Application of protocatechualdehyde in preparation of antibacterial drugs

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to in-vivo and in-vitro application of protocatechualdehyde in preparation of antibacterial medicines. According to the present invention, the research results show that the protocatechualdehyde has significant antibacterial effect on ampicillin drug-resistant Escherichia coli (ECO-RAMP for short), the method can be used for treating clinical multi-drug-resistant escherichia coli (MDR-ECO for short), clinical multi-drug-resistant klebsiella pneumoniae (MDR-KPN for short), clinical multi-drug-resistant pseudomonas aeruginosa (MDR-PAE for short), clinical carbapenem-resistant escherichia coli (CR-ECO for short), clinical carbapenem-resistant klebsiella pneumoniae (CR-KPN for short), clinical multi-drug-resistant pseudomonas aeruginosa (MDR-PAE for short), clinical multi-drug-resistant escherichia coli (MDR-ECO for short), clinical multi-drug-resistant pseudomonas aeruginosa (MDR-PAE for short) and clinical multi-drug-resistant pseudomonas aeruginosa (MDR-KPN for short). Clinical carbapenem drug-resistant pseudomonas aeruginosa (CR-PAE for short), clinical carbapenem drug-resistant bacteria acinetobacter baumannii (CR-ABA for short), mulberry enterobacter, pantoea, Ralstonia, candida albicans, fusarium moniliforme and botrytis cinerea have antibacterial effects. In addition, protocatechuic aldehyde is widely used for resisting angina pectoris and is high in safety.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and more specifically, relates to the in vivo and in vitro application of protocatechuic aldehyde in the preparation of antibacterial drugs. Background Art

[0002] Bacterial resistance has become a major challenge to global public health and poses a serious threat to human health.

[0003] In the prior art, protocatechuic aldehyde has been shown to have an effect against sensitive bacteria, or in combination with ampicillin against methicillin-resistant Staphylococcus aureus. However, the in vivo or in vitro effects of protocatechuic aldehyde alone against drug-resistant bacteria have not been reported, which limits the scope of application of protocatechuic aldehyde.

[0004] In addition, existing antibacterial treatments mainly rely on chemically synthesized antibiotics, such as carbapenem antibiotics (meropenem and imipenem, etc.), which are regarded as the "last line of defense" in clinical practice due to their powerful antibacterial effects. However, with the widespread use of these antibiotics, bacteria resistant to them continue to emerge, and the problem of drug resistance is becoming increasingly serious. In particular, the emergence of carbapenem-resistant bacteria has posed a huge challenge to existing treatment options, and there is currently a lack of specific drugs for these resistant bacteria in clinical practice. Therefore, the development of new antibacterial drugs, especially active ingredients extracted from natural resource libraries, has become an urgent task in the field of medical research.

[0005] The present invention aims to explore and utilize the antibacterial potential of protocatechuic aldehyde to develop a new type of antibacterial drug to cope with the increasingly serious problem of bacterial resistance and provide an effective treatment method for clinical use. Summary of the invention

[0006] The present invention confirms that protocatechuic aldehyde has significant antibacterial activity against both fungi and bacteria, wherein the bacteria are selected from ampicillin-resistant Escherichia coli (ECO-RAMP), clinical multidrug-resistant Escherichia coli (MDR-ECO), clinical multidrug-resistant Klebsiella pneumoniae (MDR-KPN), clinical multidrug-resistant Pseudomonas aeruginosa (MDR-PAE), clinical carbapenem-resistant Escherichia coli (CR-ECO), clinical carbapenem-resistant Klebsiella pneumoniae (CR-KPN), clinical carbapenem-resistant Pseudomonas aeruginosa (CR-PAE), clinical carbapenem-resistant Acinetobacter baumannii (CR-ABA), Enterobacter mulberry, Pantoea and Ralstonia; the fungi are selected from Candida albicans, Fusarium moniliforme, Botrytis cinerea and Alternaria alternata. The present invention further provides the use of protocatechuic aldehyde in the preparation of antibacterial or fungal infection drugs, covering in vitro antibacterial models and infected mouse in vivo models.

