Oral composition

Abstract

The present invention aims to provide an oral composition having excellent anti-aging effects. [Solution] The present inventors conducted extensive research to solve the above problem and, surprisingly, discovered that when pyrroloquinoline quinone is combined with vitamin B6 and vitamin D, excellent anti-aging effects are exhibited.

Description

[Technical Field]

[0001] The present invention relates to an oral composition containing pyrroloquinoline quinone, vitamin B6 and vitamin D. [Background Art]

[0002] In Japan, the development of medical technology has extended people's overall lifespan. On the other hand, Japan is facing problems such as impaired daily life and susceptibility to various diseases caused by age-related decline in physical and mental functions. Age-related functional decline is generally referred to as aging, and examples thereof include declines in visual acuity, hearing, memory, motor ability, immune function, organ function, etc. Therefore, suppression of aging is desired from the perspective of improving quality of life, and prevention using foods and cosmetics that can be safely used over a long period of time is important. Accordingly, the development of foods and cosmetics that exhibit such effects is expected.

[0003] As an example of foods or cosmetics that suppress aging, resveratrol (Non-Patent Document 1) is known. However, many conventional anti-aging compositions cannot necessarily be said to have sufficiently high effects. [Prior Art Documents] [Non-Patent Documents]

[0004] [Non-Patent Document 1] Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.Nature,425:191-196,2003. [Summary of the Invention] [Problems to be Solved by the Invention]

[0005] An object of the present invention is to provide an oral composition that exhibits an excellent anti-aging effect. [Means for Solving the Problems]

[0006] The inventors of this invention, after diligently conducting research to solve the above problems, surprisingly discovered that combining pyrroloquinoline quinone with vitamin B6 and vitamin D exhibits excellent anti-aging effects. This invention is a completed invention based on this finding.

[0007] In other words, the present invention is as follows: [1] An oral composition containing pyrroloquinoline quinone, vitamin B6, and vitamin D. [2] The oral composition according to [1] above, wherein the mass ratio of vitamin B6 to pyrroloquinoline quinone is vitamin B6:pyrroloquinoline quinone = 1:0.3 to 50. [3] The oral composition according to [1] or [2] above, wherein the mass ratio of vitamin D to pyrroloquinoline quinone is vitamin D:pyrroloquinoline quinone = 1:200 to 4,000. [4] An oral composition according to any one of [1] to [3] above, further containing vitamin B1. [5] The oral composition according to [4] above, wherein the mass ratio of vitamin B1 to pyrroloquinoline quinone is vitamin B1:pyrroloquinoline quinone = 1:0.1 to 60. [6] An oral composition according to any one of the above [1] to [5], characterized in that it is a food composition. [7] An oral composition according to any one of the above [1] to [6], characterized in that it is a nutritional functional food. [8] An oral composition according to any of [1] to [7] above, which is for anti-aging purposes. [9] An oral composition according to any of [1] to [7] above, for maintaining or improving vitality.

[10] An oral composition according to any of [1] to [7] above, for the purpose of maintaining the health of the skin or mucous membranes.

[11] An oral composition according to any of [1] to [7] above, for promoting protein metabolism.

[12] An oral composition according to any of the above [1] to [8] for promoting mitochondrial activity.

[13] An oral composition for nutritional supplementation, as described in any of [1] to [9] above.

[14] A beauty composition according to any of the above [1] to

[13] .

[15] An oral composition according to any of [1] to

[14] above, designed so that the daily intake of pyrroloquinoline quinone for adults is 0.01 mg to 200 mg.

[16] An oral composition according to any of [1] to

[14] above, designed to provide an adult daily intake of 0.01 mg to 200 mg of vitamin B6.

[17] An oral composition according to any of [1] to

[14] above, designed to provide an adult daily intake of 0.0001 mg to 5 mg of vitamin D.

[18] An oral composition according to any of [1] to

[14] above, designed to provide an adult daily intake of 0.01 mg to 200 mg of vitamin B1.

[19] Foods listed in any of the above [1] to

[18] that display the following: firm days, vibrant days, want to stay youthful, defy age, want to continue to shine beautifully, anti-aging care.

[20] An oral anti-aging composition containing pyrroloquinoline quinone, vitamin B6, and vitamin D.

[21] An oral composition for maintaining and improving vitality, containing pyrroloquinoline quinone, vitamin B6, and vitamin D.

