Bacteriostatic composition containing pyrolin and antibiotics and application thereof

Abstract

The invention relates to the field of bacteriostasis, in particular to a bacteriostatic composition containing pyrolin and antibiotics and application of the bacteriostatic composition. The antibacterial composition contains pyrolin and an antibiotic; wherein the antibiotic is selected from at least one kind of materials from tetracycline (Tetracycline), ciprofloxacin (Ciprofloxacin) and tobramycin (Tobramycin). The antibacterial composition disclosed by the invention not only can obviously inhibit various pathogenic bacteria, but also can obviously reduce the use of antibiotics, thereby being beneficial to reducing the possibility of occurrence of bacterial drug resistance.

Description

Technical Field

[0001] This invention relates to the field of antibacterial agents, and more specifically, to antibacterial compositions containing pyrophoric acid and antibiotics, and their applications. Background Technology

[0002] The problem of antibiotic resistance in pathogens has evolved into a global public health crisis. The application of antimicrobial drugs has expanded from traditional infection treatment to core medical areas such as surgery, cancer treatment, and organ transplantation, highlighting their strategic value. However, the overuse of antimicrobial drugs has exacerbated the spread of resistance.

[0003] The mechanisms of bacterial resistance formation include two types: (1) Inherent resistance: determined by chromosomal genetic characteristics, manifested as the natural insensitivity of bacteria to specific antimicrobial drugs; such as Escherichia coli resistance to vancomycin and Streptococcus resistance to aminoglycoside antibiotics; (2) Acquired resistance: susceptible bacteria acquire resistance genes through gene mutation or horizontal gene transfer, and then evolve metabolic pathways to escape drug killing.

[0004] Against this backdrop, the development of natural medicinal resources has become an important direction for overcoming the drug resistance dilemma. The mechanism of traditional Chinese medicine in preventing and treating infectious diseases has multiple targets and functions: (1) directly inhibiting or killing pathogenic microorganisms (bacteria, fungi, viruses, etc.); (2) enhancing the host's immune function; (3) reducing the dosage of antibiotics through multi-component action and delaying the development of drug resistance.

[0005] However, the complex chemical composition system of traditional Chinese medicine (TCM) has led to a lack of clarity regarding the identification of its active ingredients and their mechanisms of action. Crucially, there is currently a lack of efficient screening methods to systematically identify TCM components with synergistic effects—that is, combinations of active ingredients that can reduce the clinical dosage of antibiotics and thus help delay the development of drug resistance. This, to some extent, limits their application value in the control of drug-resistant bacteria. Summary of the Invention

[0006] The first objective of this invention is to provide an antibacterial composition containing pyrophoric acid and an antibiotic; wherein the antibiotic is selected from at least one of tetracycline, ciprofloxacin, and tobramycin.

[0007] The present invention also provides an antibacterial product, which provides the aforementioned antibacterial composition using one or a combination of reagents.

[0008] The present invention also provides the use of the said antibacterial composition or the said antibacterial product in therapeutic and non-therapeutic antibacterial applications, wherein the bacteria include at least one of Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis.

[0009] The present invention also provides the use of the antibacterial composition in the preparation of antibacterial products, wherein the bacteria include at least one of Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis.

[0010] The antibacterial composition of the present invention can not only significantly inhibit a variety of pathogenic bacteria, but also significantly reduce the use of antibiotics, thereby helping to reduce the possibility of bacterial resistance. Detailed Implementation

[0011] The following provides a detailed description of specific embodiments of the present invention. It should be understood that the specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the invention. Those skilled in the art can make various modifications and variations to the invention without departing from its scope or spirit. For example, features described or illustrated as part of one embodiment can be used in another embodiment to produce further embodiments.

[0012] Unless otherwise stated, all terms used to disclose this invention (including technical and scientific terms) have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Further guidance is provided below for a better understanding of the teachings of this invention. The terminology used herein in the specification of this invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

[0013] The terms "and / or," "or / and," and "and / or" as used herein include any one of two or more of the related listed items, as well as any and all combinations of the related listed items. These arbitrary and all combinations include any two related listed items, any more related listed items, or a combination of all related listed items. It should be noted that when at least three items are connected by at least two conjunctions selected from "and / or," "or / and," and "and / or," it should be understood that in this application, the technical solution undoubtedly includes technical solutions connected by "logical AND," and also undoubtedly includes technical solutions connected by "logical OR." For example, "A and / or B" includes three parallel solutions: A, B, and A+B.

