CN117069876A - Antibacterial agent for PGA and preparation method thereof - Google Patents
Antibacterial agent for PGA and preparation method thereof Download PDFInfo
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- CN117069876A CN117069876A CN202311033470.3A CN202311033470A CN117069876A CN 117069876 A CN117069876 A CN 117069876A CN 202311033470 A CN202311033470 A CN 202311033470A CN 117069876 A CN117069876 A CN 117069876A
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- 239000003242 anti bacterial agent Substances 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 229920001661 Chitosan Polymers 0.000 claims abstract description 60
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims abstract description 46
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 26
- 239000003607 modifier Substances 0.000 claims abstract description 24
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 24
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims abstract description 24
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims abstract description 13
- LOJNBPNACKZWAI-UHFFFAOYSA-N 3-nitro-1h-pyrrole Chemical compound [O-][N+](=O)C=1C=CNC=1 LOJNBPNACKZWAI-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 claims abstract description 12
- 229910001961 silver nitrate Inorganic materials 0.000 claims abstract description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 80
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 45
- 238000002156 mixing Methods 0.000 claims description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 20
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 16
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- UYBWIEGTWASWSR-UHFFFAOYSA-N 1,3-diaminopropan-2-ol Chemical compound NCC(O)CN UYBWIEGTWASWSR-UHFFFAOYSA-N 0.000 claims description 12
- PBLNBZIONSLZBU-UHFFFAOYSA-N 1-bromododecane Chemical compound CCCCCCCCCCCCBr PBLNBZIONSLZBU-UHFFFAOYSA-N 0.000 claims description 10
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 claims description 10
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 claims description 10
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 229960004979 fampridine Drugs 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- LRWZZZWJMFNZIK-UHFFFAOYSA-N 2-chloro-3-methyloxirane Chemical compound CC1OC1Cl LRWZZZWJMFNZIK-UHFFFAOYSA-N 0.000 claims description 5
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 5
- 239000008367 deionised water Substances 0.000 claims description 5
- 229910021641 deionized water Inorganic materials 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 230000007935 neutral effect Effects 0.000 claims description 5
- 239000000758 substrate Substances 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 10
- 241000894006 Bacteria Species 0.000 abstract description 6
- 230000001580 bacterial effect Effects 0.000 abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 5
- 229910052709 silver Inorganic materials 0.000 abstract description 5
- 239000004332 silver Substances 0.000 abstract description 5
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 abstract description 4
- 230000009471 action Effects 0.000 abstract description 4
- 210000000170 cell membrane Anatomy 0.000 abstract description 4
- 238000009826 distribution Methods 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 125000003700 epoxy group Chemical group 0.000 abstract description 2
- 125000002883 imidazolyl group Chemical group 0.000 abstract description 2
- 238000001556 precipitation Methods 0.000 abstract description 2
- 150000003242 quaternary ammonium salts Chemical group 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 125000003277 amino group Chemical group 0.000 abstract 1
- -1 silver ions Chemical class 0.000 abstract 1
- 229920000954 Polyglycolide Polymers 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 239000004593 Epoxy Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 125000003396 thiol group Chemical class [H]S* 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229920003232 aliphatic polyester Polymers 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002148 esters Chemical group 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical class SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/14—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings
- A01N43/16—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings with oxygen as the ring hetero atom
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
- A01N55/02—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur containing metal atoms
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
-
- Y—GENERAL 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Pest Control & Pesticides (AREA)
- General Health & Medical Sciences (AREA)
- Environmental Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Plant Pathology (AREA)
- Dentistry (AREA)
- Agronomy & Crop Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Medicinal Chemistry (AREA)
- Materials Engineering (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
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Abstract
The invention discloses an antibacterial agent for PGA and a preparation method thereof, wherein chitosan and a cross-linking agent are used as raw materials, amino groups on the chitosan and epoxy groups on the cross-linking agent react under alkaline conditions to prepare pretreated chitosan, p-carboxyphenol and 4-nitropyrrole react under the action of potassium carbonate to prepare a modifier, the pretreated chitosan and the modifier react under the action of p-toluenesulfonic acid to prepare modified chitosan, the modified chitosan reacts with silver nitrate to lead imidazole groups of the modified chitosan to coordinate with silver ions to form a metallic silver load, hydroxyl groups in the antibacterial agent can participate in the reaction of PGA, the cooperation of the antibacterial agent and PGA is increased, and meanwhile, the antibacterial agent contains various antibacterial components of quaternary ammonium salt structures, metallic silver and chitosan, so that bacteria can be quickly adsorbed, electrode distribution of bacterial cell membranes is changed, the cell membranes are destroyed, the content is leaked out, the bacteria can not normally grow, the effect of killing the bacteria is achieved, and the problem of precipitation of antibacterial components can not occur.