[22] An oral composition for maintaining the health of the skin or mucous membranes, containing pyrroloquinoline quinone, vitamin B6, and vitamin D.

[23] An oral composition for promoting protein metabolism, containing pyrroloquinoline quinone, vitamin B6, and vitamin D.

[24] An oral composition for mitochondrial activation containing pyrroloquinoline quinone, vitamin B6, and vitamin D. [Effects of the Invention]

[0008] According to the present invention, an oral composition with excellent anti-aging effects can be provided by containing pyrroloquinoline quinone, vitamin B6, and vitamin D. [Modes for carrying out the invention]

[0009] Preferred embodiments of the present invention will be described below. The present invention is not limited to the embodiments shown below, and can be modified within the range conceivable by a person skilled in the art, such as other embodiments, additions, corrections, and deletions. Any aspect is included in the scope of the present invention as long as the functions and effects of the present invention are exhibited.

[0010] The oral composition of the present invention contains pyrroloquinoline quinone, vitamin B6 and vitamin D, and may further contain vitamin B1.

[0011] Hereinafter, each component contained in the oral composition of the present invention will be described.

[0012] The present invention contains pyrroloquinoline quinone, vitamin B6 and vitamin D.

[0013] 1. Components constituting the present invention

[0014] (1) Pyrroloquinoline quinone Pyrroloquinoline quinone (chemical formula: C₁₄H₆N₂O₈) is a quinone compound known as the third coenzyme following flavin and nicotinamide. Pyrroloquinoline quinone (hereinafter sometimes referred to as PQQ) in the present invention may be an oxidized form (oxidized PQQ) represented by the following formula (1), or a reduced form (reduced PQQ) represented by the following formula (2).

[0015] [[Chemical formula]]

[0016] [[Chemical formula]]

[0017] Furthermore, the pyrroloquinoline quinone in the present invention may be in the form of a free form or a salt. Examples of pyrroloquinoline quinone salts include alkali metal salts, alkaline earth metal salts, and ammonium salts. The pyrroloquinoline quinone contained in the oral composition of the present invention can be extracted and purified from plants or fermented foods, or obtained by microbial fermentation or chemical synthesis. Commercially available products may also be used, but those obtained by microbial fermentation are particularly preferred from the viewpoint of purity. The amount of pyrroloquinoline quinone can be measured using high-performance liquid chromatography (HPLC). In the present invention, when a salt is used as pyrroloquinoline quinone, the amount of pyrroloquinoline quinone is expressed as an amount equivalent to pyrroloquinoline quinone.

[0018] (2) Vitamin B6 Vitamin B6 is a physiologically active substance classified as a water-soluble vitamin. In this invention, vitamin B6 refers to pyridoxine (pyridoxol), pyridoxal, pyridoxamine, or salts thereof. The form of vitamin B6 in salt form is not particularly limited as long as it is a salt acceptable for food and beverage use, but examples include inorganic acids such as hydrochloride, sulfate, and phosphate, and specifically pyridoxine hydrochloride. Vitamin B6 is a nutrient that contributes to maintaining the normal function of the immune system and increasing the resistance of the skin, and is also known to prevent fat accumulation in the liver and help prevent fatty liver disease. In this invention, from the viewpoint of particularly highlighting the effects of the present invention, it is particularly preferable to include pyridoxine hydrochloride as vitamin B6.

[0019] The method for incorporating vitamin B6 into the oral composition of the present invention is not particularly limited. For example, chemically synthesized pyridoxine, pyridoxal, pyridoxamine, or salts thereof, aqueous solutions containing pyridoxine, etc., or pulverized plants or extracts containing pyridoxine, etc., can be used. However, synthetic products are particularly desirable from the viewpoint of purity. The concentration of vitamin B6 can be measured by general analytical methods, and can be measured using known methods such as microbial quantification methods. In microbial quantification methods, a microorganism (such as Saccharomyces cerevisiae ATCC 9080 strain) that requires vitamin B6 as an essential nutrient and grows in proportion to the amount of vitamin B6 within a certain concentration range is used. The sample is added to a basal medium for quantification, which is a synthetic medium containing all the nutrients necessary for the growth of the microorganism, with only vitamin B6 removed, and cultured. The growth of microorganisms corresponding to the amount of vitamin B6 present in the sample can then be observed. The amount of vitamin B6 can be determined by measuring the amount of grown microorganisms as turbidity. In this invention, when a salt is used as vitamin B6, the amount of vitamin B6 is the amount converted to vitamin B6.

