Water-soluble organic ionic salts, methods for their synthesis and uses thereof

Abstract

The application relates to a water-soluble organic ion salt and a synthesis method and application thereof, and belongs to the antibacterial technical field. The water-soluble organic ion salt comprises the following steps: 1) preparing a first intermediate QBr; 2) preparing a second intermediate YDOBr; 3) adding the YDOBr into pyridine and uniformly stirring, reacting at 75-85 DEG C for 16-20 hours, cooling the system to room temperature, and precipitating orange-red solid, and then performing suction filtration, and washing the filter cake with dichloromethane to obtain orange solid, which is a target product, namely, the water-soluble organic ion salt YDOPy. The synthesis method of the water-soluble organic ion salt is simple, and pyridine ion salt is introduced based on a core element of indanedione to realize antibacterial performance.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of antibacterial technology, and particularly relates to a water-soluble organic ionic salt and a synthesis method and application thereof. BACKGROUND

[0002] Staphylococcus aureus (SA) is a gram-positive pathogenic bacterium, which can be transmitted through air, water, food and living media, etc. The latest CHINET bacterial drug resistance monitoring network in China shows that SA accounts for the third place in the constituent ratio of bloodstream infections, gram-positive cocci are mainly in children BSI pathogens, and the detection rate of SA ranks the top three. Data shows that the hospital mortality rate of staphylococcus aureus bloodstream infection can be as high as 20% to 30%. When the conditions are suitable, it can usually cause various diseases. One is invasive disease, which mainly manifests as suppurative infection of various organs, such as skin soft tissue infection, bone and joint infection, urinary tract infection, infective endocarditis, etc., and can also cause septicemia, septic syndrome, septic shock and other systemic infections. The other is toxin disease, which is caused by external toxins, and the main symptoms are acute gastroenteritis, including nausea, vomiting and diarrhea, etc. In addition, the bacteria are also closely related to medical device-related infections and deep infections, such as catheter-related infections, osteomyelitis, endocarditis, etc., which increase the mortality rate of patients and the risk of poor prognosis, and pose a major threat to human health and global public health.

[0003] Disinfection plays an important role in killing pathogenic microorganisms and controlling infection, and is an important means to cut off the transmission of diseases. Long-term use of disinfectants often induces bacterial drug resistance. Long-term irradiation of ultraviolet rays can cause skin damage, and severe cases can cause skin cancer. Due to the defects of traditional disinfectants and disinfection technologies, it is urgent to develop new bacterial control methods to eliminate bacterial contamination. Organic small molecules have the characteristics of simple synthesis and flexible and controllable structure design, and can adjust the physical and chemical properties by introducing specific functional groups to realize their antibacterial performance. SUMMARY

[0004] In view of the above problems existing in the prior art, the purpose of the present application is to design a technical scheme of a water-soluble organic ionic salt and a synthesis method and application thereof, which has a simple synthesis method and realizes its antibacterial performance by introducing a pyridine ionic salt based on the core element of indanedione.

[0005] The water-soluble organic ionic salt is characterized by a compound as shown in the following formula:

[0006]

[0007] The synthesis method of the water-soluble organic ionic salt is characterized by comprising the following steps:

[0008] 1) equal molar quantity of 5-bromo-2-(dimethylamino)benzaldehyde and 1,2-dibromoethane were mixed in acetone, and the reaction was carried out under reflux protection with nitrogen protection, and the reaction was monitored by spotting plate. When the raw material was completely reacted, the reaction system was extracted with dichloromethane and water, and the organic phase was collected and rotary evaporated to obtain a crude product. Then, column chromatography purification was carried out, 200-300 mesh silica gel powder was used as the stationary phase, and dichloromethane and ethyl acetate were mixed in a volume ratio of 9-11:1 to prepare the mobile phase to obtain the first intermediate 2-(2-bromoethoxy)-4-(dimethylamino)benzaldehyde, abbreviated as QBr, with the chemical formula of C 11 H 14 BrNO2;

