A pentapeptide-derived peptide segment RS for anti-skin aging and its application

Abstract

The present invention provides a pentapeptide-derived peptide segment RS for anti-skin aging, which relates to the field of biochemistry. The pentapeptide-derived peptide segment RS sequentially includes an amphiphilic helical peptide segment, a linker peptide segment, and KTTKS from the N-terminus to the C-terminus, wherein (b)x(a)y represents the linker peptide segment; a is an uncharged amino acid; b is a basic amino acid; x and y are independently selected from integers greater than or equal to 2. The present invention unexpectedly finds that the pentapeptide-derived peptide segment RS obtained by connecting the amphiphilic helical peptide segment and KTTKS through the linker peptide with the structure of (b)x(a)y has good hydrophilicity and high skin permeability. Direct local application can significantly increase the expression level of type I collagen, increase the skin thickness, and reduce skin wrinkles, achieving a significant anti-skin aging effect.

Description

Technical Field

[0001] The present invention relates to the field of biochemistry, and in particular to a pentapeptide-derived peptide segment RS for anti-skin aging and its application. Background Art

[0002] Skin aging is a complex process mainly caused by endogenous and exogenous factors. Endogenous factors refer to natural physiological aging. As epidermal keratinocytes and dermal fibroblasts grow slowly, the number of epidermal fibroblasts gradually decreases, and the ability to synthesize collagen is reduced. At the same time, due to the increased release of proteases, collagen degradation increases. Although the content of elastic fibers does not decrease, the elastic fiber network curls, relaxes, loses elasticity, and even disappears, causing the epidermal layer to relax and form fine wrinkles. At the same time, the thickening of fiber bundles will also deepen the depth of wrinkles. Ultraviolet radiation can also cause the degradation of collagen fiber bundles, damage the skin elasticity, and then increase wrinkles. At the same time, ultraviolet radiation can deform elastic fibers, making the fibers thicken, twist and bifurcate. Over time, skin relaxation and wrinkles will appear.

[0003] In the research of skin anti-aging, it mainly focuses on promoting cell division and proliferation, promoting the synthesis of collagen and elastic fibers, moisturizing and repairing the skin barrier function, etc. At present, the functions of many anti-aging drugs and cosmetics on the market are to promote cell division and proliferation, accelerate the exfoliation rate of epidermal keratinocytes, and stimulate the division of basal cells to improve the skin appearance in the short term. However, since normal skin cells have certain lifespan and division times limitations, excessive acceleration of cell division shortens the cycle of each cell division, but instead shortens the cell lifespan and accelerates aging. Therefore, increasing the secretion amount of skin cell collagen is an important and promising new direction for improving the skin appearance.

[0004] During the metabolism of collagen, some small peptide fragments are produced. Some small peptide fragments, such as KTTKS (pentapeptide), can stimulate fibroblasts to secrete collagen (A Pentapeptide from Type I Procollagen Promotes Extracellular Matrix Production, THE JOURNAL OF BIOLOGICAL CHEMISTRY, 1993, Vol. 268 (14): 9941-9944). Many cosmetic companies are very interested in the application of these small molecule peptides in cosmetics. However, these small molecule peptides are hydrophilic and have very weak ability to penetrate the skin. Some researchers have palmitoylated the N-termini of these small molecule peptides, and the results show that these palmitoylated small molecule peptides can effectively improve the properties of the skin (US2007 / 0099842A1). Even so, the efficiency of transdermal absorption is very limited, and it is often necessary to add some penetration enhancers to the cosmetics. In addition, the palmitoylated polypeptide molecules have poor water solubility, and organic solvents must be used when making cosmetics, which inevitably causes certain irritation to the skin. Summary of the invention

[0005] Since the skin permeability of pentapeptide KTTKS is poor and the transdermal absorption of palmitoylated KTTKS (PAL-KTTKS) still needs to be improved, the present invention modifies the N segment of pentapeptide KTTKS with an amphiphilic peptide segment of a specific structure, and unexpectedly obtains a pentapeptide-derived peptide segment RS with good water solubility and strong skin penetration ability, which has a significant anti-skin aging effect, does not require the additional application of chemical penetration enhancers, and is safer and more effective.

