Application of tylosin

Abstract

The present invention discloses an application of tylosin. It relates to the field of biomedicine technology. The application of tylosin includes the application of tylosin in the preparation of antibacterial preparations, and the antibacterial preparations are used to inhibit Mycobacterium tuberculosis and / or non-tuberculous mycobacteria. In the technical scheme of the present invention, it is clarified for the first time that tylosin has the effect of inhibiting Mycobacterium tuberculosis. The present invention finds that the drug exerts an antibacterial effect by inhibiting the synthesis of Mycobacterium tuberculosis bacterial protein, the synthesis of ATP, and the formation of biofilm. In the present invention, when tylosin is used in the preparation of drugs, the drug can effectively inhibit Mycobacterium tuberculosis.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, and in particular to an application of tylosin. Background Art

[0002] Tuberculosis (TB) is a contagious chronic infectious disease caused by Mycobacterium tuberculosis (MTB).

[0003] At present, the use of anti-tuberculosis drugs such as rifampicin and isoniazid has alleviated the threat of TB to a certain extent. However, during the treatment process, MTB has developed drug resistance. The emergence and spread of single drug resistance (SDR), multidrug resistance (MDR) and even extensive drug resistance (XDR) strains and their co-infection with HIV have made the treatment of TB face huge challenges. Therefore, it is urgent to develop new anti-tuberculosis drugs for the treatment of drug-resistant TB. Summary of the invention

[0004] The main purpose of the invention is to provide an application of tylosin, aiming at effectively inhibiting tuberculosis bacillus.

[0005] To achieve the above objectives, in a first aspect, the present invention provides a use of tylosin in the preparation of an antibacterial preparation, wherein the antibacterial preparation is used to inhibit Mycobacterium tuberculosis and / or non-tuberculous mycobacteria, wherein the antibacterial preparation is used to inhibit at least one of Mycobacterium tuberculosis H37Rv and H37Ra; the non-tuberculous mycobacteria include at least one of Mycobacterium abscessus and Mycobacterium smegmatis.

[0006] In a second aspect, the present invention provides a use of tylosin in the preparation of a drug, wherein the drug is used to inhibit Mycobacterium tuberculosis and / or non-tuberculous mycobacteria; wherein the drug is used to inhibit at least one of Mycobacterium tuberculosis H37Rv and H37Ra; the non-tuberculous mycobacteria include at least one of Mycobacterium abscessus and Mycobacterium smegmatis.

[0007] In the technical solution of the present invention, it is clarified for the first time that tylosin has the effect of inhibiting Mycobacterium tuberculosis and non-tuberculous mycobacteria. In the present invention, in the application of tylosin in the preparation of medicines, the medicine can effectively inhibit Mycobacterium tuberculosis. The present invention finds that the medicine exerts antibacterial effect by inhibiting the synthesis of Mycobacterium tuberculosis bacterial protein, the synthesis of ATP, and the formation of biofilm. Further, tylosin can be used to prepare medicines for preventing and / or treating tuberculosis. The combined use of tylosin and isoniazid has a superimposed enhancement effect, and the simultaneous use of the two has a synergistic gain effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0009] Figure 1A and Figure 1B The cytotoxicity test results of tylosin in Example 3 of the present invention in 293T and hepG2 cells are shown respectively;

[0010] Figure 2A The formation of H37Ra biofilm after 5 weeks of action of tylosin at different concentrations in Example 4 of the present invention;

[0011] Figure 2B is a bar graph showing the absorbance change of crystal violet after H37Ra biofilm staining in Example 4 of the present invention;

[0012] Figure 2C It is a bar graph of the biofilm inhibition rates of drug groups with different concentrations relative to the control group in Example 4 of the present invention;

[0013] Figure 3A The ATP detection result in Example 5 of the present invention;

[0014] Figure 3B This is a graph showing the percentage of ATP inhibition relative to the control group without drug addition in Example 5 of the present invention;

[0015] Figure 4 is a graph showing the total protein level of H37Ra after adding different concentrations of tylosin;

[0016] Figure 5 This is a diagram showing the experimental results of combining tylosin with isoniazid in Example 7;

[0017] Figure 6 Graph showing ROS levels of bacteria after tylosin administration at different multiples of the MIC concentration range in Example 8.