[0020] (3) Vitamin D Vitamin D is a type of fat-soluble vitamin that promotes the absorption of calcium from the intestines, which forms bone, and activates osteoblasts, which form bone, thereby increasing bone mass by promoting the synthesis of osteocalcin, an essential component of the bone matrix. Although vitamin D is synthesized in the body through exposure to sunlight, it tends to be deficient or insufficient in younger generations who spend less time in the sun due to modern lifestyles. Examples of vitamin D and its derivatives include vitamin D1, vitamin D3 (active vitamin D), and ergosterol. In this invention, vitamin D3 is particularly preferred from the viewpoint of particularly remarkably exhibiting the effects of the present invention.

[0021] The concentration of vitamin D can be measured by general analytical methods, including known methods such as HPLC. In this invention, when a salt is used as vitamin D, the amount of vitamin D is expressed as the amount in vitamin D equivalent. The vitamin D and its derivatives contained in this invention may be chemically synthesized or derived from natural materials, but synthetic products are particularly desirable from the viewpoint of purity.

[0022] (4) Vitamin B1 The present invention may further contain vitamin B1. The vitamin B1 in the oral composition of the present invention includes thiamine or its salts or derivatives. Examples of thiamine salts include thiamine hydrochloride and thiamine nitrate. Examples of thiamine derivatives include thiamine monophosphate, thiamine diphosphate, thiamine triphosphate, octothiamine, shikothiamine, thiamine disulfide, thiamine dicetyl sulfate, bisthiamine nitrate, dicetiamine hydrochloride, fursultiamine hydrochloride, allithiamine, bisibthiamine, bisbentiamine, fursultiamine, prosultiamine, and benfotiamine. In the present invention, from the viewpoint of particularly highlighting the effects of the present invention, it is especially preferable to include thiamine or its salts as vitamin B1.

[0023] The concentration of vitamin B1 can be measured by general analytical methods, including known methods such as HPLC. In this invention, when a salt is used as vitamin B1, the amount of vitamin B1 is expressed as an amount equivalent to vitamin B1. There are no particular limitations on the method of incorporating vitamin B1 into the oral composition of this invention. For example, chemically synthesized products of thiamine or its salts or derivatives, aqueous solutions containing thiamine, etc., or pulverized plants or extracts containing thiamine, etc., can be used, but synthetic products are particularly desirable from the viewpoint of purity.

[0024] 2. Composition of the present invention

[0025] (Pyrroloquinoline quinone content) There are no particular restrictions on the amount of PQQ contained in the oral composition of the present invention, and the proportion can be appropriately set over a wide range depending on various conditions such as purpose, shape, and target of use. For example, when the oral composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the proportion of PQQ in the composition of the present invention is preferably 0.001 to 50% by mass, more preferably 0.01 to 20% by mass, and particularly preferably 0.1 to 10% by mass, from the viewpoint of particularly demonstrating the effects of the present invention. When the oral composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), the amount of PQQ in the composition of the present invention is preferably 0.0001 to 30% by mass, more preferably 0.001 to 10% by mass, and particularly preferably 0.01 to 1% by mass, from the viewpoint of particularly demonstrating the effects of the present invention.

[0026] (Vitamin B6 content) There are no particular restrictions on the amount of vitamin B6 contained in the oral composition of the present invention, and the proportion can be appropriately set over a wide range depending on various conditions such as purpose, shape, and target of use. For example, when the oral composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the proportion of vitamin B6 in the composition of the present invention is preferably 0.001 to 50% by mass, more preferably 0.01 to 20% by mass, and particularly preferably 0.1 to 10% by mass, from the viewpoint of particularly demonstrating the effects of the present invention. When the oral composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), the amount of vitamin B6 in the composition of the present invention is preferably 0.0001 to 30% by mass, more preferably 0.001 to 10% by mass, and particularly preferably 0.01 to 1% by mass, from the viewpoint of particularly demonstrating the effects of the present invention.

