CN116617436B - Antibacterial dressing and preparation method thereof - Google Patents

Antibacterial dressing and preparation method thereof Download PDF

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Publication number
CN116617436B
CN116617436B CN202310597243.7A CN202310597243A CN116617436B CN 116617436 B CN116617436 B CN 116617436B CN 202310597243 A CN202310597243 A CN 202310597243A CN 116617436 B CN116617436 B CN 116617436B
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metal organic
organic framework
compound
deionized water
framework compound
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CN116617436A (en
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郭志睿
袁毅
潘金顺
张晨
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2nd Affiliated Hospital of Nanjing Medical University
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2nd Affiliated Hospital of Nanjing Medical University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/20Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/18Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing inorganic materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/26Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/44Medicaments
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42Use of materials characterised by their function or physical properties
    • A61L15/46Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
    • DTEXTILES; PAPER
    • D01NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01DMECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
    • D01D5/00Formation of filaments, threads, or the like
    • D01D5/0007Electro-spinning
    • D01D5/0015Electro-spinning characterised by the initial state of the material
    • D01D5/003Electro-spinning characterised by the initial state of the material the material being a polymer solution or dispersion
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • A61L2300/406Antibiotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412Tissue-regenerating or healing or proliferative agents
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides an antibacterial dressing and a preparation method thereof, wherein the preparation method comprises the following steps: step 10), sequentially adding silver nitrate, cobalt salt, nitrogen-oxygen-sulfur-containing compound and tannic acid into a container containing deionized water, uniformly stirring, heating, reacting at constant temperature, filtering and washing after the reaction is finished, and drying to obtain a binary metal organic framework compound; step 20), putting the binary metal organic framework compound into deionized water, performing ultrasonic dispersion, adding antibiotics, stirring and mixing uniformly, and filtering and drying to obtain the medicine carrying metal organic framework compound; step 30) adding the drug-loaded metal organic framework compound and medical polyurethane into N, N-dimethylformamide to prepare spinning solution, carrying out electrostatic spinning to prepare a nanofiber membrane, and carrying out vacuum drying to obtain the antibacterial dressing. The antibacterial dressing and the preparation method thereof provided by the invention have excellent antibacterial effect and can accelerate wound healing.

Description

Antibacterial dressing and preparation method thereof
Technical Field
The invention belongs to the technical field of biomedical materials, and particularly relates to an antibacterial dressing and a preparation method thereof.
Background
With the advent and widespread spread of resistant bacteria, many previously effective antibiotics no longer exhibit wonderful therapeutic effects, and many diseases such as pneumonia, tuberculosis, etc. are becoming more and more difficult to treat, and the number of deaths each year due to infection with resistant bacteria, but without effective therapeutic means, also has a tendency to increase year by year. Today, the crisis of antibiotic resistance has evolved into a major health and wellness problem of global concern. The drug-resistant bacteria infection not only increases the medical cost burden, but also improves the possibility of death of patients or causes serious sequelae and other problems.
The surgical operation inevitably causes damage to the skin and tissues at the surgical site, and when microbial contamination of the surgical incision reaches a certain level, infection at the surgical site occurs. Postoperative infection caused by multi-drug resistant bacteria presents the characteristics of complexity and intractability, and the frequency of occurrence is higher and higher in recent years, so that the safety of patients and medical staff is seriously threatened. Aiming at postoperative infection caused by multi-drug resistant bacteria, at present, antibiotic combined treatment is mostly adopted, and particularly, the combined use of antibiotics with higher toxicity can cause higher side effect on the body of a patient.
Disclosure of Invention
The invention aims at the defects and provides an antibacterial dressing and a preparation method thereof, wherein the dressing has excellent antibacterial effect and can accelerate wound healing.
In order to solve the technical problems, the embodiment of the invention adopts the following technical scheme:
in a first aspect, an embodiment of the present invention provides a method for preparing an antimicrobial dressing, including the steps of:
step 10), sequentially adding silver nitrate, cobalt salt, nitrogen-oxygen-sulfur-containing compound and tannic acid into a container containing deionized water, uniformly stirring, heating, reacting at constant temperature, filtering and washing after the reaction is finished, and drying to obtain a binary metal organic framework compound;
step 20), putting the binary metal organic framework compound into deionized water, performing ultrasonic dispersion, adding antibiotics, stirring and mixing uniformly, and filtering and drying to obtain a medicine-carrying metal organic framework compound;
step 30) adding the drug-loaded metal organic framework compound and medical polyurethane into N, N-dimethylformamide to prepare spinning solution, carrying out electrostatic spinning to prepare a nanofiber membrane, and carrying out vacuum drying to obtain the antibacterial dressing.
