CN111658668B - Functional antibacterial combination medicine and application - Google Patents
Functional antibacterial combination medicine and application Download PDFInfo
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- CN111658668B CN111658668B CN201910172240.2A CN201910172240A CN111658668B CN 111658668 B CN111658668 B CN 111658668B CN 201910172240 A CN201910172240 A CN 201910172240A CN 111658668 B CN111658668 B CN 111658668B
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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Abstract
The invention provides a functional antibacterial combination drug and application thereof, wherein the combination drug comprises the following two components which independently exist: aminophenylboronic acid and chloroauric acid trihydrate, and the combination is free of surfactants. The aminobenzene boric acid is a drug intermediate, and the method for preparing the antibacterial gold nanoparticles by taking the aminobenzene boric acid as a reducing agent in the synthesis process is simple, is not easy to induce bacteria to generate drug resistance, and has higher biological safety; the amino phenylboronic acid modified on the surface of the gold nanoparticle changes the permeability of the bacterial cell wall by combining cis diol with polysaccharide on the surface of the bacteria, so that the bacteria die and have stronger bacterial targeting; the aminophenylboric acid and the chloroauric acid are stable and easy to store, the whole preparation process is simple and controllable, and the prepared antibacterial gold nanoparticles are good in dispersibility and can realize industrial production.
Description
Technical Field
The invention belongs to the field of medicines, and relates to a functional antibacterial combination medicine with an antibacterial effect and application thereof.
Background
Many diseases caused by bacterial infections have been one of the biggest health problems worldwide, with millions of people dying from bacterial infections each year. Both gram-negative and gram-positive bacteria can cause multiple types of infection. For example, E.coli can induce gastrointestinal and urinary tract infections; klebsiella pneumoniae can cause liver abscess; staphylococcus aureus causes skin infections. Antibiotics have been widely used for the treatment of various infections since the first development in the 20 th century. However, widespread use and abuse of antibiotics rapidly leads to the development of bacterial resistance and causes new social panic. Due to the growing clinical and market demands, the development of new antibacterial agents is urgent. The nanometer material has the characteristics of large specific surface area, high surface functionalization degree and unique physical and chemical properties, and has been widely applied to the aspects of medical appliances, safe cosmetics, burn dressing, water treatment, food preservation and the like. Gold nanoparticles have many unique properties on the premise of combining the excellent properties, such as: good biocompatibility, multivalent effect, easy functionalization and rapid synthesis method. Therefore, gold nanoparticles are potential targets for the development of novel antibiotics. Many studies have shown that gold nanoparticles themselves do not have antimicrobial activity, but exhibit potent antimicrobial activity after modification by functional groups such as thiol, amine, and phosphonic acid compounds. Amino phenylboronic acid is taken as a drug intermediate, and is combined with peptidoglycan on the surface of bacteria through boric acid groups, so that the targeting property of bacteria is improved, and the utilization rate is improved; the amino in the anilino group has reducibility, and chloroauric acid can be reduced rapidly under the condition that a reducing agent is not used any more, so that the gold nanoparticles can be prepared rapidly. Based on the above considerations, the reduction of gold nanoparticles by aminophenylboronic acid is a suitable choice for the preparation of novel antibacterial agents.
Because of low risk of infection, simple management procedure and capability of effectively improving the solubility and permeability of the medicine, oral administration has become the most widely used administration route, and the preparation forms mainly comprise tablets, granules, capsules, oral liquid, dripping pills and the like. When taken orally, the drug can be absorbed through lymph and pass through gastrointestinal barrier, so that the bioavailability of the drug is improved, and the bioavailability is mainly expressed in various pharmacokinetic parameters including but not limited to the reduction of the peak time of the drug, the increase of the maximum concentration of the drug, the increase of the area under the curve and the like. The scholars at home and abroad use the existing medicines to prepare oral antibacterial agents and the application fields of the oral antibacterial agents in bacterial infection are explored. At present, the prior art discloses a nano sulfur-silver composite sol, 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 method needs high temperature and the nano silver is unstable, has strong toxicity to human body, and the use of the nano silver in medical treatment is definitely forbidden by the FDA in the United states, and the CFDA in China also limits the nano silver in the medical field. Therefore, it is of great importance to explore antibacterial agents with superior biocompatibility and low toxicity. The prior art discloses a compound spiramycin nanoemulsion oral liquid and a preparation method thereof, which remarkably improves the bioavailability and the drug stability of spiramycin by using an oral mode, but the oral liquid has wide particle size distribution and complex raw material components, and comprises the following components: surfactant, cosurfactant, oil phase, spiramycin, trimethoprim and deionized water, wherein the effective component is not more than 10%. Therefore, the novel antibacterial agent which has excellent antibacterial performance and high raw material utilization rate and can be conveniently used by oral administration is explored and has important significance. The prior art also discloses a liposome combined medicament produced by dissolving ultrafiltration, spray drying, molecular dispersion coating, hydration granulating and freeze drying, and provides a formula and a process for the mole ratio of raw materials 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, and only known medicaments can be used, so that the generation of drug resistance cannot be avoided. Therefore, it is of great importance to explore oral antibacterial agents that can effectively treat multi-drug resistant bacterial infections.