[0027] In the composition of the present invention, the mass ratio of vitamin B6 to pyrroloquinoline quinone is not particularly limited, but from the viewpoint of further enhancing the effects of the present invention, the lower limit of the amount of pyrroloquinoline quinone per 1 part by mass of vitamin B6 is preferably 0.01 parts by mass or more, more preferably 0.1 parts by mass or more, even more preferably 0.2 parts by mass or more, even more preferably 0.3 parts by mass or more, particularly preferably 0.4 parts by mass or more, and most preferably 0.5 parts by mass or more. Furthermore, from the viewpoint of further enhancing the effects of the present invention, the upper limit of the amount of pyrroloquinoline quinone per 1 part by mass of vitamin B6 is preferably 100 parts by mass or less, more preferably 70 parts by mass or less, even more preferably 50 parts by mass or less, even more preferably 30 parts by mass or less, particularly preferably 10 parts by mass or less, and most preferably 2 parts by mass or less.

[0028] (Vitamin D content) There are no particular restrictions on the amount of vitamin D contained in the oral composition of the present invention, and the proportion can be appropriately set over a wide range depending on various conditions such as purpose, shape, and target of use. For example, when the oral composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the proportion of vitamin D in the composition of the present invention is preferably 0.00001 to 5% by mass, more preferably 0.0001 to 1% by mass, and particularly preferably 0.001 to 0.1% by mass, from the viewpoint of particularly demonstrating the effects of the present invention. When the oral composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), the amount of vitamin D in the composition of the present invention is preferably 0.000001 to 0.5% by mass, more preferably 0.00001 to 0.05% by mass, and particularly preferably 0.0001 to 0.005% by mass, from the viewpoint of more significantly demonstrating the effects of the present invention.

[0029] In the oral composition of the present invention, the mass ratio of vitamin D to pyrroloquinoline quinone is not particularly limited. However, from the viewpoint of further enhancing the effects of the present invention, the lower limit of the amount of pyrroloquinoline quinone per 1 part by mass of vitamin D is preferably 10 parts by mass or more, more preferably 100 parts by mass or more, even more preferably 200 parts by mass or more, particularly preferably 250 parts by mass or more, and most preferably 500 parts by mass or more. Furthermore, from the viewpoint of further enhancing the effects of the present invention, the upper limit of the amount of pyrroloquinoline quinone per 1 part by mass of vitamin D is preferably 6,000 parts by mass or less, more preferably 4,000 parts by mass or less, even more preferably 3,000 parts by mass or less, particularly preferably 2,000 parts by mass or less, and most preferably 1,000 parts by mass or less.

[0030] (Vitamin B1 content) There are no particular restrictions on the amount of vitamin B1 contained in the oral composition of the present invention, and the proportion can be appropriately set over a wide range depending on various conditions such as purpose, shape, and target of use. For example, when the oral composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the proportion of vitamin B1 in the composition of the present invention is preferably 0.001 to 50% by mass, more preferably 0.01 to 30% by mass, and particularly preferably 0.1 to 20% by mass, from the viewpoint of particularly demonstrating the effects of the present invention. When the oral composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), the amount of vitamin B1 in the composition of the present invention is preferably 0.0001 to 30% by mass, more preferably 0.001 to 10% by mass, and particularly preferably 0.01 to 1% by mass, from the viewpoint of more significantly demonstrating the effects of the present invention.

[0031] In the oral composition of the present invention, the mass ratio of vitamin B1 to pyrroloquinoline quinone is not particularly limited. However, from the viewpoint of further enhancing the effects of the present invention, the lower limit of the amount of pyrroloquinoline quinone per 1 part by mass of vitamin B1 is preferably 0.01 parts by mass or more, more preferably 0.05 parts by mass or more, even more preferably 0.1 parts by mass or more, particularly preferably 0.15 parts by mass or more, and most preferably 0.2 parts by mass or more. Furthermore, from the viewpoint of further enhancing the effects of the present invention, the upper limit of the amount of pyrroloquinoline quinone per 1 part by mass of vitamin B1 is preferably 80 parts by mass or less, more preferably 50 parts by mass or less, even more preferably 20 parts by mass or less, particularly preferably 10 parts by mass or less, and most preferably 2 parts by mass or less.

[0032] (Daily intake amount, etc.) The daily intake of pyrroloquinoline quinone for adults incorporated into the composition of the present invention is not particularly limited, but from the viewpoint of enjoying the effects of the present invention, it is preferably 0.01 mg to 200 mg, more preferably 0.1 mg to 100 mg, and particularly preferably 10 mg to 30 mg.

[0033] The daily intake of vitamin B6 or vitamin B1 for adults incorporated into the composition of the present invention is not particularly limited, but from the viewpoint of enjoying the effects of the present invention, it is preferably 0.01 mg to 200 mg, more preferably 0.1 mg to 100 mg, and particularly preferably 1 mg to 60 mg.

