CN116077709A

CN116077709A - Antibacterial dressing, and preparation method and application thereof

Info

Publication number: CN116077709A
Application number: CN202310131127.6A
Authority: CN
Inventors: 韩宝航; 籍文艳; 张湃; 查瑞涛; 丁雪松; 程元哲
Original assignee: National Center for Nanosccience and Technology China
Current assignee: National Center for Nanosccience and Technology China
Priority date: 2023-02-17
Filing date: 2023-02-17
Publication date: 2023-05-09

Abstract

The invention relates to an antibacterial dressing, a preparation method and application thereof, wherein the antibacterial dressing comprises a fibrous membrane distributed with an antibiotic composition; the antibiotic composition comprises a square covalent organic framework material and hydrophilic antibiotics and hydrophobic antibiotics arranged on the surface of the square covalent organic framework material; the lattice covalent organic framework material comprises hydrophilic pores and hydrophobic pores which are alternately arranged. The antibacterial dressing has the advantages of simple structure, long-term antibacterial property and water-oxygen permeability, simple preparation method and wide application range.

Description

Antibacterial dressing, and preparation method and application thereof

Technical Field

The invention relates to the technical field of medical materials, in particular to an antibacterial dressing, a preparation method and application thereof.

Background

Traditional wound dressing can only help healing through physical protection, but the defects of ventilation, water permeability, antibiosis and bacteriostasis can easily lead to infection or adhesion of the wound, and the wound dressing needs to be replaced frequently, which can easily lead to secondary injury or infection of the wound. Therefore, the conventional wound dressing cannot well meet the requirements of wound care.

The combined use of antibiotics is a new important strategy for effectively combating multi-drug resistant bacterial infections. The wound healing process is often susceptible to infection by pathogenic bacteria such as e.coli, staphylococcus aureus and multidrug-resistant bacteria, which can lead to the risk of continuous inflammation and sepsis of the wound. In order to achieve good sterilization effect and maintain a long-term sterile environment of the surface, the wound dressing is required to be capable of rapidly releasing antibacterial drugs at the wound surface initially, killing bacteria efficiently and rapidly, and then releasing for a long time to maintain an effective antibacterial level. However, loading an antibiotic does not allow for controlled release and the bacteriostatic effect is difficult to maintain.

Shi et al add hydrophilic epigallocatechin gallate (EGCG) to the outer shell of a pH responsive mixed shell polymeric micelle and load ciprofloxacin into the core, the hydrophilic-hydrophobic drug co-release system has balanced biofilm spreading and killing effects (adv. Function. Mater.2022,32 (51), 2209185 (1-13)).

Fan et al redesigned the inner surface of ferritin drug carriers (ins-FDC) nanocarriers as a drug delivery platform and used a urea thermal incubation loading method to maximize simultaneous loading of hydrophilic and hydrophobic drugs (Theranostics 2022,12 (4), 1800-1815).

Compared with a single drug-carrying system, the double drug-carrying system has higher synergistic anti-tumor effect and can effectively overcome the drug resistance of tumor cells. The delivery system for loading hydrophilic and hydrophobic drugs in the prior art has a complex structure, and has difficulty in having both long-term antibacterial property and water oxygen permeability, and affecting the drug action.

It is therefore of great importance to develop an antimicrobial dressing that is a simpler and more effective dual drug delivery system.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide an antibacterial dressing, a preparation method and application thereof, wherein the antibacterial dressing has a simple structure, long-term antibacterial property and water-oxygen permeability, and the preparation method is simple and has a wide application range.

To achieve the purpose, the invention adopts the following technical scheme:

in a first aspect, the present invention provides an antimicrobial dressing comprising a fibrous membrane having an antibiotic composition distributed therein;

the antibiotic composition comprises a square covalent organic framework material (COF) and hydrophilic antibiotics and hydrophobic antibiotics arranged on the surface of the COF;

the lattice covalent organic framework material comprises hydrophilic pores and hydrophobic pores which are alternately arranged.

