pharmaceuticals, quasi-drugs, feeds and the like. The composition of the present invention may itself be a food or drink, a pharmaceutical product, a quasi-drug, a feed or the like used for improving, suppressing, maintaining or improving the concentration of nicotinamide adenine dinucleotide (NAD). , Materials or formulations used in combination with these may be used.
In addition, the composition of the present invention itself is a food or drink for improving, suppressing, maintaining or improving mitochondrial function, or for improving, suppressing, maintaining or improving the energy production ability of mitochondria. It may be a drug, a quasi-drug, a feed, or the like, or it may be a material or a preparation used in combination with these.
The composition of the present invention can be provided, as an example, in the form of an agent, but is not limited to this form. The agent can be provided as it is as a composition 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. The oral composition may be a food or drink, an oral drug, a quasi-drug, a feed or the like itself, or may be contained therein. The composition of the present invention is preferably a food or drink or an oral drug, and more preferably a food or drink.

The composition of the present invention is added in addition to at least one selected from the group consisting of NR, NMN and salts thereof, and one or more sesamins, as long as the effects of the present invention are not impaired. Agents, any component can be contained. These additives and components can be selected according to the form of the composition and the like, and generally, those that can be used for foods and drinks, pharmaceuticals, quasi-drugs, feeds and the like can be used. When the composition of the present invention is a food or drink, a pharmaceutical product, a quasi-drug, a feed or the like, the production method thereof is not particularly limited and can be produced by a general method.

For example, when the composition of the present invention is used as a food or drink, in addition to at least one selected from the group consisting of NR, NMN and salts thereof, and one or more of sesamin, components that can be used in the food and drink. (For example, food materials, food additives used as needed, etc.) can be blended to make various foods and drinks. Foods and drinks are not particularly limited, and examples thereof include general foods and drinks, health foods, health drinks, foods with functional claims, foods for specified health use, foods and drinks for the sick, and the like. The above-mentioned health foods, foods with functional claims, foods for specified health use, etc. include, for example, various types of fine granules, tablets, granules, powders, capsules, chewables, dry syrups, syrups, liquids, beverages, liquid foods, etc. It can be used as a pharmaceutical form.

When the composition of the present invention is a pharmaceutical product or a quasi-drug, for example, at least one selected from the group consisting of NR, NMN and salts thereof, and one or more sesamines, and pharmacology. Various dosage forms of pharmaceuticals or quasi-drugs can be obtained by blending a carrier that is generally acceptable, additives that are added as necessary, and the like. Such carriers, additives and the like may be pharmacologically acceptable as long as they can be used in pharmaceutical products or quasi-drugs, for example, excipients, binders, disintegrants, lubricants, etc. 1 or 2 or more of antioxidants, colorants and the like can be mentioned. Examples of the administration (ingestion) form of the drug or quasi-drug include oral or parenteral (transdermal, transmucosal, enteral, injection, etc.) administration. When the composition of the present invention is a drug or a quasi-drug, it is preferably an oral drug or a quasi-drug. Dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewables and the like. The drug may be a non-human animal drug.

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 one or more sesamin may be added to the feed. The feed also contains feed additives. Examples of the feed include livestock feed used for cattle, pigs, chickens, sheep, horses and the like; small animal feed used for rabbits, rats, mice and the like; pet food used for dogs, cats, small birds and the like.

The composition of the present invention is preferably an oral composition (a composition that is orally ingested (orally administered)). The dose (which can also be referred to as ingestion) of the composition of the present invention is not particularly limited. The dose of the composition of the present invention may be any amount as long as the effect of improving, suppressing, maintaining or improving the nicotinamide adenine dinucleotide (NAD) concentration can be obtained, and the administration form, administration method, body weight of the subject, etc. It may be set appropriately according to the above.