[0014] The terms “containing,” “comprising,” and “including” as used in this invention are synonyms and are inclusive or open-ended, not excluding additional, uncited members, elements, or method steps.

[0015] In this invention, the numerical range represented by endpoints includes all numerical values ​​and fractions contained within that range, as well as the endpoints mentioned.

[0016] This invention involves numerical values, which include fluctuations within a certain range. For example, fluctuations are allowed within a corresponding precision range. For instance, 4 can fluctuate within ±0.05%. For larger values ​​or values ​​that do not require overly fine control, even greater fluctuations are allowed. For example, 70000 can fluctuate within ranges of ±1%, ±2%, ±5%, etc.

[0017] In this invention, the terms "multiple" or "various" are used unless otherwise specified, referring to a quantity of 2 or more.

[0018] In this invention, the technical features described in an open-ended manner include both closed-ended technical solutions composed of the listed features and open-ended technical solutions that include the listed features.

[0019] In this invention, terms such as "preferred," "better," "more suitable," and "ideal" are merely descriptions of more effective implementation methods or embodiments, and should be understood not to limit the scope of protection of this invention.

[0020] In this invention, "optionally," "optionally," "optionally," "optionally," "optionally," and "optional" mean that they are optional, that is, they are selected from either "with" or "without." If multiple "optional" or "optional" terms appear in a technical solution, unless otherwise specified and there are no contradictions or mutual constraints, then each "optional" or "optional" term is independent.

[0021] In this invention, pyrolin (chemical name: 2-methyl-1,4-benzenediol, C7H8O2) refers to one of the main active ingredients in the traditional Chinese medicine *Pyrola calliantha*, which possesses a "methylhydroquinone" structure. *Pyrola calliantha* refers to the dried whole herb of *Pyrola calliantha* H. Andr., *Pyrola rotundifolia* L., or closely related plants of the same genus. Pyrolin has traditionally been used for intestinal infections or as a topical anti-inflammatory agent, but modern medicine generally considers its clinical anti-infective value to be limited.

[0022] The present invention first provides an antibacterial composition containing pyrophoric acid and an antibiotic; wherein the antibiotic is selected from at least one of tetracycline, ciprofloxacin, and tobramycin.

[0023] The present invention has found that the above-mentioned antibacterial composition can not only achieve better antibacterial effect, but also significantly reduce the amount of antibiotics used, which is beneficial to reducing the occurrence of bacterial resistance.

[0024] In some embodiments, the mass ratio of the pyrophylloidin to the antibiotic is greater than or equal to 4.

[0025] In some specific embodiments, the mass ratio of the pyrophylloidin to the antibiotic can be 4, 16, 32, 128, 256, 512, 1024, 2048, 3000, 4096, 5000, 6000, 7000, 8196, 10000, 20000, 30000, 40000, 50000, 60000, 65536.17, or 70000, etc.

[0026] In some embodiments, the antibacterial composition comprises a mixture of pyrimethamine and tetracycline, wherein the mass ratio of pyrimethamine to tetracycline is 20–5000:1. This can further improve the inhibitory effect of the antibacterial composition on bacteria such as Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis.

[0027] In some preferred embodiments, the mass ratio of pyrophoric acid to tetracycline is 3000–5000:1, more preferably 4000–4200:1, and even more preferably 4096:1. This allows for further reduction of antibiotic dosage when inhibiting Klebsiella pneumoniae, resulting in a 16-fold reduction in the minimum inhibitory concentration of the antibiotic.

[0028] In some specific embodiments, the mass ratio of pyrophoric acid to tetracycline can be 20:1, 32:1, 128:1, 512:1, 1024:1, 2048:1, 3000:1, 3500:1, 3800:1, 3900:1, 4000:1, 4096:1, 4100:1, 4200:1, 4500:1, or 5000:1, etc.

[0029] In some embodiments, the antibacterial composition comprises a mixture of pyrimethamine and ciprofloxacin, wherein the mass ratio of pyrimethamine to ciprofloxacin is 200–70,000:1. This can further improve the inhibitory effect of the antibacterial composition on bacteria such as Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis.

