Antibacterial composition as well as preparation method and application thereof

Abstract

The invention relates to the technical field of medicines, in particular to an antibacterial composition as well as a preparation method and application thereof. The invention provides an antibacterial composition. The antibacterial composition is prepared from the following components in parts by mass: 0.039 to 0.3125 part of SU3327 and 62.5 to 500 parts of citric acid. The combined use of the SU3327 and the citric acid can effectively kill and / or inhibit vibrio parahaemolyticus, escherichia coli, salmonella, acinetobacter baumannii, staphylococcus aureus, klebsiella pneumoniae and staphylococcus pseudointermediates, and the use amount of the SU3327 in the medicament for treating bacterial infection is greatly reduced; and the compound shows extremely high application value in the process of preparing medicines for treating bacterial infection.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to an antibacterial composition and a preparation method and application thereof. Background Art

[0002] Bacterial diseases are one of the main causes of illness in humans and animals. The most effective treatment for bacterial infections is generally antibiotics, but the long-term use of antibiotics has led to an increasingly serious problem of bacterial resistance, and even to the point where no drugs are available. The development of new antimicrobial drugs has become one of the important ways to curb bacterial resistance in clinical practice, but the development of new antibiotics lags far behind the rapid evolution and spread of antibiotic resistance. Compared with the discovery of new antimicrobial drugs, combined strategies can restore the sensitivity of resistant strains to existing antibiotics, thus bringing hope to clinical treatment.

[0003] SU3327, CAS No. 40045-50-9, molecular formula C5H3N5O2S3, molecular weight 261.3, is a C-JUN N-terminal kinase (JNK) selective inhibitor, also known as halicin or SU3327, is a new potential antibiotic developed by a research team led by James Collins of the Massachusetts Institute of Technology (MIT) using deep learning artificial intelligence (AI). It has a certain inhibitory effect on a variety of bacteria such as Acinetobacter baumannii, Escherichia coli, Mycobacterium tuberculosis, and Clostridium difficile (Stokes JM, Yang K, Swanson K, Jin W, Cubillos-Ruiz A, Donghia NM, MacNair CR, French S, Carfrae LA, Bloom-Ackermann Z, Tran VM, Chiappino-Pepe A, Badran AH, Andrews IW, Chory EJ, Church GM, Brown ED, Jaakkola TS, Barzilay R, Collins JJ. A Deep Learning Approach toAntibiotic Discovery.Cell.2020,180(4):688-702); In the authorized patent CN202110710023.1, the inhibitory effect of SU3327 on Actinobacillus pleuropneumoniae was further reported (patent application number: CN202310092613.1); Subsequently, SU3327 was reported on the synergistic effect of colistin against Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus containing colistin resistance gene 1 (MCR1), as well as the synergistic effect of vancomycin against enterococci (patent application number: CN202310568344.1). In the patent CN202410131623.6, it was found that SU3327 combined with the antibacterial drug colistin had a good synergistic effect. However, studies have found that long-term use of colistin may cause the development of drug resistance, especially in aquaculture, which is subject to certain restrictions.

[0004] Therefore, a new antibacterial drug is urgently needed. Summary of the invention

[0005] In view of this, in order to solve the problems raised in the above background technology, the purpose of the present invention is to provide an antibacterial composition.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solution: an antibacterial composition, comprising the following components in parts by mass: 0.039 to 0.3125 parts of SU3327 and 62.5 to 500 parts of citric acid.

[0007] Preferably, the citric acid is citric acid monohydrate.

[0008] The invention provides a method for preparing the antibacterial composition, which comprises the following steps: mixing SU3327 and citric acid to obtain the antibacterial composition.

[0009] The present invention provides application of the antibacterial composition in preparing an antibacterial preparation.

[0010] Preferably, the bacteria include one or more of Vibrio parahaemolyticus, Escherichia coli, Salmonella, Acinetobacter baumannii, Staphylococcus aureus, Klebsiella pneumoniae and Staphylococcus pseudintermedius.