[0009] 2) equal molar quantity of QBr, sodium hydroxide and 1,3-indane dione were mixed in ethanol, and the reaction was carried out under reflux protection for 10-14 hours. The reaction system was extracted with dichloromethane and water, and the organic phase was collected and rotary evaporated to obtain a crude product. Then, column chromatography purification was carried out, 200-300 mesh silica gel powder was used as the stationary phase, and dichloromethane and ethyl acetate were mixed in a volume ratio of 4-6:1 to prepare the mobile phase to obtain the second intermediate 2-(2-(2-bromoethoxy)-4-(dimethylamino)benzylidene)-1H-indene-1,3(2H)-dione, abbreviated as YDOBr, with the chemical formula of C 20 H 18 BrNO3;

[0010] 3) YDOBr was added to pyridine and stirred uniformly, pyridine was used as the solvent and reactant, and the reaction was carried out at 75-85°C for 16-20 hours. The system was cooled to room temperature, and orange-red solid was precipitated. Filtration under suction and washing the filter cake with dichloromethane obtained orange solid, which was the target product water-soluble organic ion salt (1-(2-(5-(dimethylamino)-2-((1,3-diketone-1,3-dihydro-2H-inden-2-ylidene)methyl)phenoxy)ethyl)pyridin-1-ium, abbreviated as YDOPy, with the chemical formula of C 25 H 23 N2O3 + Br - ;

[0011] The synthesis path is as follows:

[0012]

[0013] The synthesis method of the water-soluble organic ion salt is characterized in that in step 1), the volume ratio of dichloromethane to ethyl acetate is 10:1.

[0014] The synthesis method of the water-soluble organic ion salt is characterized in that in step 2), the reflux reaction time is 12 hours, and the volume ratio of dichloromethane to ethyl acetate is 5:1.

[0015] The synthesis method of the water-soluble organic ionic salt is characterized in that, in step 3), the reaction temperature is 80 DEG C, and the reaction time is 18 hours.

[0016] The water-soluble organic ionic salt is applied to preparation of an antibacterial preparation.

[0017] The water-soluble organic ionic salt is applied to preparation of an antibacterial preparation.

[0018] The water-soluble organic ionic salt and the synthesis method and the application thereof are simple in synthesis method, and the core element based on indanedione is introduced with pyridine ionic salt to realize antibacterial performance. The strain inhibition zone size of the water-soluble organic ionic salt YDOPy is 10.1 mm; the MIC value of YDOPy is 31.25 ug / mL; the YDOPy with one-fold MIC concentration can reduce the virulence of MRSA infection in vivo, and plays a role in resisting MRSA in vivo; after the Staphylococcus aureus treated by YDOPy, the cell wall of the bacteria has been destroyed or has been inhibited in the synthesis stage of the bacterial cell wall, and the antibacterial effect is shown. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 YDOPy obtained from the embodiment 1 of the application is shown in the nuclear magnetic resonance hydrogen spectrum;

[0020] Figure 2 The inhibition zone chart of the embodiment 1 of the application is shown in the figure;

[0021] Figure 3 The plate colony counting result chart of the embodiment 2 of the application is shown in the figure;

[0022] Figure 4 The survival curve chart of the larvae in different groups of the embodiment 3 of the application is shown in the figure;

[0023] Figure 5 The electron microscope chart of the embodiment 4 of the application is shown in the figure. DETAILED DESCRIPTION

[0024] In order to more clearly illustrate the application, the application is further described below in combination with preferred embodiments and the drawings. It should be understood by those skilled in the art that the specific description below is illustrative rather than limiting, and should not limit the protection scope of the application.

[0025] Embodiment 1

[0026] 1) Equimolar amount of 5-bromo-2-(dimethylamino)benzaldehyde and 1,2-dibromoethane were mixed in acetone, and the reaction was carried out under reflux with nitrogen protection. The reaction was monitored by TLC. When the starting material was consumed, the reaction was purified. The reaction system was extracted with dichloromethane and water. The organic phase was collected and rotary evaporated to obtain the crude product. The product was purified by column chromatography using 200-300 mesh silica gel powder as the stationary phase and dichloromethane and ethyl acetate (10:1 by volume) as the mobile phase to obtain the first intermediate QBr;

[0027] The molecular formula of QBr labeled with atomic numbers and its accurately attributed NMR data are as follows:

[0028]

[0029] 1 H NMR (400 MHz, Chloroform-d) δ 10.22 (d, J = 0.7 Hz, 1H, 10), 7.74 (d, J = 8.9 Hz, 1H, 1), 6.35 (ddd, J = 8.9, 2.3, 0.8 Hz, 1H, 3), 6.04 (d, J = 2.2 Hz, 1H, 5), 4.38 (t, J = 6.2 Hz, 2H, 12), 3.68 (t, J = 6.2 Hz, 2H, 13), 3.07 (s, 6H, 8, 9).

