WO2019216651A1 - Peptide having anti-wrinkle efficacy - Google Patents

Abstract

A peptide of the present invention, which is composed of a relatively short amino acid sequence, is easily absorbed in the body and excellent in anti-wrinkle efficacy, can promote collagen production, and inhibit aging genes. Therefore, the peptide of the present invention may be included in a cosmetic composition, a pharmaceutical composition, or a health functional food and exhibit excellent anti-wrinkle efficacy.

Description

Anti-wrinkle Peptides

The present invention relates to a pharmaceutical composition, a cosmetic composition and a nutraceutical comprising a peptide having excellent wrinkle improvement efficacy.

The development of anti-aging cosmetics, including wrinkle improvement, has become a major area of interest in the cosmetics industry due to the expansion of diverse consumer groups due to the aging population, the development of beauty and medical technology, and the increasing interest of consumers who want healthy and beautiful skin. Recently, women's demand for cosmetics is increasing due to the increase in income from women's social advancement and higher education, and the so-called 'early wrinkle improvement' which manages wrinkles from late 20s or early 30s due to skin aging due to stress and environmental pollution. The market for commodities' is growing.

The main symptom of skin aging is wrinkles, and the exact mechanism of its development has not been elucidated. Damage to substrate proteins such as collagen and elastic fibers, which are present on the skin, is the main cause of wrinkles. In addition, the skin is the outermost layer of the body and is one of the tissues that receive the most oxidative stress caused by external stimuli. Various external factors such as ultraviolet rays, drugs, and environmental pollutants increase the generation of free radicals in the skin. Oxidative damage occurs by binding to unsaturated fatty acids on cell membranes. Oxidative stress in skin is known as a major factor of wrinkles. Among the wrinkles caused by aging of the skin, the small wrinkles are involved in the epidermis and the upper layer of the dermis, and the large and deep wrinkles and sagging are basically attributed to the aging of the dermis, that is, the qualitative and quantitative changes of collagen and elastin.

Wrinkle-reducing functional cosmetics have been used as ingredients to improve wrinkles, such as retinol and adenosine, but they are mainly focused on one specific antioxidant component, which can cause skin troubles as well as remarkable It is difficult to expect the full efficacy.

It is an object of the present invention to provide a pharmaceutical composition, a cosmetic composition, and a health functional food comprising a peptide having excellent wrinkle improvement efficacy.

1. Pharmaceutical composition for improving wrinkles comprising a peptide consisting of one sequence selected from SEQ ID NOs: 1 to 3.

2. The pharmaceutical composition for improving wrinkles according to the above 1, comprising a peptide consisting of the sequence of SEQ ID NO: 1.

3. Cosmetic composition for improving wrinkles comprising a peptide consisting of one sequence selected from SEQ ID NOs: 1 to 3.

4. according to the above 3, cosmetic composition for improving wrinkles comprising a peptide consisting of the sequence of SEQ ID NO: 1.

5. Wrinkle improvement health functional food comprising a peptide consisting of one of SEQ ID NOs: 1 to 3.

6. In the above 5, a functional food for improving wrinkles comprising a peptide consisting of the sequence of SEQ ID NO: 1.

Peptides of the present invention is very excellent in wrinkle improvement, it can be included in pharmaceutical compositions, cosmetic compositions and health functional food to provide a significant wrinkle improvement efficacy to the user.

1 to 3 are diagrams showing the cytotoxicity of the peptide of the present invention.

4 to 6 is a diagram showing the amount of procollagen type-1 in the supernatant when the peptide of the present invention is treated in human fibroblasts.

7 to 9 are diagrams showing the production amount of intracellular procollagen type-1 when the peptide of the present invention is treated to human fibroblasts.

10 to 12 are diagrams showing the amount of MMP-1 production in the supernatant when the peptide of the present invention is treated to human fibroblasts.

13 is a diagram showing the amount of MMP-1 production in cells when the peptide consisting of the sequence of SEQ ID NO: 3 is treated to human fibroblasts

14 to 20 show oral administration of the peptide consisting of the sequence of SEQ ID NO: 1 to the mouse for 3 weeks, the effect of the photograph, mock plate image, mock plate quantitative analysis results.

