Cyclic nonapeptides with skin barrier repair and anti-inflammatory efficacy and uses thereof

Abstract

This invention discloses a cyclic nonapeptide with skin barrier repair and anti-inflammatory effects. The amino acid sequence of the cyclic nonapeptide is: cyclic (arginine-glycine-aspartic acid-serine-arginine-lysine-valine-lysine-tryptophan). The cyclic nonapeptide of this invention can increase the relative expression levels of lobe rhabdominis (LOR), filaggrin (FLG), and aquaporin 3 (AQP3) genes, and reduce the secretion of inflammatory factors IL-6 and IL-8, thereby exhibiting skin barrier repair and anti-inflammatory effects.

Description

Technical Field

[0001] This invention relates to a cyclic peptide, particularly a cyclic nonapeptide with skin barrier repair and anti-inflammatory effects, and its applications. Background Technology

[0002] The skin barrier system is the first line of defense for the human skin, mainly composed of the sebum film, keratin (keratinocytes and intercellular lipids), and the dermis. The skin barrier system can be divided into multiple dimensions, including physical barriers, pigmentary barriers, neural barriers, immune barriers, and microbial barriers. Barrier repair is generally considered to primarily involve the physical barrier, namely, stratum corneum repair. The stratum corneum is the outermost layer of the skin. Together with intercellular lipids, it forms a wall of the skin, also known as keratinocytes, which are the main cellular components of the epidermis. They differentiate from the ectoderm and are tightly connected by intercellular bridges. Keratinocytes are characterized by producing keratin during differentiation, which functions as a barrier and absorbent. They also secrete cytokines such as interleukins (IL-6, IL-8, TNF-α, etc.) and interferons, participating in the presentation of foreign antigens, protecting the skin from external damage, maintaining the skin's internal moisture balance, forming a waterproof barrier to prevent moisture loss and block the entry of harmful substances.

[0003] Studies have reported that the formation of the stratum corneum involves the expression of several important keratin intermediate filament-related proteins, including filaggrin (FLG) and loricrin (LOR). FLG is a crucial undifferentiated protein in the epidermis, participating in epidermal cell differentiation and skin barrier formation, and is mainly found in the stratum corneum and granular layer of the epidermis. FLG is hydrolyzed into natural moisturizing factors, which help maintain the water content of the stratum corneum and participate in skin hydration, playing an important role in moisturizing and barrier integrity. Loricrin (LOR) is a marker of epidermal differentiation, accounting for approximately 80% of the total keratinocyte proteins. It is a glycine-rich protein mainly found in the granular layer of the epidermis. The study also reported that aquaporins (AQPs) are involved in skin barrier formation; they are transport proteins on the cell membrane related to the permeability of neutral small molecules such as water, glycerol, and urea. AQP3 is mainly expressed in the skin and is primarily found in keratinocytes and fibroblasts. AQP3 can transport water and glycerol, and plays an important role in maintaining epidermal hydration, affecting skin hydration status and skin elasticity. It also participates in cell migration, proliferation, differentiation, lipid metabolism and barrier formation.

[0004] When the skin barrier is damaged, the skin will produce a stress response, such as dry skin and allergies. Inflammatory factors will be secreted in the cells to promote inflammation, which will aggravate the damage to the skin and make it more sensitive.

[0005] There are currently few research reports on cyclic nonapeptides, which have skin barrier repair and anti-inflammatory effects. Summary of the Invention

[0006] The purpose of this invention is to provide a cyclic nonapeptide with skin barrier repair and anti-inflammatory effects, and its applications. This invention discovers a novel cyclic nonapeptide capable of repairing the skin barrier and possessing anti-inflammatory properties.

[0007] The technical solution of the present invention is a cyclic nonapeptide with skin barrier repair and anti-inflammatory effects, wherein the amino acid sequence of the cyclic nonapeptide is: cyclic (arginine-glycine-aspartic acid-serine-arginine-lysine-valine-lysine-tryptophan).

[0008] The aforementioned cyclic nonapeptide with skin barrier repair and anti-inflammatory effects has the following structural formula: .

[0009] The present invention also provides the application of the above-mentioned cyclic nonapeptide in the preparation of cosmetics with skin barrier repair and / or anti-inflammatory effects.

[0010] In the aforementioned applications, skin barrier repair refers to repairing skin barrier damage caused by sodium lauryl sulfate.

[0011] In the aforementioned applications, the anti-inflammatory effect is on skin inflammation caused by sodium lauryl sulfate.

[0012] In the aforementioned applications, the effective concentration of the cyclic nonapeptide is 1~100 μg / mL.

