CN111658668A

CN111658668A - Functional antibacterial combined medicine and application

Info

Publication number: CN111658668A
Application number: CN201910172240.2A
Authority: CN
Inventors: 蒋兴宇; 王乐
Original assignee: National Center for Nanosccience and Technology China
Current assignee: National Center for Nanosccience and Technology China
Priority date: 2019-03-07
Filing date: 2019-03-07
Publication date: 2020-09-15
Anticipated expiration: 2039-03-07
Also published as: CN111658668B

Abstract

The invention provides a functional antibacterial combined medicament and application thereof, wherein the combined medicament comprises the following two components which are independently present: aminophenylboronic acid and chloroauric acid trihydrate, and wherein the combination drug is free of surfactants. The aminophenylboronic acid is a drug intermediate, the method for preparing the antibacterial gold nanoparticles by taking the aminophenylboronic acid as a reducing agent in the synthesis process is simple, the bacteria are not easy to induce to generate drug resistance, and the safety of the bacteria is high; the amino phenylboronic acid modified on the surface of the gold nanoparticle is combined with polysaccharide on the surface of bacteria through cis-diol, so that the permeability of the cell wall of the bacteria is changed, the bacteria die, and the bacteria have stronger bacterial targeting property; the aminophenylboronic acid and the chloroauric acid are stable and easy to store, the whole preparation process is simple and controllable, the prepared antibacterial gold nanoparticles have good dispersibility, and industrial production can be realized.

Description

Functional antibacterial combined medicine and application

Technical Field

The invention belongs to the field of medicines, and relates to a functional antibacterial combined medicine with an antibacterial effect and application thereof.

Background

Many diseases caused by bacterial infections have been one of the biggest global health problems, with millions of people dying from bacterial infections each year. Both gram-negative and gram-positive bacteria can cause many types of infections. For example, escherichia coli can induce gastrointestinal and urinary tract infections; klebsiella pneumoniae can cause liver abscess; staphylococcus aureus can cause skin infections. Antibiotics have been widely used to treat various types of infections since their first development in the 20 th century. However, widespread use and abuse of antibiotics rapidly lead to the development of bacterial resistance and the development of new social panic. Due to the increase in clinical and market demands, the development of new antibacterial agents is imminent. The nanometer material has the characteristics of large specific surface area, high surface functionalization degree and unique physical and chemical properties, and is widely applied to the aspects of medical appliances, safe cosmetics, burn dressings, water treatment, food preservation and the like. The gold nanoparticles have many unique properties on the premise of combining the above excellent properties, such as: good biocompatibility, multivalent effect, easy functionalization and fast synthesis method. Therefore, gold nanoparticles are a potential target for the development of novel antibiotics. Many studies have shown that gold nanoparticles themselves have no antibacterial activity, but show effective antibacterial activity after being modified by functional groups such as thiol, amine and phosphonic acid compounds. The amino phenylboronic acid is used as a drug intermediate, and is combined with peptidoglycan on the surface of bacteria through a boric acid group, so that the targeting property to the bacteria is improved, and the utilization rate is improved; the amino group in the aniline group has reducibility, so that chloroauric acid can be quickly reduced under the condition of no using a reducing agent, and the quick preparation of the gold nanoparticles is realized. In view of the above considerations, the preparation of gold nanoparticles as novel antimicrobial agents by reduction of aminophenylboronic acid is a suitable option.