[0018] The realization of the purpose, functional features and advantages of the present invention will be further explained with reference to the accompanying drawings by way of example. DETAILED DESCRIPTION

[0019] To make the purpose, technical scheme and advantages of the embodiment of the present invention clearer, the technical scheme in the embodiment of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiment, it is carried out according to the normal conditions or the conditions recommended by the manufacturer. If the reagents or instruments used do not specify the manufacturer, they are all conventional products that can be purchased commercially. In addition, the meaning of "and / or" appearing in the full text includes three parallel schemes, taking "A and / or B" as an example, including scheme A, or scheme B, or schemes that A and B meet at the same time. In addition, the technical schemes between the various embodiments can be combined with each other, but must be based on the ability of ordinary technicians in the field to achieve. When the combination of technical solutions is contradictory or cannot be achieved, it should be considered that the combination of such technical solutions does not exist, and is not within the scope of protection required by the present invention. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in the field without making creative work belong to the scope of protection of the present invention.

[0020] At present, the use of anti-tuberculosis drugs such as rifampicin and isoniazid has alleviated the threat of TB to a certain extent. However, during the treatment process, MTB has developed serious drug resistance problems. The emergence and spread of single drug resistance (SDR), multidrug resistance (MDR) and even extensive drug resistance (XDR) strains and their co-infection with HIV have made TB treatment face huge challenges. Therefore, it is urgent to develop new anti-tuberculosis drugs for the treatment of drug-resistant TB.

[0021] In view of this, the present invention provides an application of tylosin, an antibacterial preparation and a medicine.

[0022] In a first aspect, an embodiment of the present invention provides a use of tylosin in the preparation of an antibacterial preparation, wherein the antibacterial preparation is used to inhibit Mycobacterium tuberculosis and / or non-tuberculous Mycobacterium.

[0023] In the technical solution of the present invention, it is clarified for the first time that tylosin has the effect of inhibiting Mycobacterium tuberculosis or non-tuberculous mycobacteria. In the present invention, when tylosin is used in the preparation of medicine, the medicine can effectively inhibit Mycobacterium tuberculosis. Further, tylosin can be used to prepare medicine for the prevention and / or treatment of tuberculosis. The combined use of tylosin and isoniazid has a superimposed enhancement effect, and the simultaneous use of the two has a synergistic gain effect.

[0024] In some embodiments, the antibacterial preparation is used to inhibit at least one of Mycobacterium tuberculosis H37Rv and H37Ra; the non-tuberculous mycobacteria include at least one of Mycobacterium abscessus and Mycobacterium smegmatis.

[0025] In a second aspect, an embodiment of the present invention provides a use of tylosin in preparing a medicine, wherein the medicine is used to inhibit Mycobacterium tuberculosis and / or non-tuberculous Mycobacterium.

[0026] It should be noted that the drug was found in the present invention to exert its antibacterial effect by inhibiting the synthesis of Mycobacterium tuberculosis bacteria protein, the synthesis of ATP, and the formation of biofilm.

[0027] In some embodiments, the drug is used to inhibit at least one of Mycobacterium tuberculosis H37Rv and H37Ra; the non-tuberculous mycobacteria include at least one of Mycobacterium abscessus and Mycobacterium smegmatis.

[0028] In a third aspect, the present invention provides an antibacterial preparation for inhibiting Mycobacterium tuberculosis, wherein the antibacterial preparation comprises tylosin.

[0029] In some embodiments, the antibacterial agent further comprises isoniazid.

[0030] In a fourth aspect, the present invention provides a drug for inhibiting Mycobacterium tuberculosis, wherein the drug comprises tylosin.

[0031] In some embodiments, the medicament further comprises isoniazid.

[0032] It should be noted that the present invention unexpectedly found that the anti-tuberculosis effect of tylosin combined with isoniazid is significantly higher than the effect of using tylosin or isoniazid alone. It can be seen that the combined use of tylosin and isoniazid has a superimposed and enhanced effect, and the simultaneous use of the two has a synergistic gain effect.

[0033] In a fifth aspect, the present invention provides a drug for preventing and / or treating tuberculosis, wherein the drug comprises tylosin.

[0034] In some embodiments, the medicament further comprises isoniazid.

[0035] In some embodiments, the medicament further comprises a pharmaceutically acceptable excipient, carrier and / or diluent.