Description
Technical Field
The invention relates to the technical field of preparation of antibacterial agents, in particular to an antibacterial agent for PGA and a preparation method thereof.
Background
Polyglycolic acid is an aliphatic polyester polymer material with minimum unit carbon number, fully decomposable ester structure and highest degradation speed, and is a world-recognized material for protecting the global environment and life. PGA has very good performance advantages: excellent gas barrier property, excellent mechanical properties, and excellent degradability. Because PGA has good biocompatibility, it has been widely used in medical absorbable surgical suture lines, drug sustained release, simulation of human tissue materials, biodegradable polymer scaffolds, high-strength fiber and other high-value-added products, and because of its excellent properties, it is required to have antibacterial effect when used under partial conditions, and the traditional process is to add antibacterial agent during the preparation of PGA, but after long-term use, antibacterial components will be separated out, thereby affecting normal use.
Disclosure of Invention
The present invention aims to provide an antibacterial agent for PGA, which has a general antibacterial effect in the use process and has a problem of disappearance of antibacterial property after long-term use, and a method for producing the same.
The aim of the invention can be achieved by the following technical scheme:
the preparation method of the antibacterial agent for the PGA specifically comprises the following steps:
step A1: dispersing chitosan in deionized water, adding a cross-linking agent, reacting for 4-6 hours at the rotation speed of 120-150r/min and the temperature of 45-50 ℃ and the pH value of 9-10, filtering to remove filtrate, washing a substrate to be neutral, and drying to obtain pretreated chitosan;
step A2: uniformly mixing p-carboxyphenol, potassium carbonate and DMF (dimethyl formamide), stirring for 1-1.5h at the rotating speed of 200-300r/min and the temperature of 20-25 ℃, adding 4-nitropyrrole, reacting for 20-25h, and regulating the pH value to 4-5 to obtain a modifier;
step A3: uniformly mixing pretreated chitosan, a modifier, p-toluenesulfonic acid and DMF (dimethyl formamide), reacting for 8-10h at the rotation speed of 120-150r/min and the temperature of 110-120 ℃ to obtain modified chitosan, mixing the modified chitosan, silver nitrate, methanol and DMF, and reacting for 25-30h at the rotation speed of 150-200r/min and the temperature of 120-125 ℃ to obtain the antibacterial agent.
Further, the amount of the cross-linking agent in the step A1 is 1 to 1.5 percent of the mass of the chitosan.
Further, the molar ratio of the p-carboxyphenol, the potassium carbonate and the 4-nitropyrrole in the step A2 is 1:1.1:1.
Further, the mass ratio of the pretreated chitosan and the modifier in the step A3 is 1:1.5, the mass of the p-toluenesulfonic acid is 3% of the mass of the modifier, and the dosage ratio of the modified chitosan, the silver nitrate, the methanol and the DMF is 5.5g:10.5g:60mL:60mL.
Further, the cross-linking agent is prepared by the following steps:
step B1: uniformly mixing 1, 3-diamino-2-propanol and ethanol, introducing nitrogen for protection, stirring and adding 4-hydroxybenzaldehyde at the rotation speed of 200-300r/min and the temperature of 40-45 ℃ for reaction for 4-6 hours to obtain an intermediate 1, uniformly mixing the intermediate 1, acrylic acid, p-toluenesulfonic acid and toluene, and reacting at the rotation speed of 120-150r/min and the temperature of 100-110 ℃ for 6-8 hours to obtain an intermediate 2;
step B2: uniformly mixing the intermediate 2, mercaptopropionic acid and DMF, reacting for 1-1.5h under the condition of ultraviolet irradiation at the rotating speed of 60-80r/min and 365nm to obtain an intermediate 3, uniformly mixing the intermediate 3, 4-aminopyridine, N' -dicyclohexyl carbodiimide and DMF, and reacting for 6-8h under the condition of 200-300r/min and the temperature of 25-30 ℃ to obtain an intermediate 4;
step B3: uniformly mixing the intermediate 4, bromododecane and DMF (dimethyl formamide), reacting for 30-40min at the rotation speed of 120-150r/min and the temperature of 120-125 ℃, adding epoxy chloropropane and benzyl triethyl ammonium chloride, introducing nitrogen for protection, reacting for 2-4h at the rotation speed of 150-200r/min and the temperature of 100-105 ℃, cooling to 70-75 ℃, adding sodium hydroxide solution, and continuing to react for 15-20h to obtain the cross-linking agent.
