JP2015063510A - Moisturizing gene expression promoter for improving skin moisturizing function - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a moisture retention-related gene expression promoter involved in the moisture retention of skin.SOLUTION: A moisture retention-related gene expression promoter comprises hyaluronic acid or pharmacologically acceptable salt thereof as an active ingredient.

Description

  The present invention relates to a moisturizing-related gene expression promoter, and more particularly, to a moisturizing-related gene expression promoter that promotes the expression of a gene for a protein that controls the movement of fluid inside and outside the cell related to skin moisturizing.

Keeping skin moisturized leads to improved skin firmness and elasticity, so moisture is essential for beautiful skin.
Skin, or skin, is an organ located in the outermost layer of the human body, and one of its important functions is to prevent excessive evaporation of moisture from inside the body. When the amount of water in the skin cells decreases due to excessive evaporation of water from the body, it causes deterioration of the skin environment such as reduced skin elasticity and reduced elasticity. Therefore, suppressing excessive evaporation of moisture from the body and maintaining moisture uptake into normal cells keeps the skin moist and leads to improvements in the skin environment, such as improved elasticity and elasticity.

The skin has a three-layer structure from the surface, epidermis, dermis, and subcutaneous tissue. In particular, the epidermis prevents moisture from evaporating from the body and adjusts the moisture, and plays a role in keeping the skin moist. The epidermis is divided into stratum corneum, granule layer, spiny layer, and basal layer. The keratinocytes born from the basal layer of the epidermis are pushed up while being differentiated, become keratinocytes through the spinous layer, the granule layer, and the stratum corneum, and repeat the cycle of peeling off.

  There are two main pathways for the movement of intracellular and extracellular fluids in the epidermis, which are important for the skin's moisturizing function. A pathway that is expressed on the cell membrane of keratinocytes in the layer and plays a role of taking in low-molecular substances such as interstitial water into cells is known. The other is a pathway in which tight junctions, which are one of cell adhesion structures, control the permeation of moisture in the granule layer by adhesion between cells.

Aquaporin, a transport protein on the cell membrane known as a water channel, is known to have 13 types of aquaporins (AQP0 to AQP12) in humans. In the epidermis, aquaporin 3 is mainly present, and it is thought to play a role of taking in low-molecular compounds such as glycerol and urea involved in water and moisture retention.

A protein called tight junction exists around the cells of the epidermal granule layer in a belt-like manner, adhering adjacent cells to each other, and controlling intercellular permeation of liquids and substances such as moisture in the stratum corneum. Examples of the protein constituting the tight junction include occludin, claudin, and JAM (Junction Adhesion Molecule).

Therefore, in order to realize moisturized and beautiful skin, it is very important to promote the production of proteins that control the movement of liquid inside and outside the cells as described above.

For this reason, the skin barrier function improving agent (patent document 1) by the cactus fruit fruit extract which has a tight junction formation promotion effect, and the stable chemical substance excellent in the formation promotion effect of a tight junction are disclosed conventionally. (Patent Document 2).
It has also been disclosed that tocopheryl relinoate promotes aquaporin expression in skin cells. (Patent Document 3)

  However, there has been a demand for safer and more effective materials for use in pharmaceuticals, quasi drugs, cosmetics, and foods.

JP 2012-121871 A JP 2007-210948 A JP 2006-290873 A

  The present invention provides a moisturizing-related gene expression promoter that is effective for promoting the expression of moisturizing-related genes.

  The present inventors have found that hyaluronic acid or a pharmaceutically acceptable salt thereof promotes the expression of a moisturizing-related gene, which is a gene of a protein that controls the movement of fluid inside and outside the cell, and completes the present invention. It came to.