As a further improvement of the embodiment of the invention, in the step 10), the dosage ratio of the silver nitrate, the cobalt salt, the nitrogen-oxygen-sulfur compound, the tannic acid and the deionized water is 1 g:0.5-0.8 g:0.7-1.3 g:3-4 g:5-8 mL.
As a further improvement of the embodiment of the present invention, in the step 10), the cobalt salt is one of cobalt chloride, cobalt bromide, cobalt iodide and cobalt nitrate.
As a further improvement of the embodiment of the present invention, in the step 10), the nitrogen-oxygen-sulfur-containing compound is one of ergothioneine, cystine, and 5,5' - (dithioalkanediylbis (methylene)) bis (4- (hydroxymethyl) -2-methylpyridin-3-ol).
As a further improvement of the embodiment of the invention, in the step 10), the reaction temperature is 95-121 ℃ and the reaction time is 1-16 h.
As a further improvement of the embodiment of the present invention, in the step 20), the antibiotics are three combinations of vancomycin, polymyxin E sulfate and gentamicin sulfate.
As a further improvement of the embodiment of the present invention, in the step 20), the dosage ratio of the metal organic framework compound, deionized water, vancomycin, polymyxin E sulfate and gentamicin sulfate is 1 g:100-120 ml:0.3-0.5 g:20-75 mg:2-4 g.
As a further improvement of the embodiment of the present invention, in the step 30), the dosage ratio of the drug-loaded metal organic framework compound, the medical polyurethane and the N, N-dimethylformamide is 0.1-0.3 g/1 g/10-15 mL.
As a further improvement of the embodiment of the present invention, in the step 30), the medical polyurethane isTPU 2363-55DE、/>SP 806 and->One of the TPU 5590.
In a second aspect, the embodiment of the invention also provides an antibacterial dressing, which is prepared by the preparation method.
Compared with the prior art, the technical scheme of the invention has the following beneficial effects:
(1) In the embodiment of the invention, the lone pair electron on N, O atom of the nitrogen-oxygen-sulfur compound is represented by Co 2+ Sp of (2) 3 d 2 The empty orbitals generated by orbital hybridization are received to form coordination bonds, and the lone pair electrons on the S atom of the nitrogen-oxygen-sulfur-containing compound are replaced by Ag + The empty orbital acceptor generated by sp orbital hybridization forms a coordination bond, thereby using a nitrogenous oxysulfide compound containing a sulfhydryl group or a disulfide bond as a bridging ligand, and Co 2+ And Ag + As a coordination compound formed by a central atom, the compound is mixed with antibiotics to be used as a carrier of the antibiotics, so that the compound has higher drug loading capacity and good antibacterial property;
(2) In the embodiment of the invention, tannic acid can be reversibly self-polymerized in the aqueous solution, one part of self-polymerized tannic acid is combined with the coordination compound to form a binary metal organic frame structure, the other part of self-polymerized big tannic acid is coated outside the binary metal organic frame, and the two parts of self-polymerized tannic acid are covalently connected, so that the binary metal organic frame structure is in a redox balance state and is not easy to be oxidized to be damaged, the rapid release of antibiotics is prevented, the side effect of the medicine is reduced, and the long-term bacteriostasis effect is achieved;
(3) When the release of the antibiotic is basically complete in the later period, tannic acid is depolymerized and released, the binary metal organic framework structure is disintegrated to a certain extent, and Ag + Release can take over the action of antibiotics, while Co 2+ Can regulate and control the expression of vascular endothelial growth factor VEGF, promote the formation of new blood vessels and accelerate wound healing.
Drawings
FIG. 1 is a flow chart of a method of making an antimicrobial dressing according to an embodiment of the invention;
FIG. 2 is a comparative graph of the results of in vitro antimicrobial experiments performed on the dressings prepared in examples and comparative examples, respectively;
fig. 3 is a graph comparing healing results of treatment of a rat full-thickness infected wound surface with doctor's gauze, dressing prepared in examples and comparative examples, respectively.