21 to 27 shows the effect of a photograph, a mock plate image, a mock plate quantitative analysis when the mouse orally administered a peptide consisting of the sequence of SEQ ID NO: 1 for 6 weeks.

28 to 34 show the effect of photographs, mock plate images, and mock plate quantitative analysis when the mice were orally administered to the mice consisting of the sequence of SEQ ID NO: 1 for 9 weeks.

35 and 36 confirm the wrinkle improvement effect of the skin tissue through H & E staining, Masson's trichrome staining, respectively.

37 and 38 are quantitative analyzes of wrinkle improvement of skin tissues through H & E staining and Masson's trichrome staining, respectively.

39 to 44 shows quantitative analysis of expression levels of Procollagen type-1, MMP-1, MMP-2, MMP-3, MMP-9 and TIMP-1 by RT-qPCR after 9 weeks will be.

Hereinafter, the present invention will be described in detail.

Hereinafter, a peptide consisting of one sequence selected from SEQ ID NOs: 1 to 3 of the present invention (1: IVVPK, 2: GPK, 3: FIIE) may be abbreviated collectively as 'peptide of the present invention', and From the viewpoint of the skilled person, it is obvious that the peptide can be sufficiently identified by referring to the entire description of the specification.

The peptide of the present invention is excellent in wrinkle improvement efficacy. For example, collagen production can be promoted and aging genes can be suppressed. Thus, it can be included in the cosmetic composition, pharmaceutical composition or health functional food can exhibit excellent wrinkle improvement efficacy.

Peptides of the invention can be synthesized chemically. When prepared by chemical synthesis, it may be prepared by chemical synthesis well known in the art (Creighton, Proteins; Structures and Molecular Principles, W. H. Freeman and Co., NY, 1983). Representative methods include, but are not limited to, liquid or solid phase synthesis, fragment condensation, F-MOC or T-BOC chemistry. (Chemical Approaches to the Synthesis of Peptides and Proteins, Williams et al., Eds., CRC Press, Boca Raton Florida, 1997; A Practical Approach, Atherton & Sheppard, Eds., IRL Press, Oxford, England, 1989).

In addition, the peptide of the present invention may be prepared by genetic engineering methods, but is not limited to the following method. First, a DNA sequence encoding the peptide is prepared according to a conventional method. DNA sequences can be prepared by PCR amplification using appropriate primers. Alternatively, DNA sequences may be synthesized by standard methods known in the art, such as using automated DNA synthesizers (eg, sold by Biosearch or Applied iosystems). The constructed DNA sequence is inserted into a vector comprising one or more expression control sequences (eg, promoters, enhancers, etc.) operably linked to and regulate expression of the DNA sequence, and recombinant expression formed therefrom. Transform the host cell with the vector. The resulting transformants are cultured under appropriate media and conditions to allow the DNA sequence to be expressed, to recover substantially pure peptides encoded by the DNA sequences from the culture. The recovery can be carried out using methods known in the art (eg chromatography). By "substantially pure peptide" is meant that the peptide according to the invention is substantially free of any other protein derived from the host. For genetic engineering methods for peptide synthesis of the present invention, reference may be made to Maniatis et al., Molecular Cloning; A laboratory Manual, Cold Spring Harbor laboratory, 1982; Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press, N.Y., Second (1998) and Third (2000) Edition; Gene Expression Technology, Method in Enzymology, Genetics and Molecular Biology, Method in Enzymology, Guthrie & Fink (eds.), Academic Press, San Diego, Calif, 1991; And Hitzeman et al., J. Biol. Chem., 255: 12073-12080, 1990.

The present invention provides a pharmaceutical composition for improving wrinkles comprising a peptide consisting of one sequence selected from SEQ ID NOs: 1 to 3.

Pharmaceutical compositions comprising the peptides are formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. It can be used, but is not limited thereto.

Carriers, excipients and diluents that may be included in the compositions containing the peptides of the invention include lactose, dextrose, sucrose, dextrin, maltodextrin, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, Alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil This is not restrictive. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. which are commonly used are prepared, but are not limited thereto.

