CN113599394A

CN113599394A - A kind of bismuth oxyhalide antibacterial material and preparation method and application thereof

Info

Publication number: CN113599394A
Application number: CN202110896413.2A
Authority: CN
Inventors: 吴爱国; 房倩兰; 陈天翔; 徐晨; 任文智; 马雪华
Original assignee: Ningbo Institute of Material Technology and Engineering of CAS
Current assignee: Ningbo Institute of Material Technology and Engineering of CAS
Priority date: 2021-08-05
Filing date: 2021-08-05
Publication date: 2021-11-05

Abstract

The invention provides a bismuth oxyhalide antibacterial material, which comprises BiOX particles and a coating; the coating is a biocompatible material. The bismuth oxyhalide antibacterial material provided by the invention has excellent broad-spectrum antibacterial (resisting gram-negative bacteria and gram-positive bacteria) performance, good dispersibility and biocompatibility, is not easy to generate drug resistance, has an antibacterial mechanism similar to nano-silver, can be applied to various preventive and therapeutic broad-spectrum antibacterial scenes, and has the characteristics of simple synthesis method and batch preparation, so that the bismuth oxyhalide antibacterial material has the potential of becoming a new-generation antibacterial material.

Description

Bismuth oxyhalide antibacterial material and preparation method and application thereof

Technical Field

The invention relates to the technical field of antibacterial materials, in particular to a bismuth oxyhalide antibacterial material and a preparation method and application thereof.

Background

Bacterial infection-related diseases have become one of the major public health concerns of global medical organizations and researchers due to their high morbidity and mortality. The conventional treatment of bacterial infections is with antibiotics, and the main mechanism of action of antibiotics currently used to treat diseases is interference with important links of the bacterial cell life cycle, such as protein synthesis, unwinding of DNA replication, synthesis of cell walls, etc. It is undeniable that antibiotic therapy has made a great progress since its birth, saving countless lives, but with the increasing level of use of antibiotics, superbacteria are also increasingly frequently present in the lives of the general population.

At the G20 peak, the World Health Organization (WHO) published a global priority list of antibiotic-resistant bacteria and represented a lack of innovation in the development of new antibiotics that are undermining the effectiveness of humans in combating infection with resistant bacteria. Since some species show varying degrees of resistance by mutation or natural selection, e.g., the superbacteria escherichia coli with the mcr-1 gene are resistant to colistin, the last choice for the treatment of multidrug-resistant (MDR) bacterial infections. More and more kinds of MDR bacteria appear, which not only causes poor antibiotic treatment effect, but also increases the infection probability in a hospital due to the prolongation of the hospitalization time, and also aggravates the burden of a medical system while endangering the life safety of a patient. Therefore, it is very urgent and important to develop new broad-spectrum antibacterial drugs that are not easily resistant to drugs to solve the above problems.

Recently, researchers have found that certain types of metal materials are excellent antimicrobial agents because they have high activity and broad-spectrum bactericidal effect at low dose and are not prone to develop resistance. The antibacterial action mechanism of the metal material includes active oxygen generation, cation release, ATP consumption, membrane damage and alteration related to respiratory function, protein dysfunction and nutrient assimilation interference, and thus signal transduction inhibition in bacteria and bacterial growth inhibition.

Disclosure of Invention

In view of the above, the technical problem to be solved by the present invention is to provide a bismuth oxyhalide antibacterial material, and a preparation method and an application thereof, wherein the bismuth oxyhalide antibacterial material has a strong antibacterial function and is not easy to generate drug resistance.

The invention provides a bismuth oxyhalide antibacterial material, which comprises BiOX particles and a coating; the coating is a biocompatible material.

Preferably, the BiOX is selected from at least one of BiOF, BiOCl, BiOBr, BiOI and BiOAt.

Preferably, the biocompatible material is at least one selected from the group consisting of polyol and derivatives thereof, modified chitosan, dextran, carboxydextran, liposome, albumin, tetraethoxysilane, polyacrylic acid, KH560, KH550, F127, CO-520, diethylenetriaminepentaacetic acid, meglumine, arginine, polyglutamic acid, polypeptide, PLGA microspheres, mesoporous silica, micro-bubble microspheres, and derivatives thereof.

Preferably, the polyhydric alcohol is at least one selected from glycerol, mannitol and sorbitol.

Preferably, the BiOX particles are free of oxygen vacancy defects or have oxygen vacancy defects.

Preferably, the particle size of the bismuth oxyhalide antibacterial material is 50 nm-500 nm.

The invention provides a preparation method of a bismuth oxyhalide antibacterial material, which comprises the following steps:

A) adding a bismuth source into the solution with excessive concentrated acid to form a dispersion system of bismuth in the concentrated acid, slowly dropwise adding an alkaline solution into the system until the precipitate is not changed, and centrifuging and washing to obtain the defect-free bismuth oxyhalide antibacterial material;

B) mixing the non-defective bismuth oxyhalide antibacterial material and the biocompatible material in a solution for reaction, and centrifuging and washing a product to obtain the modified non-defective bismuth oxyhalide antibacterial material.

s1) adding a bismuth source into the solution with excessive concentrated acid to form a dispersion system of bismuth in the concentrated acid, slowly dropwise adding an alkaline solution into the system until the precipitate is not changed, and centrifuging and washing to obtain the defect-free bismuth oxyhalide antibacterial material;

s2) processing the non-defective bismuth oxyhalide antibacterial material by adopting a defect formation method to obtain a defective bismuth oxyhalide antibacterial material;

s3) mixing the defective bismuth oxyhalide antibacterial material and the biocompatible material in a solution for reaction, and centrifuging and washing the product to obtain the modified defective bismuth oxyhalide antibacterial material.

The invention provides the application of the bismuth oxyhalide antibacterial material or the bismuth oxyhalide antibacterial material prepared by the preparation method in preparing broad-spectrum nano antibacterial drugs.