In one embodiment, when the composition of the present invention is orally ingested or administered to a human (adult), the total dose of sesamin is 60 kg body weight per day, preferably 0.5 mg or more, more preferably. Is 1 mg or more, more preferably 3 mg or more, preferably 200 mg or less, more preferably 100 mg or less, still more preferably 80 mg or less. In one embodiment, the total dose of sesamin is 60 kg / day for humans (adults), preferably 0.5 to 200 mg, more preferably 1 to 100 mg, still more preferably 3 to 80 mg. It is preferable to ingest or administer the above amount at least once a day, for example, once a day or several times (for example, 2 to 3 times). In one embodiment, it is preferable to ingest or administer the above amounts of sesamin to humans. In one aspect, the compositions of the invention can be used to ingest or administer the above amounts of sesamin per day to a human body weight of 60 kg. The total dose is the total dose when two or more sesamin compounds are used. In one embodiment, sesamin and / or episesamin is added to the total daily dose of sesamin and episesamin at a body weight of 60 kg, preferably 0.5 to 200 mg, more preferably 1 to 100 mg, still more preferably 3 to 80 mg, human ( It is preferable to ingest or administer it orally to an adult).

In one embodiment, when the composition of the present invention is orally ingested or administered to a human (adult), it is composed of a group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof. The total dose of one or more selected is 60 kg / day in terms of NR, preferably 0.5 mg or more, more preferably 1 mg or more, still more preferably 3 mg or more, and preferably 20000 mg or less, more preferably. Is 10,000 mg or less, more preferably 8000 mg or less. In one embodiment, the total dose of one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof is, in terms of NR, human (adult). The body weight per day is 60 kg, 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 several times (for example, 2 to 3 times). In one embodiment, one or more selected from the group consisting of the above amounts of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof may be orally ingested or administered to humans. preferable. In one embodiment, the composition of the invention is selected from the group consisting of the above amounts of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof per 60 kg body weight per day for humans. It can be used to ingest or administer one or more species. The total dose is the total amount when two or more compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof are used.

The composition of the present invention is preferably continuously ingested or administered. It is expected that the above effects will be enhanced by continuous ingestion or administration of sesamin. In addition, the compounds selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof may enhance the above effects by continuous ingestion or administration. Be expected. In one embodiment, 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, and particularly preferably 12 weeks or longer. preferable.

The composition of the present invention may be labeled with a function exerted by improving, suppressing, maintaining or improving the concentration of nicotinamide adenine dinucleotide (NAD). Such indications include, for example, "improvement, suppression or maintenance of mitochondrial function", "improvement, suppression or maintenance of energy production ability by mitochondria", "suppression and / or delay of aging due to decrease in NAD concentration". Indication of one or more functions selected from the group consisting of "inhibition and / or delay of cell aging" and "inhibition of aging" may be attached.
In one aspect of the present invention, the composition of the present invention is preferably a food or drink with the above indication. Further, the above display may be a display to the effect that it is used to obtain the above function.

The subject to be ingested or administered (which can also be referred to as an administration subject) of the composition of the present invention is not particularly limited, and humans and non-human animals can be ingested. Examples of animals other than humans include industrial animals, pets, experimental animals and the like. Specifically, industrial animals include livestock such as cattle, horses, pigs, goats and sheep, poultry such as chickens, ducks, quail, turkeys and ostriches, as well as yellowtail, hamachi, madai, maji, koi, nigga and eel. It refers to animals that are industrially required to be bred, such as fish such as yellowtail. Pets are so-called companion animals such as dogs, cats, marmosets, birds and hamsters, and companion animals, and experimental animals are mice, rats, guinea pigs, beagle dogs, miniature pigs, lizard monkeys and crab monkeys, etc., medicine, biology, agriculture. And represents animals used for research in fields such as pharmaceuticals.