[0036] In a sixth aspect, the present invention provides a use of tylosin in the preparation of a medicament, wherein the medicament is used to prevent and / or treat a disease, or reduce the risk of a disease; the disease is tuberculosis.

[0037] In the present invention, the term "prevention and / or treatment" not only includes prevention and / or treatment of diseases, but also generally includes reducing or inhibiting the number of pathogens associated with the disease, preventing the onset of the disease, slowing down or reversing the progression of the disease, preventing or slowing down the onset of one or more symptoms associated with the disease, reducing and / or alleviating one or more symptoms associated with the disease, reducing the severity and / or duration of the disease and / or any symptom associated therewith and / or preventing the disease and / or any symptom associated therewith from further increasing in severity, preventing, reducing or reversing any physiological damage caused by the disease, and any pharmacological effects that are generally beneficial to the patient being treated. The drugs of the present application form feasible therapeutic agents that do not need to achieve complete cure or eradication of any symptoms or manifestations of the disease. As recognized in the relevant art, drugs used as therapeutic agents can reduce the severity of a given disease state, but do not need to eliminate every manifestation of the disease to be considered a useful therapeutic agent. Similarly, the treatment of prophylactic administration constitutes a feasible preventive agent that does not need to completely and effectively prevent the onset of the disease. Simply reducing the effects of the disease in a subject (e.g., by reducing the number or severity of its symptoms, or by increasing the effectiveness of another treatment, or by producing another beneficial effect), or reducing the likelihood that the disease will occur or worsen, is sufficient.

[0038] The technical solution of the present invention is further described in detail below in conjunction with specific embodiments and drawings. It should be understood that the following embodiments are only used to explain the present invention and are not used to limit the present invention.

[0039] It should be noted that the bacteria and culture conditions used in the following examples are as follows: 8 strains of Mycobacterium including Mycobacterium tuberculosis H37Rv (ATCC 27294), Mycobacterium tuberculosis H37Ra (ATCC 25177), BCG (ATCC 35734), Mycobacterium smegmatis mc2155, Mycobacteriumabscessus (ATCC 19977), Mycobacterium marinum BAA535, Mycobacterium fortuitum (ATCC 6841), Mycobacterium kansasii (ATCC 12478) were routinely cultured at Middlebrook Mycobacterium tuberculosis 28 (resistant to isoniazid, rifampicin, and ethionamide, and sensitive to streptomycin, ethambutol, amikacin, ciprofloxacin, and sodium aminosalicylate) and Mycobacterium tuberculosis 1731 (resistant to isoniazid, rifampicin, streptomycin, and ethionamide, and sensitive to ethambutol, amikacin, ciprofloxacin, and sodium aminosalicylate) were cultured in 7H9 (company information) liquid medium and solid Middlebrook 7H10 (company information) plates (10% OADC was added, 0.05% Tween-80 was added for routine culture in liquid medium, and no addition was required for culture in biofilm formation experiments). Both strains were stored in Beijing Chest Hospital Affiliated to Capital Medical University. Except for Mycobacterium marinum, which was cultured in a 30°C incubator, the remaining strains were cultured at 37°C.

[0040] The data processing used in the following examples was performed using GraphPad Prism 8.0.2. One-way ANOVA analysis of variance was used to compare the statistical differences among the three groups, and Student's t test was used to compare the statistical differences between the means of the two groups; the curve fitting calculation of IC50 in the cytotoxicity experiment was performed using the Dose-response-inhibition module of nonlinear regression.

[0041] Example 1

[0042] Minimum inhibitory concentration (MIC) determination

[0043] The MIC values ​​of the compound samples against all strains were determined in 96-well plates using the two-fold serial dilution method.

[0044] (1) Prepare bacterial culture medium: dilute the logarithmic phase bacteria to a McFarland turbidity of 1, and then inoculate the liquid culture medium corresponding to the fresh strain at a dilution of 1:100.

[0045] (2) Add 200 µL of blank culture medium around the 96-well plate to prevent drying.

[0046] (3) Add 1.28 µL of 10 mg / ml tylosin to wells B2 to D2 in the second column of the 96-well plate, and add 1.28 µL of 10 mg / ml positive control drug to wells E2 to G2 in the second column (different bacteria use different positive control drugs, for example, for H37Ra (ATCC 25177), the positive control drug is INH, and for M. Smegmatis mc2155, the positive control drug is Ofloxacin (OFX)).

