Composition for promoting hyaluronic acid production

Abstract

[Problem] To provide a composition for promoting the production of hyaluronic acid. [Solution] Provided is a composition for promoting the production of hyaluronic acid, which contains at least one component selected from the group consisting of (A) at least one component selected from the group consisting of acetic acid and propionic acid or a salt thereof, (B) a bacterial prebiotic agent for producing (A), and (C) a bacterial probiotic agent for producing (A).

Description

Technical Field

[0001] The present invention relates to a composition for promoting the production of hyaluronic acid. Background Art

[0002] In recent years, research on aging has been conducted. While aging is a major macroeconomic factor in skin aging, direct factors related to skin aging include dryness, oxidation, and the effects of sunlight (ultraviolet rays). Specific manifestations of skin aging include a decrease in mucopolysaccharides, including hyaluronic acid, collagen cross-linking, and ultraviolet-induced cell damage.

[0003] Wherein, hyaluronic acid has multiple functions, and it is the maintenance of the moisture in the intercellular space, the maintenance of the cell of the colloid matrix formed in the tissue, the maintenance of the lubricity and pliability of the tissue, the resistance to the external forces such as mechanical damage and the prevention of bacterial infection etc. (with reference to non-patent literature 1).For example, it is generally believed that the hyaluronic acid amount of skin can reduce along with age, and there will be skin aging such as fine lines, chapped skin with it.Therefore, as the improver of this aging skin, many cosmetics with hyaluronic acid, collagen have been proposed.But these existing cosmetics only play moisturizing effect on skin surface, can't improve aging skin in essence.In addition, the cosmetics of various vitamins, crude drug class as skin cell activator have been proposed, but current situation is that they also still can't improve, treat aging skin.

[0004] And then, the hyaluronic acid included in the joint fluid can coat the surface of articular cartilage, contributes to the smooth operation of joint function.The hyaluronic acid concentration in normal people's joint fluid is about 2.3mg / ml, and in the case of rheumatoid arthritis, the hyaluronic acid concentration in the joint fluid is reduced to about 1.2mg / ml, and the viscosity of joint fluid is also significantly reduced (with reference to non-patent literature 2) simultaneously.Also known, similarly to the situation of rheumatoid arthritis, suppurative arthritis, gouty arthritis etc. also can cause the reduction of hyaluronic acid content (with reference to non-patent literature 3).For above-mentioned disease, in order to improve lubrication function, coat / protect articular cartilage, suppress pain and improve or normalize morbid joint fluid, it is possible to consider increasing the hyaluronic acid amount in joint fluid.For example, when reporting that rheumatoid arthritis patients are carried out the articular injection therapy of sodium hyaluronate, it is possible to confirm the above-mentioned improvement (with reference to non-patent literature 4).Similarly, also reported for traumatic arthritis, osteoarthritis or deforming arthritis, utilizing the above-mentioned improvement effect (with reference to non-patent literature 5) of the articular injection therapy of hyaluronic acid.

[0005] Therefore, methods such as applying cosmetics containing hyaluronic acid to the skin or directly injecting hyaluronic acid into joints have been adopted. However, even external application of hyaluronic acid does not fundamentally improve function and sufficient effects cannot be expected. In particular, there is the problem that hyaluronic acid is hardly absorbed by the skin.

[0006] Therefore, there is a desire to develop substances that do not simply supply hyaluronic acid itself from the outside, but rather utilize the inherent self-repair ability of the human body to promote the ability of human skin fibroblasts to produce hyaluronic acid, thereby fundamentally improving the function of the body. Among them, various plant-derived hyaluronic acid production promoters have been developed in anticipation of safety and mild skin irritation (for example, see Patent Documents 1 to 4).

[0007] In addition, it is known that during the healing process after burns and scalds, from the initial stage when granulation tissue proliferates from under the necrotic tissue until the entire tissue is replaced by granulation tissue, the hyaluronic acid in the granulation tissue increases significantly (see non-patent document 6). As a therapeutic drug for the early stages of burns and scalds, hyaluronic acid production promoters are also expected.