[0007] The drug comprises a therapeutically effective amount of protocatechuic aldehyde and a pharmaceutically acceptable excipient, and its dosage form is at least one of powder, granules, gel, injection, oral solution or tablet; when the drug is a liquid dosage form, the concentration of protocatechuic aldehyde is preferably 0.005-2.5 mg / mL, and covers all sub-ranges within the concentration range. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 ECO-R under the action of protocatechuic aldehyde at a concentration gradient AMP survival rate;

[0009] Figure 2 ECO-R under the action time gradient of 2.5 mg / mL protocatechuic aldehyde AMP survival rate;

[0010] Figure 3 is the survival rate of multidrug-resistant bacteria under the action of 2.5 mg / mL protocatechuic aldehyde;

[0011] Figure 4 is the survival rate of CR-ECO under the action of concentration gradient protocatechuic aldehyde;

[0012] Figure 5 is the survival rate of CR-ECO, CR-KPN, CR-PAE and CR-ABA under the action of 0.5 mg / mL protocatechuic aldehyde;

[0013] Figure 6 is the survival rate of Enterobacter mulberryi, Pantoea, Ralstonia and Candida albicans under the action of 2.5 mg / mL protocatechuic aldehyde;

[0014] Figure 7 The colony growth of Fusarium moniliforme and Botrytis cinerea under the action of 2.5 mg / mL protocatechuic aldehyde within 5 days;

[0015] Figure 8 is the colony diameter of Fusarium moniliforme under the action of 2.5 mg / mL protocatechuic aldehyde;

[0016] Fig. 9 is the colony diameter of Botrytis cinerea under the action of 2.5 mg / mL protocatechuic aldehyde;

[0017] Fig.10 is the colony diameter of Alternaria alternata under the action of 2.5 mg / mL protocatechuic aldehyde;

[0018] Fig.11 Scanning electron microscope observation of ECO-R under the action of protocatechuic aldehyde AMP The cell morphology;

[0019] Fig.12 ECO-R infected by protocatechuic aldehydeAMP Survival rate of mice;

[0020] Fig.13 is the survival rate of mice infected with MDR-ECO2 under the action of protocatechuic aldehyde;

[0021] Fig.14 is the survival rate of CR-ECO18 mice infected with protocatechuic aldehyde;

[0022] Fig.15 ECO-R infected by protocatechuic aldehyde AMP Organ bacterial counts in mice. DETAILED DESCRIPTION

[0023] The present invention is further described below in conjunction with the accompanying drawings and specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0024] Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0025] Example 1: ECO-R under the action of concentration gradient ampicillin and protocatechuic aldehyde AMP Survival rate

[0026] Pick a single bacterial colony and inoculate it in 50 mL LB medium, place it in a shaker and culture it for 16-24 hours (37°C, 200 rpm). Take an appropriate amount of bacteria and centrifuge it at 5000×g for 3 min to collect the bacterial precipitate. Add 10 mL of physiological saline to resuspend the bacterial precipitate, centrifuge it at 5000×g for 3 min, collect the bacterial precipitate, and repeat three times. Suspend the obtained bacterial precipitate in M9 medium (add 2 M anhydrous sodium acetate and 1 M MgSO before use). 4 and 1 M CaCl 2 ), adjust its OD 600 nm=0.6±0.005. Protocatechuic aldehyde or ampicillin was added at a concentration of 0, 0.5, 1, 1.5, 2, 2.5, and 3 mg / mL, respectively, and incubated at 37°C, 200 rpm for 6 hours. In order to determine the number of bacteria, 100 μL of the incubated sample was serially diluted 10 times, and each 5 μL was spotted on the LB agar plate. The number of colonies was calculated after incubation at 37°C for 16 hours. Survival rate = the number of bacteria in the group with protocatechuic aldehyde or ampicillin added / the number of bacteria in the group without any substance added × 100%.

[0027] The results are as follows Figure 1As shown in the figure, compared with the control group without drug addition, as the concentration of protocatechuic aldehyde increased from 0.05 to 3 mg / mL, the bacterial survival rate decreased from 79.75% to 0.06%, and the bactericidal multiple increased from 1.25 times to 1667 times. At 2.5 mg / mL, the antibacterial efficiency basically reached a stable level. Therefore, a time gradient and expanded strain experiment were conducted at this concentration to verify the antibacterial effect of protocatechuic aldehyde on other multidrug-resistant bacteria.

[0028] Example 2: ECO-R under 2.5 mg / mL protocatechuic aldehyde action time gradient AMP Survival rate

[0029] According to the method of Example 1, 2.5 mg / mL of protocatechuic aldehyde was added or not, and ECO-R was detected. AMP Survival rates at 2, 4, 6, 8, 10, and 12 h of incubation.

