Antibacterial peptide RB12 and application thereof in preparation of medicine for preventing and / or treating uterine cavity diseases

Abstract

The invention provides an antibacterial peptide RB12 and application of the antibacterial peptide RB12 in preparation of a medicine for preventing and / or treating uterine cavity diseases. The amino acid sequence of the antibacterial peptide RB12 is as shown in SEQ ID NO: 1. The antibacterial peptide RB12 provided by the invention has antibacterial activity on four endometritis pathogenic bacteria, namely, escherichia coli, klebsiella, proteus mirabilis and staphylococcus aureus, and particularly, the antibacterial rate on the escherichia coli is close to 80%, and the antibacterial peptide RB12 can inhibit growth and proliferation of the endometritis pathogenic bacteria; according to the present invention, the antibacterial peptide RB12 can be directly obtained through solid-phase synthesis, such that the normal flora structure and the immune microenvironment of the endometrium can be easily maintained so as to achieve the effective prevention and treatment of the endometritis, the important significance is provided for the prevention and the clinical treatment of the endometritis, and the antibacterial peptide RB12 can be directly obtained through solid-phase synthesis so as to easily achieve the large-scale preparation and the clinical large-scale application of the antibacterial peptide RB12.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to an antimicrobial peptide RB12 and its use in preparing a medicament for preventing and / or treating uterine cavity diseases. Background Art

[0002] Endometritis refers to an inflammatory disease of the endometrium (the mucosal layer of the uterus). It is an inflammatory response caused by pathogens that infect the endometrium. The main clinical manifestations are lower abdominal pain, fever, abnormal vaginal discharge, and irregular menstruation. As the disease progresses, it can also cause infertility, ectopic pregnancy, and other problems. It mainly occurs in female mammals (including humans and livestock such as cattle, horses, and dogs). Based on the course of the disease, endometritis can be divided into acute endometritis and chronic endometritis. Acute endometritis manifests as a sudden infection accompanied by obvious clinical symptoms (such as fever and purulent discharge), while chronic endometritis manifests as long-term recurrent infection. The symptoms are subtle but can easily lead to complications such as infertility and miscarriage.

[0003] Currently, the main clinical treatment for endometritis is anti-infective drugs. Common clinical drugs include cephalosporins, macrolides, cephalosporins, etc., but the clinical efficacy is not ideal and drug resistance is easy to develop. Summary of the Invention

[0004] In order to solve the problems of unsatisfactory clinical efficacy and easy drug resistance in the treatment of endometritis by existing anti-infective drugs, the present invention provides an antimicrobial peptide RB12 and its use in the preparation of drugs for preventing and / or treating uterine cavity diseases.

[0005] According to a first aspect of the present invention, an antimicrobial peptide RB12 is provided. The amino acid sequence of the antimicrobial peptide RB12 is shown in SEQ ID NO: 1.

[0006] The pathological mechanism of endometritis is closely related to uterine microbial imbalance and immune microenvironment disturbances. Studies have shown that the normal uterine microbiome is dominated by Lactobacilli. However, the abnormal proliferation of pathogens such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus can disrupt the microbial balance, induce the release of pro-inflammatory cytokines (such as IL-6 and TNF-α), and lead to endometrial tissue damage and repair disorders. Mixed infections with Gram-negative and Gram-positive bacteria further exacerbate the difficulty of treating endometritis.

[0007] The inventors of this application used Litopenaeus vannamei as a research subject and isolated a short peptide with the amino acid sequence shown in SEQ ID NO: 1 from its hemolymph, which is the antimicrobial peptide RB12 provided by the present invention. Experimental verification of the antibacterial activity of the antimicrobial peptide RB12, obtained by solid-phase synthesis, revealed that the antimicrobial peptide RB12 exhibits antibacterial activity against four endometritis-causing bacteria: Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Proteus mirabilis (P. mirabils), and Staphylococcus aureus (S. aureus). In particular, the antimicrobial peptide RB12 exhibits antibacterial activity against E. coli, with an inhibition rate of nearly 80% against E. coli. The antimicrobial peptide RB12 provided by the present invention can inhibit the growth and proliferation of endometritis-causing bacteria, helping to maintain the normal microbial structure and immune microenvironment of the endometrium, thereby achieving effective prevention and treatment of endometritis. This is of great significance for the prevention and clinical treatment of endometritis. Furthermore, the antimicrobial peptide RB12 provided by the present invention can be directly obtained by solid-phase synthesis, which is conducive to the large-scale preparation and large-scale clinical application of the antimicrobial peptide RB12.