That is, the present invention
(1) A moisturizing-related gene expression promoter that promotes the expression of a moisturizing-related gene, which is a protein gene related to skin moisturizing,
Containing hyaluronic acid or a pharmaceutically acceptable salt thereof as an active ingredient,
The moisturizing-related gene is a protein gene that controls movement of liquid inside and outside the cell,
Moisturizing related gene expression promoter,
(2) In the moisturizing related gene expression promoter according to (1),
The moisturizing gene is an aquaporin gene,
Moisturizing related gene expression promoter,
(3) In the moisturizing-related gene expression promoter according to (1),
The moisturizing gene is at least one gene selected from occludin, claudin, and JAM;
Moisturizing related gene expression promoter,
It is.

  According to the above-mentioned moisturizing-related gene expression promoter, a new preparation effective for improving the moisturizing power from the inside of the skin to promote the production of protein related to skin moisturizing, which controls the movement of liquid inside and outside the cell. Provided.

  Further, hyaluronic acid or a pharmaceutically acceptable salt thereof can permeate into the stratum corneum from the skin epidermis and exert an effect. Even when taken orally, it is absorbed from the intestinal tract, reaches the skin, and can exert its effect.

  Hereinafter, the present invention will be described in detail with reference to the drawings. In the present invention, “parts” means “parts by mass” and “%” means “mass%” unless otherwise specified.

<Moisturizing gene expression promoter>
The moisturizing-related gene expression promoter of the present invention is characterized by containing hyaluronic acid or a pharmaceutically acceptable salt thereof as an active ingredient. In the present invention, the moisturizing gene refers to a protein gene involved in improving the skin moisturizing function. Furthermore, the moisturizing-related gene in the present invention is a gene of a protein that controls the movement of liquid inside and outside the cell. The moisturizing-related gene expression promoter of the present invention promotes the production of proteins involved in improving the moisturizing function of the skin by promoting the expression of the moisturizing-related gene.
There are two main pathways for the movement of intracellular and extracellular fluids in the epidermis, which are important for the skin's moisturizing function, one is by transport proteins on the cell membrane known as water channels, and the other is cell adhesion structural proteins. There are known pathways that control intercellular permeation by bringing cells into close contact with each other.
Examples of moisturizing-related proteins that control the movement of liquid inside and outside the cell include, for example, aquaporin 3, aquaporin 5, and aquaporin 9 that control water transport on the cell membrane, and tight junctions that control the permeation of liquid between cells. Occludin, claudin, JAM, and the like.

<Evaluation of gene expression promoting effect>
The moisturizing-related gene expression promoting effect of the present invention is, for example, extracting RNA from human epidermal keratinocytes after adding a moisturizing-related gene expression promoter, synthesizing cDNA, amplifying the cDNA by real-time PCR method, and measuring mRNA expression By doing so, the effect of promoting gene expression can be confirmed.

<Hyaluronic acid or a pharmaceutically acceptable salt thereof>
In the present invention, “hyaluronic acid” is a polysaccharide having one or more repeating structural units composed of disaccharides of β-D-glucuronic acid and β-DN-acetylglucosamine. That is, hyaluronic acid is a disaccharide or more containing at least one disaccharide unit in which the 1-position of β-D-glucuronic acid and the 3-position of β-DN-acetyl-glucosamine are bonded. The “pharmaceutically acceptable salt of hyaluronic acid” is not particularly limited, and examples thereof include sodium salt, potassium salt, calcium salt, zinc salt, magnesium salt, ammonium salt and the like.
Hereinafter, in the present invention, hyaluronic acid or a pharmaceutically acceptable salt thereof is also simply referred to as “hyaluronic acid”.

<Origin of hyaluronic acid>
Hyaluronic acid may be extracted from biological tissues such as animals (eg, chicken crown, umbilical cord, skin, joint fluid, etc.), or obtained by culturing microorganisms, animal cells or plant cells (eg, Streptococcus genus). Fermentation methods using bacteria, etc.), those synthesized chemically or enzymatically, and the like can be used.