[0030] The results are as follows Figure 2 As shown in the figure, with the extension of the action time, ECO-R AMP Under the action of protocatechuic aldehyde, the survival rate gradually decreases and approaches 0 infinitely. It can be seen that the antibacterial effect of protocatechuic aldehyde can be exerted to the extreme by prolonging the action time.

[0031] Example 3: Survival rate of multidrug-resistant bacteria under the action of 2.5 mg / mL protocatechuic aldehyde

[0032] According to the method of Example 1, with or without the addition of 2.5 mg / mL of protocatechuic aldehyde, the survival rates of MDR-PAE2, MDR-ECO2, and MDR-KPN3 after incubation for 6 h were detected.

[0033] The results are as follows Figure 3 As shown, the survival rates of MDR-PAE2, MDR-ECO2, and MDR-KPN3 were reduced to 0.044%, 0.035%, and 0.18%, respectively, after the action of protocatechuic aldehyde, and the bactericidal multiples reached 2273, 2857, and 556 times, respectively, which shows that the antibacterial effect of protocatechuic aldehyde has a broad spectrum.

[0034] Example 4: Survival rate of CR-ECO under the action of concentration gradient protocatechuic aldehyde

[0035] The results are as follows Figure 4 As shown in A, compared with the control group without drug addition, as the concentration of protocatechuic aldehyde increased from 0.06 to 1 mg / mL, the survival rate of CR-ECO18 decreased from 37.31% to 0.005%, and the bactericidal multiple increased from 2.68 times to 20,000 times. At 0.5 mg / mL, the bactericidal efficiency basically reached the best effect, at which time the bacterial survival rate was about 0.006% and the bactericidal multiple was 16,667 times. Figure 4As shown in Figure B, compared with the control group without drug addition, as the concentration of protocatechuic aldehyde increased from 0.06 to 1 mg / mL, the survival rate of CR-ECO28 decreased from 38.04% to 0.0087%, and the bactericidal multiple increased from 3 times to 11538 times. It can be seen that the bactericidal effect of protocatechuic aldehyde on CR-ECO also has a good concentration dependence.

[0036] The results are as follows Figure 4 As shown in A, compared with the control group without drug addition, as the concentration of protocatechuic aldehyde increased from 0.06 to 1 mg / mL, the survival rate of CR-ECO18 decreased from 37.31% to 0.005%, and the bactericidal multiple increased from 2.68 times to 20,000 times. At 0.5 mg / mL, the bactericidal efficiency basically reached the best effect, at which time the bacterial survival rate was about 0.006% and the bactericidal multiple was 16,667 times. Figure 4 As shown in Figure B, compared with the control group without drug addition, as the concentration of protocatechuic aldehyde increased from 0.06 to 1 mg / mL, the survival rate of CR-ECO28 decreased from 38.04% to 0.0087%, and the bactericidal multiple increased from 3 times to 11538 times. It can be seen that the bactericidal effect of protocatechuic aldehyde on CR-ECO also has a good concentration dependence.

[0037] Example 5: Survival rates of CR-ECO, CR-KPN, CR-PAE, and CR-ABA under the action of 0.5 mg / mL protocatechuic aldehyde;

[0038] Referring to the method of Example 1, 0.5 mg / mL of protocatechuic aldehyde was added to detect the survival rates of CR-ECO15, CR-KPN1, CR-PAE1, and CR-ABA1 after incubation for 10 h.

[0039] The results are as follows Figure 5 As shown in the figure, compared with the control group without drug addition, as the concentration of protocatechuic aldehyde increased from 0.06 to 1 mg / mL, the survival rates of CR-ECO15, CR-KPN1, CR-PAE1 and CR-ABA1 were 0.003%, 0.057%, 0.027% and 0.001%, respectively, and the bactericidal multiples reached 30000, 1765, 3750 and 75188 times, respectively. It can be seen that protocatechuic aldehyde also has a broad-spectrum bactericidal effect on carbapenem-resistant bacteria.

[0040] Example 6: Survival rate of food-derived isolates and Candida albicans under the action of 2.5 mg / mL protocatechuic aldehyde

[0041] Three food-derived isolated bacteria (Enterobacter mulberryi, Pantoea, Ralstonia) and a fungus (Candida albicans) were selected, and the bacterial solution OD was adjusted according to the method of Example 1. 600nm=0.2±0.005 and diluted 100 times, with or without the addition of 2.5 mg / mL protocatechuic aldehyde, and the survival rate after 10 h of incubation was detected.