[0006] In order to achieve the above-mentioned object of the invention, the first aspect of the present invention provides a pentapeptide-derived peptide RS for resisting skin aging, wherein the pentapeptide-derived peptide RS comprises an amphipathic helical peptide, a connecting peptide and KTTKS from the N-terminus to the C-terminus, and its structure is shown in formula (I):

[0007] Amphipathic helical peptide-(b)x(a)y-KTTKS(Ⅰ)

[0008] Wherein, (b)x(a)y represents the connecting peptide segment;

[0009] a is an uncharged amino acid;

[0010] b is a basic amino acid;

[0011] x and y are independently selected from integers of 2 or greater.

[0012] Preferably, the N-terminus of the N-terminal modified peptide is arginine.

[0013] Preferably, the amphiphilic helical peptide segment has basic amino acids and uncharged amino acids arranged alternately, with no more than 3 consecutive basic amino acids or uncharged amino acids, and the number of basic amino acids does not exceed 50%.

[0014] Preferably, the uncharged amino acids are selected from neutral amino acids and / or polar neutral amino acids.

[0015] Preferably, the uncharged amino acids are selected from one or more of threonine (T), serine (S), tyrosine (Y), glycine (G), leucine (L), serine (S), methionine (M), and glutamine (Q).

[0016] Preferably, the linking peptide segment is selected from RRGG (shown in SEQ ID NO.1) or KRGG (shown in SEQ ID NO.2).

[0017] Preferably, the amphiphilic helical peptide segment has an aabaa-bbabb structure.

[0018] Preferably, the "aabaa" is selected from RRQRR (shown in SEQ ID NO.3); and / or, the "bbabb" is selected from YGRTS (shown in SEQ ID NO.4), YGRLM (shown in SEQ ID NO.5), or TSKLM (shown in SEQ ID NO.6).

[0019] Preferably, the pentapeptide-derived peptide segment RS is selected from RRQRRYGRLM RRGGKTTKS (shown in SEQ ID NO.7) or RRQRR TSKLM KRGGKTTKS (shown in SEQ ID NO.8).

[0020] The second aspect of the present invention provides the use of the pentapeptide-derived peptide segment RS described in the above technical solution in the preparation of an anti-skin aging preparation. Preferably, the anti-skin aging includes one or more of promoting the synthesis of collagen I, increasing skin thickness, and reducing skin wrinkles.

[0021] The third aspect of the present invention provides an anti-skin aging composition, comprising an active ingredient and an adjuvant. The active ingredient comprises the pentapeptide-derived peptide segment RS described in the foregoing technical solution. Preferably, the adjuvant does not include a penetration enhancer. Preferably, the adjuvant comprises one or more of diluents, excipients, fillers, binders, wetting agents, disintegrants, surfactants, adsorption carriers, lubricants, flavoring agents, and sweetening agents acceptable in the pharmaceutical or cosmetic fields. The pentapeptide-derived peptide segment RS provided by the present invention has good hydrophilicity and lipophilicity, and can be efficiently absorbed by the skin and exert an anti-skin aging effect without the aid of chemical components such as penetration enhancers. In some specific embodiments, the anti-skin aging composition of the present invention may not contain a penetration enhancer; in some other specific embodiments, the anti-skin aging composition of the present invention may contain a penetration enhancer to assist the better penetration and absorption of the pentapeptide-derived peptide segment RS.

[0022] The anti-skin aging composition of the present invention can be made into various dosage forms such as tablets, powders, granules, ointments, etc., and the drugs of the above various dosage forms can be prepared according to the conventional methods in the pharmaceutical field. Preferably, the anti-skin aging composition is an external patch for topical administration.

[0023] The active components in the anti-skin aging composition of the present invention may further include other active ingredients having skin care effects or enhancing skin care effects and prolonging the metabolic time.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0025] Cell-penetrating polypeptides with both hydrophilicity and lipophilicity can bring polypeptides, DNA, and even larger particles into the interior of cells due to their special molecular structures (Fawell S et al. (1994) Tat-mediated delivery of heterologous proteins into cells. Proc Natl Acad Sci USA 91:664-668). The amphiphilic helix structure has basic amino acids on one side and neutral or polar neutral amino acids (uncharged) arranged in an interspersed manner, which can provide lipophilic and hydrophilic functions, but not all amphiphilic helix structures linked to KTTKS can improve the skin penetration of the KTTKS pentapeptide. The present invention unexpectedly finds that the pentapeptide-derived peptide segment RS obtained by connecting the amphiphilic helix peptide segment and KTTKS through a linker peptide with the structure of (b)x(a)y has good hydrophilicity and high skin permeability. Direct local application can significantly increase the expression level of type I collagen, increase skin thickness, and reduce skin wrinkles, achieving a significant anti-skin aging effect.

