Skin quality improver

Abstract

To provide a skin quality improver that enables the effect of lysophosphatidic acid and / or a salt thereof to be elevated to a level sufficient for practical use.SOLUTION: A skin quality improver comprises lysophosphatidic acid and / or a salt thereof, and lysophosphatidylinositol and / or a salt thereof, as active ingredients.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a technique relating to a skin quality improving agent. [Background technology]

[0002] The skin acts as a boundary between the inside and outside of the body and plays an important role in maintaining homeostasis by preventing the evaporation of moisture from the body and the intrusion of foreign substances from the outside. Skin function is perceived as skin quality, and increased sensitivity to unpleasant skin irritation caused by the use of skin care cosmetics is generally recognized as a decline in skin quality. This decline in skin quality can lead to increased inflammation and itching caused by the use of cosmetics, and ultimately to a significant decline in quality of life, such as limited use of cosmetics due to skin problems and sleep deprivation caused by itching. Against this background, the importance of skin care for improving quality of life is widely recognized (Non-Patent Document 1).

[0003] Lysophosphatidic acid, known as a lipid mediator found in humans, has been shown to increase the expression of keratinization-related factors and moisturizing-related genes in epidermal cells, and has been reported to improve skin quality by increasing the moisture content of the stratum corneum and shrinking enlarged pores (Non-Patent Documents 2 and 3). Examples of lysophosphatidic acid or its salts include sodium lysophosphatidic acid (Patent Documents 1 and 2) and aluminum lysophosphatidic acid (Patent Document 3). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2005-200370 [Patent Document 2] Japanese Patent Application Publication No. 2019-210246 [Patent Document 3] Japanese Patent Application Publication No. 2023-104455 [Non-patent literature]

[0005] [Non-Patent Document 1] ZHANG L, ADIQUE A, SARKAR P, SHENAI V, SAMPATH M, LAI R, QI J, WANG M, FARAGE MA. THE IMPACT OF ROUTINE SKIN CARE ON THE QUALITY OF LIFE. COSMETICS.2020; 7(3):59. [Non-patent document 2] YAHAGI S, KOIKE M, OKANO Y, MASAKI H. LYSOPHOSPHOLIPIDS IMPROVE SKIN MOISTURIZATION BY MODULATING OF CALCIUM-DEPENDENT CELL DIFFERENTIATION PATHWAY. INT J COSMET SCI. 2011;33(3):251-256. [Non-patent document 3] Improvement of pore size on human face through barrier improvement of functional phospholipids, Yuri Okano, Abstracts of the Annual Meeting of the Pharmaceutical Society of Japan:3(129), 223, 2009 Summary of the Invention [Problem to be solved by the invention]

[0006] Lysophosphatidic acid has an aspect of being a trigger factor of the ITCH-SCRATCH SYSTEM in the body.Therefore, in response to the demand for improving the skin quality improving effect of lysophosphatidic acid, especially the effect of reducing sensitivity to sensory irritation, if the amount of lysophosphatidic acid in cosmetics is increased, there is a concern that lysophosphatidic acid itself may cause irritation, and it is therefore considered inappropriate to increase the amount of lysophosphatidic acid.For this reason, there has not been sufficient research into means for safely and practically improving the skin quality improving effect of lysophosphatidic acid, which can be used in combination with lysophosphatidic acid without changing the amount of lysophosphatidic acid.

[0007] An object of the present invention is to provide a skin quality improving agent that has a practically sufficient enhancement of the effects of conventionally known lysophosphatidic acid and / or a salt thereof. [Means for solving the problem]

[0008] The present inventors conducted an intensive search for a compound that can sufficiently enhance the skin quality improving effect of lysophosphatidic acid and / or its salts, particularly the function of reducing sensitivity to sensory stimuli, for practical use, and discovered lysophosphatidylinositol and / or its salts, leading to the present invention.

