Polypeptide as well as preparation method and application of gel containing polypeptide

Abstract

The invention relates to a polypeptide and a preparation method and application of gel containing the polypeptide. The amino acid sequence of the polypeptide is as shown in SEQ ID No. 1.

Description

Technical Field

[0001] The present invention relates to the field of biopharmaceuticals, and particularly to a polypeptide, which can be used for the treatment of bacterial vaginitis and the control of human papillomavirus infection. Background Art

[0002] Human papillomavirus (HPV) belongs to the Papillomaviridae family. It is a class of epitheliotropic non-enveloped double-stranded DNA viruses that can cause squamous epithelial proliferation of human skin and mucous membranes, manifested as symptoms such as common warts and genital warts (condyloma acuminata).

[0003] The female vagina is an open cavity and is easily infected by human papillomavirus and bacteria. The normal flora has an occupancy protection effect on the vagina. If the balance of the female vaginal flora is disrupted, such as the overgrowth of anaerobic bacteria, it is easy to cause bacterial vaginitis. Bacterial vaginitis and human papillomavirus infection are the most common vaginal infectious diseases, accounting for nearly half of vaginal infections. Patients may have symptoms such as vaginal itching and abnormal vaginal discharge. There are many subtypes of HPV. The HPV isolated from human skin and mucous membrane tissues is divided into more than 100 subtypes, and can also be divided into "low-risk" and "high-risk" types according to its carcinogenicity. Low-risk types (such as types 6 and 11) are mainly related to genital warts and low-grade cervical epithelial necrosis. Representatives of high-risk types are types 16 and 18. Their long-term infection is the main cause of tissue malignancies, especially cervical cancer.

[0004] Patients with bacterial vaginitis need to receive treatment in a timely manner, otherwise it will increase the risk of diseases such as spontaneous abortion and postpartum endometritis. At present, the use of antibacterial drugs such as metronidazole is the first choice for the treatment of bacterial vaginitis, but long-term use is likely to form drug-resistant strains. Antibacterial polypeptides are a class of small polypeptides widely present in animals, plants, insects and humans, encoded by genes and having a specific spatial structure, with a molecular weight of about 2000 to 7000 Da, consisting of 20 to 60 amino acid residues, having good antibacterial activity, and are a class of biological macromolecules that are expected to replace traditional antibiotics and antibacterial compounds. They have a wide source, excellent antibacterial performance and are not easily prone to bacterial drug resistance. However, natural antibacterial polypeptides have certain limitations, including low antibacterial activity, instability and relatively high hemolytic activity, etc. Summary of the Invention

[0005] One aspect of the present invention provides a polypeptide, the amino acid sequence of which is shown in SEQ ID No.1.

[0006] Another aspect of the present invention provides a composition containing the polypeptide as claimed in claim 1.

[0007] In a specific embodiment, the composition further comprises a gelling agent, a humectant, a pH regulator and water.

[0008] In a specific embodiment, 0.5 to 2.0 parts by mass of polypeptide, 1 to 2 parts by mass of gelling agent, 10 to 20 parts by mass of humectant, and 500 to 700 parts by mass of sterile water.

[0009] In a specific embodiment, the gelling agent is selected from carbomer 940.

[0010] In a specific embodiment, the humectant is selected from at least one of glycerol, propylene glycol, sorbitol, and polyethylene glycol.

[0011] In a specific embodiment, the pH regulator is selected from triethanolamine and / or sodium hydroxide.

[0012] In a specific embodiment, the pH value of the composition is 4.0 to 7.5.

[0013] In a specific embodiment, the composition further includes a preservative.

[0014] In a specific embodiment, the preservative is methylparaben.

[0015] In a specific embodiment, the dosage of the preservative is 1 to 2 parts by mass.

[0016] Use of the polypeptide according to one of the present inventions and the composition according to any one of the second aspect of the present invention in the preparation of a drug for combating at least one of Staphylococcus, Streptococcus, Enterococcus, Micrococcus, Moraxella, Corynebacterium, Klebsiella, Enterobacter, Serratia, Proteus, Pseudomonas, Morganella morganii, Haemophilus, Flavimonas, Acinetobacter, and Propionibacterium.

[0017] Use of the polypeptide according to one of the present inventions and the composition according to any one of the second aspect of the present invention in the preparation of a drug for combating human papillomavirus.

