Peptide derivative and cosmetic composition comprising same

Abstract

The present invention relates to a peptide derivative and a cosmetic composition comprising same. The peptide derivative according to the present invention not only reduces senescent cells and increases collagen synthesis in the dermis, but also increases the expression of collagen-17 and VEGF expressed at the boundary between the dermis and the epidermis, thereby exhibiting skin anti-aging and anti-wrinkle effects. Therefore, the peptide derivative according to the present invention can be effectively used as a functional cosmetic material in a cosmetic composition, particularly a cosmetic composition for skin anti-aging or anti-wrinkle.

Description

Peptide derivative and cosmetic composition containing the same

[0001] The present invention relates to a peptide derivative and a cosmetic composition containing the same, and more specifically, to a peptide derivative and a cosmetic composition containing the same that exhibits anti-aging and wrinkle-improving effects by reducing senescent cells, increasing collagen synthesis in the dermis, and increasing the expression of collagen-17 and VEGF expressed at the boundary between the dermis and the epidermis.

[0002] Cell proliferation ceases upon reaching the limit of replication potential, namely the Hayflick limits, or upon exposure to various aging stress factors. Cells whose proliferation has stopped are called senescent cells, and these senescent cells induce tissue aging by secreting harmful factors such as inflammatory cytokines, immunomodulatory factors, and proteases.

[0003] The skin is composed of the epidermis, dermis, and subcutaneous tissue in descending order from the surface. As skin aging occurs, the thickness of the epidermis decreases, and collagen and elastic fibers within the dermis decline. The dermis consists of fibroblasts, collagen, elastic fibers, and the extracellular matrix. Among these, fibroblasts play a key role in the production, maintenance, and degradation of collagen, elastic fibers, and the extracellular matrix. However, as aging begins, the number of fibroblasts decreases and their productivity drops sharply, preventing the production of new collagen and elastic fibers. Consequently, skin wrinkles increase.

[0004] Recently, senolytic peptides have been suggested as ingredients to inhibit skin aging.

[0005] For example, Korean Patent Publication No. 10-2018-0108970 discloses a cosmetic composition for preventing and improving skin aging or skin wrinkles containing heptapeptide monomers and dimers as active ingredients.

[0006] However, there is still an urgent need for the development of new peptide derivatives that reduce senescent cells and increase collagen synthesis to exhibit anti-aging and wrinkle-improving effects on the skin.

[0007] The objective of the present invention is to provide a peptide derivative that exhibits skin anti-aging and wrinkle improvement effects by reducing aging cells and increasing collagen synthesis.

[0008] Another objective of the present invention is to provide a cosmetic composition comprising the peptide derivative as an active ingredient.

[0009] One embodiment of the present invention relates to a peptide derivative represented by the following chemical formula 1.

[0010] [Chemical Formula 1]

[0011]

[0012]

[0013] The peptide derivative according to the present invention can be prepared by synthesizing a peptide composed of Met-Glu-Glu-Pro and then reacting it with nicotinic acid in an amide bond reaction.

[0014] The above peptide may be produced by extracting a protein from the body and treating it with a proteolytic enzyme to reduce its molecular weight, or by using a genetic recombination and protein expression system, or preferably by a chemical synthesis method using a peptide synthesizer, etc.

[0015] The peptide derivative according to the present invention is, for example,

[0016] (1) A step of obtaining an NH2-protected peptide-resin by a conventional solid phase peptide synthesis (SPPS);

[0017] (2) a step of reacting the obtained NH2-protected peptide-resin with nicotinic acid; and

[0018] (3) It can be manufactured including a step of removing the resin.

[0019]

[0020] If a functional group is present on the side chain of an amino acid residue constituting the peptide, the peptide can be synthesized using the amino acid in which the functional group is protected in step (1), and the protecting group attached to the functional group is removed in step (3).

[0021] One specific example of the process for preparing a peptide derivative according to the present invention using an amino acid with a protected functional group is briefly shown in Reaction Scheme 1 below.

[0022] [Reaction Equation 1]

[0023]

[0024]

[0025] One embodiment of the present invention relates to a cosmetic composition comprising the above-mentioned peptide derivative, in particular a cosmetic composition for preventing skin aging or improving wrinkles.

[0026] The peptide derivative according to the present invention reduces senescent cells and increases collagen synthesis in the dermis, as well as increases the expression of collagen-17 and VEGF expressed at the boundary between the dermis and the epidermis, thereby exhibiting anti-aging and wrinkle-improving effects on the skin.

