A polypeptide having anti-tumor activity and uses thereof

Abstract

The present application belongs to the field of polypeptides, and relates to a polypeptide with anti-tumor activity and application thereof, in particular to application thereof in preparation of a medicine for preventing and / or treating cancer. The amino acid sequence of the polypeptide of the present application is shown in SEQ ID NO: 1 or SEQ ID NO: 2. The cancer is at least one of breast cancer, cervical cancer, ovarian cancer, prostate cancer, pancreatic ductal adenocarcinoma and brain glioma. The present application has the following technical effects: the polypeptide targeting the FANCI-FANCD2 complex of Fanconi anemia complementation group I protein (FANCI) and Fanconi anemia complementation group D2 protein (FANCD2) is designed and synthesized, the polypeptide shows good inhibitory activity on various different types of human cancer cells, and is expected to be a candidate molecule of broad-spectrum anticancer drugs. The synthesis process of the polypeptide is relatively simple, and the polypeptide is convenient for large-scale preparation and has low production cost.

Description

Technical Field

[0001] This invention belongs to the field of polypeptides and relates to a polypeptide with antitumor activity and its uses, specifically its use in the preparation of drugs for the prevention and / or treatment of cancer. Background Technology

[0002] Cancer is one of the major diseases threatening human health, and its treatment remains a significant challenge. Chemotherapy is currently one of the commonly used treatment methods, but chemotherapeutic drugs have poor targeting specificity, capable of killing tumor cells but also potentially damaging normal cells, easily causing significant toxic side effects. Furthermore, long-term use can easily induce multidrug resistance in tumor cells, thus affecting efficacy. In contrast, peptide drugs are composed of natural amino acids, possessing advantages such as good solubility, low immunogenicity, and high safety. They also exhibit strong targeting, capable of recognizing specific tumor-related proteins or tumor cells, and can be easily synthesized and structurally modified through processes such as solid-phase synthesis, which helps reduce production costs and promotes large-scale preparation.

[0003] The FANCI-FANCD2 complex, formed by the binding of Fanconi anemia complementation group I protein (FANCI) and Fanconi anemia complementation group D2 protein (FANCD2), is a core protein complex in the Fanconi anemia (FA) DNA repair pathway, playing a crucial role in DNA cross-link damage repair and replication fork protection. After monoubiquitination, this complex is recruited to cross-link damage sites, recruiting various endonucleases and homologous recombination repair factors, thereby promoting damage resection and subsequent DNA repair, contributing to maintaining genomic stability. Increasing research suggests that the FANCI / FANCD2 pathway is often aberrantly activated in various tumors, enhancing tumor cells' tolerance to DNA damage, thus promoting tumor cell proliferation, invasion, and survival in adverse microenvironments, and is associated with poor prognosis and alterations in the immune microenvironment. Inhibiting the function of the FANCI-FANCD2 complex is expected to weaken the ability of tumor cells to repair DNA cross-linking damage and improve their sensitivity to chemotherapy and radiotherapy. It is considered a promising anti-tumor treatment strategy, but there is currently a lack of drugs that can specifically block the interaction between FANCI and FANCD2. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and design a peptide inhibitor targeting the FANCI-FANCD2 complex, wherein the peptide has a good inhibitory effect on a variety of cancer cells.

[0005] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows: In a first aspect of the invention, a polypeptide is provided, the amino acid sequence of which is shown in SEQ ID NO: 1.

[0006] In a second aspect of the invention, a polypeptide is provided, the polypeptide being obtained by linking a transmembrane peptide to the first amino acid Lys of a polypeptide having the sequence shown in SEQ ID NO:1, the amino acid sequence of the polypeptide being shown in SEQ ID NO:2.

[0007] In a third aspect of the invention, a polypeptide is provided, the amino acid sequence of which is shown in SEQ ID NO:1 or SEQ ID NO:2, and the last amino acid His of the polypeptide is protected by an amino group.

[0008] In a fourth aspect of the invention, the use of the polypeptide described in the first, second, or third aspect in the preparation of a medicament for the prevention and / or treatment of cancer, wherein the cancer is at least one of breast cancer, cervical cancer, ovarian cancer, prostate cancer, pancreatic ductal adenocarcinoma, and glioma. The polypeptide is capable of inhibiting the proliferation of various cancer cells; wherein the cancer cells are at least one of breast cancer, cervical cancer, ovarian cancer, prostate cancer, pancreatic ductal adenocarcinoma, and glioma cells.

