A cyclic nonapeptide with antioxidant and whitening effects and its applications
By preparing the cyclic nonapeptide RGDSRKVKK, the problems of poor stability and limited variety of antioxidant peptides in existing whitening ingredients have been solved, achieving antioxidant and whitening effects in skin care products.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- PROYA COSMETICS CO LTD
- Filing Date
- 2026-07-02
- Publication Date
- 2026-07-31
AI Technical Summary
Existing whitening ingredients have poor stability and strong irritation, making it difficult to fully address skin tone problems caused by oxidative stress, and the types of antioxidant and whitening peptides are limited.
A cyclic nonapeptide RGDSRKVKK was developed and prepared by resin solid-phase synthesis. It has antioxidant and whitening effects, and can scavenge ROS and inhibit melanin production.
Cyclic nonapeptide RGDSRKVKK is harmless to cells at low toxicity concentrations and has significant antioxidant and whitening effects, capable of scavenging reactive oxygen species and inhibiting melanin production.
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Figure CN122483153A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a cyclic peptide, particularly a cyclic nonapeptide with antioxidant and whitening effects and its applications. Background Technology
[0002] Ultraviolet radiation in nature primarily originates from the sun. In recent years, with the increasing depletion of the ozone layer, the dose of ultraviolet radiation reaching the Earth's surface has increased, becoming one of the dangerous factors threatening human skin health. Medium-wave ultraviolet (UVB) radiation reaches the epidermis, causing skin damage by inducing oxidative stress and DNA damage. Keratinocytes, as the main component of the epidermis, are one of the primary sites of oxidative stress. When oxidative stress occurs, large amounts of reactive oxygen species (ROS) are produced within the cells. Excessive ROS not only attack cell membranes, proteins, and DNA, inducing inflammation and damaging the skin barrier function, but also activate melanin production pathways, leading to skin problems such as dull skin tone and age spots.
[0003] Currently available skin whitening ingredients generally suffer from poor stability and strong irritation, and they usually only act on a single pathway, making it difficult to comprehensively address skin tone problems caused by oxidative stress.
[0004] Among numerous functional peptide raw materials, polypeptides exhibit broad application prospects in the field of skin care due to their advantages such as strong sequence designability, well-defined targets, and high biocompatibility. However, the types of polypeptides currently used in the fields of anti-oxidation and whitening are still limited, and there are currently no research reports on cyclic nonapeptides that focus on anti-oxidation and whitening effects. Summary of the Invention
[0005] The purpose of this invention is to provide a cyclic nonapeptide with antioxidant and skin-whitening effects, and its applications. This invention discovers a novel cyclic nonapeptide with skin antioxidant and skin-whitening effects.
[0006] The technical solution of the present invention is: a cyclic nonapeptide with antioxidant and whitening effects, wherein the amino acid sequence of the cyclic nonapeptide is: cyclic (arginine-glycine-aspartic acid-serine-arginine-lysine-valine-lysine-lysine).
[0007] The aforementioned cyclic nonapeptide with antioxidant and whitening effects has the following structural formula: .
[0008] In the aforementioned cyclic nonapeptide with antioxidant and whitening effects, the cyclic nonapeptide is prepared by resin solid-phase synthesis using a fluorene methoxycarbonyl N-terminal protection strategy.
[0009] The present invention also provides the application of the above-mentioned cyclic nonapeptide in the preparation of skin antioxidant and / or whitening products.
[0010] In the aforementioned applications, the cellular concentration of the cyclic nonapeptide is ≤100ppm.
[0011] In the aforementioned applications, the cellular concentration of the cyclic nonapeptide is 100 ppm.
[0012] In the aforementioned applications, the product is a cosmetic, pharmaceutical, and / or health food.
[0013] A skin antioxidant and / or skin whitening cosmetic, comprising the aforementioned cyclic nonapeptide and a cosmetically acceptable carrier.
[0014] A skin antioxidant and / or skin whitening drug comprising the aforementioned cyclic nonapeptide and a pharmaceutically acceptable carrier.
[0015] A health food product for skin anti-oxidation and / or whitening, comprising the aforementioned cyclic nonapeptide and a food-grade acceptable carrier.