[0027] The cosmetic composition of the present invention may preferably contain 0.0001 to 10.0 weight% of a peptide derivative according to the present invention as an active ingredient. The content of the active ingredient may be appropriately determined according to the purpose of use.

[0028] The cosmetic composition of the present invention may include, in addition to the peptide derivative according to the present invention as an active ingredient, ingredients commonly used in cosmetic compositions, such as conventional auxiliary agents like antioxidants, stabilizers, preservatives, and fragrances, and a carrier.

[0029] The cosmetic composition of the present invention can be prepared in any formulation commonly used in the art, for example, as a solution, suspension, emulsion, paste, gel, cream, powder, spray, etc.

[0030] In the case where the formulation of the present invention is a paste, cream, or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide, etc. may be used as a carrier component.

[0031] In the case where the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, etc. may be used as a carrier component, and in particular, in the case of a spray, it may additionally include a propellant such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether.

[0032] In the case where the formulation of the present invention is a solution or an emulsion, a solvent, a solubilizing agent, or an emulsifying agent, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, propylene glycol, glycerol fatty acid ester, sorbitan fatty acid ester, etc., may be used as a carrier component.

[0033] In the case where the formulation of the present invention is a suspension, liquid diluents such as water, ethanol, or propylene glycol, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, or polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, tracanth, etc. may be used as carrier components.

[0034] The cosmetic composition of the present invention can be applied to cosmetics such as skin toner, lotion, cream, pack, color cosmetics, sunscreen, face powder, compact, lipstick, eyeshadow, etc.

[0035] The peptide derivative according to the present invention reduces senescent cells and increases collagen synthesis in the dermis, as well as increases the expression of collagen-17 and VEGF expressed at the boundary between the dermis and the epidermis, thereby exhibiting anti-aging and wrinkle-improving effects on the skin.

[0036] Accordingly, the peptide derivative according to the present invention can be effectively used as a functional cosmetic material in cosmetic compositions, particularly in cosmetic compositions for preventing skin aging or improving wrinkles.

[0037] Figure 1 is a microscopic image showing the expression pattern of SA-β-Gal, an aging-related marker, in dermal-derived fibroblasts through X-Gal staining.

[0038] Figure 2 is a graph showing the results of evaluating the collagen synthesis ability in the dermis of the peptide derivative according to the present invention in a cell aging model induced by Doxorubicin.

[0039] Figure 3 is a microscopic image showing the results of evaluating the collagen synthesis ability of the peptide derivative according to the present invention in human-derived skin tissue.

[0040] Figure 4 is a graph showing the results of evaluating the collagen synthesis ability in the dermis of the peptide derivative according to the present invention in human-derived skin tissue.

[0041] Figure 5 is a microscopic image showing the results of evaluating the synthesis ability of collagen-17 expressed at the boundary between the dermis and epidermis of the peptide derivative according to the present invention in human-derived skin tissue.

[0042] Figure 6 is a graph showing the results of evaluating the synthesis ability of collagen-17 expressed at the dermal-epidermal boundary of the peptide derivative according to the present invention in human-derived skin tissue.

[0043] Figure 7 is a graph showing the results of evaluating the IL-8 expression ability in the dermis of the peptide derivative according to the present invention in a cell aging model induced by Doxorubicin.

[0044] Figure 8 is a microscopic image showing the results of evaluating the synthesizing ability of VEGF expressed at the boundary between the dermis and epidermis of a peptide derivative according to the present invention in human-derived skin tissue.

[0045] Figure 9 is a graph showing the results of evaluating the synthesizing ability of VEGF expressed at the boundary between the dermis and epidermis of the peptide derivative according to the present invention in human-derived skin tissue.

[0046] The present invention will be explained more specifically below through examples. These examples are intended solely to illustrate the present invention, and it is obvious to those skilled in the art that the scope of the present invention is not limited to these examples.

[0047]

[0048] Example 1: Preparation of a peptide derivative represented by Chemical Formula 1

[0049] The peptide was synthesized by the solid-phase method (Fmoc Solid Phase Peptide Synthesis) using Fmoc (9-fluorenylmethoxycarbonyl) as the protecting group for the Nα-amino acid. The peptide was extended according to the HOBt-DIC (N-hydroxybenzotriazole-diisopropylcarbodiimide) method [Reference: Wang C. Chan, Peter D. White, "Fmoc solid phase peptide synthesis" Oxford].