[0008] Prior art literature

[0009] Patent Literature

[0010] Patent Document 1: Japanese Patent Application Laid-Open No. 11-209261

[0011] Patent Document 2: Japanese Patent Application Laid-Open No. 2007-84448

[0012] Patent Document 3: Japanese Patent Application Laid-Open No. 2003-55244

[0013] Patent Document 4: Japanese Patent Application Laid-Open No. 2012-56919

[0014] Non-patent literature

[0015] Non-patent document 1: "Bio Industry", vol. 8, p. 346 (1991)

[0016] Non-Patent Document 2: “Arthritis Rheumatism”, vol. 10, p. 357 (1967)

[0017] Non-patent document 3: "Joint Composition (Connective Composition)" (Kanehara Publishing), page 481, 1984

[0018] Non-patent document 4: “Inflammation” (Japanese Society of Inflammation), Vol. 11, p. 16, 1991

[0019] Non-patent document 5: "Connective tissue and diseases" (Kodansha), page 246, 1980

[0020] Non-patent document 6: "Connective tissue and diseases" (Kodansha), page 153, 1980 Summary of the Invention

[0021] The present invention provides a composition for promoting the production of hyaluronic acid.

[0022] The present inventors have surprisingly discovered that a composition containing specific ingredients can promote the production of hyaluronic acid. The present invention is based on these findings.

[0023] According to the present invention, the following inventions are provided.

[0024] (1) A composition for promoting hyaluronic acid production, comprising one or more components selected from the group consisting of the following components:

[0025] (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof,

[0026] (B) a prebiotic agent for bacteria producing (A), and

[0027] (C) Probiotics for bacteria producing (A).

[0028] (2) A composition for improving skin viscoelasticity, comprising one or more components selected from the group consisting of the following components:

[0029] (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof,

[0030] (B) a prebiotic agent for bacteria producing (A), and

[0031] (C) Probiotics for bacteria producing (A).

[0032] (3) The composition according to (2), which is used for promoting hyaluronic acid production.

[0033] (4) The composition according to any one of (1) to (3), wherein (B) comprises one or more selected from the group consisting of fructooligosaccharides, galactoligosaccharides, indigestible dextrins, α-cyclodextrins, glucans, isomaltodextrins, inulin, fucose, and cruciferous plants, or consists of one or more selected from the group consisting of fructooligosaccharides, galactoligosaccharides, indigestible dextrins, α-cyclodextrins, glucans, isomaltodextrins, inulin, fucose, and cruciferous plants.

[0034] (5) The composition according to any one of (1) to (4), wherein (C) comprises a member selected from the group consisting of Akkermansia, Anaerostipes, Anaerobutyricum, Faecalibacterium, Roseburia, Coprobacterium, Bacteroidetes, Clostridium, Propionibacterium, and Veillonella. The method comprises the following steps: the step of: selecting at least one bacterium in the group consisting of the genus Akkermansia, the genus Anaerostipes, the genus Anaerobutyricum, the genus Faecalibacterium, the genus Roseburia, the genus Coprobacterium, the genus Bacteroidetes, the genus Clostridium, the genus Propionibacterium and the genus Veillonella.

[0035] (6) The composition according to any one of (1) and (3) to (5), which is a composition for promoting hyaluronic acid production in fibroblasts.

[0036] (7) The composition according to any one of (1) to (6), which is a food composition.

[0037] (8) Use of one or more components selected from the group consisting of the following ingredients for the manufacture of a pharmaceutical agent for the purpose of promoting hyaluronic acid production,

[0038] (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof,

[0039] (B) a prebiotic agent for bacteria producing (A), and

[0040] (C) Probiotics for bacteria producing (A).

[0041] (9) Use of one or more components selected from the group consisting of the following ingredients for the manufacture of a medicament for the purpose of improving skin viscoelasticity,

[0042] (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof,

[0043] (B) a prebiotic agent for bacteria producing (A), and

[0044] (C) Probiotics for bacteria producing (A).

[0045] (10) The use according to (9), wherein the drug is further intended to promote the production of hyaluronic acid.

[0046] (11) The use according to any one of (8) to (10), wherein (B) comprises one or more selected from the group consisting of fructooligosaccharides, galactoligosaccharides, indigestible dextrins, α-cyclodextrins, glucans, isomaltodextrins, inulin, fucose, and cruciferous plants, or is composed of one or more selected from the group consisting of fructooligosaccharides, galactoligosaccharides, indigestible dextrins, α-cyclodextrins, glucans, isomaltodextrins, inulin, fucose, and cruciferous plants.