[0018] In a specific embodiment, the use is in the preparation of a drug for combating at least one of Staphylococcus aureus, Escherichia coli, Candida albicans, and Pseudomonas aeruginosa.

[0019] In a specific embodiment, the use is in the preparation of a drug for treating at least one of bacterial vaginosis.

[0020] In a specific embodiment, the use is in the preparation of a drug for combating at least one of human papillomavirus infections.

[0021] Advantages of the present invention:

[0022] The polypeptide gel prepared by the present invention has good antibacterial activity, a high effective rate against human papillomavirus infection, a low hemolysis rate, low irritation, easy spreadability of the gel, good comfort, and can also promote the transdermal absorption of drugs, achieving a better drug delivery effect, and can be used clinically for bacterial vaginitis. Description of the Drawings Figure 1 : It is the attached drawing of the minimum inhibitory concentration experiment in Example 1; Figure 2 : It is the attached drawing of the hemolysis experiment in Example 2. Detailed Description of the Invention

[0023] The above content of the present invention will be further described in detail below in the form of preferred embodiments, but it does not limit the present invention.

[0024] Unless otherwise specified, the reagents in the embodiments of the present invention can be purchased through commercial channels.

[0025] The amino acid sequence of the polypeptide of the present invention is shown in SEQ ID No.1, which is synthesized by GIL Chemical, and the content of the synthesized polypeptide is 95.7%.

[0026] The ordinary nutrient agar medium, Sabouraud dextrose solid medium, Sabouraud dextrose liquid medium and nutrient broth medium are all purchased from Beijing Solarbio Science & Technology Co., Ltd.

[0027] PBS, a phosphate buffer solution with a pH of 7.2, is purchased from Beijing Solarbio Science & Technology Co., Ltd.

[0028] Carbomer 940 is purchased from Lubrizol Specialty Chemicals (Shanghai) Co., Ltd.

[0029] Triethanolamine is purchased from Dow Chemical (China) Co., Ltd.

[0030] Staphylococcus aureus CMCC(B)26003, Escherichia coli CMCC(B)44102, Pseudomonas aeruginosa CMCC(B)10104 and Candida albicans CMCC(F)98001 are all purchased from Beijing Sanyao Science & Technology Development Co., Ltd.

[0031] Example 1

[0032] Add 100 μL of nutrient broth medium to each well of a 96-well plate. Then, add 100 μL of a polypeptide aqueous solution with a concentration of 1024 μg / mL (i.e., a mixed solution of only polypeptide and water) to the first well in the second column. Mix the nutrient broth medium and the polypeptide aqueous solution in this well evenly. Aspirate 100 μL from the second well in the first row and add it to the third well in the first row. After mixing evenly, take 100 μL from the third well in the first row and add it to the next column. Repeat this process until 100 μL is aspirated and discarded from the eleventh well in the first row. Then, dilute Staphylococcus aureus CMCC(B) 26003 to 10 4 to 10 5 CFU / mL, and inoculate 100 μL of the bacterial solution into each well of the 96-well plate. At this time, the final concentration of the polypeptide in the first well of the second column is 512 μg / mL, and the final concentration in the eleventh well of the first row is 1 μg / mL. Use purified water to prepare the twelfth column in the same manner as the second column as a negative control; use ampicillin with a final concentration of 1 μg / ml prepared in the same manner as the second column in the first column as a positive control. Incubate the 96-well plate overnight at 37 °C, and the culture temperature of Candida albicans is 28 °C. Use an enzyme-linked immunosorbent assay (ELISA) reader to measure the OD 620 value. Use the polypeptide concentration as the abscissa and the OD 620 value as the ordinate to plot a curve. The concentration corresponding to the point of the curve inflection, which is the first measurement data point on the left before the absorbance increases, is the minimum inhibitory concentration (MIC).

[0033] The determination of the minimum inhibitory concentration (MIC) for Escherichia coli CMCC(B) 44102, Candida albicans CMCC(F) 98001, and Pseudomonas aeruginosa CMCC(B) 10104 is the same as the activity determination for Staphylococcus aureus CMCC(B) 26003.

[0034] The results of the minimum inhibitory concentration (MIC) of the polypeptide against the four bacteria are shown in Table 1, Figure 1 .