[0011] Preferably, the dosage form of the preparation includes premix, tablet, oral solution, capsule, injection, pellet or lyophilized powder.

[0012] The invention provides application of SU3327 and citric acid in the preparation of an antibacterial preparation.

[0013] Preferably, the bacteria include one or more of Vibrio parahaemolyticus, Escherichia coli, Salmonella, Acinetobacter baumannii, Staphylococcus aureus, Klebsiella pneumoniae and Staphylococcus pseudintermedius.

[0014] Preferably, the dosage form of the preparation includes premix, tablet, oral solution, capsule, injection, pellet or lyophilized powder.

[0015] The present invention provides an antibacterial agent, comprising the antibacterial composition and a pharmaceutically acceptable carrier.

[0016] Beneficial Effects of the Invention

[0017] The present invention provides an antibacterial composition, which specifically uses SU3327 and citric acid; the two are not just a simple addition of functions, but a synergistic antibacterial effect, and the amount of SU3327 used in the drug for treating bacterial infection is reduced;

[0018] The combined use of SU3327 and citric acid can effectively kill and / or inhibit Vibrio parahaemolyticus, Escherichia coli, Salmonella, Acinetobacter baumannii, Staphylococcus aureus, Klebsiella pneumoniae, and Staphylococcus pseudintermedius, and greatly reduce the amount of SU3327 used in the treatment of bacterial infections, showing a strong application value in the process of preparing treatments for bacterial infections. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The results of the synergistic antibacterial chessboard assay of SU3327 combined with citric acid against Vibrio parahaemolyticus ATCC17802;

[0020] Figure 2 The results of the synergistic antibacterial chessboard assay of SU3327 combined with citric acid against Vibrio parahaemolyticus A20231088;

[0021] Figure 3 The results of the synergistic antibacterial chessboard assay of SU3327 combined with citric acid against Vibrio parahaemolyticus A20231089;

[0022] Figure 4 The results of the synergistic antibacterial chessboard method of SU3327 combined with citric acid against Vibrio parahaemolyticus A20231098;

[0023] Figure 5 The results of the synergistic antibacterial chessboard assay of SU3327 combined with citric acid against Salmonella white 1;

[0024] Figure 6 The results of the synergistic antibacterial chessboard method of SU3327 combined with citric acid against Staphylococcus aureus 02016;

[0025] Figure 7 The results of the additive antimicrobial chessboard method of SU3327 combined with citric acid against Acinetobacter baumannii A2023978;

[0026] Figure 8 The results of the additive antimicrobial disk method of SU3327 combined with citric acid against Klebsiella pneumoniae 1202;

[0027] Fig. 9 The results of the additive antibacterial chessboard method of SU3327 combined with citric acid against Escherichia coli ATCC25922;

[0028] Fig.10 The results of the synergistic antibacterial chessboard assay of SU3327 combined with citric acid against Escherichia coli MG1655;

[0029] Fig.11 The chessboard method results show the synergistic antibacterial effect of SU3327 combined with citric acid on Escherichia coli 666;

[0030] Fig.12 The results show the additive antibacterial effect of SU3327 combined with citric acid against Staphylococcus pseudintermedius 31A.

[0031] Fig.13 The results of the synergistic antibacterial chessboard assay of SU3327 combined with citric acid against Staphylococcus pseudintermedius I1847;

[0032] Fig.14 The results of the synergistic antibacterial chessboard assay of SU3327 combined with citric acid against Staphylococcus pseudintermedius Q4204;

[0033] Fig.15The results of the synergistic antibacterial chessboard assay of SU3327 combined with citric acid against Staphylococcus pseudintermedius U5129;

[0034] Fig.16 This is the sterilization curve result of SU3327 combined with citric acid against Vibrio parahaemolyticus A20231098. DETAILED DESCRIPTION

[0035] The present invention provides an antibacterial composition, which comprises the following components in parts by weight:

[0036] SU3327 0.039-0.3125 parts, preferably 0.1390-0.2125 parts, more preferably 0.17575 parts;

[0037] The amount of citric acid is 62.5 to 500 parts, preferably 212.5 to 350 parts, and more preferably 281.25 parts.