[0030] In some preferred embodiments, the mass ratio of pyrotropin to ciprofloxacin is 500–1100:1, more preferably 512–1024:1. This allows for further reduction of antibiotic dosage when inhibiting Staphylococcus aureus, resulting in a 4-fold reduction in the minimum inhibitory concentration of the antibiotic.

[0031] In some preferred embodiments, the mass ratio of pyrotropin to ciprofloxacin is 2000–2100:1, more preferably 2048:1. This enables a synergistic effect in inhibiting Klebsiella pneumoniae, further reducing the amount of antibiotic used and lowering the minimum inhibitory concentration of the antibiotic by four times.

[0032] In some specific embodiments, the mass ratio of pyrotropin to ciprofloxacin can be 200:1, 256:1, 300:1, 500:1, 512:1, 600:1, 800:1, 1000:1, 1024:1, 1100:1, 1500:1, 2000:1, 2048:1, 2100:1, 2500:1, 3000:1, 5000:1, 10000:1, 30000:1, 50000:1, 65536.17:1, or 70000:1, etc.

[0033] In some embodiments, a mixture of pyrimethamine and tobramycin is used, wherein the mass ratio of pyrimethamine to tobramycin is 4–9000:1. This can further improve the inhibitory effect of the antibacterial composition on bacteria such as Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis.

[0034] In some preferred embodiments, the mass ratio of pyrophoric acid to tobramycin is 900–1100:1, preferably 1000–1050:1, and more preferably 1024:1. This achieves a synergistic effect in inhibiting Klebsiella pneumoniae, further reducing the dosage of antibiotics and lowering the minimum inhibitory concentration of antibiotics by 8 times.

[0035] In some specific embodiments, the mass ratio of pyrophoric acid to tobramycin can be 4:1, 16:1, 256:1, 512:1, 600:1, 800:1, 900:1, 1000:1, 1024:1, 1050:1, 1100:1, 1500:1, 2048:1, 3000:1, 5000:1, 7000:1, 8192:1, or 9000:1, etc.

[0036] In some specific embodiments, the antibacterial composition further includes metal ions / nanomaterials to physically disrupt the bacterial cell structure. Specifically, these may be silver-based antibacterial agents such as silver nanoparticles (AgNPs) to release silver ions and disrupt membrane proteins; zinc / copper compounds such as zinc oxide nanoparticles (ZnO NPs) to generate reactive oxygen species (ROS); or photosensitive materials such as titanium dioxide (TiO2) to photocatalytically oxidize bacteria.

[0037] In some specific embodiments, the antibacterial composition further includes a biosynergist to inhibit drug resistance mechanisms and restore antibiotic sensitivity. Specifically, this could be an efflux pump inhibitor such as phenylalanine-arginine β-naphthylamide (PaβN) to block drug efflux by resistant bacteria; a β-lactamase inhibitor such as tazobactam to protect the activity of β-lactam antibiotics; or a biofilm dispersant such as DNase or EDTA to disrupt the physical barrier of bacterial biofilms.

[0038] In some specific embodiments, the antibacterial composition further includes a pharmaceutically acceptable carrier.

[0039] In some specific embodiments, the antibacterial composition further includes one or more of the following reagents: (1) an aqueous gel matrix, such as carbomer, hydroxypropyl cellulose (HPC), etc., for use in topical gel formulations to prolong the contact time between the drug and the skin; (2) a cream / ointment matrix, such as petrolatum, polyethylene glycol (PEG), or emulsified wax (such as cetyl alcohol), etc., as a hydrophobic carrier to encapsulate lipid-soluble antibacterial components (such as essential oils); (3) a sustained-release material, such as polylactic acid-glycolic acid copolymer (PLGA) microspheres or ethyl cellulose (EC), etc., to control the continuous release of active ingredients; (4) a transdermal penetration enhancer, such as azone or propylene glycol (≤30%), etc., to enhance the skin permeability of hydrophilic substances; (5) a stabilizer / solvent, such as cyclodextrin (encapsulating hydrophobic components), Tween-80 (solubilizing antimicrobial peptides), or citrate buffer (maintaining the activity of pH-sensitive components); (6) a solvent, such as an ethanol / water mixed solvent, etc.

[0040] In specific implementation, those skilled in the art can combine the above-mentioned embodiments with common sense to obtain more embodiments of the antibacterial composition of the present invention.

[0041] The present invention also provides an antibacterial product, which provides the aforementioned antibacterial composition using one or a combination of reagents.