[0016] Compared with the prior art, the beneficial effects of the present invention are as follows:
[0017] The cyclic nonapeptide RGDSRKVKK of this invention was prepared by resin solid-phase synthesis. Cytotoxicity tests demonstrated that RGDSRKVKK was non-toxic to HaCaT cells at concentrations ≤100 μg / mL and non-toxic to B16F10 cells at concentrations ≤250 μg / mL. Antioxidant and whitening experiments demonstrated that RGDSRKVKK possesses the ability to scavenge ROS, thus exerting an antioxidant effect; and it can inhibit melanin production, thus exerting a whitening effect.
[0018] Therefore, the cyclic nonapeptide RGDSRKVKK of the present invention has dual effects of anti-oxidation and whitening, and can be used as an active ingredient in cosmetics, pharmaceuticals or health foods for skin anti-oxidation and / or whitening. Attached Figure Description
[0019] Figure 1 This is a simulation diagram of the docking of the cyclic nonapeptide with integrin aVβ3 in this invention.
[0020] Figure 2 This is a simulation diagram of the docking of the cyclic nonapeptide and integrin a5β1 molecules in this invention.
[0021] Figure 3 This is a statistical graph showing the effect of the cyclic nonapeptide in this invention on the viability of HaCaT cells.
[0022] Figure 4 This is a statistical graph showing the effect of the cyclic nonapeptide in this invention on the viability of B16F10 cells.
[0023] Figure 5The figures show the effects of each experimental group on the ROS level of HaCaT cells; * indicates a significant difference compared to the BC group, and "****" indicates P<0.0001.
[0024] Figure 6 This is a statistical graph showing the effect of each experimental group on the melanin content of B16F10 cells; * in the graph indicates a significant difference compared to group BC, and "****" indicates P<0.0001. Detailed Implementation
[0025] The present invention will be further described below with reference to embodiments, but these embodiments are not intended to limit the scope of the invention.
[0026] Example:
[0027] Structural simulation and screening of cyclic nonapeptides:
[0028] This invention designs cyclic nonapeptides as the sequence RGDS-X1-KVK-X2, where X1 and X2 are one of 20 L-amino acids and one of 20 D-amino acids, respectively, for a total of 40×40=1600 cyclic nonapeptide candidate sequences.
[0029] The three-dimensional structures of the 1600 candidate cyclic peptides were simulated using structural simulation software. Then, the energy differences between the 1600 candidate cyclic peptides and their corresponding linear peptide sequences were calculated using molecular docking software. A structural stability score (Total_score) < 0 indicates that the cyclic peptide structure has low steric hindrance between amino acid residues, exhibits better structural stability than its linear peptide form, and can stably form a cyclic peptide structure, making it suitable for further experimental verification. The structural stability scoring table is shown in Table 1.
[0030] Table 1. Structural stability scores of different cyclic peptide sequences
[0031]
[0032] Based on the above screening criteria, this invention screened out structurally stable candidate cyclic nonapeptide RGDSRKVKK.
[0033] Molecular docking simulations were performed between the RGDSRKVKK cyclic nonapeptide structure and integrin αVβ3. Based on the crystal structure (αVβ3_PDB ID: 4MMX) in the Protein Data Bank, the RGDS sequence from the cyclic peptide was docked to the RGDS sequence in the αVβ3 complex crystal structure. The specific docking structure simulation diagram is shown below. Figure 1 As shown. Figure 1 In the diagram, the red linear structures represent the positions of the RGDS peptide segments in the known 4MMX crystal structure, while the green and blue rod-shaped structures represent cyclic nonapeptides.
[0034] The docking fraction between the cyclic nonapeptide RGDSRKVKK and integrin αVβ3 was -9.6304, which is less than -7, indicating a strong binding interaction. The docking results showed that the RMSD of the RGDS sequence of the cyclic nonapeptide and the RGDS sequence in the 4MMX crystal structure was 0.397 Å, and the positions of the amino acids and the direction of the side chain extension were very close, which is conducive to the binding of the cyclic nonapeptide to integrin αVβ3.
[0035] Subsequently, molecular docking simulations were performed between the RGDSRKVKK cyclic nonapeptide structure and integrin α5β1. Based on the crystal structure (α5β1_PDB ID: 4WK2) in the Protein Data Bank, the RGDS sequence in the cyclic peptide was docked to the RGDS sequence in the α5β1 complex crystal structure. The specific docking structure simulation diagram is shown below. Figure 2 As shown. Figure 2 In the diagram, the red linear structures represent the position of the RGDS peptide in the known crystal structure 4WK2, while the green and blue rod-shaped structures represent cyclic nonapeptides.