Solid preparations for oral administration include, but are not limited to, tablets, pills, powders, granules, capsules, and the like, but such solid preparations may include at least one excipient such as starch, calcium carbonate, or the like. , Sucrose or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.

Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The present invention provides a cosmetic composition for improving wrinkles comprising a peptide consisting of one sequence selected from SEQ ID NOs: 1 to 3.

In addition to the peptides, it may include components conventionally used in cosmetic compositions, such as conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors, and carriers.

Examples of products to which the cosmetic composition of the present invention may be added include, for example, cosmetics such as astringent cosmetics, soft cosmetics, nourishing cosmetics, various creams, essences, packs, foundations, and the like, cleansing agents, face washes, soaps, treatments, and essences. Etc., but is not limited thereto.

Specific formulations of the cosmetic composition of the present invention include skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, essence, nutrition essence, pack, Formulations such as soaps, shampoos, cleansing foams, cleansing lotions, cleansing creams, body lotions, body cleansers, emulsions, lipsticks, makeup bases, foundations, press powders, loose powders, eye shadows and the like.

The cosmetic composition of the present invention may be formulated by stabilizing the peptide contained inside the nanoliposomes. When the peptide is contained inside the nanoliposome, the components of the peptide are stabilized to solve problems such as precipitation formation and modification during formulation, and the solubility and transdermal absorption of the components can be increased to maximize the efficacy expected from the peptide. Can be expressed.

The present invention provides a functional food for improving wrinkles comprising a peptide consisting of one of SEQ ID NOs: 1 to 3.

The health functional food of the present invention can be produced and processed in the form of tablets, capsules, powders, granules, liquids, pills and the like for the purpose of improving wrinkles.

The health functional food of the present invention refers to foods manufactured and processed using raw materials or ingredients having functional properties useful for the human body according to Act No. 6767 of the Health Functional Food Act, and refer to nutrients for the structure and function of the human body. It means ingestion for the purpose of obtaining a beneficial effect for health use such as control or physiological action.

The health functional food of the present invention may include a conventional food additive, and the suitability as a food additive, unless otherwise specified, in accordance with the General Regulations of the Food Additives and General Test Methods approved by the Food and Drug Administration, etc. Judging by the standards and standards.

Examples of the items loaded on the food additive revolution include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid and cinnamon acid; Natural additives such as dark blue pigment, licorice extract, crystalline cellulose, high color pigment and guar gum; Mixed preparations such as sodium L-glutamate, algae, preservatives, tar pigments, and the like, but are not limited thereto.

For example, a dietary supplement may be granulated in a conventional manner by mixing the peptide with an excipient, a binder, a disintegrant, and other additives, and then compression-molded with a lubricant, or directly Compression molding is possible. In addition, the health functional food in the form of tablets may contain a mating agent or the like as necessary.

Hard capsules of the health functional food in the form of capsules may be prepared by filling a mixture of the peptides with additives such as excipients in a conventional hard capsule, and soft capsules gelatin mixtures of the peptides with additives such as excipients. It can be prepared by filling in a capsule base such as. The soft capsule agent may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, as necessary.

The cyclic health functional food can be prepared by molding a mixture of the peptide and excipients, binders, disintegrants, etc. by known methods, and can be avoided with white sugar or other epidermis, if necessary, or starch. It is also possible to coat the surface with a material such as talc.

The health functional food in the form of granules may be prepared by granulating a mixture of the peptide and the excipient, the binder, the disintegrating agent and the like by a conventionally known method, and may contain a flavoring agent, a mating agent, and the like, as necessary.

The health functional food is beverages, meat, chocolate, foods, confectionery. Pizza, ramen, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes and dietary supplements.

Hereinafter, the present invention will be described in detail with reference to Examples.

Example 1. Peptide Synthesis and Cytotoxicity Measurement

The peptide used in the experiment was synthesized by A & Pep (Cheongju, Korea) according to the standard Fmoc solid phase synthesis method.