<Purity of hyaluronic acid>
In addition, the purity of hyaluronic acid used in the present invention may be a level that can be used in pharmaceuticals, preferably 90% or more, and more preferably 95% or more. This purity is a value calculated from a glucuronic acid quantitative value measured by a carbazole sulfate method (for example, Japanese Pharmacopoeia).

<Measurement method of purity>
In the carbazole sulfate method, an aqueous solution of hyaluronic acid is added and mixed in a sodium borate / sulfuric acid solution, the hyaluronic acid is decomposed by heating, cooled, mixed with a carbazole / ethanol solution, heated and left to cool. This is a method for measuring absorbance (530 nm). A calibration curve is prepared using D-glucuronolactone processed in the same manner, and a D-glucuronolactone conversion value is calculated, and then multiplied by 1.102 to obtain a glucuronic acid quantitative value. The obtained glucuronic acid quantitative value is multiplied by (molecular weight of hyaluronic acid / molecular weight of glucuronic acid) to calculate the content of hyaluronic acid.

<Molecular weight of hyaluronic acid>
Moreover, the average molecular weight of hyaluronic acid used in the moisturizing-related gene expression promoter of the present invention is 100,000 or less, preferably 70,000 or less, more preferably 400- 60,000 or less, more preferably 1,000 to 10,000. If the average molecular weight of hyaluronic acid is greater than 100,000, it may be difficult to obtain the moisturizing-related gene expression promoting effect of the present invention because it cannot penetrate into the keratin when applied as an external preparation.

  In addition, the average molecular weight of the hyaluronic acid prescribed | regulated by this invention is measured with the following method.

<Measurement method of molecular weight>
That is, about 0.05 g of purified hyaluronic acid was accurately weighed and dissolved in 0.2 mol / L sodium chloride solution to make exactly 100 mL, and 8 mL, 12 mL and 16 mL of this solution were accurately weighed, and A solution obtained by adding a 2 mol / L sodium chloride solution to make exactly 20 mL is used as a sample solution. This sample solution and a 0.2 mol / L sodium chloride solution were 30.0 ± 0.1 ° C. according to the viscosity measurement method (first method capillary viscosity measurement method) of the Japanese Pharmacopoeia (14th revision) general test method. The specific viscosity is measured by (Equation (1)), and the reduced viscosity at each concentration is calculated (Equation (2)). A graph is drawn with the reduced viscosity on the vertical axis and the concentration (g / 100 mL) of the product converted to dry matter on the horizontal axis, and the intrinsic viscosity is determined from the intersection of the straight line connecting the points and the vertical axis. Substituting the intrinsic viscosity obtained here into Laurent's formula (Formula (3)) to calculate the average molecular weight (TC Laurent, M. Ryan, A. Pietruszkiewicz,: BBA, 42, 476-485 (1960)) .
(Formula 1)
Specific viscosity = {(required flow time for sample solution) / (required flow time for 0.2 mol / L sodium chloride solution)}-1
(Formula 2)
Reduced viscosity = specific viscosity / (concentration of the product in terms of dry matter (g / 100mL))
(Formula 3)
Intrinsic viscosity = 3.6 × 10 ⁻⁴ M ^0.78
M: average molecular weight

<Hyaluronic acid content>
The hyaluronic acid content in the moisturizing-related gene expression promoter of the present invention may be an amount that allows hyaluronic acid to function as an active ingredient, and is usually 1% by mass or more, preferably 5 to 95% by mass.

<Mechanism of gene expression promotion effect>
Although the mechanism of action by which the expression of the moisturizing-related gene in keratinocytes is promoted by ingestion or application of the moisturizing-related gene expression promoter of the present invention is not necessarily clear, hyaluronic acid which is the active ingredient of the present invention Alternatively, it is speculated that the pharmaceutically acceptable salt acts on keratinocytes of the skin and increases the expression of moisturizing related genes.
When hyaluronic acid having a molecular weight of 100,000 or more is applied as an external preparation, the hyaluronic acid cannot penetrate into the stratum corneum, which may make it difficult to obtain the moisturizing related gene expression promoting effect of the present invention.

