Hyaluronic acid production promoter

Abstract

To provide a method of indirectly making up loss of hyaluronic acid by ingesting a substance for promoting hyaluronic acid production, instead of a method of making up loss of hyaluronic acid by directly ingesting hyaluronic acid.SOLUTION: A promoting agent of hyaluronic acid production contains isoliquiritigenin as an active ingredient or further contains arachidic acid as another active ingredient. The promoting agent of hyaluronic acid production is expected not only to prevent skin aging caused by loss of hyaluronic acid, but also to improve a symptom accompanying loss of hyaluronic acid in other organs relating to hyaluronic acid.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a hyaluronic acid production promoter. [Background technology]

[0002] In recent years, research into preventing skin aging has been widely conducted. Aging is an important factor in skin aging, but in addition, the effects of dryness, oxidation, ultraviolet rays, etc. are also cited as direct factors related to skin aging. Specific phenomena that are known to cause skin aging include the decrease in mucopolysaccharides such as hyaluronic acid, cross-linking reactions of collagen, and cell damage caused by ultraviolet rays.

[0003] Hyaluronic acid is widely present in organs and tissues such as skin, joints, ligaments, lungs, kidneys, and brain. In particular, in the skin, it is an important factor for maintaining moisture due to its high moisturizing properties (Non-Patent Document 1). It is also known that the amount of hyaluronic acid present in the skin accounts for 50% of the total amount in the body (Non-Patent Document 2).

[0004] As a method for replenishing the decreased amount of hyaluronic acid, oral ingestion, in which hyaluronic acid is taken directly from the mouth, and transdermal absorption, in which hyaluronic acid is taken through the skin, have been proposed. It has been reported that hyaluronic acid taken orally is once broken down into smaller molecules by intestinal bacteria, then absorbed from the intestinal tract and resynthesized in the skin (see Non-Patent Document 3). On the other hand, in the case of transdermal absorption, it is known that hyaluronic acid is not absorbed through the skin because of its large molecular weight. However, the effect of preventing the skin from drying out due to the water retention of hyaluronic acid has been confirmed. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Papakonstantinou E.,:Hyaluronic acid : A Keymoleculein skin aging, Dermatoendocrinol, 4 (3), 253-8, 2012 [Non-Patent Document 2] TC Laurent and JR Fraser, “Hyaluronan,” FASEB J, Vol. 6, pp.2397-2402, 1992 [Non-Patent Document 3] Mamoru Kimura, Absorption of Orally Ingested Hyaluronic Acid, Functional Food Research 14:30-35,2018 Summary of the Invention [Problem to be solved by the invention]

[0006] By the way, the molecular weight of general hyaluronic acid is said to be 800,000 to 1,200,000. However, the molecular weight of the hyaluronic acid used in Non-Patent Document 3 is 300,000, which is smaller than the molecular weight of general hyaluronic acid. Therefore, it is unclear whether the same decomposition and resynthesis will occur even if the molecular weight increases. In addition, the results of Non-Patent Document 3 are the results of rats, and it is unclear whether the same behavior will be shown in humans. Furthermore, it is unclear how much of the decomposed hyaluronic acid is used for resynthesis. Thus, even if hyaluronic acid is directly orally ingested, it remains unclear whether the decreased hyaluronic acid can be replenished.

[0007] The present invention has been made in consideration of the above problems. That is, the object of the present invention is to provide a method for indirectly compensating for the loss of hyaluronic acid by taking a substance that promotes the production of hyaluronic acid, in addition to the method for directly compensating for the loss of hyaluronic acid by taking hyaluronic acid orally. [Means for solving the problem]

[0008] The inventors have investigated whether there is a substance that promotes the production of hyaluronic acid, and have newly discovered that the production of hyaluronic acid is promoted by taking isoliquiritigenin, which has led to the completion of the present invention.

[0009] In order to solve the above problems, the present invention is characterized by a hyaluronic acid production promoter comprising isoliquiritigenin as an active ingredient, and preferably further comprising arachidic acid as an active ingredient.

[0010] According to this configuration, the production of hyaluronic acid is promoted, thereby making it possible to compensate for the decrease in hyaluronic acid. Effect of the Invention

[0011] According to this invention, it is possible to supplement the decreased amount of hyaluronic acid by an indirect method. This allows the decreased amount of hyaluronic acid to be supplemented by a method other than direct ingestion, the effect of which is not yet fully understood. It is expected not only to prevent skin aging caused by the decrease in hyaluronic acid, but also to improve symptoms associated with the decrease in hyaluronic acid in other organs related to hyaluronic acid. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] The hyaluronic acid production promoter of the present invention may be any agent that has the effect of promoting hyaluronic acid production, and is characterized by containing at least isoliquiritigenin as an active ingredient. If necessary, it may further contain arachidic acid as an active ingredient.

[0013] Here, the "isoliquiritigenin" used in the present invention is a type of naturally occurring organic compound, and is known to be contained as one of the components of licorice, a type of herbal medicine. The isoliquiritigenin used in the present invention may be extracted and purified from a natural product, or may be industrially chemically synthesized.

[0014] However, there is no literature describing the absorption rate of isoliquiritigenin when it is taken, and the effective concentration of isoliquiritigenin is not clear. However, since the absorption rate of sesamin, which is also known as a flavonoid, is clear, it is possible to make some estimates based on sesamin. It is known that when 25 mg of sesamin is orally taken, the sesamin concentration in plasma is a maximum of 2 ng / mL. From this, assuming that isoliquiritigenin has the same absorption rate as sesamin, in the present invention, the daily intake amount of isoliquiritigenin is preferably 0.001 to 3.5 g, more preferably 0.01 to 3.0 g, and even more preferably 0.03 to 1.8 g.

