β-NMN-containing composition

Abstract

To provide a composition that exhibits improvement effect on skin function through more effective ingestion of β-NMN.SOLUTION: The present invention has been completed based on the finding by the inventors that a low dose of β-NMN, when ingested orally or applied to the skin, exerts an immediate effect of improving skin function.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition comprising β-nicotinamide mononucleotide (β-NMN). [Background technology]

[0002] NAD+ (nicotinamide adenine dinucleotide), which functions as a coenzyme in redox reactions in eukaryotic cells, plays an important role in the metabolic pathways of living organisms. NAD+ is said to decrease with age and is thought to play an important role in maintaining health. However, it is known that NAD+ is not absorbed into the body even when taken orally. Therefore, in recent years, NAD+ precursors β-NMN (β-nicotinamide mononucleotide) and NR (nicotinamide riboside) are known to be absorbed into the body, and NAD+-related substances such as NMN have been attracting attention as health materials that increase the amount of NAD in the body (Patent Document 1).

[0003] β-NMN is also used in foods, cosmetics, and topical skin preparations, and is known to improve skin function by promoting the production of collagen, elastin, hyaluronic acid, etc. by fibroblasts (Non-Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2014 / 146044 [Non-patent literature]

[0005] [Non-Patent Document 1] Shimamoto et al., Study on the effects and safety of NMN-containing foods on skin function. Pharmacology and Therapy vol.51, No.1, 2023 Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide a composition that has the effect of improving skin function by more effectively ingesting β-NMN. [Means for solving the problem]

[0007] The present inventors discovered that oral ingestion or application of low doses of β-NMN to the skin has an immediate effect of improving skin function, leading to the completion of the present invention.

[0008] in particular, (1) A composition containing β-nicotinamide mononucleotide (β-NMN), which is a rapid-acting skin improvement composition that applies 0.01 mg to 100 mg of β-NMN; (2) A fast-acting skin-improving composition according to (1) used to improve skin elasticity. (3) A fast-acting skin-improving composition according to (1), which is used to inhibit a decrease in skin moisture content. (4) A method for producing a fast-acting skin-improving composition containing β-nicotinamide mononucleotide (β-NMN), the method comprising the step of adjusting the amount of β-NMN to a concentration that can be ingested or applied in the range of 0.01 mg to 100 mg. to provide. [Effects of the Invention]

[0009] According to the present invention, an immediate effect of improving skin function can be obtained by taking a low dose or applying it to the skin. [Brief explanation of the drawings]

[0010] [Figure 1] Type I collagen gene expression level [Figure 2] HAS2 gene expression level DETAILED DESCRIPTION OF THE INVENTION

[0011] In this embodiment, β-NMN (nicotinamide mononucleotide) is represented by the following formula (I), and exists as optical isomers in α- and β-type forms. The present invention relates to β-type nicotinamide mononucleotide. While NAD is not absorbed into the body when orally ingested, β-NMN is absorbed into the body and directly induces NAD biosynthesis, thereby increasing NAD concentrations in the blood and tissues.

[0012] [ka]

[0013] In this embodiment, the method for obtaining β-NMN is not particularly limited; it may be a commonly available product (e.g., commercially available β-NMN) or may be produced by a known method. β-NMN may be a crude product or a purified product. For example, any composition containing β-NMN, such as β-NMN contained in yeast extract, may be used.

[0014] The β-NMN content in the composition of this embodiment is optional and may range from 10 μg to 2000 mg, such as 50 μg to 1000 mg, 100 μg to 500 mg, or 200 μg to 250 mg. The daily intake of β-NMN can be adjusted appropriately depending on the intake form, intended use, age, body weight, and other factors. Generally, the daily intake is adjusted to within the range of 10 mg to 1000 mg. However, in the present application, since low doses exhibit immediate effects, the daily intake is adjusted to 1 / 10 to 1 / 1000, preferably 1 / 10 to 1 / 100, of the usual amount. Therefore, the daily intake is adjusted to 0.01 mg to 100 mg. More specifically, for example, a 1 / 1000 amount is adjusted to 0.01 mg to 1 mg, a 1 / 1000 amount is adjusted to 0.1 mg to 10 mg, and a 1 / 10 amount is adjusted to 1 mg to 100 mg. When used as an external preparation such as a quasi-drug or a cosmetic, the application amount should be the same as in this paragraph.