Detailed Description
For a further understanding of the present invention, preferred embodiments of the invention are described below in conjunction with the following examples, but it should be understood that these descriptions are merely intended to further illustrate the features and advantages of the invention and are not limiting of the claims of the invention.
The embodiment of the invention provides a preparation method of an antibacterial dressing, as shown in fig. 1, comprising the following steps:
and 10) sequentially adding silver nitrate, cobalt salt, nitrogen-oxygen-sulfur-containing compound and tannic acid into a container containing deionized water, uniformly stirring, heating, reacting at constant temperature, filtering and washing after the reaction is finished, and drying to obtain the binary metal organic framework compound.
Wherein silver nitrate provides Ag + Can form coordination bond with nitrogen oxygen sulfur compound and has certain antibacterial property. And the silver nitrate has good solubility and is safe to use.
The cobalt salt is one of cobalt chloride, cobalt bromide, cobalt iodide and cobalt nitrate, and provides Co 2+ Can form coordination bond with nitrogen oxygen sulfur compound.
The covalent bonding mode of sulfur of the nitrogen-oxygen-sulfur-containing compound is sulfhydryl or disulfide, and the nitrogen and oxygen atoms can provide lone pair electrons. Preferably, the nitrogen-containing oxy-sulfur compound is one of ergothioneine, cystine, and 5,5' - (dithioalkanediylbis (methylene)) bis (4- (hydroxymethyl) -2-methylpyridin-3-ol).
Preferably, the dosage ratio of the silver nitrate, the cobalt salt, the nitrogen-oxygen-sulfur compound, the tannic acid and the deionized water is 1 g:0.5-0.8 g:0.7-1.3 g:3-4 g:5-8 mL.
Preferably, the reaction temperature is 95-121 ℃ and the reaction time is 1-16 h. Under the conditions of the temperature range and the time range, silver nitrate, cobalt salt, nitrogen-oxygen-sulfur-containing compound and tannic acid react to obtain the binary metal organic framework compound.
And 20) putting the binary metal organic frame compound into deionized water, performing ultrasonic dispersion, adding antibiotics, stirring and uniformly mixing, and filtering and drying to obtain the medicine carrying metal organic frame compound VCG_MOFs.
Preferably, the antibiotic is one, any two or three of vancomycin, polymyxin E sulfate and gentamicin sulfate. Among them, vancomycin has strong action on methicillin-resistant staphylococcus and can be used for penicillin allergic patients. Polymyxin E sulfate has remarkable effect on pseudomonas aeruginosa. Gentamicin sulfate has good antibacterial effect against various gram-negative bacteria and gram-positive bacteria, but has poor effect against methicillin-resistant staphylococcus, streptococcus pneumoniae and enterococcus.
Further preferred antibiotics are three combinations of vancomycin, polymyxin E sulfate and gentamicin sulfate. The antibiotics of the preferred embodiment adopt the combination of the three antibiotics, and the three antibiotics have different action mechanisms, can better cooperate with the antibacterial agent, have fewer drug-resistant strains compared with the common antibiotics, and improve the antibacterial performance of the dressing.
Preferably, the dosage ratio of the binary metal organic framework compound, deionized water, vancomycin, polymyxin E sulfate and gentamicin sulfate is 1 g:100-120 mL:0.3-0.5 g:20-75 mg:2-4 g.
Step 30) adding the drug-loaded metal organic frame compound VCG_MOFs and medical polyurethane into N, N-dimethylformamide to prepare spinning solution, carrying out electrostatic spinning to obtain a nanofiber membrane, and carrying out vacuum drying to obtain the antibacterial dressing.
Wherein the medical polyurethane isTPU 2363-55DE、/>SP 806One of the TPU 5590.
Preferably, the dosage ratio of the drug-loaded metal organic frame compound VCG_MOFs, medical polyurethane and N, N-dimethylformamide is 0.1-0.3 g:1 g:10-15 mL.
Preferably, the condition of electrostatic spinning is that the voltage is 15-30 kV, the receiving distance is 12-16 cm, and the injection rate is 0.5-1.2 mL/h.
The embodiment of the invention also provides an antibacterial dressing, which is prepared by adopting the preparation method.