[0038] In the present invention, the citric acid is citric acid monohydrate.

[0039] The invention provides a method for preparing the antibacterial composition, which comprises the following steps: mixing SU3327 and citric acid to obtain the antibacterial composition.

[0040] The present invention provides application of the antibacterial composition in preparing an antibacterial preparation.

[0041] In the present invention, the bacteria include one or more of Vibrio parahaemolyticus, Escherichia coli, Salmonella, Acinetobacter baumannii, Staphylococcus aureus, Klebsiella pneumoniae and Staphylococcus pseudintermedius.

[0042] In the present invention, the dosage form of the preparation includes premix, tablet, oral solution, capsule, injection, dripping pill or lyophilized powder.

[0043] The invention provides application of SU3327 and citric acid in the preparation of an antibacterial preparation.

[0044] In the present invention, the bacteria include one or more of Vibrio parahaemolyticus, Escherichia coli, Salmonella, Acinetobacter baumannii, Staphylococcus aureus, Klebsiella pneumoniae and Staphylococcus pseudintermedius.

[0045] In the present invention, the dosage form of the preparation includes premix, tablet, oral solution, capsule, injection, dripping pill or lyophilized powder.

[0046] The present invention provides an antibacterial agent, comprising the antibacterial composition and a pharmaceutically acceptable carrier

[0047] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0048] In the embodiment of the present invention, the citric acid monohydrate (purity 95%), CAS No.: 5949-29-1, linear molecular formula HOC(COOH)(CH2COOH)2·H2O, molecular weight: 210.14, was purchased from Sigma Reagent Company; the SU3327 was purchased from MedChemExpress Company, with a purity of 98.03%; SU3327 needs to be adjusted to a concentration of 10 mg / mL using dimethyl sulfoxide (DMSO) before use, and placed in a -20°C refrigerator for standby use;

[0049] Vibrio parahaemolyticus ATCC17802 was purchased from Guangdong Provincial Microbiological Culture Collection Center; Vibrio parahaemolyticus A20231088, Vibrio parahaemolyticus A20231089, Vibrio parahaemolyticus A20231098, Salmonella white 1, Staphylococcus aureus 02016, Acinetobacter baumannii A2023978, Klebsiella pneumoniae 1202, Escherichia coli ATCC25922, Escherichia coli MG1655, Escherichia coli 666, Staphylococcus pseudintermedius I1847, Staphylococcus pseudintermedius 31A, Staphylococcus pseudintermedius Q4204, Staphylococcus pseudintermedius U5129 were from National Center for Veterinary Drug Safety (Beijing);

[0050] The Mueller HintonⅡCationAdjusted broth (CAMHB broth) culture medium was purchased from BD Biosciences (Shanghai) Co., Ltd. The preparation method is as follows: weigh 22.0 g of the product in 1 L of distilled water, heat and boil until completely dissolved, sterilize at 121°C for 15 min, and set aside;

[0051] The MH agar medium was purchased from Beijing Luqiao Technology Co., Ltd. and prepared as follows: weigh 38.0 g of the product in 1 L of distilled water, heat and boil until completely dissolved, sterilize at 121° C. under high pressure for 15 min, cool to 55° C. and pour into a plate for later use;

[0052] The brain heart infusion broth medium (BHI broth medium) was purchased from Beijing Luqiao Technology Co., Ltd. and prepared as follows: 38.5 g of the product was weighed, dissolved in 1000 mL of distilled water with heating and stirring, the pH was adjusted to 7.3, and sterilized at 121° C. for 15 min for later use;

[0053] Example 1 Effects of SU3327 and citric acid alone and in combination against Vibrio parahaemolyticus, Escherichia coli, Salmonella, Acinetobacter baumannii, Staphylococcus aureus, Klebsiella pneumoniae, and Staphylococcus pseudintermedius