[0026] The transdermal absorption test on nude mice showed that the skin penetration ability of the pentapeptide-derived peptide segment RS provided by the present invention can reach more than 3.5%. In vitro and in vivo animal tests showed that the pentapeptide-derived peptide segment RS provided by the present invention has a significant stimulating effect on the secretion of collagen in HFL-1, and has the ability to penetrate the skin of nude mice, which is applicable to the skin of aged nude mice, showing obvious improvement in skin traits such as increased skin thickness and reduced skin folds. It can be seen that the pentapeptide-derived peptide segment RS of the present invention can effectively bring the pentapeptide KTTKS into the skin, maintain the activity of the pentapeptide, and at the same time can effectively improve the skin state, and has an application prospect in the preparation of cosmetics and drugs for improving skin state. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 is a perspective view of the pentapeptide-derived peptide segments RS1 and RS2 of the present invention (the red marks are basic amino acids);

[0028] Figure 2 is a detection result graph of the expression level of type I collagen mRNA after different polypeptides treated HLF-1 cells in Example 4; 1, 2, 3, and 4 in the figure are the PBS treatment group, PAL treatment group, RS1 treatment group, and RS2 treatment group respectively.

[0029] Figure 3 is a detection result graph of the expression level of type I collagen after different polypeptides treated HLF-1 cells in Example 4; 1, 2, 3, 4, and 5 in the figure represent the RS1 group, maker, RS2 group, PAL treatment group, and PBS treatment group respectively;

[0030] Figure 4 is a detection result graph of the expression level of type I collagen in cells in situ after different polypeptides treated HLF-1 cells in Example 5; 1, 2, 3, and 4 in the figure represent the PBS treatment group, PAL treatment group, RS1 treatment group, and RS2 treatment group respectively;

[0031] Figure 5 is a masson detection result graph after different polypeptide preparations were applied to the skin of nude mice for 4 weeks in Example 6; 1 is the RS1 treatment group, 2 is the RS2 treatment group, 3 is the PAL treatment group, and 4 is the blank preparation control. DETAILED DESCRIPTION OF THE INVENTION

[0032] In the present invention, without special limitation, the polypeptide is from the N-terminus to the C-terminus from left to right.

[0033] In the present invention, the "basic amino acid" refers to an amino acid with a polar R group that is dissociated and positively charged and alkaline in a neutral solution, including lysine (K), arginine (R) and histidine (H); in the present invention, the "polar neutral amino acid" refers to an amino acid with a polar R group that is not dissociated or only very weakly dissociated, including threonine (T), serine (S), cysteine ​​(C), tyrosine (Y), glutamine (Q), asparagine (N) and methionine (M). In the present invention, the "non-polar amino acid" may be glycine (G) and / or leucine (L).

[0034] The technical scheme provided by the present invention is described in detail below in conjunction with the embodiments, but they should not be understood as limiting the scope of protection of the present invention. The experimental methods in the following embodiments that do not specify specific conditions are usually carried out under conventional conditions or under conditions recommended by the manufacturer. All raw materials that do not specify the synthesis method are purchased from manufacturers such as Sinopharm, Aladdin, and Sigma-Aldrich, and are all analytically pure.

[0035] Example 1 Synthesis of Pentapeptide-derived Peptide RS

[0036] The following polypeptide fragments were synthesized according to the following method, and the reagents were purchased from Applied Biosystems, USA.

[0037] RS1(SEQ ID NO.7):RRQRRYGRLM RRGGKTTKS

[0038] RS2(SEQ ID NO.8):RRQRR TSKLM KRGGKTTKS

[0039] 1. The synthesis is carried out one by one from the C-terminus to the N-terminus and is automatically controlled by the synthesizer.

