Polypeptide with anti-inflammatory activity and application thereof

Abstract

The invention provides skin anti-inflammatory application of cyclic polypeptide, the polypeptide contains SEQ ID NO: 1, and disulfide bonds at the head and the tail of the polypeptide are cyclized. The skin anti-inflammatory agent disclosed by the invention comprises the step of inhibiting the expression of thymic stromal lymphopoietin (TSLP), interleukin-13 (IL-13), interleukin-31 (IL-31) and / or interleukin-33 (IL-33). The invention also relates to an application of the cyclic polypeptide in preparation of medicines or external skin preparations for preventing and / or treating Th2 type immune related diseases. The external skin preparations are selected from face cream, emulsion, gel, toning lotion, essence, masks, eye cream, aerosol cleaning foam, spray, shower gel or facial cleanser.

Description

Technical Field

[0001] This invention pertains to the application of polypeptides, specifically relating to a cyclic polypeptide SEQ ID NO:1 with anti-inflammatory activity, the amino acid sequence of which is CRYYLWLQVQSC-NH2, and the polypeptide is cyclized at both ends with disulfide bonds. Background Technology

[0002] Inflammatory skin problems such as sensitivity, itching, erythema, and atopic dermatitis are common symptoms that plague a large population. The core pathophysiological process behind these problems is an abnormal immune response, in which the TH2 immune response, particularly the inflammatory pathway initiated by alarmins derived from keratinocytes, plays a key role.

[0003] TSLP is a key initiation factor released by epithelial cells in response to stimulation and is considered the "master switch" for the TH2 immune response. TSLP can activate dendritic cells, thereby driving Th2 cell differentiation and producing a series of core effector cytokines, including interleukin-13 (IL-13) and interleukin-31 (IL-31). IL-13 is a major effector factor that leads to IgE production by B cells, promotes inflammation, and directly inhibits the expression of skin barrier proteins. IL-31 is recognized as the "itch factor," which can directly act on sensory neurons to induce intense itching. Scratching further damages the skin barrier, creating a vicious cycle. In addition, another alarming molecule, interleukin-33 (IL-33), can also be released by damaged keratinocytes, directly activating innate lymphoid cells 2 (ILC2s) and mast cells, rapidly amplifying the T2 immune response. TSLP, IL-13, IL-31, and IL-33 together constitute a complex inflammatory network, synergistically driving skin sensitivity and inflammatory states such as redness, swelling, and itching (see: Zhu Congcong, Pan Huijun, Zhu Quangang, Mechanism of Th2-related inflammatory factors in the pathogenesis of eczema [J], Journal of Pharmaceutical Practice, 2019, 37(1):9-13; Duca Emanuela, Sur Genel, Zaharic Teodora-Maria et al., Immunological Implications in Atopic Dermatitis [J]. International Journal of Celiac Disease, 2021, 9(2):65-67; ​​Napolitano Maddalena, Vico Francesca di, Ruggiero Angelo et al., The hidden sentinel of the skin: An overview on the role of interleukin-13 in atopic dermatitis). Frontiers in Medicine, 2023, 10; Nakajima Saeko, Tie Duerna, Nomura Takashi et al., Novel pathogenesis of atopic dermatitis from the view of cytokinesin mice and humans[J]. Cytokine, 2021, 148:155664-155664; Dubin Celina, Duca Ester Del, Guttman-Yassky Emma, ​​The IL-4, IL-13 and IL-31 pathways in atopic dermatitis, Expert Review of Clinical Immunology, 2021, 17(8):835-852.

[0004] The treatment and care of inflammatory skin diseases such as atopic dermatitis is a significant challenge in the fields of dermatology and functional skincare products. Their pathogenesis involves a complex network of cytokines, among which thymic stromal lymphopoietin (TSLP), interleukin-13 (IL-13), interleukin-31 (IL-31), and interleukin-33 (IL-33) are recognized as core pathogenic factors driving itching, inflammation, and damage to the skin barrier.

