Topical skin barrier function repair agent

Abstract

The present invention relates to a novel topical skin barrier function repair agent that not only promotes skin barrier repair in damaged skin but is also expected to have a repairing effect on skin barrier dysfunction caused by glucocorticoid use and / or psychological stress. The skin barrier function repair agent achieves skin barrier repair by any of the following promoting actions: promoting keratinocyte proliferation, promoting keratinocyte migration, promoting HAS-2 expression in keratinocytes, and promoting HBD-2 expression in keratinocytes.

Description

[Technical Field]

[0001] The present invention relates to a novel topical skin barrier function repair agent that not only promotes the repair of damaged skin barrier but also is expected to have an improving effect on skin barrier dysfunction caused by glucocorticoid use and / or psychological stress. The skin barrier function repair agent achieves skin barrier repair by any of the following promoting actions: promoting keratinocyte proliferation, promoting keratinocyte migration, promoting keratinocyte hyaluronan synthase-2 (HAS-2) expression, and promoting keratinocyte human β-defensin-2 (HBD-2) expression. [Background technology]

[0002] The skin is the first protective barrier between the body and the external environment, performing the important functions of preventing excessive water loss and blocking the invasion of harmful substances from the environment. Most of this barrier function is provided by the epidermis, a stratified epithelial tissue located in the outer layer of the skin that is constantly self-renewing. Keratinocytes (also called basal cells) in the basal layer, the innermost layer of the epidermal tissue, renew the epidermis by constantly dividing and producing progeny cells. These newly generated progeny cells gradually differentiate into spinous and granular cells as they migrate to the outer layers, and finally into keratinocytes. The outermost stratum corneum is constantly shed through the process of desquamation, and basal layer cells migrate upward to form a new stratum corneum. Therefore, maintaining epidermal barrier homeostasis requires a balance between keratinocyte proliferation, migration, and differentiation.

[0003] As the body's outermost barrier, skin is constantly bombarded by harmful factors from the external environment, potentially resulting in tissue damage and barrier disruption. After skin injury, a series of repair processes are usually immediately activated to restore skin barrier function. Skin wound repair is a highly coordinated process involving the collaborative efforts of various cell types, extracellular matrix molecules, and regulatory factors. As the major cell type in the epidermis, keratinocytes play a vital role in wound healing and epidermal barrier function restoration. Upon wounding, keratinocytes at the wound edge are immediately activated, accelerating migration and proliferation to re-epithelialize the skin, which is crucial for rapid wound healing.

[0004] In addition to accelerated proliferation and migration, keratinocytes also increase the expression of several genes with important functions, such as hyaluronic acid synthase (HAS) and human β-defensin (HBD), which promote barrier repair and maintain skin homeostasis. HAS is a key enzyme for skin cell synthesis of hyaluronic acid (HA). Keratinocytes can express three subtypes of HAS: HAS-1, HAS-2, and HAS-3. HAS-2 is the most highly expressed and is the most important synthesizing enzyme for keratinocyte HA synthesis. HA is the most abundant extracellular matrix component in skin tissue and is involved in processes such as maintaining tissue homeostasis, hydration, and wound repair. Ample research evidence has demonstrated that HA plays an important role in wound healing. During wound healing, large amounts of HA are produced at the wound site. HA and its catabolic products (medium- and low-molecular-weight HA) selectively activate the CD44 receptor on the surface of keratinocytes, mediating specific signaling pathways and regulating keratinocyte proliferation, migration, and differentiation, ultimately affecting wound healing. Studies have shown that overexpression of HAS-2 in keratinocytes increases cell migration, whereas knockdown of HAS-2 inhibits keratinocyte migration. Epidermal growth factor (EGF), keratinocyte growth factor (KGF), and all-trans retinoic acid (RA) can all increase HAS-2 expression levels in keratinocytes, further enhancing HA synthesis. This HAS-2-dependent increase in HA synthesis is directly correlated with the promoting effects of EGF, KGF, and RA on keratinocyte migration, proliferation, and wound healing. Thus, HA is not only involved in the organization of the epidermal extracellular matrix but also plays an important role in the proliferation, migration, and differentiation of keratinocytes. Therefore, increasing HAS-2 expression contributes to the rapid repair of skin damage and the maintenance of barrier homeostasis.

[0005] Human β-defensins (HBDs) are a group of cationic antimicrobial peptides containing 12–50 amino acids produced by epithelial tissues, such as the skin and respiratory tract. They possess antibacterial and antiviral activities and are involved in the formation of the first barrier of the body's innate immune system. To date, four HBDs, namely HBD-1, HBD-2, HBD-3, and HBD-4, have been identified in human skin. HBD-2 expression in skin tissues is localized in the uppermost layer of the epidermis, and its expression level significantly increases in differentiated keratinocytes. Furthermore, recent studies have shown that HBD-2 mediates the protective effect of IL-1β-induced keratinocytes against proteases secreted by Staphylococcus aureus, suggesting that promoting endogenous HBD-2 expression may be beneficial for skin barrier repair and protection against S. aureus colonization in inflammatory skin disease states. A growing number of studies have shown that the action of antimicrobial peptides goes beyond antibacterial activity and is involved in wound repair and the maintenance of skin barrier homeostasis through various routes. After wounding, local epidermal cells are stimulated by cytokines, growth factors, or bacteria to increase HBD expression, which then activates signaling pathways such as MAPK, AKT, STAT1, and STAT3, as well as increasing intracellular Ca. 2+ It accelerates skin wound healing by activating signaling and EGFR phosphorylation, and promoting keratinocyte proliferation and migration. In addition to affecting keratinocyte proliferation and migration, HBD also stimulates angiogenesis, promotes collagen production in dermal fibroblasts, and downregulates matrix metalloproteinase-1 expression, thereby promoting extracellular matrix deposition and accelerating wound healing. Another study showed that HBD can improve skin barrier function by increasing the expression of tight junction proteins in epidermal cells and by downregulating Lgr6. +It has been shown that defensins can selectively activate keratinocyte HBDs in skin stem cells to promote epidermal renewal and wound repair, suggesting that defensins also play an important role in maintaining skin barrier homeostasis. Therefore, increasing the expression level of keratinocyte HBDs contributes to improving the speed and quality of skin wound repair and regeneration.

[0006] Under normal circumstances, skin has a very strong self-repairing ability, capable of rapidly repairing common minor injuries and restoring homeostasis of tissue structure and function. However, the skin injury repair process is often affected by various adverse factors, which can disrupt the normal progression of the repair process, delay injury repair, cause skin barrier dysfunction, and potentially induce or exacerbate various skin diseases. Stress and the use of glucocorticoid medications are two common adverse factors that affect skin injury repair. Stress is a nonspecific response of the body caused by excessive or harmful stimuli. It is caused by different physiological factors (e.g., wounds, pain) and psychological factors (pressure), and can be classified as physiological stress and psychological stress. In particular, with the accelerating rhythm of life and increasing competitive pressure in various areas, psychological stress has become an unavoidable and frequent occurrence in modern life. Psychological stress can lead to a wide range of skin health problems, including impaired wound healing ability, impaired barrier function, abnormal skin immune function and reduced anti-infective capacity, and ultimately premature skin aging. Stress triggers a series of complex physiological responses characterized primarily by increased activity of the sympathetic-adrenomedullary system (SAM) and the hypothalamic-pituitary-adrenal axis (HPA axis). SAM activation leads to a rapid increase in stress hormone levels, such as adrenaline and noradrenaline. Meanwhile, increased activity of the HPA axis promotes the release of corticotropin-releasing hormone (CRH) by the hypothalamus and the secretion of adrenocorticotropic hormone (ACTH) by the pituitary gland, which in turn promotes the secretion of glucocorticoids (GCs) by the adrenal glands. In recent years, increasing research evidence has demonstrated that the skin is an important target organ for these stress hormones.Overproduction of adrenaline and noradrenaline under stress conditions directly affects β-2-adrenergic receptors on the surface of epidermal keratinocytes, inhibiting keratinocyte migration and inducing oxidative stress and DNA damage, leading to skin barrier disruption, delayed wound healing, and skin aging. Overproduction of glucocorticoids (GCs) under stress conditions can also directly affect skin cells, suppressing the expression of hyaluronic acid and lipid synthesis enzymes, reducing the hyaluronic acid and lipid content in skin tissue, negatively affecting the epidermal barrier, reducing stratum corneum hydration, and increasing transepidermal water loss. GCs also inhibit the proliferation and differentiation of epidermal keratinocytes, disrupting the integrity and adhesive strength of the stratum corneum and impairing epidermal barrier function. Furthermore, GCs suppress the expression of antimicrobial peptides, such as HBD, by keratinocytes, impairing the skin's anti-infection capabilities. The use of exogenous glucocorticoids may produce adverse effects similar to those of endogenous GCs overproduced during stress. Epidermal function defects are very common in patients with long-term glucocorticoid use. Skin atrophy and impaired barrier function are recognized side effects of topical glucocorticoids. Studies have shown that the glucocorticoid dexamethasone can significantly suppress HAS-2 expression and HA synthesis in skin fibroblasts and HaCaT keratinocytes at very low doses (1.5 nM, 150 nM, and 1.5 μM) and with an extremely short duration of action (3 hours). Consistent with this, human studies have shown that topical application of dexamethasone ointment is sufficient to induce a clear decrease in HA levels in skin tissue within a very short treatment period (3 days). In contrast, GC treatment requires 3 weeks for a reduction in type I and type III collagen synthesis to be observed in skin tissue. This suggests that downregulation of HAS-2 expression and the resulting decrease in hyaluronan synthesis may be the most crucial early step in GC-induced skin atrophy.

[0007] Natural α-ionone, a secondary metabolite of plants, has a violet scent and is widely found in various flowers, fruits such as cherries, raspberries, and grapes, tea, and various essential oils. Synthetic α-ionone is widely used as a flavoring ingredient in the food and daily necessities industries. The 2014 National Food Safety Standard: Standard for the Use of Food Additives (GB2760-2014) classifies α-ionone as a synthetic food flavoring. The U.S. FDA also approves its use as a flavoring agent. In addition to its use as a food additive, α-ionone is widely used as a flavoring excipient in cosmetics, perfumes, shampoos, soaps, and other cleaning products, as well as household and laundry detergents. According to statistics, the global annual consumption of α-ionone is approximately 100-1,000 metric tons.

[0008] Our bodies and skin frequently come into contact with α-ionone, yet its biological functions remain largely unknown. One study reported that α-ionone may have anti-photoaging properties. This study revealed that α-ionone activated the TGF-β-SMAD pathway and induced collagen expression in UV-irradiated Hs-68 human fibroblasts, while suppressing the MAPK-AP-1 signaling pathway and suppressing the expression of MMP1, MMP3, and MMP9 (Molecules 2019, 24(9), 1804). Another related study showed that α-ionone stimulated myogenesis in vitro, attenuated palmitic acid-induced myotube atrophy, and increased myotube diameter and length, fusion index, and cellular protein content. This study suggests that α-ionone may be a potential drug for enhancing skeletal muscle mass and strength. The above studies have shown that, in addition to its flavoring function, α-ionone may also have biological functions beneficial to physical health (Non-Patent Document 2, Food Funct. This journal is © The Royal Society of Chemistry 2019, published February 5, 2019).