[0040] First, weigh an appropriate amount of resin (purchased from Applied Biosystems, Inc., USA) bound to the first amino acid, Ser, and load it onto the column. Deprotect it with 20% piperidine dimethylformamide solution, wash it with dimethylformamide, dissolve the free amino acid protected by 9-fluoromethoxycarbonyl (Fmoc) in carbodiimide (DCC), hydroxybenzotriazole (HOBt) / diisopropylethylamine (DIPEA), and cycle the coupling reaction of the dissolved solution on the column for 30 minutes. Wash it with dimethylformamide and repeat the above steps from deprotection to coupling reaction until the synthesis is completed (for specific operation steps, see the Pioneer Peptide Synthesizer Operation Guide).

[0041] 2. The synthesized peptide is sheared by the following steps:

[0042] Remove the reacted resin, add shear solution type B (88% trifluoroacetic acid, 5% phenol, 5% water, 2% triisopropylsilane), react at room temperature for 2 hours, filter, add 10 volumes of pre-cooled anhydrous ether to the filtrate, centrifuge at 4000 revolutions per minute for 10 minutes, collect the precipitate and dry at room temperature.

[0043] 3. Purification of the polypeptide

[0044] Weigh a certain amount of the dried polypeptide, dissolve it in 0.1% trifluoroacetic acid, and after sample treatment, separate it by a reverse column (the eluent is 0.1% trifluoroacetic acid containing 80% acetonitrile), and collect the elution peak.

[0045] Example 2

[0046] This experiment is used to verify the ability of the pentapeptide-derived peptide segment RS to penetrate the skin of nude mice.

[0047] 1. Test samples and grouping

[0048] RS1 treatment group: The RS1 polypeptide (SEQ ID NO.7) prepared in Example 1.

[0049] RS2 treatment group: The RS2 polypeptide (SEQ ID NO.8) prepared in Example 1.

[0050] RS0 treatment group: The polypeptide RS0 prepared according to the method shown in Example 1, as shown in SEQ ID NO.9: RRQRRYGRTS MGGKT TKS.

[0051] 2. Experimental method

[0052] First, prepare ex vivo mouse skin. Take nude mice at about 8 weeks old, immediately peel off the back skin after decapitation, carefully remove the subcutaneous fat, wash it with physiological saline, and dry it for later use.

[0053] Use a vertical Franz diffusion cell. Place the skin flat at the joint of the diffusion cell, with the stratum corneum facing the supply pool and the dermis facing the receiving pool. Keep the temperature at 37°C, and the receiving medium is water. Degas it by ultrasound before use. Add the test samples and grouping to the supply pool until the concentration reaches 10 mg / mL. The stirring speed of the magnetic stirrer is 300 r·min -1 , and sample from the receiving pool for HPLC (220 nm) analysis at 1 h. The ratio of the peak area obtained to the peak area of the 10 mg / mL polypeptide solution is the skin penetration rate.

[0054] 3. Experimental results

[0055] The skin penetration rates of each group of polypeptides in nude mice are shown in Table 1. It can be seen that compared with the control group RS0 polypeptide with the linker peptide segment "SGG", both RS1 and RS2 with the linker peptide segments "RRGG" and "KRGG" respectively have better skin penetration ability, and the skin penetration ability of RS2 is better. It shows that the pentapeptide-derived peptide segment RS provided by the present invention significantly improves the skin penetration rate of the pentapeptide KTTKS.

[0056] Table 1 Skin Penetration Rates in Nude Mice

[0057]

[0058] Example 3

[0059] This experiment is used to verify the hydrophilicity of the pentapeptide-derived peptide segment RS.

[0060] 1. Test Samples and Grouping

[0061] RS1 treatment group: RS1 polypeptide (SEQ ID NO.7) prepared in Example 1.

[0062] RS2 treatment group: RS2 polypeptide (SEQ ID NO.8) prepared in Example 1.

[0063] PAL treatment group: Commercially available N-terminal palmitoylated pentapeptide PAL-KTTKS (abbreviation "PAL").

[0064] 2. Experimental Method

[0065] The polypeptides in the RS1 treatment group, RS2 treatment group and PAL treatment group are directly dissolved in water, and their solubility in water is detected.

[0066] 3. Experimental Results

[0067] The results show that the solubility of the RS polypeptides in Experimental Groups 1-2 in water is greater than 10 mg / mL, while the PAL polypeptide is hardly soluble in water and needs to be dissolved by adding the organic solvent DMSO.