[0005] Currently, interventions for this disease have the following limitations: At the level of active ingredients in skincare products, traditional plant extracts (such as dipotassium glycyrrhizate and bisabolol) mostly exert their effects through non-specific mechanisms, with unclear targets and limited efficacy. While novel synthetic peptides or biotechnological ingredients that have emerged in recent years attempt to target specific pathways, existing technologies mostly focus on single or a few targets. Examples include peptides that specifically inhibit the binding of TSLP to its receptor (CN116120405A), antibody fragments targeting IL-13 and TSLP (HK40078586A), cyclic dipeptides targeting TSLP and IL-33 (CN119185094A), or peptide immunogens that specifically target IL-31 (CN201880079547.1). These are all single-pathway or dual-pathway inhibition strategies. At the clinical treatment level, from topical glucocorticoids and calcineurin inhibitors to recent biologics (such as dupilumab, which targets IL-4Rα and mainly blocks IL-4 / IL-13 signaling) and JAK inhibitors, there is also the problem of focusing on a single or limited pathway, making it difficult to fully cover other key factors such as TSLP / IL-31.

[0006] Given the complexity and redundancy of the inflammatory network in atopic dermatitis, the aforementioned single-target strategies offer limited improvement. Therefore, there is an urgent need in the field to develop a single active ingredient capable of simultaneously inhibiting the core cytokine networks of TSLP, IL-13, IL-31, and IL-33. Developing such safe and effective ingredients with multi-target mechanisms of action suitable for topical skin application has become a significant and unmet technological requirement. Summary of the Invention

[0007] On one hand, the present invention provides a cyclic polypeptide comprising SEQ ID NO:1, having the amino acid sequence CRYYLWLQVQSC-NH2, with disulfide bonds cyclized at both ends of the polypeptide. Preferably, the molecular formula of the cyclic polypeptide is C 71 H 103 N 19 O 17 S2, the cyclic polypeptide has a purity ≥97.88% and a molecular weight of 1558.6 Da.

[0008] In a preferred embodiment, the cyclic polypeptide is prepared by the following steps: using MBHA series amino resins, the polypeptide is synthesized in a solid phase using the Fmoc strategy, and the amino acids are protected by the Fmoc strategy one by one until the N-terminal Cys condensation is complete; after removing the N-terminal main chain modification groups, the polypeptide is cleaved from the solid-phase support using the TFA cocktail method to obtain the crude polypeptide; the two Cys thiol groups are bridged by iodine oxidation to form a pair of intramolecular disulfide bonds; the product is separated and purified using a C18 reversed-phase column under the TFA system to obtain the target product collection solution; the collection solution is freeze-dried to obtain the final product.

[0009] On the other hand, the present invention also relates to the skin anti-inflammatory application of cyclic polypeptides, said polypeptides comprising SEQ ID NO:1, wherein the polypeptide is cyclized at both ends of a disulfide bond.

[0010] In a preferred embodiment, the skin anti-inflammatory effect includes inhibiting the expression of thymic stromal lymphopoietin (TSLP), interleukin-13 (IL-13), interleukin-31 (IL-31), and / or interleukin-33 (IL-33).

[0011] In a preferred embodiment, the concentration of the polypeptide used is at least 10 ppm. In a preferred embodiment, the concentration of the polypeptide used is 10 ppm to 200 ppm, more preferably 50 ppm to 200 ppm.

[0012] On the other hand, the present invention also relates to the use of cyclic polypeptides in the preparation of medicaments or topical skin agents for the prevention and / or treatment of Th2-type immune-related diseases, said polypeptide comprising SEQ ID NO:1, wherein the polypeptide is cyclized at both ends of a disulfide bond.

[0013] In a preferred embodiment, the Th2-type immune-related diseases are selected from: atopic dermatitis, eczema, allergic asthma, and allergic rhinitis.

[0014] In another aspect, the present invention also relates to a topical skin preparation comprising a cyclic polypeptide comprising SEQ ID NO:1, wherein the polypeptide is cyclized at both ends of a disulfide bond.