[0050] Specifically, 2.08 g (3 mmole) of 2-chlorotrityl chloride resin was swollen in 60 ml of the solvent dimethylformamide (N,N'-dimethylformamide, DMF) in a glass reactor for 30 minutes, after which the solvent was removed. 2.02 g (2 equivalents) of Fmoc-Pro-OH and 3.14 ml (8 equivalents) of diisopropylethylamine (N,N-diisopropylethylamine, DIPEA) were dissolved in 70 ml of dichloromethane (DCM) and added, and the mixture was reacted at room temperature for 12 hours. The reaction solution was removed by filtering, and the synthesized resin was washed sequentially with 50 ml of DCM, methyl alcohol (MeOH), DCM, and DMF, respectively.

[0051] 70 ml of 20% piperidine DMF solution was added to a proline-bound resin protected by Fmoc amino groups and reacted at room temperature for 5 minutes, after which the reaction solution was removed by filtering. 70 ml of 20% piperidine DMF solution was added once more and reacted at room temperature for 5 minutes. The reaction solution was removed by filtering, and the synthesized resin was washed sequentially with 500 ml each of DCM, MeOH, DCM, and DMF.

[0052] 5.11 g (4 equivalents) of Fmoc-Glu(tBu)-OH, 1.62 g (4 equivalents) of HOBt, and 1.86 ml (4 equivalents) of DIC were dissolved in 60 ml of DMF and added to the Fmoc-removed proline resin, and the mixture was reacted at room temperature for 4 hours. The reaction solution was filtered to remove the reaction solution, and the synthesized resin was washed sequentially with 50 ml each of DCM, MeOH, DCM, and DMF.

[0053] In this process, glutamic acid (Fmoc-Glu(tBu)-OH, 5.11 g, 4 equivalents), methionine (Fmoc-Met-OH, 4.46 g, 4 equivalents), and nicotinic acid (1.48 g, 4 equivalents) were reacted sequentially to complete the peptide basic backbone.

[0054] After vacuum drying the peptide resin (nicotinoyl-Met-Glu(tBu)-Glu(tBu)-Pro-trityl resin) synthesized above, 50 ml of cleavage cocktail (trifluoroacetic acid : triisopropylsilane : DW = 95 : 2.5 : 2.5, volume ratio) was added and reacted at room temperature for 3 hours to remove the t-butyl (tBu) group, which is a protecting group of amino acid residues, and to separate the peptide derivative represented by Chemical Formula 1 from the resin. Afterward, the reaction solution was filtered to collect the reaction mixture, and 400 ml of cold diethyl ether was added to precipitate the product. The solid product was collected using a centrifuge and washed three times with 200 ml of diethyl ether. The obtained solid product was purified using reverse phase high performance liquid chromatography (column C18, 10 μm) and freeze-dried to obtain 1.1 g of a peptide derivative represented by Chemical Formula 1 (molecular weight measured by LC mass: 609.65) with a 60% yield.

[0055]

[0056] Experimental Example 1: Evaluation of Senescent Cell Reduction in a Doxorubicin-Induced Cell Aging Model

[0057] The aging-reducing effect was evaluated by confirming the expression pattern of SA-β-Gal (senescence associated-β-galactosidase), an aging-related marker, in human dermal fibroblasts (hDF) through X-Gal staining.

[0058] Specifically, human dermal fibroblasts (hDF) were divided into non-senescent cells (blank) and cells senescent-induced with doxorubicin, and each was placed on a 2-chamber slide (Labtek) at a rate of 2.5 × 10⁶ 4 Cells were evenly seeded and cultured in DMEM (Dulbecco's Modified Eagle Media, Gibco BRL) medium for 24 hours in an incubator at 37°C under 5% CO2 conditions. During this process, senescence was induced by treatment with 200 nM doxorubicin. The peptide derivative represented by Chemical Formula 1 was dissolved in DMSO to a concentration of 10 mM to form a concentrate, which was then diluted to a concentration of 100 μM in supplement-free medium and added to each well, followed by incubation for 48 hours. After incubation, the medium was removed and the cells were washed once with PBS. Subsequently, cell fixation and staining were performed using a senescence-associated-β-galactosidase (SA-β-Gal) staining kit (Cell Signaling). Under a microscope at a 200X magnification, the blue β-galactosidase expression pattern, an indicator of senescence, was observed.

[0059] The results are shown in Fig. 1. In Fig. 1, (a) is a non-aging cell (blank), (b) is an aging cell treated with doxorubicin alone, and (c) is an aging cell treated with doxorubicin and a peptide derivative represented by Chemical Formula 1 simultaneously.

