Skin moisture content increasing agent
The skin moisture-increasing agent using tranexamic acid promotes hyaluronic acid and ceramide production to enhance skin moisture and improve skin conditions like wrinkles and barrier function, addressing the lack of effective moisture increase in existing technologies.
Patent Information
- Application Number
- JP2024021443
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-02-15
- Publication Date
- 2025-08-27
AI Technical Summary
Existing technologies have not effectively addressed the increase in skin moisture content, despite incorporating tranexamic acid, and there is a lack of clarity on its moisture-enhancing effects.
A skin moisture-increasing agent containing tranexamic acid or its salts, which acts as a hyaluronic acid and ceramide production promoter, enhancing gene expression for increased skin moisture content and improving skin conditions such as wrinkles and barrier function.
The agent effectively increases skin moisture content, improves skin hydration, reduces wrinkle depth, and enhances skin barrier function by promoting hyaluronic acid and ceramide production, while also inhibiting melanin production for skin whitening.
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Abstract
Description
[Technical Field]
[0001] The present invention relates to a skin moisture-increasing agent. [Background technology]
[0002] Patent Documents 1 to 7 describe techniques for incorporating tranexamic acid into a composition. Patent Document 1 (JP 2013-159605 A) describes a liquid skin topical composition that contains a specific amount of tranexamic acid or at least one selected from its derivatives, a specific amount of a copolymer of 2-methacryloyloxyethyl phosphorylcholine and a hydrophobic monomer, a specific amount of a hydrophilic surfactant, and glycerin, and the content of a component with a thickening effect is within a specific range (Claim 1).It is said that even though this composition contains tranexamic acids and even glycerin, the stickiness and squeaking caused by these are suppressed by the specific amount of the copolymer of 2-methacryloyloxyethyl phosphorylcholine and a hydrophobic monomer, and that the composition has a smooth feel when used and is excellent in moisturizing effects and improving rough skin (paragraph 0010).
[0003] Patent Document 2 (JP Patent Publication No. 9-95410A) describes a topical skin preparation containing tranexamic acid and a low-molecular-weight betaine (claim 1), and claims that the inclusion of tranexamic acid and a low-molecular-weight betaine provides a topical skin preparation that has an excellent effect of improving rough skin due to the synergistic effect of the two, has excellent moisturizing effect, and is easy to use (paragraph 0029).The same document also describes that the moisturizing effect was measured based on the rate of water evaporation on filter paper (paragraph 0022).
[0004] Patent Document 3 (JP Patent Publication No. 6-65053) describes a topical skin preparation that combines at least one type of lipid with tranexamic acid, or a salt thereof, or a derivative thereof, or a mixture of these (Claim 1). It states that by combining lipids with tranexamic acid, it is possible to provide a topical skin preparation that not only enhances the moisture retention ability of the stratum corneum but also maintains the epidermis itself in a healthy state, providing appropriate ``moisture'' and ``firmness,'' and having the effect of improving rough skin (Paragraph 0035).
[0005] Patent Document 4 (JP Patent Publication No. 11-193212 A) describes an external skin preparation for enhancing the maintenance of skin pH buffering capacity, which has the ability to enhance the maintenance of skin pH buffering capacity (Claim 1), and lists a number of ingredients including amino acids as ingredients that have the ability to enhance the maintenance of skin pH buffering capacity, and describes a number of ingredients including tranexamic acid as amino acids (paragraphs 0015 to 0059).
[0006] Patent Document 5 (WO 2019 / 078370) describes a composition for improving skin disorders caused by air pollutants, which contains at least one IL-8 expression inhibitor, and lists a number of ingredients, including tranexamic acid and its salts, as IL-8 expression inhibitors (claims 1 and 3). The document also describes that tranexamic acid inhibits the activation of IL-8 by UA and that it inhibits skin inflammation caused by urban airborne particulate matter, including PM2.5 (paragraph 0149).
[0007] Patent Document 6 (JP Patent Publication No. 2018-203643) describes a collagen degradation inhibitor containing tranexamic acid (Claim 1) as a technology aimed at providing a collagen degradation inhibitor and cosmetic composition that exhibits an inhibitory effect on dermis-derived plasmin and suppresses collagen degradation to prevent wrinkles and sagging (paragraph 0005).