[0009] That is, the present invention relates to the following 1) to 8). 1) A skin quality improving agent comprising lysophosphatidic acid and / or a salt thereof, and lysophosphatidylinositol and / or a salt thereof as active ingredients, wherein the content of the lysophosphatidic acid and / or a salt thereof is 0.1 parts by mass or more per 100 parts by mass of the lysophosphatidic acid and / or a salt thereof. 2) A skin quality improving agent according to 1), which has the effect of reducing the response to sensory stimuli. 3) A skin quality improving agent according to 1) or 2), which has an inhibitory effect on the increase in expression of early response factors in response to sensory stimuli. 4) The skin quality improving agent according to 3), wherein the early response factor is PTGS2. 5) The skin quality improving agent according to any one of 1) to 4), wherein the content of the lysophosphatidylinositol and / or a salt thereof is 5 parts by mass or more per 100 parts by mass of the lysophosphatidic acid and / or a salt thereof. 6) An agent for enhancing the skin quality improving function of lysophosphatidic acid and / or its salts, which contains lysophosphatidylinositol and / or its salts. 7) The enhancer according to 6), wherein the skin quality improving function is a reduction in response to sensory stimuli. 8) The enhancer according to 7), wherein the response to the sensory stimulus is the expression of PTGS2. [Effects of the Invention]

[0010] According to the present invention, there is provided a skin quality improving agent which has a practically sufficient enhancement of the skin quality improving effect of conventionally known lysophosphatidic acid, particularly the effect of reducing sensitivity to sensory stimuli. DETAILED DESCRIPTION OF THE INVENTION

[0011] Specific embodiments for carrying out the present invention will be described in detail below, but the technical scope of the present invention is not limited to the specific embodiments described below. In this specification, the range "X to Y" includes X and Y and means "X or more and Y or less." Unless otherwise specified, operations and measurements of physical properties are performed under conditions of room temperature (20 to 25°C) and a relative humidity of 40 to 50% RH.

[0012] One embodiment of the present invention is a skin quality improving agent containing, as active ingredients, at least one kind of lysophosphatidylinositol and / or a salt thereof, and at least one kind of lysophosphatidic acid and / or a salt thereof.

[0013] Lysophosphatidylinositol (hereinafter also referred to as LPI) and / or a salt thereof is a compound represented by the following formula 1.

[0014] [ka]

[0015] In the above formula 1, one of R1 and R2 is an acyl group of a fatty acid, and the other is hydrogen. The fatty acid is typically a saturated or unsaturated fatty acid having 8 to 24 carbon atoms, such as caprylic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, arachidic acid, palmitoleic acid, oleic acid, linoleic acid, α- and γ-linolenic acid, erucic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and tetracosatetraenoic acid.

[0016] The salt of lysophosphatidylinositol is not particularly limited, and examples thereof include sodium salt, potassium salt, calcium salt, triethanolamine salt, and arginine salt.

[0017] Commercially available lysophosphatidylinositol for use in the present invention includes the reagent L-α-lysophosphatidylinositol sodium salt manufactured by Sigma-Aldrich Japan Co., Ltd. Alternatively, as described in Japanese Patent Application Laid-Open No. 2002-10796, lysophosphatidylinositol can be produced by hydrolyzing lecithin obtained from soybeans, egg yolk, or the like, with a phospholipid hydrolase (phospholipase A1, hereinafter referred to as PLA1) produced by filamentous fungi of the genus Aspergillus.

[0018] The LPI and / or salts thereof may be used alone or in combination of two or more.

[0019] Lysophosphatidic acid (hereinafter also referred to as LPA) and / or a salt thereof is a compound represented by the following formula 2.

[0020] [ka]

[0021] In the above formula 2, one of R3 and R4 is an acyl group of a fatty acid, and the other is hydrogen. The fatty acid is typically a saturated or unsaturated fatty acid having 8 to 24 carbon atoms, such as caprylic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, arachidic acid, palmitoleic acid, oleic acid, linoleic acid, α- and γ-linolenic acid, erucic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and tetracosatetraenoic acid.

[0022] The salt of lysophosphatidic acid is not particularly limited, and examples thereof include sodium salt, potassium salt, calcium salt, triethanolamine salt, and arginine salt.