[0015] In a preferred embodiment, the topical skin agent is selected from the following forms: face cream, lotion, gel, toner, serum, face mask, eye cream, aerosol cleansing foam, spray, shower gel, or facial cleanser. Brief description of the attached figures

[0016] Figure 1 The HPLC spectrum of the cyclic polypeptide SEQ ID NO:1 of this application is shown.

[0017] Figure 2 The LCMS spectrum of the cyclic polypeptide SEQ ID NO:1 of this application is shown. Invention Details

[0019] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. While any methods and materials similar or equivalent to those described herein may be used to practice or test the invention, preferred methods and materials are described herein. For the purposes of this invention, the following terms are defined.

[0020] As used herein, the term "about" means a quantity, level, value, dimension, size, or amount that differs from that of a reference by as much as 30%, 20%, or 10%. Percentages used herein, unless otherwise stated, are by weight.

[0021] Throughout this specification and claims, unless otherwise required, the words “comprising” and its variations “containing” and “including” shall be understood to mean including the said whole or step, or a group of whole or steps, but not excluding any other whole or step, or other group of whole or steps.

[0022] This invention is based on the unexpected discovery that the cyclic polypeptide SEQ ID NO:1 (amino acid sequence CRYYLWLQVQSC-NH2, with disulfide bonds cyclized at both ends) can effectively inhibit key cytokines closely related to skin immune responses and sensitivity, including thymic stromal lymphopoietin (TSLP), interleukin-13 (IL-13), interleukin-31 (IL-31), and interleukin-33 (IL-33). In vitro experiments show that the cyclic polypeptide SEQ ID NO:1 can inhibit the above four key cytokines closely related to allergic diseases such as atopic dermatitis. Based on this unique multi-target inhibitory effect, this cyclic polypeptide has important application value in the preparation of drugs or skin care products for the prevention and / or treatment of Th2 immune-related diseases such as atopic dermatitis, eczema, allergic asthma, and allergic rhinitis.

[0023] Cyclic polypeptides

[0024] The technical problem to be solved by the present invention is to overcome the deficiency of the single target of active ingredients in the prior art, and to provide a single active ingredient that can simultaneously inhibit multiple key cytokines such as TSLP, IL-13, IL-31 and IL-33, so as to meet the needs of the skin care field for highly effective and multi-pathway soothing of sensitive skin.

[0025] Therefore, the present invention provides a cyclic polypeptide SEQ ID NO:1 with the amino acid sequence CRYYLWLQVQSC-NH2, and the polypeptide having disulfide bonds cyclized at both ends.

[0026] The cyclic polypeptide sequence of the present invention begins (N-terminus) and ends (C-terminus) with cysteine ​​(C), and the C-terminus is in an amidated form (-NH2). This provides a structural basis for the formation of head-to-tail disulfide cyclization, namely, the formation of a cyclic disulfide bond through the oxidation of the thiol group (-SH) of the N-terminal cysteine ​​and the thiol group of the C-terminal cysteine.

[0027] In this invention, in vitro experiments have shown that the cyclic polypeptide SEQ ID NO:1 can effectively inhibit key cytokines closely related to skin immune responses and sensitivity, including thymic stromal lymphopoietin (TSLP), interleukin-13 (IL-13), interleukin-31 (IL-31), and interleukin-33 (IL-33). This cyclic polypeptide SEQ ID NO:1 can simultaneously inhibit these four key cytokines closely related to allergic diseases such as atopic dermatitis.

[0028] In a specific embodiment, the molecular formula of the cyclic polypeptide is C1 71 H 103 N 19 O 17S2, purity ≥97.88%, molecular weight 1558.6 Da.

[0029] In a specific implementation, a cyclic polypeptide SEQ ID NO:1 provided by the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, with the amino acid sequence CRYYLWLQVQSC-NH2, is used, and the polypeptide is cyclized at both ends with disulfide bonds.