[0034] The daily intake of vitamin D for adults incorporated into the composition of the present invention is not particularly limited, but from the viewpoint of enjoying the effects of the present invention, it is preferably 0.0001 mg to 5 mg, more preferably 0.001 mg to 1 mg, and particularly preferably 0.01 mg to 0.1 mg.

[0035] The daily intake of the composition of the present invention is not particularly limited. For example, if the oral composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the daily intake is preferably 0.01 to 50 g, more preferably 0.05 to 30 g, and particularly preferably 0.1 to 10 g from the viewpoint of particularly highlighting the effects of the present invention. Also, for example, if the oral composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), the daily intake is preferably 10 to 1000 g, more preferably 30 to 750 g, and particularly preferably 50 to 500 g from the viewpoint of particularly highlighting the effects of the present invention.

[0036] The single dose of the oral composition of the present invention is not particularly limited. For example, if the oral composition of the present invention is a solid preparation (powder, granules, tablets, capsules, chewables, etc.), the dose is preferably 0.003 to 50 g, more preferably 0.01 to 30 g, and particularly preferably 0.03 to 10 g from the viewpoint of particularly highlighting the effects of the present invention. Also, for example, if the oral composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), the dose is preferably 3.3 to 1000 g, more preferably 10 to 750 g, and particularly preferably 16 to 500 g from the viewpoint of particularly highlighting the effects of the present invention.

[0037] The oral composition of the present invention may be taken before meals, between meals, after meals, or at the same time as a meal. However, from the viewpoint of anti-aging effects, it is preferable to take it before meals, after meals, or at the same time as a meal, and more preferably after meals.

[0038] (Other ingredients) The oral composition of the present invention may contain only components selected from pyrroloquinoline quinone, vitamin B6, vitamin D, and vitamin B1, or it may contain other components in addition to these. Examples of the other components include proteins, dietary fiber such as water-soluble dietary fiber and insoluble dietary fiber, vitamins other than vitamin B6, vitamin D, and vitamin B1, minerals, plants or plant products, algae, microorganisms, etc. Furthermore, if necessary, sugars such as dextrin and starch, oligosaccharides, sweeteners, acidulants, colorants, thickeners, glazing agents, excipients, nutritional supplements, binders, lubricants, stabilizers, diluents, bulking agents, emulsifiers, food additives, seasonings, etc., which are commonly used in the food industry.

[0039] (Form of composition, etc.) The form of the composition of the present invention is not particularly limited and can be any form. For example, it can be in the form of powder, granules, tablets, liquid, gel, paste, capsules such as hard capsules and soft capsules, caplets, tablets, gels, jellies, gummies, wafers, biscuits, cookies, cakes, chewables, syrups, sticks, etc. From the viewpoint of particularly demonstrating the effects of the present invention, the composition of the present invention is preferably in the form of granules, tablets, capsules, or liquid, and more preferably in the form of granules, tablets, or capsules. Here, "granules" refers to a composition obtained by granulating powder, which may be consumed directly or dissolved in a liquid such as water before consumption. "Gel" refers to a composition containing water and a thickener or gelling agent, and having viscosity or elasticity.

[0040] The packaging form of the oral composition of the present invention is not particularly limited and can be appropriately selected depending on the dosage form, etc., but examples include blister packs such as PTP, strip packaging, heat seals, aluminum pouches, film packaging using plastic or synthetic resin, glass containers such as vials, and plastic containers such as ampoules.

[0041] 3. Use as an anti-aging composition, etc. (Anti-aging composition) The oral composition of the present invention can be used as an anti-aging composition. When the present invention is an anti-aging composition, it is not particularly limited as long as it can be distinguished from other products in that it is used for anti-aging. For example, any product that displays that it has an anti-aging function on the product itself, packaging, instructions, or promotional materials is included in the scope of the present invention. Examples include so-called health foods such as pharmaceuticals (including quasi-drugs), functional foods whose efficacy has been approved by a designated institution, such as Foods for Specified Health Uses, Foods with Nutrient Function Claims, and Foods with Function Claims. Examples of so-called health foods include those that display phrases such as "firm days," "lively days," "want to stay youthful," "don't let age get the better of you," "want to continue to shine beautifully," and "aging care." The anti-aging composition of the present invention may display PQQ, vitamin B6, vitamin D, and / or vitamin B1 as active ingredients, but is not limited to products that display PQQ, vitamin B6, vitamin D, and / or vitamin B1 as active ingredients on the product packaging, etc. For example, the active ingredient may not be specified, or it may list ingredients other than PQQ, vitamin B6, vitamin D, or vitamin B1 as the active ingredient.