[0015] The compositions of the present invention include food compositions. More specifically, they are functional foods, nutritional supplements, or dietary supplements. The food compositions may contain carriers or additives that can be used in foods. Examples include, but are not limited to, surfactants, excipients, colorants, flavorings, preservatives, stabilizers, buffers, suspending agents, isotonicity agents, binders, disintegrants, lubricants, flow enhancers, and flavoring agents. Other commonly used carriers can also be used as appropriate. Specific examples include light anhydrous silicic acid, lactose, crystalline cellulose, mannitol, maltitol, sorbitol, starch, carmellose calcium, carmellose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinyl acetal diethylaminoacetate, polyvinylpyrrolidone, gelatin, medium-chain fatty acid triglycerides, polyoxyethylene hydrogenated castor oil 60, sucrose, carboxymethylcellulose, corn starch, dextrin, and inorganic salts. The form of the food composition is not particularly limited, and examples thereof include concentrated liquid, powder, granules, tablets, gum, gummy candy, candy, capsule, paste, jelly, drink, and the like.

[0016] Examples of other ingredients that can be contained in the food composition include seasonings such as sugar, salt, soy sauce, miso, and vinegar; sweeteners such as honey, maple syrup, oligosaccharides, and high-intensity sweeteners; acidulants such as citric acid, malic acid, tartaric acid, and acetic acid; bittering agents such as caffeine and naringin; spices such as oregano, pepper, cinnamon, ginger, turmeric, chili pepper, basil, paprika, and wasabi; oils such as salad oil, sesame oil, safflower oil, sunflower oil, rapeseed oil, fish oil, beef tallow, and lard; flavor oils; extracts such as yeast extract, seafood extract, beef extract, pork extract, and chicken extract; fruit juice; vegetable juice; vitamins; minerals; sugars; oligosaccharides; polysaccharides; dietary fiber; amino acids; peptides; fatty acids; coenzymes; flavorings; emulsifiers; thickeners; and colorants.

[0017] The food composition may be ingested three times a day, twice a day, or once a day to achieve the intake amount described above. In one embodiment, the food composition may be ingested as a functional food, for example, with or before or after each meal, or once a day, for example, with or before or after breakfast, lunch, or dinner. It may also be ingested between meals.

[0018] The composition of the present invention includes quasi-drugs and cosmetics. The form of these is not particularly limited, and examples thereof include skincare products such as lotions, emulsions, creams, gels, serums, sunscreen cosmetics, packs, hand creams, foot creams, body lotions, and body creams; cleansing cosmetics such as facial cleansers, makeup removers, soaps, body shampoos, shampoos, rinses, conditioners, and nail polish removers; and makeup cosmetics such as foundations, makeup bases, lip balms, lipsticks, cheek colors, eye colors, eyebrow pencils, and nail polishes. When used as quasi-drugs or cosmetics for the skin, they are preferably topical preparations, just like pharmaceuticals. By using them as topical preparations, β-NMN can directly act on skin cells to exert its effects.

[0019] The quasi-drug or cosmetic product of the present invention may contain a commonly used base or carrier, and, if necessary, various additives. Examples of additives include excipients, oils, powders, buffers, solubilizers, antioxidants, surfactants, thickeners, preservatives, pH adjusters, chelating agents, stabilizers, irritation reducers, antiseptics, pigments, colorants, fragrances, gloss-imparting agents, gelling agents, alcohols, water-soluble polymers, film-forming agents, resins, and keratolytic agents. The bases, carriers, and various additives may be used alone or in combination as necessary.

[0020] The quasi-drug or cosmetic of the present invention may contain active ingredients other than β-NMN, provided that the effects of β-NMN are not impaired. Examples include moisturizing ingredients, anti-inflammatory ingredients, antibacterial ingredients, cell activating ingredients, anti-aging ingredients, blood circulation promoting ingredients, UV protection ingredients, whitening ingredients, vitamins, proteins, peptides, amino acids, and alcohols. These active ingredients may be used alone or in combination as needed.

[0021] The quasi-drug or cosmetic product of the present invention is applied to the skin several times a day so as to achieve the above-mentioned application amount. There are no particular restrictions on the area to which it is applied, and it can be applied to any area such as the face or hands.