[0009] Furthermore, Food Industry Science and Technology 2022; 43(20): pp. 481-488 (Non-Patent Document 3) provides a summary of the known biological activities of α-ionone. Prior art documents Non-patent literature: 1, Molecules 2019, 24(9), 1804 2. Food Funct. This journal is (Copyright) The Royal Society of Chemistry 2019, published February 5, 2019 3, Food Industry Science and Technology 2022; 43(20): p. 481-488 Summary of the Invention [Problem to be solved by the invention]

[0010] As can be seen from the above findings, skin barrier function is closely related to keratinocyte proliferation, migration, and the expression of HAS-2 and HBD-2 in keratinocytes. Based on the above findings, the inventors of the present invention conducted thorough research, starting from a search for substances that regulate keratinocyte proliferation, migration, and the expression of HAS-2 and HBD-2, and worked to find a new topical skin barrier function repair agent for improving the barrier function of damaged skin and repairing skin barrier dysfunction caused by the use of glucocorticoids and / or psychological stress. [Means for solving the problem]

[0011] In order to find a substance that can promote keratinocyte proliferation, migration, and the expression of HAS-2 and HBD-2 in keratinocytes, the applicant conducted thorough research and conducted numerous experiments. As a result, the applicant unexpectedly discovered that α-ionone can promote keratinocyte proliferation, migration, and the expression of HAS-2 and HBD-2 in keratinocytes, and that adding α-ionone to a topical skin preparation as an active ingredient in a skin barrier function repair agent can significantly promote skin barrier repair. Based on this discovery, the present invention was completed.

[0012] Specifically, the present invention includes the following configurations: 1. A skin barrier function repair agent in an external skin preparation, characterized by containing α-ionone as an active ingredient that acts on keratinocytes. 2. The skin barrier function repairing agent described in 1 above, characterized in that the α-ionone acts as a keratinocyte migration promoter. 3. The skin barrier function repairing agent described in 1 above, characterized in that the α-ionone acts as a keratinocyte proliferation promoter. 4. The skin barrier function repairing agent described in 1 above, characterized in that the α-ionone acts as an agent that promotes the expression of HAS-2 in keratinocytes. 5. The skin barrier function repairing agent described in 1 above, characterized in that the α-ionone acts as an agent that promotes the expression of HBD-2 in keratinocytes. 6. The skin barrier function repair agent described in 1 above, characterized in that it is used as an agent for repairing skin barrier function disorders caused by the use of glucocorticoids and / or psychological stress. 7. The skin barrier function repair agent described in 1 above, characterized in that the topical skin preparation is a cosmetic. 8. Use of α-ionone in the manufacture of cosmetics that promote skin barrier repair, wherein the promotion of skin barrier repair is achieved by at least one promoting effect selected from the group consisting of promoting keratinocyte migration, promoting keratinocyte proliferation, promoting HAS-2 expression in keratinocytes, and promoting HBD-2 expression in keratinocytes. 9. Use of alpha-ionone in the manufacture of cosmetics to be applied to skin in a state of skin atrophy and / or skin barrier dysfunction caused by the use of glucocorticoids and / or psychological stress. 10. A keratinocyte proliferation promoter containing alpha-ionone as the active ingredient. 11. Use of α-ionone as a keratinocyte proliferation promoter. 12. Use of α-ionone in the manufacture of an external skin preparation that promotes the proliferation of skin keratinocytes. 13. A latinocyte migration promoter containing α-ionone as the active ingredient. 14. Use of α-ionone as a keratinocyte migration promoter. 15. Use of α-ionone in the manufacture of an external skin preparation that promotes migration of skin keratinocytes. 16. A promoter of HAS-2 expression in keratinocytes, containing α-ionone as an active ingredient. 17. Use of α-ionone as a promoter of HAS-2 expression in keratinocytes. 18. Use of α-ionone in the manufacture of an external skin preparation that promotes HAS-2 expression in skin keratinocytes. 19. A promoter for promoting HBD-2 expression in keratinocytes, containing α-ionone as an active ingredient. 20. Use of α-ionone as a promoter of HBD-2 expression in keratinocytes. 21. Use of α-ionone in the manufacture of an external skin preparation that promotes HBD-2 expression in skin keratinocytes. [Effects of the Invention]

[0013] The inventors of the present invention have discovered for the first time that α-ionone can act as a keratinocyte migration promoter, a keratinocyte proliferation promoter, a keratinocyte HAS-2 expression promoter, and a keratinocyte HBD-2 expression promoter, and that by promoting one or more of the effects of promoting keratinocyte proliferation, promoting keratinocyte migration, promoting keratinocyte HAS-2 expression, and promoting keratinocyte HBD-2 expression, it can achieve skin barrier repair and not only repair general skin damage, but also may repair skin atrophy and / or skin barrier dysfunction caused by glucocorticoid use and / or psychological stress. [Brief explanation of the drawings]

[0014] [Figure 1] FIG. 1 shows the effect of α-ionone in promoting HaCaT cell proliferation. [Figure 2]FIG. 2 shows the effect of α-ionone on HaCaT cell migration. [Figure 3] FIG. 3 shows the effect of α-ionone on the inhibition of HaCaT cell migration by norepinephrine (NE). [Figure 4] FIG. 4 shows the effect of α-ionone on HAS-2 expression in HaCaT cells. [Figure 5] FIG. 5 shows the effect of α-ionone on the synthesis of hyaluronic acid (HA) by HaCaT cells. [Figure 6] FIG. 6 shows the effect of α-ionone on the suppression of HAS-2 expression by dexamethasone (DEX). [Figure 7] FIG. 7 shows the effect of α-ionone on the expression of HBD-2 by HaCaT cells. [Figure 8] FIG. 8 shows the effect of α-ionone on the secretion of HBD-2 by HaCaT cells. [Figure 9] FIG. 9 shows the effect of α-ionone on the suppression of HBD-2 expression by dexamethasone (DEX). [Figure 10] FIG. 10 is a graph showing the transepidermal water loss (TEWL value) in the test area of ​​each test group. [Figure 11] FIG. 11 shows the moisture content of the stratum corneum in the test area for each test group. [Figure 12] FIG. 12 shows the barrier repair rate for each test group. [Figure 13] FIG. 13 shows the measured moisture content of the stratum corneum of the subjects. [Figure 14] FIG. 14 is a graph showing the change in moisture content of the stratum corneum of the subjects' skin compared to before peeling. [Figure 15] FIG. 15 shows TEWL measurements in test areas of subjects. [Figure 16] FIG. 16 is a graph showing the TEWL restoration rates of the subjects. DETAILED DESCRIPTION OF THE INVENTION

[0015] The present invention will be described in detail below, but the present invention is not limited to the specific embodiments listed below, and various modifications can be made to the present invention within the scope that does not deviate from the gist of the present invention.

[0016] The term "topical skin preparation" as used herein refers to any preparation applied to the skin, including, but not limited to, cosmetics, perfumes, fragrances, solid perfumes, etc. Examples include aqueous preparations such as lotions, softening lotions, moisturizing lotions, and repair lotions; spray preparations such as moisturizing sprays, anti-wrinkle sprays, and repair sprays; emulsion preparations such as moisturizing emulsions, anti-wrinkle emulsions, repair emulsions, body lotions, and hand lotions; essence preparations such as moisturizing essences, anti-wrinkle essences, and repair essences; gel preparations such as moisturizing gels, anti-wrinkle gels, and repair gels; creams or ointments such as face creams, eye creams, moisturizing creams, anti-wrinkle creams, repair creams, massage creams, hand creams, and body creams; and powders such as finishing powders, face powders, powder foundations, and Ciccarol.

[0017] Ionone has the structural formula C 13 H 20 It has a molecular weight of 192.3 g / mol and contains three isomers: α-ionone, β-ionone, and γ-ionone. α-Ionone is also known as (3E)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one, cyclocitrylideneacetone, and irisone. α-Ionone is a pale yellow, transparent liquid with a melting point of -49°C and a boiling point of 126-128°C. Its structural formula is: [ka]

[0018] Ionone is an aromatic compound found primarily in raspberries (Rubus idaeus, Raspberry), yellow carrots (Daucus carota subsp. Sativus, Carrot), sweet almonds (Prunus dulcis, Almond), and mint (Mentha, Herb), and produces a primarily floral scent.

[0019] In the present invention, the method for obtaining α-ionone is not particularly limited, and it can be obtained by isolating it from plants containing the above-mentioned ionones, by chemically synthesizing it using known preparation methods, or by using commercially available products.

[0020] The skin barrier repair agent in the new topical skin preparation of the present invention is characterized by containing α-ionone as an active ingredient that acts on keratinocytes.

[0021] The content of the α-ionone as a skin barrier repair agent in the topical skin preparation is 0.0001% by mass to 5% by mass, more preferably 0.001% by mass to 2% by mass, even more preferably 0.01% by mass to 1.5% by mass, and particularly preferably 0.1% by mass to 1% by mass.

[0022] In addition to containing α-ionone as the active ingredient of the skin barrier repair agent, the topical skin preparation of the present invention may contain other additives such as excipients and carriers, and, if necessary, ingredients that are commonly added to cosmetics may be used appropriately.

[0023] Examples of ingredients that are commonly added to cosmetics include, but are not limited to, aqueous solvents, oily ingredients, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, water-soluble polymers, thickeners, preservatives, UV absorbers, sequestering agents, amino acids, organic amines, polymer emulsions, pH adjusters, neutralizing agents, skin nutrients, vitamins, antioxidants, antioxidant aids, and fragrances.

[0024] Aqueous solvents can include, for example, water, alcohol, humectants, or mixtures thereof.

[0025] The water that can be used is water used in cosmetics, semi-pharmaceuticals, etc., such as purified water, ion-exchanged water, tap water, etc. Depending on the purpose, the aqueous phase may further contain a water-soluble alcohol.

[0026] Examples of the water-soluble alcohol include at least one selected from the group consisting of lower alcohols, polyhydric alcohols, polyol polymers, glycol alkyl ethers, glycol ether esters, glycerin monoalkyl ethers, sugar alcohols, monosaccharides, oligosaccharides, polysaccharides, and derivatives thereof.

[0027] Examples of the lower alcohol include ethanol, propanol, isopropanol, isobutanol, and tert-butanol.

[0028] Examples of polyhydric alcohols include diols (e.g., ethylene glycol, propylene glycol, trimethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, tetramethylene glycol, 2,3-butylene glycol, pentamethylene glycol, 2-butene-1,4-diol, hexylene glycol, octylene glycol, etc.); triols (e.g., glycerin, trimethylolpropane, etc.); tetraols (e.g., pentaerythritol, etc.); pentols (e.g., xylitol, etc.); and hexools (e.g., sorbitol, mannitol, etc.).

