A small molecule polypeptide and its use in the treatment of psoriasis

Abstract

The present application belongs to the technical field of polypeptide drugs, and particularly relates to a kind of small molecule polypeptide and its application in psoriasis treatment.The present application successfully designs and synthesizes a kind of small molecule polypeptide OGP6 with the effect of intervening psoriasis.By test verification, it can effectively target inhibition cGAS-STING signal pathway, intervene psoriasis inflammation start from source, avoid the existing biological preparation long-term antagonism single cytokine to cause the problem such as drug resistance antibody production, curative effect invalidation, and its still has the advantages such as small molecular weight, simple synthesis process, low cost, easy to scale production, therefore has good practical application value.

Description

Technical Field

[0001] The present invention belongs to the technical field of polypeptide drugs, and particularly relates to a small molecule polypeptide and its application in the treatment of psoriasis. Background Art

[0002] Psoriasis, commonly known as psoriasis vulgaris, is a common chronic, inflammatory, recurrent non-infectious skin disease. Among them, chronic plaque psoriasis (psoriasis vulgaris) is the most common, accounting for 85%-90% of all cases. The typical skin lesions are red plaques covered with silver-white scales. The pathological features are characterized by excessive proliferation and abnormal differentiation of epidermal keratinocytes, dilation of superficial dermal blood vessels, and infiltration of inflammatory cells mainly composed of T lymphocytes. Psoriasis is not a simple skin disease, but a systemic inflammatory disease, which can be combined with various complications such as psoriatic arthritis, metabolic syndrome, cardiovascular diseases, etc., seriously affecting the quality of life and social mental health of patients.

[0003] Currently, the clinical treatment drugs for psoriasis are mainly divided into traditional systemic drugs and biologics. Traditional drugs such as methotrexate, although they are the first-line choice for moderate to severe psoriasis and have high cost-effectiveness, have significant adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver toxicity, and pulmonary fibrosis during long-term application, and their clinical application is limited; Biologics represented by tumor necrosis factor-α (TNF-α) inhibitors, interleukin-12 / 23 (IL-12 / 23) inhibitors, and interleukin-17A (IL-17A) inhibitors, although their efficacy has been improved, there are problems such as high price (the direct cost is ten times that of traditional drugs), some patients produce anti-drug antibodies resulting in insufficient or ineffective efficacy, increased risk of opportunistic infections, and even induction of paradoxical reactions. There is still much room for improvement in the safety and efficacy persistence of existing therapies. Summary of the Invention

[0004] Aiming at the problems existing in the prior art, the present invention provides a small molecule polypeptide and its application in the treatment of psoriasis. Specifically, the present invention successfully designed and synthesized a small molecule polypeptide OGP6 with the effect of intervening in psoriasis. Through experimental verification, it can effectively target and inhibit the cGAS-STING signaling pathway, intervene in the initiation of psoriasis inflammation from the source, avoid problems such as the generation of anti-drug antibodies and ineffective efficacy caused by long-term antagonism of single cytokines by existing biologics, and has better efficacy persistence. Moreover, it also has the advantages of small molecular weight, simple synthesis process, low cost, and easy large-scale production. Based on the above research results, the present invention is completed.

[0005] Specifically, the present invention relates to the following technical solutions: In the first aspect of the present invention, a small molecule polypeptide is provided, and the amino acid sequence of the small molecule polypeptide is as shown in SEQ ID NO.1.

[0006] Furthermore, the C-terminus of the complete amino acid sequence of the small molecule polypeptide is amidated.

[0007] The small molecule polypeptide is an artificially designed and synthesized active polypeptide containing 14 amino acid residues, with a molecular weight of 2082.41 Da and an isoelectric point of 12.40. Its full amino acid sequence is arginine-arginine-arginine-tyrosine-histidine-arginine-arginine-phenylalanine-histidine-isoleucine-arginine-arginine-serine-tryptophan-NH2.

[0008] A second aspect of the present invention provides a method for preparing the above-mentioned small molecule polypeptide, the method comprising synthesizing its full sequence using an automated polypeptide synthesizer and purifying it by desalting using HPLC reversed-phase column chromatography.