The invention provides a nano antibacterial drug which comprises the bismuth oxyhalide antibacterial material or the bismuth oxyhalide antibacterial material prepared by the preparation method.

Compared with the prior art, the invention provides a bismuth oxyhalide antibacterial material, which comprises BiOX particles and a coating; the coating is a biocompatible material.

The invention obtains the following beneficial effects:

(1) the provided bismuth oxyhalide antibacterial material has the advantages of uniform particle size distribution, controllable size, good water solubility, good biocompatibility and the like;

(2) the provided bismuth oxyhalide antibacterial material has an antibacterial mechanism similar to nano-silver, but compared with the nano-silver material, the bismuth oxyhalide antibacterial material has the advantages of economy, greenness, easy preparation, capability of reaching 10g level preparation, easy expanded production, better biological safety and ideal new generation antibacterial material;

(3) the provided bismuth oxyhalide antibacterial material can be added into fabric for broad-spectrum antibiosis; adding wound plaster, wound dressing, scald ointment, etc. to inhibit bacteria at wound; antibacterial spray for oral cavity and tinea pedis ointment (antifungal) can be added to prevent and resist bacteria at susceptible pathogenic bacteria; the cosmetic is added to achieve the effects of resisting bacteria, inhibiting inflammation, tranquilizing skin and restoring skin barrier function; the shampoo is added to prevent or treat intractable dandruff caused by bacterial infection, and the like;

(4) the provided bismuth oxyhalide antibacterial material has the medical CT imaging function, and can be used for CT contrast agents, targeted drugs and carrier design thereof, separation and purification of biopolymers and cells and the like;

(5) the method for preparing the bismuth oxyhalide antibacterial material adopts a mild coprecipitation method, is simple, has economic cost, is green to synthesize, and is easy for expanded production.

Drawings

FIG. 1 is a diagram of the patent idea of bismuth oxyhalide antibacterial material;

FIG. 2 is a schematic diagram of the synthesis and application of bismuth oxyhalide antibacterial material;

FIG. 3 is a TEM image of a defect-free (left image) and defect-free (right image) bismuth oxyhalide antibacterial material;

FIG. 4 is an oxygen vacancy defect characterization of a bismuth oxyhalide antimicrobial material;

FIG. 5 is a cytotoxicity study of bismuth oxyhalide antibacterial material;

FIG. 6 is a graph showing the antibacterial effect of bismuth oxyhalide antibacterial materials on Escherichia coli (gram-negative bacteria) and Staphylococcus aureus (gram-positive bacteria).

Detailed Description

Wherein X is selected from F, Cl, Br, I or At.

In the invention, the particle size of the bismuth oxyhalide antibacterial material is preferably 50 nm-500 nm. More preferably, the upper limit of the particle size range of the bismuth oxyhalide antibacterial material is selected from 400nm, 300nm and 200nm, and the lower limit of the particle size range is selected from 100nm, 120nm and 150 nm.

Preferably, the BiOX is at least one selected from BiOF, BiOCl, BiOBr, BiOI and BiOAt. More preferably BiOCl.

In the present invention, the BiOX particles may contain no oxygen vacancy defects or have oxygen vacancy defects.

The proportion of the oxygen vacancy defects in the BiOX particles is not particularly limited in the invention, and the type and proportion of the defects in the BiOX particles can be selected by a person skilled in the art according to actual needs.

Preferably, the defect of the bismuth oxyhalide antibacterial material is 0-80%. Further preferably, the upper limit of the defect percentage content range of the bismuth oxyhalide antibacterial material is arbitrarily selected from 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%; the lower limit is optionally selected from 0%, 20%, 40%. Preferably, the bismuth oxyhalide material has a defect percentage of 50%.

Preferably, the biocompatible material is hydrophilic.

Preferably, the biocompatible material is at least one selected from the group consisting of polyol and derivatives thereof, modified chitosan, dextran, carboxydextran, liposomes, albumin, tetraethoxysilane, polyacrylic acid, KH560, KH550, F127, CO-520, diethylenetriaminepentaacetic acid, meglumine, arginine, polyglutamic acid, polypeptide, PLGA microspheres, mesoporous silica, microbubbles, microspheres and derivatives thereof.

The polyhydric alcohol is preferably at least one of glycerol, mannitol and sorbitol.

The skilled person can select the kind of bismuth oxyhalide, the biocompatible material and the ratio of the bismuth oxyhalide to the bismuth oxyhalide antibacterial material according to the actual requirement.

According to the invention, the content of the BiOX particles in the bismuth oxyhalide antibacterial material is preferably 5-90% by mass. Further preferably, the upper limit of the mass percentage content range of the BiOX particles in the bismuth oxyhalide antibacterial material is arbitrarily selected from 30%, 28%, 26%, 25%, 22%, 20% and 15%; the lower limit is selected from 6%, 8% and 10%. Preferably, the biocompatible material in the bismuth oxyhalide antibacterial material accounts for 20% by mass of the bismuth oxyhalide antibacterial material.

The invention provides a preparation method of the bismuth oxyhalide antibacterial material, which comprises the following steps:

A) adding a bismuth source into a solution with excessive concentrated acid to form a bismuth dispersion system in the concentrated acid, slowly dropwise adding an alkaline solution into the system until the precipitate is not changed, and centrifuging and washing to obtain defect-free BiOX particles;

B) and mixing the non-defective BiOX particles and the biocompatible material in a solution for reaction, and centrifuging and washing a product to obtain the modified non-defective bismuth oxyhalide antibacterial material.

In the present application, the biocompatible material should be added in an amount sufficient to cover the defect-free BiOX particles during the preparation of the bismuth oxyhalide antibacterial material, and within this range, one skilled in the art can select a suitable ratio of the biocompatible material to the defect-free BiOX particles according to specific requirements.

Preferably, the concentrated acid is selected from HCl (hydrochloric acid), H₂SO₄(sulfuric acid), HNO₃(nitric acid), HF (hydrofluoric acid), HBr (hydrobromic acid), and HI (hydroiodic acid).