[0022] The food composition, quasi-drug, and cosmetic of this embodiment can be used to improve skin function. The improvement of skin function in the present invention means improvement of skin elasticity and suppression or prevention of a decrease in skin moisture content.

[0023] In one aspect, the present invention provides a method for producing the composition. The production method of this aspect is not particularly limited and can employ a general production method. A general production method used for producing food compositions can be appropriately selected depending on the form of the food composition. For example, if the food composition is in the form of a powder, it can be produced by uniformly kneading β-NMN and other ingredients that are blended as needed. The blending amounts of each ingredient can be appropriately determined. The raw materials, blending amounts, and other conditions used in this production method are as described above. [Example]

[0024] The present invention will be specifically described below, but the present invention is not limited thereto.

[0025] (Changes in genes related to skin function) The cells used were normal human dermal fibroblasts (NHDF) (KURABO, KF-4009, neonatal derived). DMEM medium was used, and the cells were seeded onto a 24-well plate and cultured until confluent. β-NMN was added to the medium at concentrations of 1, 10, and 100 μg / ml. After addition, the cells were cultured for 24 hours, and RNA was collected using standard methods and subjected to qRT-PCR. A control was used without addition. The specific method is described below.

[0026] (Cell preparation) Normal human dermal fibroblasts were seeded at 40,000 cells / well in 24-well plates using DMEM medium containing 5% FBS. The seeded cells were cultured under conditions of 5% CO2 and 37°C until confluent. During the period until confluent, the culture medium was replaced with fresh DMEM medium (containing 5% FBS) every two days. After this culture, the medium in the well plate was replaced with DMEM medium containing 0.25% FBS. After this replacement, the cells were cultured under conditions of 5% CO2 and 37°C for 24 hours. After this culture, the medium in the well plate was replaced with DMEM medium containing 0.25% FBS. After replacement, β-NMN was added to the aforementioned concentrations. The gene expression levels of type 1 collagen, elastin, and hyaluronan synthase 2 (HAS2) following the addition of β-NMN were analyzed using the following method.

[0027] (qRT-PCR) After adding β-NMN, the cells were cultured at 37°C under 5% CO2 for 24 hours, and mRNA was purified using an RNeasy Mini Kit (QIAGEN). The purified mRNA was reverse transcribed into cDNA using PrimeScript RT Master Mix (Takara Bio Inc.). Gene expression of each target factor was then analyzed by qRT-PCR using TB Green EX TaqII Master Mix (Takara Bio Inc.) with a primer pair corresponding to each target factor. The amplification results of ribosomal protein S18 (RPS18) were used as a reference for the analysis of relative abundance changes.

[0028] The results are shown in Figure 1 (type 1 collagen) and Figure 2 (HAS2). The vertical axis represents the value when the control group value (change in expression level by relative quantification) is set to 100. The horizontal axis represents 1: control, 2: NMN 1 μg / ml, 3: NMN 10 μg / ml, and 4: NMN 100 μg / ml. * in Figure 1 indicates a significant difference compared to the control, p<0.05, and * in Figure 3 indicates a significant difference compared to the control, p<0.01. Collagen and HAS2 significantly increased at 1 μg / ml NMN compared to the control, and a tendency for gene expression to decrease with increasing concentration was observed. No significant difference was observed for elastin, but a tendency for gene expression to increase at lower concentrations was confirmed. For collagen and HAS2, gene expression significantly increased 24 hours after addition of β-NMN, suggesting that immediate skin improvement effects can be expected, especially when applied to the skin. [Industrial Applicability]

[0029] The present invention provides a composition capable of improving skin function. The composition can be used as a food composition, a composition for external application to the skin, or a cosmetic composition.

Claims

1. A composition containing β-nicotinamide mononucleotide (β-NMN) for immediate skin improvement, in which 0.01 mg to 100 mg of β-NMN is applied.

2. The fast-acting skin-improving composition according to claim 1, which is used to improve skin elasticity.

3. 2. The fast-acting skin-improving composition according to claim 1, which is used to prevent a decrease in skin moisture content.

4. A method for producing a fast-acting skin-improving composition containing β-nicotinamide mononucleotide (β-NMN), the method comprising a step of adjusting the amount of β-NMN to a concentration that can be ingested or applied in the range of 0.01 mg to 100 mg.

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