[0030] The synthesis method of cyclic peptides is as follows: MBHA series amino resins were used for solid-phase peptide synthesis using the Fmoc strategy. The Fmoc strategy was employed to protect the amino acids one by one until the N-terminal Cys condensation was complete. After removing the N-terminal main chain modification groups, the peptide was cleaved from the solid-phase support using the TFA cocktail method to obtain the crude peptide. Iodine oxidation was used to bridge the two Cys thiol groups, forming a pair of intramolecular disulfide bonds. The product was separated and purified using a C18 reversed-phase column under the TFA system to obtain the target product collection solution. The collection solution was then freeze-dried to obtain the final product.

[0031] Product purity and molecular weight are shown in [reference needed]. Figure 1 and Figure 2 .

[0032] Figure 1 The HPLC spectrum of the cyclic polypeptide SEQ ID NO:1 of this application is shown. Figure 1 As shown, the retention time of the main peak of the target peptide (SEQ ID NO:1) was 10.142 min according to HPLC detection, and the purity of the peptide was 97.88% according to the peak area normalization method.

[0033] Figure 2 The LCMS spectrum of the cyclic polypeptide SEQ ID NO:1 of this application is shown. Figure 2 As shown, the target polypeptide (SEQ ID NO:1) has the molecular formula C 71 H 103 N 19 O 17 S2 has a theoretical molecular weight of 1558.84 Da. As shown in the figure, the main signal peak detected by mass spectrometry is at a mass-to-charge ratio (m / z) of 780.3 Da, which corresponds to the divalent hydrogen ion [M+2H] of the polypeptide. 2+ Based on this mass-to-charge ratio, the experimentally measured molecular weight was calculated to be 1558.6 Da. This is consistent with the theoretical molecular weight, confirming that it is indeed the target polypeptide.

[0034] Topical skin agents

[0035] This invention also provides a topical skin agent comprising a cyclic polypeptide SEQ ID NO:1, wherein the amino acid sequence of the polypeptide is CRYYLWLQVQSC-NH2, and the polypeptide is cyclized at both ends with disulfide bonds. This topical skin agent can be used to relieve skin itching, skin inflammation, and skin barrier damage.

[0036] The term "topical skin agent" is a general term encompassing all ingredients typically used on the external surface of the skin, including cosmetic compositions and pharmaceutical compositions. Cosmetic compositions may include basic cosmetics, facial makeup, body cosmetics, hair care cosmetics, etc., with no specific restrictions on their dosage forms; appropriate formulations can be selected based on different purposes.

[0037] The cyclic polypeptide of the present invention can be added as a cosmetic additive to cosmetics such as serums, creams, lotions, eye creams, essential oils, and massage oils.

[0038] The cosmetic composition may also contain different cosmetically permissible media or matrix excipients, depending on the dosage form and purpose.

[0039] Cosmetic, dermatological, or pharmaceutically acceptable excipients that can be used in the topical skin formulations of this invention are in the form of an aqueous phase, oil phase, gel, water-in-wax emulsion, water-in-oil emulsion, or oil-in-water emulsion. The aqueous phase is a mixture of one or more water-soluble or dispersible components, which may be liquid, semi-solid, or solid at room temperature (25°C). Excipients include or may be in the form of suspensions, dispersions, or solutions in water or water-alcohol excipients, and may contain thickeners or gelling agents. Those skilled in the art can select appropriate product forms and the components contained therein based on their knowledge.

[0040] The composition may include an aqueous phase, which may contain water or a mixture of water and at least one hydrophilic organic solvent, such as alcohols, especially straight-chain or branched lower monohydric alcohols containing 2-5 carbon atoms, such as ethanol or propanol; polyhydric alcohols, such as propylene glycol, sorbitol, glycerol, panthenol, or polyethylene glycol and mixtures thereof.

[0041] When the composition of the invention is in the form of an emulsion, the composition may optionally contain a surfactant.