[0029] Examples of polyol polymers include diethylene glycol, dipropylene glycol, triethylene glycol, polypropylene glycol, tetraethylene glycol, diglycerin, triglycerin, and tetraglycerin.

[0030] Examples of glycol alkyl ethers include ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol monophenyl ether, ethylene glycol monohexyl ether, ethylene glycol mono-2-methylhexyl ether, ethylene glycol isoamyl ether, ethylene glycol benzyl ether, ethylene glycol isopropyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, and ethylene glycol dibutyl ether; diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol butyl ether, diethylene glycol methyl ethyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, propylene glycol isopropyl ether, dipropylene glycol methyl ether, dipropylene glycol ethyl ether, and dipropylene glycol butyl ether.

[0031] Examples of glycol ether esters include ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether acetate, ethylene glycol monophenyl ether acetate, ethylene glycol diadipate, ethylene glycol disuccinate, diethylene glycol monoethyl ether acetate, diethylene glycol monobutyl ether acetate, propylene glycol monomethyl ether acetate, propylene glycol monoethyl ether acetate, propylene glycol monopropyl ether acetate, and propylene glycol monophenyl ether acetate.

[0032] Examples of glycerin monoalkyl ethers include batyl alcohol, cetanol, and cetyl alcohol.

[0033] Examples of sugar alcohols include sorbitol, maltitol, maltotriose, mannitol, sucrose, erythritol, glucose, fructose, hydrolyzed starch, maltose, xylose, reduced hydrolyzed starch, etc.; tetrahydrofurfuryl alcohol; POE-tetrahydrofurfuryl alcohol; POP-butyl ether; POP·POE-butyl ether; tripropylene glycol; POP-glyceryl ether; POP-glyceryl ether phosphate; POP·POE-pentaerythritol ether, etc.

[0034] Examples of monosaccharides include trioses (e.g., D-glyceraldehyde, dihydroxyacetone, etc.), tetroses (e.g., D-erythrose, D-erythrulose, D-threose, erythritol, etc.), pentoses (e.g., L-arabinose, D-xylose, L-lyxose, D-arabinose, D-ribose, D-ribulose, D-xylulose, L-xylulose, etc.), hexoses (e.g., D-glucose, D-talose, D-psicose, D-galactose, D-fructose, L-galactose, L-maltose, etc.), and saccharides (e.g., D-maltose ... Examples of suitable sugars include at least one selected from the group consisting of sugars such as mannose, D-tagatose, etc., sugars such as heptose (e.g., heptose, heptulose, etc.), sugars such as octulose, deoxysugars (e.g., 2-deoxy-D-ribose, 6-deoxy-L-galactose, 6-deoxy-L-mannose, etc.), aminosugars (e.g., D-glucosamine, D-galactosamine, sialic acid, muramic acid, etc.), and uronic acids (e.g., D-glucuronic acid, L-guluronic acid, D-galacturonic acid, L-iduronic acid, etc.).

[0035] The oligosaccharide may include, for example, at least one selected from the group consisting of sucrose, umbelliferose, lactose, planteose, α,α-trehalose, and the like.

[0036] Examples of polysaccharides include at least one selected from the group consisting of cellulose, quince seed, chondroitin sulfate, starch, galactan, dermatan sulfate, glycogen, acacia gum, heparan sulfate, hyaluronic acid, tragacanth gum, keratan sulfate, chondroitin, xanthan gum, mucin sulfate, guar gum, dextran, locust bean gum, succinoglycan, and caronic acid.

[0037] Examples of other polyhydric alcohols include at least one selected from the group consisting of polyoxyethylene methyl glucoside (Glucam E-10), polyoxypropylene methyl glucoside (Glucam P-10), and the like.

[0038] Examples of moisturizing agents include propylene glycol, glycerin, 1,3-butylene glycol, dipropylene glycol, xylitol, sorbitol, maltitol, chondroitin sulfate, hyaluronic acid, mucin sulfate, caronic acid, atelocollagen, sodium lactate, bile salts, dl-pyrrolidone carboxylate, alkylene oxide derivatives, soluble collagen oligopeptide, diglycerin (EO)PO adduct, thorn extract, yarrow extract, melilot extract, and the like.

[0039] Examples of oily components that can be used include liquid oils and fats, solid oils and fats, waxes, hydrocarbons, higher fatty acids, higher alcohols, synthetic ester oils, silicone oils, etc. In this specification, the term "oily components" includes oils and components that can be dissolved in oils.

[0040] Examples of liquid oils and fats include avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, peach kernel oil (almond oil), wheat germ oil, camellia oil, castor oil, linseed oil, safflower oil, cottonseed oil, perilla oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, tung oil, tung oil, jojoba oil, germ oil, and triglycerides.

[0041] Examples of solid fats and oils include cocoa butter, coconut oil, horse oil, hardened coconut oil, palm oil, beef tallow, mutton tallow, hardened beef tallow, palm kernel oil, lard, beef bone fat (oil), Japan wax kernel oil, hardened oil, cow's foot oil, Japan wax, and hardened castor oil.

[0042] Examples of waxes include beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax, Ibota wax (white wax), cetyl alcohol (whale wax), montan wax, rice bran wax, lanolin, kapok wax, lanolin acetate, liquid lanolin, sugarcane wax, lanolin fatty acid isopropyl, hexyl laurate, reduced lanolin, jojoba wax, hard lanolin, shellac wax, POE lanolin alcohol ether, POE lanolin alcohol acetate, POE cholesterol ether, lanolin fatty acid polyethylene glycol, and POE hydrogenated lanolin alcohol ether.

[0043] Examples of hydrocarbon oils include liquid paraffin, ozokerite, squalane, squalene, paraffin, ceresin, squalene, petrolatum, and microcrystalline wax.

[0044] Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, undecylenic acid, tall fatty acids, isostearic acid, linoleic acid, linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

[0045] Examples of higher alcohols include straight-chain alcohols (e.g., lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, cetearyl alcohol, etc.); branched-chain alcohols (e.g., monostearyl glyceryl ether (batyl alcohol), 2-decyltetradecanol, lanolin alcohol, cholesterol, phytosterol, hexyldodecanol, isostearyl alcohol, octyldodecanol, etc.); and the like.

[0046] Synthetic ester oils include hydrogenated polydecene, isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, ethylene glycol di-2-ethylhexanoate, dipentaerythritol fatty acid esters, N-alkyl glycol monoisostearate, neopentyl glycol dicaprate, diisostearyl malate, glyceryl di-2-heptylundecanoate, trimethylolpropane tris-2-ethylhexanoate, trimethylolpropane trisisostearate, pentaerythritol tetra-2-ethylhexanoate Lithritol, glyceryl tris-2-ethylhexanoate, glyceryl trisoctanoate, glyceryl trisisopalmitate, trimethylolpropane trisisostearate, cetyl ethylhexanoate, 2-ethylhexyl palmitate, glyceryl trismyristate, glyceryl tris-2-heptylundecanoate, methyl castor oil oil fatty acid, oleyl oleate, acetylated glycerides, 2-hexyl palmitate butylundecyl, diisobutyl adipate, N-lauroyl-L-glutamic acid-2-octyldodecyl, di-2-heptylundecyl adipate, ethyl laurate, di-2-ethylhexyl sebacate, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebacate, 2-ethylhexyl succinate, triethyl citrate, and the like.

[0047] Examples of silicone oils include dimethicone, methylhydrogenpolysiloxane, methylphenylpolysiloxane, stearoyloxymethylpolysiloxane, polyether-modified organopolysiloxane, fluoroalkyl-polyoxyalkylene-co-modified organopolysiloxane, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, fluorine-modified organopolysiloxane, amino-modified organopolysiloxane, PEG-10 dimethicone, silica gel, acrylate polysiloxane, trimethylsilyloxysilicate, and organosilicon compounds such as organosilicon RTV rubber.

[0048] The oil to be used in combination with hydrogenated polyisobutene is preferably an oil that has poor compatibility with hydrogenated polyisobutene and is easily volatile. In this case, the volatile oil evaporates during application, and due to its poor compatibility, the hydrogenated polyisobutene remains on the skin to form a film, bringing about a tightening feeling.

[0049] Examples of anionic surfactants include fatty acid soaps (e.g., sodium laurate, sodium palmitate, etc.); higher alkyl sulfates (e.g., sodium lauryl sulfate, potassium lauryl sulfate, etc.); alkyl ether sulfates (e.g., POE-lauryl triethanolamine sulfate, POE-lauryl sodium sulfate, etc.); N-acyl sarcosines (e.g., sodium lauroyl sarcosine, etc.); higher fatty acid amide sulfonates (e.g., sodium N-myristyl-N-methyl taurate, sodium coconut oil fatty acid methyl taurate, sodium lauryl methyl taurate, etc.); phosphates (sodium POE-oleyl ether phosphate, POE-stearyl ether phosphate, etc.); sulfosuccinates (e.g., sodium di-2-ethylhexyl sulfosuccinate, sodium monolauroyl monoethanolamide polyoxyethylene sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate, etc. etc.); alkylbenzenesulfonates (e.g., linear dodecylbenzenesulfonate sodium, linear dodecylbenzenesulfonate triethanolamine, linear dodecylbenzenesulfonic acid, etc.); higher fatty acid ester sulfate salts (e.g., hydrogenated coconut oil fatty acid sodium glyceryl sulfate, etc.); N-acylglutamates (e.g., N-lauroylglutamic acid monosodium, N-stearoylglutamic acid disodium, N-myristyl-L-glutamic acid monosodium, etc.); sulfated oils (e.g., Turkey red oil, etc.); POE-alkyl ether carboxylic acids, POE-alkyl allyl ether carboxylic acid salts, α-olefin sulfonates, higher fatty acid ester sulfonates, secondary alcohol sulfate salts, higher fatty acid alkanolamide sulfate salts, sodium lauroylmonoethanolamide succinate, N-palmitoyl aspartic acid di-triethanolamine, sodium caseinate, potassium cetyl phosphate, etc.

[0050] Examples of cationic surfactants include alkyltrimethylammonium salts (e.g., stearyltrimethylammonium chloride, lauryltrimethylammonium chloride, etc.); alkylpyridinium salts (e.g., cetylpyridinium chloride, etc.); distearyldimethylammonium chloride, dialkyldimethylammonium salts; poly(N,N'-dimethyl-3,5-methylenepiperidinium) chloride; alkyl quaternary ammonium salts; alkyldimethylbenzylammonium salts; alkylisoquinolinium salts; dialkylmorpholinium salts; POE-alkylamines; alkylamine salts; polyamine fatty acid derivatives; pentaerythritol fatty acid ester derivatives; benzalkonium chloride; benzethonium chloride, etc.

[0051] Examples of amphoteric surfactants include imidazoline-based amphoteric surfactants (e.g., 2-undecyl-N,N,N-(hydroxyethylcarboxymethyl)-2-imidazoline sodium, 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethoxy disodium salt, etc.); betaine-based surfactants (e.g., 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkyl betaine, amido betaine, sulfobetaine, etc.).