According to the invention, through the grid covalent organic framework material provided with the hydrophilic holes and the hydrophobic holes which are alternately arranged, the hole environment is orderly, so that a double medicine carrying system with a simple structure is formed, the condition of drug-resistant bacteria infection can be effectively resisted, the application range of the dressing is enlarged, and the antibacterial effect is improved; and the antibiotic composition is combined with the fiber cloth, so that excessive use of antibiotics is avoided, the slow release of the antibiotics is further ensured to realize a long-term antibacterial effect, and the antibacterial dressing can allow water and oxygen to permeate after being tightly attached to skin, so that secondary injury to wounds is reduced.

In the present invention, "hydrophilic" in the hydrophilic antibiotics means: apparent distribution volume (V) _d ) Smaller, V _d An antibiotic which does not readily pass through lipid cell membranes and is distributed mainly in blood and body fluids, is less than 1.0L/kg.

"hydrophobic" in the hydrophobic antibiotic refers to: apparent distribution volume (V) _d ) Larger, V _d Is more than or equal to 1.0L/kg, and is easy to be communicatedAntibiotics that cross lipid cell membranes and are distributed mainly in tissues and organs.

Preferably, the hydrophilic antibiotic comprises any one or a combination of at least two of vancomycin (Van), amikacin (Ami), gentamicin (Gen), doripenem (Dor), kanamycin (Kan), daptomycin (Dap), amoxicillin (Amo) or streptomycin (Str), wherein typical but non-limiting combinations include: combinations of vancomycin, amikacin, and gentamicin, combinations of doripenem, kanamycin, daptomycin, and amoxicillin, combinations of gentamicin, doripenem, kanamycin, daptomycin, amoxicillin, and streptomycin, and the like.

Preferably, the hydrophobic antibiotic comprises any one or a combination of at least two of levofloxacin (Lev), ciprofloxacin (Cip), azithromycin (Azi), doxycycline (Dox), metronidazole (Met), linezolid (Lin), tetracycline (Tet), triclosan (Tri), rifampin (Rif), or norfloxacin (Nor), wherein typical but non-limiting combinations include: a combination of levofloxacin, ciprofloxacin and azithromycin, a combination of azithromycin, doxycycline, metronidazole, linezolid, tetracycline and triclosan, a combination of azithromycin, doxycycline, metronidazole, linezolid, tetracycline, triclosan, rifampin and norfloxacin, and the like.

Preferably, the parts by weight of the hydrophilic and hydrophobic antibiotics are each independently 10-50 parts, e.g., 15 parts, 20 parts, 25 parts, 30 parts, 35 parts, 40 parts, 45 parts, etc., based on 100 parts total mass of the square covalent organic framework material.

Preferably, in the pane covalent organic framework material, the hydrophilic group in the hydrophilic pore includes any one or a combination of at least two of an alkoxy group, a mercapto group, an amino group, a carboxylate or a sulfonate group.

Preferably, the hydrophobic groups in the hydrophobic pores comprise any one or a combination of at least two of alkyl groups, fluoroalkyl groups, or fluoroaryl groups.

Illustratively, when the hydrophilic group is an alkoxy group, the hydrophobic group is an alkyl group;

when the hydrophilic group is carbonate, the hydrophobic group is a fluorine-containing chain;

when the hydrophilic group is a sulfhydryl group, the hydrophobic group is a fluorine-containing chain;

when the hydrophilic group is an amino group, the hydrophobic group is a fluorine-containing chain;

when the hydrophilic group is phenyl, the hydrophobic group is fluorobenzene.

Illustratively, the structure of the lattice covalent organic framework material comprises: alkoxy-alkyl-COF, carbonate-fluoro-COF, mercapto-fluoro-COF, amino-fluoro-COF, benzene-fluorobenzene-COF.

In the invention, the preparation method of the square covalent organic framework material comprises the following steps: the catalyst is prepared by using an isosceles aldehyde monomer and an amino monomer as reaction raw materials through Schiff base reaction under the action of an acid catalyst.

Illustratively, the preparation process is described in particular in CN 114736344A.

Preferably, the lattice covalent organic framework material further comprises porphyrin groups.

Preferably, the fibrous membrane further comprises a carrier material.