[0008] Patent Document 7 (JP 2006-8550 A) describes an anti-aging agent containing a pro-urokinase activation inhibitor and / or a urokinase inhibitor as an active ingredient for preventing wrinkle formation due to dryness and / or improving existing wrinkles (Claim 1). It also describes that the pro-urokinase activation inhibitor is one or more selected from the group consisting of amides of tranexamic acid having a specific structure and cosmetically acceptable salts thereof (Claim 3). [Prior art documents] [Patent documents]
[0009] [Patent Document 1] Japanese Patent Application Laid-Open No. 2013-159605 [Patent Document 2] Japanese Patent Application Publication No. 9-95410 [Patent Document 3] Japanese Patent Application Publication No. 6-65053 [Patent Document 4] Japanese Patent Application Publication No. 11-193212 [Patent Document 5] International Publication No. 2019 / 078370 [Patent Document 6] Japanese Patent Application Publication No. 2018-203643 [Patent Document 7] Japanese Patent Application Laid-Open No. 2006-8550 Summary of the Invention [Problem to be solved by the invention]
[0010] On the other hand, none of the above Patent Documents 1 to 7 clarified the effect of tranexamic acids on the actual moisture content of the skin. The present invention provides a new technology for increasing skin moisture content. [Means for solving the problem]
[0011] According to the present invention, the following skin moisture-increasing agent is provided. [1] A skin moisture-increasing agent containing at least one member selected from the group consisting of tranexamic acid and its salts. [2] The skin moisture content increasing agent described in [1], which is a hyaluronic acid production promoter. [3] A skin moisture-increasing agent according to [1] or [2], which is an enhancer of hyaluronic acid production-promoting factors. [4] The skin moisture-increasing agent according to [3], wherein the hyaluronic acid production-promoting factor is HAS3. [5] A skin moisture-increasing agent according to any one of [1] to [4], which is used to improve wrinkles. [6] The skin moisture-increasing agent according to any one of [1] to [5], further comprising dipotassium glycyrrhizinate. [7] The skin moisture-increasing agent according to any one of [1] to [6], which is a ceramide production promoter. [8] The skin moisture content increasing agent according to any one of [1] to [7], which is an enhancer of a ceramide production factor. [9] The skin moisture-increasing agent according to [8], wherein the ceramide-producing factor is SPTLC1.
[10] The skin moisture content increasing agent according to any one of [1] to [9], which is an external preparation or a cosmetic.
[11] A skin moisture content increasing agent according to any one of [1] to
[10] , wherein the content of tranexamic acid and its salt in the skin moisture content increasing agent is 0.005% by mass or more and 10% by mass or less relative to the total amount of the skin moisture content increasing agent.
[0012] According to the present invention, a new technique for increasing skin moisture content can be provided. [Brief explanation of the drawings]
[0013] [Figure 1] FIG. 1 is a diagram showing the evaluation results of the moisture content of the stratum corneum in the examples. [Figure 2] FIG. 10 is a diagram showing the results of wrinkle evaluation in the examples. [Figure 3] FIG. 1 shows the results of evaluation of the expression level of the HAS3 gene in an example. [Figure 4]FIG. 1 shows the results of evaluation of the gene expression level of TGM1 in an example. [Figure 5] FIG. 1 shows the results of evaluation of the expression level of the SPTLC1 gene in an example. [Figure 6] FIG. 1 shows the results of evaluation of the gene expression level of LOR in an example. [Figure 7] FIG. 1 shows the results of evaluation of the expression level of the KRT10 gene in an example. [Figure 8] FIG. 1 shows the results of evaluation of the expression level of FLG genes in an example. [Figure 9] FIG. 1 shows the results of evaluation of the gene expression level of EDN2 in an example. [Figure 10] FIG. 1 shows the results of evaluation of the gene expression level of FGF2 in an example. DETAILED DESCRIPTION OF THE INVENTION
[0014] Hereinafter, an embodiment of the present invention will be described. In this embodiment, the composition may contain each component either alone or in combination of two or more. In this specification, the symbol "to" indicating a numerical range means "greater than or equal to" or "less than or equal to," and both of the numerical values at both ends are included.