[0068] Example 4

[0069] This experiment is used to verify the ability of the pentapeptide-derived peptide segment to promote the synthesis of type I collagen in human lung fibroblasts.

[0070] 1. Test Samples and Grouping

[0071] RS1 treatment group: RS1 polypeptide (SEQ ID NO.7) prepared in Example 1.

[0072] RS2 treatment group: RS1 polypeptide (SEQ ID NO.8) prepared in Example 1.

[0073] PBS treatment group: PBS buffer

[0074] PAL treatment group: Commercially available N-terminal palmitoylated pentapeptide PAL-KTTKS (abbreviation: "PAL").

[0075] 2. Experimental methods

[0076] Human lung fibroblasts HFL-1 were purchased from the Cell Bank of the Chinese Academy of Sciences' Committee for the Preservation of Type Cultures. HFL-1 cells were cultured in DMEM medium containing 10% fetal bovine serum and placed in an incubator at 37°C with 7% CO 2 , 93% air for culturing.

[0077] One dish (6 cm in diameter) of confluent HFL-1 cells was digested with 0.25% trypsin (weight / volume) and collected. The cells were passaged into 2.5 dishes (6 cm in diameter). After overnight culture, each group of test samples was added to a final concentration of 2 μg / mL of the polypeptide (first dissolve the polypeptide in PBS, and then add it to the cell culture medium at a volume ratio of 10%. When adding the drug, the cells should not exceed 50 - 60% confluence). After continued culture for 24 hours, the mRNA expression level of type I collagen was detected by RT-PCR. The results are as Figure 2 shown; the protein expression level of type I collagen in the cells was detected by Western blot. The results are as Figure 3 shown.

[0078] One dish (6 cm in diameter) of HLF-1 cells treated with the polypeptide was taken. Total cellular RNA was extracted according to the method of the Trizol kit (Invitrogen). 1 μg of RNA was taken for reverse transcription, and 2 μL of cDNA was used as a template for PCR amplification. Agarose gel electrophoresis was used to detect the difference in the mRNA expression level of type I collagen in cells treated with different concentrations of the polypeptide, with GAPDH as a reference. The results are shown in Figure 2 .

[0079] Take 1 dish (6 cm in diameter) of HLF-1 cells treated with the polypeptide, and lyse the cells with the lysis buffer (formulation: Tris-HCl (pH 7.5), 150 mM NaCl, 1 mM EDTA, 2 mM DTT, 2 mM PMSF, and 1% Triton X-100). After centrifuging the lysis buffer at 10,000 rpm, take the supernatant and detect its protein content by the Bradford method. Add an equal amount of protein to each loading well, separate by 10% polyacrylamide gel electrophoresis, and then transfer to a PVDF membrane (for the methods of electrophoresis and electrotransfer to the PVDF membrane, see Sambrook et al., Molecular Cloning: A Laboratory Manual (New York: Cold Spring Harbor Laboratory Press, 1989)). After blocking the electrotransferred PVDF membrane with PBS containing 1% BSA and 1% goat serum, detect it with an antibody against type I collagen, and the antibody used is the antibody produced by abcom company. The results are shown in Figure 3 。

[0080] 3. Experimental Results

[0081] As Figure 2 shown, compared with the HLF-1 cells treated with the control group RS0, the mRNA and protein expression levels of type I collagen in the HLF-1 cells treated with RS1, RS2, and PAL were significantly increased. In the figure, 1, 2, 3, and 4 represent the PBS group, PAL group, RS1 group, and RS2 group, respectively.

[0082] As Figure 3 shown, the content of type I collagen in the HLF-1 cells treated with RS1 and RS2 was similar and higher than that in the PAL treatment group. Moreover, the pentapeptide-derived peptide segment RS provided by the present invention has better water solubility and does not need to be dissolved with an organic solvent when formulated into a preparation.

[0083] As Figure 3 shown, compared with the PBS control group, the expression levels of type I collagen in the HLF-1 cells treated with RS1, RS2, and PAL were all increased to a certain extent, and the expression levels of type I collagen in the HLF-1 cells treated with RS1 and RS2 were higher than that in the PAL treatment group. In the figure, 1, 2, 3, 4, and 5 represent the RS1 group, Marker group, RS2 group, PAL group, and PBS group, respectively.