[0047] (12) The use according to any one of (8) to (11), wherein (C) comprises a species selected from the genus Akkermansia, the genus Anaerostipes, the genus Anaerobutyricum, the genus Faecalibacterium, the genus Roseburia, the genus Coprobacterium, the genus Bacteroidetes, the genus Clostridium, the genus Propionibacterium, and the genus Veillonella. The invention also provides a method for preparing the present invention for the present invention to provide a method for preparing the present invention for the present invention, wherein the method comprises: selecting one or more bacteria in the group consisting of, or consisting of one or more bacteria selected from the group consisting of Akkermansia, Anaerostipes, Anaerobutyricum, Faecalibacterium, Roseburia, Coprobacterium, Bacteroidetes, Clostridium, Propionibacterium and Veillonella.

[0048] (13) The use according to any one of (8) and (10) to (12), wherein the promotion of hyaluronic acid production includes promoting hyaluronic acid production in fibroblasts.

[0049] (14) The use according to any one of (8) to (13), wherein the drug is a food composition.

[0050] (15) Use of a composition for promoting hyaluronic acid production, the composition comprising one or more components selected from the group consisting of the following components:

[0051] (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof,

[0052] (B) a prebiotic agent for bacteria producing (A), and

[0053] (C) Probiotics for bacteria producing (A).

[0054] (16) Use of a composition for improving skin viscoelasticity, the composition comprising one or more selected from the group consisting of the following components:

[0055] (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof,

[0056] (B) a prebiotic agent for bacteria producing (A), and

[0057] (C) Probiotics for bacteria producing (A).

[0058] (17) The use according to (16), further used for promoting the production of hyaluronic acid.

[0059] (18) The use according to any one of (15) to (17), wherein (B) comprises one or more selected from the group consisting of fructooligosaccharides, galactoligosaccharides, indigestible dextrins, α-cyclodextrins, glucans, isomaltodextrins, inulin, fucose and cruciferous plants, or is composed of one or more selected from the group consisting of fructooligosaccharides, galactoligosaccharides, indigestible dextrins, α-cyclodextrins, glucans, isomaltodextrins, inulin, fucose and cruciferous plants.

[0060] (19) The use according to any one of (15) to (18), wherein (C) comprises a species selected from the genus Akkermansia, the genus Anaerostipes, the genus Anaerobutyricum, the genus Faecalibacterium, the genus Roseburia, the genus Coprobacterium, the genus Bacteroidetes, the genus Clostridium, the genus Propionibacterium, and the genus Veillonella. The invention also provides a method for preparing the present invention for the present invention to provide a method for preparing the present invention for the present invention, wherein the method comprises: selecting one or more bacteria in the group consisting of, or consisting of one or more bacteria selected from the group consisting of Akkermansia, Anaerostipes, Anaerobutyricum, Faecalibacterium, Roseburia, Coprobacterium, Bacteroidetes, Clostridium, Propionibacterium and Veillonella.

[0061] (20) The use according to any one of (15) and (17) to (19), wherein promoting hyaluronic acid production includes promoting hyaluronic acid production in fibroblasts.

[0062] (21) The use according to any one of (15) to (20), wherein the composition is a food composition.

[0063] (22) one or more components selected from the group consisting of the following components for promoting the production of hyaluronic acid,

[0064] (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof,

[0065] (B) a prebiotic agent for bacteria producing (A), and

[0066] (C) Probiotics for bacteria producing (A).

[0067] (23) One or more ingredients selected from the group consisting of the following ingredients for improving skin viscoelasticity,

[0068] (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof,

[0069] (B) a prebiotic agent for bacteria producing (A), and

[0070] (C) Probiotics for bacteria producing (A).

[0071] (24) One or more components selected from the group consisting of the following components according to (23) for promoting the production of hyaluronic acid,

[0072] (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof,

[0073] (B) a prebiotic agent for bacteria producing (A), and

[0074] (C) Probiotics for bacteria producing (A).

[0075] (25) One or more components selected from the group consisting of the following components according to (23) or (24) for promoting the production of hyaluronic acid in fibroblasts,

[0076] (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof,

[0077] (B) a prebiotic agent for bacteria producing (A), and

[0078] (C) Probiotics for bacteria producing (A).