[0009] A third aspect of the present invention provides the use of the above-mentioned small molecule polypeptide in the preparation of a drug for treating psoriasis.

[0010] The treatment for psoriasis includes one or more of the following effects: (a) Inhibition of the cGAS-STING pathway; (b) Reduces increased epidermal thickness, Munro abscesses, hyperkeratosis, and parakeratosis; (c) Inhibit the expression of inflammatory factors in skin tissue.

[0011] In (a), the inhibition of the cGAS-STING pathway is achieved by small molecule peptides binding to STING; In (c), the inflammatory factors include CXCL10 and ISG15.

[0012] In the aforementioned applications, the small molecule polypeptide can be used as the sole active ingredient, or it can be used in combination with other active ingredients that have therapeutic effects on psoriasis, thereby improving the therapeutic effect.

[0013] The drug also includes pharmaceutically acceptable excipients.

[0014] In another specific embodiment of the present invention, the pharmaceutically acceptable excipient is selected from one or more combinations of wetting agents, emulsifiers, preservatives, antioxidants, buffers, excipients, diluents, lubricants, antibacterial agents, suspending agents, suspending aids, solubilizers, thickeners, and stabilizers.

[0015] In another specific embodiment of the present invention, the pharmaceutically acceptable excipient is selected from at least one of lactose, mannose, calcium phosphate, alginate, polyvinylpyrrolidone, cellulose, water, phosphate, sodium chloride and methylcellulose.

[0016] In another specific embodiment of the present invention, the administration method of the drug is selected from local, intradermal or subcutaneous injection.

[0017] In another specific embodiment of the present invention, the drug may be administered via subcutaneous injection.

[0018] In the above applications, psoriasis includes various types of mild, moderate and severe psoriasis and psoriasis-related complications.

[0019] In a fourth aspect, the present invention provides a medicament for treating psoriasis, the medicament comprising the aforementioned small molecule polypeptide.

[0020] In another specific embodiment of the present invention, the drug further comprises at least one other pharmaceutically active ingredient and / or at least one pharmaceutically acceptable excipient.

[0021] A fifth aspect of the present invention provides a method for treating psoriasis, the method comprising administering the above-described small molecule polypeptide or the above-described drug to a subject.

[0022] The subjects can be humans or non-human mammals, such as mice, rats, pigs, cattle, sheep, orangutans, etc. In some embodiments, the subjects are mice, and more specifically, psoriasis mouse models constructed with imiquimod.

[0023] The beneficial technical effects of one or more of the above technical solutions: The aforementioned technical solution provides a synthetic peptide, OGP6, which has a small molecular weight, simple synthesis process, low cost, and is easy to scale up, solving the problem of high price of existing biological agents. OGP6 exhibits extremely low cytotoxicity, with very low hemolytic activity and eukaryotic cytotoxicity. Its selectivity index (SI = IC50 / EC50 = 23.5) provides a good safety window, overcoming the drawbacks of traditional drugs with significant side effects. OGP6 is highly effective in treating psoriasis, being efficiently taken up by cells (good uptake is achieved within 30 minutes and is time-dependent). In animal models of psoriasis, its effects in alleviating skin lesions, reducing PASI scores, reducing epidermal thickening, reducing Munro abscesses, and downregulating inflammatory factor expression are all superior to those of the traditional treatment drug dexamethasone. OGP6 has a novel mechanism of action, targeting and inhibiting the cGAS-STING signaling pathway, intervening in the initiation of psoriasis inflammation at its source. This avoids the problems of drug resistance antibody production and efficacy failure caused by long-term antagonism of single cytokines in existing biological agents, resulting in better efficacy persistence.

[0024] In summary, the above-mentioned technical solutions provide new active ingredients and treatment methods for psoriasis, and therefore have good practical application value. Attached Figure Description

[0025] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0026] Figure 1 This is a high-performance liquid chromatography (HPLC) purity chromatogram of the polypeptide OGP6 of this invention.

[0027] Figure 2 This invention relates to the cellular uptake detection of the fluorescently labeled peptide OGP6 and the half-maximal inhibitory concentration (IC50) and half-maximal effective concentration (EC50) of peptide OGP6; wherein, A represents the time gradient detection of the uptake of the fluorescently labeled peptide OGP6 in cells, and B represents the half-inhibitory concentration IC50. 50 and half-maximal effect concentration EC 50 result.