[0036] The docking fraction between the cyclic nonapeptide RGDSRKVKK and integrin α5β1 was -11.1479, which is less than -7, indicating a strong binding interaction. The docking results showed that the RMSD of the RGDS sequence of the cyclic nonapeptide and the RGDS sequence in the crystal structure 4WK2 was 0.718 Å, and the positions of the amino acids and the direction of the side chain extension were very close, which is conducive to the binding of the cyclic nonapeptide to integrin α5β1.
[0037] The above molecular docking simulation results indicate that the structure of the cyclic nonapeptide is conducive to binding integrin αVβ3 and α5β1.
[0038] The amino acid sequence of the cyclic nonapeptide of the present invention is: cyclic (arginine-glycine-aspartic acid-serine-arginine-lysine-valine-lysine-lysine), i.e., Cyclo(Arg-Gly-Asp-Ser-Arg-Lys-Val-Lys-Lys), and the cyclic sequence is shown in SEQ ID NO.1. The structural formula is: .
[0039] The preparation method of cyclic nonapeptide is as follows:
[0040] S1. Using natural amino acids arginine-glycine-aspartic acid-serine-arginine-lysine-valine-lysine-lysine as starting materials, a fluorene methoxycarbonyl (Fmoc) N-terminal protection strategy is adopted, and the corresponding amino acids are sequentially linked according to the resin solid-phase synthesis method, during which the Fmoc- protecting group is sequentially removed to obtain a resin containing a linear nonapeptide chain.
[0041] The specific steps are as follows:
[0042] 1) Swelling resin:
[0043] 0.6 g of 2-Cl Trt-Lys resin (degree of substitution SD = 0.39 mmol / g) was added to the reactor, and DCM (10 mL / g) was added as a swelling agent to induce swelling for 5 min.
[0044] 2) Resin deprotection:
[0045] Vacuum-dry the swollen reagent DCM, add 20% piperidine (Pip) / DMF (10 mL / g) as a deprotection agent, stir for 5 min, dry under vacuum, and then add 20% piperidine (Pip) / DMF (10 mL / g) and stir for 5 min.
[0046] 3) Remove protective washing:
[0047] The protective reagent Pip / DMF was removed by vacuum drying, and the resin was washed 5 times with DMF (10 mL / g), stirring for 20-30 seconds each time and then dried for 20 seconds to obtain resin-1.
[0048] 4) Deprotection detection:
[0049] Take about 20 resin-1 particles and put them into a test tube. Add 1 mL of ninhydrin detection reagent to the test tube, and then put the test tube into a metal bath at 120°C or above for 2 minutes. Take it out and observe the color of the resin. If the resin color becomes darker, it is a positive result, indicating that the deprotection was successful.
[0050] 5) Condensation of the second amino acid:
[0051] Add 3 equivalents of Fmoc-Val-OH and 3 equivalents of Oxyma to resin-1, dissolve in 10 mL of DMF, add 3 equivalents of DIC, activate for 5 min, pour into a reactor, and stir to react for 1 h.
[0052] 6) Reaction washing:
[0053] The reaction reagent DMF was dried under vacuum, and the mixture was washed 5 times with DMF (10 mL / g), stirring for 20-30 seconds each time and then dried under vacuum for 20 seconds to obtain resin-2.
[0054] 7) Reaction detection:
[0055] Take about 20 resin-2 particles and put them into a test tube. Add 1 mL of ninhydrin test reagent to the test tube, and then put the test tube into a metal bath at 120°C or above for 2 minutes. Take it out and observe the color of the resin. If there is no obvious change in the color of the resin, it indicates that the reaction condensation is successful.
[0056] 8) Repeat steps 2)-7), condensing the subsequent amino acids in the sequence from right to left according to the polypeptide sequence, namely Fmoc-Lys(Boc)-OH, Fmoc-Lys(Boc)-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Gly-OH, Fmoc-Asp(OtBu)-OH, Fmoc-Ser(tBu)-OH until Fmoc-Arg(Pbf)-OH ends, to obtain resin-3.
[0057] 9) Deprotection:
[0058] Add 20% Pip / DMF (10 mL / g) by volume to resin-3 as a deprotection agent, stir for 5 min and then dry under vacuum. Add 20% Pip / DMF (10 mL / g) by volume again and stir for 5 min.