[0042] The composition may also comprise a film-forming polymer, such as a polyurethane, a polyacrylic acid homopolymer or copolymer, a polyester, a hydrocarbon-based resin, and / or a siloxane resin. The polymer may be dissolved or dispersed in a cosmetically acceptable excipient and optionally incorporated with a plasticizer.

[0043] The compositions of the present invention may further comprise any of the components commonly used in the cosmetics field. These components include preservatives, aqueous phase thickeners (extractive biopolymers, synthetic polymers) and fatty phase thickeners, fragrances, hydrophilic and lipophilic active agents, and mixtures thereof.

[0044] The compositions of the present invention may also contain an additional particulate phase, which may be pigments and / or pearlescent agents and / or fillers used in cosmetic compositions.

[0045] Pigments can be present in the composition. Suitable inorganic pigments include titanium oxide, zirconium oxide, and cerium oxide, as well as zinc oxide, iron oxide, and iron blue; suitable organic pigments include barium, strontium, calcium, and aluminum lakes and carbon black.

[0046] Pearlizing agents can be present in the composition, and suitable pearlizing agents include mica coated with titanium dioxide, iron oxide, or natural pigments.

[0047] Fillers may be present in the composition. Suitable fillers include talc, silica, zinc stearate, mica, kaolin, nylon powder, polyethylene powder, Teflon, starch, boron nitride, and copolymer microspheres, such as siloxane resin microspheres.

[0048] The compositions of the present invention can be formulated into any suitable product form. Such product forms include, but are not limited to, aerosol sprays, creams, lotions, solids, liquids, dispersions, foams, gels, lotions, mousses, ointments, powders, patches, hair oils, solutions, pump sprays, sticks, masks, and wet wipes. The compositions of the present invention can be conveniently used in the preparation or as topical cosmetic, dermatological, or pharmaceutical products by various methods well known in the art.

[0049] The topical skin composition of the present invention may include one or more of the following components: anti-allergic agents, anti-inflammatory agents, moisturizers, antimicrobial agents, antioxidants, chelating agents, colorants, depigmenting agents, emollients, emulsifiers, epidermal exfoliants, film-forming agents, fragrances, insect repellents, lubricants, pharmaceutical activators, humectants, lightfastness agents, preservatives, skin care agents, skin penetration enhancers, sunscreens, stabilizers, surfactants, thickeners, viscosity modifiers, vitamins, or any combination thereof. Detailed Implementation

[0050] The present invention is further illustrated below with reference to specific embodiments. However, the scope of the present invention is not limited to these embodiments, which are intended to illustrate the technical solutions of the present invention and do not constitute a limitation on the scope of the present invention. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, all percentages and parts are by weight.

[0051] The amino acid sequence of the cyclic polypeptide is CRYYLWLQVQSC-NH2, with disulfide bonds cyclized at both ends. This sequence was provided by the Shanghai Institute of Materia Medica, Chinese Academy of Sciences.

[0052] EpiGrowth culture medium was purchased from Guangdong Boxi Shaanxi Branch.

[0053] Example 1: Add 54 μl of DMSO to 0.54 mg of sample to prepare a stock solution with a final concentration of 1%.

[0054] Example 2: Take Example 1, dilute it with culture medium to prepare a 10 ppm concentration, and use it as the test solution.

[0055] Example 3: Take Example 1, dilute it with culture medium to prepare a concentration of 50 ppm, and use it as the test solution.

[0056] Example 4: Take Example 1, dilute it with culture medium to prepare a concentration of 100 ppm, and use it as the test solution.

[0057] Example 5: Take Example 1, dilute it with culture medium to prepare a concentration of 200 ppm, and use it as the test solution.

[0058] Test Example 1: Detection based on a 3D skin model resembling eczema

[0059] 1. Experimental materials

[0060] 1.1 Cells: The model used in this test was a 3D epidermal skin model (EpiKutis®), batch number: ES250103, provided by Guangdong Boxi Shaanxi Branch.