[0015] Isoliquiritigenin may be used as a solid or as a liquid by dissolving it in a solvent. Examples of the solvent include an aqueous sodium hydroxide solution, ethanol, DMSO, etc., and among these, an aqueous sodium hydroxide solution or ethanol is preferred. In the present invention, it is preferred to dissolve it in an aqueous sodium hydroxide solution from the viewpoint of operability.

[0016] The "arachidic acid" used in the present invention is known as a saturated fatty acid contained in peanut oil. It is also known that arachidic acid can be produced by hydrogenating arachidonic acid. The arachidic acid used in the present invention may be extracted and purified from natural products, or may be industrially chemically synthesized.

[0017] As with isoliquiritigenin, the effective concentration of arachidic acid has not been clarified. However, based on the assumption of EPA and DHA, which are fatty acids like isoliquiritigenin, the absorption rate of arachidic acid can be roughly estimated. Assuming that the absorption rate of arachidic acid is the average value of EPA and DHA, in the present invention, the daily intake of arachidic acid is preferably 0.001-10.0 mg, more preferably 0.005-5.0 mg, and even more preferably 0.01-3.3 mg.

[0018] Arachidic acid may be used as a solid or as a liquid by dissolving it in a solvent. Examples of the solvent include alcohols such as methanol, ethanol, or propanol, ethers, and chloroform, among which alcohols are preferred. In the present invention, it is preferred to dissolve arachidic acid in ethanol from the viewpoint of operability.

[0019] The form of the hyaluronic acid production promoter of the present invention may be either solid or liquid, and may be arbitrarily selected depending on the form in which the hyaluronic acid production promoter of the present invention is used.

[0020] Furthermore, the hyaluronic acid production promoter of the present invention can be used by being contained in food and drink.For example, it can be used in dairy products such as fermented milk and lactic acid bacteria drinks, butter, egg processed products such as mayonnaise, and sweet breads such as butter cake.It can also be suitably used in processed foods such as instant noodles and cookies.Other than the above, it can be in the form of a formulation (for example, powder, granule, capsule, tablet, etc.) by adding suitable carriers and additives as necessary.

[0021] The hyaluronic acid production promoter of the present invention is also useful when incorporated into foods for specified health uses, nutritional supplements, functional foods, etc., in addition to general beverages and foods. EXAMPLES

[0022] The present invention will be described in more detail below, but the present invention is not limited thereto. In this example, the hyaluronic acid producing ability was evaluated using cultured cells.

[0023] (Preparation of Reagents) First, the reagents were prepared. First, isoliquiritigenin (Tokyo Chemical Industry Co., Ltd.) was dissolved in 0.1N sodium hydroxide aqueous solution to a concentration of 10 mM. Next, arachidic acid (Sigma Co., Ltd.) was dissolved in ethanol with a concentration of 95% or higher to a concentration of 10 mM.

[0024] (Preparation of cultured cells) Next, cultured cells were prepared. In this example, normal human dermal fibroblasts (NHDF) were used. First, NHDF were cultured at 37°C and 5% CO2 using DMEM (Dulbecco's Modified Eagle Medium, Gibco) supplemented with 10% inactivated FBS (Biowest) and Penicillin-Streptomycin (Invitrogen). Then, 1.0 × 10 5 NHDF cells were seeded at 100 cells / well and then cultured under the above culture conditions for 72 hours.

[0025] (Hyaluronic acid production ability evaluation test) After cell culture, the culture supernatant was replaced with DMEM without FBS. Next, a solution of isoliquiritigenin and arachidic acid serially diluted with PBS (PBS(-) pH 7.4, Gibco) was added to give final concentrations of 0.001μM, 0.01μM, 0.05μM, 0.1μM, and 1μM, either alone or mixed at the same concentration. The reason for the above concentrations is that in the case of cultured cells, unlike oral intake, the absorption rate is not relevant. Therefore, the addition concentration was determined based on the above-mentioned preferred range.

[0026] After adding the reagent, the cells were cultured for 24 hours under the conditions of 37°C and 5% CO2. After the culture, the medium was collected, and the hyaluronic acid concentration in the culture supernatant was measured using Hyaluronan, DuoSet Kit (R&D Systems). In this example, no reagent was added as a negative control (NC). Hyaluronic acid production ability was evaluated by assuming NC as 100%.

[0027] The results are shown in Table 1.

[0028] [Table 1]

[0029] As is clear from Table 1, when isoliquiritigenin was added, the promotion of hyaluronic acid production was observed at all concentrations. The results showed that the production promotion ability was particularly high at 0.01 to 0.05 μM. Next, when arachidic acid was added, the production promotion ability was high at 0.01 μM or less and at 1 μM. In other words, it was suggested that the production of hyaluronic acid was promoted even when isoliquiritigenin or arachidic acid was added alone.

[0030] Next, the effect of using isoliquiritigenin and arachidic acid together was confirmed. From Table 1, it can be seen that at concentrations of 0.1μM or less, the production of hyaluronic acid is promoted more than when added alone. In particular, at concentrations of 0.01-0.1μM, the promotion of hyaluronic acid production is higher than when added alone.

[0031] As explained above, it is suggested that the hyaluronic acid production promoter of the present invention can indirectly compensate for the loss of hyaluronic acid, apart from the method of directly orally taking hyaluronic acid.Therefore, it is expected not only to prevent skin aging caused by the loss of hyaluronic acid, but also to improve the symptoms associated with the loss of hyaluronic acid in other organs related to hyaluronic acid.

Claims

1. A hyaluronic acid production promoter containing isoliquiritigenin as an active ingredient.

2. The hyaluronic acid production promoter according to claim 1, further comprising arachidic acid as an active ingredient.

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