[0013] In the aforementioned applications, the effective concentration of the cyclic nonapeptide is 100 μg / mL.

[0014] A cosmetic composition with skin barrier repair function, comprising the above-mentioned cyclic nonapeptide.

[0015] A cosmetic composition with anti-inflammatory effects, comprising the aforementioned cyclononapeptide.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0017] The cyclic nonapeptide of the present invention, at a concentration of 100 μg / mL, can increase the relative expression levels of lobe rhinoceros protein (LOR), filaggrin (FLG) and aquaporin (AQP3) genes, thereby achieving the effects of moisturizing, improving skin elasticity, promoting cell migration, proliferation, differentiation, lipid metabolism and barrier formation, and has the function of skin barrier repair.

[0018] Cyclononapeptide, at a concentration of 100 μg / mL, can reduce the secretion of inflammatory factors IL-6 and IL-8, thereby achieving an anti-inflammatory effect. 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 The bar charts show the effects of each experimental group on the relative expression levels of skin barrier repair-related genes in keratinocytes. In the chart, A represents the relative expression level of LOR; B represents the relative expression level of FLG; and C represents the relative expression level of AQP3. Statistical analysis was performed. * indicates a significant difference compared to groups B and C, where "*" indicates P < 0.05, "**" indicates P < 0.01, and "***" indicates P < 0.001. # indicates a significant difference compared to the SDS group, where "#" indicates P < 0.05, "##" indicates P < 0.01, and "###" indicates P < 0.001. & indicates a significant difference compared to the modeling agent + sample group, where "&" indicates P < 0.05, "&&" indicates P < 0.01, and "&&&" indicates P < 0.001.

[0022] Figure 4 The bar charts show the effects of each experimental group on the secretion of inflammatory factors in keratinocytes. In the chart, A represents the secretion of IL-6, and B represents the secretion of IL-8. Statistical analysis was performed. * indicates a significant difference compared to groups B and C; "*" indicates P < 0.05, "**" indicates P < 0.01, and "***" indicates P < 0.001. # indicates a significant difference compared to the SDS group; "#" indicates P < 0.05, "##" indicates P < 0.01, and "###" indicates P < 0.001. & indicates a significant difference compared to the modeling agent + sample group; "&" indicates P < 0.05, "&&" indicates P < 0.01, and "&&&" indicates P < 0.001. Detailed Implementation

[0023] 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.

[0024] Example:

[0025] The cyclic nonapeptide was designed as 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.

[0026] Subsequently, structural simulation software was used to simulate the three-dimensional structures of the aforementioned 1600 cyclic peptides, and molecular docking software was used to calculate the energy difference between the 1600 cyclic peptides and linear peptide sequences. A structural simulation score (Total_score) < 0 indicates that the steric hindrance between the amino acid residues of the candidate cyclic peptide structure is small, making it suitable for forming a cyclic peptide structure and suitable for experimental verification. Thus, the structurally stable candidate cyclic nonapeptide RGDSRKVKW was selected.

[0027] Table 1. Difference between the energies of cyclic nonapeptide sequences and their corresponding linear peptide sequences.

[0028]

[0029] First, molecular docking simulations were performed between the RGDSRKVKW 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.

[0030] The docking fraction between the cyclic nonapeptide RGDSRKVKW and integrin αVβ3 was -10.0131, 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 1.594 Å, and the positions of each amino acid and the direction of side chain extension were very close, which is conducive to the binding of the cyclic nonapeptide to integrin αVβ3.

[0031] Subsequently, molecular docking simulations were performed between the RGDSRKVKW 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.

[0032] The docking fraction between the cyclic nonapeptide RGDSRKVKW and integrin α5β1 was -10.3699, 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 0.949 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.

[0033] The above molecular docking simulation results indicate that the structure of the cyclic nonapeptide is conducive to binding integrin αVβ3 and α5β1.

[0034] The amino acid sequence of the cyclic nonapeptide of the present invention is: cyclic (arginine-glycine-aspartic acid-serine-arginine-lysine-valine-lysine-tryptophan), i.e., Cyclo(Arg-Gly-Asp-Ser-Arg-Lys-Val-Lys-Trp), and the cyclic sequence is shown in SEQ ID NO.1. The structural formula is: .

[0035] The preparation method of cyclic nonapeptide is as follows:

[0036] S1. Using natural amino acids arginine-glycine-aspartic acid-serine-arginine-lysine-valine-lysine-tryptophan as starting materials, and employing a fluorene methyloxycarbonyl (Fmoc) N-terminal protection strategy, the corresponding amino acids are sequentially linked according to the resin solid-phase synthesis method, and the Fmoc- protecting groups are sequentially removed during the process to obtain a resin containing linear nonapeptide chains.