[0023] LPA and its salts may be either commercially available or synthetic. Commercially available products include reagents from Sigma-Aldrich Japan (e.g., 3-sn-phosphatidic acid sodium salt from egg yolk lecithin) and the phospholipid product "LPA" (LPA content 25% by mass) from Nikko Chemicals Co., Ltd. Synthetic LPAs can be synthesized by any method, including, for example, obtaining phospholipids from soybeans or egg yolks containing high concentrations of phosphatidic acid and partially hydrolyzing them. Specifically, LPA can be easily obtained by hydrolyzing phosphatidylcholine obtained from soybeans or egg yolks with phospholipase D. Alternatively, LPA and its salts can be easily synthesized by organic chemistry, for example, by reacting glycerol phosphate with fatty acid chloride in the presence of a base or by treating fatty acid monoglycerides and / or fatty acid diglycerides with various phosphorylating agents. Alternatively, a salt of LPA may be obtained by dissolving LPA in a suitable solvent such as isopropyl alcohol, acetone, or hexane, neutralizing the solution with an ethanol solution of sodium hydroxide, an ethanol solution of potassium hydroxide, an aqueous solution of triethanolamine, or an arginine solution, and then distilling off the solvent under reduced pressure.

[0024] LPA and its salts may be used alone or in combination of two or more.

[0025] The content of LPI and / or a salt thereof is 0.1 parts by mass or more relative to 100 parts by mass of LPA and / or a salt thereof (the content of LPI and / or a salt thereof is 0.1% by mass or more relative to LPA and / or a salt thereof). By having an LPI and / or a salt thereof content of 0.1 parts by mass or more, the skin quality improving effect of LPA, particularly the effect of reducing the response to sensory stimuli, is enhanced. The content of LPI and / or a salt thereof is preferably 0.5 parts by mass or more, 1 part by mass or more, 2 parts by mass or more, or 5 parts by mass or more relative to 100 parts by mass of LPA and / or a salt thereof. Furthermore, in terms of saturation of the effect, the content of LPI and / or a salt thereof is preferably 100 parts by mass or less, 90 parts by mass or less, 80 parts by mass or less, 70 parts by mass or less, 60 parts by mass or less, or 50 parts by mass or less relative to 100 parts by mass of LPA and / or a salt thereof. The content of LPI and / or its salt is preferably 0.1 to 100 parts by mass, 0.5 to 90 parts by mass, 1 to 80 parts by mass, 2 to 70 parts by mass, 5 to 60 parts by mass, or 5 to 50 parts by mass per 100 parts by mass of LPA and / or its salt. When two or more types of LPA and / or salts thereof are used, the content of LPA and / or its salt refers to the total amount. When two or more types of LPI and / or salts thereof are used, the content of LPI and / or its salt refers to the total amount.

[0026] In the present invention, the form of the lysophosphatidylinositol and / or its salt and lysophosphatidic acid and / or its salt is not particularly limited as long as it contains the lysophosphatidylinositol and / or its salt and the lysophosphatidic acid and / or its salt, and may be a lysophospholipid mixture containing other phospholipids. Examples of other phospholipids include lysophosphatidylethanolamine (LPE), lysophosphatidylserine (LPS), lysophosphatidylglycerol (LPG), sphingosine 1-phosphate, and lysophosphatidylcholine (LPC). The phospholipid may be derived from soybean, egg yolk, sunflower, or microalgae.

[0027] The term "skin quality improving agent" refers to an agent that can significantly improve skin quality compared to the skin quality before application, and specifically, it is preferably any of an agent that reduces the response to sensory stimuli (a skin quality improving agent that has the effect of reducing the response to sensory stimuli); an agent that improves the decline in skin barrier function; and an agent that improves the increase in enlarged pores, and more preferably an agent that reduces the response to sensory stimuli (a skin quality improving agent that has the effect of reducing the response to sensory stimuli). Here, "reducing the response to sensory stimuli" refers to, for example, a decrease in the self-assessment score in a stinging test using a sensory stimuli (agent).

[0028] The sensory stimulant (agent) may be at least one selected from the group consisting of acetic acid or a salt thereof, and a hydroxycarboxylic acid or a salt thereof. Examples of hydroxycarboxylic acids include aliphatic hydroxycarboxylic acids such as lactic acid, citric acid, tartaric acid, malic acid, isocitric acid, tartronic acid, glyceric acid, glycolic acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid (hydroxyisobutyric acid), 4-hydroxyacetic acid, leucinic acid, mevalonic acid, quinic acid, pantoic acid, and dimethylolpropionic acid; and aromatic hydroxycarboxylic acids such as shikimic acid, salicylic acid (orthohydroxybenzoic acid), parahydroxybenzoic acid, metahydroxybenzoic acid, 2-hydroxy-6-naphthoic acid, 2-hydroxy-3-naphthoic acid, 1-hydroxy-4-naphthoic acid, 4-hydroxy-4'-carboxydiphenyl ether, 2,6-dichloro-parahydroxybenzoic acid, 2-chloro-parahydroxybenzoic acid, 2,6-difluoro-parahydroxybenzoic acid, and 4-hydroxy-4'-biphenylcarboxylic acid. Among these, the sensory stimulant (agent) is preferably an aliphatic hydroxycarboxylic acid, and particularly preferably lactic acid and / or citric acid.