Because of low infection risk, simple management procedure and capability of effectively improving the solubility and permeability of the drug, oral administration has become the most widely used administration route, and the preparation forms mainly comprise tablets, granules, capsules, oral liquid, dropping pills and the like. When orally administered, the drug is absorbed lymphatically, and passes through the gastrointestinal barrier, resulting in improved bioavailability of the drug, primarily in terms of various pharmacokinetic parameters including, but not limited to, decreased peak time of the drug, increased maximum concentration of the drug, and increased area under the curve. Scholars at home and abroad use the existing medicines to prepare oral antibacterial agents and explore some fields of application of the oral antibacterial agents in the aspect of bacterial infection. At present, the prior art discloses a nano sulfur-silver composite sol and a preparation method and application thereof, wherein sulfur powder is added into polyethylene glycol, and then silver nitrate is added to obtain the nano sulfur-silver composite sol. However, the preparation reaction of the method needs high temperature, the nano silver is unstable, and the method has strong toxicity to human bodies, the U.S. FDA has definitely prohibited the use of the nano silver in the medical aspect, and China CFDA also limits the nano silver in the medical field. Therefore, it is of great significance to search for antibacterial agents with superior biocompatibility and low toxicity. The prior art discloses a compound spiramycin nano-emulsion oral liquid and a preparation method thereof, the oral mode is utilized to obviously improve the bioavailability and the drug stability of spiramycin, but the oral liquid has wide particle size distribution and complex raw material components, and comprises the following steps: surfactant, cosurfactant, oil phase, spiramycin, trimethoprim and deionized water, wherein the effective components are not more than 10%. Therefore, the discovery of a novel antibacterial agent which has excellent antibacterial performance and high utilization rate of raw materials and can be conveniently taken orally has important significance. The prior art also discloses a liposome combined medicament produced by dissolution ultrafiltration, spray drying, molecular dispersion coating, hydration granulation and freeze drying, and provides a formula and a process for the molar ratio of each component of the liposome oral preparation, but the preparation process is complex, the components are various, the mutual influence among the components is not clear, only known medicaments can be used, and the generation of drug resistance cannot be avoided. Therefore, it is of great significance to explore oral antibacterial agents that can effectively treat multidrug resistant bacterial infections.

Disclosure of Invention

Therefore, the invention aims to overcome the defects in the prior art and provide a functional gold antibacterial combination drug with antibacterial effect and application thereof. The functional gold nanoparticles have broad-spectrum antibacterial activity, particularly aim at multidrug-resistant bacteria, and can be used for preparing novel effective antibacterial drugs. The medicine has simple components, can be quickly synthesized in the strong acid environment in the stomach, and is used by oral administration.

Before setting forth the context of the present invention, the terms used herein are defined as follows:

the term "ABA" means: aminophenylboronic acid.

The term "2 ABA" means: o-aminophenylboronic acid.

The term "3 ABA" means: m-aminophenylboronic acid.

The term "4 ABA" means: p-aminobenzoic acid.

The term "Au _4ABAe NPs" refers to: under the condition of pH 2, the p-aminobenzene boric acid reduces the gold nanoparticles formed by the chloroauric acid.

The term "Au _4ABAi NPs" refers to: mixing the aminobenzene boric acid and the chloroauric acid in the stomach in a one-to-one manner to form the gold nanoparticles.

In order to achieve the above object, a first aspect of the present invention provides a functional antibacterial combination drug comprising the following two components each independently present: aminophenylboronic acid and chloroauric acid trihydrate, and wherein the combination drug is free of surfactants.

The combination according to the first aspect of the invention, wherein the aminophenylboronic acid is selected from one or more of the following: p-aminobenzene boric acid, m-aminobenzene boric acid and o-aminobenzene boric acid.

The combination drug according to the first aspect of the invention, wherein the molar ratio of the aminophenylboronic acid to the chloroauric acid trihydrate in the combination drug is 1: 0.1-100, preferably 1: 0.2-5.

The combination according to the first aspect of the present invention, wherein the medicament is an oral medicament.

The combination drug according to the first aspect of the present invention, wherein the drug is a solid oral preparation or a liquid oral preparation.

Preferably, the solid oral dosage form is selected from one or more of the following: tablets, granules, capsules and pills; and/or

The liquid oral preparation is a solution combination in which two components, namely aminobenzene boric acid and chloroauric acid trihydrate, independently exist.

The combination drug according to the first aspect of the present invention, wherein the combination drug further comprises pharmaceutically acceptable excipients.