Disclosure of Invention
Therefore, the invention aims to overcome the defects in the prior art and provide a functional gold functional antibacterial combination medicament with antibacterial effect and application thereof. The functional gold nanoparticles have broad-spectrum antibacterial activity, particularly for multi-drug resistant bacteria, and can be used for preparing novel effective antibacterial drugs. The medicine has simple components, can be rapidly synthesized in the strong acid environment in the stomach, and can be used by oral administration.
Before setting forth the present disclosure, the terms used herein are defined as follows:
the term "ABA" refers to: amino phenylboronic acid.
The term "2ABA" refers to: o-aminophenylboronic acid.
The term "3ABA" refers to: m-aminophenylboronic acid.
The term "4ABA" refers to: para-aminophenylboronic acid.
The term "au_4ABAe NPs" refers to: gold nanoparticles formed by reduction of chloroauric acid with para-aminophenylboronic acid at ph=2.
The term "au_4ABAi NPs" refers to: the para-aminophenylboric acid and the chloroauric acid are mixed in the stomach according to a ratio to form gold nanoparticles.
To achieve the above object, a first aspect of the present invention provides a functional antibacterial combination comprising, independently of each other, the following two components: aminophenylboronic acid and chloroauric acid trihydrate, and the combination is free of surfactants.
The combination according to the first aspect of the present invention, wherein the aminophenylboronic acid is selected from one or more of the following: para-aminophenylboronic acid, meta-aminophenylboronic acid, ortho-aminophenylboronic acid.
The combination according to the first aspect of the present invention, wherein the molar ratio of the aminophenylboronic acid to chloroauric acid trihydrate is 1:0.1 to 100, preferably 1:0.2 to 5.
The combination according to the first aspect of the invention, wherein the medicament is an oral medicament.
The combination according to the first aspect of the present invention, wherein the pharmaceutical solid oral preparation or the liquid oral preparation.
Preferably, the solid oral dosage form is selected from one or more of the following: tablets, granules, capsules and dripping pills; and/or
The liquid oral preparation is a solution combination of two components of aminophenylboric acid and chloroauric acid trihydrate which exist independently.
The combination according to the first aspect of the present invention, wherein the combination further comprises pharmaceutically acceptable excipients.
Preferably, the pharmaceutically acceptable excipients are selected from one or more of the following: fillers, disintegrants and lubricants.
A second aspect of the present invention provides the use of a functional antibacterial combination according to the first aspect for the preparation of an antibacterial product;
preferably, the bacteria are selected from E.coli and/or P.aeruginosa.
