Composition for improving skin turnover cycle containing compound k

Abstract

The present disclosure relates to a composition for improving a skin turnover cycle, which comprises compound K. Specifically, the composition for improving a skin turnover cycle according to the present disclosure increases the expression of p63 and KLF4, which are markers associated with keratinocyte formation and stemness in the epidermal layer, so that keratinocytes can be continuously self-replicated and can undergo sustained keratin formation through cell division promotion, thereby effectively restoring a skin turnover cycle from the prolonged cycle caused by suppressed epidermal cell proliferation.

Description

Composition for improving skin turnover cycle containing compound K

[0001] The present disclosure relates to a composition for improving skin turnover cycle containing compound K.

[0002] Cross-reference to related applications

[0003] This application claims priority to Republic of Korea Patent Application No. 10-2024-0045898, filed April 4, 2024, the entire contents of which are incorporated herein by reference.

[0004] As skin tissue ages, its inflammatory response increases, and external stimuli such as UVB rays, fine dust, and blue light (high-energy visible light) are known to induce skin aging. These external stimuli are believed to further accelerate the natural aging reactions.

[0005] The epidermis maintains a constant skin turnover cycle through continuous keratin formation and shedding. If the skin turnover cycle is not maintained and becomes shorter or longer, the normal functions of the epidermis, including the skin's ability to defend itself against irritation, are lost. The skin turnover cycle is a repetitive process in which keratinocytes in the basal layer of the skin proliferate and differentiate, ascending to the stratum corneum to form new keratinocytes and shed the existing stratum corneum. The proliferation of keratinocytes is an important factor in regulating the skin turnover cycle. When keratinocytes age due to inflammation or external stimuli, their stem cell capacity for self-renewal decreases and their cell proliferation ability declines, preventing new keratinocytes from forming, causing the epidermis to thin and the skin turnover cycle to become longer.

[0006] Therefore, in order to improve the skin turnover cycle, it is necessary to improve the proliferation capacity of keratinocytes and thereby enhance their keratinogenic capacity.

[0007] [Prior Art Literature]

[0008] [Patent Document]

[0009] (Patent Document 1) Republic of Korea Patent Publication No. 10-2014-0003198

[0010] The present disclosure provides a composition that effectively restores the skin turnover cycle, which is prolonged due to inhibition of epidermal cell proliferation, by increasing the expression of p63 and KLF4, which are markers related to keratinogenesis and stem cell potential in the epidermal layer, thereby enabling keratinocytes to continuously self-replicate and promoting cell division to enable continuous keratinogenesis.

[0011] To achieve the above-mentioned purpose, one embodiment of the present invention provides a composition for improving skin turnover cycle containing compound K.

[0012] The composition for improving the skin turnover cycle according to the present disclosure can effectively restore the skin turnover cycle that is prolonged due to inhibition of epidermal cell proliferation by increasing the expression of p63 and KLF4, which are markers related to keratinogenesis and stem cell potential in the epidermal layer, thereby enabling keratinocytes to continuously self-replicate and promoting cell division to enable continuous keratinogenesis.

[0013] Figure 1 shows the results of a skin cytotoxicity test of compound K.

[0014] Figures 2a and 2b show the results of confirming changes in the expression of p63 and KLF4 in an environment of accelerated skin aging caused by UVB treatment.

[0015] Figures 3a and 3b show the results of confirming changes in the expression of p63 and KLF4 in an environment of accelerated skin aging caused by fine dust (PM2.5) treatment.

[0016] Figures 4a and 4b show the results of confirming changes in the expression of p63 and KLF4 in an environment of accelerated skin aging caused by blue light (HEV) treatment.

[0017] Figures 5a to 5c show the results of confirming the efficacy of compound K on artificial skin for accelerated skin aging by UVB treatment.

[0018] Hereinafter, the present invention will be described in detail.

[0019] In one aspect, the present invention may relate to a composition for improving skin turnover cycle containing compound K.

[0020] In one aspect, the present invention may relate to a method for improving skin turnover cycle, comprising applying or administering an effective amount of compound K to a subject in need thereof.

[0021] In one aspect, the present invention may relate to the use of compound K for preparing a composition for improving skin turnover cycle.

[0022] In one aspect, the present invention may relate to a compound K for use in improving skin turnover cycle.

[0023] In one aspect, the present invention may relate to non-therapeutic uses of compound K for improving skin turnover cycle.