[0047] (4) Add 198.72 µL of the bacterial culture medium prepared in (1) to wells B2 to G2 (the final concentration of the drug is 64 µg / mL); at the same time, add 100 µL of the bacterial culture medium to wells B2 to G22 in the remaining columns except the 11th column; wells B2 to D2 in the 11th column are added with a bacterial culture medium containing the same concentration and allowed to grow normally as a positive control, and wells E2 to G2 are negative control wells containing only culture medium without drug addition.

[0048] (5) Serial dilution: Use a dispenser to pipette and mix the sample in column 2, and transfer 100 µL to column 3 and pipette and mix. Repeat this process until column 10, and discard the remaining 100 µL. The concentrations of the compounds are: 64 µg / mL, 32 µg / mL, 16 µg / mL, 8 µg / mL, 4 µg / mL, 2 µg / mL, 1 µg / mL, 0.5 µg / mL, and 0.25 µg / mL.

[0049] (6) After sealing with sealing film, place it at 37°C and culture it until the logarithmic growth phase of the bacteria, and observe the experimental results. The lowest drug concentration at which there is no visible bacterial growth is the minimum inhibitory concentration of the compound.

[0050] Specifically, the minimum inhibitory concentration (MIC) was tested in 3 strains of MTB and 5 strains of non-MTB bacteria (the experimental results are shown in Table 1). The results showed that for MTB, the MIC of tylosin for MTB H37Ra was 4 μg / mL, and the MIC value for H37Rv was 2.5 μg / mL. The MIC for MTB clinical multidrug-resistant strain 28 was 1.25~2.5 μg / mL, and the MIC value for 1731 was 2.5~5μg / mL. In addition, for non-MTB (NTM) M. smegmatis and M.abscessus It also has significant antibacterial activity (see Table 1).

[0051] Table 1. Minimum inhibitory concentration of tylosin against mycobacteria

[0052]

[0053] Among them, INH (H), EMB (E), and Ofloxacin (OFX) in Table 1 are positive control drugs corresponding to different bacteria, and “-” means there is no experimental data.

[0054] Example 2

[0055] Minimum bacterial concentration (MBC) determination, the specific method is as follows:

[0056] (1) Treat H37Ra with 1×~16×MIC tylosin samples for 7~10 days. Dilute the strains in each experimental group 10-fold, from 10 to 10. 100 μL of each dilution gradient was applied to 7H10 plates and cultured at 37℃ until single colonies grew and were counted. CFU / mL = colony count × 10 × dilution factor.

[0057] (2) Taking the initial colony count in the culture medium as a reference, the concentration of the compound that reduces the colony count by 99.9% is the minimum bactericidal concentration.

[0058] (3) Classification of drugs: MBC of bactericides ≥ MIC (but not more than 4 times); MBC of antibacterial agents > 4 × MIC.

[0059] The MBC value of tylosin for H37Ra was 64 μg / mL, which indicated that tylosin was an antibacterial agent for H37Ra.

[0060] Example 3

[0061] In order to evaluate the safety of tylosin and determine whether the concentration range in which the drug is active is a safe dose, cytotoxicity experiments on kidney and liver cells were further conducted.

[0062] Test the TC of tylosin on hepatocytes HepG2 and kidney cells 293T 50 Value (half toxic concentration in drug toxicity tests). Specifically:

[0063] (1) Take cells in logarithmic growth phase, digest them and count them, with 4×10 cells per well. 3 The cells were seeded in a 96-well cell culture plate and incubated in a 37°C, 5% CO2 cell culture incubator;

[0064] (2) Cultivate 293T and HepG2 cells for 24 h, and then add different concentrations of tylosin after the cells adhere to the wall. Perform 3-fold dilutions from 1000 μg / ml for 9-10 times, with 3 parallel wells in each group, and treat the cells for 72 h.

[0065] (3) Add the detection solution according to the CCK-8 kit and obtain the corresponding absorbance on the microplate reader.

[0066] (4) Calculate cell survival rate: Cell survival rate % = (OD 450nm - Background OD 450nm ) / (control cell OD 450nm - Background OD 450nm )×100%.

[0067] (5) Calculation of IC using curve fitting on GraphPad Prism 8.0.2 (GraphPad Software) 50 value.