[0008] According to a second aspect of the present invention, a gene encoding the antimicrobial peptide RB12 is provided.

[0009] According to the third aspect of the present invention, an expression cassette containing the above encoding gene is provided.

[0010] According to a fourth aspect of the present invention, a recombinant bacterium containing the above-mentioned encoding gene is provided.

[0011] According to a fifth aspect of the present invention, a recombinant vector containing the above-mentioned encoding gene is provided.

[0012] According to a sixth aspect of the present invention, there is provided use of the antimicrobial peptide RB12 in the preparation of a medicament for preventing and / or treating uterine cavity diseases.

[0013] Preferably, the above-mentioned uterine cavity disease includes endometritis.

[0014] Preferably, the drug has an inhibitory effect on at least two of Escherichia coli, Klebsiella, Proteus mirabilis, and Staphylococcus aureus.

[0015] The antimicrobial peptide RB12 provided by the present invention is used in the preparation of a drug for preventing and / or treating uterine cavity diseases. The drug can inhibit the growth and proliferation of endometritis pathogens, which is beneficial to maintaining the normal flora structure and immune microenvironment of the endometrium, thereby achieving effective prevention and treatment of endometritis, which is of great significance for the prevention and clinical treatment of endometritis.

[0016] According to a seventh aspect of the present invention, a pharmaceutical composition for preventing and / or treating uterine cavity diseases is provided, wherein the pharmaceutical composition comprises the above-mentioned antimicrobial peptide RB12.

[0017] Preferably, the above-mentioned uterine cavity disease includes endometritis. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is the high performance liquid chromatogram of the antimicrobial peptide RB12 provided in Example 1.

[0019] Figure 2 This is the mass spectrum of the antimicrobial peptide RB12 provided in Example 1.

[0020] Figure 3 This is the 3D structural model predicted for the antimicrobial peptide RB12 in Example 2.

[0021] Figure 4 This is a graph showing the calculated results of the inhibition rates of the antimicrobial peptide RB12 solutions of different concentrations against Escherichia coli and Staphylococcus aureus provided in Example 3.

[0022] Figure 5 This is a plate effect diagram of the antibacterial experiment of the antimicrobial peptide RB12 solution with a concentration of 0.5 mg / mL provided in Example 4 on four pathogenic bacteria.

[0023] Figure 6 This is a graph showing the calculation results of the antibacterial rate of the antimicrobial peptide RB12 solution with a concentration of 0.5 mg / mL provided in Example 4 against four pathogenic bacteria. DETAILED DESCRIPTION

[0024] The following is a further clear and complete description of the technical features of the technical solution provided by the present invention in conjunction with specific embodiments. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without making creative efforts are within the scope of protection of the present invention.

[0025] Example 1 Acquisition, solid phase synthesis, purification and identification of antimicrobial peptide RB12

[0026] An antimicrobial peptide RB12, the amino acid sequence of which is shown in SEQ ID NO: 1, and the specific amino acid sequence is as follows: GVARIRDLLII, which is prepared by the following steps:

[0027] 1. Acquisition of antimicrobial peptide RB12

[0028] The inventors of the present application isolated a short peptide with an amino acid sequence as shown in SEQ ID NO: 1 from the hemolymph of Litopenaeus vannamei through a large number of experimental studies and named it antimicrobial peptide RB12.

[0029] 2. Solid-Phase Synthesis of Antimicrobial Peptide RB12

[0030] (1) Resin

[0031] In this example, Fmoc-Ala-Wang resin (functional group content of 0.33 mmol / g) was used as the resin in the synthesis of antimicrobial peptide RB12.

[0032] (2) Reagents

[0033] The reagents used in the solid phase synthesis of antimicrobial peptide RB12 are shown in Table 1.