[0042] (Use as a composition for maintaining and improving vitality, etc.) The oral composition of the present invention can increase the production of adenosine triphosphate (ATP) by activating mitochondria. As a result, it exhibits excellent effects such as maintaining and improving vitality, maintaining the health of the skin or mucous membranes, and promoting protein metabolism.

[0043] Here, ATP, which is energy, is necessary for cells to function. Approximately 90% of this ATP is produced by oxidative phosphorylation in mitochondria in almost all cells except red blood cells. Therefore, it is thought that promoting mitochondrial activity, which is a common energy production mechanism regardless of cell type, can lead to the maintenance and improvement of various cell functions. Specifically, these effects include maintaining and improving vitality, maintaining the health of the skin or mucous membranes, and promoting protein metabolism.

[0044] For example, neuronal cell death, a contributing factor to decreased vitality, is known to be induced by decreased mitochondrial activity (Kitagawa, Kazuo, et al. "Results and Clinical Applications of Neuronal Cell Death Research." Stroke 30.6(2008):862-868). Therefore, promoting mitochondrial activity is thought to help maintain and improve vitality.

[0045] Furthermore, it is known that in epidermal cells, promoting mitochondrial activity enhances the production of fibroblast growth factor (FGF) and epidermal growth factor (EGF) (Kazuhiko Honjo. "Cytological effects of plant fermented paste AO via mitochondria and antioxidant activity." Pharmacology and Therapeutics 45.7(2017):1141-1152.). Also, in airway epithelial cells, decreased mitochondrial activity is known to cause excessive mucin secretion (Aguilera-Aguirre, Leopoldo, et al. "Mitochondrial dysfunction increases allergic airway inflammation." The Journal of Immunology 183.8(2009):5379-5387.). Therefore, it is thought that promoting mitochondrial activity contributes to maintaining the health of the skin or mucous membranes.

[0046] Furthermore, it has been reported that promoting mitochondrial activity in muscle cells increases muscle mass (Sugimoto, Ken. "3. Mitochondrial function of skeletal muscle and the significance of Myokine in sarcopenia." Journal of the Japan Geriatrics Society 49.2(2012):199-202.). Therefore, it is thought that promoting mitochondrial activity contributes to promoting protein metabolism.

[0047] Therefore, the compositions of the present invention can be used as compositions for maintaining and improving vitality, compositions for maintaining the health of the skin or mucous membranes, and compositions for promoting protein metabolism.

[0048] If the present invention is a composition for maintaining and improving vitality, it is not particularly limited as long as it can be distinguished from other products in that it is used for maintaining and improving vitality. For example, any product that displays that it has the function of maintaining and improving vitality on the product itself, packaging, instructions, or promotional materials is included in the scope of the present invention. Examples include so-called health foods such as pharmaceuticals (including quasi-drugs), functional foods whose efficacy has been approved by a designated institution, such as Foods for Specified Health Uses, Foods with Nutrient Function Claims, and Foods with Function Claims. Examples of Foods with Nutrient Function Claims include those that display "maintain vitality," "keep vitality," "support daily vitality," "suppress decline in vitality," "for those concerned about vitality," "enhance vitality," "promote vitality," "vitality," etc. The present invention's composition for maintaining and improving vitality may display PQQ, vitamin B6, vitamin D, and / or vitamin B1 as active ingredients, but is not limited to products that display PQQ, vitamin B6, vitamin D, and / or vitamin B1 as active ingredients on the product packaging, etc. For example, the active ingredient may not be specified, or it may list ingredients other than PQQ, vitamin B6, vitamin D, or vitamin B1 as the active ingredient.