[0037] The specific steps are as follows:

[0038] 1) Swelling resin:

[0039] 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.

[0040] 2) Resin deprotection:

[0041] 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.

[0042] 3) Remove protective washing:

[0043] 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.

[0044] 4) Deprotection detection:

[0045] 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.

[0046] 5) Condensation of the second amino acid:

[0047] Add 3 equivalents of Fmoc-Val-OH and 3 equivalents of Oxyma to resin 1, dissolve it in 10 mL of DMF, add 3 equivalents of DIC, activate it for 5 min, pour it into the reactor, and stir to react for 1 h.

[0048] 6) Reaction washing:

[0049] 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.

[0050] 7) Reaction detection:

[0051] 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.

[0052] 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-Arg(Pbf)-OH, Fmoc-Ser(tBu)-OH, Fmoc-Asp(OtBu)-OH, Fmoc-Gly-OH, Fmoc-Arg(Pbf)-OH until Fmoc-Trp-OH, to obtain resin-3.

[0053] 9) Deprotection:

[0054] Add 20% Pip / DMF (10 mL / g) as a deprotection agent to resin-3, stir for 5 min and then dry it. Add 20% Pip / DMF (10 mL / g) and stir for 5 min.

[0055] 10) Remove protective wash:

[0056] 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.

[0057] 11) Deprotection detection:

[0058] 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 above for 2 minutes, remove and observe the resin color. A darker resin color indicates a positive result, signifying successful deprotection.

[0059] 12) Washing:

[0060] The resin was washed 45 times with methanol (10 mL) and vacuum dried for 10 min to complete solid-phase condensation, yielding a resin containing linear nonapeptide chains.

[0061] 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.

[0062] The specific steps are as follows:

[0063] 13) Resin-protected pyrolysis:

[0064] The resin containing the linear peptide 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.

[0065] 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.

[0066] The specific steps are as follows:

[0067] 14) Modification cyclization reaction:

[0068] Weigh out the fully protected polypeptide solid to be cyclic, dissolve it in AR grade DMF to obtain a polypeptide solution with a polypeptide concentration of 1 mM; after dissolution, weigh out 2 eq PyBOP and transfer 4 eq DIEA using an electronic balance, add them to the polypeptide solution, and stir at room temperature for 10 h to obtain a cyclic peptide containing a protecting group.

[0069] S4. The cyclic peptide containing the protecting group was purified by preparative HPLC to obtain cyclic nonapeptide.

[0070] The specific steps are as follows:

[0071] 15) Rotary freeze-drying:

[0072] After the reaction was complete, the reaction solution was concentrated using a rotary evaporator. After concentration, 30% acetonitrile / water solution was added to dissolve it, and then the solution was freeze-dried on the wall. Finally, the solution was purified by preparative HPLC to obtain the cyclic compound (arginine-glycine-aspartic acid-serine-arginine-lysine-valine-lysine-tryptophan).

[0073] Experimental example:

[0074] Laboratory consumables: Biosafety cabinet (Likang Biomedical Technology Holding Co., Ltd., NU-437-400S), CO2 incubator (Panasonic Electric Works Co., Ltd., MCO-18AIC), centrifuge (Sigma-Aldrich, USA, 2-16p), analytical balance (Sartorius Group, Germany, QUINTIX224-1CN), microscope (Japan Optical Industries Co., Ltd., Ts2R-FL), microplate reader (Tecan (Shanghai) Trading Co., Ltd., SPARK), real-time quantitative PCR instrument (Thermo Fisher Scientific, QuantStudio3).

[0075] Experimental reagents: Phosphate buffer (Lanjieke Technology Co., Ltd., BL302A), high-glucose DMEM medium (GibcoLife Technologies, 3062439), 0.25% trypsin solution (Gibco Life Technologies, 27250018), secondary antibody (Gibco Life Technologies, 15240062), fetal bovine serum (Shanghai Beyotime Biotechnology Co., Ltd., C0234), CCK-8 reagent (Yacoin Biotechnology Co., Ltd., BMU106), FastPure®® Cell / Tissue Total RNA Isolation Kit V2 (Nanjing Novizan Biotechnology Co., Ltd., RC112-01), HiScript®® II Q RT SuperMix for qPCR (+gDNA wiper) (Nanjing Novizan Biotechnology Co., Ltd., R223-01), Taq Pro Universal SYBR qPCR Master Mix (Nanjing Novizan Biotechnology Co., Ltd., Q712-02), IL-6 ELISA kit (Beijing Solarbio Science & Technology Co., Ltd., SEKH-0013), IL-8 ELISA kit (Beijing Solarbio Science & Technology Co., Ltd., SEKH-0016), sodium dodecyl sulfate (Shanghai Aladdin Biochemical Technology Co., Ltd., F2224167), cyclic nonapeptide (Genscript Biotech Co., Ltd., C6772NNNG0-1).