[0028] Figure 3 The severity of skin lesions in psoriasis model mice is determined by the intervention of the present invention's polypeptide OGP6; where A represents the actual skin lesion condition of the psoriasis model mice, B represents the PASI score result, and C represents the weight change result of the psoriasis model mice.

[0029] Figure 4 The results show the spleen weight of mice with a psoriasis model after intervention with the OGP6 peptide of this invention.

[0030] Figure 5 The results of flow cytometry analysis of the percentage of Th17 cells in the spleen of mice with a psoriasis model treated with the OGP6 peptide of this invention are shown.

[0031] Figure 6 This invention relates to the analysis of HE staining and inflammatory factor expression in skin sections of psoriasis model mice treated with the OGP6 peptide; wherein, A is the HE staining result of skin sections of psoriasis model mice on the back (scale bar = 100 μm), and B is the expression level of inflammatory factors in the skin lesion tissue detected by qPCR.

[0032] Figure 7 This study aims to determine the binding constant of the present invention's polypeptide OGP6 to STING protein.

[0033] Figure 8 This is the docking result of the polypeptide OGP6 and the STING protein molecule of the present invention. Detailed Implementation

[0034] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of this application. Unless otherwise specified, 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 application pertains.

[0035] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments according to this application. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof. Experimental methods in the following specific embodiments, unless specific conditions are specified, generally follow conventional methods and conditions in molecular biology within the art, which are fully explained in the literature.

[0036] The pathogenesis of psoriasis involves complex interactions between keratinocytes and immune cells, with the IL-23 / Th17 cell axis and its downstream effector factors considered key pathways driving inflammation. Recent studies have revealed that abnormally accumulated autologous DNA fragments in the cytoplasm are important endogenous triggers for psoriatic inflammation. The circular GMP-AMP synthase (cGAS) / interferon gene stimulating factor (STING) signaling pathway is a natural immune signaling pathway that senses abnormal DNA. cGAS recognizes abnormal DNA and activates the STING protein, which then binds to TANK-binding kinase 1 (TBK) and induces activation of transcription factors IRF3 and NF-κB, leading to the production of type I interferon and various pro-inflammatory factors, amplifying the inflammatory response. Abnormal activation of this signaling pathway has been observed in the skin lesions and peripheral immune cells of psoriasis patients. Therefore, targeting and inhibiting the cGAS-STING signaling pathway holds promise for intervening in the key inflammatory initiation stage of psoriasis at its source, providing an important direction for developing novel therapeutic strategies with novel mechanisms of action, fewer potential side effects, and the potential to overcome the limitations of existing biologics.

[0037] In view of this, the present invention provides a small molecule polypeptide OGP6 that has the effect of intervening in psoriasis. It can effectively target and inhibit the cGAS-STING signaling pathway, intervene in the initiation of psoriasis inflammation from the source, and has the advantages of small molecular weight, simple synthesis process, low cost, and easy large-scale production.

[0038] The following examples further illustrate the present invention, but do not constitute a limitation thereof. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the invention.

[0039] Example 1: Preparation of polypeptide OGP6 I. Chemical synthesis method of polypeptide OGP6: According to the amino acid sequence described in the invention, its full sequence was synthesized using an automated polypeptide synthesizer (433A, Applied Biosystems), and purified by HPLC reversed-phase column chromatography for desalting.

[0040] II. Molecular weight was determined using electrospray mass spectrometry.

[0041] III. The purity of the purified polypeptide OGP6 was identified by high performance liquid chromatography (HPLC) (Welch XB C18 4.6*250 mm), the molecular weight was determined by electrospray mass spectrometry, the isoelectric point was determined by isoelectric focusing electrophoresis, and the amino acid sequence structure was determined by an automated amino acid sequencer.

[0042] The results of high performance liquid chromatography (HPLC) purity identification are as follows: Figure 1 As shown, peptide OGP6 exhibits a single symmetrical peak at 16.890 min.