[0079] (26) A method for promoting hyaluronic acid production in a subject,

[0080] The method comprises administering at least one selected from the group consisting of the following components in an effective amount,

[0081] (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof,

[0082] (B) a prebiotic agent for bacteria producing (A), and

[0083] (C) Probiotics for bacteria producing (A).

[0084] (27) A method for improving skin viscoelasticity in a subject,

[0085] The method comprises administering at least one selected from the group consisting of the following components in an effective amount,

[0086] (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof,

[0087] (B) a prebiotic agent for bacteria producing (A), and

[0088] (C) Probiotics for bacteria producing (A).

[0089] (28) The method according to (27), further used for promoting hyaluronic acid production.

[0090] (29) The method according to any one of (26) to (28), wherein (B) comprises one or more selected from the group consisting of fructooligosaccharides, galactoligosaccharides, indigestible dextrins, α-cyclodextrins, glucans, isomaltodextrins, inulin, fucose and cruciferous plants, or is composed of one or more selected from the group consisting of fructooligosaccharides, galactoligosaccharides, indigestible dextrins, α-cyclodextrins, glucans, isomaltodextrins, inulin, fucose and cruciferous plants.

[0091] (30) The method according to any one of (26) to (29), wherein (C) comprises a species selected from the genus Akkermansia, the genus Anaerostipes, the genus Anaerobutyricum, the genus Faecalibacterium, the genus Roseburia, the genus Coprobacterium, the genus Bacteroidetes, the genus Clostridium, the genus Propionibacterium, and the genus Veillonella. The invention also provides a method for preparing the present invention for the present invention to provide a method for preparing the present invention for the present invention, wherein the method comprises: selecting one or more bacteria in the group consisting of, or consisting of one or more bacteria selected from the group consisting of Akkermansia, Anaerostipes, Anaerobutyricum, Faecalibacterium, Roseburia, Coprobacterium, Bacteroidetes, Clostridium, Propionibacterium and Veillonella.

[0092] (31) The method according to any one of (26) and (28) to (30), which is used to promote hyaluronic acid production in fibroblasts.

[0093] (32) The method according to any one of (26) to (31), wherein one or more components selected from the group consisting of the following components are in the form of a composition (preferably a food composition),

[0094] (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof,

[0095] (B) a prebiotic agent for bacteria producing (A), and

[0096] (C) Probiotics for bacteria producing (A).

[0097] According to the present invention, a composition for promoting the production of hyaluronic acid is provided. In addition, according to the present invention, a composition for improving the viscoelasticity of the skin is also provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0098] Figure 1 This is a graph showing the evaluation results of the effects of each component on the mRNA expression of the COL1A1 gene in human fibroblasts.

[0099] Figure 2 This is a graph showing the evaluation results of the effects of each component on the mRNA expression of the COL3A1 gene in human fibroblasts.

[0100] Figure 3 This is a graph showing the evaluation results of the effects of each component on the mRNA expression of the COL7A1 gene in human fibroblasts.

[0101] Figure 4 This is a graph showing the evaluation results of the effects of each component on the mRNA expression of the HAS2 gene in human fibroblasts.

[0102] Figure 5 This is a graph showing the correlation between the skin viscoelasticity (R2) of the arms of test subjects and the amount of propionic acid in feces.

[0103] Figure 6 This is a graph showing the correlation between the facial skin viscoelasticity (R2) of the test subjects and the amount of propionic acid in feces.

[0104] Figure 7 This is a graph showing the correlation between the skin viscoelasticity (R7) of the arms of test subjects and the amount of propionic acid in feces.

[0105] Figure 8 This is a graph showing the correlation between the viscoelasticity of the skin on the arm of a test subject (R7) and the amount of acetic acid in feces. DETAILED DESCRIPTION

[0106] According to one embodiment of the present invention, a composition for promoting hyaluronic acid production is provided, comprising: (A) one or more species selected from the group consisting of acetic acid and propionic acid, or salts thereof; (B) a prebiotic agent for bacteria producing (A); and (C) one or more species selected from the group consisting of a probiotic agent for bacteria producing (A). This composition has an excellent effect of promoting hyaluronic acid production and can be used to prevent skin aging, maintain skin tension and elasticity, prevent / treat arthritis, and provide initial treatment for burns and scalds.