[0042] The results are as follows Figure 6 As shown in the data, the survival rates of Enterobacter mulberry, Pantoea, Ralstonia and Candida albicans were reduced to 0.615%, 0.090%, 0.015% and 4.138% respectively after the action of protocatechuic aldehyde, and the bactericidal multiples reached 163, 1111, 666 and 24 times respectively, which further illustrates that the antibacterial effect of protocatechuic aldehyde is broad-spectrum.

[0043] Example 7: Inhibitory effect of 2.5 mg / mL protocatechuic aldehyde on hyphae growth of Fusarium moniliforme and Botrytis cinerea

[0044] Potato dextrose agar (PDA) medium containing 2.5 mg / mL protocatechuic aldehyde was prepared, and a control group without protocatechuic aldehyde was used. A PDA medium with uniform mold distribution cultured at 25°C for 5-7 days was selected, and a 6 mm diameter cake was punched with a hole puncher, and the cake was inverted into the center of the PDA medium (the hyphae directly contacted the PDA medium). Inverted culture was carried out at 25°C for 5 days, and 3 replicates were set for each treatment. Using the cross method, the colony diameter was measured every 24 h, and the average growth inhibition rate of protocatechuic aldehyde on hyphae was calculated = (control colony diameter-treated colony diameter) / (control colony diameter-bacteria cake diameter)×100%.

[0045] Figure 7 Fusarium moniliforme ( Figure 7 A) and Botrytis cinerea ( Figure 7 B) Colony changes within 5 days of cultivation. After 5 days of cultivation, the average colony diameter of the control group of Fusarium moniliforme reached about 54 mm, while the colony diameter of Fusarium moniliforme grown in the medium supplemented with 2.5 mg / mL protocatechuic aldehyde was about 20 mm (see Figure 2). Figure 8 ), it can be seen that the average growth inhibition rate of protocatechuic aldehyde on Fusarium moniliforme is 79.26%. After 5 days of cultivation, the average colony diameter of the control group of Botrytis cinerea reached about 28.3 mm, while the colony diameter of Botrytis cinerea grown in the medium supplemented with 2.5 mg / mL protocatechuic aldehyde was about 8.58 mm (such as Fig. 9 ), it can be seen that the average growth inhibition rate of protocatechuic aldehyde on Botrytis cinerea is 83.37%. This further shows that protocatechuic aldehyde also has a broad-spectrum antibacterial effect on fungi.

[0046] Example 8: Scanning electron microscope observation of ECO-R under the action of Protocatechu AMP Form

[0047] Pick a single bacterial colony and inoculate it into 50 mL LB medium, and place it in a shaker for 16-24 hours (37°C, 200 rpm). Take the bacteria that have been cultured to saturation in the LB medium, collect the bacterial precipitate by centrifugation, and rinse the bacterial precipitate twice with physiological saline. Then suspend the bacteria in fresh LB medium and adjust the bacterial concentration to OD 600 nm = 0.6. After adding 2.5 mg / mL protocatechuic aldehyde or ampicillin, the mixture was placed in a shaker and incubated for 6 h. A control group was set up without adding either of the two. The incubated bacterial solution was taken and the OD 600 nm =1.0, take 20 mL of this bacterial solution and centrifuge at 12000×g for 5 min, discard the supernatant, add 40 mL of 2.5% glutaraldehyde fixative and mix well, and place in a 4℃ refrigerator for fixation for more than 2 h. After fixation, centrifuge at 5000×g for 5 min to remove the supernatant, rinse the precipitate with 5 mL of physiological saline, and repeat 3 times. Dehydrate with 50%, 70%, 90% and 100% ethanol in sequence, that is, add 5 mL of each concentration of ethanol, let it stand for 10 min, and centrifuge at 5000×g for 5 min to remove the supernatant. After dehydration, add 200 μL of pure tert-butanol solution to suspend the bacterial precipitate, let it stand at 4℃ for 30 min, and centrifuge at 5000×g for 3 min to remove the supernatant. Add 200 μL of pure tert-butanol solution again, resuspend the bacterial precipitate, place it in a freeze dryer pre-cooled at -10℃ and vacuum dry it for 24 h, and then take it out. The dried sample was gold-plated with an ion sputtering instrument, and then observed and photographed with a scanning electron microscope.