[0052] Examples of lipophilic nonionic surfactants include sorbitan fatty acid esters (e.g., sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, sorbitan penta-2-ethylhexanoate diglyceryl, sorbitan tetra-2-ethylhexanoate diglyceryl, etc.); polyglycerin fatty acid glyceryl (e.g., mono-cottonseed oil fatty acid glyceryl, Examples include glyceryl monoerucate, glyceryl sesquioleate, glyceryl monostearate, α,α'-oleic acid pyroglutamate, glycerin malate monostearate, etc.); propylene glycol fatty acid esters (e.g., propylene glycol monostearate, etc.); hydrogenated castor oil derivatives; glycerin alkyl ethers; PEG-10 dimethicone, glyceryl stearate, PPG-13-decyltetradeceth-24, PEG-5 glyceryl stearate, etc.

[0053] Examples of hydrophilic nonionic surfactants include POE-sorbitan fatty acid esters (e.g., POE-sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan monooleate, POE-sorbitan tetraoleate, etc.); POE-sorbitol fatty acid esters (e.g., POE-sorbitol monolaurate, POE-sorbitol monooleate, POE-sorbitol pentaoleate, POE-sorbitol monostearate, etc.); POE-glycerin fatty acid esters (e.g., POE-glyceryl monostearate, POE-glyceryl tetraoleate, etc.); acrylate, POE-glyceryl monoisostearate, POE-glyceryl trisisostearate, POE-monooleate, etc.; POE-fatty acid esters (e.g., POE-distearate, POE-monodioleate, ethylene glycol distearate, etc.); POE-alkyl ethers (e.g., POE-lauryl ether, POE-oleyl ether, POE-stearyl ether, POE-behenyl ether, POE-2-octyldodecyl ether, POE-cholestanol ether, etc.); Pluronic types (e.g., Pluroni c, etc.); POE·POP-alkyl ethers (e.g., POE·POP-cetyl ether, POE·POP-2-decyltetradecyl ether, POE·POP-monobutyl ether, POE·POP-hydrogenated lanolin, POE·POP-glyceryl ether, etc.); tetra-POE·tetraPOP-ethylenediamine condensates (e.g., Tetronic, etc.); POE-castor oil·hydrogenated castor oil derivatives (e.g., POE-castor oil, POE-hydrogenated castor oil, POE-hydrogenated castor oil monoisostearate, POE-hydrogenated castor oil trisisostearate, etc.) , POE-hydrogenated castor oil monopyroglutamic acid monoisostearate diester, POE-hydrogenated castor oil maleic acid, etc.); POE-beeswax and lanolin derivatives (e.g., POE-sorbitol beeswax, etc.); alkanolamides (e.g., coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide, etc.); POE-propylene glycol fatty acid esters; POE-alkylamines; POE-fatty acid amides; sucrose fatty acid esters; alkylethoxydimethylamine oxide; trioleic acid phosphate;Examples of natural water-soluble polymers include oleth-10, PEG-100 stearate, methoxy PEG / PPG-25 / 4 dimethicone, polysorbate-60, PEG-40 stearate, and sucrose stearate. Examples of natural water-soluble polymers include plant-derived polymers (e.g., acacia gum, tragacanth gum, galactan, guar gum, carob bean gum, karaya gum, carrageenan, pectin, agar, quince seed, algae colloid (brown algae extract), starch (rice, corn, potato, wheat), and glycyrrhizic acid); microbial-derived polymers (e.g., xanthan gum, dextran, succinoglycan, pullulan, etc.); and animal-derived polymers (e.g., collagen, casein, albumin, gelatin, etc.);

[0054] Examples of semi-synthetic water-soluble polymers include starch-based polymers (e.g., carboxymethyl starch, methylhydroxypropyl starch, etc.); cellulose-based polymers (methyl cellulose, ethyl cellulose, methylhydroxypropyl cellulose, hydroxyethyl cellulose, sodium cellulose sulfate, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, crystalline cellulose, cellulose powder, etc.); alginic acid-based polymers (e.g., sodium alginate, propylene glycol alginate, etc.); (PEG-240 / decyltetradeceth-20 / HDI) copolymer, (acrylates / alkyl acrylate (C10-30)) crosspolymer, etc.

[0055] Examples of thickeners include polyacrylic acid thickeners such as carbomer, (acrylates / C10-30 alkyl acrylate) crosspolymer, sodium acrylate / sodium acryloyldimethyltaurate copolymer, acrylate / ceteareth-20 itaconate copolymer, acrylate / ceteareth-20 methacrylate copolymer, acrylate / myrithreth-25 acrylate copolymer, acrylate / steareth-20 itaconate copolymer, acrylate / steareth-20 methacrylate copolymer, acrylate / steareth-50 acrylate copolymer, acrylate / VA crosslinked polymer, PAA (polyacrylic acid), sodium acrylate / vinyl isodecanoate crosslinked polymer, carbomer (polyacrylic acid) and its sodium salt.

[0056] Examples of preservatives include aromatic preservatives such as phenoxyethanol, benzyl alcohol, methylparaben, and p-hydroxyacetophenone.

[0057] Examples of the ultraviolet absorber include benzoic acid-based ultraviolet absorbers (e.g., para-aminobenzoic acid (hereinafter abbreviated as PABA), PABA monoglyceryl, N,N-dipropoxy PABA ethyl, N,N-diethoxy PABA ethyl, N,N-dimethyl PABA ethyl, N,N-dimethyl PABA butyl, N,N-dimethyl PABA ethyl, etc.); anthranilic acid-based ultraviolet absorbers (e.g., N-acetylanthranilic acid homomenthryl); salicylic acid-based ultraviolet absorbers (e.g., amyl salicylate, menthol salicylate, homomenthryl salicylate, etc.); phenyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, para-isopropanol phenyl salicylate, etc.); cinnamic acid-based ultraviolet absorbers (e.g., octyl methoxycinnamate, ethyl 4-isopropylcinnamate, methyl 2,5-diisopropylcinnamate, ethyl 2,4-diisopropylcinnamate, methyl 2,4-diisopropylcinnamate, propyl paramethoxycinnamate, isopropyl paramethoxycinnamate, isoamyl paramethoxycinnamate, octyl paramethoxycinnamate (2-ethylhexyl paramethoxycinnamate), para 2-ethoxyethyl methoxycinnamate, cyclohexyl paramethoxycinnamate, ethyl α-cyano-β-phenylcinnamate, 2-ethylhexyl α-cyano-β-phenylcinnamate, glyceryl mono-2-ethylhexanoyl-di-paramethoxycinnamate, etc.; benzophenone-based ultraviolet absorbers (e.g., 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 2-hydroxy- 4-Methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-phenylbenzophenone, 2-ethylhexyl-4'-phenyl-benzophenone-2-carboxylate, 2-hydroxy-4-normal octoxybenzophenone, 4-hydroxy-3-carboxybenzophenone, etc.; 3-(4'-methylbenzylidene)-d,l-camphor, 3-benzylidene-d,l-camphor; 2-phenyl-5-methylbenzoxazole;Examples include 2,2'-hydroxy-5-methylphenylbenzotriazole; 2-(2'-hydroxy-5'-tert-octylphenyl)benzotriazole; 2-(2'-hydroxy-5'-methylphenylbenzotriazole; dibenzamide; dianisoylmethane; 4-methoxy-4'-tert-butyldibenzoylmethane; 5-(3,3-dimethyl-2-norbornylidene)-3-pentan-2-one, dimorpholinodizinone; 2-ethylhexyl-2-cyano-3,3-diphenylacrylate; 2,4-bis-{[4-(2-ethylhexyloxy)-2-hydroxy]-phenyl}-6-(4-methoxyphenyl)-(1,3,5)-triazine, and the like.

[0058] Examples of sequestering agents include 1-hydroxyethane-1,1-diphosphonic acid, 1-hydroxyethane-1,1-diphosphonic acid tetrasodium salt, disodium edetate (EDTA2Na), trisodium edetate (EDTA3Na), tetrasodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, phosphoric acid, citric acid, ascorbic acid, succinic acid, edetic acid, and trisodium ethylenediamine N-(2-hydroxyethyl)-N,N',N'-triacetate.

[0059] Examples of amino acids include neutral amino acids (e.g., threonine, cysteine, etc.), basic amino acids (e.g., hydroxylysine, etc.), etc. Examples of amino acid derivatives include sodium acyl sarcosine (sodium lauroyl sarcosine), acyl glutamate, sodium acyl β-alanine, glutathione, pyrrolidone carboxylic acid, etc.

[0060] Examples of organic amines include monoethanolamine, diethanolamine, triethanolamine, morpholine, trisisopropanolamine, 2-amino-2-methyl-1,3-propanediol, and 2-amino-2-methyl-1-propanol.

[0061] Examples of polymer emulsions include acrylic resin emulsions, polyethyl acrylate emulsions, acrylic resin solutions, polyacrylic acid alkyl ester emulsions, polyvinyl acetate resin emulsions, and natural rubber latex.

[0062] Examples of pH adjusters include buffers such as lactic acid-sodium lactate, citric acid-sodium citrate, and succinic acid-sodium succinate.

[0063] Examples of the neutralizing agent include potassium hydroxide, sodium hydroxide, aminomethylpropanol, and arginine.

[0064] Examples of vitamins include vitamins A, B1, B2, B6, C, E and their derivatives, pantothenic acid and its derivatives, biotin, etc.

[0065] Examples of antioxidants include tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, and gallic acid esters.

[0066] Examples of antioxidant aids include phosphoric acid, citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, cephalin, hexametaphosphate (ester), phytic acid, and ethylenediaminetetraacetic acid.

[0067] [Test example] Test Example 1. The effect of α-ionone on promoting the proliferation of HaCaT cells The CCK8 (Cell Counting Kit-8) assay was used to confirm the effect of α-ionone on the proliferation of HaCaT cells. HaCaT cells are immortalized human keratinocytes derived from normal adult skin. They have similar biological properties to primary keratinocytes and retain the ability to differentiate into epidermis. They are frequently used as an in vitro surrogate model for keratinocyte-related epidermal biology research. 5 x 10 HaCaT cells 3 Cells were seeded into a 96-well cell culture plate at a density of 1000 cells / well and cultured for 24 hours in a cell culture incubator. Subsequently, different concentrations of α-ionone (1-400 μM) were added and incubated for 24 hours (Figure 1, top) or 48 hours (Figure 1, bottom). After incubation, 10 μl of CCK-8 solution was added to each well, and the culture plate was incubated in the incubator for 1 hour. After incubation, the absorbance (OD) value at 450 nm of each well was measured using a microplate reader. The proliferation rate of HaCaT cells was calculated based on the percentage of the OD value of each experimental group relative to the OD value of the control group. The results are shown in Figure 1. Data in the figure are mean ± SD from three repeated experiments; **p<0.01 vs. the blank control group. As shown in Figure 1, α-ionone can effectively promote HaCaT cell proliferation within the dose range of 1 to 200 μM, with the strongest cell proliferation-promoting effect at a dose of 50 μM. At doses above 100 μM, the proliferation-promoting effect did not increase further and instead became somewhat weaker (Figure 1). Therefore, α-ionone can directly act on HaCaT cells to promote cell proliferation, with the effective dose range being 1 to 200 μM.