Preferably, the concentration of the concentrated acid is not less than 10 mol/L; more preferably, the concentration of the concentrated acid is 10 mol/L-40 mol/L; more preferably, the concentration of the concentrated acid is 15 mol/L-35 mol/L; more preferably, the concentration of the concentrated acid is 20mol/L to 25 mol/L.

Preferably, the bismuth source is selected from Bi (NO)₃)₃、Bi₂O₃、Bi₂(SO₄)₃、Bi(NO₃)₃·5H₂O、Bi(PO₃)₃、BiH(PO₃)₂、BiH₂PO₃、Bi₂(CO₃)₃、Bi₂(SO₄)₃、Bi(FeO₂)₃Or a combination thereof.

The concentration of the bismuth source in the solution is preferably 10-100 g/L.

Preferably, the alkaline solution is selected from KOH (potassium hydroxide), Ca (OH)₂(calcium hydroxide), NaOH (sodium hydroxide), Ba (OH)₂(barium hydroxide), CsOH (cesium hydroxide), Mg (OH)₂(magnesium hydroxide), Al (OH)₃(aluminum hydroxide), Zn (OH)₂(Zinc hydroxide), Fe (OH)₃(iron hydroxide), Fe (OH)₂(ferrous hydroxide), Cu (OH)₂(copper hydroxide), NH₃.H₂O (ammonia), Na₂CO₃(sodium carbonate), NaHCO₃(sodium bicarbonate).

The concentration of the alkaline solution is preferably less than 0.1 mol/L.

Preferably, in the step B), the mass concentration of the biocompatible material in the solution is 1% to 8%.

Preferably, the time of the mixing reaction is 10-60 min; further preferably, the time of the mixing reaction is 20-40 min; further preferably, the time of the mixing reaction is 30 to 35 min.

The temperature of the mixing reaction is 20-80 ℃; further preferably, the temperature of the mixing reaction is 20-60 ℃; further preferably, the temperature of the mixing reaction is 20 to 30 ℃.

The invention also provides a preparation method of the bismuth oxyhalide antibacterial material, which comprises the following steps:

s1) adding a bismuth source into the solution with excessive concentrated acid to form a dispersion system of bismuth in the concentrated acid, slowly dropwise adding an alkaline solution into the system until the precipitate is not changed, and centrifuging and washing to obtain defect-free BiOX particles;

s2) processing the non-defective BiOX particles by adopting a defect forming method to obtain defective BiOX particles;

s3) mixing the defective BiOX particles and the biocompatible material in a solution for reaction, and centrifuging and washing the product to obtain the modified defective bismuth oxyhalide antibacterial material.

The parameters of the step S1) are the same as those of the step a), which is not described herein again.

The defect formation method of the present invention is not particularly limited, and may be a defect formation method known to those skilled in the art.

The invention preferably forms defects by means of ultraviolet lamp irradiation. Preferably, the power of the ultraviolet lamp is 10-500W.

Preferably, the non-defective BiOX particles are mixed with the chelate solution and then irradiated by an ultraviolet lamp. The irradiation time of the ultraviolet lamp is preferably 1-3 hours, and more preferably 2 hours.

The chelate is preferably oxalic acid.

In other preferred embodiments of the present invention, the defects are formed by a high temperature calcination process.

The high-temperature calcination temperature is preferably 200-400 ℃, and more preferably 300 ℃.

The high-temperature calcination time is preferably 3-5 h, and more preferably 4 h.

The high-temperature calcination is preferably performed in an inert gas atmosphere, more preferably in a nitrogen atmosphere.

The parameters of the step S3) are the same as those of the step B), which is not described herein again.

As a preferred embodiment of the present invention, the preparation process of the bismuth oxyhalide antibacterial material is as follows:

preparing BiOX powder by adopting a coprecipitation method: dissolving bismuth source in excessive concentrated acid solution to obtainBiX₃Aqueous HCl system; and (3) adjusting the pH value of the solution to 2-3 by using ammonia water (AR, Rankem) to form a white colloid. The colloid is heated at 40 deg.C for half an hour to obtain a powdered biological crystal material consisting of platelet-shaped crystals. The product is filtered and purified, washed with distilled water until the solution is free of element X, and then dried in an oven at 40 ℃ for 6 hours for later use.

Specifically, the preparation process comprises the following steps:

(1) preparation of defect-free BiOX particles: to a 250mL beaker was added an excess of concentrated HCl, Bi₂O₃Dissolving in excessive concentrated hydrochloric acid to obtain BiCl₃And dropwise adding ammonia water at the speed of 0.2-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 30-40 ℃ for 10-60min until white colloid does not increase. The colloid is heated at 40-100 deg.C for half an hour to obtain white powder. Washing the obtained white powder with water and ethanol alternately, centrifuging at 8000-15000 rpm for precipitation, re-dispersing in water, and storing at 0-4 deg.C.

(2) Defect-free BiOX particle modification: weighing 10mL of defect-free BiOX particles obtained in the step (1) with the mass concentration of 3-5 mg/mL, adding 10-50mL of 1-10mg/mL of biocompatible material, magnetically stirring at 30-40 ℃ for 8-24h at the rotation speed of 500-2000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 8000-15000 rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defect-free bismuth oxyhalide antibacterial material.

Or comprises the following steps:

(3) preparing defective BiOX particles: weighing 10mL of defect-free BiOX particles with the mass concentration of 3-5 mg/mL, adding 10-50mL of chelate with the mass concentration of 1-10mg/mL, irradiating at 30-40 ℃, using a 10-500W ultraviolet lamp, and magnetically stirring at the rotating speed of 500-2000rpm for 1-4h to obtain the dispersion. Washing the obtained dispersion liquid with water and ethanol alternately, centrifuging and precipitating at 8000-15000 rpm, re-dispersing in water, and storing at 0-4 deg.C.