[0009] Furthermore, the cancer mentioned is breast cancer.

[0010] Furthermore, the polypeptide can be used in combination with a pharmaceutically acceptable carrier. When used as a drug, the polypeptide can be used directly or in the form of a pharmaceutical composition. The dosage form of the pharmaceutical composition is selected from injections, lyophilized powder injections, infusions, liposomes, or nanoformulations. To ensure efficacy, the polypeptide is preferably administered to the patient requiring treatment via injection, such as intravenous, intramuscular, subcutaneous, or intraperitoneal injection.

[0011] Furthermore, the polypeptide or a pharmaceutically acceptable salt thereof serves as the active pharmaceutical ingredient.

[0012] Further, the mass fraction of the active pharmaceutical ingredient is 0.1% to 99%; more preferably, the mass fraction of the active pharmaceutical ingredient is 0.1% to 20%.

[0013] Furthermore, the polypeptide can be used in combination with other drugs. The polypeptide and other drugs can be used in combination via simultaneous administration, sequential administration, or alternating administration.

[0014] The features of this invention are as follows: This invention designs and synthesizes multiple peptides targeting the tumor protein complex FANCI-FANCD2. Experiments have shown that the peptide shown in SEQ ID NO: 1 has good anti-cancer effects. Considering that large molecular weight peptides are difficult to enter cells to exert their effects, a membrane-penetrating peptide is introduced before the first amino acid of SEQ ID NO: 1 to enhance the cellular uptake capacity of the peptide. The resulting peptide is shown in SEQ ID NO: 2. To increase the structural stability of the peptide, the carboxyl group of the last amino acid of the peptide in SEQ ID NO: 2 reacts with an amino compound. Finally, the peptides obtained by this invention exhibit excellent inhibitory activity against various types of human cancer cells, providing an option for broad-spectrum peptide-based anti-cancer drugs.

[0015] Compared with existing technologies, this invention has the following advantages: This invention designs a novel sequence-specific polypeptide and, for the first time, discovers that the polypeptide provided by this invention exhibits excellent inhibitory activity against various types of human cancer cells, providing an option for broad-spectrum polypeptide anticancer drugs. The polypeptide synthesis process used in this invention is simple, the constituent amino acids are all natural amino acids, resulting in low production costs and high safety. Attached Figure Description

[0016] Figure 1 This shows the amino acid sequence and structural formula of the polypeptide.

[0017] Figure 2 The results of the designed peptides I-III on the inhibition of tumor cells are shown. Among them, A is the inhibition result of peptide I-III on HCC1806 cells; B is the inhibition result of peptide I-III on MDA-MB-453 cells; and C is the inhibition result of peptide I-III on MCF-7 cells.

[0018] Figure 3 The results show the toxicity of the peptides to various normal human breast epithelial cells and their inhibitory effects on human breast cancer cells, human cervical cancer cells, human ovarian cancer cells, human prostate cancer cells, human pancreatic ductal adenocarcinoma cells, and human glioma.

[0019] Figure 4The results show the in vivo inhibition of human breast cancer xenograft tumors in nude mice by the peptide. In the figures, A represents the euthanasia of nude mice 21 days after administration, followed by tumor tissue dissection and photographic observation; B represents tumor volume measured every 2 days after administration, presented as a line graph; C represents tumor mass after treatment with the solvent group and the 25 mg / kg peptide; D represents the body weight of nude mice measured every 2 days after administration, presented as a line graph; EF represents the anesthesia of nude mice after administration, followed by orbital blood collection to measure serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities to evaluate the hepatotoxicity of the peptide; G represents the measurement of serum creatinine levels to evaluate the nephrotoxicity of the peptide. In the figures, ns indicates no statistically significant difference between the two groups, and * indicates statistically significant differences between the two groups. P <0.05. Detailed Implementation

[0020] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments, but the present invention is not limited to the following technical solutions.