[0068] Test Example 2: The effect of α-ionone on promoting migration of HaCaT cells Using a cell scratch assay, we confirmed the effect of α-ionone on promoting HaCaT cell migration. 2 x 10 HaCaT cells 5Cells were seeded into 6-well cell culture plates at a cell density of 1000 cells / well and cultured in a cell culture incubator. When the cells reached 90% confluence, the medium was aspirated, and a straight line was drawn perpendicular to the cell plane with a 20 μl sterile pipette tip to create a "scratch." After washing with PBS, 2 ml of complete medium containing different concentrations of α-ionone (1, 10, 25, 50 μM) was added, and the cells were cultured for 24 hours. At different times after scratch creation (0, 12, and 24 hours), observations and photographs were taken under an inverted microscope. The scratch area was calculated using Image J software, and the cell migration rate was calculated according to the following formula: Cell migration rate (%) = (initial scratch area - scratch area after culture) / initial scratch area × 100% The results are shown in Figure 2. The data in the figure are Mean±SD (n=4), *p<0.05 vs. the vehicle control group. As can be seen from Figure 2, α-ionone promoted HaCaT cell migration in a dose-dependent manner over the dose range of 10–50 μM. Although a moderate increase in cell migration rate was observed at the relatively low dose of 1 μM, it did not reach statistical significance compared to the blank control group, suggesting that α-ionone is largely ineffective at doses below 1 μM. The 50 μM α-ionone group did not significantly increase cell migration rate compared to the 25 μM group; rather, it only slightly decreased at 24 h, suggesting that further increases in the α-ionone dose did not further enhance its cell migration-promoting effect (Figure 2). Therefore, α-ionone can promote HaCaT cell migration, and its effective dose range is 10–50 μM.

[0069] Test Example 3: α-ionone effectively attenuates the inhibitory effect of norepinephrine (NE) on HaCaT cell migration The stress hormone norepinephrine (NE) is known to inhibit keratinocyte migration, thereby delaying skin wound healing. To examine the effect of α-ionone on NE-induced inhibition of HaCaT cell migration, confluent monolayer HaCaT cells were scratched and then treated with 10 μM NE or NE (10 μM) plus α-ionone (25 or 50 μM) for 24 hours. At different times (0, 12, and 24 hours) after scratch creation, the cells were observed and photographed under an inverted microscope. The scratch area was calculated using Image J software, and the cell migration rate was calculated. The results are shown in Figure 3. Data are mean ± SD (n = 4). *p < 0.05 vs. blank control group, #p < 0.05 vs. NE alone group. As can be seen from the results in Figure 3, the action of NE (10 μM) alone significantly inhibited the migration of HaCaT cells, and the cell migration rate in the NE + α-ionone (25, 50 μM) experimental group was significantly increased compared to the NE alone group, indicating that α-ionone can effectively attenuate the inhibitory effect of NE on cell migration.

[0070] Test Example 4: Effect of α-ionone on HAS-2 expression in HaCaT cells The effect of α-ionone alone on HAS-2 gene expression was confirmed in normal cultured HaCaT cells. 2 x 10 HaCaT cells 5 Cells were seeded into 6-well cell culture plates at a density of 1000 cells / well and cultured for 24 hours in a cell culture incubator. Subsequently, different concentrations of α-ionone (1, 10, 25, 50, 100 μM) were added and allowed to react for 9 hours. The intracellular HAS-2 mRNA expression level was measured by real-time quantitative PCR (qPCR), and the results are shown in Figure 4. Data in the figure are mean ± SD from three repeated experiments, **p<0.01. As is clear from the results in Figure 4, α-ionone increased HAS-2 gene expression levels in a dose-dependent manner in the dose range of 10 to 50 μM, and at a higher dose of 100 μM, its pharmacological activity did not increase further and was actually attenuated. Therefore, α-ionone has a promoting effect on HAS-2 expression in HaCaT cells, and its effective dose range is 10 to 50 μM.

[0071] Test Example 5. The effect of α-ionone on promoting HA synthesis by HaCaT cells In this study, the inventors quantitatively measured HA levels in the culture supernatant of HaCaT cells 24 hours after α-ionone stimulation. 2 x 10 HaCaT cells 5 Cells were seeded into 6-well cell culture plates at a density of 1000 cells / well and cultured for 24 hours in a cell culture incubator. Different concentrations of α-ionone (25 and 50 μM) were added and allowed to act for 24 hours. The cell culture supernatant was collected and the HA concentration in the cell culture supernatant was measured by ELISA. The results are shown in Figure 5. Data in the figure are mean ± SD from three repeated experiments, **p<0.01. The results in Figure 5 demonstrate that 24-hour treatment with α-ionone (25, 50 μM) significantly increased the HA level in the culture supernatant of HaCaT cells, demonstrating that α-ionone promoted HA synthesis by increasing the expression of the hyaluronan synthase HAS-2. Therefore, these results further confirmed the pharmacological activity of α-ionone in inducing the expression of hyaluronan synthase.

[0072] Test Example 6: Effect of α-ionone on the suppression of HAS-2 expression by dexamethasone (DEX) Glucocorticoids reduce HA synthesis by suppressing HAS-2 expression in keratinocytes, which is one of the major pathological mechanisms by which glucocorticoids and psychological stress cause skin atrophy and skin barrier dysfunction. DEX is a synthetic, potent glucocorticoid agent that is more active and stable than endogenous glucocorticoids and is therefore frequently used as a tool drug to study glucocorticoid action, and DEX-stimulated HaCaT cells are frequently used as a skin stress cell model. In this study, we examined the effect of α-ionone on DEX-induced suppression of HAS-2 expression in a DEX-induced skin stress cell model. 2 x 10 HaCaT cells 5 Cells were seeded into 6-well cell culture plates at a density of 1000 cells / well and cultured for 24 hours in a cell culture incubator. Different concentrations of α-ionone (1, 10, 25, 50, 100 μM) were added for 3 hours, followed by 1 μM DEX for 6 hours. The intracellular HAS-2 mRNA expression level was measured by real-time quantitative PCR (qPCR), and the results are shown in Figure 6. Data in the figure are mean ± SD from three repeated experiments, *p<0.05, **p<0.01. As is clear from the results in Figure 6, DEX (1 μM) significantly suppresses HAS-2 expression in HaCaT cells. α-ionone can effectively alleviate the inhibitory effect of DEX on HAS-2 expression in the dose range of 10 to 50 μM, indicating that it can enhance HAS-2 expression levels in keratinocytes in response to stress hormones. Therefore, α-ionone has an antagonistic effect on DEX-induced suppression of HAS-2 expression, with its effective dose range being 10 to 50 μM.

[0073] Test Example 7. The effect of α-ionone on promoting HBD-2 expression in HaCaT cells The effect of α-ionone alone on HBD-2 gene expression was confirmed in normal cultured HaCaT cells. 2 x 10 HaCaT cells 5Cells were seeded into 6-well cell culture plates at a density of 1000 cells / well and cultured for 24 hours in a cell culture incubator. Different concentrations of α-ionone (1, 10, 25, 50, 100 μM) were added and incubated for 9 hours. Intracellular HBD-2 mRNA expression levels were measured by real-time quantitative PCR (qPCR), and the results are shown in Figure 7. Data in the figure are mean ± SD from three repeated experiments, **p<0.01. As is clear from the results in Figure 7, α-ionone can effectively increase the HBD-2 gene expression level in the dose range of 10 to 50 μM. These results confirmed the pharmacological activity of α-ionone in inducing HBD-2 expression.

[0074] Test Example 8: Effect of α-ionone on HBD-2 secretion by HaCaT cells In this study, the inventors quantitatively measured HBD-2 levels in the culture supernatant of HaCaT cells 24 hours after α-ionone stimulation. 2 x 10 HaCaT cells 5 Cells were seeded into 6-well cell culture plates at a density of 1000 cells / well and cultured for 24 hours in a cell culture incubator. Different concentrations of α-ionone (25 and 50 μM) were added and allowed to react for 24 hours. The cell culture supernatant was collected and the HBD-2 concentration in the cell culture supernatant was measured by ELISA. The results are shown in Figure 8. Data in the figure are mean ± SD from three repeated experiments, *p<0.05. As shown in Figure 8, 24-hour treatment with α-ionone (25 and 50 μM) significantly increased HBD-2 levels in the culture supernatant of HaCaT cells, demonstrating that α-ionone promoted HBD-2 synthesis and secretion through HBD-2 expression. Therefore, these results further confirmed the pharmacological activity of α-ionone in inducing HBD-2 expression.

[0075] Test Example 9: Effect of α-ionone on the suppression of HBD-2 expression in HaCaT cells by dexamethasone (DEX) Glucocorticoid suppression of HBD-2 expression in keratinocytes is one of the important pathological mechanisms underlying increased susceptibility to microbial infection and impaired epidermal barrier function due to glucocorticoid use and psychological stress. In this study, we further examined the effect of α-ionone on DEX-induced suppression of HBD-2 expression in a DEX-induced skin stress cell model. 2 x 10 HaCaT cells 5 Cells were seeded into 6-well cell culture plates at a density of 1000 cells / well and cultured for 24 hours in a cell culture incubator. Different concentrations of α-ionone (1, 10, 25, 50, 100 μM) were added for 3 hours, followed by 1 μM DEX for 6 hours. Intracellular HBD-2 mRNA expression levels were measured by real-time quantitative PCR (qPCR), and the results are shown in Figure 9. Data in the figure are mean ± SD from three replicate experiments, **p<0.01. As shown in Figure 9, DEX (1 μM) significantly suppressed HBD-2 expression in HaCaT cells, and α-ionone effectively reduced the inhibitory effect of DEX on HBD-2 expression at doses ranging from 10 to 50 μM, thereby enhancing HBD-2 expression in keratinocytes in response to stress hormones. These results indicate that α-ionone has an antagonistic effect on DEX-induced suppression of HBD-2 expression, with the effective dose range being 10 to 50 μM.