[0076] Preparation of cyclic nonapeptide solution: Reagent grade, a water-soluble raw material. The powder can be directly dissolved in an EP tube containing 1 mL of deionized water, shaken to mix, and after complete dissolution, this is used as the stock solution concentration. During the experiment, it can be diluted with deionized water to the corresponding concentration.

[0077] 1. Cytotoxicity test:

[0078] 1.1 Experimental Groups: A blank control group, a sample group, and a zero-adjustment group were set up. Blank control group: contained only cells and culture medium; Sample group: contained cells and a certain concentration of sample; Zero-adjustment group: contained no cells, only culture medium. Within the sample group, each sample was set up with 7 concentration gradients (1, 3, 5, 10, 30, 50, 100 μg / mL), with 6 replicate wells for each concentration gradient.

[0079] 1.2 Experimental Methods: After resuscitating HaCaT cells, passage them through one generation. When the confluence of passaged cells reaches 70%–80%, seed them into 96-well plates, 100 μL per well. The zero-cell group and the outer wells of the 96-well plate are cell-free; add 100 μL of PBS to prevent evaporation of the cell culture medium. Incubate the 96-well plates overnight in an incubator (37°C, 5% CO2).

[0080] When the cell confluence in the 96-well plate 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 the corresponding concentration of the sample was added to each well of the sample group; 100 μL of culture medium was added to each well of the blank control group; if PBS in the zeroing group and the outer wells of the 96-well plate evaporated, it could be replenished appropriately. After loading the samples, the 96-well plate was incubated in an incubator (37℃, 5% CO2) for 48 h. After 48 h of incubation, the supernatant was discarded, and CCK-8 reagent was added. The plate was incubated at 37℃ in the dark for 1–4 h. After incubation, the OD value was read at 450 nm.

[0081] According to the formula, the relative cell viability (%) = (sample well OD - zeroing well OD) / (blank control well OD - zeroing well OD) × 100%.

[0082] The specific design scheme is shown in Table 2.

[0083] Table 2. Cytotoxicity Experimental Design

[0084]

[0085] 1.2 Experimental Results:

[0086] The results of the cytotoxicity assay for cyclic nonapeptide are shown in Table 3.

[0087] Table 3. Effects of cyclic nonapeptide on keratinocyte toxicity

[0088]

[0089] As shown in Table 3, the concentration of cyclic nonapeptide ranges from 1 to 100 μg / mL. When keratinocytes are treated, the cell viability reaches over 90%, and it is non-toxic to keratinocytes.

[0090] 2. Skin barrier repair experiment:

[0091] 2.1 Experimental Groups: A blank control group, a modeling agent group, a modeling agent + sample group, and a sample group were set up, with 3 replicates per group. Blank control group: Contains only cells and culture medium; Modeling agent group: Contains cells and a certain concentration of sodium dodecyl sulfate (SDS); Modeling agent + sample group: Contains cells, a certain concentration of modeling agent, and sample; Sample group: Contains cells and a certain concentration of sample.

[0092] 2.2 Experimental Methods: After resuscitating HaCaT cells, when the cell confluence reached 70%–80%, they were seeded into 6-well plates (2 mL per well). After mixing, the plates were incubated overnight at 37°C in a 5% CO2 incubator. When the cell confluence in the 6-well plates reached 40%–60% under a microscope, the old culture medium was discarded, and the medium was changed and drug administered to the affected groups. For the control group, 2 mL of culture medium was added to each well; for the model group, 2 mL of culture medium containing the corresponding concentration of sodium dodecyl sulfate (SDS) was added to each well. After stimulation for 30 min, for the sample group, 2 mL of culture medium containing the corresponding concentration of the sample was added to each well. After loading, the 6-well plates were incubated for 24 h.

[0093] Total RNA was extracted from cells in each group, and then the expression levels of LOR, FLG, and AQP3 genes in the cells were detected according to the instructions for real-time quantitative PCR, using GAPDH as an internal reference gene.

[0094] The specific design scheme is shown in Table 4.