[0024] The 'skin turnover cycle' is a cellular cycle that occurs in the epidermis, the most superficial layer of the skin. It refers to the process in which keratinocytes in the basal layer at the very bottom of the epidermis proliferate and differentiate, rise to the stratum corneum, form a new stratum corneum, accumulate, and then shed the existing stratum corneum. Epidermal turnover is affected by the speed at which new epidermis is created and the speed at which dead skin cells are shed, and both of these speeds are known to decrease with age. If the epidermal turnover cycle is prolonged due to poor new cell creation or poor stratum corneum shedding, the skin barrier function, which is the main function of the epidermis, will not function properly. Therefore, maintaining the skin turnover cycle is essential for the epidermis to function normally, and normalizing the speed at which new epidermis is created is important in improving the skin turnover cycle.

[0025] In one embodiment, the compound K may be represented by the following chemical formula 1.

[0026]

[0027] In one embodiment, the compound K may be contained in an amount of 0.0002 to 0.04 wt% relative to the total weight of the composition. Specifically, the compound K may be included in an amount of 0.0002 wt% or more, 0.0003 wt% or more, 0.0004 wt% or more, 0.0005 wt% or more, 0.0006 wt% or more, 0.0007 wt% or more, 0.0008 wt% or more, 0.0009 wt% or more, 0.001 wt% or more, 0.002 wt% or more, 0.003 wt% or more, 0.004 wt% or more, 0.005 wt% or more, 0.006 wt% or more, 0.007 wt% or more, 0.008 wt% or more, 0.009 wt% or more, 0.01 wt% or more, or 0.02 wt% or more, relative to the total weight of the composition, and further, the compound K may be included in an amount of 0.04 wt% or less, 0.03 wt% or less, relative to the total weight of the composition, It may be included in an amount of 0.02 wt% or less, 0.01 wt% or less, 0.009 wt% or less, 0.008 wt% or less, 0.007 wt% or less, 0.006 wt% or less, 0.005 wt% or less, 0.004 wt% or less, 0.003 wt% or less, 0.002 wt% or less, 0.001 wt% or less, 0.0009 wt% or less, 0.0008 wt% or less, 0.0007 wt% or less, 0.0006 wt% or less, 0.0005 wt% or less, 0.0004 wt% or less, or 0.0003 wt% or less.

[0028] In one embodiment, the compound K can increase the expression of p63.

[0029] In one embodiment, the compound K can increase the expression of KLF4.

[0030] p63 is a marker that regulates the division and differentiation of keratinocytes. A decrease in p63 inhibits keratinocyte division and thus keratinogenesis. KLF4 is a marker related to stem cell potential, and a decrease in KLF4 indicates a decrease in stem cell potential. Decreased expression of p63 and KLF4 in skin keratinocytes indicates a loss of the proliferative function of the epidermis. Therefore, the regulation of p63 and KLF4 expression is crucial for regulating the skin turnover cycle in the epidermis.

[0031] In one embodiment, the compound K can increase the expression of one or more of p63 and KLF4 in keratinocytes of the epidermal layer.

[0032] In one embodiment, the compound K can improve skin turnover cycle in the epidermal layer by increasing the expression of one or more of p63 and KLF4.

[0033] In one embodiment, the compound K can restore the prolonged skin turnover cycle in the epidermal layer by increasing the expression of one or more of p63 and KLF4.

[0034] In one embodiment, the daily dose of the compound K may be 0.5 mg / kg body weight to 10 mg / kg body weight. Specifically, the daily application amount, application amount or intake amount of the compound K is 0.5 mg / kg (body weight) or more, 1 mg / kg (body weight) or more, 1.5 mg / kg (body weight) or more, 2 mg / kg (body weight) or more, 2.5 mg / kg (body weight) or more, 3 mg / kg (body weight) or more, 3.5 mg / kg (body weight) or more, 4 mg / kg (body weight) or more, 4.5 mg / kg (body weight) or more, 5 mg / kg (body weight) or more, 5.5 mg / kg (body weight) or more, 6 mg / kg (body weight) or more, 6.5 mg / kg (body weight) or more, 7 mg / kg (body weight) or more, 7.5 mg / kg (body weight) or more, 8 mg / kg (body weight) or more, 8.5 mg / kg (body weight) or more, 9 mg / kg (body weight) or more or 9.5 mg / kg(body weight) or more, and further, the daily application amount of the compound K may be 10 mg / kg(body weight) or less, 9.5 mg / kg(body weight) or less, 9 mg / kg(body weight) or less, 8.5 mg / kg(body weight) or less, 8 mg / kg(body weight) or less, 7.5 mg / kg(body weight) or less, 7 mg / kg(body weight) or less, 6.5 mg / kg(body weight) or less, 6 mg / kg(body weight) or less, 5.5 mg / kg(body weight) or less, 5 mg / kg(body weight) or less, 4.5 mg / kg(body weight) or less, 4 mg / kg(body weight) or less, 3.5 mg / kg(body weight) or less, 3 mg / kg(body weight) or less, 2.5 mg / kg(body weight) or less, 2 mg / kg(body weight) or less, 1.5 mg / kg(body weight) or less or 1 May be less than mg / kg (body weight).