[0054] Vibrio parahaemolyticus ATCC17802 (ATCC17802), Vibrio parahaemolyticus A20231088 (A20231088), Vibrio parahaemolyticus A20231089 (A20231089), Vibrio parahaemolyticus A20231098 (A20231098), Salmonella white 1 (white 1), Staphylococcus aureus 02016 (02016), Acinetobacter baumannii A2023978 (A2023978), Klebsiella pneumoniae 1202 ( 1202), Escherichia coli ATCC25922 (ATCC25922), Escherichia coli MG1655 (MG1655), Escherichia coli 666 (666), Staphylococcus pseudintermedius 31A (31A), Staphylococcus pseudintermedius I1847 (I1847), Staphylococcus pseudintermedius Q4204 (Q4204), Staphylococcus pseudintermedius U5129 (U5129) were inoculated into BHI broth medium for enrichment culture, and cultured at 37°C, 200 rpm for 6 hours to obtain a bacterial solution;

[0055] The chessboard method was used to investigate the effects of SU3327 and citric acid alone and in combination on various bacteria. The specific steps were as follows: SU3327 and citric acid monohydrate were diluted in CAMHB broth at the highest concentrations of 5 μg / mL and 2000 μg / mL, respectively. The concentrations of citric acid monohydrate were 2000 μg / mL, 1000 μg / mL, 500 μg / mL, 250 μg / mL, 125 μg / mL, 62.5 μg / mL, 31.25 μg / mL, and 0 μg / mL, respectively. The concentrations of SU3327 and citric acid monohydrate were 15 μg / mL, 20 μg / mL, ... The concentrations were 5 μg / mL, 2.5 μg / mL, 1.25 μg / mL, 0.625 μg / mL, 0.3125 μg / mL, 0.15625 μg / mL, 0.0781 μg / mL, 0.039 μg / mL, 0.0195 μg / mL, and 0 μg / mL; 50 μL of CAMHB broth containing different concentrations of SU3327 and monohydrate citric acid was added along the horizontal and vertical axes of the 96-well culture plate, and then 50 μL of various pathogenic bacteria solutions were added, so that the final bacterial count in each well was 2×10 5 CFU, incubate in a 37°C constant temperature incubator for 18 hours, and observe the results; record the minimum inhibitory concentration (MIC) of the two drugs when used alone and in combination, and calculate the FICI value (fractional inhibitory concentration index) according to the following formula:

[0056] FICI of SU3327 and citric acid monohydrate = MIC (SU3327 combined) / MIC (SU3327 alone) + MIC (citric acid combined) / MIC (citric acid alone); judgment criteria: FICI ≤ 0.5, synergistic effect; 0.5 < FICI ≤ 1, additive effect; 1 < FICI ≤ 2, no effect; FICI > 2, antagonistic effect. The test results are shown in Table 1 and Figures 1 to 15 shown.

[0057] Table 1 Test results of the effects of SU3327 and citric acid monohydrate alone or in combination on various bacteria

[0058]

[0059]

[0060] From Table 1 and Figures 1 to 15 It can be seen that for Vibrio parahaemolyticus ATCC17802, the MICs of SU3327 and citric acid alone were 0.15625 μg / mL and 500 μg / mL, respectively, and the MICs of the combined use of the two were 0.039 μg / mL and 62.5 μg / mL, respectively, and the synergy index FICI was 0.375;

[0061] For Vibrio parahaemolyticus A20231088, the MICs of SU3327 and citric acid alone were 0.625 μg / mL and 500 μg / mL, respectively. When the two were used together, the MICs were 0.15625 μg / mL and 125 μg / mL, respectively. The synergy index FICI was 0.5.

[0062] For Vibrio parahaemolyticus A20231089, the MICs of SU3327 and citric acid alone were 0.625 μg / mL and 500 μg / mL, respectively. When the two were used together, the MICs were 0.0781 μg / mL and 125 μg / mL, respectively. The synergy index FICI was 0.375.