[0021] The human breast cells used in the following examples are normal breast epithelial cells 184A1, 184B5, and MCF10A; the human breast cancer cells are human breast cancer cells SKBR3, T47D, MCF-7, HCC1500, SUM149PT, HCC1806, MDA-MB-453, BT549, HCC1937, MDA-MB-231, and MDA-MB-468; the human cervical cancer cells are human cervical cancer cells HeLa; the human ovarian cancer cells are human ovarian cancer cells SK-OV-3; the human prostate cancer cells are human prostate cancer cells PC-3; the human pancreatic ductal adenocarcinoma cells are SW1990; and the human glioma cells are human glioblastoma cells U87. All the conventional cancer cells used were obtained from Kunming Medical University.

[0022] Unless otherwise specified, all reagents used in the embodiments of this invention are commercially available. RPMI 1640 medium, DMEM medium, and DMEM / F12 medium were purchased from Thermo Fisher Scientific; fetal bovine serum was purchased from Lanzhou Rongye Biotechnology Co., Ltd.; phosphate-buffered saline (PBS), 0.25% trypsin (containing EDTA), and CCK8 reagent were purchased from Dalian Meilun Biotechnology Co., Ltd.

[0023] Cell lines were cultured in RPMI 1640, DMEM, or DMEM / F12 medium containing 10% fetal bovine serum at 37°C, 5% CO2, and 90% humidity.

[0024] Example 1: Peptide Synthesis The core amino acid sequence of the polypeptide provided by this invention is shown in SEQ ID NO: 1 (specifically: KEIVSEIIGLLMLEAH). A membrane-penetrating peptide is linked before the first amino acid Lys of the polypeptide. The polypeptide sequence after linking the membrane-penetrating peptide is shown in SEQ ID NO: 2. The last amino acid His of the polypeptide sequence is protected by an amino group. The polypeptide amino acid sequence and structural formula are as follows: Figure 1 As shown.

[0025] The peptide synthesis process is as follows: The peptide is synthesized from the carboxyl terminus (C-terminus) to the amino terminus (N-terminus) using the Fmoc solid-phase peptide synthesis method. First, the carboxyl group of Fmoc-protected tyrosine (Tyr) is covalently linked to a polymer resin. After removing the Fmoc protecting group at the amino terminus, Fmoc-protected glycine (Gly) monomer is added. An amide bond is formed between these two amino acids using a condensing agent. Through a cyclical process of "deprotection-coupling-washing," the peptide chain is gradually extended from the carboxyl terminus to the amino terminus according to the amino acid sequence, sequentially adding arginine (Arg), lysine (Lys), arginine (Arg), arginine (Arg), and glutamine (Gly). The N-terminus of the polypeptide is linked with a combination of arginine (Arg), lysine (Lys), glutamic acid (Glu), isoleucine (Ile), valine (Val), serine (Ser), glutamic acid (Glu), isoleucine (Ile), glycine (Gly), leucine (Leu), methionine (Met), leucine (Leu), glutamic acid (Glu), alanine (Ala), and histidine (His). Finally, piperidine is used to remove the FMOC protecting group at the N-terminus, and a primary amine (-NH2) group is introduced. The polypeptide chain is then cleaved from the solid support using trifluoroacetic acid to obtain polypeptide I, which is linked to the membrane-penetrating peptide. The sequence is shown in SEQ ID NO: 2, with the last amino acid His protected by an amine group. The specific structure is as follows: YGRKKRRQRRRKEIVSEIIGLLMLEAH-NH2. The structure of the polypeptide linked to the membrane-penetrating peptide is shown in [image missing]. Figure 1 As shown.

[0026] The purity of the peptide was determined by high-performance liquid chromatography (HPLC). Buffer solutions of 0.1% trifluoroacetic acid in 100% acetonitrile (Solution A) and 0.1% trifluoroacetic acid in 100% water (Solution B) were prepared. A C18 column was installed on the HPLC system, and the column was conditioned. A mixture of 5% Solution A and 95% Solution B was used to wash the column for 15 min at a flow rate of 40 mL / min. The column was then equilibrated with a 50% mixture (containing 0.1% trifluoroacetic acid) for 15 min. The synthesized peptide was then packed into the column. The peptide was eluted using a linear gradient of 5%–40% Solution A and 95%–60% Solution B for 25 min at a flow rate of 1.0 mL / min. UV detection was performed at 220 nm. The purity of the obtained peptide was determined to be 95.08%.