[0035] Table 1 Polypeptide antibacterial results

[0036] Bacterial name Minimum inhibitory concentration (μg / mL) Staphylococcus aureus CMCC(B) 26003 2 Escherichia coli CMCC(B) 44102 4 Pseudomonas aeruginosa CMCC(B) 10104 8 Candida albicans CMCC(F) 98001 32

[0038] According to Table 1, Figure 1 it can be seen that the polypeptide has good antibacterial effects against Escherichia coli, Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus at concentrations above 32 μg / mL.

[0039] Example 2

[0040] The red blood cell solution used for detecting the hemolysis rate of animal red blood cells by the polypeptide is 4% Mianyang red blood cells (purchased from Beijing Solarbio Science & Technology Co., Ltd.).

[0041] The method for detecting the hemolytic activity rate of the polypeptide is as follows: Wash the red blood cell solution with PBS buffer (pH 7.2, purchased from Beijing Solarbio Science & Technology Co., Ltd.), then centrifuge (1500 r, 15 min) and discard the supernatant. Mix the 0.9 wt% sodium chloride aqueous solution with a volume ratio of 92:8 and the red blood cell solution after discarding the supernatant to prepare an 8% red blood cell suspension. Take 0.5 mL of the 8% red blood cell suspension into 11 1.5 mL plastic centrifuge tubes, and number them from left to right as CG x , 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, CG 0 , and then add the polypeptide aqueous solution (prepared by dissolving the polypeptide in purified water) to the centrifuge tubes numbered 1 - 10, so that the final concentrations of the polypeptide in the centrifuge tubes numbered 1 - 10 are respectively: 4 μg / mL; 8 μg / mL; 16 μg / mL; 32 μg / mL; 64 μg / mL; 128 μg / mL; 256 μg / mL; 512 μg / mL; 1024 μg / mL; 2048 μg / mL. Add PBS to the centrifuge tube CG 0 as a negative control, and add Triton X-100 to the centrifuge tube CG x to a final concentration of 0.1% (V / V) as a positive control. Incubate at 37 °C for 1 h, centrifuge at 1500 rpm for 5 minutes, transfer 100 μL of the supernatant to a new 96-well plate, and measure the OD 414 value using an enzyme-linked immunosorbent assay reader. Calculate the hemolytic rate of the polypeptide according to the OD 414 value, and the results are shown in Table 2 Figure 2 .

[0042] Table 2 Detection results of the hemolytic activity of the polypeptide

[0043] Polypeptide concentration μg / mL Polypeptide hemolysis rate (%) 4 0.16 8 0.27 16 0.25 32 0.58 64 1.23 128 2.2 256 3.7 512 6.6 1024 9.3 2048 18.2

[0045] The smaller the hemolytic rate value of the polypeptide, the lower the hemolytic toxicity of the polypeptide. As can be seen from Table 2 Figure 2 , the hemolytic rate of the polypeptide is very low, especially when it is below 2048 μg / mL, there is no significant hemolysis phenomenon.

[0046] Select carbomer, glycerol, and adjust the pH with triethanolamine, and design an orthogonal experiment with 3 levels and 3 factors (see Table 3) to obtain 9 formulations of polypeptide gels from Sample 1 to Sample 9, as shown in Table 4 specifically.

[0047] Table 3 Orthogonal design table of 3 levels and 3 factors

[0048]

[0049] Table 4 Polypeptide gels obtained through orthogonal experiments

[0050] Sample Carbomer (g) Glycerol (g) pH 1 1.0 10 4.5 2 1.5 15 4.5 3 2.0 20 4.5 4 2.0 10 5.5 5 1.5 15 5.5 6 1.0 20 5.5 7 1.0 10 6.5 8 1.5 15 6.5 9 2.0 20 6.5

[0051] The preparation steps of the polypeptide gel are as follows:

[0052] Step 1: Weigh carbomer and glycerol respectively according to Table 4.

[0053] Step 2: Take 500 g of sterile water, sprinkle the carbomer 940 powder into it under high-speed stirring, and continue stirring until the powder is completely dispersed in the sterile water. Add triethanolamine under low-speed stirring to adjust its pH to the value in Table 4 to form a gel matrix.

[0054] Step 3: Take 1.0 g of polypeptide and add it to 100 g of sterilized sterile water, mix evenly, add glycerol, stir and mix evenly, and then gradually add it to the gel matrix to prepare the polypeptide gel.

[0055] Step 4: Fill and subpackage the polypeptide gel into vaginal applicators at a rate of 3 ml per vial, and then package to obtain the product.