[0060] As shown in Figure 1, a significant increase in SA-β-Gal staining was observed in a cell aging model induced by doxorubicin, and the effect of significantly inhibiting SA-β-Gal staining by treatment with the peptide derivative represented by Formula 1 of the present invention was confirmed. That is, a significant decrease in aging cells was observed by treatment with the peptide derivative represented by Formula 1 of the present invention.

[0061] Therefore, it can be seen that the peptide derivative represented by Chemical Formula 1 of the present invention is effective in preventing skin aging.

[0062]

[0063] Experimental Example 2: Evaluation of dermal collagen synthesis in a doxorubicin-induced cellular aging model

[0064] Using a doxorubicin-induced cell aging model in human dermal fibroblasts (hDF), we analyzed whether treatment with a peptide derivative represented by Formula 1 of the present invention is effective in increasing dermal collagen.

[0065] Specifically, human dermal fibroblasts (hDF) were divided into non-senescent cells (blank) and cells senescent-induced with doxorubicin, and each was placed in a 12-well plate at a rate of 5 × 10⁶ 4Cells were evenly seeded and cultured in DMEM (Dulbecco's Modified Eagle Media, Gibco BRL) medium for 24 hours in an incubator at 37°C under 5% CO2 conditions. During this process, aging was induced by treatment with 200 nM of doxorubicin. The peptide derivative represented by Formula 1 of the present invention was dissolved in DMSO to a concentration of 10 mM to form a concentrate, which was then diluted to a concentration of 100 μM in supplement-free medium and applied to each well, followed by incubation for 72 hours. The culture supernatant obtained after incubation was analyzed using a type 1 collagen ELISA kit. First, antibodies against type 1 collagen were coated onto a 96-well plate and sufficiently blocked using a blocking buffer. Subsequently, the fibroblast culture supernatant was applied to the 96-well plate coated with the type 1 collagen antibody and reacted at room temperature for 2 hours. After the reaction was complete, the supernatant was removed and the plates were washed with PBS (PBST) solution containing 0.05% Tween 20. Subsequently, biotin-conjugated secondary antibodies were applied to a 96-well plate and incubated at room temperature for 1 hour. Once the reaction was finished, the remaining supernatant was removed and the plates were washed with PBST using the same method as before. Afterward, SA-HRP (Streptavidin-Horseradish peroxidase, Sigma) was conjugated to measure the conjugated collagen. To confirm the color reaction, TMB (3,3'-5,5' tetramethylbenzidine, Sigma) was added as a substrate and incubated at room temperature in the dark for 15 minutes. The reaction was then stopped with 2N hydrochloric acid, and the absorbance was measured at 450 nm. For comparison of effects, the degree of type 1 collagen biosynthesis for the argireline-treated group was also measured.

[0066] The results are shown in Figure 2.

[0067] As shown in Figure 2, collagen synthesis was reduced in cells induced with doxorubicin (control group) compared to non-aging cells (blank), but collagen synthesis was increased in the treatment group of the peptide derivative (compound) represented by Formula 1 of the present invention. In particular, the treatment group of the peptide derivative (compound) represented by Formula 1 of the present invention showed superior collagen synthesis ability compared to the Argireline treatment group.

[0068]

[0069] Experimental Example 3: Evaluation of Collagen Synthesis Ability in Skin Tissue

[0070] To analyze whether treatment with a peptide derivative represented by Chemical Formula 1 of the present invention affects the increase of collagen in the dermis, the degree of collagen expression was analyzed using human-derived skin tissue.

[0071] Specifically, NativeSkin access®, manufactured by Genoskin of France for research purposes, was used for the evaluation. The received skin tissues were stabilized for one hour before the evaluation was conducted. Ultraviolet (UVB) radiation of 50 mJ / cm² was applied to the tissues, excluding the normal tissue group. 2After irradiation, approximately 20 μl of a solution of the peptide derivative represented by Formula 1 of the present invention, diluted in distilled water to concentrations of 20 ppm and 40 ppm respectively, was applied to the surface of skin tissue and cultured for 48 hours. After 48 hours, the skin tissue was collected, washed, and fixed at room temperature for 48 hours with 10% formalin. After fixation, the tissue was washed with running water, dehydrated, and embedded in paraffin to produce a paraffin block. The prepared paraffin block was sectioned into 5 μm sections and used for collagen expression analysis. To confirm the level of collagen in the dermis of the skin, Masson's trichrome staining method, a special staining technique that specifically stains collagen, was used. After staining, images were acquired using a microscope and used for analysis. The obtained images were analyzed using the Image J (NIH, USA) program. The results are shown in Table 1 and Figures 3 and 4 below.