[0059] 10) Remove protective wash:
[0060] The protective reagent Pip / DMF was removed by vacuum drying, and then washed 5 times with DMF (10 mL / g), stirring for 20-30 s each time and drying for 20 s to obtain resin-4.
[0061] 11) Deprotection detection:
[0062] Place approximately 20 resin-4 particles into a test tube, add 1 mL of ninhydrin detection reagent, place the test tube in a metal bath at 120°C or higher for 2 minutes, remove and observe the resin color. A darker resin color indicates a positive result, signifying successful deprotection.
[0063] 12) Washing:
[0064] The resin was washed 5 times with 10 mL of methanol and then vacuum dried for 10 min to complete solid-phase condensation, yielding a resin containing linear nonapeptide chains.
[0065] S2. Cut the resin containing the linear nonapeptide chain, cut the linear nonapeptide chain off the resin, remove the remaining protecting groups of the peptide chain, collect the cutting fluid containing the crude linear nonapeptide chain, and obtain a fully protected polypeptide solid to be cyclic.
[0066] The specific steps are as follows:
[0067] 13) Resin-protected pyrolysis:
[0068] The resin containing the linear nonapeptide chain was loaded into a boat-shaped reactor, and 10 mL / g lysis buffer (TFE:DCM volume ratio of 30:70) was added. The mixture was lysed three times at room temperature for 1 hour each time. The reaction solution was filtered out, and the solvent was concentrated and evaporated using a rotary evaporator. After evaporation, the sample was dissolved in 30% acetonitrile / water solution and lyophilized to obtain a fully protected peptide solid.
[0069] S3. The fully protected polypeptide solid to be cyclized is mixed with polypeptide coupling agent, activator, etc., and then cyclized to obtain a cyclic peptide containing a protecting group.
[0070] The specific steps are as follows:
[0071] 14) Modification cyclization reaction:
[0072] Weigh out the fully protected polypeptide solid to be cyclic, dissolve it in AR grade DMF to obtain a polypeptide solution with a concentration of 1 mM; after dissolution, weigh out 2 eq PyBOP using an electronic balance, and transfer 4 eq DIEA to the polypeptide solution, stir at room temperature for 10 h to obtain a cyclic peptide containing a protecting group.
[0073] S4. The cyclic peptide containing the protecting group was purified by preparative HPLC to obtain cyclic nonapeptide.
[0074] The specific steps are as follows:
[0075] 15) Rotary freeze-drying:
[0076] After the reaction was complete, the cyclic peptide reaction solution containing the protecting group was concentrated using a rotary evaporator. After concentration, 30% (v / v) acetonitrile / water solution was added to dissolve it, followed by freeze-drying on the wall. Finally, preparative HPLC was used to purify the cyclic peptide to obtain cyclic (arginine-glycine-aspartic acid-serine-arginine-lysine-valine-lysine-lysine).
[0077] Experimental example:
[0078] Laboratory consumables: Biosafety cabinet (Nuaire, USA, NU-543-600s), CO2 incubator (Panasonic Corporation, MCO-18AIC), centrifuge (Eppendorf AG, Germany, Centrifuge 5804R), mini cryogenic centrifuge (Sigma, Germany, 1-14K), analytical balance (Sartorius Group, Germany, BCE224-1CCN), microscope (Carl Zeiss Microscopes (Germany) GmbH, Axio Observer3), microplate reader (Tecan Group, Switzerland, SPARK), ultraviolet irradiator (Hangzhou Genofe Biotechnology Co., Ltd., UV-621111801).
[0079] Experimental reagents: Phosphate-buffered saline (PBS, Beijing Lanjieke Technology Co., Ltd., BL1425A), high-glucose DMEM medium (Thermo Fisher Scientific, Gibco, 11965092), low-glucose DMEM medium (Thermo Fisher Scientific, Gibco, 11885084), 0.25% trypsin solution (Thermo Fisher Scientific, Gibco, 25200056), penicillin-streptomycin (Thermo Fisher Scientific, Gibco, 15070063), fetal bovine serum (Shanghai Beyotime Biotechnology Co., Ltd., C0234), ROS detection kit (Shanghai Beyotime Biotechnology Co., Ltd., S0033M), CCK8 kit (Shanghai Beyotime Biotechnology Co., Ltd., C0038), NaOH solution containing 10% DMSO (Shanghai Maclean Biochemical Technology Co., Ltd., S804530).