Preferably, the carrier material comprises any one or a combination of at least two of Polycaprolactone (PCL), gelatin, polyvinyl butyral (PVB), polyglycolic acid (PGA), polyethylene oxide (PEO), polylactic acid-glycolic acid copolymer (PLGA), polyvinyl alcohol (PVA), or polylactic acid (PLA), wherein typical but non-limiting combinations include: a combination of polycaprolactone and gelatin, a combination of polyvinyl butyral, polyglycolic acid, polyethylene oxide, and a polylactic acid-glycolic acid copolymer, a combination of polylactic acid-glycolic acid copolymer, polyvinyl alcohol, and polylactic acid, and the like, and a combination of polycaprolactone and gelatin is further preferable.

Preferably, the mass ratio of polycaprolactone to gelatin is 10: (1-5), wherein 1-5 may be 1.5, 2, 2.5, 3, 3.5, 4, 4.5, etc.

Preferably, the antibiotic composition is present in an amount of 10 to 50 parts by weight, e.g. 15 parts, 20 parts, 25 parts, 30 parts, 35 parts, 40 parts, 45 parts, etc., based on 100 parts by weight of the total mass of the carrier material.

In a second aspect, the present invention provides a method for preparing the antimicrobial dressing according to the first aspect, the method comprising the steps of:

(1) The hydrophilic antibiotics and the hydrophobic antibiotics are arranged on the surface of the grid covalent organic framework material, so that an antibiotic composition is obtained;

(2) The antibacterial dressing is obtained by preparing a fibrous membrane distributed with an antibacterial composition.

Preferably, in step (1), the setting mode specifically includes: mixing hydrophilic antibiotics, hydrophobic antibiotics and check covalent organic framework materials with a solvent, and separating the obtained mixed solution to obtain the anti-biological composition.

Preferably, the mass concentration of the hydrophilic antibiotics and the hydrophobic antibiotics is respectively 0.1% -3%.

Preferably, the mixing comprises means comprising stirring.

Preferably, the mixing specifically comprises: the hydrophilic antibiotics, the hydrophobic antibiotics and the solvent are mixed for the first time and then mixed with the square covalent organic framework material for the second time.

Preferably, the rotational speed of the first and second mixing is each independently 100-2000rpm, e.g. 200rpm, 400rpm, 600rpm, 800rpm, 1000rpm, 1200rpm, 1400rpm, 1600rpm, 1800rpm, etc.

Preferably, the time of the first mixing is 10-30min.

Preferably, the time of the second mixing is 15-48 hours, such as 20 hours, 25 hours, 30 hours, 35 hours, 40 hours, 45 hours, etc.

Preferably, the means of separation comprises centrifugation.

Preferably, after the separation, washing and drying are also included.

Preferably, the washed solvent comprises water and/or ethanol.

Preferably, the drying temperature is 40-100deg.C, such as 50deg.C, 60deg.C, 70deg.C, 80deg.C, 90deg.C, etc.

Preferably, in the step (2), the preparation method of the fiber membrane comprises electrospinning.

In the invention, the nanofiber membrane prepared by electrostatic spinning has specific pore size distribution besides physical protection effect, and can allow water and oxygen to permeate after being tightly attached to skin, so that secondary damage to wounds is reduced.

Preferably, the spinning solution used for the electrospinning comprises a carrier material, an antibiotic composition and a solvent.

Preferably, the method of preparing the dope comprises stirring the carrier material, the antibiotic composition and the solvent.

Preferably, the stirring time is 6-10 hours, such as 7 hours, 8 hours, 9 hours, etc.

Preferably, the mass concentration of the carrier material in the dope is 1% -10%, such as 2%, 4%, 6%, 8%, 10%, etc.

Preferably, the dope concentration of the antibiotic composition in the dope is 100-500. Mu.g/mL, e.g. 200. Mu.g/mL, 300. Mu.g/mL, 400. Mu.g/mL, 450. Mu.g/mL, etc.

Preferably, the solvent used in the dope comprises Hexafluoroisopropanol (HFIP).

Preferably, in the electrostatic spinning, the positive voltage is 10-20kV (e.g. 12kV, 14kV, 16kV, 18kV, etc.), and the negative voltage is-3 to-5 kV (e.g. -3.5kV, -4kV, -4.5kV, etc.).

Preferably, in the electrospinning, the distance between the receiving plate and the needle is 10-15cm, for example 11cm, 12cm, 13cm, 14cm, etc.