Before confirming the anti-wrinkle efficacy of the peptide was confirmed cytotoxicity in human fibroblasts, it was confirmed that there is no cytotoxicity. (Figures 1-3)

Example 2. Evaluation of wrinkle improvement effect by measuring the amount of procollagen type-1 production

Procollagen type-1 production was compared at concentrations at which no cytotoxicity of the peptide of the present invention occurred.

After the peptide was treated to human fibroblasts by concentration, the supernatant was extracted to measure procollagen type-1 production, and concentration-dependent procollagen type-1 production was confirmed to increase. (FIGS. 4-6)

After the peptide was treated to human fibroblast cells by concentration, the intracellular procollagen type-1 production was measured, and the procollagen type 1 production was increased depending on the concentration. (FIGS. 7-9)

Example 3. Evaluation of wrinkle improvement effect by measuring the degree of inhibition of expression of MMP-1

After the peptide was treated to human fibroblasts by concentration, the supernatant was extracted to measure MMP-1 production, and it was confirmed that MMP-1 production decreased in a concentration-dependent manner. (FIGS. 10-12)

After the peptide consisting of the sequence of SEQ ID NO: 3 to the cells treated with human fibroblasts by concentration, the intracellular MMP-1 production was measured, and it was confirmed that the MMP-1 production decreased in a concentration-dependent manner. (Figure 13)

Example 4 Evaluation of Wrinkle Improvement Efficacy on In vivo

1. Experiment Method

After wrinkles were generated for 9 weeks using SKH: HR-1 hairless mice (6 weeks old), peptide (IVVPK) consisting of the sequence of SEQ ID NO: 1 was treated by dose to confirm the effect of wrinkle improvement, and Verification was conducted.

Normal group (UVB untreated), IVVPK treated group (IVVPK 200mg / kg, UVB untreated), UVB induction group (UVB treated), low molecular collagen peptide treated group (200mg / kg, UVB treated) as a positive control, was set, IVVPK was set to low, medium, and high dose treatment groups (50, 100, 200 mg / kg, UVB treatment) to conduct the experiment.

In order to periodically check the effect of improving wrinkles, images were taken and mock-ups were produced every 3, 6, and 9 weeks after oral administration. The mock-ups were quantitatively analyzed using software.

Nine weeks later, rat back tissues were isolated, and RNA expression and RT-qPCR were used to measure the expression level of the mechanism of action genes related to wrinkle improvement.

2. Experimental Results

(1) 3 weeks after oral administration

Image and mock plate analysis showed that wrinkles were reduced in IVVPK treatment group compared to normal group, and wrinkles were clearly observed in UVB induction group compared to normal group. Compared to the induction group, the IVVPK group (50, 100, 200mg / kg) was confirmed that the dose-dependent decrease (Fig. 14, 15).

As a result of the quantitative analysis of the mock plate to verify the wrinkle improvement effect of IVVPK, the wrinkle-related value was significantly increased in the UVB-induced group compared to the normal group in the quantitative value, and IVVPK-treated group (50, 100, 200 mg / kg) was confirmed that the dose-dependent decrease (Figs. 16 to 20). Specifically, in the UVB induction group compared to the normal group, 50%, 40%, 62%, 44%, and 26% increased in the number of wrinkles, the total wrinkles and the average length, the total wrinkles, and the average depth, respectively. The IVVPK medium dose decreased by 7%, 9%, 23%, 14% and 58% in each treatment group, and the IVVPK medium dose decreased by 17%, 19%, 59%, 31% and 72% in each treatment group. The treatment group showed 42%, 51%, 76%, 41% and 92% reduction for each item. The low molecular weight collagen peptide showed 28%, 53%, 52%, 55% and 74% reduction for each item.

As a result of oral administration of the peptide consisting of the sequence of SEQ ID NO: 1 for 3 weeks, the dose, depth and length of the wrinkles were dose-dependently reduced compared to the UVB induction group. / kg) showed better efficacy than this molecule of low molecular weight collagen peptide.