Further, the molar ratio of the 1, 3-diamino-2-propanol and the 4-hydroxybenzaldehyde in the step B1 is 1:2, the molar ratio of the intermediate 1 and the acrylic acid is 1:1, and the dosage of the p-toluenesulfonic acid is 3-5% of the mass of the intermediate 1 and the acrylic acid.
Further, the molar ratio of the intermediate 2 to the mercaptopropionic acid in the step B2 is 1:1, and the molar ratio of the intermediate 3, 4-aminopyridine to the N, N' -dicyclohexylcarbodiimide is 1:1:1.1.
Further, the molar ratio of the intermediate 4, bromododecane, epichlorohydrin, benzyl triethylammonium chloride and sodium hydroxide solution in the step B3 is 1:1:2:6.75:250, and the mass fraction of the sodium hydroxide solution is 30%.
The invention has the beneficial effects that: the invention prepares a PGA with antibacterial agent by taking chitosan and cross-linking agent as raw materials, amino on chitosan and epoxy on cross-linking agent react under alkaline condition to prepare pretreated chitosan, p-carboxyl phenol and 4-nitropyrrole react under the action of potassium carbonate to make phenolic hydroxyl on p-carboxyl phenol react with nitro on p-nitropyrrole, then pH is regulated to acidity to prepare modifier, pre-treated chitosan and modifier are esterified with partial hydroxyl on pre-treated chitosan under the action of p-toluenesulfonic acid to prepare modified chitosan, modified chitosan is reacted with silver nitrate to make imidazole group of modified chitosan coordinate with silver ion to form metallic silver load, cross-linking agent reacts with amino on 1, 3-diamino-2-propanol and 4-hydroxybenzaldehyde to prepare intermediate 1, 3-diamino-2-propanol react with aldehyde on 4-hydroxybenzaldehyde, intermediate 1 and acrylic acid react with hydroxy on p-toluenesulfonic acid to prepare intermediate 2, and hydroxy on epoxy 2-pyridines react with intermediate 3 to prepare mercapto 2-pyridines, finally react with thiol on intermediate 2, and 4-pyridines react with intermediate 2 to prepare mercapto 2, and prepare mercapto-pyridines, finally react with intermediate 2, and prepare mercapto-2-pyridines under the condition, the novel epoxy group is formed, and the cross-linking agent is prepared, wherein the hydroxyl group contained in the antibacterial agent can participate in the reaction of the PGA, so that the cooperation of the antibacterial agent and the PGA is increased, meanwhile, the antibacterial agent contains various antibacterial components of quaternary ammonium salt structure, metallic silver and chitosan, bacteria can be adsorbed quickly, the electrode distribution of bacterial cell membranes is changed, the cell membranes are damaged, the content is leaked, the bacteria cannot grow normally, the effect of killing the bacteria is achieved, and the problem of precipitation of the antibacterial components is avoided.
Detailed Description
The following description of the technical solutions in the embodiments of the present invention will be clear and complete, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
The preparation method of the antibacterial agent for the PGA specifically comprises the following steps:
step A1: dispersing chitosan in deionized water, adding a cross-linking agent, reacting for 4 hours under the conditions that the rotating speed is 120r/min, the temperature is 45 ℃ and the pH value is 9, filtering to remove filtrate, washing a substrate to be neutral, and drying to obtain pretreated chitosan;
step A2: uniformly mixing p-carboxyphenol, potassium carbonate and DMF (dimethyl formamide), stirring for 1h at the rotation speed of 200r/min and the temperature of 20 ℃, adding 4-nitropyrrole, reacting for 20h, and regulating the pH value to be 4 to prepare a modifier;
step A3: uniformly mixing pretreated chitosan, a modifier, p-toluenesulfonic acid and DMF (dimethyl formamide), reacting for 8 hours at the temperature of 110 ℃ at the speed of 120r/min to obtain modified chitosan, mixing the modified chitosan, silver nitrate, methanol and DMF, and reacting for 25 hours at the temperature of 120 ℃ at the speed of 150r/min to obtain the antibacterial agent.