[0056] Performance tests of the 9 prepared samples for product appearance, visible foreign matters, viscosity, pH, and antibacterial activity were carried out at 25 ± 2 °C. The specific test methods are as follows:

[0057] (1) Appearance: Visually observe whether the appearance of the polypeptide gel is a colorless to light yellow gel with uniform color under an illuminance of 3000 to 5000 lx. The test results are shown in Table 5.

[0058] (2) Visible foreign matters: According to the visible foreign matters inspection method in the fourth part of the Chinese Pharmacopoeia 2020 edition, page 0904: Visually detect the polypeptide gel filled in the vaginal applicator under an illuminance of 1000 to 1500 lx. Result determination: No obvious visible foreign matters such as metal shavings, glass shavings, fibers longer than 2 mm, and lumps with a maximum particle size exceeding 2 mm shall be detected in the polypeptide gel. The test results are shown in Table 5.

[0059] (3) Viscosity: Use a digital viscometer to measure the viscosity according to the method specified in the Chinese Pharmacopoeia 2020 edition. Take the average value of three measurements for the same sample. The test results are shown in Table 5.

[0060] (4) pH value: Adopt the direct measurement method of diluting the pH meter with 10-fold purified water. Take the average value of three measurements for the same sample. The test results are shown in Table 5.

[0061] (5) Detection of antibacterial rate: It is carried out according to the antibacterial rate detection method of the national health industry standard WS / T 650-2019 of the People's Republic of China, specifically as follows:

[0062] Inoculate Staphylococcus aureus CMCC(B)26003 on ordinary nutrient agar medium. After culturing for 24 hours, wash it off with PBS buffer solution and dilute it with PBS buffer solution to about 5.0×105 CFU / mL to 4.5×10 6 CFU / mL bacterial suspension to obtain the test bacterial suspension. Take 5.0 mL of the polypeptide gel and add it to a sterile test tube. Place it in a water bath at 20°C ± 1°C for 5 min, then add 0.1 mL of the test bacterial suspension, mix quickly to obtain the test sample, and start timing immediately. After the Staphylococcus aureus in the test sample interacts with the polypeptide solution for 10 min, respectively pipette 1.0 mL of the test sample and inoculate it into 2 petri dishes. When the colonies in the subsequent culture are too dense to be counted, perform 10-fold serial dilutions with PBS buffer, and then select an appropriate dilution factor for the same operation, that is, respectively pipette 1.0 mL and inoculate it into 2 petri dishes; then pour ordinary nutrient agar medium into the petri dishes containing the test sample and mix evenly, and then culture at 36°C ± 1°C for 48 h for colony counting. Calculate the bacterial content in the test sample based on the colony count. The test is repeated 3 times. At the same time, use PBS buffer instead of the polypeptide gel for parallel testing as a positive control. After colony counting, calculate that the bacterial content in the positive control is between 1.0×10 4 CFU / mL to 9.0×10 4 CFU / mL. Take PBS buffer and liquid ordinary nutrient medium of the same batch without adding the test bacterial suspension as negative controls respectively. Calculate the antibacterial rate The formula for calculating the antibacterial rate is as follows:

[0063]

[0064] In the formula:

[0065] X—the antibacterial rate, %;

[0066] X 0 —the bacterial content of the positive control, in units of CFU / mL;

[0067] X 1 —the bacterial content of the test sample, in units of CFU / mL;

[0068] The results obtained from the above detection items are shown in Table 5.

[0069] Table 5 Test results of the polypeptide gel

[0070]

[0071] According to Table 5, it can be seen that Samples 1 to 9 can all meet the requirements. Among them, Sample 5 is the best, that is, adjusting the pH to 5.5 with triethanolamine, 15 g of glycerol, and 1.5 g of carbomer, and the product performance is the best.

[0072] Example 4

[0073] Take the polypeptide gel samples 1 to 9 prepared in Example 3 and place them in a test chamber at a temperature of 25 ± 2°C, a relative humidity of 60 ± 10%, and a light intensity of 200 ± 10 LX for 6 months. Samples are taken at the end of the 0th, 1st, 2nd, 3rd, and 6th months respectively for the investigation of key stability items. Among them, the specific investigation indicators are appearance, visible foreign matters, viscosity, pH, and antibacterial activity. The investigation method is the same as that in Example 3.