Aiming at the problem of infection of multi-drug resistant bacteria, the invention provides a method for preparing gold nanoparticle antibacterial agent by molecular reduction chloroauric acid with low cost, good biological safety and good curative effect on multi-drug resistant bacteria, and can be orally used for treating abdominal infection. The gold nanoparticles destroy bacterial cell walls by targeting polysaccharides on the surfaces of bacteria so as to increase the permeability of cell membranes, and the bacteria die. In the work, the inventor prepares the functional gold nanoparticle antibacterial agent by reducing chloroauric acid by aminobenzene boric acid (ABA ortho-position 2ABA, meta-position 3ABA and para-position 4 ABA), and has good antibacterial effect on sensitive strains of gram-negative bacteria and clinically separated multi-drug resistant strains. The aminophenylboric acid contains two functional groups of a boric acid group and an anilino group, the anilino 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 groups can target polysaccharides on the surface of bacteria, and the bacterial death is caused by destroying the cell wall of the bacteria and further increasing the permeability of the cell membrane. In the oral use process, antibacterial gold nanoparticles can be rapidly formed in the stomach by the aminophenylboronic acid and the chloroauric acid, and the antibacterial gold nanoparticles reach the whole body through the gastrointestinal barrier and blood circulation, so that the bioavailability of the medicine is improved. Compared with the existing method for synthesizing gold nano-particles, the gold nano-antibacterial particles have stability to extreme changes of temperature and pH. The surface of the synthesized antibacterial gold nanoparticle is negatively charged, so that the antibacterial gold nanoparticle has excellent biocompatibility. A schematic diagram of the design of the present invention is shown in fig. 1. The feasibility of treating intraperitoneal infections by oral administration was further verified 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 antibacterial agents, wherein the small molecules are derivatives of phenylboronic acid with higher biological safety, and the substituent on the benzene ring is amino. The substituent positions are ortho, meta and para.
According to the synthesis method of the antibacterial agent for preparing gold nanoparticles by reducing chloroauric acid with aminophenylboronic acid, which is provided by the invention, the ratio of chloroauric acid to aminophenylboronic acid (namely the molar mass ratio) is 1:5-5:1 during the synthesis of gold nanoparticles. The pH value of the synthesis condition is 2 to 12, preferably 2 to 7, and more preferably 2 in order to better simulate the strong acid environment of the stomach. The average particle size of the gold nanoparticles with antibacterial effect is below 50 nm. More preferably 2-10nm.
The selected aminophenylboronic acid contains two functional groups of a boric acid group and an anilino group, the anilino 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 bacterial death is caused by destroying the cell wall of the bacteria and further increasing the permeability of cell membranes, so that the antibacterial effect is realized.
The gold nanoparticle reduced by the aminophenylboronic acid prepared by the method has excellent antibacterial property and can resist multi-drug resistant bacteria. In the oral use process, antibacterial gold nanoparticles can be rapidly formed in the stomach by the aminophenylboronic acid and the chloroauric acid, and the antibacterial gold nanoparticles reach the whole body through the gastrointestinal barrier and blood circulation, so that the bioavailability of the medicine is improved. Compared with the existing method for synthesizing gold nano-particles, the gold nano-antibacterial particles have stability to extreme changes of temperature and pH. The surface of the synthesized antibacterial gold nanoparticle is negatively charged, so that the antibacterial gold nanoparticle has excellent biocompatibility. Can be used for preparing tablets, oral liquid and capsules, and is an extremely excellent antibacterial agent.
The functional antibacterial combination of the present invention may have, but is not limited to, the following beneficial effects:
1. the aminobenzene boric acid is a drug intermediate, and the method for preparing the antibacterial gold nanoparticles by taking the aminobenzene boric acid as a reducing agent in the synthesis process is simple, can not induce bacteria to generate drug resistance, and has higher biological safety;
2. the amino phenylboronic acid modified on the surface of the gold nanoparticle changes the permeability of the bacterial cell wall by combining cis diol with polysaccharide on the surface of the bacteria, so that the bacteria die and have stronger bacterial targeting;
3. the aminophenylboric 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, can not be limited by temperature, pH value and rotating speed, and can be orally taken. Compared with the prepared gold nanoparticle solution, the reagent stored by the raw materials is more stable, the phenomenon of coagulation can not occur, the surfactant can not be used, and the components are purer.
Drawings
Embodiments of the present invention are described in detail below with reference to the attached drawing figures, wherein:
FIG. 1 shows a schematic diagram of the antibacterial gold nanoparticles prepared by synthesizing aminophenylboronic acid-reduced chloroauric acid and treating abdominal infection by oral administration.
Figure 2 shows the morphological characterization of the para-aminophenylboronic acid modified gold nanoparticles of example 1 and their antimicrobial properties.
Figure 3 shows the morphological characterization of the m-aminophenylboronic acid modified gold nanoparticles of example 2 and their antibacterial properties.
Figure 4 shows the morphological characterization of the gold nanoparticles modified with anthranilic acid of example 3 and their antibacterial properties.
FIG. 5 shows the morphology characterization and the antibacterial performance of the para-aminophenylboronic acid modified gold nanoparticles of example 4 under different pH values.