[0042] In some embodiments, the pyrrolizin and the antibiotic may be provided separately in two reagents of the antibacterial product. In some embodiments, the pyrrolizin and the antibiotic may be provided simultaneously in one reagent of the antibacterial product.

[0043] In some specific embodiments, the antibacterial product also includes a wound dressing for topical application of the antibacterial composition, such as sodium alginate hydrocolloid.

[0044] The present invention also provides the use of the described antibacterial composition or the described antibacterial product in therapeutic and non-therapeutic antibacterial applications, wherein the bacteria include at least one of Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis. That is, the present invention also provides an antibacterial method comprising: using the described antibacterial composition in combination. The following further limitations on application also apply to the described antibacterial method.

[0045] The present invention also provides the use of the antibacterial composition in the preparation of antibacterial products, wherein the bacteria include at least one of Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis.

[0046] In some embodiments, the antibacterial effect includes at least one of the following:

[0047] (a) Pyrrosin and ciprofloxacin are used in combination to inhibit Staphylococcus aureus; preferably, the mass ratio of pyrrosin to ciprofloxacin is 500 to 1100:1, more preferably 512 to 1024:1;

[0048] (b) Pyrrosin and tetracycline are used in combination to inhibit Klebsiella pneumoniae; preferably, the mass ratio of pyrrosin to tetracycline is 3000 to 5000:1, more preferably 4000 to 4200:1, and even more preferably 4096:1;

[0049] (c) Pyrrosin and ciprofloxacin are used in combination to inhibit Klebsiella pneumoniae; preferably, the mass ratio of pyrrosin to ciprofloxacin is 2000 to 2100:1, more preferably 2048:1.

[0050] (d) Pyrrosin and tobramycin are used in combination to inhibit Klebsiella pneumoniae; preferably, the mass ratio of pyrrosin to tobramycin is 900-1100:1, more preferably 1000-1050:1, and even more preferably 1024:1.

[0051] In some embodiments, pyrophoric acid is used to reduce the minimum inhibitory concentration (MIC) of the antibiotic.

[0052] In some preferred embodiments, pyrophoric acid is used to reduce the minimum inhibitory concentration of the antibiotic by 4 to 16 times (e.g., 4 times, 8 times, or 16 times).

[0053] In some specific embodiments, the pyrophylloidin and the antibiotic may be used simultaneously or sequentially (without being limited to a specific order).

[0054] In some specific embodiments, the Staphylococcus aureus is Staphylococcus aureus subsp. aureus, such as ATCC 33591.

[0055] In some specific embodiments, the Klebsiella pneumoniae is ATCC700603.

[0056] In some specific embodiments, the Enterococcus faecalis is a vancomycin-resistant Enterococcus faecalis, such as ATCC 51299.

[0057] The embodiments of the present invention will be described in detail below with reference to examples. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. For experimental methods in the following embodiments where specific conditions are not specified, please refer to the guidelines given in this invention, or follow experimental manuals or conventional conditions in the art, or other experimental methods known in the art, or follow the conditions recommended by the manufacturer.

[0058] In the specific embodiments described below, the measurement parameters involving raw material components may have slight deviations within the weighing accuracy range unless otherwise specified. Temperature and time parameters are subject to acceptable deviations due to instrument testing accuracy or operational precision.

[0059] Example

[0060] 1. Materials

[0061] 1.1 Test bacteria:

[0062] Gram-negative bacteria: Klebsiella pneumoniae ATCC 700603.

[0063] Gram-positive bacteria: Staphylococcus aureus subsp. aureus ATCC 33591 and vancomycin-resistant Enterococcus faecalis ATCC 51299.

[0064] 1.2 Culture media: TSA (solid), MHB (liquid).

[0065] 1.3 Reagents: Pyrroside, Tetracycline (Tc), Ciprofloxacin (Cip), Cabenicillin (Cab), Tobramycin (Tob).

[0066] 1.4 Experimental materials: sterile culture dishes, McFarland turbidimeter, multi-row pipettes, sterile test tubes, sterile physiological saline (0.9% NaCl), 96-well plates, sterile inoculation loops, etc.