[0035] In one embodiment, the composition may be a cosmetic composition.

[0036] The cosmetic composition according to one embodiment of the present invention may contain a cosmetically or dermatologically acceptable medium or base. This may be provided in any formulation suitable for topical application, for example, in the form of a solution, gel, solid, anhydrous paste, an emulsion obtained by dispersing an oil phase in an aqueous phase, a suspension, a microemulsion, a microcapsule, a microgranule, or a vesicular dispersion of ionic (liposomes) and non-ionic types, or in the form of a cream, toner, lotion, powder, ointment, spray, or concealer stick. These compositions may be prepared according to methods conventional in the art. The cosmetic composition may also be used in the form of an aerosol composition further containing a propellant compressed in the form of a foam.

[0037] The above cosmetic composition is not particularly limited in its formulation and may be appropriately selected depending on the intended purpose. For example, it may be manufactured in the form of a skin lotion, skin softener, skin toner, lotion, milk lotion, moisture lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, foundation, essence, nutrition essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, cleansing water, powder, body lotion, body cream, body oil, body cleanser, and body essence.

[0038] When the formulation of the above cosmetic composition is a paste, cream or gel, animal fiber, plant fiber, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component.

[0039] When the formulation of the above cosmetic composition is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and particularly in the case of a spray, a propellant such as chlorofluorohydrocarbon, propane / butane or dimethyl ether may be additionally included.

[0040] When the formulation of the above cosmetic composition is a solution or emulsion, a solvent, solvating agent or emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.

[0041] When the formulation of the above cosmetic composition is a suspension, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth, etc. can be used as a carrier component.

[0042] When the formulation of the above cosmetic composition is a surfactant-containing cleansing, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, linolenic derivative, or ethoxylated glycerol fatty acid ester may be used as a carrier component.

[0043] The above cosmetic composition may further include functional additives and ingredients included in general cosmetic compositions in addition to the above compound K. The functional additives may include ingredients selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high molecular weight peptides, high molecular weight polysaccharides, sphingolipids, and seaweed extracts.

[0044] In addition to the functional additives, the composition may also contain ingredients typically found in cosmetic compositions, as needed. Other ingredients to be included include, but are not limited to, oil-based ingredients, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH regulators, alcohols, pigments, fragrances, blood circulation promoters, cooling agents, antiperspirants, purified water, and the like.

[0045] In one embodiment, the composition may be a non-therapeutic oral composition or a food composition.

[0046] The dosage form of the above non-therapeutic oral composition or food composition is not particularly limited, but may be formulated as, for example, tablets, granules, pills, powders, liquids such as drinks, caramels, gels, bars, tea bags, etc. In addition to the active ingredient, the non-therapeutic oral composition or food composition of each dosage form can be appropriately selected and combined by a person skilled in the art according to the dosage form or purpose of use by appropriately selecting the ingredients commonly used in the relevant field, and a synergistic effect may occur when applied simultaneously with other raw materials. The above composition can be administered in various ways such as simple ingestion, drinking, injection administration, spray administration, or squeeze administration.

[0047] In a non-therapeutic oral composition or food composition according to one embodiment of the present invention, the determination of the dosage or intake amount of the active ingredient is within the level of a person skilled in the art, and may vary depending on various factors such as the age, health condition, and complications of the subject to be administered or consumed.

[0048] A non-therapeutic oral composition or food composition according to one embodiment of the present invention may be, for example, various food products such as chewing gum, caramel products, candy, ice cream, and confectionery, beverage products such as soft drinks, mineral water, and alcoholic beverages, and oral products containing vitamins or minerals.