[0030] 2) Equimolar amount of QBr and 1,3-indanedione were mixed in ethanol, and 1 equivalent of NaOH was added. The reaction was carried out under reflux with nitrogen protection for 12 hours. The reaction system was extracted with dichloromethane and water. The organic phase was collected and rotary evaporated to obtain the crude product. The product was purified by column chromatography using 200-300 mesh silica gel powder as the stationary phase and dichloromethane and ethyl acetate (5:1 by volume) as the mobile phase to obtain the second intermediate YDOBr;

[0031] The molecular formula of YDOBr labeled with atomic numbers and its accurately attributed NMR data are as follows:

[0032]

[0033] 1 H NMR (400 MHz, Chloroform-d) δ 9.32 (d, J = 9.2 Hz, 1H, 2), 8.46 (s, 1H, 20), 7.93 - 7.88 (m, 2H, 17, 18), 7.74 - 7.67 (m, 2H, 16, 19), 6.50 (dd, J = 9.2, 2.4 Hz, 1H, 5), 6.14 (d, J = 2.4 Hz, 1H, 7), 4.41 (t, J = 6.6 Hz, 2H, 22), 3.79 - 3.73 (m, 2H, 23), 3.16 (s, 6H, 10, 11).

[0034] 3) YDOBr was added into pyridine under uniform stirring, pyridine as solvent and reactant, 80℃ reaction for 18 hours, the system was cooled to room temperature, orange-red solid was precipitated, suction filtration, the filter cake was washed with dichloromethane to obtain orange solid, which was the target product water-soluble organic ionic salt YDOPy.

[0035] The molecular formula of YDOPy labeled with atomic number and its accurate nuclear magnetic data are as follows:

[0036]

[0037] 1 H NMR (400MHz, Methanol-d4) δ 9.32-9.22 (m, 3H, 2, 26, 30), 8.71-8.64 (m, 1H, 28), 8.31 (t, J = 7.1 Hz, 2H, 27, 29), 8.12 (s, 1H, 20), 7.92-7.84 (m, 2H, 17, 18), 7.80 (dd, J = 5.5, 3.1 Hz, 2H, 16, 19), 6.50 (dd, J = 9.3, 2.4 Hz, 1H, 5), 6.18 (d, J = 2.4 Hz, 1H, 7), 5.25 (t, J = 4.9 Hz, 2H, 22), 4.68 (t, J = 4.8 Hz, 2H, 23), 3.17 (s, 6H, 10, 11).

[0038] In Example 1, the volume ratio of dichloromethane: ethyl acetate in step 1) is 11:1 or 9:1; the reflux reaction time in step 2) is 10 hours or 14 hours, the volume ratio of dichloromethane: ethyl acetate is 4:1 or 6:1; the reaction temperature in step 3) is 75℃ or 85℃, and the reaction time is 16 hours or 20 hours; the target product water-soluble organic ionic salt YDOPy can also be obtained.

[0039] The water-soluble organic ionic salt obtained by the application has antibacterial effect, and the antibacterial effect on Staphylococcus aureus is particularly remarkable.

[0040] The antibacterial effect of the water-soluble organic ionic salt YDOPy is further proved by the following corresponding experimental data.

[0041] Experiment 1: paper disc diffusion method

[0042] 1. Preparation of bacterial solution: single colonies were picked from Staphylococcus aureus plates into sterile TSB broth, 37℃, 280r / min shaking culture for 12h. The next day, the bacterial solution was diluted to a concentration of 0.5 McFarland turbidity, and then diluted 100 times with fresh MH broth for standby.

[0043] 2. Preparation of the bacteriostatic stock solution: 16 mg of YDOPy was dissolved in 2 mL of MH broth to prepare a 8 mg / mL stock solution, which was stored in a sterile centrifuge tube.

[0044] 3. Inoculation: An appropriate amount of diluted bacterial solution was taken and spread evenly on the MH agar medium plate with a sterile inoculation rod, ensuring that the bacterial solution was evenly distributed on the surface of the agar plate.