[0067] 2 methods

[0068] 2.1 Inoculation of test bacteria and preparation of bacterial suspension

[0069] Remove the cryovials from the -80°C freezer. Under aseptic conditions, unscrew the cryovials and, using a sterile inoculation loop (or sterile pipette tip), dip a small amount of bacterial suspension into TSA medium and streak it onto the medium to obtain single colonies. Immediately return the cryovials to the freezer for cryopreservation. The inoculated plates will be placed in a 37°C incubator and inverted for 16 to 24 hours. These plates can be stored at 4°C for up to two weeks before use. Using a sterile inoculation loop, pick single colonies from the primary culture dish and streak them onto TSA medium to prepare a second-generation culture. Incubate the second-generation culture dish inverted for 16 to 24 hours. Pick 3-5 colonies from the second-generation culture dish and dissolve them directly in 3 mL of sterile physiological saline (0.9% NaCl) to prepare a bacterial suspension for inoculation. Then, adjust the turbidity to 0.5 McFarland turbidity standard using a turbidimeter. 0.5 McFarland turbidity is equivalent to 1.5 x 10⁻⁶. 8 CFU / mL bacterial count. This can be adjusted by picking more colonies or adding 0.9% NaCl.

[0070] 2.2 Determination of Minimum Inhibitory Concentration (MIC)

[0071] Under aseptic conditions, take a clean 96-well plate. Except for the first column, add 50 μL of MHB medium to each well in A2-A12, B2-B12, C2-C12, F2-F12, G2-G12, H2-H12, D12, and E12 (control). Add 100 μL of the high-concentration antimicrobial substance to the first column. Mix thoroughly, and then dilute sequentially by a factor of 2 until the last column. Discard 50 μL from the last column, ensuring each well contains 50 μL of liquid. The bacterial suspension obtained after overnight culture is diluted in saline (0.9% NaCl) using a McFarland turbidimeter and the concentration is adjusted to 0.5 McFarland units (approximately 1.5 x 10⁻⁶ cells / well). 8 (CFU / mL) for later use. Dilute 50-fold in MHB culture medium, add 50 μL to a 96-well plate, and incubate in a constant temperature incubator for 18 to 20 hours. Observe its growth to determine the minimum inhibitory concentration.

[0072] 2.3 Micro-broth dilution checkerboard method

[0073] Under aseptic conditions, take a clean 96-well plate and add 50 μL of MHB to each well. Well H1 is a blank control, with no antibacterial drugs added. Prepare 1 mL of 4 times the highest concentration of drug A stock solution in MHB, mix well, and then add 50 μL to wells A1 to A11. Prepare 500 μL of 8 times the highest concentration of drug A stock solution in MHB, mix well, and then add 50 μL to well A12. Transfer 50 μL from wells A1 to A12 to wells A2 to A12, and mix thoroughly by pipetting at least three times. Then transfer 50 μL to the next column, repeating this operation until row G. Discard 50 μL from wells G1 to G12. Prepare 1 mL of 4-fold maximum concentration of drug B stock solution in MHB, mix thoroughly, and then add 50 μL to the last column A12 to H12. For serially diluted drug B (two-fold), transfer 50 μL from A12 to H12 to A11 to H11 wells, mix thoroughly by pipetting at least three times, and then transfer 50 μL to the next column. Repeat this process until the second column, discarding 50 μL from A2 to A12 wells. Add 50 μL of the prepared bacterial suspension to all wells. The final inoculum size is approximately 5 x 10⁻⁶. 5 CFU / mL. The inoculated 96-well plates were incubated at 37°C for 16-20 hours. MIC was read and FICI was calculated.

[0074] 2.4 Calculation and Judgment of FICI (Fraction inhibitory concentration index)

[0075] FICI = MIC of drug A in combination / MIC of drug A alone + MIC of drug B in combination / MIC of drug B alone. Among them, FICI ≤ 0.5 indicates synergistic effect, 0.5 < FICI ≤ 1.0 indicates additive effect, 1 < FICI ≤ 2.0 indicates no effect, and FICI > 2.0 indicates antagonistic effect.

[0076] 3. Result Analysis

[0077] 3.1 Determination Results of MIC of Pyrolin and Common Antibiotics against Pathogenic Bacteria

[0078] By determining the minimum inhibitory concentration (MIC) of tetracycline, ciprofloxacin, carbenicillin, tobramycin and pyrolin against 5 common pathogenic bacteria, the results are shown in Table 1. Among them, Klebsiella pneumoniae showed resistance to carbenicillin, and the measured MIC was higher than 256 μg / mL.