[0027] In addition, peptides II and III targeting the tumor protein complex FANCI-FANCD2 were designed, and peptides II and III linked to the membrane-penetrating peptide were synthesized according to the above method: The sequence of polypeptide II following the transmembrane peptide is shown in SEQ ID NO: 3. The last amino acid His in the polypeptide sequence is protected by an amino group. The specific structure is as follows: YGRKKRRQRRRVANETFCLEIMDSLRRC-NH2.

[0028] The sequence of polypeptide III following the transmembrane peptide is shown in SEQ ID NO: 4, with the last amino acid His protected by an amino group. The specific structure is as follows: YGRKKRRQRRRSSKVTEAFDY-NH2.

[0029] Activity assays were performed using peptides I-III linked to the membrane-penetrating peptide. In the following examples: peptide I is peptide I linked to the membrane-penetrating peptide (sequence shown in SEQ ID NO: 2). peptide II is peptide II linked to the membrane-penetrating peptide (sequence shown in SEQ ID NO: 3). peptide III is peptide III linked to the membrane-penetrating peptide (sequence shown in SEQ ID NO: 4).

[0030] Example 2: Peptide toxicity test and antitumor activity test The CCK-8 (Cell Counting Kit-8) method was used to detect the inhibitory effect of peptides on cancer cell growth. The CCK-8 reagent contains highly water-soluble 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonylbenzene)-2H-tetrazole monosodium salt, which can be reduced by surviving cells to a water-soluble orange-yellow formazan product in the presence of intracellular dehydrogenases and electron carriers. This product has a characteristic absorption peak at a wavelength of 450 nm, and its absorbance is positively correlated with the number of live cells. Therefore, it can be used to quantitatively detect cell number and cell viability.

[0031] The peptides prepared in Example 1 were dissolved in 50% PBS (phosphate-buffered saline) + 50% DMSO (dimethyl sulfoxide) solution, and then concentrated to concentrations of 2500, 1250, 625, 312.5, and 156.25 μM. Breast cancer cells HCC1806, MDA-MB-453, and MCF-7 were seeded into 96-well plates at 3000 cells per well and cultured at 37°C with 5% CO2 for 24 h. Different concentrations of peptide were then added to each well of the cell culture, with final peptide concentrations of 25, 12.5, 6.25, 3.125, and 1.5625 μM, and a final DMSO concentration of 0.5%. The control group cell cultures were treated with equal volumes of PBS and DMSO and cultured for 72 h. Add 10 μL of CCK8 solution to each well and incubate for 1 h. Measure the absorbance at 450 nm using a microplate reader. The percentage of absorbance in the experimental group relative to the control group represents the cell viability or proliferation level; the control group is assumed to be 100%. Calculate the half-maximal inhibitory concentration (IC50) of the peptide on cell proliferation. 50 ), the results are shown Figure 2 See Table 1.

[0032] according to Figure 2 As shown in Table 1, peptide I exhibited good inhibitory activity against breast cancer cells HCC1806, MDA-MB-453, and MCF-7, with an IC50 concentration of [missing value]. 50 The concentrations were 7.048, 3.06, and 7.758 μM, respectively. Peptide II exhibited weak inhibitory activity against breast cancer cells, but the IC50 concentration was low. 50 All values ​​were >25 μM. Peptide III showed no inhibitory activity against breast cancer cells.

[0033] .

[0034] Example 3: Inhibition of breast cancer cells by polypeptide I The peptides obtained in Example 1, and peptide I with the best activity as determined in Example 2, were dissolved in 50% PBS (phosphate buffer) + 50% DMSO (dimethyl sulfoxide) solution. The peptides were then prepared into concentrated solutions with concentrations of 2500, 1250, 625, 312.5 and 156.25 μM. Normal breast epithelial cells (184A1, 184B5, MCF10A) and breast cancer cells (SKBR3, T47D, MCF-7, HCC1500, SUM149PT, HCC1806, MDA-MB-453, BT549, HCC1937, MDA-MB-231, and MDA-MB-468) were seeded into 96-well plates at 3000 cells per well and cultured at 37°C with 5% CO2 for 24 h. Then, different concentrations of peptides were added to each well of the cell culture. The final concentrations of peptides used to treat cells were 25, 12.5, 6.25, 3.125, and 1.5625 μM, and the final concentration of DMSO was 0.5%. The control group cell culture was incubated with equal volumes of PBS and DMSO for 72 h. Add 10 μL of CCK8 solution to each well and incubate for 1 hour. Measure the absorbance at 450 nm using a microplate reader. The percentage of absorbance in the experimental group relative to the control group represents the cell viability or proliferation level; the control group is assumed to be 100%. Calculate the half-maximal inhibitory concentration (IC50) of the peptide on cell proliferation. 50 ), the results are shown Figure 3 And Table 2.