[0049] In addition to the above, the non-therapeutic oral composition or food composition according to one embodiment of the present invention may include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the non-therapeutic oral composition or food composition according to one embodiment of the present invention may include fruit pulp for the production of natural fruit juice and fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of these additives is not so critical, but is typically included in the range of 0 to about 60 parts by weight per 100 parts by weight of the composition according to one embodiment of the present invention.

[0050]

[0051] The present invention may provide, as an example, the following embodiments.

[0052] The first embodiment can provide a composition for improving skin turnover cycle containing compound K.

[0053] A second embodiment can provide a composition in which, in the first embodiment, the compound K is contained in an amount of 0.0002 to 0.04 wt% based on the total weight of the composition.

[0054] A third embodiment can provide a composition according to at least one of the first embodiment and the second embodiment, wherein the compound K increases the expression of p63.

[0055] A fourth embodiment can provide a composition according to one or more of the first to third embodiments, wherein the compound K increases the expression of KLF4.

[0056] A fifth embodiment can provide a composition according to one or more of the first to fourth embodiments, wherein the compound K improves the skin turnover cycle in the epidermal layer.

[0057] A sixth embodiment can provide a composition according to one or more of the first to fifth embodiments, wherein the compound K restores a prolonged skin turnover cycle in the epidermal layer.

[0058] The seventh embodiment can provide a composition according to at least one of the first to sixth embodiments, wherein the daily application amount of the compound K is 0.5 mg / kg (body weight) to 10 mg / kg (body weight).

[0059] The eighth embodiment can provide a composition that is a cosmetic composition according to one or more of the first to seventh embodiments.

[0060] The ninth embodiment can provide a composition that is a non-therapeutic oral composition according to one or more of the first to eighth embodiments.

[0061]

[0062] Hereinafter, the present invention will be described in more detail through experimental examples. However, these experimental examples are provided merely to facilitate understanding of the present invention, and the scope of the present invention is not limited to these experimental examples. Modifications, substitutions, and insertions commonly known in the art may be performed, and such modifications are also included within the scope of the present invention.

[0063]

[0064] [Experimental Example 1] Skin Cell Toxicity Experiment

[0065] To determine the cytotoxicity of compound K on human epidermal keratinocytes, 1x10 4 After seeding, the cells were cultured for 24 hours. After that, the cells were treated with the final concentration of Compound K per well of 0.5 ppm, 1 ppm, 2 ppm, and 4 ppm, respectively, and cultured for 24 hours. 10 μl Cell Counting Kit-8 (CCK-8) solution was treated to each well and cultured at 37°C for 2 hours, and the absorbance was measured at 450 nm. The cell proliferation and toxicity effects were calculated as a percentage based on the absorbance of the control group. The results are shown in Fig. 1.

[0066] From the results in Fig. 1, it was confirmed that compound K did not cause cytotoxicity at concentrations of 0.5 ppm to 4 ppm.

[0067]

[0068] [Experimental Example 2] Experiment to accelerate skin aging

[0069] To confirm the acceleration of skin aging due to external stimuli, human epidermal keratinocytes were seeded at 1x10 in a 96-well plate. 4 After seeding, the cells were cultured for 24 hours. Afterwards, an inflammatory response was induced by treating the medium with IL-17A, an inflammatory aging factor, at a concentration of 50 μg / ml. After 24 hours, the culture medium was removed and replaced with PBS, and then exposed to ultraviolet (UVB) light at 20 mJ / cm 2 Investigate or treat 100μg / ml of fine dust (PM2.5) or 40 J / cm of blue light (HEV) 2, and cultured for an additional 24 hours after replacing the medium with IL-17A at a concentration of 50 μg / ml. After that, total RNA was extracted from skin keratinocytes using an RNA extraction kit (Quiagen, RNease Mini kit), and cDNA was synthesized from the extracted RNA (Invitrogen, SuperScript VILO Master Mix). Then, the expression levels of p63 and KLF4 were observed using a 7500 Fast Real-time PCR System (Thermo Fisher Scientific) and a Taqman probe (Applied Biosystems). The results are shown in Figs. 2a and 2b (ultraviolet treatment), 3a and 3b (fine dust treatment), and 4a and 4b (blue light treatment).