[0049] If the present invention is a composition for maintaining the health of the skin or mucous membranes, it is not particularly limited as long as it can be distinguished from other products in that it is used for maintaining the health of the skin or mucous membranes. For example, any product in which the body, packaging, instructions, or promotional materials of the present invention indicate that it has the function of maintaining the health of the skin or mucous membranes is included in the scope of the present invention. Examples include so-called health foods such as pharmaceuticals (including quasi-drugs), functional foods whose efficacy has been approved by a designated institution, such as Foods for Specified Health Uses, Foods with Nutrient Function Claims, and Foods with Function Claims. Examples of Foods with Nutrient Function Claims include those which indicate "helps maintain the health of the skin and mucous membranes," "maintains skin health," "supports the maintenance of the health of the skin and mucous membranes," "keeps skin healthy," "improves skin condition," "maintains moisture of mucous membranes," and "maintains the barrier function of the skin and mucous membranes." The present invention's composition for maintaining the health of the skin or mucous membranes may indicate PQQ, vitamin B6, vitamin D, and / or vitamin B1 as active ingredients, but is not limited to products in which PQQ, vitamin B6, vitamin D, and / or vitamin B1 are indicated as active ingredients on the product packaging, etc. For example, the active ingredient may not be specified, or it may list ingredients other than PQQ, vitamin B6, vitamin D, or vitamin B1 as the active ingredient.

[0050] If the present invention is a composition for promoting protein metabolism, it is not particularly limited as long as it can be distinguished from other products in that it is used to promote protein metabolism. For example, any product that displays that it has the function of promoting protein metabolism on the product itself, packaging, instructions, or promotional materials is included in the scope of the present invention. Examples include so-called health foods such as pharmaceuticals (including quasi-drugs), functional foods whose efficacy has been approved by a designated institution, such as Foods for Specified Health Uses, Foods with Nutrient Function Claims, and Foods with Function Claims. Examples of foods with nutritional function claims include those that display "supports protein absorption," "promotes muscle formation," "supports muscle strength maintenance," "keeps muscles healthy," "supports protein supplementation after exercise," "helps maintain muscle mass," and "participates in protein metabolism and contributes to maintaining health." The protein metabolism-promoting composition of the present invention may be labeled as containing PQQ, vitamin B6, vitamin D, and / or vitamin B1 as active ingredients, but is not limited to those in which PQQ, vitamin B6, vitamin D, and / or vitamin B1 are labeled as active ingredients on the product packaging, etc. For example, the active ingredient may not be specified, or a component other than PQQ, vitamin B6, vitamin D, or vitamin B1 may be labeled as the active ingredient. [Examples]

[0051] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples, and can take various forms as long as it can solve the problems of the present invention.

[0052] (Test: Evaluation of anti-aging effect) This study evaluated the amount of activated mitochondria. Mitochondria are organelles that play a central role in energy production within cells, and it is known that decreased mitochondrial activity and function are closely related to diseases such as cancer, aging, Alzheimer's disease, and Parkinson's disease, as well as skin aging. When mitochondrial function declines due to aging, the amount of reactive oxygen species generated when mitochondria produce energy increases, making mitochondrial DNA more susceptible to damage and leading to further functional decline. Conversely, when mitochondrial function is good, the amount of reactive oxygen species generated decreases, and it is thought that more energy can be produced. Therefore, by confirming the mitochondrial activation effect, it becomes possible to evaluate the anti-aging effect. In addition, as mentioned above, mitochondrial activation is also an indicator of maintaining and improving vitality, maintaining the health of the skin or mucous membranes, and promoting protein metabolism.

[0053] (Test substance) The following substances were used as test substances. • Pyrroloquinoline quinone: PQQ produced using a commercially available fermentation method was used. • Vitamin B6: A commercially available pyridoxine hydrochloride reagent was used. • Vitamin D: A commercially available vitamin D3 reagent was used. • Vitamin B1: A commercially available thiamine hydrochloride reagent was used.

[0054] (Preparation of the test substance) Each test substance was prepared using DMEM medium containing 0.5% DMSO and 10% fetal bovine serum (FBS). The mixing ratios of the test substances used in the following tests are shown in Tables 1 and 2.