[0045] 4. Paper patching: The paper was carefully placed on the bacterial plate using sterile tweezers, with 6 pieces of paper on each plate, ensuring that the distance between the paper and the edge of the plate was not less than 15 mm, and the distance between the papers was not less than 24 mm. The bacteriostatic stock solution was diluted to 2 mg / mL, and 10 μL of the antibacterial solution was added to the paper, with a negative control of 10 μL of MH medium and a positive control of 10 μL of penicillin-streptomycin antibiotic.

[0046] 5. Cultivation: The agar plate with the paper patch was placed in an incubator and incubated at 37°C for 24 hours.

[0047] 6. Reading of the diameter of the bacteriostatic circle: The diameter of the bacteriostatic circle on the back of the culture dish was measured with a ruler. If there was no bacteriostatic circle, the diameter of the bacteriostatic circle was consistent with the diameter of the paper, i.e. 5 mm.

[0048] Results: The paper disc diffusion experiment was performed on four kinds of bacteriostatic molecules, among which M1 was YDOPy, M5 was MH medium (negative control), M6 was penicillin-streptomycin antibiotic (positive control), and the bacteriostatic circle was as shown in Figure 1 , with a strain bacteriostatic circle size of 10.1 mm.

[0049] Experiment 2: Determination of the minimum bacteriostatic concentration (MIC)

[0050] The micro-broth dilution method was used to determine the MIC value of YDOPY on the Staphylococcus aureus strains used in the experiment, according to the CLSL 2022 standard, with the following specific steps:

[0051] 1. Preparation of the antibiotic stock solution: Penicillin-streptomycin antibiotic was dissolved in an appropriate solvent according to the antibacterial instructions, and stored at -80°C. Before use, it was diluted to the required concentration.

[0052] 2. Add sample: Take 200 μL of the prepared probe solution (8000 μg / mL) in a sterile 96-well plate, and add 200 μL of fresh MH broth to make the concentration of the first well 4000 μg / mL. Take 200 μL of the mixed solution in the first well to the second well with a pipette, and add 200 μL of broth. Blow the solution in the well with a pipette to mix the probe evenly. Take 200 μL of the solution from the second well to the third well, and dilute to the ninth well in turn. Discard the excess 200 μL of the solution in the last well. Obtain a concentration gradient of 4000 μg / mL, 2000 μg / mL, 1000 μg / mL, 500 μg / mL, 250 μg / mL, 125 μg / mL, 62.5 μg / mL, 31.25 μg / mL, and 15.63 μg / mL, each well containing 200 μL.

[0053] 3. Inoculation: After shaking the prepared bacterial solution, take 200 μL and add it to wells 1-9 (equivalent to 1-fold dilution of the bacterial solution). Finally, obtain a concentration gradient of 2000 μg / mL, 1000 μg / mL, 500 μg / mL, 250 μg / mL, 125 μg / mL, 62.5 μg / mL, 31.25 μg / mL, 15.63 μg / mL, and 7.81 μg / mL. The tenth well is a positive control with the addition of 1x penicillin-streptomycin antibiotics, the eleventh well is a negative control with the addition of bacterial solution and an equal volume of medium, and the twelfth well is a blank control with only the addition of medium. Each experiment is repeated three times.

[0054] 4. Culture: Seal the 96-well plate with a sealing film, place it on a micro-vibrator to mix evenly, and incubate it in a 37°C incubator for 24 h.

[0055] 5. Bacterial counting: Determine the antibacterial activity of YDOPy on Staphylococcus aureus by plate colony counting. Take 100 μL of the solution in the well where no bacteria grow and spread it evenly on a medium plate. Incubate it in a 37°C incubator for 24 h.

[0056] Results: The minimum concentration at which no bacteria grow on the plate is the MIC value of YDOPy on Staphylococcus aureus. The positive control group has turbidity and bacterial growth, while the negative control group is clear and has no bacterial growth, which indicates that the results are valid. Determine the MIC value of the antibacterial molecule on Staphylococcus aureus strain by micro-broth dilution method, and the results are shown in Figure 2 .

[0057] The plate colony counting results are shown in Figure 3 . The MIC value of YDOPy is 31.25 μg / mL.