[0061] 1.2 Reagents: EpiGrowth culture medium (Guangdong Boxi Shaanxi Branch), PBS (Solepro), PolyI:C (Sigma), lipopolysaccharide LPS (E. coli. Sigma), dexamethasone (National Institutes for Food and Drug Control), AG RNAex Pro Reagent (Abcam), reverse transcription kit (Abcam), fluorescent dye (Abcam), TSLP ELISA kit (Abcam).

[0062] 1.3 Main Equipment

[0063] CO2 incubator (Thermo, 150I), clean bench (Sujing Antai, SW-CJ-2F), conventional PCR instrument (Bori, TC-XP-G), real-time PCR instrument (Roche, Lightcycler 480 II), microplate reader (BioTek, Epoch).

[0064] 2. Experimental Methods: 2.1 Preparation of test solution PolyI:C+LPS induction working solution: Take 1.44 mL of 5 mg / mL PolyI:C stock solution and 3 mL of 2 mg / mL LPS stock solution, dissolve them in the skin model culture medium, with a total volume of 300 mL, so that the final concentration of PolyI:C is 24 μg / mL and the final concentration of LPS is 20 μg / mL.

[0065] 2.2 Drug administration and induction

[0066] 1) According to the test group, transfer the model to the 6-well plate and mark the test group number on the 6-well plate.

[0067] 2) Drug administration: The BC group and NC group were given model culture medium, the PC group was given the corresponding positive control working solution, and the sample group was given the working solution of the sample evenly applied to the model surface and incubated in a CO2 incubator (37℃, 5% CO2) for 24h.

[0068] 3) Stimulation: After incubation, remove the 6-well plates from the incubator. Gently wipe the model surface with a sterile cotton swab. Discard any remaining culture medium in the wells. Add PolyI:C and LPS induction working solution to the NC group, PC group, and sample group. Add model culture medium to the BC group. After completion, transfer all 6-well plates to a CO2 incubator (37℃, 5% CO2) for incubation for 24 hours.

[0069] 2.3 TSLP Detection

[0070] After incubation, the 3D epidermal skin model culture medium was collected in centrifuge tubes. After collection, the samples used for ELISA detection were frozen at -80°C and analyzed according to the ELISA kit instructions.

[0071] 2.4 Gene Expression Detection

[0072] After incubation, wash twice with 1 mL / well of PBS, add 1 mL of AG RNAex Pro Reagent to each well, lyse the cells by pipetting, and collect the samples. Extract RNA, reverse transcribe it into cDNA, and perform quantitative real-time PCR detection. Calculate the results using the 2-ΔΔCT method.

[0073] 2.5 Calculation of Inhibition Rate

[0074] 2.6 Statistical Analysis of Results

[0075] GraphPad Prism was used for plotting, and the results are expressed as Mean ± SD. Comparisons between groups were performed using... t -test statistical analysis. All statistical analyses are two-tailed. Compared with the BC group, significance is indicated by #, P-value < 0.05 is indicated by #, P-value < 0.01 is indicated by ##; compared with the NC group, significance is indicated by This means that a p-value < 0.05 indicates that... A p-value < 0.01 indicates that... ; 2.7 Experimental Results Table 1: TSLP Detection Results

[0076] The TSLP detection results show that the cyclic polypeptide SEQ ID NO:1 has an inhibitory effect on TSLP in the concentration range of 10ppm-200ppm, and exhibits a certain concentration dependence.

[0077] Table 2: IL13 Detection Results

[0078] The IL13 detection results show that the cyclic polypeptide SEQ ID NO:1 has an inhibitory effect on IL13 in the concentration range of 50ppm-200ppm, and exhibits a certain concentration dependence.

[0079] Table 3: IL31 Detection Results

[0080] The IL31 detection results show that the cyclic polypeptide SEQ ID NO:1 has an inhibitory effect on IL31 in the concentration range of 50ppm-200ppm, and exhibits a certain concentration dependence.