[0074] The results are shown in Tables 6, 7, 8, 9, 10, 11, 12, 13, and 14.

[0075] Table 6 Results of the Stability Investigation of Sample 1 Polypeptide Gel

[0076]

[0077] Table 7 Results of the Stability Investigation of Sample 2 Polypeptide Gel

[0078]

[0079] Table 8 Results of the Stability Investigation of Sample 3 Polypeptide Gel

[0080]

[0082] Table 9 Results of the Stability Investigation of Sample 4 Polypeptide Gel

[0083]

[0084] Table 10 Results of the Stability Investigation of Sample 5 Polypeptide Gel

[0085]

[0086] Table 11 Results of the Stability Investigation of Sample 6 Polypeptide Gel

[0087]

[0089] Table 12 Results of the Stability Investigation of Sample 7 Polypeptide Gel

[0090]

[0091] Table 13 Results of the Stability Investigation of Sample 8 Polypeptide Gel

[0092]

[0093] Table 14 Results of the Stability Investigation of Sample 9 Polypeptide Gel

[0094]

[0095] As can be seen from Tables 6, 7, 8, 9, 10, 11, 12, 13, and 14, the 6-month stability study shows that there are no significant changes in the indicators of the appearance, visible foreign matters, viscosity, pH, and antibacterial activity, indicating that the polypeptide gel has good stability.

[0096] Example 5

[0097] 1. Detection basis: "Disinfection Technical Specification" (2002 Edition), 2.3.5 Vaginal Mucosa Irritation Test; 2. Sample preparation: Use the polypeptide gel of Sample 5 prepared in Example 3.

[0098] 3. Test method:

[0099] 3.1 Preparation of experimental animals: Select healthy, newly adult female white New Zealand rabbits of the same strain, weighing 2.0 Kg to 2.5 Kg. Before the test, carefully check the vaginal orifice of the animals for no secretions, congestion, edema, and other injuries. Divide them into a stimulation group and a control group, with 3 animals in each group.

[0100] 3.2 Stimulation method: Fix the animals, expose the perineum and vaginal orifice, moisten the vaginal applicator filled with 3 mL of the test polypeptide gel with the test solution, and gently insert it 4 cm to 5 cm into the vagina, slowly inject 3 mL of the test polypeptide gel, and then withdraw the vaginal applicator to complete the stimulation. The animals in the control group are treated in the same way with normal saline. At 24 h after stimulation, the animals are sacrificed by air embolism, and the intact vagina is taken out, longitudinally incised for observation and fixation. Tissue sections are prepared from 3 parts at both ends and the center of the vagina, stained with HE, and then subjected to histopathological examination. Scoring and grading are carried out according to the relevant regulations in the "Disinfection Technical Specification" (2002 Edition), and then the vaginal irritation index is calculated.

[0101] Among them, the calculation formula of the vaginal irritation index is as follows:

[0102] Irritation index = average score of the stimulation group - average score of the control group. The results are shown in Table 15.

[0103] Table 15 Record Table of Pathological Examination of Vaginal Mucosa Irritation Test in New Zealand Rabbits

[0104]

[0105] As can be seen from Table 15, the score of the polypeptide gel on the vaginal mucosa of New Zealand rabbits is 0.45, and the reaction intensity of the vaginal irritation test on New Zealand rabbits is non-irritating.

[0106] Example 6

[0107] The difference between the polypeptide gel formulation and preparation method and Sample 5 in Example 3 is that glycerol is replaced by propylene glycol.

[0108] The stability study is the same as that in Example 3, and the results are shown in Table 16.

[0109] Example 7

[0110] The polypeptide gel formulation and preparation method are different from those of Sample 5 in Example 3 in that glycerol is replaced by sorbitol.

[0111] The stability investigation was the same as that in Example 3, and the results are shown in Table 16.

[0112] Example 8

[0113] The polypeptide gel formulation and preparation method are different from those of Sample 5 in Example 3 in that glycerol is replaced by polyethylene glycol.

[0114] The stability investigation was the same as that in Example 3, and the results are shown in Table 16.

[0115] Table 16 Bacteriostatic Rates of Examples 6, 7, and 8 by Month

[0116]

[0117] According to the results of Samples 1-9 in Example 3 and Examples 5 to 8, the pH range of the polypeptide is 4.5 - 6.5. Carbomer 940 is suitable as the gelling agent. Glycerol, propylene glycol, sorbitol, and polyethylene glycol are suitable as the humectants, among which glycerol is the best.