Preferably, the pharmaceutically acceptable excipients are selected from one or more of the following: fillers, disintegrants and lubricants.

The second aspect of the invention provides the use of the functional antibacterial combination drug of the first aspect for preparing an antibacterial product;

preferably, the bacteria are selected from escherichia coli and/or pseudomonas aeruginosa.

Aiming at the infection problem of multidrug resistant bacteria, the invention provides a method for preparing a gold nanoparticle antibacterial agent by molecular reduction chloroauric acid, which has low cost, good biological safety and good curative effect on the multidrug resistant bacteria, and can be orally taken to treat abdominal infection. The gold nanoparticles destroy the cell wall of bacteria by targeting polysaccharide on the surface of the bacteria, so that the permeability of cell membranes is increased, and the bacteria die. In this work, the inventor prepares the functional gold nanoparticle antibacterial agent by reducing chloroauric acid through aminobenzeneboronic acid (ABA ortho-2 ABA, meta-3 ABA and para-4 ABA), and the functional gold nanoparticle antibacterial agent has good antibacterial effect on sensitive strains of gram-negative bacteria and clinically-separated multidrug-resistant strains. The aminophenylboronic acid contains functional groups of a boric acid group and an aniline group, the aniline group has reducibility, chloroauric acid can be directly reduced into gold nanoparticles under the condition of not using a reducing agent, and ligand molecules are stably connected to the gold nanoparticles; the boric acid group can target polysaccharide on the surface of bacteria, and the permeability of cell membranes is increased by destroying the cell walls of the bacteria, so that the bacteria die. In the process of oral administration, the aminobenzene boric acid and the chloroauric acid in the stomach can quickly form antibacterial gold nanoparticles, and the antibacterial gold nanoparticles can reach the whole body through the gastrointestinal tract barrier via blood circulation, so that the bioavailability of the medicine is improved. Compared with the existing method for synthesizing the gold nano-particles, the gold nano-antibacterial particles have stability to extreme changes of temperature and pH. The synthesized antibacterial gold nanoparticles have excellent biocompatibility due to negative charge on the surfaces. The schematic diagram of the design of the present invention is shown in fig. 1. The feasibility of oral treatment of abdominal infections was further demonstrated by a mouse infection model.

In order to achieve the purpose, the invention adopts the following technical scheme:

according to the invention, small molecule reduced gold nanoparticles are provided as an antibacterial agent, wherein the small molecule is a derivative of phenylboronic acid with higher biological safety, for example, a substituent on a benzene ring is an amino group. The substituent positions are ortho, meta and para.

According to the synthesis method for preparing the gold nanoparticle antibacterial agent by reducing chloroauric acid with aminophenylboronic acid, provided by the invention, the ratio of chloroauric acid to aminophenylboronic acid is 1:5-5:1 (namely, molar mass ratio) when the gold nanoparticles are synthesized. The pH value of the synthetic condition is 2 to 12, preferably the pH value of the pH value is 2 to 7, and in order to better simulate the strong acid environment of the stomach, the pH value of the pH value is more preferably 2. The average particle diameter of the gold nanoparticles with the antibacterial effect is below 50 nm. More preferably 2-10 nm.

The selected aminophenylboronic acid contains two functional groups, namely a boric acid group and an aniline group, and the aniline group has reducibility, so that chloroauric acid can be directly reduced into gold nanoparticles under the condition of not using a reducing agent, and ligand molecules are stably connected to the gold nanoparticles; the boric acid group can target the polysaccharide on the surface of bacteria, and the permeability of cell membranes is increased by destroying the cell walls of the bacteria, so that the bacteria die, and the antibacterial effect is realized.