[0070] From the results of Figures 2a and 2b, it was confirmed that the expression of p63 and KLF4 was significantly reduced in an accelerated aging environment treated with UVB after IL-17A treatment, compared to when treated with only IL-17A or only with ultraviolet light (UVB).

[0071] Similarly, from the results of FIGS. 3a and 3b and 4a and 4b, it was confirmed that the expression of p63 and KLF4 was significantly reduced in the accelerated aging environment where PM2.5 or HEV was treated after IL-17A treatment, compared to when only IL-17A was treated or only fine dust (PM2.5) or blue light (HEV) was treated.

[0072] From the above experimental results, it was found that the expression of p63 and KLF4 was more significantly reduced in an environment where aging was accelerated by external stimuli (ultraviolet rays, fine dust, blue light) in addition to general aging.

[0073]

[0074] [Experimental Example 3] Experiment to confirm the efficacy of compound K at different concentrations on aging skin caused by UV treatment.

[0075] To determine the efficacy of compound K at different concentrations on aged skin caused by UV treatment, human epidermal keratinocytes were seeded in a 96-well plate at a density of 1x10 4 After seeding, the cells were cultured for 24 hours and then treated with compound K at concentrations of 0.5 ppm, 1 ppm, 2 ppm, and 4 ppm. After 30 minutes, IL-17A was additionally treated to the medium at a concentration of 50 μg / ml. After 24 hours, the culture medium was removed, replaced with PBS, and exposed to ultraviolet (UVB) light at 20 mJ / cm 2 and cultured for 24 hours. Afterwards, total RNA was extracted from skin keratinocytes using an RNA extraction kit (Quiagen, RNease Mini kit), and cDNA was synthesized from the extracted RNA (Invitrogen, SuperScript VILO Master Mix). Then, the expression levels of p63 and KLF4 were observed using a 7500 Fast Real-time PCR System (Thermo Fisher Scientific) and Taqman probe (Applied Biosystems). The results are shown in Table 1 below.

[0076] Stimulus treatment concentration p63 expression level (Fold) KLF4 expression level (Fold) Control (untreated) - (unstimulated) - 11 Control (untreated) IL-17A + UVB - 0.64 0.58 Compound K 0.5 ppm 0.60 0.69 1 ppm 0.57 0.822 ppm 0.73 1.01 4 ppm 0.75 0.98 EGCG 10 μM 0.43 1.04

[0077] From the results in Table 1, it was confirmed that when skin keratinocytes were pretreated with 1 ppm, 2 ppm, and 4 ppm of compound K, respectively, and then treated with IL-17A and UVB to accelerate aging, the reduced expression of p63 and KLF4 was restored. In particular, when treated with 2 ppm and 4 ppm, the effect of restoring p63 expression was significantly greater than that of the positive control, EGCG, and the effect of restoring KLF4 expression was similar to that of the positive control, EGCG. Among them, it was confirmed that the expression restoration rate of p63 and KLF4 was the best when treated with 2 ppm.

[0078]

[0079] [Experimental Example 4] Experiment to Confirm the Efficacy of Compound K on Aged Skin Treated with Fine Dust

[0080] To confirm the efficacy of compound K against aging caused by fine dust (PM2.5), human epidermal keratinocytes were seeded in a 96-well plate at a density of 1x10 4After seeding, the cells were cultured for 24 hours and then treated with compound K at a concentration of 2 ppm. After 30 minutes, IL-17A was additionally treated to the medium at a concentration of 50 μg / ml, and after 24 hours, the culture medium was removed and replaced with PBS, and then 100 μg / ml of fine dust (PM2.5) was treated, and the medium was replaced with IL-17A at a concentration of 50 μg / ml and compound K at a concentration of 2 ppm, and then cultured for an additional 24 hours. Afterwards, total RNA was extracted from skin keratinocytes using an RNA extraction kit (Quiagen, RNease Mini kit), and cDNA was synthesized from the extracted RNA (Invitrogen, SuperScript VILO Master Mix), and then the expression levels of p63 and KLF4 were observed using a 7500 Fast Real-time PCR System (Thermo Fisher Scientific) and Taqman probe (Applied Biosystems). 10 μM EGCG was used as a positive control. The results are shown in Table 2 below.