(4) Defective BiOX particle modification: weighing 10mL of defective BiOX particles obtained in the step (3) with the mass concentration of 3-5 mg/mL, adding 10-50mL of 1-10mg/mL of biocompatible material, magnetically stirring at 30-40 ℃ and 2000rpm for 8-24h, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 8000-15000 rpm, re-dispersing in water, and preserving at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

The invention also provides the application of the bismuth oxyhalide antibacterial material or the bismuth oxyhalide antibacterial material prepared by the preparation method in preparing broad-spectrum nano antibacterial drugs.

In order to further illustrate the present invention, the following will describe the bismuth oxyhalide antibacterial material provided by the present invention in detail with reference to the examples, and the preparation method and application thereof. It should be understood that these examples are for illustrative purposes only and do not limit the scope of the present application. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out according to conventional conditions or according to conditions recommended by the manufacturers.

The instruments and test conditions used in the examples were as follows:

TEM

testing an instrument: JEOL-2100 model Transmission Electron microscope; and (3) testing conditions are as follows: 200Kv, 101. mu.A; and the nano particles to be tested are dispersed in water for testing.

Cytotoxicity assays

1. 4T1 cells were plated in 96-well plates at a concentration of 1 x 10^6/mL, 100. mu.L in 100. mu.L of 95 v/v% 1640 medium plus 5 v/v% fetal bovine serum, and incubated overnight.

2. The culture solution was aspirated, and different concentrations of bismuth oxyhalide antibacterial material were added to 100. mu.L per well at concentrations of 100,200,300, 400,500. mu.g/mL, and incubated for 24 h.

After 3.20h, the material was aspirated and washed 2-3 times with PBS, and 100. mu.L of the above culture medium was added, and 5% MTT (dissolved in DMSO) was added and incubation was continued for 4 h.

4. All the liquids were aspirated, 100. mu.L of DMSO was added, and the absorbance of each well of the 96-well plate was measured using a microplate reader at a wavelength of 550nm, and the cell viability was calculated.

Particle size distribution

The material particle size test was performed using a zetasizer Nano 2S model dynamic light scattering particle size analyzer.

Example 1 preparation of sample # 1

(1) Preparation of defect-free BiOX particles: to a 50mL beaker was added 10mL of concentrated HCl and 1g of Bi was added₂O₃Dissolving in excessive concentrated hydrochloric acid to obtain BiCl₃And dropwise adding ammonia water at the speed of 0.2-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 30 ℃ for 10min until white colloid is not increased any more. The gel was heated at 40 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Defect-free BiOX particle modification: weighing 10mL of defect-free BiOX particles obtained in the step (1) with the mass concentration of 3mg/mL, adding 50mL of PEG aqueous solution, magnetically stirring at 25 ℃ and 2000rpm for 12h, centrifugally washing after stirring, alternately washing the obtained dispersion with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defect-free bismuth oxyhalide antibacterial material.

The morphology of the defect-free bismuth oxyhalide antibacterial material is detected, and the result is shown in fig. 3, wherein fig. 3 is a TEM image of the bismuth oxyhalide antibacterial material, wherein the left image is defect-free, and the right image is defect-free. The left picture of fig. 3 shows that the white bismuth oxyhalide antibacterial material has good crystal growth and complete structure.

Example 2 preparation of sample 2#

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: 20mL of concentrated hydrochloric acid was added to a 100mL beaker, and 2g of Bi was added₂O₃Dissolving in excessive concentrated hydrochloric acid to obtain BiCl₃And dropwise adding ammonia water at the speed of 1-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 30 ℃ for 20min until white colloid is not increased any more. Heating the colloid at 40 deg.C for half an hourTo obtain white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Modification of defect-free bismuth oxyhalide antibacterial material: weighing 10mL of the defect-free bismuth oxyhalide antibacterial material obtained in the step (1) with the mass concentration of 3mg/mL, adding 50mg/mL of PVP aqueous solution 50mL, magnetically stirring at 25 ℃ and the rotating speed of 500-2000rpm for 12h, centrifugally washing after stirring, alternately washing the obtained dispersion with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defect-free bismuth oxyhalide antibacterial material.

Example 3 preparation of sample # 3

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: 50mL of concentrated hydrochloric acid was added to a 250mL beaker, and 5g of Bi was added₂O₃Dissolving in excessive concentrated hydrochloric acid to obtain BiCl₃And dropwise adding ammonia water at the speed of 1-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 50 ℃ for 50min until white colloid is not increased any more. The gel was heated at 100 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Modification of defect-free bismuth oxyhalide antibacterial material: weighing 5mL of defect-free bismuth oxyhalide antibacterial material with the mass concentration of 3mg/mL obtained in the step (1), adding 45mL of 50mg/mL PEI aqueous solution, magnetically stirring at 25 ℃ and 2000rpm for 24h, centrifugally washing after stirring, alternately washing the obtained dispersion with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defect-free bismuth oxyhalide antibacterial material.

Example 4 preparation of sample # 4

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: to a 500mL beaker was added 100mL of concentrated hydrochloric acid, and 10g of Bi was added₂O₃Dissolving in excessive concentrated hydrochloric acid to obtain BiCl₃Dropwise adding ammonia water at the speed of 1-2 mL/s to adjust the pH value of the solution to 2-3, and quickly stirring at the temperature of 50 DEG C100min until no further increase in white colloid appeared. The gel was heated at 100 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Modification of defect-free bismuth oxyhalide antibacterial material: weighing 10mL of the defect-free bismuth oxyhalide antibacterial material obtained in the step (1) with the mass concentration of 3mg/mL, adding 90mL of 50mg/mL PLGA aqueous solution, magnetically stirring at 25 ℃ and 2000rpm for 24h, centrifugally washing after stirring, alternately washing the obtained dispersion with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defect-free bismuth oxyhalide antibacterial material.