The gold nanoparticles reduced by the aminobenzene boric acid prepared by the method have excellent antibacterial property and can resist multi-drug resistant bacteria. In the process of oral administration, the aminobenzene boric acid and the chloroauric acid in the stomach can quickly form antibacterial gold nanoparticles, and the antibacterial gold nanoparticles can reach the whole body through the gastrointestinal tract barrier via blood circulation, so that the bioavailability of the medicine is improved. Compared with the existing method for synthesizing the gold nano-particles, the gold nano-antibacterial particles have stability to extreme changes of temperature and pH. The synthesized antibacterial gold nanoparticles have excellent biocompatibility due to negative charge on the surfaces. Can be used for preparing tablets, oral liquid and capsules, and is an excellent antibacterial agent.

The functional antibacterial combination drug of the present invention can have the following beneficial effects, but is not limited to:

1. the aminophenylboronic acid is a drug intermediate, the method for preparing the antibacterial gold nanoparticles by taking the aminophenylboronic acid as a reducing agent in the synthesis process is simple, the drug resistance of bacteria can not be induced, and the safety of organisms is high;

2. the amino phenylboronic acid modified on the surface of the gold nanoparticle is combined with polysaccharide on the surface of bacteria through cis-diol, so that the permeability of the cell wall of the bacteria is changed, the bacteria die, and the bacteria have stronger bacterial targeting property;

3. the aminophenylboronic acid and the chloroauric acid are stable and easy to store, the whole preparation process is simple and controllable, the prepared antibacterial gold nanoparticles have good dispersibility, and industrial production can be realized; the synthesis method is convenient and fast, can not be limited by temperature, pH value and rotating speed, and can be orally used. Compared with the prepared gold nanoparticle solution, the reagent stored by the raw materials is more stable, the coagulation phenomenon can not occur, and the surfactant can not be used, so that the components are purer.

Drawings

Embodiments of the invention are described in detail below with reference to the attached drawing figures, wherein:

FIG. 1 shows the schematic diagram of the preparation of antibacterial gold nanoparticles by reduction of chloroauric acid with synthetic aminophenylboronic acid and oral administration for treating abdominal infection.

Fig. 2 shows the morphology characterization and antibacterial properties of the aminobenzoic acid-modified gold nanoparticles of example 1.

Fig. 3 shows the morphology characterization and antibacterial properties of the m-aminobenzoic acid modified gold nanoparticles of example 2.

Fig. 4 shows the morphology characterization and antibacterial properties of the orthoaminophenylboronic acid-modified gold nanoparticles of example 3.

Fig. 5 shows the morphological characterization and antibacterial performance of the aminobenzoic acid modified gold nanoparticles in example 4 under different pH values.

Fig. 6 shows the antibacterial mechanism characterization of the aminobenzoic acid modified gold nanoparticles at pH 2 in example 4.

Figure 7 shows the aminobenzoic acid, chloroauric acid and gold nanoparticles and biosafety characterization of example 4.

Fig. 8 shows the metabolism of the oral gold nanoparticles of aminobenzeneboronic acid-reduced chloroauric acid in blood and different organs over time in example 5.

Figure 9 shows the therapeutic effect of the oral administration of gold nanoparticles to mice for abdominal infection and mouse weight monitoring of aminobenzene boronic acid reduced chloroauric acid of example 5.

Detailed Description

The invention is further illustrated by the following specific examples, which, however, are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.

This section generally describes the materials used in the testing of the present invention, as well as the testing methods. Although many materials and methods of operation are known in the art for the purpose of carrying out the invention, the invention is nevertheless described herein in as detail as possible. It will be apparent to those skilled in the art that the materials and methods of operation used in the present invention are well within the skill of the art, provided that they are not specifically illustrated.

The reagents and instrumentation used in the following examples are as follows: reagent:

chloroauric acid trihydrate, available from national pharmaceutical group chemical reagents, ltd;

sulfanilic acid, metasulfanilic acid, anthranilic acid, purchased from Sigma;

tween 80, purchased from alatin biotechnology limited;

dialysis bags, purchased from Solarbio;

filters, purchased from Millipore.