(2) 6 weeks after oral administration

It was confirmed that the wrinkles are significantly increased in the UVB induction group compared to the normal group through the image, mock plate, quantitative analysis results, and dose-dependent decrease in the IVVPK treatment group (FIGS. 21 to 27).

To quantify the effect of IVVPK on the wrinkle improvement, quantitative analysis of the mock plate showed 87%, 98%, and 39% of wrinkles, total wrinkles and average length, total wrinkles and average depth in the UVB induction group compared to the normal group, respectively. %, 46%, 32% increase. The IVVPK low-dose treated group decreased 71%, 65%, 51%, 80%, 75% compared to the UVB-induced group, and 96%, 87%, 85%, 117%, 92 in the IVVPK medium-dose treated group. The percentage reduction was 105%, 103%, 133%, 128% and 123% in the IVVPK high dose group. In the case of low molecular collagen peptides, there were 121%, 108%, 86%, 117%, and 128% reduction for each item.

As a result of oral administration of the peptide consisting of the sequence of SEQ ID NO: 1 for 6 weeks, the number, depth, and length of wrinkles showed a dose-dependent decrease compared to the UVB induction group, and the peptide high dose treatment group consisting of the sequence of SEQ ID NO: 1 200 mg / kg) showed the same or better efficacy than the same low molecular collagen peptide.

(3) 9 weeks after oral administration

It was confirmed that the wrinkles increase significantly in the UVB induction group compared to the normal group through the image, mock plate, quantitative analysis results, and dose-dependent decrease in the IVVPK administration group (FIGS. 28 to 34).

To quantify the effect of IVVPK on wrinkling, quantitative analysis of the mock plate revealed that the number of wrinkles, total wrinkles and average length, total wrinkles and average depth in the UVB-induced group compared to the normal group were 61%, 39%, and 35, respectively. %, 66%, 24% increase. In the IVVPK low dose treatment group, 48%, 43%, 67%, 50% and 64% decreased in the IVVPK treatment group, and 84%, 88%, 149%, 85% and 69 in the IVVPK treatment group. The percentage decrease was 124%, 124%, 167%, 89%, and 89% in the IVVPK high dose group. In the case of low molecular collagen peptides, there were 117%, 102%, 159%, 99%, and 89% reduction for each item.

After administration of the peptide consisting of the sequence of SEQ ID NO: 1 for 9 weeks, the dose, depth, and length of wrinkles showed a dose-dependent decrease compared to the UVB induction group, and the peptide high dose treatment group consisting of the sequence of SEQ ID NO: 1 (200 mg / kg) showed the same or better efficacy than the same dose of low molecular collagen peptide.

(4) Verification of anti-wrinkle efficacy through tissue staining

In order to confirm the efficacy of wrinkle improvement, sacrifice was performed 9 weeks after oral administration, and the back tissues were separated, and epidermal thickness and collagen density were measured by H & E (hematoxylin and eosin) and Masson's trichrome staining.

Compared to the normal group, the epidermal thickness and collagen fibers were increased in the IVVPK-only group. In addition, the UVB induction group showed increased epidermal thickness and collagen fiber reduction compared to the normal group, and in the IVVPK treatment group (50, 100, 200 mg / kg) compared to the UVB induction group, dose-dependent epidermal thickness reduction and collagen fiber were observed. It was confirmed that the increase (Figs. 35, 36).

To verify the above results numerically, the images were quantified using the Image j program. H & E staining was quantified by measuring the thickness of the epidermis, Masson's trichrome staining was measured for collagen fibers (Fig. 37, 38).

As a result of quantitative H & E staining, the epidermal thickness was increased by 142% in the UVB-induced group compared to the normal group and significantly decreased in the IVVPK treated group (23%, 32%, 52%). The low molecular weight collagen peptide treated group (200 mg / kg), a positive control, showed similar efficacy as the high dose treated group (200 mg / kg).

Masson ’s trichrome staining quantitatively showed that collagen fibers showed a significant dose-dependent increase (10%, 25%, 66%) in the IVVPK treated group compared to the UVB induced group. The low molecular collagen peptide treated group (200 mg / kg), a positive control group, showed an efficacy between the medium dose treated group (100 mg / kg) and the high dose treated group (200 mg / kg).