[0035] .

[0036] according to Figure 3 As shown in Table 2, the IC50 of peptide I against normal human mammary epithelial cells 184A1, 184B5, and MCF10A is... 50 The corresponding values ​​are 16.92 μM, 23.65 μM, and >25 μM, respectively, indicating larger IC values. 50 The values ​​indicate that peptide I has low cytotoxicity to normal cells. Peptide I exhibits strong inhibitory activity against breast cancer cell lines SKBR3, T47D, MCF-7, HCC1500, SUM149PT, HCC1806, MDA-MB-453, BT549, HCC1937, MDA-MB-231, and MDA-MB-468, with IC50 values ​​of [missing value]. 50 are 9.167 μM, 5.546 μM, 7.758 μM, 4.925 μM, 4.417 μM, 7.048 μM, 3.06 μM, 8.485 μM, 10.41 μM, 18.51 μM and 5.447 μM respectively.

[0037] Example 4: Inhibition of cervical cancer cells by polypeptide I The human breast cancer cells from Example 3 were replaced with human cervical cancer cells (HeLa), and all other procedures were the same as in Example 3. Inhibition and IC50 were observed. 50 The results of the values ​​are shown below. Figure 3 And Table 3.

[0038] .

[0039] according to Figure 3 As shown in Table 3, polypeptide I exhibits strong cytotoxic activity against the human cervical cancer cell line HeLa, with an IC50 value of [missing information]. 50 The value is 14.16 μM.

[0040] Example 5: Inhibition of ovarian cancer cells by polypeptide I The human breast cancer cells from Example 3 were replaced with human ovarian cancer cells SK-OV-3, and all other procedures were the same as in Example 3. Inhibition and IC50 were observed. 50 The results of the values ​​are shown below. Figure 3 And Table 4.

[0041] .

[0042] according to Figure 3 As shown in Table 4, peptide I exhibits strong cytotoxic activity against the human ovarian cancer cell line SK-OV-3, with an IC50 value of [missing information]. 50 The value is 6.81 μM.

[0043] Example 6: Inhibition of prostate cancer cells by polypeptide I The human breast cancer cells from Example 3 were replaced with human prostate cancer cells PC-3, and all other procedures were the same as in Example 3. Inhibition and IC50 were observed. 50 The results of the values ​​are shown below. Figure 3 See Table 5.

[0044] .

[0045] according to Figure 3 As shown in Table 5, peptide I exhibits strong cytotoxic activity against the human prostate cancer cell line PC-3, with an IC50 value of [missing information]. 50 The value is 4.792 μM.

[0046] Example 7: Inhibition of pancreatic ductal adenocarcinoma cells by polypeptide I The human breast cancer cells from Example 3 were replaced with human pancreatic ductal adenocarcinoma cells SW1990, and all other procedures were the same as in Example 3. Inhibition and IC50 were also observed. 50 The results of the values ​​are shown below. Figure 3 See Table 6.

[0047] .

[0048] according to Figure 3 As shown in Table 6, polypeptide I exhibits cytotoxic activity against the human pancreatic ductal adenocarcinoma cell line SW1990, with an IC50 value of [missing information]. 50 It is 22.18 μM.

[0049] Example 8: Inhibition of glioma by polypeptide I The human breast cancer cells from Example 3 were replaced with U87 human glioma cells, and all other procedures were the same as in Example 3. Inhibitory effect and IC50 were observed. 50 The results of the values ​​are shown below. Figure 3 See Table 7.

[0050] .

[0051] according to Figure 3 As shown in Table 7, peptide I exhibits strong cytotoxic activity against the human glioblastoma U87 cell line, with an IC50 value of [missing value]. 50 It is 5.356 μM.