The instrument comprises the following steps:

transmission electron microscope, available from FEI company, USA, model Tecnai G220S-TWIN;

a microplate reader, available from Tecan, model Tecan infinite M200;

UV-vis absorption spectrum, purchased from Shimadzu, Japan, model UV 2450.

Figure 1 is a flow chart of the synthesis and therapeutic use. The following is illustrated by specific examples:

example 1

This example is intended to illustrate the preparation of functional gold nanoparticles according to the invention.

The method comprises the following steps:

(1) in a round-bottomed flask, 0.05 mmol of chloroauric acid trihydrate (molecular weight 393.83, national pharmaceutical group chemicals, Ltd.) and 30 mg of tween 80 were added to 10 ml of deionized water. Under different reaction conditions (rotation speed: 1000 rpm, 500 rpm and 100 rpm; temperature: 0 ℃ and 25 ℃), 1 ml of an aqueous solution containing 0.05 mmol of sulfanilic acid (4ABA molecular weight 136.941, Sigma) was added dropwise, the color of the solution in the bottle immediately turned brown, and the reaction was maintained for another 2 hours.

(2) The obtained gold nanoparticles reduced with p-aminobenzoic acid were dialyzed with a dialysis bag (14kDa MW cut-off, Solarbio) for 24 hours to remove untreated chemicals. The nanoparticles were filter sterilized through a 0.22 micron filter (Millipore) and stored in a 4 ℃ freezer for use. Morphology characterization of the gold particles was performed by transmission electron microscopy (TEM, Tecnai G220S-TWIN, FEI company, USA) and the observations are shown in FIG. 2A. The results of the ultraviolet-visible absorption spectrum (UV-Vis) test of the sample are shown in fig. 2B.

(3) Escherichia coli (E.coli) and multidrug resistant Escherichia coli (MDR E.coli) are cultured in liquid bacteria culture medium, gold nanoparticles are diluted by 2-128 times and added into the culture medium inoculated with bacteria respectively, and the inoculation concentration is 1 × 10⁴CFU/mL, turbidity of bacterial suspension at 600nm (OD) after 12 hours and 24 hours of incubation at 37 ℃ respectively_600nm) The antibacterial activity of the gold nanoparticles was analyzed by the optical density of (2C), and the results are shown in fig. 2C.

Example 2

The method comprises the following steps:

(1) in a round-bottomed flask, 0.05 mmol of chloroauric acid trihydrate (molecular weight 393.83, national pharmaceutical group chemicals, Ltd.) and 30 mg of tween 80 were added to 10 ml of deionized water. Under different reaction conditions (rotation speed: 1000 rpm, 500 rpm and 100 rpm; temperature: 0 ℃ and 25 ℃), 1 ml of an aqueous solution containing 0.05 mmol of m-aminobenzoic acid (3ABA molecular weight 136.941, Sigma) was added dropwise, the color of the solution in the bottle immediately turned brown, and the reaction was maintained for another 2 hours.

(2) The processing and particle characterization of the m-aminobenzoic acid reduced gold nanoparticles were the same as in example 1, with the results shown in fig. 3A-B.

(3) The characterization of antibacterial activity of the gold nanoparticles reduced with m-aminobenzoic acid was the same as that of example 1, and the results are shown in fig. 3C.

Example 3

The method comprises the following steps:

(1) in a round-bottomed flask, 0.05 mmol of chloroauric acid trihydrate (molecular weight 393.83, national pharmaceutical group chemicals, Ltd.) and 30 mg of tween 80 were added to 10 ml of deionized water. Under different reaction conditions (rotation speed: 1000 rpm, 500 rpm and 100 rpm; temperature: 0 ℃ and 25 ℃), 1 ml of an aqueous solution containing 0.05 mmol of o-aminobenzeneboronic acid (2ABA molecular weight 136.941, Sigma) was added dropwise, the color of the solution in the bottle immediately turned brown, and the reaction was maintained for another 2 hours.

(2) The treatment and particle characterization of ortho-aminobenzeneboronic acid reduced gold nanoparticles were the same as in example 1, with the results shown in fig. 4A-B.