As a result, it can be seen that the peptide consisting of the sequence of SEQ ID NO: 1 significantly reduced the epidermal thickness and increased the amount of collagen in the dermis.

(5) Study of genome expression change through RT-qPCR

After 9 weeks, the dorsal tissue was separated and genome expression was measured as a mechanism of action related to wrinkle improvement through RNA extraction and RT-qPCR. Procollagen type 1, a precursor of collagen in skin tissues, and genome expression levels of its degradation enzymes, MMP-1, MMP-2, MMP-3, and MMP-9, were identified. In addition, the genome expression level of TIMP-1, which acts as an inhibitor of MMP, was measured.

Procollagen type 1 genome expression was increased by 40% in IVVPK-treated group compared to normal group. When UVB treatment, the expression level of the genome decreased to 36%, and IVVPK was dose-dependently treated with 29% in the low-dose group, 72% in the medium-dose group, and 94% in the high-dose group. Increased. The low molecular weight collagen peptide 200 mg / kg treatment group, a positive control, increased by 92%. The IVVPK high dose treated group showed similar genomic expression as the normal group (FIG. 39).

The expression level of MMP-1 genome was decreased by 8% in IVVPK-treated group and 220% in UVB-treated group compared to normal group. When treated by IVVPK dose, MMP-1 gene expression decreased by 57% in the low-dose group, 74% in the medium-dose group, and 96% in the high-dose group, resulting in a dose-dependent decrease. The low molecular weight collagen peptide 200 mg / kg treatment group had a 96% reduction. In the IVVPK high-dose group, genome expression was similar to that of the normal group (FIG. 40).

The expression level of MMP-2 genome was decreased by 6% in IVVPK-treated group and 179% in UVB-treated group. When treated by IVVPK dose, MMP-2 gene expression decreased to 48% in the low-dose group, 62% in the medium-dose group, and 86% in the high-dose group, showing a dose-dependent decrease. The low molecular weight collagen peptide 200 mg / kg treatment group was reduced by 80% (FIG. 41).

The expression level of MMP-3 genome was reduced by 9% in IVVPK-treated group and 164% in UVB-treated group. MMP-3 gene expression decreased by 27% in the low-dose group, 59% in the medium-dose group, and 72% in the high-dose group. The low molecular weight collagen peptide 200 mg / kg treatment group was reduced by 68% (FIG. 42).

MMP-9 genome expression was decreased by 8% in IVVPK-treated group compared to normal group, and increased by 103% in UVB-treated group. When treated by IVVPK dose, MMP-9 gene expression decreased to 21% in the low-dose group, 58% in the medium-dose group, and 77% in the high-dose group, showing a dose-dependent decrease. The low molecular weight collagen peptide 200 mg / kg treatment group was reduced by 78% (FIG. 43).

The expression level of TIMP-1 genome was increased by 8% in IVVPK-treated group compared to normal group, and increased by 45% in UVB-treated group. When treated by IVVPK dose, TIMP-1 gene expression increased to 20% in the low-dose group, 45% in the medium-dose group and 55% in the high-dose group, showing a dose-dependent increase. The low molecular weight collagen peptide 200 mg / kg treatment group had a 63% increase (FIG. 44).

Claims (6)

1. Wrinkle improvement pharmaceutical composition comprising a peptide consisting of one sequence selected from SEQ ID NOs: 1 to 3.
2. The pharmaceutical composition for improving wrinkles according to claim 1, comprising a peptide consisting of the sequence of SEQ ID NO: 1.
3. Wrinkle improvement cosmetic composition comprising a peptide consisting of one sequence selected from SEQ ID NOs: 1 to 3.
4. The cosmetic composition for improving wrinkles according to claim 3, comprising a peptide consisting of the sequence of SEQ ID NO: 1.
5. Wrinkle improvement health functional food comprising a peptide consisting of one of SEQ ID NOs: 1 to 3.
6. The health functional food for improving wrinkles according to claim 5, comprising a peptide consisting of the sequence of SEQ ID NO: 1.

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