[0029] The present inventors have found that treatment with an agent comprising at least one of lysophosphatidic acid (LPA) and / or a salt thereof and at least one of lysophosphatidylinositol (LPI) and / or a salt thereof conferred resistance to increased PTGS2 expression in epidermal cells induced by hydroxycarboxylic acids, compared to treatment with an agent comprising at least one LPA (see Example 2 below). That is, a skin quality improving agent according to one embodiment of the present invention significantly suppresses the increase in the expression of early response factors in epidermal cells in response to sensory stimulants, compared to treatment with an agent comprising LPA and / or a salt thereof. Therefore, a skin quality improving agent according to one embodiment of the present invention has the effect of suppressing the expression of early response factors in epidermal cells in response to sensory stimulants. In this case, the early response factors are preferably selected from, but not limited to, one or more of PTGS2, IL1β, IL6, FN1, etc., with PTGS2 being more preferred.

[0030] The skin quality improving agent of the present invention may improve either chronically deteriorated or temporarily deteriorated skin quality, but preferably improves chronically deteriorated skin quality. In human tests, the inventors have found that an agent containing at least one of lysophosphatidic acid (LPA) and / or its salt, and at least one of lysophosphatidylinositol (LPI) and / or its salt, exhibits a significant improving effect on subjects with sensitive skin characteristics (e.g., subjects who tested positive in a lactic acid stinging test) (see the application examples described below). Furthermore, this improving effect is preferably an improving effect on a decrease in self-diagnosed scores in the stinging test.

[0031] Another embodiment of the present invention is an agent for enhancing the skin quality improving function of lysophosphatidic acid and / or a salt thereof, which comprises lysophosphatidylinositol and / or a salt thereof.

[0032] The skin quality improving function of lysophosphatidic acid and / or its salts is preferably any one of a reduction in response to sensory stimuli, an improvement in the deterioration of skin barrier function, and an improvement in the increase of enlarged pores, and more preferably a reduction in response to sensory stimuli. Specifically, the response to sensory stimuli is the expression of early response factors in epidermal cells in response to sensory stimulants. Examples of early response factors include, but are not limited to, one or more selected from PTGS2, IL1β, IL6, FN1, etc., and more preferably PTGS2.

[0033] The enhancer is preferably added so that the content of lysophosphatidylinositol and / or a salt thereof is 0.1 parts by mass or more per 100 parts by mass of lysophosphatidic acid and / or a salt thereof.

[0034] The present invention also provides an external skin preparation or cosmetic for improving skin quality, which contains lysophosphatidic acid and / or a salt thereof, and lysophosphatidylinositol and / or a salt thereof as active ingredients, in which the content of the lysophosphatidic acid and / or a salt thereof is 0.1 parts by mass or more per 100 parts by mass of lysophosphatidic acid and / or a salt thereof.

[0035] The content (total amount) of LPI and / or a salt thereof and LPA and / or a salt thereof in the external skin preparation or cosmetic is preferably 0.0003 to 30.0 mass %, more preferably 0.003 to 3.0 mass %.

[0036] A variety of additives typically used in external skin preparations or cosmetics containing the skin quality improving agent of the present invention can be blended into the external skin preparations or cosmetics containing the skin quality improving agent of the present invention, within the scope of not impairing the effects of the present invention, such as liquid paraffin, squalane, vegetable oils and fats, waxes, synthetic ester oils, silicone-based oil phase components, fluorine-based oil phase components, higher alcohols, fatty acids, thickeners, ultraviolet absorbers, powders, pigments, coloring materials, anionic surfactants, cationic surfactants, nonionic surfactants, amphoteric surfactants, polyhydric alcohols, sugars, polymeric compounds, physiologically active ingredients, transdermal absorption enhancers, solvents, antioxidants, fragrances, preservatives, anti-inflammatory agents, agents for preventing / improving rough skin, and agents for preventing / improving pigmentation.