(3) The characterization of antibacterial activity of the orthoaminophenylboronic acid-reduced gold nanoparticles was the same as in example 1, and the results are shown in fig. 4C.

Example 4

This example is used to illustrate the preparation method and performance evaluation of functional gold nanoparticles of the present invention.

The method comprises the following steps:

(1) using hydrochloric acid to prepare 10 ml of solutions with pH values of 2 and 4 respectively; preparing 10 ml of solutions with pH values of 10 and 12 respectively by using sodium hydroxide; 10 ml of deionized water was used as the pH 7 solution.

(2) P-aminobenzeneboronic acid was added to each of the solutions of different pH values to prepare 1 ml of a solution containing 0.05 mmol of aminobenzeneboronic acid.

(3) The prepared solution of the p-aminobenzoic acid with different pH values is respectively added into 0.05 millimole of chloroauric acid trihydrate (molecular weight 393.83, national drug group chemical reagent company limited) solution, the solution in the bottle is shaken for 2 to 3 times, the color of the solution in the bottle is immediately changed into brown, and then the synthesized gold nano-particles under different pH values can be obtained. The reaction feeding sequence and the feeding mode have no influence on the product. (4) The treatment and particle characterization of gold nanoparticles reduced by p-aminobenzoic acid in different acid-base environments were the same as in example 1, and the results are shown in fig. 5A-B.

(5) The characterization of the antibacterial activity of the gold nanoparticles reduced by aminobenzoic acid in different acid-base environments is the same as that of example 1, and compared with levofloxacin, the antibacterial effect of the gold nanoparticles is more effective in treating multidrug-resistant bacteria, and the results are shown in fig. 5C-D. The stomach is a strong acid environment, and in order to better simulate the in vivo environment, the inventor uses gold nanoparticles (Au _ ABAe NPs) reduced by aminobenzoic acid under the condition of pH 2 to research the antibacterial mechanism and biological safety. The inventors shaken bacteria (sensitive strains of escherichia coli (e.coli) and pseudomonas aeruginosa (P.a) and multidrug resistant strains (MDR e.coli, MDR P.a)) with different concentrations of gold nanoparticles on a shaker at 260 rpm for 4 hours. The bacteria were centrifuged, fixed, dehydrated, and sliced into ultrathin sections, which were observed by scanning and transmission electron microscopy, and the results are shown in FIGS. 6A-B.

(6) For further clinical applications, the inventors measured the samples at 540nm (OD) by a microplate reader (Tecan infinite M200)_540nm) The densitometry of (A) was conducted to test gold nanoparticles of various concentrations and raw materials (sulfanilic acid (4 ABA)) and chloroauric acid (HAuCl) for synthesizing the gold nanoparticles₄) For example) using saline as a negative control and water as a positive control, the results are shown in fig. 7A. The cytotoxicity of mouse fibroblast (3T3) cells was evaluated in vitro by testing their viability under different sample treatments, and the results are shown in fig. 7B.

Example 5

The method comprises the following steps:

(1) p-aminobenzoic acid (4ABA) was prepared as a 0.05 mmol solution, and chloroauric acid trihydrate was prepared as a 0.05 mmol solution. (2) Subjecting aminobenzoic acid (4ABA) and chloroauric acid (HAuCl)₄) The two components are respectively infused into the body of a mouse by a gastric perfusion mode according to different volume ratios so as to explore the synthesis and metabolism conditions of the two components in the body, and the metabolism condition of the gold nanoparticles synthesized in vitro is taken as a reference when the pH value is 2 in example 4. Mice were randomized into 4 groups (n-5) for gastric lavage, group 1(4ABA and HAuCl)₄The intragastric volume was 150 microliters: 50 microliters (3: 1)); group 2(4ABA and HAuCl)₄The intragastric volume is 100 microliters: 100 microliters (1: 1) Au _4ABAi NPs); group 3(4ABA and HAuCl)₄The intragastric volume was 50 microliters: 150 microliters (1: 3)); group 4 (gold nanoparticles (Au — 4ABAe NPs) synthesized in vitro in a simulated gastric environment, which were the gold nanoparticles synthesized in example 4, the raw material ratio was 0.05 mmol of sulfanilic acid and 0.05 mmol of chloroauric acid at pH 2.