[0015] (Skin moisture increaser) In this embodiment, the skin moisture-increasing agent contains at least one selected from the group consisting of tranexamic acid and salts thereof. Specifically, the skin moisture-increasing agent is a composition containing at least one member selected from the group consisting of tranexamic acid and its salts (hereinafter also referred to as "ingredient (A)") as an active ingredient.
[0016] In this embodiment, the moisture content of the skin can be effectively increased by using at least one selected from the group consisting of tranexamic acid and its salts. According to this embodiment, for example, it is also possible to obtain the effect of increasing the moisture content of the stratum corneum over time.
[0017] The skin moisture content-increasing agent is preferably a production promoter of at least one selected from the group consisting of hyaluronic acid and ceramide, thereby enabling a more stable increase in skin moisture content.
[0018] For example, when the skin moisture content increasing agent is a hyaluronic acid production promoter, the skin moisture content increasing agent is preferably an enhancer of hyaluronic acid production promoter, in order to increase skin moisture content more stably.In the same respect, the hyaluronic acid production promoter is preferably the gene related to hyaluronic acid production, more preferably hyaluronic acid synthase 3 (HAS3). The skin moisture content increasing agent may also be an agent for enhancing the expression level of a gene involved in hyaluronic acid production.
[0019] Furthermore, when the skin moisture-increasing agent is a ceramide production promoter, the skin moisture-increasing agent is preferably an enhancer of a ceramide production factor, in order to increase skin moisture more stably. Similarly, the ceramide production promoter is preferably a gene related to ceramide production, more preferably a gene related to a ceramide synthase such as serine palmitoyltransferase (e.g., SPTLC1). The skin moisture content increasing agent may also be an agent for enhancing the expression level of a gene involved in ceramide production.
[0020] Furthermore, by increasing the moisture content of the skin, it is possible to impart an effect of improving skin wrinkles, for example. That is, it is also preferable that the skin moisture increasing agent is for improving wrinkles. Furthermore, since the skin moisture-increasing agent contains component (A), it is also possible to obtain the effect of enhancing the expression of genes related to wrinkle improvement, for example. Specifically, the gene related to wrinkle improvement is fibroblast growth factor 2 (FGF2). Increased FGF2 promotes collagen production, increases skin moisture, and improves wrinkles. Furthermore, by increasing the moisture content of the skin, it is possible to obtain, for example, a moisturizing effect on the skin and an effect of preventing the skin from drying out.
[0021] Furthermore, since the skin moisture-increasing agent contains component (A), it can also have the effect of inhibiting the expression of at least one gene selected from the group consisting of genes related to melanin production and melanocyte-stimulating factors. This can inhibit melanin production in the skin. By inhibiting melanin production, it can be possible to inhibit melanin retention, thereby imparting a skin whitening effect. A gene involved in melanin production is specifically the gene for endothelin 2 (EDN2).
[0022] Furthermore, since the skin moisture-increasing agent contains component (A), it can also enhance the expression level of genes related to promoting differentiation of skin cells, as described below, which can also improve the skin's barrier function.
[0023] (Dosage form, etc.) The skin moisture-increasing agent is preferably an external preparation such as a skin topical preparation; or a cosmetic such as a skin cosmetic. This allows the skin moisture-increasing agent to be selectively applied to a desired area. The skin moisture-increasing agent may be a quasi-drug (such as a medicated cosmetic) or a pharmaceutical. The skin moisture-increasing agent is preferably a cosmetic, an external preparation for skin, or a quasi-drug (such as a medicated cosmetic). At this time, the skin hydration agent is applied to the skin, preferably by spreading it on the skin.
[0024] The dosage form of the external preparation can be, for example, a liquid preparation for external use including a liniment or a lotion; a cream; a spray preparation including an aerosol or a pump spray; or a gel. Here, the liniment is specifically a liquid or muddy external preparation that is rubbed into the skin. Furthermore, the lotion is specifically an external preparation in which an active ingredient is dissolved, emulsified, or finely dispersed in an aqueous liquid.
[0025] Examples of cosmetics include lotions, emulsions, serums, creams, gels, makeup removers, facial cleansers, sunscreens, makeup bases, foundations, lip balms, shampoos, conditioners, body soaps, etc. The cosmetics may be filled in pump spray containers or aerosol containers.
[0026] The skin moisture-increasing agent may be an oral composition, which can be easily ingested, or a pharmaceutical composition.