[0055] (Mitochondrial activity measurement) (1) Normal human dermal fibroblasts (NHDF) were cultured in a 75 cm² flask in a 37°C, 5 vol. % CO₂ incubator using DMEM medium containing 10% fetal bovine serum (FBS). (2) Cells suspended by trypsin treatment were seeded at a cell density of 8 × 10^3 cells / well in each well of a 96-well plate (collagen coated) and pre-cultured for 24 hours in a 37°C, 5V %CO2 incubator. (3) After removing the culture medium from each well, 100 μL / well of culture medium containing the test substance, prepared to the predetermined concentration, was added and incubated for 24 hours at 37°C in a 5 vol. %CO2 incubator. (4) DMEM medium containing 0.5% DMSO and 10% FBS was used as the culture medium, and the total concentration of the test substance in the medium was set to 1 μg / mL. (5) After 24 hours of incubation, the culture medium was removed, and each well was washed twice with 200 μL of serum-free DMEM. Then, 50 μL of 1 μM rhodamine diluted with serum-free DMEM was added to each well. (6) After staining the cells by incubating them in a 37°C, 5V %CO2 incubator for 60 minutes, the reagents were removed and the cells were washed twice with PBS 200 μL / well. (7) 200 μL of PBS was added, and the fluorescence intensity (excitation wavelength Ex. 507 nm, fluorescence wavelength Em. 529 nm) was measured. (8) Based on the obtained data, the percentage of control was calculated. % of control =(Data sample - Data blank) / (Data control - Data blank)× 100 The denominator (baseline), "Data control - Data blank," is the value obtained by subtracting the fluorescence intensity of "blank" from the fluorescence intensity of the sample without the test substance (Control). On the other hand, the numerator, "Data sample - Data blank," is the value obtained by subtracting the fluorescence intensity of "blank" from the fluorescence intensity of the sample with the test substance added. Since the value obtained by subtracting the fluorescence intensity of blank from the fluorescence intensity of the sample is proportional to the amount of activated mitochondria, the calculated "% of control" serves as an indicator of mitochondrial activity. (9) Tables 1 and 2 show the relative values ​​when the control value without the test substance is set to 100.

[0056] [Table 1]

[0057] [Table 2]

[0058] The groups administered PQQ, vitamin B6, and vitamin D (Examples 1, 3-13) all showed higher mitochondrial activity compared to the groups administered only one of these (Comparative Examples 1-3). Furthermore, higher mitochondrial activity was also observed compared to the group administered PQQ and vitamin B6 (Comparative Example 5). Since no increase in mitochondrial activity was observed in the group administered PQQ and vitamin B6 (Comparative Example 5) compared to the control, it was found that the combination of PQQ, vitamin B6, and vitamin D exhibits a mitochondrial activity-promoting effect. Therefore, it was found that the oral composition of the present invention, by containing PQQ, vitamin B6, and vitamin D, exhibits excellent anti-aging effects.

[0059] Furthermore, in the group administered with added vitamin B1 (Examples 2, 14-19), higher mitochondrial activity was observed compared to the group administered with only vitamin B1 (Comparative Example 4). In addition, in a comparison between Example 1, which administered PQQ, vitamin B6, and vitamin D, and Example 2, which also administered vitamin B1, higher mitochondrial activity was observed in Example 2 compared to Example 1. From this, it was found that combining PQQ, vitamin B6, vitamin D, and vitamin B1 further enhances mitochondrial activity. From this, it was found that the composition of the present invention, containing PQQ, vitamin B6, vitamin D, and further containing vitamin B1, exhibits excellent anti-aging effects.

[0060] (Examples 20-31: Tablets) The raw materials were mixed according to the formulations in Table 3, and then compressed using a rotary tablet press to produce the tablets of Examples 20-31. The tablets were manufactured with a diameter of 8 mmφ, a thickness of 4.5 mm, a weight of 250 mg, and a hardness of 5 kgf or more. All of the tablets described in Manufacturing Examples 20-31 exhibited anti-aging effects when taken at a dose of 1-2 tablets per day with 100 ml of water or other liquid. All of the tablets in Manufacturing Examples 20-31 can be safely and continuously taken orally over a long period of time.

[0061] [Table 3]

[0062] (Examples 32-43: Granules) After mixing the raw materials according to the formulations in Table 4, fluid bed granulation was performed using a granulator to produce the granules described in Examples 32-43. All of the granules described in Examples 32-43 exhibited anti-aging effects when ingested at a dose of 3 g per day, dissolved in 100 ml of a solvent such as water. All of the granules in Production Examples 32-43 can be safely and continuously ingested orally over a long period of time.

[0063] [Table 4] [Industrial applicability]

[0064] The oral composition of the present invention exhibits excellent anti-aging effects, and therefore has high industrial utility.

Claims

1. An oral composition containing pyrroloquinoline quinone, vitamin B6, and vitamin D.

2. Furthermore, the oral composition according to claim 1 contains vitamin B1.

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