[0043] The polypeptide OGP6 contains 14 amino acid residues, has a molecular weight of 2082.41 Da, an isoelectric point of 12.40, and its full sequence is arginine-arginine-arginine-tyrosine-histidine-arginine-arginine-phenylalanine-histidine-isoleucine-arginine-arginine-serine-tryptophan-NH2 (C-terminal amidation).

[0044] Example 2: Detection of cellular uptake of fluorescently labeled peptide OGP6 I. Preparation and cell treatment of fluorescently labeled peptide OGP6: The fluorescent group was coupled to the N-terminus of peptide OGP6 using the conventional fluorescein isothiocyanate (FITC) labeling method. After the reaction, the free fluorescent group was removed by HPLC purification to obtain fluorescently labeled peptide OGP6.

[0045] II. Cell treatment and incubation: The target cells were seeded in culture plates and cultured at 37°C and 5% CO2 until they adhered stably. Then, a certain concentration of the fluorescently labeled peptide OGP6 was added for incubation.

[0046] III. Incubation time gradient detection: Incubation was terminated at 5 min, 30 min, 1 h and 4 h respectively. The cells were thoroughly washed with PBS to remove untaken peptides, and intracellular fluorescence signals were observed using a fluorescence microscope or laser confocal microscope.

[0047] Cellular uptake time gradient detection: The reaction was terminated after incubation for 0 min, 15 min, 30 min, 1 h, 2 h and 4 h, respectively. Unbound peptides were removed by washing with PBS, and the distribution and intensity changes of intracellular fluorescence signals were observed by fluorescence microscopy or laser confocal microscopy.

[0048] OGP6 intake results are as follows Figure 2 As shown in Figure A, OGP6 achieved good cellular uptake within 30 minutes. With prolonged incubation, the intracellular fluorescence signal gradually increased, and the cell morphology remained good, suggesting that the peptide OGP6 could be effectively uptaken by cells and that the uptake increased in a time-dependent manner.

[0049] Example 3: Cytotoxic IC50 of peptide OGP6 50 and effectiveness EC 50 Detection I. Cytotoxic IC 50 Assay: Using the CCK-8 assay, cells were treated with different concentration gradients of peptide OGP6. After 24 h of incubation, cell viability was assessed, and dose-response curves were plotted. The half-inhibitory concentration (IC50) of peptide OGP6 was calculated. 50 ).

[0050] II. Effectiveness EC 50 Assay: Cells were treated with different concentrations of the peptide OGP6 within a non-cytotoxic concentration range. Changes in the expression levels of the inflammatory factor ISG15 were detected, and effect-dose curves were plotted to calculate the half-maximal effect concentration (Cmax). 50 ).

[0051] The results are as follows Figure 2 As shown in Figure B, peptide OGP6 exhibits no significant cytotoxicity to cells within a certain concentration range and demonstrates a clear dose-dependent effect on the target biological response. The selectivity index SI = IC was calculated. 50 / EC 50 = 23.5, which offers good selectivity and a safety window.

[0052] Example 4: Experiment on the intervention of peptide OGP6 in a mouse model of psoriasis I. Establishment of an animal model of psoriasis: Five-week-old female C57BL / 6 mice were selected and their back skin was treated with 62.5 mg of 5% imiquimod (IMQ) cream for 6 consecutive days to induce the formation of a psoriasis-like skin lesion model.

[0053] II. Grouping and administration: Mice were randomly divided into a normal control group, a psoriasis-like model group, a dexamethasone positive control group, and a peptide OGP6 treatment group. One hour after each application of IMQ, mice were administered 1 mg / kg of dexamethasone or 5 mg / kg of peptide OGP6 via intraperitoneal injection.

[0054] III. PASI Score Assessment: During the experiment, the skin lesions of mice were dynamically observed, and scores were given according to the degree of erythema, scaling and skin thickening. The comprehensive PASI score was calculated to evaluate the improvement effect of peptide OGP6 on psoriasis-like skin lesions. The scoring details are shown in Table 1.

[0055] Table 1 PASI Scoring Details

[0056] The results are as follows Figure 3 As shown in Figures A to C, compared with the model group, the mice treated with the peptide OGP6 showed significant improvement in skin lesions, a significant decrease in PASI scores, and a recovery in body weight, and the therapeutic effect was superior to that of the dexamethasone positive control group.