[0027] The oral composition is preferably a solid such as a solid preparation, which can improve the storage stability of the skin moisture-increasing agent and can also be easily ingested. The dosage form of the oral composition may be, for example, tablets, granules, pills, powders, gummies, or jellies, and preferably tablets. Examples of tablets include plain tablets, plain tablets, sugar-coated tablets, orally disintegrating tablets, film-coated tablets, and chewable tablets. The tablets may also be multi-layer tablets formed by compressing two or more layers of powders or granules with different compositions. The film may be given properties such as immediate solubility, delayed solubility, gastric solubility, or enteric solubility depending on the desired composition. Next, the ingredients contained in the skin moisture increasing agent will be described.
[0028] (Component (A)) Component (A), i.e., at least one selected from the group consisting of tranexamic acid and its salts, is a known compound and can be produced by known methods or commercially available products. For example, tranexamic acid is listed in the 18th edition of the Japanese Pharmacopoeia.
[0029] Specific examples of salts of tranexamic acid salts include hydrohalides such as hydrofluoride, hydrochloride, hydrobromide, and hydroiodide; inorganic acid salts such as nitrates, perchlorates, sulfates, and phosphates; Alkanesulfonates having from 1 to 4 carbon atoms, such as methanesulfonates, trifluoromethanesulfonates, and ethanesulfonates; arylsulfonates such as benzenesulfonates and p-toluenesulfonates; organic acid salts such as acetate, malate, fumarate, succinate, citrate, ascorbate, tartrate, oxalate, maleate, etc.; alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts and magnesium salts; Organic amine salts such as N-methylmorpholine salts, triethylamine salts, tributylamine salts, diisopropylethylamine salts, dicyclohexylamine salts, N-methylpiperidine salts, pyridine salts, 4-pyrrolidinopyridine salts, and picoline salts; and Examples thereof include one or more salts selected from the group consisting of salts with amino acids such as glycine salts, lysine salts, arginine salts, ornithine salts, glutamic acid salts, and aspartic acid salts.
[0030] Component (A) preferably contains tranexamic acid, more preferably tranexamic acid, which allows the skin moisture-increasing effect to be more stably obtained.
[0031] The content of component (A) in the skin moisture content-increasing agent is preferably 0.005% by mass or more, more preferably 0.01% by mass or more, even more preferably 0.1% by mass or more, and even more preferably 0.5% by mass or more, based on the total amount of the skin moisture content-increasing agent, thereby further enhancing the skin moisture content-increasing effect. The content of component (A) in the skin moisture content-increasing agent is preferably 10% by mass or less, more preferably 8% by mass or less, even more preferably 6% by mass or less, and even more preferably 3% by mass or less, based on the total amount of the skin moisture content-increasing agent, thereby enabling the skin moisture content-increasing effect to be obtained more stably.
[0032] The content of component (A) in the skin moisture-increasing agent may be determined appropriately depending on, for example, the gender, age, symptoms, etc. of the recipient, and the daily dosage is, for example, 50 to 3000 mg. The daily application amount of component (A) is preferably 50 mg or more, more preferably 100 mg or more, and even more preferably 250 mg or more, and can be administered, for example, 1 to 3 times a day, thereby further enhancing the effect of increasing skin moisture content. The daily application amount of component (A) is preferably 3000 mg or less, more preferably 2500 mg or less, and even more preferably 2000 mg or less, and can be administered, for example, 1 to 3 times a day, thereby achieving a more stable effect of increasing skin moisture content.
[0033] The amount of the skin moisture content increasing agent to be applied can be determined, for example, depending on the form of the skin moisture content increasing agent. The number of times per day that the skin moisture-increasing agent is applied may be, for example, 1 to 10 times, preferably 1 to 5 times, and more preferably 1 to 3 times.
[0034] The skin moisture-increasing agent may further contain components other than component (A). For example, the skin moisture content can be increased by further containing dipotassium glycyrrhizinate, which can further enhance the enhancing effect of at least one selected from the group consisting of the hyaluronic acid production factors and ceramide production factors, thereby enabling a more stable increase in skin moisture content.
[0035] Furthermore, by further containing dipotassium glycyrrhizinate, the skin moisture-increasing agent can enhance the expression level of genes related to promoting differentiation of skin cells, thereby improving, for example, the skin barrier function. Specifically, the gene associated with promoting differentiation of skin cells is one or more genes selected from the group consisting of loricrin (LOR), transglutaminase 1 (TGM1), keratin 10 (KRT10), and filaggrin (FLG).