[0107] In particular, the present inventors have shown that the amount of acetic acid or propionic acid in the feces of a test subject is correlated with skin viscoelasticity (see Reference Examples and Figures 5 to 8 Therefore, according to another embodiment of the present invention, a composition for improving skin viscoelasticity is provided, comprising one or more components selected from the group consisting of (A) one or more components selected from the group consisting of acetic acid and propionic acid or salts thereof, (B) a prebiotic agent for bacteria that produce (A), and (C) a probiotic agent for bacteria that produce (A). The improvement in skin viscoelasticity caused by this composition may be achieved by promoting hyaluronic acid production, or may be achieved independently of the promotion of hyaluronic acid production.

[0108] Typically, various indicators are used to evaluate the health of the skin. For example, the presence or absence of skin tension is used as an indicator of health and aging. "Tension" is divided into tension originating from the stratum corneum / epidermis and tension originating from the dermis. In particular, tension originating from the dermis has an elasticity similar to the rebound of the skin when pressed with a finger, and refers to the state of rapid recovery after the finger is removed. Physically, this is also called viscoelasticity. Skin viscoelasticity in the present invention refers to this physical property of the skin.

[0109] The specific method for evaluating skin viscoelasticity in the present invention is not particularly limited. For example, it can be based on measurement results obtained using a CUTOMETER / Skin Viscoelasticity Measuring Device (trade name) (manufactured by Courage+Khazaka Electronic GmbH). This device draws a negative pressure probe into the skin surface, measures the length of skin drawn into the opening using a prism, then releases the suction and measures the displacement length (recovery) upon release in the same manner. This measurement result is used as a parameter to determine skin viscoelasticity (see the product's instruction manual).

[0110] The evaluation of the skin viscoelasticity of the present invention is not particularly limited and can be performed based on parameters commonly used as indicators of skin viscoelasticity. Examples of such parameters include: R2: the ratio of the final recovery of the skin upon release of attraction to the maximum length of the skin stretched during attraction (R2 = Ua / Uf), R5: the ratio of the instantaneous recovery of the skin upon release of attraction to the length of the skin stretched during attraction (R5 = Ur / Ue), and R7: the ratio of the immediate (instantaneous) contraction to the length of the skin stretched during attraction (R7 = Ur / Uf). In the formula, Uf, Ur, Ue, and Ua respectively represent: Uf: the maximum stretch of the skin during attraction, Ur: the immediate (instantaneous: 0.1 second) recovery of the skin after the removal of attraction, Ue: the immediate (instantaneous: 0.1 second) stretch of the skin caused by attraction, and Ua: the final recovery of the skin after the removal of attraction. The skin viscoelasticity of the present invention can be evaluated based on one or more parameters selected from the group consisting of R2, R5, and R7.

[0111] In the present invention, skin viscoelasticity can be assessed at any location on the skin without limitation, including the face (e.g., forehead, cheeks, etc.), forearms, upper arms, back, abdomen, etc. Skin viscoelasticity can be assessed at beauty salons, cosmetics stores, or beauty salons, and can also be performed using non-diagnostic methods or diagnostic-assisted methods.

[0112] According to one embodiment of the present invention, the composition of the present invention comprises (A) one or more selected from the group consisting of acetic acid and propionic acid, or salts thereof.

[0113] The acetate of the present invention is not particularly limited. Examples of the acetate of the present invention include sodium acetate and potassium acetate.

[0114] The propionate salt of the present invention is not particularly limited. Examples of the propionate salt of the present invention include sodium propionate and potassium propionate.

[0115] According to a preferred embodiment of the present invention, the composition of the present invention comprises acetic acid, sodium acetate, propionic acid or sodium propionate.

[0116] According to another embodiment of the present invention, the composition of the present invention comprises (B) a prebiotic agent for bacteria producing (A).

[0117] (B) of the present invention is not particularly limited as long as it is a substance for inducing the growth or activity of the bacteria producing (A), and examples thereof include growth promoters and metabolic activators of the bacteria producing (A).