Preferably, in the electrospinning, the spraying rate of the spinning solution is 0.5 to 1.0mm/min, for example, 0.6mm/min, 0.7mm/min, 0.8mm/min, 0.9mm/min, etc.

As a preferable technical scheme, the preparation method comprises the following steps:

(1) Mixing hydrophilic antibiotics, hydrophobic antibiotics and solvent for 10-30min at 100-2000rpm, mixing with square covalent organic frame material for 15-48 hr at 100-2000rpm, centrifuging, washing, and drying at 40-100deg.C to obtain antibiotic composition;

(2) Stirring a carrier material, an antibiotic composition and a solvent for 6-10 hours to form a spinning solution, carrying out electrostatic spinning under the conditions that the positive voltage is 10-20kV, the negative voltage is-3 to-5 kV, the distance between a receiving plate and a needle head is 10-15cm, and the spraying rate of the spinning solution is 0.5-1.0mm/min, so as to obtain the antibacterial dressing.

In a third aspect, the present invention provides an anti-tumour medicament comprising the antimicrobial dressing of the first aspect.

Compared with the prior art, the invention has the following beneficial effects:

(1) The antibacterial dressing has long-term antibacterial property and water-oxygen permeability, and the preparation method is simple and has wide application range.

(2) In the antibiotic combination of the antibacterial dressing, the loading rate of the hydrophilic antibiotics is more than 18%, the loading rate of the hydrophobic antibiotics is more than 15%, the release rate of the hydrophilic antibiotics after 30 hours is more than 79%, and the release rate of the hydrophobic antibiotics after 30 hours is within 50%; the water contact angle of the antibacterial dressing is 20-55 degrees; the water vapor permeability is 1900-2430 g.m ^-2 Tiantian (heaven) ^-1 The oxygen transmittance is 690-890cm ³ ·m ^-2 Tiantian (heaven) ^-1 。

Drawings

FIG. 1 is a graph of infrared data for materials related to example 1;

FIG. 2 is a graph of the release rates of two antibiotics in the antibiotic compositions described in example 1;

FIG. 3a is an external view of a fibrous membrane after electrospinning of a support material as described in example 1;

FIG. 3b is an appearance of the fiber film after electrospinning of the carrier material and COF described in example 1;

FIG. 3c is an external view of the antibacterial dressing described in comparative example 1;

FIG. 3d is an external view of the antibacterial dressing described in comparative example 2;

FIG. 3e is an external view of the antimicrobial dressing according to example 1;

FIG. 4a is a scanning electron microscope image of a fibrous membrane after electrospinning of a support material as described in example 1;

FIG. 4b is a scanning electron microscope image of the support material and the fiber film after COF electrospinning as described in example 1;

FIG. 4c is a scanning electron microscope image of the antimicrobial dressing described in comparative example 1;

FIG. 4d is a scanning electron microscope image of the antimicrobial dressing described in comparative example 2;

FIG. 4e is a scanning electron microscope image of the antimicrobial dressing described in example 1;

fig. 5 is a schematic structural diagram of the COF described in embodiment 1;

wherein 1-the antibiotic composition of example 1; 2-antibiotic composition of comparative example 2; 3-antibiotic composition of comparative example 1; 4-pane covalent organic framework material; 5-levofloxacin; 6-vancomycin.

Detailed Description

To facilitate understanding of the present invention, examples are set forth below. It will be apparent to those skilled in the art that the examples are merely to aid in understanding the invention and are not to be construed as a specific limitation thereof.

In the present invention, the source information of part of the raw materials in each embodiment is as follows:

polycaprolactone: purchased from Beijing Hua Li De technology Co., ltd. (brand: sigma-Aldrich), brand 440744;

gelatin: purchased from Beijing Ding national biotechnology Co., ltd (brand: sigma-Aldrich), trade name G9382;

COF (example 1) name: alkoxy-alkyl-COFs; the structural schematic diagram is shown in fig. 5, and the chemical formula is as follows:

COF (example 4) name: carbonate-fluoro chain-COF; the chemical formula is as follows:

COF (example 5) name: mercapto-fluoro chain-COF; the chemical formula is as follows:

COF (example 6) name: amino-fluoro chain-COF; the chemical formula is as follows:

COF (example 7) name: benzene-fluorobenzene-COF; the chemical formula is as follows:

the preparation method of the COF comprises the following steps: the catalyst is prepared by using an isosceles aldehyde monomer and an amino monomer as reaction raw materials through Schiff base reaction under the action of an acid catalyst.