The subject (which may also be the subject of administration) to which the composition of the present invention is ingested or administered is preferably a human or non-human mammal, and more preferably a human.
In one embodiment, the subject to be administered includes a subject who needs or desires to improve, suppress, maintain or improve the nicotinamide adenine dinucleotide (NAD) concentration. Such subjects include, for example, middle-aged and elderly people, subjects who need or desire to improve, suppress, maintain or improve mitochondrial function, improve, suppress, maintain or improve mitochondrial energy production. Examples include desired subjects, subjects that require or desire to suppress and / or delay aging due to a decrease in NAD concentration. The middle-aged person may be, for example, a person aged 40 years or older. Among the middle-aged and elderly people in one aspect, the elderly are preferable as the target. The elderly person may be, for example, a person aged 60 years or older or 65 years or older. The composition of the present invention is used, for example, for a healthy person for the purpose of preventing or preventing a symptom or disease that can be prevented or expected to be improved by improving, suppressing, maintaining or improving the nicotinamide adenine dinucleotide (NAD) concentration. You can also do it.

The present invention also includes the following methods.
Nicotinamide adenine dinucleotide (NAD) to which one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more of sesamines are administered. How to increase the concentration.
Nicotinamide adenine dinucleotide (NAD) to which one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more of sesamines are administered. A method for improving, suppressing, maintaining or improving the concentration.
Aged-decreased nicotinamide adenine to which one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more sesamines are administered. A method for improving, suppressing, maintaining or improving a dinucleotide (NAD) concentration.

The present invention also includes the following uses.
Nicotinamide One or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof for increasing the concentration of nicotinamide adenine dinucleotide (NAD), as well as sesamin. Use of one or more types.
One selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof for improving, suppressing, maintaining or improving the concentration of nicotinamide adenine dinucleotide (NAD). The above, and the use of one or more sesamin.
From the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof for improving, suppressing, maintaining or improving the nicotinamide adenine dinucleotide (NAD) concentration that decreased with age. Use of one or more selected species, as well as one or more sesamin species. The methods and uses may be therapeutic or non-therapeutic methods or uses.
Nicotinamide adenine dinucleotide (by administering one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more sesamines. NAD) It is possible to improve, suppress, maintain or improve the concentration. This makes it possible to improve, suppress, maintain or improve mitochondrial function, improve, suppress, maintain or improve mitochondrial energy production, and suppress and / or delay aging due to a decrease in NAD concentration.

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

In the above method and use, a desired action (an action of increasing the nicotinamide adenine dinucleotide (NAD) concentration, that is, an action of improving, suppressing, maintaining or improving the NAD concentration, thereby improving or suppressing the decrease of mitochondrial function, An amount (effective amount) that can obtain a maintenance or ameliorating action, an improvement in the energy production ability of mitochondria, a decrease suppression, a maintenance or improvement effect, and / or an aging suppression and / or a delay effect due to a decrease in NAD concentration. ), One or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more sesamines may be used. The above-mentioned book describes preferable doses, administration targets, etc. of one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more sesamin. It is the same as the composition of the invention. One or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more sesamin may be administered as they are, and include them. It may be administered as a composition. For example, the composition of the present invention described above may be used.

In the above use, a composition containing one or more of sesamines and a composition containing one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof. Nicotinamide ribosides as intended by the present invention can be prepared individually with the product and taken at about the same time, or if one composition is taken and then the other composition is taken while the effect is sustained. Effect of combined use of one or more selected from the group consisting of (NR), nicotinamide mononucleotide (NMN) and salts thereof and one or more sesamines (effect of increasing NAD concentration, that is, improvement of NAD concentration). , Suppression of decline, maintenance or improvement, thereby improvement of mitochondrial function, suppression of decline, maintenance or improvement, improvement of energy production ability of mitochondria, suppression of decline, maintenance or improvement, and / or reduction of NAD concentration (Suppression and / or delay of aging) is obtained. Therefore, a composition containing one or more of sesamines and a composition containing one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof. Kits and the like containing the same are also included in the scope of the composition of the present invention.

The present invention comprises one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof for producing the composition of the present invention, and one of sesamin. Including use with more than seeds.