[0080] Preparation of cyclic nonapeptide solution: Reagent grade, which is a water-soluble raw material. Dissolve the cyclic nonapeptide powder directly in PBS solution, shake to mix, and use this as the stock solution concentration after complete dissolution. Dilute with PBS solution to the appropriate concentration during the experiment.
[0081] 1. Cytotoxicity test:
[0082] 1.1 Experimental grouping: A blank control group (BC), a sample group, and a zeroing group were set up.
[0083] 1.2 Experimental Methods: Human immortalized keratinocytes (HaCaT cells) or mouse skin melanoma cells (B16F10 cells) were cultured at a concentration of 1×10⁻⁶ cells. 4 The cells were evenly seeded into 96-well plates at a uniform density. The plates were incubated overnight in an incubator (37°C, 5% CO2). When the cell confluence reached 40%–60% under a microscope, the old culture medium was discarded, and the medium was changed and drug administered to the groups. 100 μL of culture medium containing different concentrations of cyclic nonapeptide was added to each well of the sample group; 100 μL of culture medium was added to each well of the blank control group; and 100 μL of PBS solution was added to each well of the zeroing group and the outer wells of the 96-well plate. After loading, the 96-well plates were incubated for 48 h in an incubator (37°C, 5% CO2). The experiment was performed according to the Beyotime CCK8 kit instructions, measuring the absorbance of each well and calculating cell viability. Data analysis software was used for data analysis and plotting.
[0084] The specific design scheme is shown in Table 2.
[0085] Table 2. Cytotoxicity Experimental Design
[0086]
[0087] The formula for calculating the cell viability of cyclic nonapeptide is: relative cell viability (%) = (OD of sample well - OD of zeroing well) / (OD of blank control well - OD of zeroing well) × 100%.
[0088] 1.3 Experimental Results:
[0089] The cytotoxicity results of the cyclic nonapeptide are shown in Table 3. Figure 3 and Figure 4 As shown.
[0090] Table 3. Effects of cyclic nonapeptide on cytotoxicity
[0091]
[0092] Based on the toxicity test results, from Table 3, Figure 3 and Figure 4 It can be seen that when HaCaT cells were treated with cyclic nonapeptide, the cell viability reached more than 90% at a concentration ≤100μg / mL compared with the blank control group, and it was non-toxic to the cells; when B16F10 cells were treated with cyclic nonapeptide, the cell viability reached more than 90% at a concentration ≤250μg / mL compared with the blank control group, and it was non-toxic to the cells.
[0093] 2. Antioxidant experiment:
[0094] 2.1 Experimental grouping: A blank control group, a model control group, a positive control group, and a sample group were set up, with 3 replicates in each group.
[0095] 2.2 Experimental Methods: HaCaT cells were cultured at 1.0 × 10⁻⁶ cells / cells. 5 Inoculate cells per well evenly into 12-well plates and incubate overnight in an incubator (37℃, 5% CO2). When the cell confluence in the 12-well plates reaches 70%-90% under a microscope, discard the old culture medium, change the medium and administer drugs to the groups, and then incubate the 12-well plates in an incubator (37℃, 5% CO2) for 24 hours. The model control group, positive control group, and sample group receive 210 mJ / cm² water. 2 Cells were irradiated with UVB once, and then incubated in a 12-well plate in an incubator (37℃, 5% CO2) for 24 h. Following the instructions of the reactive oxygen species (ROS) detection kit (Beyotime), the DCFH-DA probe was incubated. After incubation, cells were collected and counted. Fluorescence intensity was measured at an excitation wavelength of 488 nm and an emission wavelength of 525 nm for each group, and the relative fluorescence intensity and scavenging rate of ROS were calculated. Data analysis software was used for data analysis and plotting. Statistical comparisons were performed using t-tests or one-way ANOVA, with P < 0.05 considered statistically significant.
[0096] The specific experimental design is shown in Table 4.
[0097] Table 4. Experimental protocol for the effect of cyclic nonapeptide on ROS levels in HaCaT cells.
[0098] 2.3 Experimental Results:
[0099] The antioxidant experimental results of cyclic nonapeptide RGDSRKVKK are shown in Table 5. Figure 5 As shown.