In the invention, the equipment used for each electrostatic spinning is ET-2535 selected from Beijing Yongkangle science and technology development Co.

COF (comparative example 3): the COF was prepared as described in example 1 using a combination of multiple co-terminal monomers of 2',5' -bis (2- (2-methoxyethoxy) ethoxy) - [1,1':4',1 '-triphenyl ] -4,4' -dicarboxaldehyde and 2',5' -bis (heptyloxy) - [1,1':4',1 '-triphenyl ] -4,4' -dicarboxaldehyde to form a disordered pore environment.

Example 1

The present embodiment provides an antimicrobial dressing comprising a fibrous membrane having an antibiotic composition distributed therein; the antibiotic composition comprises a square covalent organic framework material and hydrophilic antibiotics and hydrophobic antibiotics arranged on the surface of the square covalent organic framework material; the lattice covalent organic framework material comprises hydrophilic pores and hydrophobic pores which are alternately distributed.

The antibacterial dressing is obtained by a preparation method which comprises the following steps:

(1) 50mg of COF was added to 10mg of levofloxacin Van,10mg of vancomycin Lev and 5mL of acetic acid, stirring was continued at 500rmp for 24 hours, centrifugal separation was performed at 10000rpm for 15 minutes, the particles were collected, washed three times with deionized water, and then dried at 50℃to obtain an antibiotic composition COF@Van & Lev.

(2) Taking polycaprolactone and gelatin with the mass ratio of 10:3 as carrier materials for electrostatic spinning, dissolving the carrier materials in hexafluoroisopropanol, stirring for 6 hours, and adding COF@Van & Lev, wherein the mass ratio of the carrier materials to the COF@Van & Lev is 100:1, continuously stirring for 6 hours to obtain spinning solution, and carrying out electrostatic spinning, wherein the adjustment parameters are as follows: the positive voltage is 15kV, the negative voltage is-3 kV, the distance between the receiving plate and the needle is 15cm, and the spraying rate of the spinning solution is 0.5mm/min, so that the fiber membrane, namely the antibacterial dressing, is obtained.

Examples 2 to 3

Examples 2 to 3 differ from example 1 in that Van and Lev were added in amounts of 2.5mg (example 2, antibiotic concentration of 0.5%) and 5mg (example 3, antibiotic concentration of 1%) respectively, and the remainder was the same as example 1 (antibiotic concentration of 2%).

Example 4

The present embodiment provides an antimicrobial dressing comprising a fibrous membrane having an antibiotic composition distributed therein; the antibiotic composition comprises a square covalent organic framework material and hydrophilic antibiotics and hydrophobic antibiotics arranged on the surface of the square covalent organic framework material; the lattice covalent organic framework material includes hydrophilic pores and hydrophobic pores.

(1) 50mg of COF was added to 10mg Cip,10mg Ami and 5mL of acetic acid, stirring was continued at 500rmp for 24 hours, centrifugation was carried out at 10000rpm for 15 minutes, the particles were collected, washed three times with deionized water, and then dried at 50℃to obtain antibiotic composition COF@Cip & Ami.

(2) Taking polycaprolactone and gelatin with the mass ratio of 10:3 as carrier materials for electrostatic spinning, dissolving the carrier materials in hexafluoroisopropanol, stirring for 6 hours, and adding COF@Cip & Ami, wherein the mass ratio of the carrier materials to the COF@Van & Lev is 100:1, continuously stirring for 6 hours to obtain spinning solution, and carrying out electrostatic spinning, wherein the adjustment parameters are as follows: the positive voltage is 15kV, the negative voltage is-3 kV, the distance between the receiving plate and the needle is 15cm, and the spraying rate of the spinning solution is 0.5mm/min, so that the fiber membrane, namely the antibacterial dressing, is obtained.