[0034] Table 1 Reagents used in the solid phase synthesis of antimicrobial peptide RB12

[0035]

[0036]

[0037] (3) Synthesis of antimicrobial peptide RB12

[0038] ① Weigh Fmoc-Ala-Wang resin (0.05 mmol) and place it in a solid phase reactor. Add DCM (8 mL) thereto to allow the Fmoc-Ala-Wang resin to swell overnight, then remove the DCM by decompression. Add 200 mL / L piperidine solution (8 mL) to the solid phase reactor containing the Fmoc-Ala-Wang resin and react at room temperature for 5 min, then drain. Continue to add 200 mL / L piperidine solution (8 mL) to the solid phase reactor and react at room temperature for 20 min, then drain. Add DMF (8 mL) to the solid phase reactor to wash the Fmoc-Ala-Wang resin for 1 min, and wash it 3 times in total. Accurately measure the α-amino group of the amino acid solution protected by Fmoc (0.2 mL) mol), HBTU solution (0.2 mmol), and HOBt solution (0.195 mol) were added to a solid phase reactor and reacted for 5 min, then DIEA solution (0.4 mmol) was added and reacted under nitrogen bubble oscillation at room temperature for 2 h; DMF (8 mL) was added to wash the Fmoc-Ala-Wang resin for 1 min, and washed 3 times in total; a piperidine solution (8 mL) with a concentration of 200 mL / L was added to the solid phase reactor and reacted for 5 min at room temperature, and then drained, and a piperidine solution (8 mL) with a concentration of 200 mL / L was continuously added to the solid phase reactor and reacted for 20 min at room temperature, and then drained; DMF (8 mL) was added to the solid phase reactor and washed the Fmoc-Ala-Wang resin for 1 min, and washed 3 times in total;

[0039] ② According to the above steps, the antimicrobial peptide RB12 (amino acid sequence: GVARIRDLLII) is synthesized successively from the carbon end to the nitrogen end of the peptide chain;

[0040] ③ After the synthesis of the antimicrobial peptide RB12 is completed, the Fmoc-Ala-Wang resin with the short peptide chain is washed with DMF and DCM respectively, and the Fmoc-Ala-Wang resin is placed in a vacuum drying oven to dry for later use;

[0041] ④ Cleavage of short peptides: After the Fmoc-Ala-Wang resin is dried, use a spatula to break up the resin as much as possible, transfer it to a chicken heart bottle, add a magnetic stirrer, and slowly add 10 mL of cutting solution for removing the resin (calculated according to the mass ratio, TFA: pure water: anisole: phenol: dithiol = 82.5:5:5:5:2.5) in an ice-water bath, and react in an ice-water bath for 2 hours; after the reaction is completed, transfer the reaction solution together with the Fmoc-Ala-Wang resin to the filter, filter it with a water pump, place the filtrate in a round-bottom flask, and fill it with nitrogen. The mixture was placed in a round-bottom flask and dried under a nitrogen stream. When the sample in the round-bottom flask was blown to a viscous state, the nitrogen tube was removed, and about 20 mL of ice ether pre-cooled at 4°C was poured into the round-bottom flask. After mixing, the mixture was thoroughly dispersed. The resulting mixture was placed in a refrigerated centrifuge and centrifuged at 4°C and 8000 r / min for 15 min. The supernatant was discarded, and the resulting precipitate was dispersed in 20 mL of ice ether pre-cooled at 4°C and centrifuged. The above dispersion and centrifugation operations were repeated three times. The final precipitate was vacuum dried to obtain the crude antimicrobial peptide RB12 provided in this example.

[0042] 3. Purification and Identification of Antimicrobial Peptide RB12

[0043] The crude antimicrobial peptide RB12 obtained by solid phase synthesis was purified and identified by reverse phase high performance liquid chromatography (HPLC). The reagents and specific parameters used in HPLC are shown in Table 2.

[0044] Table 2 Specific parameters of HPLC

[0045]

[0046] The HPLC chromatogram of the crude antimicrobial peptide RB12 is as follows: Figure 1 As shown. Figure 1 The HPLC chromatogram shown is obtained by collecting the eluate from 11.4 to 12.5 minutes, removing the organic acetonitrile from the eluate using a rotary evaporator, and then freezing the remaining antimicrobial peptide RB12 aqueous solution into ice cubes in a refrigerator. Finally, the water is removed using a freeze dryer to obtain a fluffy solid powder, which is the pure antimicrobial peptide RB12 provided in this example.