[0036] The content of dipotassium glycyrrhizinate in the skin moisture-increasing agent is preferably 0.05% by mass or more based on the total amount of the skin moisture-increasing agent, thereby further enhancing the skin moisture-increasing effect. The content of dipotassium glycyrrhizinate in the skin moisture-increasing agent is preferably 5% by mass or less relative to the total amount of the skin moisture-increasing agent, which allows for safer use. The content of dipotassium glycyrrhizinate in the skin moisture-increasing agent may be, for example, 12% by mass or less relative to the total amount of the skin moisture-increasing agent.
[0037] The mass ratio of the content of dipotassium glycyrrhizinate to the content of component (A) in the skin moisture content-increasing agent (dipotassium glycyrrhizinate / (A)) is preferably 0.01 or more, preferably 0.1 or more, more preferably 0.2 or more, and even more preferably 2 or more. This allows the effect of increasing skin moisture content to be exerted more effectively. Furthermore, the mass ratio (dipotassium glycyrrhizinate / (A)) is preferably 10 or less, and more preferably 6 or less. This allows the effect to be exerted more stably. Furthermore, the mass ratio may be, for example, 0.5 or less or 0.25 or less.
[0038] (Other ingredients) In this embodiment, the skin moisture content-increasing agent may contain, as appropriate, various ingredients used in ordinary cosmetics, quasi-drugs, pharmaceuticals, etc., other than the above-mentioned ingredients, within a range that does not impair the effects of the present invention. For example, the skin moisture content-increasing agent may contain one or more ingredients selected from the group consisting of oily ingredients such as fats and oils (vegetable oils, etc.), waxes, hydrocarbon oils, ester oils, higher alcohols, higher fatty acids, and silicone oils; ultraviolet absorbers; ultraviolet scattering agents; moisturizers; surfactants; water-soluble polymers; thickeners; skin protectants; plant extracts; preservatives; sequestering agents; antioxidants; pearlescent agents; colorants; refreshing agents; and fragrances.
[0039] Specific examples of the moisturizer include polyhydric alcohols such as 1,3-butylene glycol, glycerin, and methyl gluceth 10. The content of the moisturizer in the skin moisture content increaser can be, for example, 0.1 to 20% by mass based on the total mass of the skin moisture content increaser. Specific examples of surfactants include one or more selected from the group consisting of nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants. Among these, examples of nonionic surfactants include polyoxyethylene sorbitan fatty acid esters such as polysorbate-80, and polyoxyethylene hydrogenated castor oils such as PEG-60 hydrogenated castor oil. The content of the nonionic surfactant in the skin moisture-increasing agent can be, for example, 0.01 to 2% by mass based on the total weight of the skin moisture-increasing agent. The surfactant may also be an emulsifier. Examples of thickeners include one or more selected from the group consisting of natural polymers such as guar gum, carrageenan, xanthan gum, sodium hyaluronate, pullulan, agar, alginate, etc., and synthetic polymers such as hydroxyethyl cellulose, hydroxymethyl cellulose, carboxyvinyl polymer, polyacrylate, polyvinyl alcohol, acrylic acid-alkyl methacrylate copolymer, etc. The content of the thickener is, for example, preferably 0.001 to 5% by mass, more preferably 0.005 to 3% by mass, and even more preferably 0.01 to 2% by mass, based on the total weight of the skin moisture-increasing agent. A specific example of the skin protective agent is trehalose. The content of the skin protective agent in the skin moisture content increasing agent can be, for example, 0.01 to 1% by mass based on the total amount of the skin moisture content increasing agent. A specific example of the preservative is phenoxyethanol. The content of the preservative in the skin moisture content increasing agent can be, for example, 0.01 to 1% by mass based on the total amount of the skin moisture content increasing agent.
[0040] In this embodiment, the skin moisture-increasing agent can be obtained by a production method including a step of mixing at least one selected from the group consisting of tranexamic acid and its salts with other appropriate ingredients. The other ingredients can be selected depending on, for example, the dosage form and desired performance of the skin moisture-increasing agent. When the skin moisture-increasing agent is an external preparation, the skin moisture-increasing agent can be produced according to the usual method described in, for example, the 18th edition of the Japanese Pharmacopoeia.