[0048] The results are as follows Fig.10 As shown, the ECO-R AMP Short rod-shaped with smooth surface; ECO-R treated with ampicillin AMP The surface was damaged to some extent; the protocatechuic aldehyde treated group ECO-R AMP The shapes were irregular, and the bacterial surface was seriously damaged. It can be seen that protocatechuic aldehyde can cleave ECO-R AMP This indicates that protocatechuic aldehyde has good application potential in in vitro antibacterial activities.

[0049] Example 9: Evaluation of the in vivo antibacterial effect of protocatechuic aldehyde

[0050] (1) Effect of protocatechuic aldehyde on ECO-R infection AMP Effects on the survival rate of mice

[0051] ECO-R AMP The glycerol bacteria were transferred to fresh LB medium at a ratio of 1:50 and cultured in a shaker (37°C, 200 rpm) until the bacterial concentration reached OD 600nm=1.0±0.05 (about 4 h). Centrifuge at 5000×g for 3 min and collect the bacterial precipitate. Resuspend the bacterial precipitate with fresh LB and centrifuge at 5000×g for 3 min. Collect the bacterial precipitate and repeat twice. After that, adjust the bacterial solution concentration to OD with fresh LB. 600 nm=2.0. The bacterial solution was centrifuged and 3 / 4 of the supernatant was removed to obtain a 4-fold concentrated bacterial solution. 60 μL of this bacterial solution was injected intraperitoneally into mice, equivalent to 2.54×10 8 CFU count. One hour later, 100 μL of a solution of protocatechuic aldehyde (injection concentration of 10, 20, 30 mg / kg) or ampicillin (injection concentration of 20 mg / kg) prepared in fresh LB medium was intramuscularly injected, and LB medium without protocatechuic aldehyde or ampicillin was used as the control group. The number of surviving mice was observed and recorded for 7 consecutive days.

[0052] The results are as follows Fig.11 As shown in Figure 2, at day 7, the survival rate of mice in all groups stabilized. AMP All mice died. When the concentration of protocatechuic aldehyde was 10 mg / kg, the survival rate of mice was increased by 30%; when the concentration of protocatechuic aldehyde was 20 and 30 mg / kg, the survival rate of mice was increased by 60%. Therefore, the optimal in vivo therapeutic concentration of protocatechuic aldehyde is 20 mg / kg. The same concentration of ampicillin treatment can only increase the survival rate of mice by 20%, which is 40% worse than that of protocatechuic aldehyde.

[0053] (2) Survival rate of MDR-ECO2-infected mice under the action of protocatechuic aldehyde

[0054] The MDR-ECO2 glycerol bacteria were transferred to fresh LB medium at a ratio of 1:50 and cultured in a shaker (37°C, 200 rpm) until the bacterial concentration reached OD 600 nm=1.0±0.05 (about 4 h). Centrifuge at 5000×g for 3 min and collect the bacterial precipitate. Resuspend the bacterial precipitate with fresh LB and centrifuge at 5000×g for 3 min. Collect the bacterial precipitate and repeat twice. After that, adjust the bacterial solution concentration to OD with fresh LB. 600 nm=1.0, dilute the bacterial solution 2 times. Inject 100 μL of the bacterial solution intraperitoneally into mice, equivalent to 5.3×10 7 CFU count. 1 h later, 100 μL of protocatechuic aldehyde prepared in fresh LB medium was injected intramuscularly at a concentration of 20 mg / kg. LB medium without protocatechuic aldehyde was used as the control group. The number of mice surviving was observed and recorded for 7 consecutive days.

[0055] The results are as follows Fig.12As shown in the figure, on the 7th day, the survival rate of mice in all groups tended to be stable. At this time, all mice infected with MDR-ECO2 in the control group without drug treatment died. When the concentration of protocatechuic aldehyde was 20 mg / kg, the survival rate of mice was 50%, which increased the survival rate by 40%. These results show that protocatechuic aldehyde can improve the survival rate of mice infected with drug-resistant bacteria and has application potential in the treatment of drug-resistant bacterial infections in vivo.

[0056] (3) Survival rate of CR-ECO18 mice infected with protocatechuic aldehyde

[0057] The CR-ECO18 glycerol bacteria were transferred to fresh LB medium at a ratio of 1:50 and cultured in a shaker (37°C, 200 rpm) until the bacterial concentration reached OD 600 nm=1.0±0.05 (about 2 h). Centrifuge at 5000×g for 3 min and collect the bacterial precipitate. Resuspend the bacterial precipitate with fresh LB and centrifuge at 5000×g for 3 min. Collect the bacterial precipitate and repeat twice. After that, adjust the bacterial solution concentration to OD with fresh LB. 600 nm=1.0. 100 μL of this bacterial solution was injected intraperitoneally into mice, equivalent to 2×10 8 CFU count. 1 hour later, 100 μL of 2.5 mg / kg and 10 mg / kg protocatechuic aldehyde prepared in fresh LB medium was intramuscularly injected. LB medium without protocatechuic aldehyde was used as the control group. The number of mice surviving was observed and recorded for 7 consecutive days.