[0047] In addition, the antimicrobial peptide RB12 pure product obtained above was identified by mass spectrometry. Figure 2 As shown. Figure 2 It can be seen that the molecular weight of the antimicrobial peptide RB12 is about 1279 Daltons (Da), and its doubly charged ion ([M+2H] 2+ ) and singly charged ions ([M+H] +) showed good signal intensity and clear ion peaks at m / z = 640.6 and m / z = 1279.8, respectively. These data indicate that the obtained antimicrobial peptide RB12 peptide sample is of high quality and suitable for subsequent further sequence analysis and identification experiments.

[0048] Example 2 Identification of the physicochemical properties of the antimicrobial peptide RB12

[0049] This example aims to identify the physicochemical properties of the antimicrobial peptide RB12 provided in Example 1. The results are shown in Table 1. Next, the antimicrobial peptide RB12 was predicted using the AlphaFold3 (http: / / https: / / alphafoldserver.com / ) website, and a model was automatically built for this sequence. The model was then opened using PyMOL software, and the 3D structural model of the antimicrobial peptide RB12 was shown in Figure 1. Figure 3 As shown, Figure 3 The 3D structure of the antimicrobial peptide RB12 at different positions is shown.

[0050] Table 3 Physicochemical properties of antimicrobial peptide RB12

[0051] Property Parameter Sequence GVARIRDLLII Molecular weight 1238.544Da Total hydrophobic ratio 64％ Total net charge at pH 7 +1 Hydrophobicity <h> ) < / h> 1.05 Average hydropathy 1.291 Molar extinction coefficient 1490

[0052] Depend on Figure 3 From the 3D structural model, it can be seen that the 5th to 9th amino acids of the antimicrobial peptide RB12 form an α-helical structure.

[0053] Example 3 Minimum inhibitory concentration of antimicrobial peptide RB12 against Escherichia coli and Staphylococcus aureus

[0054] This example aims to study the antibacterial activity of the antimicrobial peptide RB12 provided in Example 1 against Escherichia coli and Staphylococcus aureus to obtain the minimum inhibitory concentration (MIC) of the antimicrobial peptide RB12. The specific experimental steps are as follows:

[0055] 1. Materials and Reagent Preparation

[0056] (1) Synthesis of antimicrobial peptide RB12

[0057] The antimicrobial peptide RB12 was synthesized according to the steps of Example 1.

[0058] (2) Main reagents

[0059] The main reagents used in this example and their sources are shown in Table 4.

[0060] Table 4 Main reagents and their sources

[0061]

[0062]

[0063] (3) Preparation of solutions and culture media

[0064] Antimicrobial peptide RB12 solutions of different concentrations: Take out the freeze-dried powdered antimicrobial peptide RB12 pure product from the -20°C refrigerator, equilibrate it at room temperature for 1 hour, weigh the freeze-dried powdered antimicrobial peptide RB12 pure product, add sterile PBS buffer with a concentration of 0.01M and a pH value of 7.4 to dissolve and mix, and prepare an antimicrobial peptide RB12 solution with a concentration of 500 μg / mL. Use gradient dilution to prepare antimicrobial peptide RB12 solutions with different concentration gradients, and store them in aliquots at -20°C for later use.

[0065] Broth medium (liquid): Weigh 10 g of peptone, 5 g of beef extract, and 5 g of NaCl, add 800 mL of distilled water, adjust the pH to 7.2 with 5 M NaOH, make up to 1000 mL, and autoclave at 121°C for 20–30 min. Store at room temperature.