[0068] Test results see Figure 1A-1B The results showed that the IC 50 They are 71.45 μg / mL and 73.73 μg / mL respectively. According to the definition of safety selection index (SI), combined with the MIC value of tylosin against H37Rv, the SI index is greater than 28. The high safety index of tylosin indicates that tylosin has potential application in the preparation of drugs.

[0069] Example 4

[0070] Biofilm formation inhibition assay

[0071] After washing H37Ra in the logarithmic growth phase with PBS for three times, add the corresponding volume of Middlebrook7H9 without Tween-80 to make the OD of the bacterial solution between 0.3-0.5. Add tylosin with different MIC multiple gradients (2x, 1x, 0.75x, 0.5x, 0.25x, 0x) to each tube with 2 ml of bacterial solution. After static culture in a 37°C incubator for 4-5 weeks, take photos and record the biofilms and stain with crystal violet.

[0072] Results Figures 2A-2C ,in Figure 2A The formation of H37Ra biofilm after 5 weeks of action of different concentrations of tylosin. From left to right, the concentrations of tylosin are different multiples of the MIC concentration: 2X, 1X, 0.75X, 0.5X, 0.25X, 0XMic; Figure 2B-2C After crystal violet staining of the biofilm, Figure 2B The bar graph shows the absorbance change of crystal violet after staining. Figure 2C It is a bar graph of the biofilm inhibition rate of different drug concentration groups relative to the control group. Figure 2B-2C The horizontal axes of the graphs represent different multiples of the MIC concentration of tylosin. * indicates p <0.05.

[0073] Since 80% of chronic infections are related to the formation of biofilms. MTB can form biofilms, which can lead to phenotypic drug resistance. The presence of highly resistant MTB in the biofilm can escape the attack of the body's immune system and resist the killing of first-line anti-tuberculosis drugs such as isoniazid and rifampicin. This may be one of the main reasons for the extension of the TB treatment cycle. After destroying the biofilm of Mycobacterium tuberculosis, the resistant bacteria regain sensitivity to anti-tuberculosis drugs. MTB biofilms are mainly composed of polysaccharides, proteins, eDNA and lipids. Since tylosin mainly targets bacterial proteins, we further studied whether tylosin has an inhibitory effect on the formation of MTB biofilms. The results showed that tylosin has an inhibitory effect on the biofilm formation of MTB H37Ra, and this inhibitory effect is concentration-dependent. As the concentration of tylosin increases, the inhibitory effect becomes more obvious.

[0074] Example 5

[0075] ATP detection

[0076] BacTiter-Glo™ microbial cell viability (Promega (Beijing) Biotechnology Co., Ltd.) was used to determine the ATP levels of drug treatment and control groups. In an opaque wall 96-well plate (Shanghai Biyuntian Biotechnology Co., Ltd.), 100 μL of H37Ra in the logarithmic growth period was added with different MIC multiple concentration gradients of tylosin for 12 to 16 hours and then ATP was detected. The detection process was carried out at room temperature according to the instructions of the kit, and the luminescence value was read using an ELISA reader (Shenzhen Boxing Biotechnology Co., Ltd.). In this example, drug treatment refers to the addition of tylosin, and the untreated control group refers to the absence of tylosin.

[0077] ATP is the main energy storage and transfer molecule in cells. MTB needs energy for life activities such as growth, division and survival; ATP is involved in many biosynthetic pathways of MTB, including the synthesis of nucleic acids, proteins, lipids, etc. These biomolecules are essential for the structure and function of bacteria. In order to explore whether tylosin exerts its antibacterial activity by inhibiting the ATP level of MTB H37Ra, the ATP level of bacteria was detected after adding different concentrations of tylosin. The results are shown in Figure 3A-3B , where the ordinate of 3A represents ATP, measured by luminescence intensity, and the ordinate of 3B represents the percentage of ATP inhibition relative to the untreated control group (0xMIC group). Figure 3A and3B The horizontal axis represents different multiples of MIC concentrations of tylosin. ** indicates p<0.01, **** indicates p<0.0001. It can be seen that tylosin indeed inhibited the ATP level of H37Ra, and the ATP level increased with the decrease of tylosin concentration below 0.5 times MIC, that is, as the concentration of tylosin decreased, the ATP inhibition effect on MTB weakened.

[0078] Example 6

[0079] H37Ra total protein SDS-PAGE determination.