[0058] The results are as follows Fig.13 As shown in the results, the survival rate of mice infected with CR-ECO18 without drug treatment, that is, the control group, was 30%. The administration of protocatechuic aldehyde at a concentration of 2.5 mg / kg could slightly delay the death rate. When the administration concentration was increased to 10 mg / kg, the survival rate of mice was 80%, which was 50% higher than that of the control group. These results show that protocatechuic aldehyde can improve the survival rate of mice infected with CR-ECO18 and has application potential in the treatment of carbapenem-resistant Escherichia coli infections in vivo.

[0059] (4) Effect of protocatechuic aldehyde on infection of ECO-R AMP Effects of Bacterial Clearance on Mice

[0060] Refer to (1) in this example to establish an infected mouse model and administer 20 mg / kg protocatechuic aldehyde or ampicillin, with the unadministered group as a control. At the 12th hour of the drug treatment, the mice were killed by cervical dislocation and dissected, and the kidneys, spleen and liver of the mice were taken out in a 1.5 mL sterile centrifuge tube and weighed. Add 3 grinding beads and sterile saline at a ratio of 2 mL / g, and grind evenly using a high-speed low-temperature tissue grinder, with an operating frequency of 70 Hz, a running time of 30 s, a pause time of 10 s, a running number of 10 (liver) / 15 (kidney, spleen) times, and a set temperature of 0°C. Dilute the homogenate with saline every 10 times, take 5 μL and spot it on an LB agar square plate at one time. Incubate at 37°C for 12 h and count to detect the bacterial content (CFU / g) in the organs.

[0061] The results are as follows Fig.14 As shown in the figure, compared with the untreated group, the bacterial counts in the liver, kidney, and spleen of mice at a concentration of 20 mg / kg protocatechuic aldehyde were significantly reduced, and the clearance was promoted by 4, 3, and 5 times, respectively. However, the bacterial counts in the liver, kidney, and spleen of mice under the action of the same concentration of ampicillin did not decrease significantly. These results indicate that protocatechuic aldehyde can promote the elimination of drug-resistant bacteria in the internal organs of infected mice, thereby improving the survival rate, and this effect is better than the same concentration of ampicillin.

[0062] The above is only a preferred embodiment of the present invention, and the present invention is not limited to the above implementation. As long as the technical effects of the present invention are achieved by the same or equivalent means, they should belong to the protection scope of the present invention. Within the protection scope of the present invention, its technical scheme and / or implementation method can have various modifications and changes.

Claims

1. A novel use of protocatechuic aldehyde in the preparation of a drug for treating or preventing fungal or bacterial infectious diseases, characterized in that: The concentration of the protocatechuic aldehyde is 0.005 mg / mL~3 mg / mL; the bacteria are selected from ampicillin-resistant Escherichia coli (ECO-RAMP), clinical multidrug-resistant Escherichia coli (MDR-ECO), clinical multidrug-resistant Klebsiella pneumoniae (MDR-KPN), clinical multidrug-resistant Pseudomonas aeruginosa (MDR-PAE), clinical carbapenem-resistant Escherichia coli (CR-ECO), clinical carbapenem-resistant Klebsiella pneumoniae (CR-KPN), clinical carbapenem-resistant Pseudomonas aeruginosa (CR-PAE), clinical carbapenem-resistant Acinetobacter baumannii (CR-ABA), Enterobacter mulberry, Pantoea and Ralstonia; the fungi are selected from Candida albicans, Fusarium moniliforme, Botrytis cinerea and Alternaria alternata.

2. Use of protocatechuic aldehyde according to claim 1 in the preparation of drugs for treating or preventing fungal and bacterial infectious diseases.

3. A drug, characterized in that Its components are the pharmaceutical composition according to claim 1 and a pharmaceutically acceptable carrier.

4. The drug according to claim 3, characterized in that The dosage form of the drug is selected from powder, granules, capsules, injections, oral liquids or tablets.

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