[0037] The external skin preparation or cosmetic containing the skin quality improving agent of the present invention may be in any dosage form, including skin lotion, lotion, emulsion, cream, pack, ointment, dispersion, solid, mousse, etc. [Example]

[0038] The present invention will be explained in more detail below by way of examples, but the technical scope of the present invention is not limited to these examples.

[0039] Example 1: Inhibitory effect of the agent of the present invention on early response factors of epidermal cells to sensory stimulants [1-1. Experimental Method] Epidermal cells (human normal epidermal keratinocytes, NHEKS) were added to 1.5 × 10 4Cells were seeded at a seeding density of 10 ...

[0040] Then, the cells were treated with 0.2% lactic acid for 6 hours and then subjected to TaqMan® Gene Expression Cells-to-CT. TM cDNA was prepared according to the kit's protocol, and expression levels of early response genes were measured by qPCR (Applied Biosystems) using the Taqman® Gene Expression assay kit. Primers used were Assay ID: HS00153133_M1 (PTGS2) and Assay ID: HS99999905_M1. In Table 1, PTGS2 expression levels are expressed relative to the expression level of the untreated control (72 hours of culture), which is set at 100. The unstimulated control in Table 1 was measured for PTGS2 expression after 72 hours of culture and 6 hours without treatment.

[0041] [1-2. Results] To simulate sensitive skin, an in vitro test system was used to detect early response factors that change upon lactic acid stimulation of epidermal cells (Table 1). Gene expression of PTGS2, an early response factor in epidermal cells, was found to increase 5.2-fold after lactic acid stimulation compared to untreated controls. In Example 1, in which LPA was used in combination with LPI, the increase in PTGS2 expression after lactic acid stimulation was approximately 2.2-fold compared to untreated controls, demonstrating a significant suppression. In Comparative Example 1, in which the same concentration of LPA alone was used, the increase in PTGS2 expression after lactic acid stimulation was 4.7-fold, and in Comparative Example 2, in which LPI alone was used, the increase in PTGS2 expression after lactic acid stimulation was 4.9-fold, demonstrating the potentiation of LPA action by LPI. The potentiation of LPA action by LPI was also confirmed in Examples 2 and 3, in which the ratio of LPI to LPA was varied. From this, it was confirmed that although LPI does not have a stronger effect on improving skin quality than LPA, when used in combination with LPA, it significantly enhances the effect of LPA in reducing the initial response to sensory stimuli.

[0042] [Table 1]

[0043] <Application Example 1. Evaluation of the skin quality improvement effect of the agent of the present invention in human trials> This study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Healthy women aged 37 to 50 were selected as potential study participants. Skin characteristics on both cheeks were observed, and 13 subjects with positive lactic acid stinging test results were selected as subjects. The lactic acid stinging test was performed as follows: 50 μL of 10% lactic acid solution was applied to the cheek, and the subjective sensation of irritation was scored on a 4-point scale 2.5 minutes and 5.0 minutes later (score: 0 = no irritation, 1 = mild irritation, 2 = moderate irritation, 3 = severe irritation). The two scores were added together, and subjects with a total score of 3 or higher were considered to have positive lactic acid irritation. The selected subjects were asked to apply a placebo formulation and the formulation of Application Example 1 (a cream formulation containing 0.10% by mass of a lysophospholipid mixture containing 20% ​​by mass of LPA and 10% by mass of LPI) to either the left or right half of their face twice a day (after washing their face in the morning and evening) for four consecutive weeks. Lactic acid stinging was evaluated before and after four weeks of use. The measurements were taken 30 minutes after the subjects entered a constant temperature and humidity room at a temperature of 20°C and humidity of 50% after removing the formulation from the skin surface with a cleansing agent and facial cleanser. [1-1. Lactic acid stinging test] As shown in Table 2, compared to the placebo formulation, the subjects who had used the formulation of Application Example 1 for four weeks had a significant decrease in their self-assessment scores in the lactic acid stinging test compared to the initial values. Considering this together with the results of the PTGS2 gene expression inhibitory effect mentioned above, this was thought to be due to the improved skin quality improvement effect of the combined use of LPI and LPA.