In the embodiment of the invention, the lone pair electron on N, O atom of the nitrogen-oxygen-sulfur compound is represented by Co 2+ Sp of (2) 3 d 2 The empty orbitals generated by orbital hybridization are received to form coordination bonds, and the lone pair electrons on the S atom of the nitrogen-oxygen-sulfur-containing compound are replaced by Ag + The empty orbital acceptor generated by sp orbital hybridization forms a coordination bond, thereby using a nitrogenous oxysulfide compound containing a sulfhydryl group or a disulfide bond as a bridging ligand, and Co 2+ And Ag + As a coordination compound formed by the central atom, the compound is mixed with antibiotics to be used as a carrier of the antibiotics, and has higher drug loading capacity and good antibacterial property. Tannic acid can be reversibly and automatically polymerized in aqueous solution, one part of tannic acid is combined with coordination compound to form a binary metal organic framework structure, the other part of tannic acid is coated outside the binary metal organic framework, and the two parts of tannic acid are covalently connected, so that the binary metal organic framework structure is in oxidation-reduction equilibrium state and is not easy to oxidize to be damaged, antibiotics are prevented from being released rapidly, side effects of the medicines are reduced, and long-term bacteriostasis effect is achieved. When the release of the antibiotic is basically complete in the later period, tannic acid is depolymerized and released, the binary metal organic framework structure is disintegrated to a certain extent, and Ag + Release can take over the action of antibiotics, while Co 2+ Can regulate and control the expression of vascular endothelial growth factor VEGF, promote the formation of new blood vessels and accelerate wound healing.
Specific examples are provided below to demonstrate the superior performance of the antimicrobial dressing made by the method of the present invention.
Example 1
Step 1), adding 1.0g of silver nitrate, 0.67g of cobalt chloride, 1.2g of ergothioneine and 3.2g of tannic acid into a three-neck flask containing 5.5mL of deionized water, magnetically stirring, heating to 115 ℃ for constant-temperature reaction for 14 hours, filtering a sample after the reaction is finished, fully washing with the deionized water, and drying to obtain a binary metal organic frame compound;
step 2) adding 1.0g of a binary metal organic framework compound into 105mL of water, carrying out ultrasonic dispersion, sequentially adding 0.38g of vancomycin, 55mg of polymyxin E sulfate and 3.6g of gentamicin sulfate, fully stirring and uniformly mixing, filtering and drying to obtain VCG_MOFs;
step 3) combining 0.28g of VCG_MOFs with 1gTPU 2363-55DE is added into 12mL of N, N-dimethylformamide to prepare spinning solution, the voltage is 20kV, the receiving distance is 15cm, the injection rate is 1.0mL/h, the nanofiber membrane is prepared by electrospinning, and the antibacterial dressing is obtained by vacuum drying.
Example 2
Step 1), adding 1.0g of silver nitrate, 0.50g of cobalt nitrate, 0.7g of cystine and 3g of tannic acid into a three-neck flask containing 5mL of deionized water, magnetically stirring, heating to 95 ℃ and reacting for 1h at constant temperature, filtering a sample after the reaction is finished, fully washing with deionized water, and drying to obtain a binary metal organic framework compound;
step 2) adding 1.0g of a binary metal organic framework compound into 100mL of water, carrying out ultrasonic dispersion, sequentially adding 0.3g of vancomycin, 20mg of polymyxin E sulfate and 2g of gentamicin sulfate, fully stirring and uniformly mixing, filtering and drying to obtain VCG_MOFs;
step 3) combining 0.1g of VCG_MOFs with 1gSP 806 is added into 10mL of N, N-dimethylformamide to prepare spinning solution, the voltage is 15kV, the receiving distance is 12cm, the injection rate is 0.5mL/h, the nanofiber membrane is prepared by electrospinning, and the antibacterial dressing is obtained by vacuum drying.
Example 3
Step 1) adding 1.0g of silver nitrate, 0.80g of cobalt bromide, 1.3g of 5,5' - (dithioalkanediylbis (methylene)) bis (4- (hydroxymethyl) -2-methylpyridin-3-ol) and 4g of tannic acid into a three-neck flask containing 8mL of deionized water, magnetically stirring, heating to 121 ℃ and reacting for 16 hours at constant temperature, filtering a sample after the reaction is finished, fully washing with the deionized water, and drying to obtain a binary metal organic framework compound;
step 2) adding 1.0g of a binary metal organic framework compound into 120mL of water, carrying out ultrasonic dispersion, sequentially adding 0.5g of vancomycin, 75mg of polymyxin E sulfate and 4g of gentamicin sulfate, fully stirring and uniformly mixing, filtering and drying to obtain VCG_MOFs;
step 3) combining 0.3g of VCG_MOFs with 1gTPU 5590 is added into 15mL of N, N-dimethylformamide to prepare spinning solution, the voltage is 30kV, the receiving distance is 16cm, the injection rate is 1.2mL/h, the nanofiber membrane is prepared by electrospinning, and the antibacterial dressing is obtained by vacuum drying.