[0058] Experiment 3: Animal experiment to detect the effect of antibacterial molecules on the virulence of Staphylococcus aureus

[0059] An in vivo infection model was constructed using invertebrate Galleria mellonella to detect the effect of YDOPy at different concentrations of 125 ug / mL, 62.5 ug / mL, and 31.25 ug / mL on the virulence of Staphylococcus aureus, and to study the antibacterial effect of YDOPy on Staphylococcus aureus in vivo. Galleria mellonella larvae weighing between 350-450 mg (to ensure that each larva weighs the same) and measuring about 25-30 mm in length with a milk-white body were selected. They were stored in a 4°C dark environment and used within 1 week of purchase.

[0060] The specific steps are as follows:

[0061] 1. Preparation of bacterial solution: Staphylococcus aureus strain was taken from a -80°C freezer and placed in fresh sterile MH medium. It was incubated at 37°C overnight with shaking to the logarithmic growth phase. The concentration of the bacterial solution was adjusted to 109 CFU / mL for standby use.

[0062] 2. Grouping: The larvae were randomly divided into 5 groups (A-C groups as experimental groups, D-E groups as control groups), with 10 larvae in each group. Group A was injected with MIC concentration YDOPy + bacterial solution, group B was injected with 1 / 2 MIC concentration YDOPy + bacterial solution, group C was injected with only bacterial solution, group D was injected with sterile MH medium as control, and group E was not treated as blank control.

[0063] 3. Preparation of drug solution: YDOPy was prepared as a 4mg / mL stock solution. In 5mL of MH medium, add YDOPy stock solution to make the final concentration of MIC and 1 / 2 MIC, respectively.

[0064] 4. Infection: Each Galleria mellonella larva in groups A-C was injected with 20μL of diluted bacterial solution using a 20μL Hamilton syringe or microsyringe through the right front leg. The injected Galleria mellonella was placed in a sterile culture dish and incubated at 37°C for 2h. (The used Hamilton syringe was washed with sterile saline for 3 times and reserved for use.)

[0065] 5. Injection: After 2h, the culture dishes were removed, and group A larvae were injected with 20μL of MIC concentration YDOPy, group B larvae were injected with 20μL of 1 / 2 MIC concentration YDOPy, group C and group D were injected with the same volume of MH medium, and group E larvae were not treated as blank control. The injection process required to be fast and accurate, avoiding multiple injections at the same site and unnecessary mechanical damage to the larvae.

[0066] 6. Incubation: After treatment, the larvae were placed in a plastic culture dish, marked with the injection time, and incubated in a 37°C incubator. The survival of the larvae was recorded every 12 hours (when the larvae showed no response to physical stimulation, they were considered dead), and the process lasted for 72 hours.

[0067] 7. Result analysis: The obtained data were entered into Graphpad Prism 9 software, and the survival curve of the larvae in different groups was plotted. Results: The antibacterial effect of G.cocoonae after infection is shown in Figure 4 compared with the control group, the survival rate of G.cocoonae larvae infected with MRSA in the MIC group was significantly prolonged, and there was a statistically significant difference in survival rate between the two groups (P<0.05), while there was no significant difference in survival rate between the 1 / 2 MIC group and the control group (P>0.05). The experimental results showed that one-fold MIC concentration of daphne showed reduced virulence of MRSA infection in vivo and played a role in the body against MRSA.

[0068] Experiment 4: Observation of the effect of daphne on the ultrastructure of MRSA cells under scanning electron microscope

[0069] 1. Preparation of bacterial solution: 5 μL of bacterial preservation solution was taken into 5 mL of broth, and incubated at 37°C until the logarithmic growth phase. The concentration of the bacterial solution was adjusted to 0.5 McFarland turbidity with sterile saline, and the diluted bacterial solution was inoculated within 15 minutes.

[0070] 2. Bacterial pretreatment: YDOPy mother liquor was added to the drug-containing group to a final concentration of MIC (31.25 μg / mL), and the control group without YDOPy was incubated at 37°C in a constant temperature incubator for 24 h. The pretreated bacterial solution was centrifuged at 8000 x g for 10 min, and the supernatant was discarded. The precipitate was fixed with 2.5% glutaraldehyde for 4 h (or overnight at 4°C), and then washed with 0.2M PBS buffer (pH=6.8) for 3 times, each time for 15-20 min. Dehydrate with 30%, 50%, 70%, 85% and 95% ethanol for 15-20 min each time, and then with 100% ethanol for 15-20 min twice. Replace with acetic acid isoamyl ester (tert-butyl alcohol) for more than 3 hours, preferably overnight.