[0081] Stimulated p63 expression level (Fold) KLF4 expression level (Fold) Control group (untreated) - (unstimulated) 11 Control group (untreated) IL-17A + PM2.5 0.6 10.39 Compound K 0.78 0.59 EGCG 0.65 0.87

[0082] From the results in Table 2, when skin keratinocytes were pretreated with 2 ppm of compound K and then treated with IL-17A and PM2.5 to induce accelerated skin aging, it was confirmed that compound K significantly suppressed the decrease in the expression of p63 and KLF4, and this effect was similar to or even superior to that of EGCG, the positive control.

[0083]

[0084] [Experimental Example 5] Experiment to Confirm the Efficacy of Compound K on Aged Skin Treated with Blue Light

[0085] To determine the efficacy of compound K against blue light (HEV)-induced aging, human epidermal keratinocytes were seeded in a 96-well plate at a density of 1x10 4 After seeding, the cells were cultured for 24 hours and then treated with compound K at a concentration of 2 ppm. After 30 minutes, IL-17A was additionally treated to the medium at a concentration of 50 μg / ml. After 24 hours, the culture medium was removed and replaced with PBS, and then exposed to blue light (HEV) at 40 J / cm. 2 , and the medium was replaced with a medium containing 50 μg / ml of IL-17A and 2 ppm of compound K, and then cultured for an additional 24 hours. Afterwards, total RNA was extracted from skin keratinocytes using an RNA extraction kit (Quiagen, RNease Mini kit), and cDNA was synthesized from the extracted RNA (Invitrogen, SuperScript VILO Master Mix), and the changes in the expression levels of p63 and KLF4 were observed using a 7500 Fast Real-time PCR System (Thermo Fisher Scientific) and a Taqman probe (Applied Biosystems). 10 μM EGCG was used as a positive control. The results are shown in Table 3 below.

[0086] Stimulated p63 expression level (Fold) KLF4 expression level (Fold) Control group (untreated) - (unstimulated) 11 Control group (untreated) IL-17A + HEV 0.7 3 0.60 Compound K 0.9 1 0.95 EGCG 0.8 9 1.06

[0087] From the results in Table 3, when skin keratinocytes were pretreated with 2 ppm of compound K and then treated with IL-17A and HEV to induce accelerated skin aging, it was confirmed that compound K significantly suppressed the decrease in the expression of p63 and KLF4, and this effect was similar to or even superior to that of EGCG, the positive control.

[0088]

[0089] [Experimental Example 6] Experiment to Confirm the Efficacy of Compound K on Cell Proliferation

[0090] To investigate the efficacy of compound K on cell proliferation in skin accelerated aging conditions, human epidermal keratinocytes were seeded at 1x10 in a 96-well plate. 4 After seeding, the cells were cultured for 24 hours. Afterwards, an inflammatory response was induced by treating the medium with IL-17A, an inflammatory aging factor, at a concentration of 50 μg / ml. After 24 hours, the culture medium was removed and replaced with PBS, and then exposed to ultraviolet (UVB) light at 20 mJ / cm 2 Investigate or treat 100μg / ml of fine dust (PM2.5) or 40 J / cm of blue light (HEV) 2 We investigated, and after changing the medium to contain 50 μg / ml of IL-17A and 2 ppm of compound K, the cells were cultured for an additional 24 hours. After that, 10 μl of Cell Counting Kit-8 (CCK-8) solution was treated to each well, and the cells were cultured at 37°C for 2 hours, and the absorbance was measured at 450 nm. The cell proliferation effect was calculated as a percentage based on the absorbance of the control group, and the results are shown in Table 4 below.

[0091] Sample Stimulation Cell Count (%) DMSO-100 DMSOIL-17A + UVB68 Compound K115 EGCG95 DMSOIL-17A + PM2.575 Compound K109 EGCG101 DMSOIL-17A + HEV80 Compound K112 EGCG106

[0092] As shown in Table 4, when accelerated skin aging was induced by treatment with inflammatory factors (IL-17A) and aging-accelerating factors (UVB, PM2.5, HEV) in skin keratinocytes, the decreased cell proliferation was significantly restored by Compound K, and it was confirmed that the cell proliferation restoration efficacy of Compound K was much superior to that of the positive control, EGCG.