<Other ingredients used for moisturizing gene expression promoters>
The moisturizing-related gene expression promoter of the present invention can contain other raw materials in addition to the active ingredient hyaluronic acid as long as the effects of the present invention are not impaired. Examples of such raw materials are water, excipients, antioxidants, preservatives, wetting agents, thickeners, buffers, adsorbents, solvents, emulsifiers, stabilizers, surfactants, lubricants, Water-soluble polymers, sweeteners, flavoring agents, acidulants, alcohols and the like can be mentioned.
The moisturizing-related gene expression promoter of the present invention can contain other active ingredients as long as the effects of the present invention are not impaired. Specific examples of the active ingredient include, for example, an antioxidant component, an anti-aging component, an anti-inflammatory component, a whitening component, a cell activation component, vitamins, a blood circulation promoting component, a moisturizing component, a DNA damage preventing and / or repairing action. The component which has, an anti-glycation component, a peptide or its derivative (s), an amino acid or its derivative (s), a hydroquinone glycoside, its ester, etc. are mentioned. Moreover, the component by which the moisturizing related gene expression promotion effect similar to the moisturizing related gene expression promoting agent of this invention is anticipated can also be included. For example, ginger extract, watercress extract, mussel extract, ajuga kuru kestanka extract, phosphatidic acid, dipotassium glycyrrhizinate, amacha extract, lavender extract, hikikoshi extract, castus fruit fruit extract, goldfish extract, saffron extract, retinoic acid, crypto Xanthine and the like.

<Dosage form of moisturizing gene expression promoter>
The dosage form of the moisturizing-related gene expression promoter of the present invention is not particularly limited, but when the moisturizing-related gene expression promoter of the present invention is taken orally, for example, tablets, powders, fine granules, granules, capsules, pills Oral administration agents such as liquid preparations such as solid preparations such as liquid preparations, suspensions, syrups and emulsions.
Moreover, when apply | coating as an external preparation, a liquid agent, a suspension agent, an emulsion, a cream agent, an ointment, a gel agent, a liniment agent, a lotion agent, a poultice agent etc. are mentioned, for example.

<Intake and application amount of moisturizing gene expression promoter>
Since hyaluronic acid is a biological substance, it is considered that there is no side effect even when ingested or applied in a large amount or is extremely low, but the amount of hyaluronic acid and / or its salt taken as a moisturizing gene expression promoter of the present invention The standard can be 10 mg to 1000 mg, preferably 100 to 500 mg per day. The number of administrations can be selected once or multiple times per day.
In addition, when applied as an external preparation, it varies depending on the condition, age, sex, etc. of the target skin, but 0.01 mg to 1000 mg, preferably 0.5 to 500 mg, should be applied to the skin several times a day. That's fine.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to an Example.

<Examples 1 and 2>
Each of the following hyaluronic acids was dissolved in sterilized water to obtain each moisturizing gene expression promoter.
Example 1: Hyaluronic acid (average molecular weight 8,000, white powder, manufactured by QP Corporation)
Example 2: Hyaluronic acid (average molecular weight 2,000, white powder, manufactured by QP Corporation)

<Test Example 1>
In Test Example 1, in order to confirm the moisturizing related gene expression promoting effect of low molecular weight hyaluronic acid, a medium containing low molecular weight hyaluronic acid was added to the keratinocytes and incubated, and then the expression of various moisturizing related genes was measured. .