[0076] [Example] Example 1. Lotion A lotion containing α-ionone as a skin barrier repair active ingredient was prepared according to the following formulation using a conventional cosmetic manufacturing process. Component Content (mass%) Add water up to 100% Dipropylene Glycol 5 PPG-13-decyltetradeceth-24 1 Phenoxyethanol 0.6 EDTA-2Na 0.02 α-ionone 0.02

[0077] Example 2: Lotion A lotion containing α-ionone as a skin barrier repair active ingredient was prepared according to the following formulation using a conventional cosmetic manufacturing process. Component Content (mass%) Add water up to 100% Dipropylene Glycol 5 PPG-13-decyltetradeceth-24 1 Phenoxyethanol 0.6 EDTA-2Na 0.02 α-ionone 0.1

[0078] Example 3. Emulsion According to the following formulation, an emulsion containing α-ionone as a skin barrier repair active ingredient was prepared using a conventional cosmetic manufacturing process. Component Content (mass%) Add water up to 100% Butylene Glycol 5 Carbomer 0.12 Potassium hydroxide 0.08 Behenic acid 0.3 Stearic acid 0.2 Isostearic acid 0.3 Glyceryl stearate 1.2 PEG-5 Glyceryl Stearate 1.2 Dimethicone 1 Cetyl ethylhexanoate 3 Methylparaben 0.2 α-ionone 0.02

[0079] Example 4. Emulsion According to the following formulation, an emulsion containing α-ionone as a skin barrier repair active ingredient was prepared using a conventional cosmetic manufacturing process. Component Content (mass%) Add water up to 100% Butylene Glycol 5 Carbomer 0.12 Potassium hydroxide 0.08 Behenic acid 0.3 Stearic acid 0.2 Isostearic acid 0.3 Glyceryl stearate 1.2 PEG-5 Glyceryl Stearate 1.2 Dimethicone 1 Cetyl ethylhexanoate 3 Methylparaben 0.2 α-ionone 0.1

[0080] Example 5. Cream A cream containing α-ionone as a skin barrier repair active ingredient was prepared according to the following formulation using a conventional cosmetic manufacturing process. Component Content (mass%) Add water up to 100% Ethanol 5 Dipropylene Glycol 5 Dimethicone 3 (PEG-240 / Decyltetradeceth-20 / HDI) copolymer 1.2 Carbomer 0.3 (Acrylates / C10-30 alkyl acrylate) crosspolymer 0.03 Potassium hydroxide 0.1 Phenoxyethanol 0.5 α-ionone 0.02

[0081] Example 6. Cream A cream containing α-ionone as a skin barrier repair active ingredient was prepared according to the following formulation using a conventional cosmetic manufacturing process. Component Content (mass%) Add water up to 100% Ethanol 5 Dipropylene Glycol 5 Dimethicone 3 (PEG-240 / Decyltetradeceth-20 / HDI) copolymer 1.2 Carbomer 0.3 (Acrylates / C10-30 alkyl acrylate) crosspolymer 0.03 Potassium hydroxide 0.1 Phenoxyethanol 0.5 α-ionone 0.1

[0082] Example 7. Hydrogel A hydrogel containing α-ionone as a skin barrier repair active ingredient was prepared according to the following formulation. An appropriate amount of deionized water was heated to 85°C in a water bath, and Carbomer U20 powder was gradually added to the water and stirred until uniformly dissolved. Then, 10% arginine was added to neutralize the mixture. p-Hydroxyacetophenone and 1,2-hexanediol were weighed and dissolved in an appropriate amount of deionized water with slight heating. The mixture was then added to the Carbomer U20 gel and stirred uniformly to obtain the hydrogel base. After the hydrogel base was cooled to below 40°C, α-ionone was added and stirred uniformly to obtain the α-ionone hydrogel. Ingredients Content (g) α-ionone 0.1 Carbomer U20 0.25 Arginine (10%) 2.5 p-Hydroxyacetophenone 0.4 1,2-Hexanediol 0.4 Add deionized water to bring the total to 100g

[0083] Example 8. Hydrogel A hydrogel containing α-ionone as a skin barrier repair active ingredient was prepared according to the following formulation and the manufacturing process described in Example 7. Ingredients Content (g) α-Ionone 1 Carbomer U20 0.25 Arginine (10%) 2.5 p-Hydroxyacetophenone 0.4 1,2-Hexanediol 0.4 Add deionized water to bring the total to 100g

[0084] [Example of effectiveness test] 1. Test Principle Human clinical trials mainly analyze the improvement effect on the subjects' skin condition before and after use of the test product through subjective evaluation and objective skin index measurement, and the results are more intuitive and suitable for evaluating the efficacy of finished or semi-finished cosmetic products. In this study, healthy volunteers will be recruited to form a subject group, and a model of skin barrier damage on the flexor side of the forearm will be created using tape stripping. The effectiveness of cosmetics in promoting skin barrier repair will be evaluated by measuring changes in physiological indicators such as the moisture content of the stratum corneum and transepidermal water loss (TEWL) before and after using the cosmetics.

[0085] 2. Materials and Equipment 2.1 Test Sample: [Table 1] How to use the test sample: Apply the test product to the area on the flexor side of the forearm where tape was removed, approximately 2 mg / cm once a day. 2 An area that has been tape removed but no product is used is set up as a model control. 2.2 Equipment Stratum corneum moisture content meter (C&K, Germany, Corneometer CM825); transepidermal water loss meter (Delfin, Finland, Vapometer).

[0086] 3. Test Method 3.1 Subjects In accordance with the Declaration of Helsinki, subject selection must follow medical and ethical standards for human research, and all subjects must be voluntary and sign an informed consent document before the study. Before subjects sign the informed consent document, investigators must inform subjects of the purpose of the study, the possible benefits, potential risks and issues, and their associated rights and obligations. 3.1.1 Number of subjects Target number of subjects: 32 3.1.2 Selection criteria: Age 18 to 65 years old; The skin on the flexor forearm is healthy and even in color, with no scars or other conditions that could affect the test. Follow-up and skin testing is available upon request. 3.1.3 Exclusion criteria: are pregnant or breastfeeding; Have a history of allergies to skin care products, cleansing and protection products, or are allergic to certain ingredients in the test products and related samples; Those suffering from serious systemic diseases or other skin diseases, such as systemic lupus erythematosus or psoriasis; undergoing cosmetic procedures in the test area; Currently participating in other clinical trials or prior to the start of this study. 3.1.4 Exit (dropout) criteria: subject loss to follow-up and requesting voluntary withdrawal; Low compliance, failure to use samples on time and in the correct quantities, and failure to follow up as required; Use other cosmetic products similar to the test sample during the research process; Throughout the study period, new diseases occur that have a direct impact on the clinical status assessment, including skin diseases; those who develop severe illness throughout the study period; subjects who become pregnant during the study period; Those who cannot tolerate this study; Those who experience serious adverse events (SAEs) throughout the study period.

[0087] 3.2 Measurement indicators 3.2.1 Skin stratum corneum water content The moisture content of the stratum corneum is measured using the skin moisture content measurement probe (Corneometer CM825) of the German company CK's multi-function skin meter MPA580. This probe uses the capacitance method to measure the moisture content of the skin's surface layer. The dielectric constant of water in the skin's surface layer is much higher than that of other substances, and changes in the dielectric constant of the skin's surface layer are mainly caused by changes in the moisture content of the skin's surface layer. Measuring the dielectric constant of the skin's surface layer allows the moisture content of the skin's surface layer to be analyzed. The measurement value is a relative value expressed in CU (Corneometer Units), with a higher value indicating a higher moisture content in the skin's surface layer. 3.2.2 Transepidermal Water Loss (TEWL) Transepidermal water loss (TEWL) is measured using a vapometer manufactured by Delfin, a Finnish company. This meter has an open-ended circular aperture at the top, which forms a sealed cavity when it comes into contact with the skin, and a high-precision humidity sensor inside the cavity records the change in air humidity in the cavity. The rate of change in air humidity over a specific period after skin contact can be used to calculate the rate at which water evaporates through the skin. The measurement is expressed in g / (m 2 ·h), and the lower the value, the lower the water evaporation rate on the skin surface and the better the skin barrier function. 3.3 Measurement site Four 3cm x 3cm areas were selected as test areas on the flexor side of the forearm, spaced at least 1cm apart, and tape stripping was performed five times each day for three consecutive days from day 0 to day 2. Based on a random table, three of the test areas were designated as sample areas, and the test product was used once each day, while the remaining area was designated as a model control, with no test product used. 3.4 Test environment The subject exposes the skin on the flexor side of the forearm and acclimates to an environment of 20-22°C temperature and 40-60% humidity for 20 minutes before skin measurements are taken. 3.5 Test Procedure On Day 0, subjects signed an informed consent document and then underwent screening. Subjects who passed the screening were selected to participate in the study. Four 3cm x 3cm areas were marked as test areas on the flexor forearm. After acclimatizing to a constant temperature and humidity environment for 20 minutes, the moisture content and TEWL of the stratum corneum of the test areas were measured. Tape stripping was then performed on the test areas, with each area being stripped five times. On Days 1 and 2, tape stripping was performed on the test areas every day, with each area being stripped five times. After tape stripping was completed, approximately 2mg / cm of the product was applied to the sample areas. 2 On days 3-7, apply approximately 2 mg / cm of product to the sample area every day. 2 After tape removal was completed on the second day and on the seventh day, the test area was acclimated to a constant temperature and humidity environment for 20 minutes, and then the moisture content and TEWL of the stratum corneum of the test area were measured. 3.6 Adverse Events If any adverse events occur in the volunteers, they should immediately discontinue use of the test product and seek medical advice at the research center, who will decide whether to terminate the use of the sample depending on the circumstances. Any adverse events and other related events occurring during the study should be recorded and reflected in the report. 3.7 Data Analysis The mean and standard deviation of each measurement index for all subjects at each time point were calculated. The barrier repair rate for each test group was calculated based on the rate of change in the TEWL value for each test group after the end of treatment (day 7) compared to the TEWL value on day 0 (baseline TEWL value) and the TEWL value after tape removal on day 2. The calculation formula is as follows: Barrier repair rate (%) = (T2-T7) / (T2-T0) x 100% In the formula, T2 is the TEWL value measured immediately after tape removal on day 2, T7 is the TEWL value of each test group after treatment on day 7, and TO is the baseline TEWL value measured on day 0 before tape application. The data group was statistically analyzed using SPSS22.0 software, using one-way ANOVA followed by Dunnett's post-hoc test for multiple comparisons.