Example 5 preparation of sample # 5

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: to a 50mL beaker was added 10mL of concentrated HCl and 1g of Bi was added₂O₃Dissolving in excessive concentrated hydrochloric acid to obtain BiCl₃And dropwise adding ammonia water at the speed of 0.2-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 30 ℃ for 10min until white colloid is not increased any more. The gel was heated at 40 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Preparing defective bismuth oxyhalide antibacterial material: weighing 1mL of defect-free bismuth oxyhalide antibacterial material with the mass concentration of 3mg/mL, adding 9mL of 50mg/mL oxalic acid solution, and irradiating for 2h at 25 ℃ by using a 500W ultraviolet lamp to obtain a dispersion liquid. Washing the obtained dispersion with water and ethanol alternately, centrifuging at 12000rpm for precipitation, re-dispersing in water, and storing at 0-4 deg.C.

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 1mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 9mL of PEG aqueous solution with the mass concentration of 50mg/mL, magnetically stirring at 25 ℃ for 12h at the rotation speed of 1000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

The morphology of the prepared defective bismuth oxyhalide antibacterial material is detected, and the result is shown in fig. 3, fig. 3 is a TEM image of the bismuth oxyhalide antibacterial material, wherein the right image is defective. As can be seen from the right graph of FIG. 3, the defect bismuth oxyhalide material has many defects at the edge of the crystal structure, which are the activation sites of surface oxygen and the antibacterial active sites, and the antibacterial performance of the defect bismuth oxyhalide material is greatly improved.

Fig. 4 is a representation of oxygen vacancy defects of the bismuth oxyhalide antibacterial material, and it can be seen from fig. 4 that the surface of the defective bismuth oxyhalide material prepared by the defect has obvious oxygen vacancy characteristics.

Example 6 preparation of sample No. 6

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: 20mL of concentrated hydrochloric acid was added to a 100mL beaker, and 2g of Bi was added₂O₃Dissolving in excessive concentrated hydrochloric acid to obtain BiCl₃And dropwise adding ammonia water at the speed of 1-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 30 ℃ for 20min until white colloid is not increased any more. The gel was heated at 40 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Preparing defective bismuth oxyhalide antibacterial material: weighing 2mL of defect-free bismuth oxyhalide antibacterial material with the mass concentration of 3mg/mL, adding 18mL of 50mg/mL oxalic acid solution, and irradiating for 2h at 25 ℃ by using a 500W ultraviolet lamp to obtain a dispersion liquid. Washing the obtained dispersion with water and ethanol alternately, centrifuging at 12000rpm for precipitation, re-dispersing in water, and storing at 0-4 deg.C.

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 2mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 18mL of 50mg/mL PEG aqueous solution, magnetically stirring at 25 ℃ for 12h at the rotating speed of 1000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

Example 7 preparation of sample 7#

(2) Preparing defective bismuth oxyhalide antibacterial material: weighing 5mL of defect-free bismuth oxyhalide antibacterial material with the mass concentration of 3mg/mL, adding 45mL of 50mg/mL ethylene glycol solution, and irradiating for 2h at 25 ℃ by using a 500W ultraviolet lamp to obtain a dispersion liquid. Washing the obtained dispersion with water and ethanol alternately, centrifuging at 12000rpm for precipitation, re-dispersing in water, and storing at 0-4 deg.C.

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 5mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 45mL of 50mg/mL PEI aqueous solution, magnetically stirring at 25 ℃ for 12h at the rotation speed of 1000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

Example 8 preparation of sample No. 8

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: to a 500mL beaker was added 100mL of concentrated HCl and 10gBi₂O₃Dissolving in excessive concentrated hydrochloric acid to obtain BiCl₃And dropwise adding ammonia water at the speed of 1-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 50 ℃ for 100min until white colloid is not increased any more. The gel was heated at 100 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Preparing defective bismuth oxyhalide antibacterial material: weighing 10mL of flawless bismuth oxyhalide antibacterial material with the mass concentration of 3mg/mL, adding 90mL of 50mg/mL oxalic acid solution, and irradiating for 2 hours at 25 ℃ by using a 500W ultraviolet lamp to obtain dispersion liquid. Washing the obtained dispersion with water and ethanol alternately, centrifuging at 12000rpm for precipitation, re-dispersing in water, and storing at 0-4 deg.C.

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 10mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 90mL of PVP aqueous solution with the mass concentration of 50mg/mL, magnetically stirring at 25 ℃ for 12h at the rotating speed of 1000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

Example 9 preparation of sample # 9

(2) Preparing defective bismuth oxyhalide antibacterial material: weighing 1g of flawless bismuth oxyhalide antibacterial material powder, placing the powder in a sample porcelain boat to be wrapped by tinfoil paper, and placing the sample porcelain boat in a tubular furnace to be calcined for 4 hours at 300 ℃ under nitrogen atmosphere to obtain dark powder. The dark powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water and stored at 0-4 ℃.

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 10mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 90mL of 50mg/mL PEI ethanol solution, magnetically stirring at 25 ℃ by using the rotation speed of 1000rpm for 12h, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

Example 10 preparation of sample No. 10

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: to a 500mL beaker was added 100mL of concentrated HCl and 10gBi₂O₃Dissolving in excessive concentrated hydrochloric acid to obtain BiCl₃And dropwise adding ammonia water at the speed of 1-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 30 ℃ for 100min until white colloid is not increased any more. The gel was heated at 40 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Preparing defective bismuth oxyhalide antibacterial material: weighing 3g of flawless bismuth oxyhalide antibacterial material powder, placing the powder in a sample porcelain boat to be wrapped by tinfoil paper, and placing the sample porcelain boat in a tubular furnace to be calcined for 4 hours at 300 ℃ under nitrogen atmosphere to obtain dark powder. The dark powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water and stored at 0-4 ℃.