<Cell culture and RNA extraction>
Normal human adult epidermal keratinocytes NHEK (Kurashiki Spinning Co., Ltd.) are dispensed into SUMILON 24well Multi Well Plates 1 × 10 ^{5 at a} time using normal human epidermal keratinocyte basal medium (HuMedia-KG2 Kurashiki Spinning Co., Ltd.), CO ₂ Cultivate under conditions of 5% and 37 ° C. After culturing until confluent and removing the supernatant, the medium is replaced with a basal medium containing normal human epidermal keratinocytes containing 1.8 mM calcium ion, and cultured for 2 to 4 days at 37 ° C. with a CO ₂ concentration of 5%. After removing the medium, a normal human epidermal keratinocyte basal medium containing 1.8 mM calcium ion containing the moisturizing gene expression promoter of Example 1 or Example 2 was added so that the final hyaluronic acid concentration was 0.01 μg / mL. And incubated at 37 ° C. under a CO ₂ concentration of 5% for 3 hours or 6 hours. Thereafter, the supernatant was removed, the cells were collected, and the total RNA was adjusted.

<Real-time PCR>
Based on the total RNA, cDNA was synthesized using Affinity Script cDNA Synthesis Kit (Agilent Technology Co., Ltd.). Real-time PCR equipment (Mx3005 Agilent Technologies, Inc.) using Brilliant III Ultra Fast SYBR Green QPCR Master Mix (Agilent Technologies, Inc.) and various primers shown in Table 1 (100 pmoL / μL, Hokkaido System Science, Inc.) ) Was used to quantify the mRNA expression level of moisturizing related genes. That is, amplification of mRNA expression level is measured by performing amplification reaction that repeats heat denaturation (95 ° C, 10 seconds) and annealing (60 ° C, 20 seconds) 40 times, and simultaneously monitoring the fluorescence of SYBR Green binding to DNA. did. The mRNA expression levels of aquaporin 3, occludin, claudin 1 and JAM-1 as moisturizing-related genes were determined as a ratio to the GAPDH mRNA expression level as an internal standard, and expressed as an expression ratio when the control was 1. In addition, what added only the culture medium was made into the comparative example (control). The results of each gene expression level measurement are shown in Table 2.

<Primer sequence>
The primer sequences used for real-time PCR are shown in Table 1.

From Table 2, it was shown that in Examples 1 and 2 to which low molecular weight hyaluronic acid having an average molecular weight of 100,000 or less was added, the expression of moisturizing-related genes in human epidermal keratinocytes was promoted.
Moreover, since the gene expression is promoted in the short incubation time of 3 hours after the incubation than in the case of the 6 hour incubation, the low molecular weight hyaluronic acid is effective in promoting the moisturizing related gene expression in a short time. Was considered high.

  The prescription example of the moisturizing related gene expression promoter according to the present invention is shown below. The present invention is not limited by this formulation example.

<Prescription Example 1>
Using the hyaluronic acid (hyaluronic acid having an average molecular weight of 8,000) used in Example 1 as a moisturizing-related gene expression promoter, a powder (granule) having the following composition was prepared.

[Combination ratio]
Moisturizing gene expression promoter (hyaluronic acid of Example 1) 10%
Lactose 60%
Corn starch 25%
Hypromellose 5%
――――――――――――――――――――――――――――――――――――
100%

<Prescription Example 2>
Using the hyaluronic acid (hyaluronic acid having an average molecular weight of 8,000) used in Example 1 as a moisturizing-related gene expression promoter, tablets having the following formulation were produced.

[Combination ratio]
Moisturizing-related gene expression promoter (hyaluronic acid of Example 1) 25%
Lactose 24%
20% crystalline cellulose
Corn starch 15%
Dextrin 10%
Emulsifier 5%
Silicon dioxide 1%
――――――――――――――――――――――――――――――――――――
100%

<Prescription Example 3>
Using the hyaluronic acid (hyaluronic acid having an average molecular weight of 2,000) used in Example 2 as a moisturizing-related gene expression promoter, soft capsules having the following composition were prepared.

[Combination ratio]
Moisturizing related gene expression promoter (hyaluronic acid of Example 2) 20%
50% olive oil
Beeswax 10%
Medium chain fatty acid triglyceride 10%
Emulsifier 10%
――――――――――――――――――――――――――――――――――――
100%

<Prescription Example 4>
Using the hyaluronic acid of Example 1 or 2 as a moisturizing gene expression promoter, an emulsion having the following composition was prepared.