[0088] 4. Test results Thirty-two subjects who met the criteria were recruited for this study, including three men and 29 women, aged 24 to 58 years, with an average age of 41.2 ± 10.7 years. No adverse events were reported during the study period. The results of measurements of transepidermal water loss (TEWL) and stratum corneum moisture content in the test areas for each test group are as follows: 4.1 Transepidermal water loss (TEWL value) for each test group The change trends of TEWL values ​​in the test areas of each test group are shown in Figure 10: (#p<0.05 compared to normal skin control group, *p<0.05 compared to blank hydrogel base group) As is clear from the measurement results of the TEWL value in the test area of ​​each test group, after three consecutive days of tape peeling, the TEWL value of each test area was reduced to the baseline value of 5 g / m 2 13g / m after tape peeling on the second day 2 The TEWL value increased to 1.5 h, indicating that tape removal clearly damaged the epidermal barrier function. After tape removal, the test product was used once daily for up to 7 days. The TEWL values ​​in the test areas of each test group significantly decreased compared to those after tape removal on the second day, indicating that the damaged epidermal barrier had been repaired to some extent. Furthermore, the decrease in TEWL values ​​was greater in the areas treated with the test samples "0.1% α-ionone hydrogel" and "1% α-ionone hydrogel," and the TEWL values ​​were statistically significantly different from those in the test group using the "blank hydrogel base" and the model group that was only tape removed and did not use any test sample. This suggests that the use of the test samples "0.1% α-ionone hydrogel" and "1% α-ionone hydrogel" can accelerate the repair of the epidermal barrier damaged by tape application. 4.2 Moisture content of the stratum corneum in each test group The change in moisture content of the stratum corneum in the test area of ​​each test group is shown in Figure 11: (*p<0.05 compared to blank hydrogel base group, #p<0.05 compared to normal skin control group) Measurements of stratum corneum moisture content in the test areas of each test group revealed that tape stripping for three consecutive days did not significantly change the moisture content of each test area. However, tape stripping caused a significant decrease in the moisture content of the stratum corneum in the model group (tape stripping only, no test samples) on day 7, with a mean decrease of 9.13% compared to baseline. This indicates that increased transepidermal water loss due to tape stripping further drier skin. Meanwhile, the mean moisture content of the stratum corneum in the test areas treated with the "blank hydrogel base," "0.1% α-ionone hydrogel," and "1% α-ionone hydrogel" also decreased compared to baseline, but the decreases were smaller: 7.71%, 3.99%, and 2.81%, respectively. The measured moisture content of the stratum corneum in the area where the test sample "blank hydrogel base" was used was not significantly different from that of the model group (p≧0.05), whereas the measured moisture content of the stratum corneum in the areas where the test samples "0.1% α-ionone hydrogel" and "1% α-ionone hydrogel" were used was both significantly higher than that of the model group (p<0.05). This further suggests that the use of the test samples "0.1% α-ionone hydrogel" and "1% α-ionone hydrogel" may accelerate the repair of the epidermal barrier damaged by tape application, thereby increasing the moisture content of the stratum corneum in the test area. 4.3 Barrier repair rate in each test group The barrier repair rate calculated based on the rate of change in TEWL value for each test group is shown in Figure 12: (*p<0.05 compared to blank hydrogel base group, **p<0.01 compared to blank hydrogel base group) As is clear from the results of the barrier repair rate calculated based on the rate of change in TEWL values ​​for each test group, the barrier repair rate of the test group using the test sample "blank hydrogel base" was not significantly different from that of the model group not using any test sample, whereas the barrier repair rates of the test groups using the test samples "0.1% α-ionone hydrogel" and "1% α-ionone hydrogel" were significantly increased compared to the model group and the "blank hydrogel base" group. These results demonstrate that the use of the test samples "0.1% α-ionone hydrogel" and "1% α-ionone hydrogel" can indeed accelerate the repair of the epidermal barrier damaged by tape application, and therefore have repair effectiveness.

[0089] 5 Conclusion As is clear from the measurement results of this test, the test sample "blank hydrogel base" has no repair efficacy, while "0.1% α-ionone hydrogel" and "1% α-ionone hydrogel" have repair efficacy.

[0090] [Cosmetics effectiveness test] In order to verify the effects of the cosmetics of the present invention, the inventors conducted effect tests on the lotions, emulsions, and creams of Examples 1 to 6. Specifically, the tests were carried out as follows.

[0091] [Table 2]

[0092] B. Test Method B.1 Subjects B.1.1 Target number of people: 30 people. B.1.2 Selection criteria Age 30-50 years old; The skin on the arms is of even complexion and free of skin problems that may affect the test, such as folliculitis or eczema; consent to tape stripping of the skin on the arm; Do not use any other products on the test site during the test period; Informed consent is obtained, and the product can be used according to the researchers' requirements and appropriate testing can be completed. B.1.3 Exclusion criteria Pregnant or breastfeeding women; those with serious systemic diseases and those currently taking medications for systemic diseases; undergoing skin treatments, cosmetic procedures, and other tests in the study area that may affect the results; People with allergic diseases or who are prone to allergies to cosmetics; Currently participating in other clinical trials or prior to the start of this study. B.1.4 Exclusion criteria subject loss to follow-up and requesting voluntary withdrawal; Low compliance, failure to use samples on time and in the correct quantities, and failure to follow up as required; Use other cosmetic products similar to the test sample during the research process; Throughout the study period, new diseases occur that have a direct impact on the clinical status assessment, including skin diseases; those who develop severe illness throughout the study period; subjects who become pregnant during the study period; Those who cannot tolerate this study; Those who experience serious adverse events (SAEs) throughout the study period. B.2 Equipment Transepidermal water loss meter (C&K, Tewameter, Germany); Skin stratum corneum moisture content meter (Germany C&K, Corneometer). B.3 Metrics B.3.1 The moisture content of the stratum corneum is one of the indicators used to evaluate the repair efficacy of cosmetics. A higher value of this indicator indicates a higher moisture content in the stratum corneum. After creating a model of minor skin barrier damage using tape stripping, if the moisture content of the stratum corneum in the area where the product was used is significantly increased compared to the area where the product was not used or the control area, the product can be proven to have repair efficacy. B.3.2 Transepidermal water loss (TEWL) is one of the indices used to evaluate the repair effectiveness of cosmetics. The higher the value of this index, the faster the rate of water evaporation from the skin surface and the poorer the skin barrier function. After creating a model of slight damage to the skin barrier using tape stripping, if the TEWL in the area where the product was used is significantly reduced compared to the area where the product was not used or the control area, the product can be proven to have repair effectiveness. B.4 Measurement site The measurement sites for the moisture content of the stratum corneum and TEWL were both on the inside of the arm, in an area where slight damage to the skin barrier had occurred by tape removal. B.5 Test Environment The subject exposes the skin at the measurement site and acclimates to an environment with a temperature of 20-22°C and a humidity of 40-60% for 20 minutes before skin measurement. B.6 Test Procedures (1) On day 0, subjects signed an informed consent document and then underwent screening. Subjects who passed the screening were selected to participate in the study. After washing the skin on the flexor side of the forearm with soapy water, 11 3cm x 3cm areas were marked as test areas. After acclimatizing to a constant temperature and humidity environment for 20 minutes, the moisture content of the stratum corneum and TEWL of the test areas were measured. Furthermore, tape stripping was performed on 10 of the test areas, with each area stripped 10 times. The remaining area was left unstripped as a blank control. After 15 minutes, the moisture content and TEWL of the test areas were measured. Based on a random table, the product was applied quantitatively to the 9 tape-stripped areas, with approximately 2mg / cm2 applied to each area. 2 One area was tape-stripped and no product was used, serving as a model control. After 6 hours, the moisture content and TEWL of the stratum corneum of the test area were measured. (2) On days 1-9, apply the product twice daily to the sample area, each time at approximately 2 mg / cm 2 No product is used in the model control and blank control areas. (3) On the 1st, 3rd, 7th, and 10th days, the skin on the flexor side of the forearm is washed with soapy water and allowed to acclimate to a constant temperature and humidity environment for 20 minutes, after which the moisture content of the stratum corneum and TEWL of the test area are measured. B.7 Adverse Events If any adverse events occur in the volunteers, they should immediately discontinue use of the test product and seek medical advice at the research center, who will decide whether to terminate use of the product depending on the circumstances. Any adverse events and other related events occurring during the study should be recorded and reflected in the report. B.8 Data Analysis The average value and standard deviation of each measurement index for all subjects at each time point are calculated. The change and rate of change in the moisture content of the stratum corneum compared to before peeling are calculated. The calculation formula is as follows: [ka] In the formula, T0 is the measured value before peeling of the measurement indicator, and T n is the measured value of the measurement indicator at the nth follow-up, where n is the number of follow-ups. The TEWL repair rate at each site was calculated using the following formula: [ka] In the formula, T c is the TEWL value immediately after the tape is peeled off, and T s is the TEWL value after product use, and T b is the TEWL value before the tape was peeled off. The data will be statistically analyzed using SPSS22.0 software, and the intergroup test will be performed using single-factor analysis of variance, and multiple comparisons will be performed using the LSD method. Both tests will be two-sided tests, with a test level of α=0.05.

[0093] C. Test Results Thirty subjects were recruited for this study, all of whom were Chinese, including 5 men and 25 women, aged 30-50, with an average age of 38.0±5.5 years. All 30 subjects completed the study. The results are as follows: C.1 Stratum corneum water content The moisture content of the stratum corneum is one of the indicators used to evaluate the repair efficacy of cosmetics. A higher value of this index indicates a higher moisture content in the stratum corneum. After creating a model of minor skin barrier damage using tape stripping, if the moisture content of the stratum corneum in the area where the product was used is significantly higher than in the area where the product was not used or the control area, the product can be proven to have repair efficacy. The measured moisture content of the stratum corneum of the subjects is shown in Figure 13. a: Three water samples, b: Three emulsion samples; c: three cream samples; Significant difference analysis between measurements of model control and blank control, #p<0.05; Significant difference analysis between measurements of sample 2, sample 3 and sample 1, *p<0.05. The changes in the moisture content of the stratum corneum of the subjects compared to before peeling are shown in Figure 14. a: Three water samples, b: three emulsion samples; c: three cream samples; Significant difference analysis of the change values ​​between model control and blank control, #p<0.05; Significant difference analysis of the change values ​​between Sample 2, Sample 3 and Sample 1, *p<0.05. Table 1 shows the percentage change in the average moisture content of the stratum corneum during the test period compared to before peeling.