[0041] (packaging) In this embodiment, the package includes a skin moisture-increasing agent and a container for storing the agent. For example, when the skin moisture content increasing agent is an external preparation or a cosmetic, these preparations can be directly placed in a container made of a polyolefin resin such as polyethylene or polypropylene, and then further placed in a moisture-proof bag containing a metal such as aluminum to form a package.
[0042] (Method to increase skin moisture) In this embodiment, the method for increasing skin moisture content (excluding medical procedures on humans) includes, for example, applying the skin moisture content increasing agent of this embodiment to a subject, more preferably applying the skin moisture content increasing agent of this embodiment to the skin of the subject, and even more preferably applying the skin moisture content increasing agent of this embodiment to the skin of the subject. In this embodiment, the skin moisture content increasing agent has the above-mentioned excellent effects, and by applying it to a subject, it is possible to increase the skin moisture content of the subject over time, and also to obtain, for example, an effect of improving wrinkles in the subject.
[0043] Although the embodiments of the present invention have been described above, these are merely examples of the present invention, and various other configurations can also be adopted. [Example]
[0044] The present embodiment will be specifically described below with reference to examples, but the present embodiment is not limited to these examples.
[0045] (Test Example 1) In this example, the following topical preparations were prepared and evaluated.
[0046] (Method for preparing topical preparations) The ingredients were mixed according to the formulations in Table 1 to obtain preparations of Example 1 (tranexamic acid preparation) and Comparative Example 1 (placebo preparation). In Example 1, 120 g of tranexamic acid and 300 g of liquid paraffin were added to 3825.54 g of purified water, and then appropriate amounts of an emulsifier, preservative, moisturizer, and thickener were added and mixed. The pH was then adjusted to 4.5 to 6.5 using citric acid and sodium hydroxide, thereby preparing a test topical preparation with a total volume of 6000 g (tranexamic acid concentration: 2% by mass). In Comparative Example 1, a test external preparation was obtained in the same manner as in Example 1, except that 120 g of tranexamic acid was replaced with 120 g of purified water.
[0047] [Table 1]
[0048] (evaluation) The skin moisture content and wrinkle condition were evaluated by the following methods when each topical preparation was continuously applied to the subjects.
[0049] (overview) Observation dates: before standardization period, before use, after 4 weeks of use, after 8 weeks of use, after 12 weeks of use Observation area: corners of the left and right eyes How to use the topical agent: Apply to the face twice a day, morning and evening, during skin care for 12 weeks. Evaluation items: - Measurement of stratum corneum moisture content: Corneometer (before standardization period, before use, after 4 weeks of use, after 8 weeks of use, after 12 weeks of use) Wrinkle grade assessment: Photographic evaluation by a doctor (before use, after 4 weeks, after 8 weeks, after 12 weeks)
[0050] (Subject grouping and standardization) Thirty healthy Japanese women aged 45 to 65 years old, with wrinkles mainly corresponding to Grade 3 to 5 (Journal of the Japanese Society of Cosmetic Science, 2006, Vol. 30, No. 4, pp. 316-322) at the corners of both eyes, were divided into Group O (15 subjects) and Group P (15 subjects). The subjects in Group O used the formulation of Example 1 on the right half of their faces, including the corners of their right eyes, and the formulation of Comparative Example 1 on the left half of their faces, including the corners of their left eyes. The subjects in Group P used the formulation of Example 1 on the left half of their faces, including the corners of their left eyes, and the formulation of Comparative Example 1 on the right half of their faces, including the corners of their right eyes.
[0051] (Measurement of stratum corneum moisture content) After washing the face, the area around both eyes was measured three times using a Corneometer CM825 (manufactured by Courage+Khazaka), and the average value of the three measurements was used. The measurement results are shown in Figure 1(a) and Figure 1(b). The vertical axis of these figures indicates skin moisture content (AU), with larger values indicating greater moisture content.
[0052] (Wrinkle grade determination) The doctor in charge of the test evaluated the photographs taken on each evaluation day in accordance with the wrinkle grade criteria (Journal of the Japanese Society of Cosmetic Science, Vol. 30, No. 4, pp. 316-322, 2006). The evaluation results are shown in Figure 2. The vertical axis of these figures indicates the degree of wrinkles, taking into account the depth and clarity of the wrinkles, and the lower the wrinkle grade, the smaller the wrinkles.