Example 5

(1) 5mg of COF was added to 10mg Amo,10mg Met and 5mL of acetic acid, stirring was continued at 500rmp for 24 hours, centrifugation was performed at 10000rpm for 15 minutes, the particles were collected, washed three times with deionized water, and then dried at 50℃to obtain an antibiotic composition COF@Amo & Met.

(2) Taking polycaprolactone and gelatin with the mass ratio of 10:3 as carrier materials for electrostatic spinning, dissolving the carrier materials in hexafluoroisopropanol, stirring for 6 hours, and adding COF@Amo & Met, wherein the mass ratio of the carrier materials to the COF@Van & Lev is 100:1, continuously stirring for 6 hours to obtain spinning solution, and carrying out electrostatic spinning, wherein the adjustment parameters are as follows: the positive voltage is 15kV, the negative voltage is-3 kV, the distance between the receiving plate and the needle is 15cm, and the spraying rate of the spinning solution is 0.5mm/min, so that the fiber membrane, namely the antibacterial dressing, is obtained.

Example 6

(1) 5mg of COF was added to 10mg Gen,10mg Nor and 5mL of acetic acid, stirring was continued at 500rmp for 24 hours, centrifugation was performed at 10000rpm for 15 minutes, the particles were collected, washed three times with deionized water, and then dried at 50℃to obtain an antibiotic composition COF@Gen Nor.

(2) Taking polycaprolactone and gelatin with the mass ratio of 10:3 as carrier materials for electrostatic spinning, dissolving the carrier materials in hexafluoroisopropanol, stirring for 6 hours, and adding COF@Gen Nor, wherein the mass ratio of the carrier materials to the COF@Van & Lev is 100:1, continuously stirring for 6 hours to obtain spinning solution, and carrying out electrostatic spinning, wherein the adjustment parameters are as follows: the positive voltage is 15kV, the negative voltage is-3 kV, the distance between the receiving plate and the needle is 15cm, and the spraying rate of the spinning solution is 0.5mm/min, so that the fiber membrane, namely the antibacterial dressing, is obtained.

Example 7

(1) 5mg of COF was added to 10mg Lin,10mg Dap and 5mL of acetic acid, stirring was continued at 500rmp for 24 hours, centrifugation was performed at 10000rpm for 15 minutes, the particles were collected, washed three times with deionized water, and then dried at 50℃to obtain an antibiotic composition COF@dap & Lin.

(2) Taking polycaprolactone and gelatin with the mass ratio of 10:3 as carrier materials for electrostatic spinning, dissolving the carrier materials in hexafluoroisopropanol, stirring for 6 hours, and adding COF@dap & Lin, wherein the mass ratio of the carrier materials to the COF@Van & Lev is 100:1, continuously stirring for 6 hours to obtain spinning solution, and carrying out electrostatic spinning, wherein the adjustment parameters are as follows: the positive voltage is 15kV, the negative voltage is-3 kV, the distance between the receiving plate and the needle is 15cm, and the spraying rate of the spinning solution is 0.5mm/min, so that the fiber membrane, namely the antibacterial dressing, is obtained.

Comparative example 1

This comparative example differs from example 1 in that Van is not added and the resulting antibiotic composition is COF@Lev and the remainder is the same as example 1.

Comparative example 2

This comparative example differs from example 1 in that no Lev was added and the resulting antibiotic composition was cof@van, the remainder being the same as example 1.

Comparative example 3

This comparative example differs from example 1 in that the COF was replaced with an equal mass of other COF in which the pore environment was disordered, the remainder being the same as example 1.

Performance testing

The antimicrobial dressings described in examples 1-7 and comparative examples 1-3 were subjected to the following test:

(1) Release rate and loading rate of antibiotics: the antibiotic compositions were tested for loading and release rates of antibiotics.

m _a Mass, m, of the antibiotic of the load _a+COF M is the total mass of the loaded antibiotic and COF _r Is the mass of the antibiotic released.

(2) Appearance of the antimicrobial dressing: the appearance of the antimicrobial dressing was observed.

(3) Distribution of antibiotic composition in antimicrobial dressing: and observing through a scanning electron microscope.

(4) Water contact angle of the antimicrobial dressing: the test was performed using a water contact angle analyzer.