[0094] Table 1. Results of the rate of change in the average moisture content of the stratum corneum compared to before peeling [Table 3]

[0095] Result description: (1) There was no significant difference in the moisture content of the stratum corneum in all test areas before tape removal. 2) Immediately after tape stripping, the percentage changes in stratum corneum moisture content in the blank control, model control, water 1, water 2, water 3, emulsion 1, emulsion 2, emulsion 3, cream 1, cream 2, and cream 3 areas were -3.4%, 128.6%, 116.9%, 127.5%, 123.3%, 130.4%, 126.4%, 127.5%, 127.9%, 129.1%, and 124.1%, respectively. The areas that had undergone tape stripping had a significant increase in stratum corneum moisture content compared to the blank control, but there was no significant difference between the areas that had undergone tape stripping. (3) Six hours after tape removal and initial product application, the changes in the moisture content of the stratum corneum in the blank control, model control, water 1, water 2, and water 3 areas were -4.6%, 71.0%, 84.0%, 94.3%, and 92.4%, respectively. On the first day of the test, the percentage changes in the moisture content of the stratum corneum in the blank control, model control, water 1, water 2, and water 3 areas were -4.6%, 29.2%, 25.0%, 33.3%, and 34.7%, respectively. On the third day of the test, the percentage changes in the moisture content of the stratum corneum in the blank control, model control, water 1, water 2, and water 3 regions were -4.7%, -36.2%, -27.7%, -27.0%, and -23.1%, respectively. On the seventh day of the test, the change rates of the stratum corneum moisture content in the blank control, model control, Water 1, Water 2, and Water 3 regions were -2.0%, -24.7%, -18.0%, -12.0%, and -2.1%, respectively; the stratum corneum moisture content of Water 2 was higher than that of Water 1, and the stratum corneum moisture content of Water 3 was significantly higher than that of Water 1; the change value of the stratum corneum moisture content of Water 2 was higher than that of Water 1, and the change value of the stratum corneum moisture content of Water 3 was significantly higher than that of Water 1. On the 10th day of the test, the change rates of the stratum corneum moisture content in the blank control, model control, Water 1, Water 2, and Water 3 regions were -0.6%, -13.5%, -1.6%, 7.2%, and 16.5%, respectively; the stratum corneum moisture content of Water 2 was higher than Water 1, and the stratum corneum moisture content of Water 3 was significantly higher than Water 1; the change value of the stratum corneum moisture content of Water 2 was higher than Water 1, and the change value of the stratum corneum moisture content of Water 3 was significantly higher than Water 1. (4) Six hours after tape removal and initial product application, the changes in the moisture content of the stratum corneum in the blank control, model control, emulsion 1, emulsion 2, and emulsion 3 areas were -4.6%, 71.0%, 91.8%, 98.6%, and 111.1%, respectively. On the first day of the test, the percentage changes in the moisture content of the stratum corneum in the blank control, model control, emulsion 1, emulsion 2, and emulsion 3 areas were -4.6%, 29.2%, 35.3%, 38.1%, and 39.7%, respectively. On the third day of the test, the percentage changes in the moisture content of the stratum corneum in the blank control, model control, emulsion 1, emulsion 2, and emulsion 3 areas were -4.7%, -36.2%, -23.7%, -24.9%, and -22.6%, respectively. On the seventh day of the test, the percentage changes in stratum corneum moisture content in the blank control, model control, emulsion 1, emulsion 2, and emulsion 3 areas were -2.0%, -24.7%, -6.5%, -2.8%, and 3.9%, respectively; the stratum corneum moisture content of emulsion 2 was higher than that of emulsion 1, and the stratum corneum moisture content of emulsion 3 was significantly higher than that of emulsion 1. On the 10th day of the study, the percentage changes in stratum corneum moisture content in the blank control, model control, emulsion 1, emulsion 2, and emulsion 3 areas were -0.6%, -13.5%, 15.3%, 18.6%, and 25.9%, respectively; the stratum corneum moisture content of emulsion 2 was higher than that of emulsion 1, and the stratum corneum moisture content of emulsion 3 was significantly higher than that of emulsion 1. (5) Six hours after tape removal and initial product application, the changes in the moisture content of the stratum corneum in the blank control, model control, cream 1, cream 2, and cream 3 areas were -4.6%, 71.0%, 92.3%, 95.8%, and 95.5%, respectively. On the first day of the test, the percentage changes in the moisture content of the stratum corneum in the blank control, model control, cream 1, cream 2, and cream 3 areas were -4.6%, 29.2%, 36.2%, 38.7%, and 43.5%, respectively. On the third day of the test, the percentage changes in the moisture content of the stratum corneum in the blank control, model control, cream 1, cream 2, and cream 3 areas were -4.7%, -36.2%, -22.1%, -21.6%, and -14.4%, respectively. On the 7th day of the test, the change rates of the stratum corneum moisture content in the blank control, model control, cream 1, cream 2, and cream 3 areas were -2.0%, -24.7%, -1.1%, 3.1%, and 12.8%, respectively; the stratum corneum moisture content of cream 2 was higher than that of cream 1, and the stratum corneum moisture content of cream 3 was significantly higher than that of cream 1; the change value of the stratum corneum moisture content of cream 2 was higher than that of cream 1, and the change value of the stratum corneum moisture content of cream 3 was significantly higher than that of cream 1. On the 10th day of the test, the change rates of the stratum corneum moisture content in the blank control, model control, cream 1, cream 2, and cream 3 areas were -0.6%, -13.5%, 21.6%, 25.2%, and 35.7%, respectively; the stratum corneum moisture content of cream 2 was higher than that of cream 1, and the stratum corneum moisture content of cream 3 was significantly higher than that of cream 1; the change value of the stratum corneum moisture content of cream 2 was higher than that of cream 1, and the change value of the stratum corneum moisture content of cream 3 was significantly higher than that of cream 1.

[0096] C.2 Transepidermal Water Loss (TEWL) Transepidermal water loss (TEWL) is one of the indices used to evaluate the repair effectiveness of cosmetics; a higher value indicates a faster rate of water evaporation from the skin surface and a poorer skin barrier function. After creating a model of slight skin barrier damage using tape stripping, if the TEWL in the area where the product was used is significantly reduced compared to the area where the product was not used or the control area, the product can be proven to have repair effectiveness. The TEWL measurements for the test areas of the subjects are shown in Figure 15. In Figure 15, a: Three water samples, b: three emulsion samples; c: three cream samples; Significant difference analysis between measurements of model control and blank control, #p<0.05; Significant difference analysis between measurements of sample 2, sample 3 and sample 1, *p<0.05. The TEWL recovery rate of the subjects is shown in Figure 16. In Figure 16, a: Three water samples, b: three emulsion samples; c: three cream samples; Significant difference analysis of repair rate between sample 2, sample 3 and sample 1, *p<0.05.

[0097] Result description: (1) There was no significant difference in TEWL in all test areas before tape removal. (2) Immediately after tape peeling, TEWL significantly increased in the tape-peeled areas compared with the blank control, but there was no significant difference between the tape-peeled areas. (3) Six hours after tape removal and initial product application, the TEWL recovery rates for the model control, water 1, water 2, and water 3 were 1.7%, 8.0%, 4.1%, and 2.2%, respectively. On the first day of the study, the TEWL recovery rates for the model control, Water 1, Water 2, and Water 3 were 8.9%, 22.5%, 21.3%, and 19.5%, respectively. On the third day of the study, the TEWL recovery rates for the model control, water 1, water 2, and water 3 were 41.3%, 49.0%, 47.3%, and 51.4%, respectively. On the seventh day of the study, the TEWL recovery rates for the model control, water 1, water 2, and water 3 were 74.4%, 83.2%, 82.5%, and 82.6%, respectively. On the 10th day of the study, the TEWL recovery rates for the model control, water 1, water 2, and water 3 were 79.4%, 84.8%, 87.2%, and 87.2%, respectively. (4) Six hours after tape removal and initial product application, the TEWL recovery rates for the model control, emulsion 1, emulsion 2, and emulsion 3 were 1.7%, 7.4%, 4.5%, and 4.2%, respectively. On the first day of the study, the TEWL recovery rates for the model control, emulsion 1, emulsion 2, and emulsion 3 were 8.9%, 20.0%, 11.4%, and 15.0%, respectively. On the third day of the study, the TEWL recovery rates for the model control, emulsion 1, emulsion 2, and emulsion 3 were 41.3%, 48.5%, 39.3%, and 51.2%, respectively. On the seventh day of the study, the TEWL recovery rates for the model control, emulsion 1, emulsion 2, and emulsion 3 were 74.4%, 75.6%, 76.2%, and 83.3%, respectively. On the 10th day of the study, the TEWL recovery rates for the model control, emulsion 1, emulsion 2, and emulsion 3 were 79.4%, 83.8%, 80.1%, and 84.0%, respectively. (5) Six hours after tape removal and initial product application, the TEWL recovery rates for the model control, Cream 1, Cream 2, and Cream 3 were 1.7%, 6.9%, -7.6%, and -0.6%, respectively. On the first day of the study, the TEWL recovery rates for the model control, Cream 1, Cream 2, and Cream 3 were 8.9%, 14.9%, 6.6%, and 13.5%, respectively. On the third day of the study, the TEWL recovery rates for the model control, Cream 1, Cream 2, and Cream 3 were 41.3%, 43.1%, 42.3%, and 44.3%, respectively. On the seventh day of the study, the TEWL recovery rates for the model control, Cream 1, Cream 2, and Cream 3 were 74.4%, 75.8%, 80.0%, and 82.7%, respectively. On the 10th day of the study, the TEWL recovery rates for the model control, Cream 1, Cream 2, and Cream 3 were 79.4%, 80.5%, 81.5%, and 85.9%, respectively.

[0098] D Conclusion In summary, the repair effectiveness of the test samples Water 2 is superior to Water 1, and Water 3 has significantly more repair effectiveness than Water 1; Emulsion 2 has superior repair effectiveness than Emulsion 1, and Emulsion 3 has significantly more repair effectiveness than Emulsion 1; Cream 2 has superior repair effectiveness than Cream 1, and Cream 3 has significantly more repair effectiveness than Cream 1.

[0099] [Industrial Applicability] The present inventors have found that α-ionone has a regulating and controlling effect on keratinocyte function, promoting the proliferation and migration of HaCaT cells and attenuating the inhibitory effect of norepinephrine on cell migration. Furthermore, α-ionone has been found to induce the gene expression of HAS-2 and HBD-2, promoting the synthesis of HA and HBD-2 by HaCaT cells, and attenuating the inhibitory effect of dexamethasone on HAS-2 and HBD-2 expression. The above findings by the present inventors suggest that α-ionone may have an effect of promoting skin wound repair.

[0100] Therefore, according to the present invention, α-ionone can be used as an active ingredient of a skin barrier repair agent in a topical skin preparation, and as an agent for repairing skin barrier dysfunction caused by the use of glucocorticoids and / or psychological stress. α-ionone is used in topical skin preparations, particularly cosmetics, to repair the skin barrier, for example, to moisturize the skin, promote repair of damaged skin, and promote repair of skin barrier damage caused by topical glucocorticoids and stress.

Claims

1. A skin barrier function repairing agent in an external skin preparation, characterized by containing α-ionone as an active ingredient acting on keratinocytes.

2. The skin barrier function repairing agent according to claim 1, wherein the α-ionone acts as a keratinocyte migration promoter.

3. The skin barrier function repairing agent according to claim 1, wherein the α-ionone acts as a keratinocyte proliferation promoter.

4. The skin barrier function repairing agent according to claim 1, wherein the α-ionone acts as an expression promoter of hyaluronic acid synthase-2 in keratinocytes.

5. The skin barrier function repairing agent according to claim 1, wherein the α-ionone acts as an agent for promoting the expression of human β-defensin-2 in keratinocytes.

6. The skin barrier function repair agent according to claim 1, characterized in that it is used as an agent for repairing skin barrier function disorders caused by the use of glucocorticoids and / or psychological stress.

7. The skin barrier function repairing agent according to claim 1, wherein the topical skin preparation is a cosmetic.

8. Use of α-ionone in the manufacture of cosmetics that promote skin barrier repair, wherein the promotion of skin barrier repair is achieved by at least one promoting action selected from the group consisting of promoting keratinocyte migration, promoting keratinocyte proliferation, promoting HAS-2 expression in keratinocytes, and promoting HBD-2 expression in keratinocytes.

9. Use of α-ionone in the manufacture of cosmetics to be applied to skin in a state of skin atrophy and / or skin barrier dysfunction caused by the use of glucocorticoids and / or psychological stress.

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