[0063] For Vibrio parahaemolyticus A20231098, the MICs of SU3327 and citric acid alone were 0.625 μg / mL and 500 μg / mL, respectively. When the two were used together, the MICs were 0.15625 μg / mL and 125 μg / mL, respectively. The synergy index FICI was 0.5.

[0064] For Salmonella enterica serovar White 1, the MICs of SU3327 and citric acid used alone were 10 μg / mL and 2000 μg / mL, respectively, and the MICs of their combined use were 2.5 μg / mL and 125 μg / mL, respectively, and the synergy index FICI was 0.3125;

[0065] For Staphylococcus aureus 02016, the MICs of SU3327 and citric acid used alone were 10 μg / mL and 1000 μg / mL, respectively, and the MICs of their combined use were 2.5 μg / mL and 250 μg / mL, respectively, and the synergy index FICI was 0.5;

[0066] For Acinetobacter baumannii A2023978, the MICs of SU3327 and citric acid used alone were >20 μg / mL and 1000 μg / mL, respectively. When used in combination, the MICs were 5 μg / mL and 500 μg / mL, respectively, and the combined inhibition index FICI was 0.625.

[0067] For Klebsiella pneumoniae 1202, the MICs of SU3327 and citric acid alone were >20 μg / mL and 2000 μg / mL, respectively. When used in combination, the MICs were 10 μg / mL and 1000 μg / mL, respectively. The combined inhibition index FICI was 0.75.

[0068] For E. coli ATCC25922, the MICs of SU3327 and citric acid used alone were 20 μg / mL and 1000 μg / mL, respectively, and the MICs of their combined use were 2.5 μg / mL and 500 μg / mL, respectively, and the combined inhibition index FICI was 0.625;

[0069] For E. coli MG655, the MICs of SU3327 and citric acid used alone were 10 μg / mL and 2000 μg / mL, respectively, and the MICs of their combined use were 2.5 μg / mL and 500 μg / mL, respectively, and the synergy index FICI was 0.5;

[0070] For E. coli 666, the MICs of SU3327 and citric acid used alone were 20 μg / mL and 1000 μg / mL, respectively, and the MICs of their combined use were 5 μg / mL and 250 μg / mL, respectively, and the synergy index FICI was 0.5;

[0071] For Staphylococcus pseudintermedius 31A, the MICs of SU3327 and citric acid alone were 10 μg / mL and 500 μg / mL, respectively, and the MICs of their combined use were 5 μg / mL and 62.5 μg / mL, respectively, and the combined inhibition index FICI was 0.625;

[0072] For Staphylococcus pseudintermedius I1847, the MICs of SU3327 and citric acid alone were >20 μg / mL and 500 μg / mL, respectively, and the MICs of their combined use were 2.5 μg / mL and 125 μg / mL, respectively, with a synergy index of 0.3125;

[0073] For Staphylococcus pseudintermedius Q4204, the MICs of SU3327 and citric acid used alone were 10 μg / mL and 1000 μg / mL, respectively, and the MICs of their combined use were 2.5 μg / mL and 250 μg / mL, respectively, with a synergistic index of 0.5;

[0074] For Staphylococcus pseudintermedius U5129, the MICs of SU3327 and citric acid used alone were 10 μg / mL and 1000 μg / mL, respectively, and the MICs of their combined use were 2.5 μg / mL and 250 μg / mL, respectively, with a synergistic index of 0.5;

[0075] In summary, SU3327 has a good antibacterial effect on Vibrio parahaemolyticus, Escherichia coli, Salmonella, Acinetobacter baumannii, Staphylococcus aureus, Klebsiella pneumoniae, and Staphylococcus pseudintermedius. At the same time, the combination of SU3327 and citric acid has obvious synergistic and additive antibacterial effects, and the FICI ranges from 0.75 to 0.3125.