[0072] Figure 3 shows an image obtained with a microscope, and Figure 4 shows a graph of the degree of collagen expression.

[0073]

[0074] Normal Tissue Group (No Treatment) Control Group (UV Treatment) Test Group 1 (Peptide Derivative 20 ppm) Test Group 2 (Peptide Derivative 40 ppm) Collagen Expression (%) 100.0±35.621 10.9±8.751 69.7±29.22 * 193.7±27.19 *

[0075] (*p<0.05 vs. normal tissue)

[0076]

[0077] Through Table 1, Figures 3 and 4 above, it can be seen that the expression of collagen in the dermis of the skin increases as a result of treatment with the peptide derivative represented by Formula 1 of the present invention.

[0078] Specifically, when the peptide derivative represented by Formula 1 of the present invention was treated at a concentration of 20 ppm (test group 1), the expression of collagen increased significantly by 58.8% compared to the control group, and when treated at a concentration of 40 ppm (test group 2), it increased significantly by 82.8% compared to the control group.

[0079]

[0080] Experimental Example 4: Evaluation of the efficacy of increasing Collagen-17 in skin tissue

[0081] To analyze whether treatment with a peptide derivative represented by Chemical Formula 1 of the present invention affects the increasing efficacy of collagen-17, a protein involved in the boundary between the dermis and the epidermis, the expression level of collagen-17 was analyzed using human-derived skin tissue.

[0082] Specifically, NativeSkin access®, manufactured by Genoskin of France for research purposes, was used for the evaluation. The received skin tissues were stabilized for one hour before evaluation. UVB irradiation of 50 mJ / cm² was applied to tissues, excluding the normal tissue group. 2After irradiation, approximately 20 μl of a solution of the peptide derivative represented by Formula 1 of the present invention, diluted in distilled water to concentrations of 20 ppm and 40 ppm respectively, was applied to the surface of skin tissue and cultured for 48 hours. After 48 hours, the skin tissue was collected, washed, and fixed at room temperature for 48 hours with 10% formalin. After fixation, the tissue was washed with running water, dehydrated, and embedded in paraffin to produce a paraffin block. The prepared paraffin block was sectioned into 5 μm sections and used for analysis of collagen-17 expression. To confirm the degree of collagen-17 expression at the dermal-epidermal boundary of the skin, the tissue was stained using immunohistochemical staining with a collagen-17 antibody (Abcam, ab184996), and images were acquired using a fluorescence microscope for analysis. The obtained images were analyzed using the Image J (NIH, USA) program. The results are shown in Table 2 and Figures 5 to 6 below.

[0083] Figure 5 shows an image obtained with a microscope, and Figure 6 shows a graph of the expression level of collagen-17.

[0084] In Figure 5, the green area is the expression area of ​​collagen-17 and the blue area is the DAPI(4',6-diamidino-2-phenylindole)(cell nucleus) area, and the white dotted line indicates the boundary between the dermis and the epidermis.

[0085]

[0086] Normal tissue group (untreated group) Control group (UV-treated group) Test group 1 (peptide derivative 20 ppm) Test group 2 (peptide derivative 40 ppm) Collagen-17 expression (%) 100.0±35.86 28.9±19.045 27.1±143.737 12.9±177.32

[0087]

[0088] Through Table 2, Figures 5 and 6 above, it can be seen that the expression of collagen-17 expressed at the boundary between the dermis and epidermis of the skin increases as a result of treatment with the peptide derivative represented by Formula 1 of the present invention.

[0089] Specifically, when the peptide derivative represented by Formula 1 of the present invention was treated at a concentration of 20 ppm (test group 1), the expression of collagen-17 increased significantly by 498.2% compared to the control group, and when treated at a concentration of 40 ppm (test group 2), it increased significantly by 684% compared to the control group.

[0090]

[0091] Experimental Example 5: Evaluation of efficacy in reducing inflammatory cytokine expression

[0092] We evaluated whether the peptide derivative represented by Formula 1 of the present invention affects IL-8 expression, an aging-associated secretory phenotype (SASP), under Doxorubicin-induced aging conditions.