[0071] 3. Electron microscopy observation: Take the mixed bacterial suspension and drop it on a cover glass and freeze it at -80°C. After drying and ion sputtering, the sample was observed and photographed under a scanning electron microscope.

[0072] Results: The morphology of S. aureus without YDOPy treatment was complete, the surface was smooth and round, and the shape and size were uniform; when the concentration of YDOPy was MIC, the number of bacteria was reduced, the cell morphology and size were different, part of the bacterial cell morphology was irregular, and the bacteria began to appear invagination and wrinkles; after YDOPy treatment, the cell wall of S. aureus was destroyed or the synthesis of the cell wall was inhibited, and the antibacterial effect was shown.

[0073] Obviously, the above embodiments of the present application are only examples for clearly illustrating the present application, and are not intended to limit the embodiments of the present application. For those skilled in the art, other different forms of changes or variations can be made on the basis of the above description, and it is impossible to enumerate all the embodiments here. Any obvious changes or variations derived from the technical solutions of the present application still fall within the protection scope of the present application.

Claims

1. A water-soluble organic ionic salt, characterized in that, A compound as shown in the following formula: 。 2. The method of claim 1, wherein the water soluble organic ionic salt is synthesized by the reaction of the water soluble organic acid and the water soluble organic base. comprising the following steps: 1) Equal molar quantity of 5-bromo-2-(dimethylamino)benzaldehyde and 1,2-dibromoethane were mixed in acetone, and the reaction was carried out under reflux protection with nitrogen. The reaction was monitored by TLC. When the starting material was completely consumed, the reaction mixture was purified. The reaction system was extracted with dichloromethane and water. The organic phase was collected and rotary evaporated to obtain the crude product. The product was then purified by column chromatography using 200-300 mesh silica gel powder as the stationary phase and a mobile phase of dichloromethane and ethyl acetate in a volume ratio of 9-11:1 to obtain the first intermediate 2-(2-bromoethoxy)-4-(dimethylamino)benzaldehyde, referred to as QBr, with the chemical formula C 11 H 14 BrNO2; 2) equimolar quantities of QBr, sodium hydroxide and 1,3-indanedione were mixed in ethanol and refluxed under nitrogen protection for 10-14 hours. The reaction system was extracted with dichloromethane and water, and the organic phase was collected and rotary evaporated to obtain the crude product. Next, column chromatography was used for purification, using 200-300 mesh silica gel powder as the stationary phase and a mobile phase of dichloromethane and ethyl acetate in a volume ratio of 4-6:1 to obtain the second intermediate 2-(2-(2-bromoethoxy)-4-(dimethylamino)benzylidene)-1H-indene-1,3(2H)-dione, referred to as YDOBr, with the chemical formula C 20 H 18 BrNO3; 3) YDOBr was added into pyridine under uniform stirring, pyridine as solvent and reactant, 75-85℃ reaction for 16-20 hours, the system was cooled to room temperature, orange-red solid was precipitated, suction filtration, the filter cake was washed with dichloromethane to obtain orange solid, which was the target product water-soluble organic ion salt (1-(2-(5-(dimethylamino)-2-((1,3-diketone-1,3-dihydro-2H-inden-2-ylidene)methyl)phenoxy)ethyl)pyridin-1-ium, abbreviated as YDOPy, chemical formula: C 25 H 23 N2O3 + Br - ; The synthetic route thereof is: 。 3. The method of claim 1, wherein the water soluble organic ionic salt is synthesized by the reaction of the water soluble organic acid and the water soluble organic base. In step 1): the volume ratio of dichloromethane: ethyl acetate is 10:

1.

4. The method of claim 1, wherein the water soluble organic ionic salt is synthesized by the reaction of the water soluble organic acid and the water soluble organic base. In step 2): the reflux reaction time is 12 hours, and the volume ratio of dichloromethane: ethyl acetate is 5:

1.

5. The method of claim 1, wherein the water soluble organic ionic salt is synthesized by the reaction of the water soluble organic acid and the water soluble organic base in the presence of the water soluble inorganic salt. In step 3): the reaction temperature is 80℃, and the reaction time is 18 hours.

6. Use of the water-soluble organic ionic salt of claim 1 in the preparation of an anti-Staphylococcus aureus preparation.

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