(5) Structure of antibiotic composition: obtained by infrared testing.

(6) Water oxygen permeability: the water oxygen transmittance device is tested, and the water oxygen transmittance device is specifically:

the Water Vapor Transmission Rate (WVTR) of the sample is determined according to ASTM F1249-13 using a WVTR tester (W3-010, labthink, china). The test was carried out at 25℃and 75% Relative Humidity (RH).

Samples were tested for Oxygen Transmission (OTR) using an isostatic pressure method using a permeability tester (OTR-x 1, harke, china) according to ISO 15105-1 at a temperature of 23℃and at different humidity values (50% RH).

The test results are summarized in table 1 and fig. 1-4 e.

TABLE 1

From analysis of the data in table 1, it can be seen that in the antibiotic combination of the antibacterial dressing according to the present invention, the loading rate of the hydrophilic antibiotics is 18% or more, the loading rate of the hydrophobic antibiotics is 15% or more, the release rate of the hydrophilic antibiotics after 30 hours is 79% or more, and the release rate of the hydrophobic antibiotics after 30 hours is within 50%; the water contact angle of the antibacterial dressing is 24.45-52.33 degrees; the water vapor permeability is 1900-2430 g.m ^-2 Tiantian (heaven) ^-1 The oxygen transmittance is 690-890cm ³ ·m ^-2 Tiantian (heaven) ^-1 The method comprises the steps of carrying out a first treatment on the surface of the The antibacterial dressing has long-term antibacterial property and water-oxygen permeability, and the preparation method is simple and has wide application range.

In order to achieve good sterilization effect and maintain a long-term sterile environment of the wound surface, the wound surface dressing is required to be capable of releasing antibacterial drugs at the wound surface in an initial burst mode, rapidly killing bacteria, and then releasing for a long time to maintain an effective antibacterial level. Wound exudates facilitate the rapid release of the carried hydrophilic drug and the sustained release of the carried hydrophobic drug. Thus, the loading of the antibiotic is important in terms of the long-term release of the antibiotic, i.e. the therapeutic effect, in stages.

Analysis of comparative examples 1-2 and example 1 shows that comparative examples 1-2 perform less well than example 1, demonstrating that the antimicrobial dressing of the present invention performs better than a single drug delivery system.

Analysis of comparative example 3 with example 1 shows that comparative example 3 does not perform as well as example 1, shows a lower antibiotic loading, and a nearly simultaneous rapid release rate, demonstrating better performance of the antimicrobial dressing formed with the checkered covalent organic framework material.

FIG. 1 summarizes the infrared test results relating to antibiotic composition 1 (COF@Van & Lev) of example 1, antibiotic composition 2 (COF@Van) of comparative example 2, antibiotic composition 3 (COF@Lev) of comparative example 1, square covalent organic framework material 4 (COF), levofloxacin 5 (Van), vancomycin 6 (Lev), demonstrating that the preparation method described herein successfully prepared the antibiotic composition.

Fig. 2 shows, by way of example 1, a graph of the release rate of two antibiotics in the antibiotic composition over time, demonstrating the long-term antimicrobial properties of the antimicrobial dressing according to the invention.

Figures 3a-3e provide an appearance of several groups of fibrous films, including in particular the antimicrobial dressings described in example 1, comparative example 1 and comparative example 2, as well as fibrous films prepared with the carrier materials, carrier materials and COFs referred to in example 1.

Fig. 4 a-4 e provide several sets of sem images of fibrous films, including in particular the antimicrobial dressings described in example 1, comparative example 1 and comparative example 2, and fibrous films prepared with the carrier material, carrier material and COF as referred to in example 1, demonstrating that the preparation methods described in the present invention successfully prepared the antimicrobial dressings.

The applicant states that the detailed method of the present invention is illustrated by the above examples, but the present invention is not limited to the detailed method described above, i.e. it does not mean that the present invention must be practiced in dependence upon the detailed method described above. It should be apparent to those skilled in the art that any modification of the present invention, equivalent substitution of raw materials for the product of the present invention, addition of auxiliary components, selection of specific modes, etc., falls within the scope of the present invention and the scope of disclosure.