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

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

^{<Comparative Examples 1 to 3, Example 1: Evaluation test of intracellular NAD +} concentration (intracellular NAD concentration) with sesamin / episesamin mixture (SE) and nicotinamide riboside (NR)>
To investigate the effect on intracellular NAD ⁺ ^{concentration, 0.5 × 10 4} cells / well Hepa1-6 cells were seeded in 96-well plates and DMEM medium (Nacalai Tesque) under the conditions of _{37 ° C. and CO 2 (5%).} Co., Ltd.) was cultured for 96 hours in (containing 10% FBS). After 96 hours of culturing, DMEM medium (containing 1% albumin, without FBS (Comparative Example 1)) containing no sesamine / episesamine mixture (SE) and nicotine amide riboside (using NR chloride (Carbosys Limited)), DMEM medium containing 0.3 μM SE (containing 1% albumin, without FBS (Comparative Example 2)), DMEM medium containing 30 μM NR (containing 1% albumin, without FBS (Comparative Example 3)), or with SE 0.3 μM. DMEM medium containing 30 μM NR (containing 1% albumin, without FBS (Example 1)) was replaced with the medium in each well and cultured for another 24 hours. Then, the added medium is removed, the cells in the well are washed with D-PBS (Nacalai Tesque, Inc.), and then Lysis Buffer (Amplite (registered trademark) Coloretic NAD / NADH Ratio Assay Kit, AAT Bioquest) is added. The cell extract was collected. Then, the intracellular NAD ⁺ concentration was analyzed according to the Kit manual. The intracellular NAD ⁺ concentration was calculated as a value per protein concentration by measuring the protein concentration of the cell extract (Pierce® BCA Protein Assay Kit, Thermo Scientific). The significance test was performed by an unpaired t-test (significance level: p <0.05, relative to the control group).
The obtained results (average of N = 3) are shown in FIG. 1 (*: p <0.05).

From FIG. 1, the intracellular NAD ⁺ concentration was 2.3% in the SE 0.3 μM group of Comparative Example 2 and 3. in the NR 30 μM group of Comparative Example 3 with respect to Comparative Example 1 (medium containing no SE and NR). A 1% increase was observed. On the other hand, an increase of 14.6% was observed in the combination group of SE 0.3 μM and NR 30 μM in Example 1, which is a simple increase in the increase rate by SE 0.3 μM treatment in Comparative Example 2 and the increase rate by NR 30 μM treatment in Comparative Example 3. It was significantly larger than the value added to (5.4%). From the above, the synergistic effect of increasing the ^{intracellular NAD +} concentration by treating SE and NR in combination at a molar ratio (SE: NR) of 1: 100 was confirmed.

^{<Comparative Examples 4 to 6, Example 2: Evaluation test of intracellular NAD +} concentration (intracellular NAD concentration) with sesamin / episesamin mixture (SE) and nicotinamide riboside (NR)>
To investigate the effect on intracellular NAD ⁺ ^{concentration, 1.0 × 10 4} cells / well Hepa1-6 cells were seeded in 96-well plates and DMEM medium (Nacalai Tesque) under the conditions of _{37 ° C. and CO 2 (5%).} Co., Ltd.) was cultured for 48 hours in (containing 10% FBS). After 48 hours of culture, DMEM medium containing no sesamine / episesamine mixture (SE) and nicotine amide riboside (NR, using chloride) (with 1% albumin, without FBS (Comparative Example 4)), DMEM containing 10 μM SE. Medium (1% albumin-containing, no FBS (Comparative Example 5)), DMEM medium containing 10 μM NR (1% albumin-containing, no FBS (Comparative Example 6)), or DMEM medium containing 10 μM SE and 10 μM NR (1%). Albumin-containing, FBS-free (Example 2)) was replaced with the medium in each well and cultured for an additional 24 hours. Then, the added medium is removed, the cells in the well are washed with D-PBS (Nacalai Tesque, Inc.), and then Lysis Buffer (Amplite (registered trademark) Coloretic NAD / NADH Ratio Assay Kit, AAT Bioquest) is added. The cell extract was collected. Then, the intracellular NAD ⁺ concentration was analyzed according to the Kit manual. The intracellular NAD ⁺ concentration was calculated as a value per protein concentration by measuring the protein concentration of the cell extract (Pierce® BCA Protein Assay Kit, Thermo Scientific). The obtained results (average of N = 3) are shown in FIG. 2 (*: p <0.05).