[0079] Table 1

[0080]

[0081] 3.2 Analysis of the Combined Effect of Pyrolin and Antibiotics

[0082] By determining the minimum inhibitory concentration (MIC) of each drug alone and in combination, calculating its fraction inhibitory concentration index (FICI), and simultaneously calculating the reduction multiple of MIC of antibiotic drugs in combination compared to their single use, the combined effect of pyrolin and antibiotics was evaluated. The following Table 2, Table 3 and Table 4 are the analysis of relevant experimental results:

[0083] Table 2 Inhibitory Effect of the Combination of Pyrolin and Antibiotics on Staphylococcus aureus

[0084]

[0085] Table 3 Inhibitory Effect of the Combination of Pyrolin and Antibiotics on Klebsiella pneumoniae

[0086]

[0087]

[0088] In the table, "-" represents not tested or no conclusion.

[0089] Table 4 Inhibitory Effect of the Combination of Pyrolin and Antibiotics on Enterococcus faecalis

[0090]

[0091] In the table, "-" indicates that no test was conducted or no conclusion was reached.

[0092] The above experimental results show that the antibacterial effects of the combination groups related to the antibacterial compositions of the present invention are greater than those of the antibiotic-only groups, while the minimum inhibitory concentration (MIC) required for antibiotics to inhibit the test bacteria is also reduced (2-16 times). Specifically, synergistic antibacterial effects were achieved when pyrolytic agent was combined with ciprofloxacin or tobramycin to inhibit Klebsiella pneumoniae. When pyrolytic agent was combined with ciprofloxacin to inhibit Staphylococcus aureus or Klebsiella pneumoniae, the antibiotic dosage was reduced by 4 times. When pyrolytic agent was combined with tetracycline to inhibit Klebsiella pneumoniae, the antibiotic dosage was reduced by 16 times. When pyrolytic agent was combined with tobramycin to inhibit Klebsiella pneumoniae, the antibiotic dosage was reduced by 8 times. This finding provides a new approach to solving the problem of antibiotic resistance.

[0093] The above-described embodiments are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of protection of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention.

Claims

1. An antibacterial composition comprising pyrophoric acid and an antibiotic; in, The antibiotic is selected from at least one of tetracycline, ciprofloxacin, and tobramycin.

2. The antibacterial composition according to claim 1, wherein, The mass ratio of the deer antler extract to the antibiotic is greater than or equal to 4.

3. The antibacterial composition according to claim 1, comprising a mixture of pyrimethamine and tetracycline, wherein, The mass ratio of pyrotropin to tetracycline is 20–5000:1, preferably 3000–5000:

1.

4. The antibacterial composition according to claim 1, comprising a mixture of pyrimethamine and ciprofloxacin, wherein, The mass ratio of pyrotropin to ciprofloxacin is 200–70000:1, preferably 500–1100:1 or 2000–2100:

1.

5. The antibacterial composition according to claim 1, comprising a mixture of pyrimethamine and tobramycin, wherein, The mass ratio of pyrophoric acid to tobramycin is 4–9000:1, preferably 900–1100:

1.

6. An antibacterial product comprising one or a combination of reagents, providing the antibacterial composition according to any one of claims 1 to 5.

7. The use of the antibacterial composition according to any one of claims 1 to 5 or the antibacterial product according to claim 6 in antibacterial activity for non-therapeutic purposes, wherein, The bacteria include at least one of Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis.

8. The use of the antibacterial composition according to any one of claims 1 to 5 in the preparation of antibacterial products, wherein, The bacteria include at least one of Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecalis.

9. The application according to claim 7 or 8, wherein, The antibacterial properties include at least one of the following: (a) Pyrodactylin combined with ciprofloxacin is used to inhibit Staphylococcus aureus; (b) Pyrodactylin combined with tetracycline for the inhibition of Klebsiella pneumoniae; (c) Pyrrocin combined with ciprofloxacin is used to inhibit Klebsiella pneumoniae; (d) Pyrodactylin combined with tobramycin was used to inhibit Klebsiella pneumoniae.

10. The application according to any one of claims 7 to 9, wherein, Pyrroside is used to reduce the minimum inhibitory concentration (MIC) of the antibiotic; preferably, pyrroside is used to reduce the MIC of the antibiotic by 4 to 16 times.

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