[0057] Example 5: Flow cytometry detection of the proportion of Th17 cells in mouse spleen I. Spleen Tissue Acquisition and Single-Cell Suspension Preparation: After modeling, mice in each group were sacrificed, and spleen tissue was harvested under aseptic conditions and placed in pre-cooled PBS. The spleen tissue was gently ground using an aseptic grinding method and filtered through a 40 μm cell sieve to prepare a spleen single-cell suspension. Subsequently, red blood cells were lysed with red blood cell lysis buffer for 10 minutes, washed with PBS, and the cell concentration was counted.

[0058] II. Surface staining: Take an appropriate amount of spleen single-cell suspension and use anti-mouse CD4-FITC fluorescent labeling antibody, anti-mouse CD45Cy5 fluorescent labeling antibody, and anti-mouse CD3-KO525 fluorescent labeling antibody to stain the surface of the cells under light-protected conditions.

[0059] III. Fixation, permeabilization, and intracellular staining: Spleen cell suspensions were fixed and permeabilized using eBioscience flow cytometry fixation and permeabilization solution (00-5521-00). After washing, anti-mouse IL-17A-PE fluorescently labeled antibody was added for intracellular staining. All operations were performed under light-protected conditions.

[0060] IV. Flow Cytometry Detection and Analysis: Flow cytometry was used for detection. First, CD45 was delineated in the FSC / SSC plot. + Lymphocyte population, followed by CD3 + Analysis of CD4 in cell populations + IL-17A + Cell ratio, CD4 + IL-17A + The cell is defined as a Th17 cell.

[0061] The results are as follows Figure 4 As shown, compared with the model group, the abnormal spleen enlargement in mice treated with the peptide OGP6 was significantly alleviated. Figure 5 As shown, the number of Th17 cells in the spleen of mice treated with the peptide OGP6 was significantly reduced, and the therapeutic effect was better than that of the dexamethasone positive control group.

[0062] Example 6: HE staining analysis of mouse skin sections I. Skin tissue collection and processing: After modeling, the mice were euthanized, and the skin tissue from the back of the mice was collected, fixed in 4% paraformaldehyde solution, and then dehydrated, embedded, and sectioned.

[0063] II. HE staining: Skin tissue sections were dewaxed and hydrated, and hematoxylin-eosin (HE) staining was performed using a Leica ST5010 fully automated staining machine. Histopathological changes were observed using an optical microscope.

[0064] The results are as follows Figure 6 As shown in Figure A, compared with the model group, the OGP6 peptide treatment group showed significant relief of skin thickening, reduced Munro abscesses, and significant relief of abnormal epidermal keratosis, with better results than the dexamethasone positive control group.

[0065] Example 7: RT-qPCR detection of inflammatory factor expression in mouse skin tissue I. RNA extraction and reverse transcription: Skin tissue from each group of mice was ground with 4 mm zirconia beads, and total RNA was extracted using the Trizol method and reverse transcribed to synthesize cDNA.

[0066] II. RT-qPCR detection: The mRNA expression levels of psoriasis-related inflammatory factors CXCL10, ISG15, and STING were detected using real-time quantitative PCR, and standardized analysis was performed using an internal reference gene. Primer sequences are shown in Table 2.

[0067] Table 2 Primer sequences of psoriasis-related inflammatory factors

[0068] The results are as follows Figure 6 As shown in Figure B, compared with the model group, STING was significantly inhibited in the OGP6-treated group, and the expression levels of inflammatory factors CXCL10 and ISG15 were significantly downregulated, suggesting that OGP6 can inhibit psoriasis-related inflammatory responses at the molecular level.

[0069] Example 8: Experiment on the determination of the binding constant of peptide OGP6 and STING protein using micro-thermal surge technique The binding constant (Kd) of OGP6 to STING protein was determined using a NanoTemper NT.115 microthermophoresis system. Following the labeling method provided in the kit (Monolith NT™ Protein Labeling Kit), the N-terminus of OGP6 was labeled with biotin and dissolved in 50 mM citrate buffer (pH 6.0). Different concentrations of biotin-OGP6 (0.5 mM–3.8 nM) were added to 10 nM STING protein solution. The mixtures were then incubated at 25°C for 10 min, followed by aspiration using a standard glass capillary tube in the microthermophoresis system. Analysis was performed at 30°C with 30% LED and 40% MST parameters. Kd values ​​were calculated using the software included with the NanoTemper NT.115.