(3) Periorbital bleeds and dissections were performed on the gavage mice at different time points (1, 2, 6, 12, 18, 24, 48 and 72 hours) to obtain the stomach, liver, spleen and kidney; blood and organs were subjected to nitrolysis with aqua regia (nitric acid: hydrochloric acid 1:3), and the content of gold nanoparticles in each organ was analyzed using an inductively coupled plasma analyzer (ICP, iCAP 6300, Thermo Scientific, USA). The results are shown in FIGS. 8A-D, with different volume ratios of 4ABA and HAuCl₄Reaches a maximum in the initial phase of synthesis in the stomach, demonstrating the feasibility of oral administration; the plasma concentration-time curve shows that the gold atom concentration in blood increases rapidly 6 hours after intragastric administration and decreases within 24 hours. The gold concentration in the kidney and liver dropped to essentially 0 after 72 hours, indicating a high clearance efficiency. Group 2 showed the most similar trend compared to the levels of each organ in Au _4ABAe NPs.

(4) The antibacterial effect of oral gold nanoparticles in a mouse acute peritonitis model was explored using the ratio of group 2. Coli andinjection of multidrug resistant strain (MDR E. coli) into abdominal cavity of mouse at injection concentration of 1 × 10⁶CFU/mL. After 1 and 6 hours of infection, 5 millimoles 4ABA per liter and 5 millimoles HAuCl per liter₄Gavage was performed at 100 μ l each, sterile physiological saline as a negative control, levofloxacin as a positive control, and the mortality and body weight of mice were monitored as shown in fig. 9. Shown, illustrate 4ABA and HAuCl₄When the medicine is taken orally, the effect of treating the abdominal cavity infection caused by multi-drug resistant bacteria is better and more obvious than that of commonly used antibiotic levofloxacin.

Although the present invention has been described to a certain extent, it is apparent that appropriate changes in the respective conditions may be made without departing from the spirit and scope of the present invention. It is to be understood that the invention is not limited to the described embodiments, but is to be accorded the scope consistent with the claims, including equivalents of each element described.

Claims

1. A functional antibacterial drug combination, which is characterized by comprising the following two components independently existing in each case: aminophenylboronic acid and chloroauric acid trihydrate, and wherein the combination drug is free of surfactants.

2. The combination as claimed in claim 1, wherein the aminophenylboronic acid is selected from one or more of the following: p-aminobenzene boric acid, m-aminobenzene boric acid and o-aminobenzene boric acid.

3. The combination drug according to claim 1 or 2, wherein the molar ratio of the aminophenylboronic acid to the chloroauric acid trihydrate in the combination drug is 1: 0.1-100, preferably 1: 0.2-5.

4. The combination as claimed in any one of claims 1 to 3, wherein the medicament is an oral medicament.

5. The combination according to any one of claims 1 to 4, wherein the medicament is a solid oral formulation or a liquid oral formulation.

6. The combination as claimed in claim 5, wherein:

the solid oral dosage form is selected from one or more of the following: tablets, granules, capsules and pills; and/or

7. The combination as claimed in any one of claims 1 to 5, wherein the combination further comprises pharmaceutically acceptable excipients.

8. The combination as claimed in claim 7, wherein the pharmaceutically acceptable excipients are selected from one or more of the following: fillers, disintegrants and lubricants.

9. Use of the functional antibacterial combination drug of any one of claims 1 to 8 for the preparation of an antibacterial product.

10. Use according to claim 9, wherein the bacteria are selected from escherichia coli and/or pseudomonas aeruginosa.