[0081] Table 4: IL33 Detection Results

[0082] The IL33 detection results show that the cyclic polypeptide SEQ ID NO:1 has an inhibitory effect on IL33 in the concentration range of 50ppm-200ppm, and exhibits a certain concentration dependence.

[0083] Application examples

[0084] The cyclic polypeptide of the present invention can be used in the preparation of topical skin agents. The topical skin agent is preferably a cosmetic composition, such as a face cream, lotion, gel, toner, serum, mask, eye cream, aerosol (cleansing foam), spray, shower gel, facial cleanser, etc. The weight percentage of the cyclic polypeptide in the topical skin agent is 0.0001%-1% (w / w).

[0085] The following are specific application examples of the cyclic polypeptides in topical skin preparations, along with the formulations and preparation methods of these dosage forms. In the tables below, "-" indicates no additives.

[0086] Application Example 1: Preparation of Face Cream

[0087] Application Example 2: Emulsion Preparation

[0088] Application Example 3: Preparation of Gel

[0089] Application Example 4: Preparation of Toner

[0090] Application Example 5: Preparation of Serum

[0091] Application Example 6: Preparation of Facial Masks

[0092] Application Example 7: Preparation of Eye Cream

[0093] Application Example 8: Preparation of Aerosol (Cleaning Bubble)

[0094] Application Example 9: Preparation of Spray

[0095] Application Example 10: Preparation of Shower Gel

[0096] Application Example 11: Preparation of Facial Cleanser

Claims

1. A cyclic polypeptide comprising SEQ ID NO:1, having an amino acid sequence of CRYYLWLQVQSC-NH2, wherein the polypeptide is cyclized at both ends with disulfide bonds.

2. The cyclic polypeptide according to claim 1, characterized in that, The molecular formula of the cyclic polypeptide is C 71 H 103 N 19 O 17 S2, the cyclic polypeptide has a purity ≥97.88% and a molecular weight of 1558.6 Da.

3. The cyclic polypeptide according to claim 1, characterized in that, The cyclic polypeptide was prepared by the following steps: using MBHA series amino resins, the polypeptide was synthesized in a solid phase using the Fmoc strategy, and the amino acids were protected by the Fmoc strategy one by one until the N-terminal Cys condensation was completed; after removing the N-terminal main chain modification groups, the polypeptide was cleaved from the solid support using the TFA cocktail method to obtain the crude polypeptide; the two Cys thiol groups were bridged by iodine oxidation to form a pair of intramolecular disulfide bonds. The target product was separated and purified using a C18 reversed-phase column and a TFA system; the collected solution was then freeze-dried to obtain the final product.

4. The anti-inflammatory application of the cyclic polypeptide as described in claim 1, wherein, The skin anti-inflammatory treatment includes inhibiting the expression of thymic stromal lymphopoietin (TSLP), interleukin-13 (IL-13), interleukin-31 (IL-31), and / or interleukin-33 (IL-33).

5. The application as described in claim 4, characterized in that, The concentration of the polypeptide used is at least 10 ppm.

6. The application as described in claim 5, characterized in that, The concentration of the polypeptide used is 50ppm-200ppm.

7. The use of a cyclic polypeptide in the preparation of a medicament or topical skin agent for the prevention and / or treatment of Th2-type immune-related diseases, wherein the polypeptide comprises SEQ ID NO:1, with disulfide bonds cyclized at the head and tail of the polypeptide.

8. The application as described in claim 7, wherein the Th2 immune-related disease is selected from: atopic dermatitis, eczema, allergic asthma, and allergic rhinitis.

9. A topical skin preparation comprising a cyclic polypeptide, said polypeptide comprising SEQ ID NO:1, wherein the polypeptide is cyclized at both ends of a disulfide bond.

10. The topical skin agent of claim 9, wherein the topical skin agent is selected from the following forms: face cream, lotion, gel, toner, serum, mask, eye cream, aerosol cleansing foam, spray, shower gel, or facial cleanser.

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