[0095] Table 4. Experimental Group Design Scheme

[0096]

[0097] 2.3 Experimental Results:

[0098] The results of the skin barrier repair experiment of cyclic nonapeptide are as follows: Figure 3As shown in the results, compared with the blank control group, the relative expression levels of LOR, FLG, and AQP3 genes in the modeling agent group were significantly downregulated, with downregulation rates of 79.85%, 45.49%, and 53.38%, respectively. However, compared with the modeling agent group, the relative expression levels of these genes in the SDS + cyclic nonapeptide-100 μg / mL group were significantly upregulated, with upregulation rates of 406.42%, 83.05%, and 124.67%, respectively. The relative expression levels of these genes in the cyclic nonapeptide-100 μg / mL group alone were significantly upregulated, with upregulation rates of 261.67%, 67.69%, and 153.68%, respectively. This indicates that cyclic nonapeptide, at a concentration of 100 μg / mL, can increase the relative expression levels of LOR, FLG, and AQP3 genes, thereby playing a role in skin barrier repair and enhancing skin barrier function.

[0099] Therefore, it is a cyclic nonapeptide with skin barrier repair function.

[0100] 3. Anti-inflammatory efficacy experiment:

[0101] 3.1 Experimental Groups: A blank control group, a modeling agent group, a modeling agent + sample group, and a sample group were set up, with 3 replicates per group. Blank control group: Contains only cells and culture medium; Modeling agent group: Contains cells and a certain concentration of SDS; Modeling agent + sample group: Contains cells, a certain concentration of modeling agent, and sample; Sample group: Contains cells and a certain concentration of sample.

[0102] 3.2 Experimental Methods: After resuscitating HaCaT cells, when the cell confluence reached 70%–80%, they were seeded into 6-well plates (2 mL per well). After mixing, the cells were incubated overnight at 37°C in a 5% CO2 incubator. When the cell confluence in the 6-well plates reached 40%–60% under a microscope, the old culture medium was discarded, and the medium was changed and drug administered to the affected groups. For the control group, 2 mL of culture medium was added to each well; for the model group, 2 mL of culture medium containing the corresponding concentration of SDS was added to each well. After stimulation for 30 min, for the sample group, 2 mL of culture medium containing the corresponding concentration of the sample was added to each well. After loading, the 6-well plates were incubated for 24 h. The supernatant from each well was collected into centrifuge tubes, centrifuged at 1000 rpm for 10 min, and the supernatant was collected for the detection of inflammatory factor secretion.

[0103] The specific design scheme is shown in Table 5.

[0104] Table 5. Anti-inflammatory design scheme

[0105]

[0106] 3.3 Experimental Results:

[0107] Experimental results of the anti-inflammatory efficacy of cyclic nonapeptide Figure 4 As shown.

[0108] The results showed that, compared with the blank control group, the secretion of inflammatory factors IL-6 and IL-8 was significantly increased in the modeling agent group, with increases of 238.41% and 55.08%, respectively. However, compared with the modeling agent group, the secretion of inflammatory factors IL-6 and IL-8 was significantly decreased in the SDS + cyclic nonapeptide 100 μg / mL group, with inhibition rates of 30.67% and 15.61%, respectively. Cyclic nonapeptide alone (100 μg / mL) also significantly decreased the secretion of inflammatory factors IL-6 and IL-8, with inhibition rates of 80.42% and 32.87%, respectively. This indicates that cyclic nonapeptide at a concentration of 100 μg / mL can reduce the secretion of inflammatory factors IL-6 and IL-8, thereby achieving an anti-inflammatory effect. Therefore, it is a cyclic nonapeptide with anti-inflammatory properties.

[0109] 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 skin barrier repair and anti-inflammatory effects, characterized in that: The amino acid sequence of the cyclic nonapeptide is: cyclic (arginine-glycine-aspartic acid-serine-arginine-lysine-valine-lysine-tryptophan).

2. The cyclic nonapeptide with skin barrier repair and anti-inflammatory effects according to claim 1, characterized in that: The structural formula of the cyclic nonapeptide is: .

3. The use of the cyclic nonapeptide according to any one of claims 1-2 in the preparation of cosmetics with skin barrier repair and / or anti-inflammatory effects.

4. The application according to claim 3, characterized in that: Skin barrier repair refers to repairing skin barrier damage caused by sodium lauryl sulfate.

5. The application according to claim 3, characterized in that: The inflammation is caused by sodium lauryl sulfate.

6. The application according to claim 3, characterized in that: The effective concentration of the cyclic nonapeptide is 1~100 μg / mL.

7. The application according to claim 3, characterized in that: The effective concentration of the cyclic nonapeptide is 100 μg / mL.

8. A cosmetic composition with skin barrier repair function, characterized in that: It includes the cyclic nonapeptide as described in any one of claims 1-2.

9. A cosmetic composition with anti-inflammatory effects, characterized in that: It includes the cyclic nonapeptide as described in any one of claims 1-2.

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