[0093]

[0094] [Experimental Example 7] Experiment to Confirm the Efficacy of Compound K on Artificial Skin Aged by UV Treatment

[0095] To confirm the efficacy of compound K on aging artificial skin by UV treatment, compound K was treated in the medium at a concentration of 2 ppm in an artificial skin epidermal model (MatTek Life Science). After 30 minutes, IL-17A was additionally treated in the medium at a concentration of 100 μg / ml. After 24 hours, the culture medium was removed and replaced with PBS, and then exposed to UV light (UVB, Bio-Sun, Viber) at 100 mJ / cm 2 After examining, the medium was replaced with a medium containing IL-17A at a concentration of 100 μg / ml and compound K at a concentration of 2 ppm, and cultured for an additional 48 hours. After that, paraffin blocks were made with artificial skin tissue, and the amounts of Ki67, p63, and KLF4 were measured by staining them with antibodies (Abcam, NOVUS BIOLOGICALS). Ki67 is a representative marker of cell proliferation, and the recovery of reduced Ki67 expression means that cell proliferation capacity is normalized. The results are shown in Figs. 5a to 5c, respectively.

[0096] From the results of Figures 5a to 5c, it was confirmed that when artificial skin epidermal tissue was pretreated with compound K and then treated with IL-17A and UVB to accelerate aging, the reduced expression of Ki67, p63, and KLF4 was significantly restored. (Blue: DAPI (nuclear staining), green: KLF4).

[0097]

[0098] From the above experimental results, it was found that Compound K effectively suppressed the decrease in expression of Ki67, p63, and KLF4 in an environment where aging was accelerated by external stimuli (ultraviolet rays, fine dust, blue light) in addition to general aging. Through this, it was found that Compound K can effectively restore the skin turnover cycle that is prolonged due to inhibition of epidermal cell proliferation by enabling keratinocytes in the epidermal layer to continuously self-replicate and promoting cell division to enable continuous keratinogenesis.

[0099]

[0100] [Formulation Example 1] Lotion

[0101] Ingredients (weight) Compound K 0.03 L-ascorbic acid-2-magnesium phosphate 1.00 Soluble collagen (1% aqueous solution) 1.00 Sodium citrate 0.10 Citric acid 0.05 Licorice extract 0.20 1,3-butylene glycol 3.00 Remaining tablet amount

[0102] [Formulation Example 2] Cream

[0103] Ingredient content (weight) Compound K0.03 Polyethylene glycol monostearate 2.00 Glycerin 5.00 Cetyl alcohol 4.00 Squalene 4.00 Liquid paraffin 10.00 Tris-2-ethylhexane glyceryl 6.00 Sphingoglycolipid 1.00 1,3-butylene glycol 7.00 Remaining tablet amount

[0104] [Formulation Example 3] Pack

[0105] Ingredients (weight) Compound K0.03 Polyvinyl alcohol 13.00 L-ascorbic acid-2-phosphate magnesium salt 1.00 Lauroyl hydroxyproline 1.00 Water-soluble collagen (1% aqueous solution) 2.00 1,3-butylene glycol 3.00 Ethanol 5.00 Remaining tablet amount

[0106] [Formulation Example 4] Toner

[0107] Ingredient content (weight) Compound K 0.03 Glycerin 3.0 Butylene glycol 2.0 Propylene glycol 2.0 Carboxyvinyl polymer 0.1 PEG-12 Nonylphenyl ether 0.2 Polysorbate-80 0.4 Ethanol 10.0 Triethanolamine 0.1 Preservative, colorant, fragrance Appropriate amount of purified water remaining

[0108]

[0109] While specific portions of this specification have been described in detail above, it should be apparent to those skilled in the art that these specific descriptions are merely preferred implementation examples and do not limit the scope of this specification. Therefore, the substantial scope of this specification is defined by the appended claims and their equivalents.

Claims

1. A composition for improving skin turnover cycle containing compound K.

2. In paragraph 1, A composition wherein the compound K is contained in an amount of 0.0002 to 0.04 wt% based on the total weight of the composition.

3. In paragraph 1, The above compound K is a composition that increases the expression of p63.

4. In paragraph 1, The above compound K is a composition that increases the expression of KLF4.

5. In paragraph 1, The above compound K is a composition that improves the skin turnover cycle in the epidermal layer.

6. In paragraph 1, The above compound K is a composition that restores the prolonged skin turnover cycle in the epidermal layer.

7. In paragraph 1, A composition wherein the daily application amount of the compound K is 0.5 mg / kg (body weight) to 10 mg / kg (body weight).

8. In any one of paragraphs 1 to 7, A composition, which is a cosmetic composition.

9. In any one of paragraphs 1 to 7, A composition which is a non-therapeutic oral composition.

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