Comparative example 1 (SNO free Compound)
Step 1), adding 1.0g of silver nitrate, 0.67g of cobalt chloride and 3.2g of tannic acid into a three-neck flask containing 5.5mL of deionized water, magnetically stirring, heating to 115 ℃ and reacting for 14 hours at constant temperature, filtering a sample after the reaction is finished, fully washing with the deionized water, and drying to obtain powder;
step 2) adding 1.0g of powder into 105mL of water, performing ultrasonic dispersion, sequentially adding 0.38g of vancomycin, 55mg of polymyxin E sulfate and 3.6g of gentamicin sulfate, fully stirring and uniformly mixing, filtering and drying to obtain VCG_powder;
step 3) mixing 0.28g of VCG-powder with 1gTPU 2363-55DE is added into 12mL of N, N-dimethylformamide to prepare spinning solution, the voltage is 20kV, the receiving distance is 15cm, the injection rate is 1.0mL/h, the nanofiber membrane is prepared by electrospinning, and the dressing is obtained by vacuum drying.
Comparative example 2 (no tannic acid)
Step 1), adding 1.0g of silver nitrate, 0.67g of cobalt chloride and 1.2g of ergothioneine into a three-neck flask containing 5.5mL of deionized water, magnetically stirring, heating to 115 ℃ and reacting for 14 hours at constant temperature, filtering a sample after the reaction is finished, fully washing with deionized water, and drying to obtain binary metal MOFs;
step 2) adding 1.0g of binary metal MOFs into 105mL of water, performing ultrasonic dispersion, sequentially adding 0.38g of vancomycin, 55mg of polymyxin E sulfate and 3.6g of gentamicin sulfate, fully stirring and uniformly mixing, filtering and drying to obtain VCG_MOFs;
step 3) combining 0.28g of VCG_MOFs with 1gTPU 2363-55DE is added into 12mL of N, N-dimethylformamide to prepare spinning solution, the voltage is 20kV, the receiving distance is 15cm, the injection rate is 1.0mL/h, the nanofiber membrane is prepared by electrospinning, and the dressing is obtained by vacuum drying.
Comparative example 3 (cobalt-free salt)
Step 1), adding 1.0g of silver nitrate, 1.2g of ergothioneine and 3.2g of tannic acid into a three-neck flask containing 5.5mL of deionized water, magnetically stirring, heating to 115 ℃ and reacting for 14h at constant temperature, filtering a sample after the reaction is finished, fully washing with deionized water, and drying to obtain MOFs;
step 2) adding 1.0g MOFs into 105mL of water, performing ultrasonic dispersion, sequentially adding 0.38g of vancomycin, 55mg of polymyxin E sulfate and 3.6g of gentamicin sulfate, fully stirring and uniformly mixing, filtering and drying to obtain VCG_MOFs;
step 3) combining 0.28g of VCG_MOFs with 1gTPU 2363-55DE is added into 12mL of N, N-dimethylformamide to prepare spinning solution, the voltage is 20kV, the receiving distance is 15cm, the injection rate is 1.0mL/h, the nanofiber membrane is prepared by electrospinning, and the dressing is obtained by vacuum drying.
Evaluation of antimicrobial Properties of textiles using GB/T20944.3-2008 part 3: the dressings prepared in examples 1 to 3 and comparative examples 1 to 3 were tested for their antibacterial effects on clinically obtained methicillin-resistant staphylococcus aureus (MRSA) and multidrug-resistant pseudomonas aeruginosa (PDR-PA) by the methods listed in Oscillating method, respectively, and the results are shown in FIG. 1.
A rat full-layer infection wound model was constructed, the wound was photographed every 2 days using medical gauze, the dressings prepared in examples 1 to 3 and comparative examples 1 to 3, and the wound area was circled with ImageJ software and calculated to obtain the wound healing rate= (wound initial area-wound area)/wound initial area, and the result is shown in fig. 2.