[0100] Table 5. Effects of cyclic nonapeptide on ROS levels in HaCaT cells
[0101]
[0102] The experimental results showed that the ROS fluorescence intensity of the model control group (UVB) was significantly enhanced compared with the blank control group (BC). Compared with the model control group, the ROS fluorescence intensity of both the positive control group (UVB-rapamycin) and the sample group (UVB-cyclic nonapeptide) was significantly reduced, with statistically significant differences. The cyclic nonapeptide RGDSRKVKK at an experimental concentration of 100 μg / mL achieved a 20.94% ROS scavenging rate in HaCaT cells, indicating that the cyclic nonapeptide has the ability to scavenge ROS, thereby exerting an antioxidant effect.
[0103] 3. Whitening Experiment:
[0104] 3.1 Experimental grouping: A blank control group, a positive control group, and a sample group were set up, with 3 replicates in each group.
[0105] 3.2 Experimental Methods: B16F10 cells were cultured at a density of 2 × 10⁶ cells per well. 5 Cells were evenly seeded in 6-well plates and incubated overnight in an incubator (37℃, 5% CO2). When the cell confluence reached 70%-90% under a microscope, the old culture medium was discarded, and the cells were grouped and treated according to the methods in Table 6. The 6-well plates were then incubated for 48 hours in an incubator (37℃, 5% CO2). Cells were washed with pre-cooled PBS, and 180 μL of 1M NaOH (containing 10% DMSO) solution was added to each well. Cells were incubated at 80℃ for 30 minutes. After incubation, 80 μL of each cell was transferred to a new 96-well plate, and the OD value was read at 405 nm using a microplate reader to detect the melanin content. Data analysis software was used for data analysis and plotting. Statistical comparisons were performed using t-tests or one-way ANOVA, with P < 0.05 considered statistically significant.
[0106] The specific experimental design is shown in Table 6.
[0107] Table 6. Experimental protocol for the effect of cyclic nonapeptide on melanin content in B16F10 cells.
[0108] 3.3 Experimental Results:
[0109] The whitening experimental results of cyclic nonapeptide RGDSRKVKK are shown in Table 7. Figure 6 As shown.
[0110] Table 7. Effects of cyclic nonapeptide on melanin content in B16F10 cells
[0111]
[0112] The experimental results showed that, compared with the blank control group (BC), the melanin content of the positive control group (α-arbutin) and the sample group (cyclic nonapeptide) was significantly reduced, with statistically significant differences. Cyclic nonapeptide at an experimental concentration of 100 μg / mL inhibited melanin production in B16F10 cells by 16.15%, indicating that cyclic nonapeptide can exert a whitening effect by inhibiting melanin production.
[0113] It should be understood that the above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit them. Those skilled in the art can modify the technical solutions described in the above embodiments, or make equivalent substitutions for some of the technical features; and all such modifications and substitutions should fall within the protection scope of the appended claims of the present invention.
Claims
1. A cyclic nonapeptide with antioxidant and whitening effects, characterized in that: The amino acid sequence of the cyclic nonapeptide is: cyclic (arginine-glycine-aspartic acid-serine-arginine-lysine-valine-lysine-lysine).
2. The cyclic nonapeptide with antioxidant and whitening effects according to claim 1, characterized in that: The structural formula of the cyclic nonapeptide is: .
3. The cyclic nonapeptide with antioxidant and whitening effects according to claim 1 or 2, characterized in that: The cyclic nonapeptide was prepared by resin solid-phase synthesis using a fluorene methyloxycarbonyl N-terminal protection strategy.
4. The use of the cyclic nonapeptide according to any one of claims 1-2 in the preparation of skin antioxidant and / or whitening products.
5. The application according to claim 4, characterized in that: The cellular concentration of the cyclic nonapeptide is ≤100ppm.
6. The application according to claim 4, characterized in that: The cellular concentration of the cyclic nonapeptide is 100 ppm.
7. The application according to claim 4, characterized in that: The products mentioned are cosmetics and / or pharmaceuticals.
8. A skin antioxidant and / or whitening cosmetic, characterized in that: It includes the cyclic nonapeptide as described in any one of claims 1-2.
9. A skin antioxidant and / or whitening medicine, characterized in that: It includes the cyclic nonapeptide as described in any one of claims 1-2.