[0053] As can be seen from Figures 1(a) and 1(b), continuous use of the preparation of Example 1 significantly increased the moisture content of the stratum corneum at the application site. In addition, as can be seen from FIG. 2, continued use of the preparation of Example 1 also improved the wrinkle grade at the application site.
[0054] (Test Example 2) In this example, the gene expression levels in human epidermal keratinocytes were measured by the following procedure. The following test solutions were used: Control 1: Phosphate buffered saline (PBS) Example 2 (1 mM TA): 1 mM tranexamic acid in PBS Example 3 (1 mM TA + 1 mM GK2): PBS solution of 1 mM tranexamic acid and 1 mM dipotassium glycyrrhizinate
[0055] Human immortalized keratinocyte cell line (HaCat) was cultured in Dulbecco's Modified Eagle Medium (Gibco) at 9.5 × 10 5 The cells were seeded at 100 cells / dish. The day after seeding, the medium was removed and replaced with a test solution containing each test substance diluted to 1 mM in Dulbecco's Modified Eagle Medium (Gibco), and the cells were cultured for 48 hours. After culture, RNA was extracted using an RNeasy Mini Kit (QIAGEN), and cDNA was synthesized by reverse transcription using a Verso cDNA Synthesis Kit (Thermo Fisher). The expression levels of various genes (RNA) were then measured by real-time PCR.
[0056] Measurements were performed three times for each test example for the following genes: HAS3 (Figure 3), TGM1 (Figure 4), SPTLC1 (Figure 5), LOR (Figure 6), KRT10 (Figure 7), FLG (Figure 8), EDN2 (Figure 9), and FGF2 (Figure 10). Measurements were performed for some of the genes in the test solution of Example 2. The results for each gene are shown in the figures in parentheses above.
[0057] As shown in Figure 7, in Example 2, the addition of tranexamic acid enhanced the expression of a gene (KRT10) associated with promoting differentiation of skin cells, and in Example 3, i.e., the addition of tranexamic acid and dipotassium glycyrrhizinate, further enhanced the expression. As shown in Figure 9, in Example 2, the addition of tranexamic acid suppressed the expression of a gene (EDN2) related to melanin production, and in Example 3, the addition of tranexamic acid and dipotassium glycyrrhizinate further suppressed the expression. 3 to 6, 8, and 10, the addition of tranexamic acid and dipotassium glycyrrhizinate in Example 3 enhanced the expression of genes involved in hyaluronic acid production (HAS3), genes involved in ceramide synthase (SPTLC1), genes involved in promoting differentiation of skin cells (TGM1, LOR, FLG), and genes involved in wrinkle improvement (FGF2). Furthermore, the expression of these genes was also enhanced when tranexamic acid and dipotassium glycyrrhizinate were added compared to when tranexamic acid alone was added.
Claims
1. A skin moisture-increasing agent comprising at least one member selected from the group consisting of tranexamic acid and salts thereof.
2. The skin moisture content increasing agent according to claim 1, which is a hyaluronic acid production promoter.
3. The skin moisture content increasing agent according to claim 1 or 2, which is an enhancer of a hyaluronic acid production promoting factor.
4. The skin moisture-increasing agent according to claim 3, wherein the hyaluronic acid production-promoting factor is HAS3.
5. The skin moisture-increasing agent according to claim 1 or 2, which is used to improve wrinkles.
6. The skin moisture-increasing agent according to claim 1 or 2, further comprising dipotassium glycyrrhizinate.
7. The skin moisture-increasing agent according to claim 6, which is a ceramide production promoter.
8. The skin moisture-increasing agent according to claim 6, which is an enhancer of a ceramide-producing factor.
9. The skin moisture-increasing agent according to claim 8, wherein the ceramide-producing factor is SPTLC1.
10. 3. The skin moisture-increasing agent according to claim 1, which is an external preparation or a cosmetic.
11. The skin moisture content increasing agent according to claim 10, wherein the content of tranexamic acid and its salt in the skin moisture content increasing agent is 0.005% by mass or more and 10% by mass or less based on the total amount of the skin moisture content increasing agent.
Citation Information
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