Claims

1. An antimicrobial dressing, characterized in that the antimicrobial dressing comprises a fibrous membrane with an antibiotic composition distributed therein;

the antibiotic composition comprises a square covalent organic framework material and hydrophilic antibiotics and hydrophobic antibiotics arranged on the surface of the square covalent organic framework material;

2. The antimicrobial dressing of claim 1, wherein the hydrophilic antibiotic comprises any one or a combination of at least two of vancomycin, amikacin, gentamicin, doripenem, kanamycin, daptomycin, amoxicillin, or streptomycin;

preferably, the hydrophobic antibiotic comprises any one or a combination of at least two of levofloxacin, ciprofloxacin, azithromycin, doxycycline, metronidazole, linezolid, tetracycline, triclosan, rifampin or norfloxacin;

preferably, the parts by weight of the hydrophilic and hydrophobic antibiotics are each independently 10-50 parts based on 100 parts of the total mass of the lattice covalent organic framework material.

3. The antimicrobial dressing of claim 1 or 2, wherein in the lattice covalent organic framework material, the hydrophilic groups in the hydrophilic pores comprise any one or a combination of at least two of an alkoxy group, a sulfhydryl chain, an amino chain, a carboxylate, or a sulfonate group;

preferably, the hydrophobic groups in the hydrophobic pores comprise any one or a combination of at least two of alkyl, fluoroalkyl or fluoroaryl groups;

4. The antimicrobial dressing of claims 1-3, wherein the fibrous membrane further comprises a carrier material;

preferably, the carrier material comprises any one or a combination of at least two of polycaprolactone, gelatin, polyvinyl butyral, polyglycolic acid, polyethylene oxide, polylactic acid-glycolic acid copolymer, polyvinyl alcohol, or polylactic acid;

preferably, the mass ratio of polycaprolactone to gelatin is 10: (1-5);

preferably, the antibiotic composition is present in an amount of 10 to 50 parts by weight based on 100 parts by weight of the total mass of the carrier material.

5. A method of preparing an antimicrobial dressing according to any one of claims 1 to 4, comprising the steps of:

6. The method according to claim 5, wherein in the step (1), the setting mode specifically includes: mixing hydrophilic antibiotics, hydrophobic antibiotics and check covalent organic framework materials with a solvent, and separating the obtained mixed solution to obtain the anti-biological composition;

preferably, the mass concentration of the hydrophilic antibiotics and the hydrophobic antibiotics is respectively 0.1% -3%;

preferably, the mixing comprises stirring;

preferably, the mixing specifically comprises: mixing hydrophilic antibiotics, hydrophobic antibiotics and solvent for the first time, and then mixing with the grid covalent organic framework material for the second time;

preferably, the rotational speeds of the first and second mixing are each independently 100-2000rpm;

preferably, the time of the first mixing is 10-30min;

preferably, the time of the second mixing is 15-48 hours;

preferably, the means of separation comprises centrifugation.

7. The method of claim 6, further comprising washing and drying after the separating;

preferably, the washed solvent comprises water and/or ethanol;

preferably, the drying temperature is 40-100 ℃.

8. The method according to any one of claims 5 to 7, wherein in the step (2), the method for producing a fiber film comprises electrospinning;

preferably, the spinning solution used for the electrostatic spinning comprises a carrier material, an antibiotic composition and a solvent;

preferably, the method of preparing the dope comprises stirring a carrier material, an antibiotic composition and a solvent;

preferably, the stirring time is 6-10h;

preferably, in the spinning solution, the mass concentration of the carrier material is 1% -10%;

preferably, the doping concentration of the antibiotic composition in the spinning solution is 100-500 mug/mL;

preferably, the solvent used in the dope comprises hexafluoroisopropanol;

preferably, in the electrostatic spinning, the positive voltage is 10-20kV, and the negative voltage is-3 to-5 kV;

preferably, in the electrostatic spinning, the distance between the receiving plate and the needle head is 10-15cm;

preferably, in the electrostatic spinning, the spraying rate of the spinning solution is 0.5-1.0mm/min.

9. The preparation method according to any one of claims 5 to 8, characterized in that the preparation method comprises the steps of:

10. An antitumor drug comprising the antibacterial dressing according to any one of claims 1 to 4.