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 10mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 90mL of 50mg/mL PEG ethanol solution, magnetically stirring at 25 ℃ for 12h at the rotating speed of 1000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

Example 11 preparation of sample # 11

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: 10mL of concentrated hydrofluoric acid was added to a 50mL beaker, and 1g of Bi was added₂O₃Dissolving in excessive concentrated hydrofluoric acid to obtain BiF₃Dropwise adding 0.2-2 mL/s ammonia water to adjust the pH value of the solution to 2-3, and rapidly stirring at 30 ℃ for 10minUntil no further increase in white colloid appeared. The gel was heated at 40 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Modification of defect-free bismuth oxyhalide antibacterial material: weighing 10mL of the defect-free bismuth oxyhalide antibacterial material obtained in the step (1) with the mass concentration of 3-5 mg/mL, adding 50mL of a 50mg/mL PEI aqueous solution, magnetically stirring at 25 ℃ and the rotation speed of 500-2000rpm for 12h, centrifugally washing after stirring, alternately washing the obtained dispersion with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defect-free bismuth oxyhalide antibacterial material.

EXAMPLE 12 preparation of sample No. 12

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: 100mL of concentrated hydrofluoric acid was added to a 500mL beaker, and 10g of Bi was added₂O₃Dissolving in excessive concentrated hydrofluoric acid to obtain BiF₃And dropwise adding ammonia water at the speed of 1-2 mL/s to adjust the pH value of the solution to 2-3, and quickly stirring at the temperature of 50 ℃ for 100min until white colloid is not increased any more. The gel was heated at 100 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

Example 13 preparation of sample # 13

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: to a 50mL beaker was added 10mL of concentrated hydrobromic acid and 1g of Bi₂O₃Dissolving in excessive concentrated hydrobromic acid to obtain BiBr₃The aqueous HBr system is ready for use,and dropwise adding ammonia water at the speed of 0.2-2 mL/s to adjust the pH value of the solution to 2-3, and quickly stirring for 10min at the temperature of 30 ℃ until white colloid does not increase any more. The gel was heated at 40 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Modification of defect-free bismuth oxyhalide antibacterial material: weighing 10mL of the defect-free bismuth oxyhalide antibacterial material obtained in the step (1) with the mass concentration of 3-5 mg/mL, adding 10-50mL of PLGA ethanol solution with the mass concentration of 50mg/mL, magnetically stirring at 25 ℃ and the rotating speed of 500-2000rpm for 12h, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defect-free bismuth oxyhalide antibacterial material.

EXAMPLE 14 preparation of sample No. 14

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: 100mL of concentrated hydrobromic acid was added to a 500mL beaker and 10g of Bi was added₂O₃Dissolving in excessive concentrated hydrobromic acid to obtain BiBr₃And (3) dropwise adding ammonia water at the speed of 1-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 50 ℃ for 100min until white colloid does not increase. The gel was heated at 100 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Modification of defect-free bismuth oxyhalide antibacterial material: weighing 10mL of the defect-free bismuth oxyhalide antibacterial material obtained in the step (1) with the mass concentration of 3mg/mL, adding 90mL of PVP ethanol solution with the mass concentration of 50mg/mL, magnetically stirring at 25 ℃ and the rotating speed of 500-2000rpm for 24h, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defect-free bismuth oxyhalide antibacterial material.

Example 15 preparation of sample # 15

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: to a 50mL beaker was added 10mL of concentrated hydroiodic acid and the mixture was added1g Bi₂O₃Dissolving in excessive concentrated hydroiodic acid to obtain BiI₃And (3) adding an HI aqueous solution system for later use, dropwise adding ammonia water at the speed of 0.2-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 30 ℃ for 10min until white colloid is not increased any more. The gel was heated at 40 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Modification of defect-free bismuth oxyhalide antibacterial material: weighing 10mL of the defect-free bismuth oxyhalide antibacterial material obtained in the step (1) with the mass concentration of 3-5 mg/mL, adding 10-50mL of PVP aqueous solution with the mass concentration of 50mg/mL, magnetically stirring at 25 ℃ and the rotating speed of 500-2000rpm for 12h, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defect-free bismuth oxyhalide antibacterial material.

EXAMPLE 16 preparation of sample No. 16

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: 100mL of concentrated hydroiodic acid was added to a 500mL beaker and 10g of Bi was added₂O₃Dissolving in excessive concentrated hydroiodic acid to obtain BiI₃And (3) adding dropwise ammonia water at the speed of 1-2 mL/s to adjust the pH value of the solution to 2-3 for standby, and quickly stirring at the temperature of 50 ℃ for 100min until white colloid does not increase any more. The gel was heated at 100 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Modification of defect-free bismuth oxyhalide antibacterial material: weighing 10mL of the defect-free bismuth oxyhalide antibacterial material obtained in the step (1) with the mass concentration of 3mg/mL, adding 90mL of a 50mg/mL PEG DMF solution, magnetically stirring at 25 ℃ and 2000rpm for 24h, centrifugally washing after stirring, alternately washing the obtained dispersion with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defect-free bismuth oxyhalide antibacterial material.

Example 17 preparation of sample # 17

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: 10mL of concentrated hydrofluoric acid was added to a 50mL beaker, and 1g of Bi was added₂O₃Dissolving in excessive concentrated hydrofluoric acid to obtain BiF₃And dropwise adding ammonia water at the speed of 0.2-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 30 ℃ for 10min until white colloid is not increased any more. The gel was heated at 40 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Preparing defective bismuth oxyhalide antibacterial material: weighing 1mL of flawless bismuth oxyhalide antibacterial material with the mass concentration of 3mg/mL, adding 9mL of 50mg/mL oxalic acid solution, and irradiating for 2 hours at 25 ℃ by using a 500W ultraviolet lamp to obtain dispersion. Washing the obtained dispersion with water and ethanol alternately, centrifuging at 12000rpm for precipitation, re-dispersing in water, and storing at 0-4 deg.C.

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 1mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 9mL of 50mg/mL PEI DMF solution, magnetically stirring at 25 ℃ for 12h at the rotation speed of 1000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

EXAMPLE 18 preparation of sample No. 18

(2) Preparing defective bismuth oxyhalide antibacterial material: weighing 10mL of flawless bismuth oxyhalide antibacterial material with the mass concentration of 3mg/mL, adding 90mL of 50mg/mL oxalic acid solution, and irradiating for 2 hours at 25 ℃ by using a 500W ultraviolet lamp to obtain dispersion. Washing the obtained dispersion with water and ethanol alternately, centrifuging at 12000rpm for precipitation, re-dispersing in water, and storing at 0-4 deg.C.