FIG. 6 shows the characterization of the antibacterial mechanism of para-aminophenylboronic acid modified gold nanoparticles at pH 2 in example 4.
FIG. 7 shows the para-aminophenylboronic acid, chloroauric acid and gold nanoparticles and biosafety characterization of example 4.
FIG. 8 shows the metabolism of example 5 aminophenylboronic acid reduced chloroauric acid orally administered gold nanoparticles in blood and different organs over time.
Figure 9 shows the therapeutic effect of oral administration of gold nanoparticles of example 5 aminophenylboronic acid reduced chloroauric acid on celiac infection in mice and weight monitoring of mice.
Detailed Description
The invention is further illustrated by the following specific examples, which are, however, to be understood only for the purpose of more detailed description and are not to be construed as limiting the invention in any way.
This section generally describes the materials used in the test of the present invention and the test method. Although many materials and methods of operation are known in the art for accomplishing the objectives of the present invention, the present invention will be described in as much detail herein. It will be apparent to those skilled in the art that in this context, the materials and methods of operation used in the present invention are well known in the art, if not specifically described.
The reagents and instrumentation used in the following examples were as follows: reagent:
chloroauric acid, available from national pharmaceutical group chemical company, inc;
para-aminophenylboronic acid, meta-aminophenylboronic acid, ortho-aminophenylboronic acid, purchased from Sigma;
dialysis bags, purchased from Solarbio;
filters, available from Millipore.
Instrument:
transmission electron microscopy, available from FEI company, USA, model Tecnai G2 20S-TWIN;
the enzyme-labeled instrument is purchased from Tecan, model Tecan infinite M200;
ultraviolet-visible absorption spectra, available from Shimadzu, japan, model UV2450.
FIG. 1 is a flow chart of a synthetic method and therapeutic use. The following is described by way of specific examples:
example 1
This example is used to illustrate the preparation method of the functional gold nanoparticles of the present invention.
The method comprises the following steps:
(1) In a round bottom flask, 0.05 mmol of chloroauric acid trihydrate (molecular weight 393.83, national pharmaceutical chemicals limited) 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 ℃ C.), 1 ml of an aqueous solution containing 0.05 mmol of p-aminophenylboronic acid (4 ABA molecular weight: 136.941, sigma) was added dropwise, and the color of the solution in the bottle immediately turned brown, and the reaction condition was maintained for another 2 hours.
(2) The obtained para-aminophenylboronic acid reduced gold nanoparticles were dialyzed with a dialysis bag (14 kDa 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 degree celsius refrigerator for use. The morphology of the gold particles was characterized by transmission electron microscopy (TEM, tecnai G2 20S-TWIN, FEI company, USA) and the observations are shown in FIG. 2A. The ultraviolet-visible absorption spectrum (UV-Vis) test results of the sample are shown in fig. 2B.
(3) Coli (e.coli) and multidrug resistant escherichia coli (MDR e.coli) were cultured in liquid bacterial media. Diluting gold nanoparticles by 2-128 times, adding into culture medium containing bacteria, and inoculating at concentration of 1×10 4 CFU/mL, bacterial suspensions were tested for turbidity at 600nm (OD after incubation at 37℃for 12 hours and 24 hours, respectively 600nm ) The antibacterial activity of the gold nanoparticles was analyzed and the results are shown in fig. 2C.
Example 2
This example is used to illustrate the preparation method of the functional gold nanoparticles of the present invention.
The method comprises the following steps:
(1) In a round bottom flask, 0.05 mmol of chloroauric acid trihydrate (molecular weight 393.83, national pharmaceutical chemicals limited) 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 ℃ C.), 1 ml of an aqueous solution containing 0.05 mmol of m-aminophenylboronic acid (3 ABA molecular weight: 136.941, sigma) was added dropwise, and the color of the solution in the bottle immediately turned brown, and the reaction condition was maintained for another 2 hours.
(2) The treatment and particle characterization of the metaaminophenylboronic acid reduced gold nanoparticles were the same as in example 1, and the results are shown in fig. 3A-B.
(3) The antibacterial activity characterization of the meta-aminophenylboronic acid reduced gold nanoparticles was the same as in example 1, and the results are shown in fig. 3C.
Example 3
This example is used to illustrate the preparation method of the functional gold nanoparticles of the present invention.