From FIG. 2, the intracellular NAD ⁺ concentration was 1.5% in the SE10 μM group of Comparative Example 5 and 11.6% in the NR10 μM group of Comparative Example 6 with respect to Comparative Example 4 (medium containing no SE and NR). Was observed to increase. On the other hand, an increase of 15.7% was observed in the combination group of SE10 μM and NR10 μM of Example 2, which is a value obtained by simply adding the increase rate of SE10 μM treatment of Comparative Example 5 and the increase rate of NR10 μM treatment of Comparative Example 6. It was clearly larger than (13.1%). From the above, the synergistic effect of increasing the ^{intracellular NAD +} concentration by treating SE and NR in combination at a molar ratio (SE: NR) of 1: 1 was confirmed.

^{<Comparative Examples 7 to 9, Examples 3 and 4: Evaluation test of intracellular NAD +} concentration (intracellular NAD concentration) with sesamin / episesamin mixture (SE) and nicotinamide riboside (NR)>
To investigate the effect on intracellular NAD ⁺ ^{concentration, 1.0 × 10 4} cells / well Hepa1-6 cells were seeded in 96-well plates and DMEM medium (Nacalai Tesque) under the conditions of _{37 ° C. and CO 2 (5%).} Co., Ltd.) was cultured for 48 hours in (containing 10% FBS). After 48 hours of culture, DMEM medium containing no sesamine / episesamine mixture (SE) and nicotine amide riboside (NR, using chloride) (with 1% albumin, without FBS (Comparative Example 7)), DMEM containing 10 μM NR. Medium (containing 1% albumin, without FBS (Comparative Example 8)), DMEM medium containing 30 μM NR (containing 1% albumin, without FBS (Comparative Example 9)), DMEM medium containing 3 μM SE and 10 μM NR (containing 1% albumin) , FBS-free (Example 3)) or DMEM medium containing 3 μM SE and 30 μM NR (1% albumin-containing, no FBS (Example 4)) was replaced with the medium in each well and cultured for another 24 hours. Then, the added medium is removed, the cells in the well are washed with D-PBS (Nacalai Tesque, Inc.), and then Lysis Buffer (Amplite (registered trademark) Coloretic NAD / NADH Ratio Assay Kit, AAT Bioquest) is added. The cell extract was collected. Then, the intracellular NAD ⁺ concentration was analyzed according to the Kit manual. The intracellular NAD ⁺ concentration was calculated as a value per protein concentration by measuring the protein concentration of the cell extract (Pierce® BCA Protein Assay Kit, Thermo Scientific). The obtained results (average of N = 3) are shown in FIG. 3 (*: p <0.05).

From FIG. 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 (medium containing no SE and NR). Was observed to increase. On the other hand, an increase of 17.5% was observed in the combination group of SE3 μM and NR10 μM of Example 3, and an increase of 21.8% was observed in the combination group of SE3 μM and NR30 μM of Example 4. Here, although there was no test example treated with DEME medium containing SE3 μM, a 2.3% increase in NAD concentration was observed in the SE0.3 μM group of Comparative Example 2 and SE10 μM of Comparative Example 5 above. Since a 1.5% increase in NAD concentration was observed in the group, it is inferred that the NAD concentration increased at the same rate in the SE3 μM group as well. Then, the value obtained by simply adding the increase rate (2.3 to 1.5%) of the NAD concentration considered to be obtained by SE3 μM to the increase rate of the NAD concentration in Comparative Example 8 or the above-mentioned Comparing the rate of increase in NAD concentration in Example 3 and Example 4, it can be seen that the rate of increase in Example 3 and Example 4 is clearly large. From the above, the synergistic effect of increasing the ^{intracellular NAD +} concentration by treating SE and NR in combination at a molar ratio (SE: NR) of 1: 3.3 or 1:10 was confirmed.