[0044] [Table 2]

[0045] The cosmetic preparation described below was prepared using the present invention. The obtained cosmetic preparation has excellent moisturizing properties and a penetrating feel, and achieves improvement in skin quality. Unless otherwise specified, "%" means % by mass.

[0046] hair tonic (A) Sodium lysophosphatidic acid 0.05% Lysophosphatidylinositol 0.03% NIKKOL VC-PMG 0.10% Dipotassium glycyrrhizinate 0.05% Glycerin 3.00% 1,3-Butylene Glycol (BG) 3.00% L-menthol 0.10% NIKKOL HCO-50 0.30% Polyglyceryl-10 Laurate 0.30% Methylparaben 0.20% Ethanol 30.00% Purified water remainder *NIKKOL VC-PMG: Ascorbyl phosphate MG (manufactured by Nikko Chemicals) *NIKKOL HCO-50: PEG-50 hydrogenated castor oil (manufactured by Nikko Chemicals) <Preparation method> Heat Phase A to 60°C and dissolve evenly. Cool to 35°C while stirring.

[0047] Anti-aging lotion (A) Lysophospholipid mixture containing 20% ​​LPA and 10% LPI 0.50% Ascorbyl glucoside 2.00% Niacinamide 2.00% NIKKOL DECAGLYN 1-M 1.00% Glycerin 5.00% Propanediol 7.00% Xanthan gum 0.10% Phenoxyethanol 0.30% Citric acid 0.02% Citric acid 3Na 0.04% Purified water remainder (B) NIKKOL Nicofine CIO 2.00% Purified water 10.00% *NIKKOL DECAGLYN 1-M: Polyglyceryl-10 myristate (manufactured by Nikko Chemicals) *NIKKOL Nicofine CIO: Cetyl ethylhexanoate, PEG-50 hydrogenated castor oil, sorbitan oleate, DPG, phenoxyethanol, sodium citrate, citric acid, water (manufactured by Nikko Chemicals) <Preparation method> Heat Phase A to 60°C and dissolve uniformly, then cool to 35°C while stirring. Mix Phase B at room temperature. Add Phase B to Phase A at room temperature and stir thoroughly.

[0048] cleansing lotion (A) Lysophospholipid mixture containing 20% ​​LPA and 10% LPI 0.10% NIKKOL TRIGLYN 1-KF 2.50% NIKKOL TRIGLYN 1-L 2.50% Glycerin 5.00% Propanediol 7.00% Methylparaben 0.20% Citric acid 0.02% Citric acid 3Na 0.04% Purified water remainder (B) Cellulose nanofiber 0.10% Purified water 10.00% *NIKKOL TRIGLYN 1-KF: Polyglyceryl-3 caprylate (manufactured by Nikko Chemicals) *NIKKOL TRIGLYN 1-L: Polyglyceryl-3 laurate (manufactured by Nikko Chemicals) <Preparation method> Heat Phase A to 80°C and dissolve uniformly, then cool to room temperature. Disperse Phase B thoroughly at room temperature. Add Phase B to Phase A and stir thoroughly.

[0049] Milk Essence (A) NIKKOL PurePhos α 0.70% Cetyl alcohol 1.50% NIKKOL MGS-BV2 0.50% NIKKOL Batyl Alcohol EX 0.50% NIKKOL Sugar Squalane 2.00% NIKKOL TRIFAT S-308 2.00% Cyclopentasiloxane 1.00% Dimethicone 0.50% NIKKOL VC-IPVS 0.50% Tocopherol 0.10% (B) Arginine 0.30% Lysophospholipid mixture containing 20% ​​LPA and 10% LPI 0.01% Glycerin 7.00% Propylene glycol 5.00% Phenoxyethanol 0.30% Purified water remainder *NIKKOL PurePhos α: Cetyl phosphate (manufactured by Nikko Chemicals) *NIKKOL MGS-BV2: Glyceryl stearate (manufactured by Nikko Chemicals) *NIKKOL Batyl Alcohol EX: Batyl alcohol (manufactured by Nikko Chemicals) *NIKKOL Sugar Squalane: Squalane (manufactured by Nikko Chemicals) *NIKKOL TRIFAT S-308: Triethylhexanoin (manufactured by Nikko Chemicals) *NIKKOL VC-IPVS: Ascorbyl tetrahexyldecanoate (manufactured by Nikko Chemicals) <Preparation method> Heat both Phase A and Phase B until uniformly dissolved, then add Phase A to Phase B and emulsify with sufficient stirring. Cool to 35°C while stirring.