[0070] The results are as follows Figure 7 As shown, the peptide OGP6 can bind to the STING protein with a binding constant of 2.07 μM.

[0071] Example 9: Molecular docking analysis of peptide OGP6 and STING protein The STING protein (PDB: 4EMT) was used as the initial structure for subsequent molecular docking. The initial structure was processed using AutoDock Tools 1.5.6 to preserve the protein's original charge and generate a pdbqt file for docking. The OGP6 peptide molecular structure was constructed using the online website AlphaFold. The molecular structure was optimized using the MOPAC program, and the PM3 atomic charge was calculated for subsequent molecular docking. The ligand structure was processed using AutoDock Tools 1.5.6, generating a pdbqt file for docking.

[0072] Studies have shown that the binding site of the substrate c-di-GMP on the STING protein is mainly located in the cavity formed at the center of the protein. Therefore, this invention also targets this pocket as the active site of the peptide molecule and the protein, enabling it to competitively inhibit substrate binding. Molecular docking was performed using the AutoDock 4.2.6 software package. The docking pocket was set to a 40 Å × 40 Å × 40 Å square pocket with a grid distance of 0.05 nm. The number of docking attempts was set to 100, and the remaining parameters used default values. The binding posture of the candidate drug and the protein, and the optimal binding energy of the protein-ligand complex interaction were obtained using AutoDock Vina 1.2.2. The binding interface of the protein-ligand complex was systematically analyzed using PLIP and LigPlus, and the interaction-related details were supplemented using pyMOL 2.5 software. The results are as follows: Figure 8 As shown.

[0073] Depend on Figure 8It is evident that peptide OGP6 completely occupies the active cavity for substrate binding within the STING protein. OGP6 can bind efficiently to the protein, with its binding site located in the binding pocket formed by serine (SER) at position 162, aspartic acid (ASP) at position 210, lysine (LYS) at position 224, arginine (ARG) at position 238, serine (SER) at position 241, tyrosine (TYR) at position 245, leucine (LEU) at position 259, threonine (THR) at position 267, tyrosine (TYR) at position 167, and glutamate (GLU) at position 260. The molecule interacts with SER-162, ASP-210, LYS-224, ARG-238, SER-241, TYR-245, LEU-259, and THR-267 via hydrogen bonds, binds to TYR-167 via π-π stacking interactions, and further stabilizes the complex structure with ASP-210 and GLU-260 via salt bridges.

[0074] The amino acid sequence involved in this invention Peptide OGP6: RRRYHRRFHIRRSW-NH2 (SEQ ID NO.1).

[0075] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A small molecule polypeptide, characterized in that, The amino acid sequence of the small molecule polypeptide is shown in SEQ ID NO.1, and the C-terminus of the full amino acid sequence of the small molecule polypeptide is amidated.

2. The method for preparing the small molecule polypeptide according to claim 1, characterized in that, The preparation method includes synthesizing the full sequence of the peptide using an automated peptide synthesizer and purifying it by desalting using HPLC reverse-phase column chromatography.

3. The use of the small molecule polypeptide according to claim 1 in the preparation of a drug for treating psoriasis.

4. The application as described in claim 3, characterized in that, The specific manifestations of the treatment for psoriasis include inhibiting the cGAS-STING pathway; the inhibition of the cGAS-STING pathway is achieved by the small molecule peptide binding to STING.

5. The application as described in claim 3, characterized in that, The specific manifestations of the treatment for psoriasis include reducing the increase in epidermal thickness, Munro's abscesses, hyperkeratosis, and parakeratosis.

6. The application as described in claim 3, characterized in that, The specific manifestations of the treatment for psoriasis include inhibiting the expression of inflammatory factors in skin tissue.

7. The application as described in claim 6, characterized in that, The inflammatory factors include CXCL10 and ISG15.

8. The application as described in claim 3, characterized in that, The drug is administered via subcutaneous injection.

9. A medicine for treating psoriasis, characterized in that, The drug comprises the small molecule polypeptide as described in claim 1.

Images