[Combination ratio]
Moisturizing related gene expression promoter (hyaluronic acid of Example 1 or 2) 0.20%
Propylene glycol 7.71%
Trehalose 0.03%
Ceramide 3 0.05%
Hinokitiol 0.01%
Citric acid 0.05%
Glycolic acid 0.05%
Mineral oil 3.00%
Trioctanoin 1.50%
Squalane 1.00%
Stearic acid 0.50%
Cetearyl alcohol 0.50%
Lanolin 0.30%
Paraffin 0.20%
Sorbitan stearate 1.40%
Tetraoleic acid sol base-30 1.00%
Polysorbate 60 0.80%
Methylparaben 0.20%
Propylparaben 0.10%
Ethanol 0.01%
Phenoxyethanol appropriate amount carbomer 0.10%
Potassium hydroxide 0.10%
Arginine 0.05%
BHT 0.02%
Tocopherol appropriate amount EDTA-2 sodium 0.02%
Remaining amount of purified water ――――――――――――――――――――――――――――――――――――――――
100%

<Prescription Example 5>
In this test example, the hyaluronic acid of Example 1 or 2 was used as a moisturizing-related gene expression promoter, and a warming sensation cataplasm containing the following composition was produced.

[Combination ratio]
Moisturizing related gene expression promoter (hyaluronic acid of Example 1 or 2) 0.20%
Sodium polyacrylate 4.00%
Sodium carboxymethylcellulose 2.00%
Kaolin 5.00%
Gelatin 3.00%
Glycerin 20.00%
Pepper extract 0.15%
Hyaluronic acid 5.00%
Purified water remaining ―――――――――――――――――――――――――――――――――――――
100.00%

<Prescription Example 6>
In this test example, the hyaluronic acid of Example 1 or 2 was used as a moisturizing related gene expression promoter, and an ointment having the following composition was produced.

[Combination ratio]
Moisturizing related gene expression promoter (hyaluronic acid of Example 1 or 2) 0.5%
White petrolatum 25.0%
Stearyl alcohol 20.0%
Propylene glycol 12.0%
Polyoxyethylene hydrogenated castor oil 60 4.0%
Glycerol monostearate 1.0%
Methyl paraoxybenzoate 0.1%
Propyl paraoxybenzoate 0.1%
Purified water remaining ―――――――――――――――――――――――――――――――――――――
100%

<Prescription Example 7>
In the present Example, the hyaluronic acid of Example 1 or 2 was used as a moisturizing related gene expression promoter, and a lotion having the following composition was produced.

[Combination ratio]
Moisturizing related gene expression promoter (hyaluronic acid of Example 1 or 2) 0.2%
Acetylated hyaluronic acid 0.1%
Chondroitin sulfate 0.1%
Collagen peptide 0.1%
1,3-butylene glycol 5.0%
Glycerol 3.0%
Isostearyl alcohol 0.1%
Tocopherol acetate 0.1%
POE (20) sorbitan monolaurate 0.5%
POE (15) lauryl alcohol ether 0.5%
Zinc pyrrolidonecarboxylate 0.1%
Retinoic acid 0.5%
Lavender extract 0.3%
Ginger extract 0.3%
Watercress extract 0.3%
Keyhole extract 0.3%
Saffron extract 0.3%
Ethylparaben 0.1%
Methylparaben 0.15%
Ethanol 5.0%
Perfume Appropriate amount of purified water Remaining amount ―――――――――――――――――――――――――――――――――――――
100%

<Prescription Example 8>
In the present Example, the hyaluronic acid of Example 1 or 2 was used as a moisturizing related gene expression promoter, and an emulsion having the following composition was prepared.