[0076] Example 2 Determination of the minimum bactericidal combination concentration (MBC) of SU3327 and citric acid used alone and in combination

[0077] 10 μL of the solution from each well of the 96-well culture plate in Example 1 where no bacteria grew was spotted on MH agar medium and cultured in a 37°C constant temperature incubator for 18 h. The lowest concentration in the wells where no bacteria grew was the MBC. The results are shown in Table 2.

[0078] Table 2 MBC values ​​of SU3327 and citric acid monohydrate alone or in combination against various bacteria

[0079]

[0080] As can be seen from Table 2, for Vibrio parahaemolyticus ATCC17802, the MBCs of SU3327 and citric acid alone were 0.3125 μg / mL and 500 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 0.0781 μg / mL and 62.5 μg / mL, respectively;

[0081] For Vibrio parahaemolyticus A20231088 strain, the MBCs of SU3327 and citric acid alone were 1.25 μg / mL and 500 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 0.3125 μg / mL and 31.25 μg / mL, respectively;

[0082] For Vibrio parahaemolyticus A20231089, the MBCs of SU3327 and citric acid alone were 0.625 μg / mL and 500 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 0.625 μg / mL and 31.25 μg / mL, respectively;

[0083] For Vibrio parahaemolyticus A20231098, the MBCs of SU3327 and citric acid alone were 1.25 μg / mL and 500 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 0.3125 μg / mL and 62.5 μg / mL, respectively;

[0084] For Salmonella white 1, the MBCs of SU3327 and citric acid alone were >20 μg / mL and >2000 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 10 μg / mL and 125 μg / mL, respectively;

[0085] For Staphylococcus aureus 02016, the MBCs of SU3327 and citric acid alone were >20 μg / mL and >2000 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 5 μg / mL and 250 μg / mL, respectively;

[0086] For Acinetobacter baumannii A2023978, the MBCs of SU3327 and citric acid alone were >20 μg / mL and 1000 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 5 μg / mL and 500 μg / mL, respectively;

[0087] For Klebsiella pneumoniae 1202, the MBCs of SU3327 and citric acid alone were >20 μg / mL and >2000 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 2.5 μg / mL and 2000 μg / mL, respectively;

[0088] For E. coli ATCC25922, the MBCs of SU3327 and citric acid alone were >20μg / mL and >2000μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 20μg / mL and 2000μg / mL, respectively;

[0089] For E. coli MG1655, the MBCs of SU3327 and citric acid alone were 20 μg / mL and 2000 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 5 μg / mL and 250 μg / mL, respectively;

[0090] For E. coli 666, the MBCs of SU3327 and citric acid alone were >20 μg / mL and >2000 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 10 μg / mL and 500 μg / mL, respectively;

[0091] For Staphylococcus pseudintermedius 31A, the MBCs of SU3327 and citric acid alone were 20 μg / mL and 1000 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 10 μg / mL and 62.5 μg / mL, respectively;

[0092] For Staphylococcus pseudintermedius I1847, the MBCs of SU3327 and citric acid alone were >20 μg / mL and 2000 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 20 μg / mL and 1000 μg / mL, respectively;

[0093] For Staphylococcus pseudintermedius Q4204, the MBCs of SU3327 and citric acid alone were >20 μg / mL and 2000 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 20 μg / mL and 1000 μg / mL, respectively;

[0094] For Staphylococcus pseudintermedius U5129, the MBCs of SU3327 and citric acid alone were >20 μg / mL and 2000 μg / mL, respectively, and the minimum bactericidal combination concentrations of the two were 20 μg / mL and 1000 μg / mL, respectively;

[0095] In summary, the combined treatment of SU3327 and citric acid has obvious synergistic bactericidal function against Vibrio parahaemolyticus, Escherichia coli, Salmonella, Acinetobacter baumannii, Staphylococcus aureus, Klebsiella pneumoniae, and Staphylococcus pseudintermedius.