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 10mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 90mL of 50mg/mL of PVP DMF solution, magnetically stirring at 25 ℃ for 12h at the rotating speed of 1000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

Example 19 preparation of sample No. 19

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: to a 50mL beaker was added 10mL of concentrated hydrobromic acid and 1g of Bi₂O₃Dissolving in excessive concentrated hydrobromic acid to obtain BiBr₃And dropwise adding ammonia water at the speed of 0.2-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 30 ℃ for 10min until white colloid is not increased any more. The gel was heated at 40 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 1mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 9mL of 50mg/mL of PLGA DMF solution, magnetically stirring at 25 ℃ for 12h at the rotating speed of 1000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

EXAMPLE 20 preparation of sample No. 20

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 10mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 90mL of 50mg/mL rBSA aqueous solution, magnetically stirring at 25 ℃ for 12h at the rotation speed of 1000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

Example 21 preparation of sample No. 21

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: to a 50mL beaker was added 10mL of concentrated hydroiodic acid and 1g of Bi was added₂O₃Dissolving in excessive concentrated hydroiodic acid to obtain BiI₃And (3) adding an HI aqueous solution system for later use, dropwise adding ammonia water at the speed of 0.2-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 30 ℃ for 10min until white colloid is not increased any more. The gel was heated at 40 ℃ for half an hour to give a white powder. What is needed isWashing the obtained white powder with water and ethanol alternately, centrifuging at 12000rpm for precipitation, re-dispersing in water, and storing at 0-4 deg.C.

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 1mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 9mL of 50mg/mL rBSA aqueous solution, magnetically stirring at 25 ℃ for 12h at the rotation speed of 1000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

EXAMPLE 22 preparation of sample No. 22

EXAMPLE 23 preparation of sample # 23

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: to a 50mL beaker was added 10mL of concentrated HCl and 1g of Bi was added₂O₃Dissolving in excessive concentrated hydrochloric acid to obtain BiCl₃And dropwise adding sodium hydroxide at the speed of 0.2-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 30 ℃ for 10min until white colloid is not increased any more. The gel was heated at 40 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Modification of defect-free bismuth oxyhalide antibacterial material: weighing 10mL of the defect-free bismuth oxyhalide antibacterial material obtained in the step (1) with the mass concentration of 3-5 mg/mL, adding 10-50mL of 50mg/mL rBSA glycol solution, magnetically stirring at 25 ℃ at the rotating speed of 500-2000rpm for 12h, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defect-free bismuth oxyhalide antibacterial material.

EXAMPLE 24 preparation of sample No. 24

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 1mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 9mL of 50mg/mL rBSA ethylene glycol solution, magnetically stirring at 25 ℃ for 12h at the rotation speed of 1000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

EXAMPLE 25 preparation of sample No. 25

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: to a 50mL beaker was added 10mL of concentrated HCl and 1g of Bi was added₂O₃Dissolving in excessive concentrated hydrochloric acid to obtain BiCl₃And dropwise adding sodium bicarbonate at the speed of 0.2-2 mL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 30 ℃ for 10min until white colloid does not increase any more. The gel was heated at 40 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

Example 26 preparation of sample No. 26

EXAMPLE 27 preparation of sample No. 27

(2) Modification of defect-free bismuth oxyhalide antibacterial material: weighing 10mL of defect-free bismuth oxyhalide antibacterial material with the mass concentration of 3-5 mg/mL obtained in the step (1), adding 10-50mL of 50mg/mL PLGA aqueous solution, magnetically stirring at 25 ℃ for 12h at the rotating speed of 500-2000rpm, centrifugally washing after stirring is finished, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defect-free bismuth oxyhalide antibacterial material coated by the PLGA microspheres.

EXAMPLE 28 preparation of sample No. 28

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: to a 50mL beaker was added 10mL of concentrated HCl and 1g of Bi was added₂O₃Dissolving in excessive concentrated hydrochloric acid to obtain BiCl₃And dropwise adding ammonia water at the speed of 0.2-2 mlL/s to adjust the pH value of the solution to be 2-3, and quickly stirring at the temperature of 30 ℃ for 10min until white colloid is not increased any more. The gel was heated at 40 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 1mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 9mL of PLGA aqueous solution with the mass concentration of 3mg/mL, magnetically stirring at 25 ℃ for 12h at the rotating speed of 1000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material coated by the PLGA microspheres.

Example 29 preparation of sample # 29

(1) Preparing a defect-free bismuth oxyhalide antibacterial material: to a 50mL beaker was added 10mL of concentrated HCl and 1g of Bi was added₂O₃Dissolving in excessive concentrated hydrochloric acid to obtain BiCl₃An aqueous HCl solution system, using 0.2-2 mL of ammonia waterAnd (5) dropping at the speed of s to adjust the pH value of the solution to be 2-3, and quickly stirring for 10min at the temperature of 30 ℃ until the white colloid is not increased any more. The gel was heated at 40 ℃ for half an hour to give a white powder. The obtained white powder was washed with water and ethanol alternately, precipitated by centrifugation at 12000rpm, redispersed in water, and stored at 0-4 ℃.

(2) Modification of defect-free bismuth oxyhalide antibacterial material: weighing 10mL of the defect-free bismuth oxyhalide antibacterial material obtained in the step (1) with the mass concentration of 3-5 mg/mL, adding 10-50mL of dextran with the mass concentration of 50mg/mL, magnetically stirring at 25 ℃ and the rotation speed of 500-2000rpm for 12h, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defect-free bismuth oxyhalide antibacterial material.