[0093] Specifically, human dermal fibroblasts (hDF) were divided into non-senescent cells (blank) and cells senescent-induced with doxorubicin, 5 × 10⁶ 4 Cells were evenly seeded and cultured in DMEM (Dulbecco's Modified Eagle Media, Gibco BRL) medium in an incubator at 37°C and 5% CO2 for 24 hours. During this time, aging was induced by treatment with doxorubicin at 200 nM. A peptide derivative represented by Chemical Formula 1 was dissolved in DMSO at a concentration of 10 mM to form a concentrate, which was then diluted to a concentration of 100 μM in supplement-free medium and added to each well, followed by 24 hours of incubation. The culture medium after 24 hours of incubation was collected and analyzed using an IL-8 ELISA kit (R&D system S000C).

[0094] The results are shown in Figure 7 below.

[0095] As shown in Figure 7, IL-8 expression increased in cells induced with doxorubicin (control group) compared to non-aging cells (blank), and IL-8 expression decreased in cells (compound) simultaneously treated with the peptide derivative represented by Formula 1 of the present invention. Through this, it can be confirmed that the peptide derivative represented by Formula 1 of the present invention affects the aging-associated secretory phenotype factor (SASP).

[0096]

[0097] Experimental Example 6: Evaluation of VEGF (vascular endothelial growth factor) increasing efficacy

[0098] To analyze whether treatment with a peptide derivative represented by Chemical Formula 1 of the present invention affects the increase of VEGF, a protein involved in skin tissue regeneration, the degree of VEGF expression was analyzed using human-derived skin tissue.

[0099] Specifically, NativeSkin access®, manufactured by Genoskin of France for research purposes, was used for the evaluation. The received skin tissues were stabilized for one hour before the evaluation was conducted. Ultraviolet (UVB) radiation of 50 mJ / cm² was applied to the tissues, excluding the normal tissue group. 2After irradiation, approximately 20 μl of a solution of the peptide derivative represented by Formula 1 of the present invention, diluted in distilled water to concentrations of 20 ppm and 40 ppm respectively, was applied to the surface of skin tissue and incubated for 48 hours. After 48 hours, the skin tissue was collected, washed, and fixed at room temperature for 48 hours in 10% formalin. After fixation, the tissue was washed with running water, dehydrated, and embedded in paraffin to produce a paraffin block. The prepared paraffin block was sectioned into 5 μm sections and used for VEGF expression analysis. To confirm the degree of VEGF expression at the dermal-epidermal boundary of the skin, the tissue was stained using immunohistochemical staining with a VEGF antibody (Abfrontier, LF-PA50075), and images were acquired using a fluorescence microscope for analysis. The obtained images were analyzed using the Image J (NIH, USA) program. The results are shown in Table 3 and Figures 8 and 9.

[0100] Figure 8 shows an image obtained with a microscope, and Figure 9 shows a graph of the expression level of VEGF.

[0101] In Figure 8, the red area is the VEGF expression area and the blue area is the DAPI(4',6-diamidino-2-phenylindole)(cell nucleus) area, and the white dotted line indicates the boundary between the dermis and the epidermis.

[0102]

[0103] Normal tissue group (untreated group) Control group (UV-treated group) Test group 1 (peptide derivative 20 ppm) Test group 2 (peptide derivative 40 ppm) VEGF expression (%) 100±6 7.95 35.5±15.69 300 0.4±145.12 20.9±27 3.86

[0104]

[0105] Through Table 3, Figures 8 and 9 above, it can be seen that the expression of VEGF at the boundary between the dermis and epidermis of the skin increases as a result of treatment with the peptide derivative represented by Formula 1 of the present invention.

[0106] Specifically, when the peptide derivative represented by Chemical Formula 1 of the present invention was treated at a concentration of 20 ppm (test group 1), the expression of VEGF increased significantly by 264.9% compared to the control group, and when treated at a concentration of 40 ppm (test group 2), it increased significantly by 385.4% compared to the control group.

[0107]

[0108] As specific parts of the present invention have been described in detail above, it is evident to those skilled in the art that such specific descriptions are merely preferred embodiments and do not limit the scope of the present invention. Those skilled in the art will be able to make various applications and modifications within the scope of the present invention based on the above description.

[0109] Accordingly, the substantial scope of the present invention shall be defined by the appended claims and their equivalents.

Claims

1. A peptide derivative represented by the following chemical formula 1: [Chemical Formula 1] 2. A cosmetic composition comprising a peptide derivative according to claim 1.

3. A cosmetic composition according to paragraph 2, characterized as being for preventing skin aging.

4. A cosmetic composition characterized by being for wrinkle improvement in paragraph 2.

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