[0118] (B) of the present invention may contain or consist of an ingredient or food ingredient that has the effect of inducing the growth or activity of the bacteria that produce (A). Preferred ingredients include fructooligosaccharides, galacto-oligosaccharides, indigestible dextrins, α-cyclodextrins, glucans, isomaltodextrins, inulin, or fucose. Furthermore, preferred food ingredients include cruciferous plants, more preferably broccoli sprouts.

[0119] According to a preferred embodiment of the present invention, the composition of the present invention comprises (B) a prebiotic agent for bacteria that produces (A), wherein the aforementioned (B) comprises one or more selected from the group consisting of fructooligosaccharides, galactoligosaccharides, indigestible dextrins, α-cyclodextrin, glucan, isomaltodextrin, inulin, fucose and cruciferous plants, or consists of one or more selected from the group consisting of fructooligosaccharides, galactoligosaccharides, indigestible dextrins, α-cyclodextrin, glucan, isomaltodextrin, inulin, fucose and cruciferous plants.

[0120] According to another embodiment of the present invention, the composition of the present invention comprises (C) a probiotic for bacteria producing (A).

[0121] (C) of the present invention comprises or consists of bacteria that produce (A).

[0122] In the present invention, the bacteria producing (A) are not particularly limited.

[0123] According to a preferred embodiment of the present invention, the bacterium producing (A) in the present invention is of the genus Akkermansia, more preferably Akkermansia muciniphila.

[0124] According to another preferred embodiment of the present invention, the bacterium producing (A) in the present invention is an anaerobic bacterium of the genus Anaerostipes, more preferably Anaerostipes caccae.

[0125] According to another preferred embodiment of the present invention, the bacterium producing (A) in the present invention is Anaerobutyricum (Eubacterium), more preferably Anaerobutyricum hallii (Eubacterium hallii).

[0126] According to another preferred embodiment of the present invention, the bacterium producing (A) in the present invention is of the genus Faecalibacterium, more preferably Faecalibacterium prausnitzii.

[0127] According to another preferred embodiment of the present invention, the bacterium producing (A) in the present invention is of the genus Roseburia, more preferably Roseburia intestinalis.

[0128] According to another preferred embodiment of the present invention, the bacterium producing (A) in the present invention is of the genus Coprobacter.

[0129] According to another preferred embodiment of the present invention, the bacterium producing (A) in the present invention is of the genus Bacteroidetes.

[0130] According to another preferred embodiment of the present invention, the bacterium producing (A) in the present invention is of the genus Clostridium, more preferably of Clostridium cluster IX.

[0131] According to another preferred embodiment of the present invention, the bacterium producing (A) in the present invention is of the genus Propionibacterium.

[0132] According to another preferred embodiment of the present invention, the bacterium producing (A) in the present invention is of the genus Veillonella.

[0133] According to another preferred embodiment of the present invention, the composition of the present invention comprises (C) a probiotic agent for bacteria producing (A), wherein the aforementioned (C) comprises a species selected from the group consisting of Akkermansia, Anaerostipes, Anaerobutyricum, Faecalibacterium, Roseburia, Coprobacterium, Bacteroidetes, Clostridium, Propionibacterium and Veillonella. The present invention also provides a kind of bacteria selected from the group consisting of the genus Anaerostipes, the genus Anaerobutyricum, the genus Faecalibacterium, the genus Roseburia, the genus Coprobacterium, the genus Bacteroidetes, the genus Clostridium, the genus Propionibacterium and the genus Veillonella.

[0134] The composition of the present invention may contain (A), (B), and (C) alone or in combination.

[0135] The composition of the present invention can be used both in vivo and in vitro.

[0136] The cells to which the composition of the present invention is applicable are not limited, and for example, cells in vivo, cells obtained from a living organism, passaged cells thereof, or cells derived from cell lines can be used. These cells can also be differentiated as needed. The cells of the present invention are preferably fibroblasts.

[0137] When the composition of the present invention is applied to an object, the object of application is not limited, and examples thereof include: primates including humans and chimpanzees; pet animals such as dogs and cats; livestock animals such as cows, horses, sheep, and goats; rodents such as mice and rats, and other mammals, preferably humans.

[0138] The composition of the present invention is not particularly limited and can also be made into a food composition. When the composition of the present invention is made into a food composition, it can further be mixed with known ingredients (additives) that can be mixed in a food composition. As such ingredients, for example, sweeteners, high-intensity sweeteners (aspartame, sucralose (sucralose), glycyrrhizic acid, saccharin, stevia, glucosamine, sucralose (trichloro-sucrose), thaumatin, acesulfame potassium, etc.), spices, colorants, acidulants, antioxidants, emulsifiers, preservatives, stabilizers, etc. can be mentioned.