[0050] skin care cream (A) NIKKOL Nicolipid 81S 3.50% Behenyl alcohol 0.50% Stearyl alcohol 0.25% NIKKOL GS-MHL 10.00% NIKKOL Sugar Squalane 4.00% NIKKOL Macadamia Nut Oil 4.00% NIKKOL Retinol H10 0.30% (B) Lysophosphatidic acid 0.10% Lysophosphatidylinositol arginine 0.05% Xanthan gum 0.20% Hydroxyethylcellulose 0.05% Carbomer 0.05% Acrylates / C10-30 alkyl acrylate crosspolymer 0.05% 1,3-BG 7.00% Sodium hydroxide 0.03% Phenoxyethanol 0.30% Purified water remainder *NIKKOL Nikolipid 81S: Batyl alcohol, stearic acid, lecithin, tri(caprylic / capric acid)glyceryl (manufactured by Nikko Chemicals Co., Ltd.) *NIKKOL GS-MHL: Methylheptyl laurate (manufactured by Nikko Chemicals) *NIKKOL Sugar Squalane: Squalane (manufactured by Nikko Chemicals) *NIKKOL Macadamia Nut Oil: Macadamia seed oil (manufactured by Nikko Chemicals) *NIKKOL Retinol H10: Hydrogenated retinol, caprylic / capric triglyceride (manufactured by Nikko Chemicals) <Preparation method> Heat both Phase A and Phase B until uniformly dissolved, then add Phase A to Phase B and emulsify with sufficient stirring. Cool to 35°C while stirring.

[0051] Body cream (A) NIKKOL WAX-230 6.00% Cetearyl Alcohol 3.00% White petrolatum 8.00% Shea butter 5.00% NIKKOL TRIFAT S-308 10.00% NIKKOL VF-LINOV 0.30% NIKKOL Jojoba Oil S 2.00% Ceramide NP 1.00% Ceramide NG 0.30% (B) Lysophosphatidic acid 0.50% Lysophosphatidylinositol 0.30% Sodium hyaluronate 0.01% Hydroxyethylcellulose 0.20% Glycerin 5.00% Phenoxyethanol 0.30% Purified water remainder *NIKKOL WAX-230: Arachidex-20, stearyl alcohol (manufactured by Nikko Chemicals Co., Ltd.) *NIKKOL TRIFAT S-308: Triethylhexanoin (manufactured by Nikko Chemicals) *NIKKOL Jojoba Oil S: Jojoba oil (manufactured by Nikko Chemicals) *NIKKOL VF-LINOV: Ethyl linoleate (manufactured by Nikko Chemicals) <Preparation method> Heat both Phase A and Phase B until uniformly dissolved, then add Phase A to Phase B and emulsify with sufficient stirring. Cool to 35°C while stirring.

[0052] sunscreen cream (A)SSQP50ZJEJ 18.00% SSQP40TIJ 18.00% Ethylhexyl triazone 3.00% NIKKOL Nikomurus 41S 4.00% NIKKOL Triestar F-810 5.00% Cetearyl Alcohol 2.00% (B) Lysophospholipid mixture containing 20% ​​LPA and 10% LPI 1.00% NIKKOL SMT 0.20% Tranexamic acid 0.30% Hydroxyethylcellulose 0.20% Glycerin 5.00% Phenoxyethanol 0.30% Purified water remainder *SSQP50ZJEJ: Zinc oxide, squalane, polyhydroxystearic acid, jojoba ester (manufactured by KOBO Dispatec) *SSQP40TIJ: Squalane, titanium oxide, aluminum hydroxide, isostearic acid, polyhydroxystearic acid (manufactured by KOBO Dispatec Co., Ltd.) *NIKKOL Nikomulus 41S: Behenyl alcohol, Polyglyceryl-10 pentastearate, Sodium stearoyl lactylate (manufactured by Nikko Chemicals Co., Ltd.) *NIKKOL Triester F-810: Tri(caprylic / capric acid)glyceryl (manufactured by Nikko Chemicals) *NIKKOL SMT: Stearoyl Methyl Taurine Na (manufactured by Nikko Chemicals Co., Ltd.) <Preparation method> Heat both Phase A and Phase B until uniformly dissolved, then add Phase B to Phase A and emulsify with sufficient stirring. Cool to 35°C while stirring.