^{<Comparative Examples 10 to 12, Example 5: Evaluation test of intracellular NAD +} concentration (intracellular NAD concentration) with sesamin / episesamin mixture (SE) and nicotinamide riboside (NR)>
In order to investigate the effect on intracellular NAD ⁺ ^{concentration, 1.5 × 10 4} cells / well HepG2 cells were seeded in a 96-well plate, and DMEM medium (Nacalai Tesque, Inc.) was used under the conditions of _{37 ° C. and CO 2 (5%).} It was cultured for 96 hours in (containing 10% FBS). After 96 hours of culturing, DMEM medium (containing 1% albumin, no FBS (Comparative Example 10)) containing no sesamine / episesamine mixture (SE) and nicotine amide riboside (NR, using chloride), SE was 0.3 μM. DMEM medium containing 1% albumin (containing 1% albumin, without FBS (Comparative Example 11)), DMEM medium containing 10 μM NR (containing 1% albumin, without FBS (Comparative Example 12)), or SE is 0.3 μM and NR is 10 μM. The DMEM medium containing DMEM medium (containing 1% albumin, without FBS (Example 5)) was replaced with the medium in each well, and the medium was further cultured for 24 hours. Then, the added medium is removed, the cells in the well are washed with D-PBS (Nacalai Tesque, Inc.), and then Lysis Buffer (Amplite (registered trademark) Coloretic NAD / NADH Ratio Assay Kit, AAT Bioquest) is added. The cell extract was collected. Then, the intracellular NAD ⁺ concentration was analyzed according to the Kit manual. The intracellular NAD ⁺ concentration was calculated as a value per protein concentration by measuring the protein concentration of the cell extract (Pierce® BCA Protein Assay Kit, Thermo Scientific).

The intracellular NAD ⁺ concentration was increased by 5.0% in the SE 0.3 μM group of Comparative Example 11 and the NR 10 μM group of Comparative Example 12 with respect to Comparative Example 10 (medium containing no Cont, SE and NR). No increase was observed in. On the other hand, an increase of 8.0% was observed in the combination group of SE 0.3 μM and NR 10 μM in Example 5, which was 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 clearly larger than. From the above, the synergistic effect of increasing the ^{intracellular NAD +} concentration by treating SE and NR in combination at a molar ratio (SE: NR) of 1:33 was confirmed.

From the above, it was clarified that the composition containing the sesamin / episesamin mixture and nicotinamide riboside (NR) exhibits a synergistic effect of ^{intracellular NAD + concentration increasing action.}

^{<Comparative Examples 13 to 16, Examples 6 and 7: Evaluation test of intracellular NAD +} concentration (intracellular NAD concentration) by sesamine / episesamine mixture (SE) and nicotinamide mononucleotide (NMN)>
In order to investigate the effect on intracellular NAD ⁺ ^{concentration, HepG2 cells of 2.5 × 10 4} cells / well were seeded in 96-well plates and DMEM medium (Nacalai Tesque, Inc.) under the conditions of _{37 ° C. and CO 2 (5%).} It was cultured for 48 hours in (containing 10% FBS). After 48 hours of culture, DMEM medium (1% albumin-containing, FBS-free (Comparative Example 13)) containing no sesamine / episesamine mixture (SE) and nicotine amide mononucleotide (NMN), DMEM medium containing 10 μM SE (1% albumin). DMEM medium containing 30 μM of NMN (containing 1% albumin, without FBS (Comparative Example 15)), DMEM medium containing 100 μM of NMN (containing 1% albumin, without FBS (Comparative Example 16)). )), DMEM medium containing 30 μM SE10 μM and NMN (1% albumin-containing, no FBS (Example 6)) or DMEM medium containing 100 μM SE10 μM and NMN (1% albumin-containing, no FBS (Example 7)). It was replaced with the medium in each well and cultured for another 24 hours. Then, the added medium is removed, the cells in the well are washed with D-PBS (Nacalai Tesque, Inc.), and then Lysis Buffer (Amplite (registered trademark) Coloretic NAD / NADH Ratio Assay Kit, AAT Bioquest) is added. The cell extract was collected. Then, the intracellular NAD ⁺ concentration was analyzed according to the Kit manual. The intracellular NAD ⁺ concentration was calculated as a value per protein concentration by measuring the protein concentration of the cell extract (Pierce® BCA Protein Assay Kit, Thermo Scientific). The obtained results (average of N = 3) are shown in FIG. 4 (*: p <0.05).