[0139] The food composition of the present invention can be a health functional food such as a nutritional functional food, a specific health food, a functional label food, etc., and can also be manufactured in the form of a therapeutic diet (i.e., a diet that serves a therapeutic purpose, or a diet prepared by a nutritionist according to a dietary prescription formulated by a doctor and cooked based on a recipe), a diet therapy diet, a nursing diet, etc.

[0140] The pharmaceutical composition of the present invention can be prepared into a composition.

[0141] Example

[0142] The present invention will be specifically described based on the following examples, but the present invention is not limited to these examples. Unless otherwise specified, the content is expressed in mass %.

[0143] Test Example 1: Evaluation of the Effects of Each Component on the Production of Hyaluronic Acid and Other Substances in Human Fibroblasts

[0144] Human fibroblasts (product name: "skin fibroblasts", manufactured by KURABO INDUSTRIES LTD.) were dispersed in Dulbecco's Modification of Eagle's Medium (DMEM) containing 10% fetal bovine serum (FBS) to prepare 2.5×10 5 Cells / mL. 2 mL of each was inoculated into each well of a 6-well plate (Corning Costar 3516). The human fibroblasts inoculated on the 6-well plate were cultured in an incubator set at 37°C and 5% CO2. After 48 hours, the culture medium was removed and replaced with DMEM containing 1% antibacterial agent (product name: Antibiotic-Antimycotic Mixed Stock Solution (100x) (Stabilized), manufactured by Nacalai Tesque), and culture was continued for another 24 hours.

[0145] After 24 hours, the medium was removed and replaced with DMEM containing the components listed in Table 1 below, and cultured for another 18 hours to prepare cells cultured under four different conditions (Examples 1 and 2 and Comparative Examples 1 and 2).

[0146] [Table 1]

[0147] Table 1: Examples 1 and 2 and Comparative Examples 1 and 2

[0148]

[0149] The mRNA expression of COL1A1, COL3A1, COL7A1 and HAS2 genes of the four cells was evaluated. First, RNeasy Mini Kit (QIAGEN) was used to extract / purify the mRNA of COL1A1, COL3A1, COL7A1 and HAS2 genes from the four cells according to the provided protocol. Using the RNA extracted, TaqMan RNA-toCT 1-step Kit (Thermo Fisher SCIENTIFIC) was used to perform semi-quantitative PCR (Light Cycler 480; Roche) of COL1A1, COL3A1, COL7A1 and HAS2 genes according to the provided protocol. It should be noted that beta-actin was used as an internal standard to calibrate the expression of each gene. As primers, the following materials (all manufactured by Thermo Fisher SCIENTIFIC) were used.

[0150] COL1A1:Hs00164004_m1

[0151] COL3A1:Hs00943809_m1

[0152] COL7A1:Hs00164310_m1

[0153] HAS2:Hs00193435_m1

[0154] β-actin: Hs01060665_g1

[0155] The ratio of the COL1A1 mRNA expression levels obtained from the cell groups of Comparative Example 2, Example 1, and Example 2 is shown in Table 1, where the COL1A1 mRNA expression level obtained from the control (Comparative Example 1) is 100. Figure 1In addition, when the mRNA expression level of COL3A1 obtained from the control (Comparative Example 1) is set as 100, the ratio of the mRNA expression levels of COL3A1 obtained from the cell groups of Comparative Example 2, Example 1 and Example 2 is shown in Figure 2 Furthermore, when the mRNA expression level of COL7A1 obtained from the control (Comparative Example 1) is set as 100, the ratio of the mRNA expression levels of COL71A1 obtained from the cell groups of Comparative Example 2, Example 1 and Example 2 is shown in Figure 3 In addition, when the mRNA expression level of HAS2 obtained from the control (Comparative Example 1) is taken as 100, the ratio of the mRNA expression level of HAS2 obtained from the cell groups of Comparative Example 2, Example 1 and Example 2 is shown in Figure 4 .