As can be seen from fig. 1 and 2, the dressing prepared in examples 1 to 3 shows a remarkable antibacterial effect, and the dressing prepared in comparative example 2 and comparative example 3 also has a good antibacterial effect. However, the dressings prepared in comparative examples 2 and 3 have great influence on the stability of the binary metal organic frame because tannic acid and cobalt salt are not added, so that medicines such as vancomycin, polymyxin E sulfate, gentamicin sulfate and the like are suddenly released, and although the antibacterial effect is remarkable, the concentration is too large to cause a cytotoxic effect, so that the dressings prepared in comparative examples 2 and 3 have poor treatment effect on wounds infected with rats. The dressing prepared in comparative example 1 has no drug-carrying property and can only rely on Ag combined with tannic acid because of no sulfur-containing oxynitride as bridging structure binary metal organic framework + Provides weak antibacterial properties, and thus, has poor healing effect on infected wounds. The dressing prepared in examples 1-3 constructs a binary metal organic frame structure, and the binary metal organic frame structure is stabilized by the outer tannic acid self-assembly body to adsorb and control release various antibiotics, so as to achieve the long-term antibacterial effect of the wound surface, and the tannic acid structure is recycled to release Co in the later period of wound healing 2+ Promoting the regeneration of blood vessels and accelerating the healing of wound surfaces.
The foregoing has shown and described the basic principles, principal features and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the specific embodiments described above, and that the above specific embodiments and descriptions are provided for further illustration of the principles of the present invention, and that various changes and modifications may be made therein without departing from the spirit and scope of the invention as defined in the appended claims.

Claims (7)

1. A method of making an antimicrobial dressing comprising the steps of:
step 10), sequentially adding silver nitrate, cobalt salt, nitrogen-oxygen-sulfur-containing compound and tannic acid into a container containing deionized water, uniformly stirring, heating, reacting at constant temperature, filtering and washing after the reaction is finished, and drying to obtain a binary metal organic framework compound;
step 20), putting the binary metal organic framework compound into deionized water, performing ultrasonic dispersion, adding antibiotics, stirring and mixing uniformly, and filtering and drying to obtain a medicine-carrying metal organic framework compound;
step 30) adding the drug-loaded metal organic framework compound and medical polyurethane into N, N-dimethylformamide to prepare spinning solution, carrying out electrostatic spinning to prepare a nanofiber membrane, and carrying out vacuum drying to obtain an antibacterial dressing;
in the step 10), the dosage ratio of the silver nitrate, the cobalt salt, the nitrogen-oxygen-sulfur compound, the tannic acid and the deionized water is 1: 1 g:0.5-0.8: 0.8 g:0.7-1.3: 1.3 g:3-4 g:5-8 mL;
in the step 10), the nitrogen-oxygen-sulfur-containing compound is one of ergothioneine, cystine and 5,5' - (dithioalkanediylbis (methylene)) bis (4- (hydroxymethyl) -2-methylpyridin-3-ol);
in the step 10), the reaction temperature is 95-121 ℃ and the reaction time is 1-16 h.
2. The method of claim 1, wherein in step 10), the cobalt salt is one of cobalt chloride, cobalt bromide, cobalt iodide, and cobalt nitrate.
3. The method of claim 1, wherein in step 20), the antibiotic is a combination of three of vancomycin, polymyxin E sulfate, and gentamicin sulfate.
4. The method of claim 3, wherein in the step 20), the metal organic framework compound, deionized water, vancomycin, polymyxin E sulfate and gentamicin sulfate are used in a ratio of 1: 1 g:100-120: 120 mL:0.3-0.5: 0.5 g:20-75 mg:2-4 g.
5. The method of claim 1, wherein in the step 30), the drug-loaded metal organic framework compound, the medical polyurethane and the N, N-dimethylformamide are used in a ratio of 0.1-0.3 g:1 g:10-15: 15mL.
6. The method of manufacturing an antimicrobial dressing according to claim 1, wherein in the step 30), the medical polyurethane is one of Pellethane TPU 2363-55DE, elastollan SP 806 and Texin TPU 5590.
7. An antimicrobial dressing, characterized in that it is produced by the production method according to any one of claims 1 to 6.
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