From FIG. 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 (medium containing no SE and NR). An increase of 21.3% was observed in the NMN 100 μM group of Comparative Example 16. On the other hand, an increase of 38.0% was observed in the combination group of SE10 μM and NMN30 μM of Example 6, which is a value obtained by simply adding the increase rate of SE10 μM treatment of Comparative Example 14 and the increase rate of NMN30 μM treatment of Comparative Example 15. It was clearly larger than (33.1%).
Further, an increase of 74.6% was observed in the combination group of SE10 μM and NMN100 μM of Example 7, which is a value obtained by simply adding the increase rate of SE10 μM treatment of Comparative Example 14 and the increase rate of NMN100 μM treatment of Comparative Example 16. It was clearly larger than (35.5%).
From the above, the synergistic effect of increasing the ^{intracellular NAD +} concentration by treating SE and NMN in combination at a molar ratio (SE: NMN) of 1: 3 or 1:10 was confirmed.

From the above, the composition containing a combination of NMN and / or a salt thereof known as an NAD intermediate metabolite and one or more kinds of sesamin (preferably a mixture of sesamin and episesamin) is also sesamin. -Similar to the episesamin mixture and the composition containing NR, it was clarified that it showed a synergistic effect of ^{intracellular NAD + concentration increasing action.}

Claims

A composition containing at least one selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and at least one sesamin as an active ingredient.
The composition according to claim 1, wherein one or more of the sesamin are sesamin and / or episesamin.
The molar ratio of one or more selected from the group consisting of NR, NMN and their salts to sesamin (one or more selected from the group consisting of NR, NMN and their salts / sesamin) is 1 to 100. The composition according to claim 1 or 2.
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.
The composition according to any one of claims 1 to 4, which improves, suppresses, maintains or improves the concentration of nicotinamide adenine dinucleotide (NAD).
The composition according to any one of claims 1 to 5, which improves, suppresses, maintains or improves mitochondrial function.
The composition according to any one of claims 1 to 6, which improves, suppresses, maintains or improves the energy producing ability of mitochondria.
The composition according to any one of claims 1 to 7, which is used for suppressing and / or delaying aging associated with 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 a food or drink.
The composition according to any one of claims 1 to 11 with the indication of "suppression and / or delay of aging associated with a decrease in NAD concentration" and / or "suppression and / or delay of cell aging".
Nicotinamide adenine dinucleotide (NAD) to which one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more of sesamines are administered. How to increase the concentration.
Nicotinamide adenine dinucleotide (NAD) to which one or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof, and one or more of sesamines are administered. A method for improving, suppressing, maintaining or improving the concentration.
Nicotinamide One or more selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof for increasing the concentration of nicotinamide adenine dinucleotide (NAD), as well as sesamin. Use of one or more types.
One selected from the group consisting of nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and salts thereof for improving, suppressing, maintaining or improving the concentration of nicotinamide adenine dinucleotide (NAD). The above, and the use of one or more sesamin.