[0066] 2. Antibacterial activity verification - minimum inhibitory concentration (MIC) determination

[0067] The antibacterial activity of the antimicrobial peptide RB12 provided in Example 1 was verified by referring to the following method, and the specific process is as follows:

[0068] (1) Two experimental endometritis pathogens (Escherichia coli and Staphylococcus aureus) stored at -80°C were first activated in small amounts. Specifically, 50 μL of Escherichia coli and Staphylococcus aureus were inoculated into 1 mL of broth liquid culture medium and cultured in a constant temperature shaker at 37°C for 6-12 h until the logarithmic growth phase;

[0069] (2) Prepare bacterial suspension and dilute the bacterial suspension to a concentration of 10 6 CFU / mL;

[0070] (3) Take 50 μL of the diluted bacterial solution and mix it with equal volumes of antimicrobial peptide RB12 solution of different concentrations, and incubate it in a constant temperature water bath at 30°C for 2 h to obtain a mixed solution;

[0071] (4) Take 10 μL of the above mixture and add it to 100 μL of LB liquid medium, with two replicates per group, and incubate at 37°C overnight. At the same time, sterile PBS buffer with a concentration of 0.01 M and a pH of 7.4 was used as a negative control;

[0072] (5) The minimum inhibitory concentration (MIC) was measured on a 96-well plate reader (Biotek Epoch) at a wavelength of 600 nm. The lowest concentration of the antimicrobial peptide RB12 solution that inhibited 80% bacterial growth was defined as the MIC.

[0073] 3. Results Analysis

[0074] The calculation results of the inhibition rate of different concentrations of antimicrobial peptide RB12 solution against Escherichia coli and Staphylococcus aureus are as follows Figure 4 As shown, the horizontal axis Concentration of RB12 represents the concentration of the antimicrobial peptide RB12 solution (μg / mL), and the vertical axis Bacteria Inhibition represents the inhibition rate (%).

[0075] Depend on Figure 4 It can be seen that the minimum inhibitory concentration of the antimicrobial peptide RB12 solution against Escherichia coli is 250 μg / mL, and the minimum inhibitory concentration against Staphylococcus aureus is 62.5 μg / mL.

[0076] Example 4

[0077] This example aims to study the antibacterial activity of the antimicrobial peptide RB12 provided in Example 1 against different types of pathogenic bacteria. The specific experimental steps are as follows:

[0078] 1. Materials and Reagent Preparation

[0079] (1) Synthesis of antimicrobial peptide RB12

[0080] The antimicrobial peptide RB12 was synthesized according to the steps of Example 1.

[0081] (2) Pathogenic bacteria

[0082] The four pathogenic bacteria used in this example include Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Proteus mirabilis (P. mirabills) and Staphylococcus aureus (S. aureus).

[0083] (3) Main reagents

[0084] Bovine trypsin, beef extract, agar powder, sodium chloride, and sodium hydroxide were purchased from Guangzhou Weijia Technology Co., Ltd.

[0085] (4) Preparation of solutions and culture media

[0086] 0.5 mg / mL antimicrobial peptide RB12 solution: Take out the lyophilized powdered antimicrobial peptide RB12 pure product from the -20°C refrigerator and equilibrate it at room temperature for 1 hour. Weigh the lyophilized powdered antimicrobial peptide RB12 pure product and add 1 mL of sterile PBS buffer with a concentration of 0.01 M and a pH value of 7.4 to dissolve and mix to obtain an antimicrobial peptide RB12 solution with a concentration of 0.5 mg / mL. Aliquot and store at -20°C for later use.

[0087] Broth medium (liquid): Weigh 10 g of peptone, 5 g of beef extract, and 5 g of NaCl, add 800 mL of distilled water, adjust the pH to 7.2 with 5 M NaOH, make up to 1000 mL, and autoclave at 121°C for 20–30 min. Store at room temperature.

[0088] Broth medium (solid): Weigh 10 g of peptone, 5 g of beef extract, 5 g of NaCl, and 15 g of agar powder, add 800 mL of distilled water, adjust the pH to 7.2 with 5 M NaOH, make up to 1000 mL, and autoclave at 121°C for 20–30 min. Store at room temperature.