[0156] These results show that IL-22 has almost no effect on the mRNA expression of COL1A1, COL3A1, COL7A1, and HAS2 genes, but sodium acetate and sodium propionate significantly increase the mRNA expression of the HAS2 gene.

[0157] Reference Example

[0158] In this example, the correlation between skin viscoelasticity and the amount of short-chain fatty acids in feces is shown below.

[0159] Determination of skin viscoelasticity

[0160] The viscoelasticity of the skin (R2 or R7 on the face or arm) of a human subject was measured by the following method.

[0161] The viscoelasticity of the skin on the cheeks and inner upper arms of 20 healthy women aged 20 to 50 was measured using a measuring instrument (Cutometer MPA580 (manufactured by Courage+Khazaka Electronic GmbH)) according to the following procedure. First, the face and inner upper arms of the subjects, which were to be measured, were cleansed and then acclimated for 30 minutes in a constant temperature and humidity chamber (temperature 21±2°C, humidity 45%±5%) in a quiet state. Next, a φ2mm probe was used to repeat the pattern of suction for 1 second and then stop for 1 second 30 times within 60 seconds at a suction pressure of 400mb, and three measurements were performed, with the average value being the measured value. The measurement on the cheek of the subject was performed by marking the intersection of the lower part of the nose and the outer corner of the eye with an L-shaped caliper, and then measuring 3cm downward and 3cm to the left from this point. In addition, the measurement on the inner upper arm of the subject was performed by marking a position 1.5cm inward and 5cm to the shoulder from the tip of the inner elbow as the starting point, and then measuring 1.5cm inward and 4.5cm to the shoulder from this point.

[0162] Determination of short-chain fatty acids in feces

[0163] The amounts of short-chain fatty acids (acetic acid and propionic acid) in feces of human subjects were measured by the following method.

[0164] Stool was collected from 20 healthy women aged 20 to 50 using a stool collection kit (product name: Stool Collection Kit, manufactured by TechnoSuruga Laboratory Co., Ltd.) and the amount of short-chain fatty acids (μmol / g) in the stool was quantified. Quantification was outsourced to a specialized third-party organization.

[0165] Statistical processing

[0166] The correlation between skin viscoelasticity and the amount of short-chain fatty acids in feces was studied. The skin viscoelasticity and the amount of short-chain fatty acids in feces were plotted in a scatter plot, and the correlation coefficient was calculated. The results showed that the skin viscoelasticity and the amount of short-chain fatty acids in feces had a significant correlation or a significant tendency to correlation ( Figure 5 :p=0.05323、 Figure 6 :p=0.04442、 Figure 7 :p=0.05711、 Figure 8 :p=0.08162).

Claims

1. A composition for promoting hyaluronic acid production, comprising one or more selected from the group consisting of the following components: (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof, (B) a prebiotic agent for bacteria producing (A), and (C) Probiotics for bacteria producing (A).

2. A composition for improving skin viscoelasticity, comprising one or more selected from the group consisting of the following components, (A) one or more selected from the group consisting of acetic acid and propionic acid or salts thereof, (B) a prebiotic agent for bacteria producing (A), and (C) Probiotics for bacteria producing (A).

3. The composition according to claim 1 or 2, wherein (B) contains one or more kinds selected from the group consisting of fructooligosaccharides, galactoligosaccharides, indigestible dextrins, α-cyclodextrins, glucans, isomaltodextrins, inulin, fucose and crucifers, or consists of one or more kinds selected from the group consisting of fructooligosaccharides, galactoligosaccharides, indigestible dextrins, α-cyclodextrins, glucans, isomaltodextrins, inulin, fucose and crucifers.

4. The composition according to claim 1 or 2, wherein (C) comprising one or more bacteria selected from the group consisting of Akkermansia, Anaerostipes, Anaerobutyricum, Faecalibacterium, Roseburia, Coprobacterium, Bacteroidetes, Clostridium, Propionibacterium, and Veillonella, Or it is composed of one or more bacteria selected from the group consisting of Akkermansia, Anaerostipes, Anaerobutyricum, Faecalibacterium, Roseburia, Coprobacterium, Bacteroidetes, Clostridium, Propionibacterium and Veillonella. The composition according to claim 1 , which is a composition for promoting hyaluronic acid production in fibroblasts. The composition according to claim 1 or 2, which is a food composition.

Images