The method comprises the following steps:
(1) In a round bottom flask, 0.05 mmol of chloroauric acid trihydrate (molecular weight 393.83, national pharmaceutical chemicals limited) 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-aminophenylboronic acid (2 ABA molecular weight 136.941, sigma) was added dropwise, the color of the solution in the bottle immediately turned brown, and the reaction conditions were maintained for a further 2 hours.
(2) The treatment and particle characterization of the anthranilic acid-reduced gold nanoparticles were the same as in example 1, and the results are shown in fig. 4A-B.
(3) The antibacterial activity characterization of the anthranilic acid-reduced gold nanoparticles was the same as in example 1, and the results are shown in fig. 4C.
Example 4
The embodiment is used for explaining the preparation method and performance evaluation of the functional gold nanoparticles.
The method comprises the following steps:
(1) Preparing 10 milliliters of solution with pH value of 2 and 4 by using hydrochloric acid; preparing 10 milliliters of solution with pH values of 10 and 12 by using sodium hydroxide; as a solution at pH 7, 10 ml of deionized water was used.
(2) P-aminophenylboronic acid was added to solutions of different pH values to prepare 1 ml of a solution containing 0.05 mmole of the amino-phenylboronic acid.
(3) The prepared solutions of the para-aminophenylboronic acid with different pH values are respectively added into 0.05 millimole solution of trichlorogold acid (molecular weight 393.83, national medicine group chemical reagent Co., ltd.) and are shaken for 2-3 times, and the color of the solution in the bottle immediately turns brown, thus obtaining the synthesized gold nanoparticles under different pH values. The reaction charging sequence and charging mode have no influence on the products. (4) The treatment and particle characterization of gold nanoparticles reduced by para-aminophenylboronic 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 the para-aminophenylboric acid under different acid-base environments is the same as that of the embodiment 1, and compared with that of levofloxacin, the antibacterial effect of the gold nanoparticles is more effective in treating multi-drug 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 the para-aminophenylboronic acid under the condition of pH=2 to conduct the exploration of an antibacterial mechanism and biosafety. The inventors shake sensitive strains of bacteria (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. Bacteria were centrifuged, fixed, dehydrated, and then cut into ultra-thin sections, and observed by scanning and transmission electron microscopy, and the results are shown in fig. 6A-B.
(6) For further clinical application, the inventors measured the sample at 540nm (OD) by a microplate reader (Tecan infinite M200) 540nm ) The optical density method of (1) tests the raw materials of gold nanoparticles with different concentrations and synthetic gold nanoparticles (para-aminophenylboronic acid (4 ABA) and chloroauric acid (HAuCl) 4 ) Hemolysis performance using saline as a negative control and water as a positive control, the results are shown in fig. 7A. The in vitro cytotoxicity was assessed by testing the viability of mouse fibroblasts (3T 3) cells under different sample treatments, the results of which are shown in fig. 7B.
Example 5
The method comprises the following steps:
(1) Para-aminophenylboronic acid (4 ABA) was formulated as a 0.05 millimolar solution and chloroauric acid trihydrate was formulated as a 0.05 millimolar solution. (2) Para-aminophenylboronic acid (4 ABA) and chloroauric acid (HAuCl) 4 ) The two components are respectively infused into the body of the mouse in different volume proportions in a gastric lavage mode to explore the synthesis and metabolism conditions of the two components in the body, and the metabolism conditions of the gold nanoparticles synthesized in vitro are taken as reference basis when the pH is 2 in the embodiment 4. Mice were randomly divided into 4 groups (n=5) for gastric lavage experiments, group 1 (4 ABA and HAuCl) 4 The lavage volume was 150 μl: 50 microliters (3:1)); group 2 (4 ABA and HAuCl) 4 The lavage volume was 100 μl: 100 microliters (1:1) of Au_4ABAI NPs); group 3 (4 ABA and HAuCl) 4 The lavage volume was 50 μl: 150 microliters (1:3)); group 4 (in vitro gastric environment simulated synthetic gold nanoparticle (Au_4ABae NPs)) the particles were the gold nanoparticles synthesized in example 4, at pH 2, at a raw material ratio of 0.05 mM pairGold nanoparticles synthesized by aminobenzene boric acid and 0.05 millimole chloroauric acid.