[0089] 2. Antibacterial activity verification - plate colony counting method

[0090] The antibacterial activity of the antimicrobial peptide RB12 provided in Example 1 was verified by referring to the following method, and the specific process is as follows:

[0091] (1) First, activate a small amount of the above four pathogenic bacteria. Specifically, 50 μL of pathogenic bacteria liquid was inoculated into 1 mL of broth liquid culture medium and cultured in a constant temperature shaker at 37°C for 6-12 h until the logarithmic growth phase;

[0092] (2) Prepare bacterial suspension from the activated bacterial solution and dilute the bacterial solution to a concentration of 5 × 10 3 CFU / mL, take 50 μL of the diluted bacterial suspension of the four pathogens and mix them with 50 μL of the antimicrobial peptide RB12 solution with a concentration of 0.5 mg / mL, place them in a constant temperature shaker at 37°C for 2 h to obtain a mixed solution, take 30 μL of the mixed solution to spread on the plate, invert and culture at 37°C for 12 to 24 h, then count the colonies and take pictures. At the same time, sterile PBS buffer with a concentration of 0.01 M and a pH value of 7.4 was used as a control (Control).

[0093] (3) Calculate the antibacterial rate (%) = (number of colonies in the negative control group - number of colonies in the experimental group) / number of colonies in the negative control group × 100.

[0094] 3. Results Analysis

[0095] The plate effect diagram of the antibacterial experiment of the antimicrobial peptide RB12 solution with a concentration of 0.5 mg / mL against four pathogenic bacteria, namely Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Proteus mirabilis (P. mirabills) and Staphylococcus aureus (S. aureus) is shown in the figure. Figure 5 As shown in the figure, the calculation results of Bacteria Inhibition (inhibition rate) are as follows Figure 6 As shown, in which Figure 5 In the table, Control refers to the negative control of sterile PBS buffer with a concentration of 0.01 M and a pH of 7.4. Figure 6 In the figure, the vertical axis Bacteria Inhibition represents the inhibition rate (%).

[0096] Depend on Figure 5 and Figure 6 It can be seen that the antimicrobial peptide RB12 has significant antibacterial activity against four pathogenic bacteria, namely Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Proteus mirabilis (P. mirabills) and Staphylococcus aureus (S. aureus). Among the four pathogenic bacteria, the antimicrobial peptide RB12 has the highest antibacterial activity against Escherichia coli, with an inhibition rate of up to 90%, and the lowest antibacterial activity against Staphylococcus aureus, only about 30%.

[0097] In summary, the antimicrobial peptide RB12 provided by the present invention has antibacterial activity against four endometritis pathogens: Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Proteus mirabilis (P. mirabills), and Staphylococcus aureus (S. aureus). In particular, the antimicrobial rate against E. coli is close to 80%. The antimicrobial peptide RB12 can inhibit the growth and proliferation of endometritis pathogens, which is beneficial for maintaining the normal flora structure and immune microenvironment of the endometrium, thereby achieving effective prevention and treatment of endometritis. This is of great significance for the prevention and clinical treatment of endometritis. In addition, the antimicrobial peptide RB12 provided by the present invention can be directly obtained by solid-phase synthesis, which is conducive to the large-scale preparation and large-scale clinical application of the antimicrobial peptide RB12.

[0098] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents, but these modifications or replacements are all within the scope of protection of the present invention.

Claims

1. An antimicrobial peptide RB12, characterized in that: The amino acid sequence of the antimicrobial peptide RB12 is shown in SEQ ID NO:

1.

2. A gene encoding the antimicrobial peptide RB12 according to claim 1.

3. An expression cassette containing the coding gene according to claim 2.

4. A recombinant bacterium containing the coding gene as claimed in claim 2.

5. A recombinant vector containing the coding gene as claimed in claim 2.

6. Use of the antimicrobial peptide RB12 according to claim 1 in the preparation of a medicament for preventing and / or treating uterine cavity diseases.

7. Use of the antimicrobial peptide RB12 according to claim 6 in the preparation of a medicament for preventing and / or treating uterine cavity diseases, characterized in that: The uterine cavity disease includes endometritis.

8. Use of the antimicrobial peptide RB12 according to claim 7 in the preparation of a medicament for preventing and / or treating uterine cavity diseases, characterized in that: The drug has an inhibitory effect on at least two of Escherichia coli, Klebsiella, Proteus mirabilis, and Staphylococcus aureus.

9. A pharmaceutical composition for preventing and / or treating uterine cavity diseases, characterized in that: The pharmaceutical composition comprises the antimicrobial peptide RB12 according to claim 1.

10. The pharmaceutical composition for preventing and / or treating uterine cavity diseases according to claim 9, characterized in that: The uterine cavity disease includes endometritis.

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