EXAMPLE 30 preparation of sample No. 30

(3) Defective bismuth oxyhalide antibacterial material modification: weighing 1mL of defective bismuth oxyhalide antibacterial material obtained in the step (2) with the mass concentration of 3mg/mL, adding 9mL of dextran with the mass concentration of 50mg/mL, magnetically stirring at 25 ℃ for 12h at the rotating speed of 1000rpm, centrifugally washing after stirring, alternately washing the obtained dispersion liquid with water and ethanol, centrifugally precipitating at 12000rpm, re-dispersing in water, and storing at 0-4 ℃ to obtain the defective bismuth oxyhalide antibacterial material.

EXAMPLE 31 broad-spectrum antimicrobial application of sample # 1

Preparing a liquid bacterial culture medium LB: respectively dissolving 10g of tryptone, 5g of yeast extract and 10g of NaCl in 1L of deionized water, and then placing the mixed solution in an autoclave for sterilization to obtain a liquid LB culture medium for culturing staphylococcus aureus (S.aureus) and escherichia coli (E.coli).

Preparing a solid bacterial culture medium LB: dissolving 15g of agar, 10g of tryptone, 5g of yeast extract and 10g of NaCl in 1L of deionized water, placing the mixed solution in an autoclave for sterilization, pouring the culture medium into a culture dish with the diameter of 10cm after the sterilization is finished, cooling the LB culture medium to form gel, and placing the gel in a refrigerator at 4 ℃ for later use.

The antibacterial material prepared in example 1 was prepared into solutions of 100,200,300, 400, 500. mu.g/mL, and was mixed with S.aureus bacterial solution (10. mu.g/mL) respectively⁹CFU/mL), E.coli liquid (concentration 10)⁹CFU/mL), and placing the mixture in a shaking box for shaking culture, wherein the temperature of the shaking box is set to be 37 ℃, and the rotating speed is set to be 120 rpm;

after shaking for 1, 2, 4, 8, 12 and 24 hours, 50 mu L of bacterial liquid is respectively taken and diluted by 10⁵Spinning on an agar culture plate, and then placing the agar culture plate in an incubator for continuous culture; after 18 hours, the bacteria on the agar plates were counted, with the diluted broth without material as a blank.

The results are shown in FIG. 6.

Through calculation, the in-vitro inhibition rate of the antibacterial material in the embodiment 1 on gram-positive bacteria represented by staphylococcus aureus can reach 99%, and the in-vitro inhibition rate on gram-negative bacteria represented by escherichia coli can reach 94%.

The same procedure was used for the antibacterial test, and the results are shown in Table 1:

TABLE 1 results of examples 1-10 antibacterial experiments

In conclusion, the invention provides a novel broad-spectrum bismuth oxyhalide antibacterial material which has good performance of inhibiting the growth and reproduction of bacteria, low toxic and side effects, good dispersibility, strong antibacterial function and difficult generation of drug resistance.

The above description of the embodiments is only intended to facilitate the understanding of the method of the invention and its core idea. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.

Claims

1. A bismuth oxyhalide antibacterial material, comprising BiOX particles and a coating; the coating is a biocompatible material.

2 . The bismuth oxyhalide antibacterial material according to claim 1 , wherein the BiOX is selected from at least one of BiOF, BiOCl, BiOBr, BiOI, and BiOAt. 3 .

3. The bismuth oxyhalide antibacterial material according to claim 1, wherein the biocompatible material is selected from the group consisting of polyols and derivatives thereof, modified chitosan, dextran, carboxydextran , Liposome, Albumin, Ethyl Orthosilicate, Polyacrylic Acid, KH560, KH550, F127, CO-520, Diethylene Triamine Pentaacetic Acid, Meglumine, Arginine, Polyglutamic Acid, Polypeptide, PLGA At least one of microspheres, mesoporous silica, microbubble microspheres and derivatives thereof.

4. The bismuth oxyhalide antibacterial material according to claim 3, wherein the polyol is selected from at least one of glycerol, mannitol, and sorbitol.

5 . The bismuth oxyhalide antibacterial material according to claim 1 , wherein the BiOX particles do not contain or have oxygen vacancy defects. 6 .

6 . The bismuth oxyhalide antibacterial material according to claim 1 , wherein the particle size of the bismuth oxyhalide antibacterial material is 50 nm to 500 nm. 7 .

7. a preparation method of bismuth oxyhalide antibacterial material, comprising the following steps:

A) Add bismuth source to the solution with excess concentrated acid, form the dispersion system of bismuth in concentrated acid, use alkaline solution to slowly drip into the system, until the precipitate does not change, after centrifugation and washing, obtain no Defective bismuth oxyhalide antibacterial material;

B) The above-mentioned defect-free bismuth oxyhalide antibacterial material and the biocompatible material are mixed and reacted in a solution, and the product is centrifuged and washed to obtain a modified defect-free bismuth oxyhalide antibacterial material.

8. a preparation method of bismuth oxyhalide antibacterial material, comprising the following steps:

S1) in the solution with excess concentrated acid, add bismuth source, form the dispersion system of bismuth in concentrated acid, use alkaline solution to slowly drip into the system, until the precipitate no longer changes, after centrifugation, washing, obtain no Defective bismuth oxyhalide antibacterial material;

S2) using a defect formation method to process the non-defective bismuth oxyhalide antibacterial material to obtain a defective bismuth oxyhalide antibacterial material;

S3) mixing and reacting the above-mentioned defective bismuth oxyhalide antibacterial material and the biocompatible material in a solution, and the product is centrifuged and washed to obtain a modified defective bismuth oxyhalide antibacterial material.

9 . The application of the bismuth oxyhalide antibacterial material according to any one of claims 1 to 6 or the bismuth oxyhalide antibacterial material prepared by the preparation method according to any one of claims 7 to 8 in the preparation of broad-spectrum nanometer antibacterial drugs.

10. A nanometer antibacterial drug, comprising the bismuth oxyhalide antibacterial material according to any one of claims 1 to 6 or the bismuth oxyhalide antibacterial material prepared by the preparation method according to any one of claims 7 to 8.