[Combination ratio]
Moisturizing related gene expression promoter (hyaluronic acid of Example 1 or 2) 0.3%
Pentylene glycol 5.0%
Glycerol 3.0%
Squalane 5.0%
Stearic acid 0.5%
Stearyl alcohol 2.0%
Vaseline 4.0%
Sorbitan stearate 1.0%
POE (10) monostearate 1.0%
Carboxy vinyl polymer 0.5%
Polyquaternium-51 0.1%
Dipotassium glycyrrhizinate 0.1%
Phosphatidic acid 0.5%
Cryptoxanthine 0.5%
Ajuaga Gurkestanka Extract 0.3%
Amateur extract 0.3%
Toad extract 0.3%
Castus fruit extract 0.3%
Kinginga extract 0.3%
Methylparaben 0.15%
Propylparaben 0.1%
Potassium hydroxide 0.1%
BHT 0.02%
EDTA-2 sodium 0.02%
Perfume Appropriate amount of purified water Remaining amount ―――――――――――――――――――――――――――――――――――――
100%

<Prescription Example 9>
In this example, hyaluronic acid of Example 1 or 2 was used as a moisturizing-related gene expression promoter to produce a cream (emollient cream) having the following composition.

[Combination ratio]
Moisturizing related gene expression promoter (hyaluronic acid of Example 1 or 2) 0.5%
Polyethylene glycol 4.0%
1,3-propanediol 6.0%
Squalane 11.0%
Dimethicone 1.0%
Cetanol 6.0%
Stearic acid 2.0%
Hydrogenated cocoglyceryl 4.0%
Tricaprylin 8.0%
Glycerol monostearate 3.0%
POE (20) cetyl alcohol ether 2.0%
Coenzyme Q10 0.03%
Ceramide 0.1%
Dilauroyl glutamate ricin sodium 0.1%
EDTA-2 sodium 0.02%
Propylparaben 0.1%
Methylparaben 0.15%
Perfume Appropriate amount of purified water Remaining amount ―――――――――――――――――――――――――――――――――――――
100%

<Prescription Example 10>
In this example, using the hyaluronic acid of Example 1 or 2 as a moisturizing related gene expression promoter, a cosmetic liquid (whitening moisturizing essence) having the following composition was prepared.

[Combination ratio]
Moisturizing related gene expression promoter (hyaluronic acid of Example 1 or 2) 0.8%
1,3-butylene glycol 5.0%
Glycerin 1.5%
POE sorbitan monostearate 1.0%
Sorbitan monostearate 0.5%
Xanthan gum 0.2%
Sodium alginate 0.2%
Carboxyvinyl polymer 0.2%
Potassium hydroxide 0.1%
Olive oil 0.2%
Tocopherol 0.1%
EDTA-2 sodium 0.02%
Arginine 0.15%
Dipotassium glycyrrhizinate 0.05%
Arbutin 0.2%
Retinol palmitate 0.2%
Cousin extract 0.2%
Seaweed extract 0.2%
Tranexamic acid 0.1%
Elastin 0.1%
Collagen 0.1%
Magnesium phosphate ascorbate 0.1%
Sodium citrate 1.0%
Citric acid 0.1%
Propylparaben 0.1%
Methylparaben 0.15%
Perfume Appropriate amount of purified water Remaining amount ―――――――――――――――――――――――――――――――――――――
100%

Claims (3)

A moisturizing-related gene expression promoter that promotes the expression of a moisturizing-related gene, which is a gene of a protein related to skin moisturizing,
Containing hyaluronic acid or a pharmaceutically acceptable salt thereof as an active ingredient,
The moisturizing-related gene is a protein gene that controls movement of liquid inside and outside the cell,
Moisturizing related gene expression promoter. In the moisturizing related gene expression promoter according to claim 1,
The moisturizing gene is an aquaporin gene,
Moisturizing related gene expression promoter. In the moisturizing related gene expression promoter according to claim 1,
The moisturizing gene is at least one gene selected from occludin, claudin, and JAM;
Moisturizing related gene expression promoter.