[0084] Example 5

[0085] This experiment verified the effect of the pentapeptide-derived peptide segment RS on promoting the expression of type I collagen in human lung fibroblasts by immunofluorescence detection

[0086] 1. Test Samples and Grouping

[0087] RS1 treatment group: RS1 polypeptide (SEQ ID NO.7) prepared in Example 1.

[0088] RS2 treatment group: RS1 polypeptide (SEQ ID NO.8) prepared in Example 1.

[0089] PBS treatment group: PBS buffer

[0090] PAL treatment group: Commercially available N-terminally palmitoylated pentapeptide PAL-KTTKS (abbreviation "PAL").

[0091] 2. Experimental method

[0092] HLF-1 cells were cultured according to the method of Example 2. After the cells grew confluent, they were seeded onto cover slips at a ratio of 1:2.5. The test samples and groupings (2 μg / mL) were added to the cultured cells respectively. After 24 hours, the cells were fixed with 4% paraformaldehyde (dissolve paraformaldehyde in PBS (pH 7.5) and fix at room temperature for 15 minutes), and then placed in a refrigerator at 4°C for standby.

[0093] During the experiment, first add 0.2% tritonX100 and treat for 10 minutes, then wash with PBS 3 times, 5 minutes each time. Incubate it in PBS containing 1% skim milk powder for 30 minutes, then incubate with anti-type I collagen antibody at 37°C for 2 hours. Incubate with FITC-labeled secondary antibody at 37°C for 2 hours. Observe under a fluorescence microscope. The test results are shown in Figure 4 .

[0094] 3. Experimental results

[0095] As Figure 4 shown, compared with the PBS control group, the expression levels of type I collagen in HLF-1 cells treated with RS1, RS2, and PAL were all significantly increased, and the expression levels in the RS1 and RS2 groups were higher than those in the PAL group.

[0096] Example 6

[0097] This experiment was used to verify the anti-skin aging effect of the pentapeptide-derived peptide segment RS.

[0098] 1. Test samples and groupings

[0099] RS1 treatment group: RS1 polypeptide (SEQ ID NO.7) prepared in Example 1.

[0100] RS2 treatment group: RS1 polypeptide (SEQ ID NO.8) prepared in Example 1.

[0101] PAL treatment group: Commercially available N-terminally palmitoylated pentapeptide PAL-KTTKS (abbreviation "PAL").

[0102] The test samples and groups to be tested were each prepared into test sample and group solutions with a concentration of 200 μg / mL using water as a solvent for standby.

[0103] 2. Experimental method

[0104] Nine 9-month-old nude mice were taken. The test samples and groups to be tested were evenly applied (200 μg / mL) to one side of the skin on the back of the nude mice, and the RS0 preparation was applied to the corresponding skin on the other side as a control group. It was applied once a day for 4 consecutive weeks. After 4 weeks, the skin at the drug-applied site of the nude mice was taken to prepare paraffin sections, and then stained with MASSAN to detect the changes in the skin state after drug administration. The results are as Figure 5 shown.

[0105] 3. Experimental results

[0106] As Figure 5 shown, after the samples of RS1, RS2, and PAL were applied, the skin thickness of the nude mice was significantly thicker than that of the blank control group. Among them, the skin wrinkles treated with RS1 and RS2 were significantly fewer than those of the PAL treatment group, indicating that the anti-skin aging effect after the treatment with the pentapeptide-derived peptide segment RS provided by the present invention is better than that of PAL. In the figure, 1, 2, and 3 are the RS1, RS2, and PAL preparations respectively, and 4 is the blank control.

[0107] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A pentapeptide-derived peptide segment RS for anti-skin aging, characterized in that, The pentapeptide-derived peptide segment RS is selected from RRQRRYGRLMRRGGKTTKS or RRQRRTSKLMKRGGKTTKS.

2. Use of the pentapeptide-derived peptide segment RS according to claim 1 in the preparation of an anti-skin aging preparation.

3. The application according to claim 2, wherein The anti-skin aging as described above includes one or more of promoting the synthesis of collagen I, increasing the skin thickness, and reducing skin wrinkles.

4. An anti-skin aging composition, characterized in that, It includes an active ingredient and excipients, and the active ingredient includes the pentapeptide-derived peptide segment RS according to claim 1.

5. The anti-skin aging composition according to claim 4, wherein, The excipients as described above do not include a penetration enhancer.

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