[0053] Liquid foundation (A) NIKKOL Nikomurus 41S 2.50% Ethylhexyl methoxycinnamate 7.00% Bis-ethylhexyloxyphenol methoxyphenyl triazine 1.00% NIKKOL Triestar F-810 3.00% (B) NIKKOL SMT 0.50% Xanthan gum 0.10% Polyacrylate Crosspolymer-6 0.40% Methylparaben 0.20% Purified water remainder (C)SYMPHOLIGHT WW-E 8.40% SYMPHOLIGHT RW-TE 0.25% SYMPHOLIGHT YW-TE 1.20% SYMPHOLIGHT BW-TE 0.15% 1,3-BG 5.00% (D) Calcium lysophosphatidate 0.20% Potassium lysophosphatidylinositol 0.20% Purified water 7.00% (E)ARON AC-1000 5.00% *NIKKOL Nikomurus 41S: Behenyl alcohol, Polyglyceryl-10 pentastearate, Sodium stearoyl lactylate (manufactured by Nikko Mikals Co., Ltd.) *NIKKOL Triester F-810: Tri(caprylic / capric acid)glyceryl (manufactured by Nikko Chemicals) *NIKKOL SMT: Stearoyl Methyl Taurine Na (manufactured by Nikko Chemicals Co., Ltd.) *SYMPHOLIGHT WW-E: titanium oxide, alumina, silica *SYMPHOLIGHT RW-TE: iron oxide, silica *SYMPHOLIGHT YW-TE: iron oxide, silica *SYMPHOLIGHT BW-TE: iron oxide, silica *ARON AC-1000: Acrylates copolymer, water, arginine (manufactured by Nikko Chemicals) <Preparation method> Heat phases A and B until homogenous. Mix and disperse phase C evenly using a three-roller. Heat phase D to 60°C and dissolve homogenously, then cool to 35°C while stirring. Gradually add phase A while stirring phase B and emulsify. Cool phases A+B to 35°C while stirring. Add phase C to phase A+B and mix homogenously, then add phase D and mix. Add phase E and mix homogenously.

[0054] From the above, it has been demonstrated that the skin quality improving effect of LPA (particularly, the effect of reducing the initial response of epidermal cells to sensory stimulants) can be improved sufficiently for practical use by using LPA in combination with LPI in the skin quality improving agent of the present invention. The skin quality improving agent of the present invention is highly effective for users who suffer from a decline in QOL caused by unpleasant sensory stimuli, etc.

Claims

1. The present invention comprises lysophosphatidic acid and / or a salt thereof, and lysophosphatidylinositol and / or a salt thereof as active ingredients, A skin quality improving agent, wherein the content of the lysophosphatidylinositol and / or a salt thereof is 0.1 parts by mass or more per 100 parts by mass of the lysophosphatidic acid and / or a salt thereof.

2. The skin quality improving agent according to claim 1, which has an effect of reducing the response to sensory stimuli.

3. The skin quality improving agent according to claim 1 or 2, which has an effect of suppressing an increase in the expression of early response factors in response to sensory stimuli.

4. The skin quality improving agent according to claim 3, wherein the early response factor is PTGS2.

5. The skin quality improving agent according to claim 1 or 2, wherein the content of the lysophosphatidylinositol and / or a salt thereof is 5 parts by mass or more per 100 parts by mass of the lysophosphatidic acid and / or a salt thereof.

6. An agent for enhancing the skin quality improving function of lysophosphatidic acid and / or a salt thereof, which comprises lysophosphatidylinositol and / or a salt thereof.

7. The enhancing agent according to claim 6 , wherein the skin quality improving function is a reduction in response to sensory stimuli.

8. The enhancer according to claim 7 , wherein the response to the sensory stimulus is the expression of PTGS2.

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