[0052] Example 9: Detection of in vivo antitumor activity of peptide I HCC1806 cells in logarithmic growth phase were digested with trypsin, centrifuged to remove supernatant, resuspended in pre-cooled 1×PBS, counted, and the concentration was adjusted to 1×10⁻⁶. 6 Cells / ml, 75 μL of cell suspension was taken from each spot (i.e., 10 cells / ml). 6 Add 25 μL of matrix gel to each cell and mix well. Inject the mixture into the axilla of nude mice using a syringe. Measure the tumor volume one week after inoculation, when the subcutaneous tumor volume reaches 50-70 mm. 3 Nude mice were randomly divided into a DMSO control group and a peptide I (25 mg / kg) group, with 5 mice in each group. Peptide I was prepared with 1% DMSO, and 100 μL was injected intraperitoneally into each mouse. The DMSO control group was injected with a solvent without peptide I. Administration was once daily for 21 consecutive days. During this period, body weight and tumor volume (tumor volume = 0.5 x long axis x wide axis²) were measured regularly. After administration, the mice were sacrificed, tumor tissue was separated, weighed, photographed, and serum was collected for liver and kidney function testing. The drug used in this example was peptide I.

[0053] Figure 4 This represents the inhibitory effect of peptide I on human breast cancer in vivo. Figure 4 Image A is a picture of the tumor after the drug administration was completed. Figure 4 B represents the tumor volume measured every 2 days after drug treatment, and is represented by a line graph. Figure 4 C represents the tumor mass after drug administration, expressed as a bar chart. Figure 4According to AC, compared with the DMSO control group, the volume and weight of breast cancer tumors in nude mice were significantly lower after administration of 25 mg / kg peptide I. Figure 4 D represents the change in body weight of nude mice during drug administration, represented by a line graph; after drug administration, orbital blood was collected from mice to detect the serum alanine aminotransferase (ALT) level. Figure 4 E) and aspartate aminotransferase (AST) Figure 4 The content of F) was measured to evaluate the hepatotoxicity of peptide I in nude mice; serum creatinine levels were also measured. Figure 4 The content of G) was used to evaluate the nephrotoxicity of peptide I in nude mice; by Figure 4 According to DG, peptide I does not affect the weight of nude mice and has no liver or kidney toxicity to nude mice.

[0054] In summary, peptide I exhibits good in vivo anti-breast cancer activity, effectively inhibiting the growth of breast cancer cells in nude mice, without significantly affecting the weight and liver and kidney function of the nude mice.

[0055] It should be noted that the embodiments described above are only for explaining the present invention and do not constitute any limitation on the present invention. The present invention has been described with reference to typical embodiments, but it should be understood that the words used therein are descriptive and explanatory terms, not limiting terms. Modifications can be made to the present invention within the scope of the claims, and revisions can be made to the present invention without departing from the scope and spirit of the present invention. Although the present invention described herein relates to specific methods, materials, and embodiments, it does not mean that the present invention is limited to the specific examples disclosed herein; on the contrary, the present invention extends to all other methods and applications having the same function.

Claims

1. A polypeptide, characterized in that, The amino acid sequence of the polypeptide is shown in SEQ ID NO:

1.

2. A polypeptide, characterized in that, The polypeptide is obtained by linking a transmembrane peptide to the first amino acid Lys of the polypeptide with the sequence shown in SEQ ID NO:1, and the amino acid sequence of the polypeptide is shown in SEQ ID NO:

2.

3. A polypeptide, characterized in that, The amino acid sequence of the polypeptide is shown in SEQ ID NO:1 or SEQ ID NO:2, and the last amino acid His of the polypeptide is protected by an amino group.

4. The use of the polypeptide according to any one of claims 1-3 in the preparation of drugs for the prevention and / or treatment of cancer, characterized in that, The cancer is at least one of breast cancer, cervical cancer, ovarian cancer, prostate cancer, pancreatic ductal adenocarcinoma, and glioma.

5. The application according to claim 4, characterized in that, The cancer in question is breast cancer.

6. The application according to claim 4, characterized in that, The peptide is used in combination with a pharmaceutically acceptable carrier.

7. The application according to claim 4, characterized in that, The polypeptide or its pharmaceutically acceptable salt is used as the active pharmaceutical ingredient.

8. The application according to claim 7, characterized in that, The mass fraction of the active pharmaceutical ingredient is 0.1% to 99%.

9. The application according to claim 4, characterized in that, The peptide is used in combination with other drugs.

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