[0096] Example 3 Bactericidal effect of SU3327 and citric acid alone and in combination against Vibrio parahaemolyticus A20231098

[0097] Vibrio parahaemolyticus A20231098 was inoculated into BHI broth medium for enrichment culture at 37°C, 200 rpm, and cultured for 6 hours to obtain bacterial liquid; the bacterial liquid was divided into 4 groups: 0.15625 μg / mL SU3327 group, 125 μg / mL citric acid group, 125 μg / mL citric acid + 0.15625 μg / mL SU3327 group and control group (control);

[0098] SU3327 was added to the bacterial solution of the 0.15625 μg / mL SU3327 group to prepare a mixed solution, wherein the final concentration of SU3327 was 0.15625 μg / mL; citric acid monohydrate was added to the bacterial solution of the 125 μg / mL citric acid group to prepare a mixed solution, wherein the concentration of citric acid monohydrate was 125 μg / mL; SU3327 and citric acid monohydrate were added to the bacterial solution of the 125 μg / mL citric acid + 0.15625 μg / mL SU3327 group to prepare a mixed solution, wherein the final concentration of SU3327 was 0.15625 μg / mL, and the concentration of citric acid monohydrate was 125 μg / mL; 0.5% dimethyl sulfoxide was added to the bacterial solution of the control group to prepare a mixed solution;

[0099] The mixed solution was placed in a 37°C constant temperature incubator for culture. After 1 h, 3 h, 6 h, 12 h, and 24 h of culture, 100 μL of each mixed solution was spread on a 10 cm diameter MH agar medium. After overnight culture, the colonies were counted. The statistical results are shown in the table below. Fig.16 shown.

[0100] from Fig.16 It can be seen that for Vibrio parahaemolyticus A20231098 strain, at the 24th hour, compared with the control group, SU3327 and citric acid alone had no significant effect on the bacterial colony count; when SU3327 and citric acid were treated together, at the 3rd hour of treatment, the colony count was significantly lower than that of the control group and the citric acid alone treatment group, until 12 hours, there was no bacterial growth and the colony count was 0; therefore, the combined treatment of SU3327 and citric acid had an obvious synergistic bactericidal effect on Vibrio parahaemolyticus A20231098.

[0101] It can be seen from the above embodiments that the present invention provides an antibacterial composition and a preparation method and application thereof. The combined use of SU3327 and citric acid can effectively kill and / or inhibit Vibrio parahaemolyticus, Escherichia coli, Salmonella, Acinetobacter baumannii, Staphylococcus aureus, Klebsiella pneumoniae, and Staphylococcus pseudintermedius.

[0102] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. An antibacterial composition, characterized in that The antibacterial composition comprises the following components in parts by mass: 0.039 to 0.3125 parts of SU3327 and 62.5 to 500 parts of citric acid.

2. The antibacterial composition according to claim 1, characterized in that The citric acid is citric acid monohydrate.

3. The method for preparing the antibacterial composition according to claim 1 or 2 comprises the following steps: mixing SU3327 and citric acid to obtain the antibacterial composition.

4. Use of the antibacterial composition according to claim 1 or 2 in the preparation of an antibacterial preparation.

5. The use according to claim 4, characterized in that: The bacteria include one or more of Vibrio parahaemolyticus, Escherichia coli, Salmonella, Acinetobacter baumannii, Staphylococcus aureus, Klebsiella pneumoniae and Staphylococcus pseudintermedius.

6. The use according to claim 5, characterized in that: The dosage forms of the preparation include premix, tablet, oral solution, capsule, injection, dripping pill or lyophilized powder.

7. Application of SU3327 and citric acid in the preparation of antibacterial preparations.

8. The use according to claim 7, characterized in that: The bacteria include one or more of Vibrio parahaemolyticus, Escherichia coli, Salmonella, Acinetobacter baumannii, Staphylococcus aureus, Klebsiella pneumoniae and Staphylococcus pseudintermedius.

9. The use according to claim 8, characterized in that: The dosage forms of the preparation include premix, tablet, oral solution, capsule, injection, dripping pill or lyophilized powder.

10. An antibacterial agent, characterized in that: The invention comprises the antibacterial composition according to claim 1 or 2 and a pharmaceutically acceptable carrier.

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