[0080] Detect whether different concentrations of tylosin affect the protein of H37Ra to exert antibacterial activity

[0081] After 10-fold dilution of H37Ra in the logarithmic growth phase, the cells were divided into groups according to different concentrations of tylosin, with 2 mL per group. After culturing at 37°C and 180 rpm for 7 days, the precipitate was collected by centrifugation at 5000 × g for 10 min. The corresponding volume of thermo B-PER™ bacterial protein extraction reagent and 0.1 mm glass beads were added according to the weight of the precipitate. The cells were centrifuged at 5000 RPM for 1 min, 3-5 cycles, and cooled on ice for 5 min. The supernatant was collected by centrifugation at 12000 × g, 4°C for 5 min, and the corresponding volume of 5xSDS loading buffer (Shanghai Biotech Co., Ltd.) was added. The metal bath was 95°C for 10 min, and then SDS-PAGE electrophoresis was performed.

[0082] Results Figure 4 , Figure 4 2xMic, 0.5xMic, and CTRL are 2xMIC drug group, 0.5xMIC drug group, and 0xMIC (i.e., untreated control group). It can be seen that the total protein level of H37Ra was detected after adding different concentrations of tylosin. The results showed that the addition of tylosin reduced most of the proteins of H37Ra, and this effect became more obvious as the concentration of the compound increased.

[0083] Example 7

[0084] Combination therapy with isoniazid

[0085] In the logarithmic growth phase, take an appropriate amount of bacterial solution 7H9 and dilute it to OD 600nm0.001, 100 μL bacterial solution per well, using the chessboard method, the horizontal direction is INH dilution from 1 times MIC, the vertical direction is tylosin dilution from 1 times MIC. OD was measured after 7-10 days of static culture in a 37°C incubator 600nm After measuring the absorbance, 30 μL of resazurin (0.05% resazurin and 10% TWEEN-80) was added to each well for color development. The images were recorded and photographed using a Deli High Speed ​​Flash Photographer (Deli Group Co., Ltd.).

[0086] The checkerboard method was used to add drugs with a 1-fold MIC concentration to a 96-well plate to start serial dilutions, and to observe whether the MIC of H37Ra changed under the action of two different drug concentrations. The results showed that under the action of tylosin, the MIC of INH decreased from the original 0.125 μg / mL to 0.015625 μg / mL; at the same time, tylosin also decreased from the original 4 μg / mL to <0.125μg / mL ( Figure 5 ), the above data show that the two drugs have a synergistic effect (Table 2). The synergistic effect of tylosin and isoniazid brings hope for reducing drug dosage, shortening treatment course, and reducing medication cycle.

[0087] Table 2 Tylosin and INH chessboard method combined drug experiment

[0088]

[0089] Example 8

[0090] Since tylosin has a bactericidal effect on H37Ra, in order to explore whether tylosin affects the ROS level of Mycobacterium tuberculosis, the ROS level of bacteria after adding tylosin at different multiples of the MIC concentration range was tested. The results are shown in Figure 6 It can be seen that except for the increase in bacterial ROS levels in the 0.5 times MIC concentration range, there was no statistical difference compared with the control group in other concentration ranges.

[0091] The above are only preferred embodiments of the present invention, and do not limit the patent scope of the present invention. For those skilled in the art, the present invention may have various changes and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the patent protection scope of the present invention.

Claims

1. Use of a composition of tylosin and isoniazid in the preparation of an antibacterial preparation, characterized in that: The antibacterial preparation is used to inhibit Mycobacterium tuberculosis and / or non-tuberculous mycobacteria, wherein the Mycobacterium tuberculosis includes at least one of Mycobacterium tuberculosis H37Rv, H37Ra, Mycobacterium tuberculosis 28, and Mycobacterium tuberculosis 1731; and the non-tuberculous mycobacteria include at least one of Mycobacterium abscessus and Mycobacterium smegmatis.

2. Use of a composition of tylosin and isoniazid in the preparation of a medicine, characterized in that: The drug is used to inhibit Mycobacterium tuberculosis and / or non-tuberculous mycobacteria; wherein the Mycobacterium tuberculosis includes at least one of Mycobacterium tuberculosis H37Rv, H37Ra, Mycobacterium tuberculosis 28, and Mycobacterium tuberculosis 1731; and the non-tuberculous mycobacteria include at least one of Mycobacterium abscessus and Mycobacterium smegmatis.

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