(3) Orbital bleeding and interpretation of mice after intragastric administration at different time points (1, 2, 6, 12, 18, 24, 48, and 72 hours) gave 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 HAuCl 4 Reaching the maximum value in the initial stage of synthesis in the stomach, proving the feasibility of oral administration; the plasma concentration-time curve shows that the gold atom concentration in the blood increases rapidly 6 hours after intragastric administration and decreases within 24 hours. The gold concentration of the kidneys and liver decreased to substantially 0 after 72 hours, indicating a high clearance efficiency. Group 2 showed the most similar trend compared to the individual organ levels in au—4ABAe NPs.
(4) The antibacterial effect of oral gold nanoparticles in the mice model of acute peritonitis was investigated using the ratio of group 2. Injecting sensitive strain (E.coli) and multi-drug resistant strain (MDR E.coli) of Escherichia coli in exponential phase into abdominal cavity of mice at injection concentration of 1×10 6 CFU/mL. After 1 and 6 hours of infection, 5 mmoles per liter of 4ABA and 5 mmoles per liter of HAuCl were added 4 Gastric lavage was performed at 100 μl each, sterile saline was used as a negative control, levofloxacin was used as a positive control, and mortality and body weight of mice were monitored as shown in fig. 9. Shown, illustrate 4ABA and HAuCl 4 When the composition is orally taken, the effect of treating abdominal cavity infection caused by multi-drug resistant bacteria is better and more remarkable than that of common antibiotics levofloxacin.
Although the present invention has been described to a certain extent, it is apparent that appropriate changes may be made in the individual conditions without departing from the spirit and scope of the invention. It is to be understood that the invention is not to be limited to the described embodiments, but is to be given the full breadth of the claims, including equivalents of each of the elements described.
Claims (11)
1. A functional antimicrobial combination, characterized in that the combination comprises the following two components, each independently present: aminophenylboronic acid and chloroauric acid trihydrate, and the combination is free of surfactants;
the method can directly reduce chloroauric acid into gold nanoparticles without using a reducing agent, and stably connect ligand molecules on the gold nanoparticles.
2. The combination according to claim 1, wherein the aminophenylboronic acid is selected from one or more of the following: para-aminophenylboronic acid, meta-aminophenylboronic acid, ortho-aminophenylboronic acid.
3. The combination according to claim 1, wherein the molar ratio of the aminophenylboronic acid to the chloroauric acid trihydrate is 1:0.1-100.
4. A combination according to claim 3, wherein the molar ratio of aminophenylboronic acid to chloroauric acid trihydrate is 1:0.2-5.
5. The combination of claim 1, wherein the medicament is an oral medicament.
6. The combination of claim 5, wherein the drug is a solid oral formulation or a liquid oral formulation.
7. A combination according to claim 6, wherein:
the solid oral formulation dosage form is selected from one or more of the following: tablets, granules, capsules and dripping pills; and/or
The liquid oral preparation is a solution combination of two components of aminophenylboric acid and chloroauric acid trihydrate which exist independently.
8. The combination of claim 1, further comprising a pharmaceutically acceptable adjuvant.
9. The combination of claim 8, wherein the pharmaceutically acceptable excipients are selected from one or more of the following: fillers, disintegrants and lubricants.
10. Use of a functional antibacterial combination according to any one of claims 1 to 9 for the preparation of an antibacterial product.
11. Use according to claim 10, wherein the antibacterial product is an antibacterial product, the bacteria being selected from escherichia coli and/or pseudomonas aeruginosa.
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| CN102426157B (en) * | 2011-11-16 | 2013-02-27 | 江南大学 | Method for analyzing tyrosinase activity based on functional Au nanoparticles |
| CN102962471B (en) * | 2012-11-13 | 2014-10-01 | 武汉理工大学 | Glucose responsive gold nanoparticle and preparation method and application thereof |
| CN107412780B (en) * | 2016-05-23 | 2022-04-15 | 国家纳米科学中心 | Antibacterial agent based on gold nanoparticle surface modified nitrogen heterocyclic micromolecules |
| EP3543263A4 (en) * | 2016-11-16 | 2019-11-27 | Zhejiang University | Polyolefin-based emulsifier and application thereof for preparing high internal phase emulsion and porous polymeric material |
| CN109108275B (en) * | 2017-06-22 | 2022-05-03 | 国家纳米科学中心 | Amino sugar modified antibacterial gold nanoparticles, and preparation method and application thereof |
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