[0118] Example 9

[0119] Therapeutic Effect of the Polypeptide Contained in the Combined Gel of the Present Invention on Female Human Papillomavirus (HPV) Infection

[0120] Thirty-six female patients infected with human papillomavirus (HPV) were selected and randomly divided into an observation group and a blank group, with 18 cases in each group.

[0121] Inclusion Criteria: 1. Female; 2. Clinically diagnosed and confirmed to be infected with human papillomavirus (HPV); 3. Tested positive for human papillomavirus (HPV) infection by an epithelial tissue staining test strip; 4. Without serious diseases of important organs such as the heart, liver, and kidneys; 5. Non-pregnant or lactating patients; 6. Without any of the following situations: a) Suffering from malignant tumors; b) Systemic immune diseases; c) Cognitive impairment.

[0122] Specific Implementation Method: The observation group used the polypeptide gel preparation described in Sample 5 of Example 3 of the present invention. After cleaning the vulva before going to bed, 1 tube (3 ml) was pushed into the vaginal stump, 1 tube per day. After maintaining the sitting or lying position for 5 minutes, the patient could get up. It was discontinued during menstruation and continuously used for 60 days (counted by natural days). The blank group was given the gel in the same way as the observation group, and the difference in the administered gel from that in Example 3 was that it did not contain the polypeptide described in the present invention.

[0123] Observation indicators: It is considered effective if the human papillomavirus (HPV) infection turns negative after treatment. The detection method is the trans-epithelial tissue staining test strip method (purchased from Cofoe Medical Technology Co., Ltd.). The observation points are 30 days and 60 days.

[0124] The treatment results of the observation group and the blank group after treatment are shown in Table 17

[0125] Table 17 Comparison of the negative conversion rates of the observation group and the blank group at 30 days and 60 days

[0126]

[0127] The results in Table 17 show that for the observation group using Sample 5 gel in Example 3 of the present invention, the negative conversion rate after the treatment of human papillomavirus (HPV) infection reaches 88.9%, and the negative conversion rate of the blank group is 11.1%, showing a significant difference. The polypeptide and the gel containing the same of the present invention can effectively treat human papillomavirus (HPV) infection.

[0128] The above are only the preferred embodiments of the present invention, and do not limit the patent scope of the present invention accordingly. Any equivalent composition or equivalent use transformation made by using the polypeptide described in the specification of the present invention and the gel containing the same, or directly or indirectly applied in other related technical fields, shall be similarly included in the patent protection scope of the present invention.

Claims

1. A polypeptide, the amino acid sequence of which is shown in SEQ ID No.

1.

2. A composition comprising the polypeptide according to claim 1.

3. The composition according to claim 2, characterized in that The composition also includes a gelling agent, a moisturizing agent, a pH adjusting agent and water.

4. The composition according to claim 3, characterized in that 0.5 to 2.0 parts by mass of polypeptide, 1 to 2 parts by mass of gelling agent, 10 to 20 parts by mass of moisturizing agent, and 500 to 700 parts by mass of sterile water.

5. The composition according to claim 3, characterized in that The gel is selected from Carbomer 940.

6. The composition according to claim 3, characterized in that The moisturizing agent is selected from at least one of glycerin, propylene glycol, sorbitol and polyethylene glycol.

7. The composition according to claim 3, characterized in that The pH regulator is selected from triethanolamine and / or sodium hydroxide.

8. The composition according to claim 3, characterized in that The pH of the composition is 4.0 to 7.

5.

9. Use of the polypeptide according to claim 1 or the composition according to any one of claims 2 to 9 for preparing a medicament against at least one of Staphylococcus, Streptococcus, Enterococcus, Micrococcus, Moraxella, Corynebacterium, Klebsiella, Enterobacter, Serratia, Proteus, Pseudomonas, Morganella morganii, Haemophilus, Xanthomonas, Acinetobacter and Propionibacterium; Preferably, the application is an application in the preparation of a drug for resisting at least one of Staphylococcus aureus, Escherichia coli, Candida albicans and Pseudomonas aeruginosa; Preferably, the application is an application in the preparation of at least one of a drug for treating bacterial vaginosis and / or a drug for resisting human papillomavirus infection.

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