The amount of the cross-linking agent in the step A1 is 1% of the mass of the chitosan.
The molar ratio of the p-carboxyphenol, the potassium carbonate and the 4-nitropyrrole in the step A2 is 1:1.1:1.
The mass ratio of the pretreated chitosan to the modifier in the step A3 is 1:1.5, the mass of the p-toluenesulfonic acid is 3% of the mass of the modifier, and the dosage ratio of the modified chitosan, the silver nitrate, the methanol and the DMF is 5.5g:10.5g:60 mL.
The cross-linking agent is prepared by the following steps:
step B1: uniformly mixing 1, 3-diamino-2-propanol and ethanol, introducing nitrogen for protection, stirring and adding 4-hydroxybenzaldehyde under the conditions of the rotating speed of 200r/min and the temperature of 40 ℃ for reaction for 4 hours to obtain an intermediate 1, uniformly mixing the intermediate 1, acrylic acid, p-toluenesulfonic acid and toluene, and reacting for 6 hours under the conditions of the rotating speed of 120r/min and the temperature of 100 ℃ to obtain an intermediate 2;
step B2: uniformly mixing the intermediate 2, mercaptopropionic acid and DMF, reacting for 1h under the condition of ultraviolet irradiation at the rotating speed of 60r/min and 365nm to obtain an intermediate 3, uniformly mixing the intermediate 3, 4-aminopyridine, N' -dicyclohexylcarbodiimide and DMF, and reacting for 6h under the condition of the rotating speed of 200r/min and the temperature of 25 ℃ to obtain an intermediate 4;
step B3: uniformly mixing the intermediate 4, bromododecane and DMF, reacting for 30min at the rotation speed of 120r/min and the temperature of 120 ℃, adding epoxy chloropropane and benzyl triethyl ammonium chloride, introducing nitrogen for protection, reacting for 2h at the rotation speed of 150r/min and the temperature of 100 ℃, cooling to 70 ℃, adding sodium hydroxide solution, and continuing to react for 15h to obtain the cross-linking agent.
The mol ratio of the 1, 3-diamino-2-propanol to the 4-hydroxybenzaldehyde in the step B1 is 1:2, the mol ratio of the intermediate 1 to the acrylic acid is 1:1, and the dosage of the p-toluenesulfonic acid is 1 mass percent of the intermediate 1 to the acrylic acid and 3 mass percent of the intermediate.
The molar ratio of the intermediate 2 to the mercaptopropionic acid in the step B2 is 1:1, and the molar ratio of the intermediate 3, 4-aminopyridine to the N, N' -dicyclohexyl-carbodiimide is 1:1:1.1.
The mol ratio of the intermediate 4, bromododecane, epichlorohydrin to benzyl triethyl ammonium chloride to the sodium hydroxide solution in the step B3 is 1:1:2:6.75:250, and the mass fraction of the sodium hydroxide solution is 30%.
Example 2
The preparation method of the antibacterial agent for the PGA specifically comprises the following steps:
step A1: dispersing chitosan in deionized water, adding a cross-linking agent, reacting for 5 hours under the conditions that the rotating speed is 120r/min, the temperature is 48 ℃ and the pH value is 9, filtering to remove filtrate, washing a substrate to be neutral, and drying to obtain pretreated chitosan;
step A2: uniformly mixing p-carboxyphenol, potassium carbonate and DMF (dimethyl formamide), stirring for 1.3 hours at the rotating speed of 300r/min and the temperature of 23 ℃, adding 4-nitropyrrole, reacting for 23 hours, and regulating the pH value to be 4 to prepare a modifier;
step A3: uniformly mixing pretreated chitosan, a modifier, p-toluenesulfonic acid and DMF (dimethyl formamide), reacting for 9 hours at the temperature of 115 ℃ at the speed of 120r/min to obtain modified chitosan, mixing the modified chitosan, silver nitrate, methanol and DMF, and reacting for 28 hours at the temperature of 125 ℃ at the speed of 150r/min to obtain the antibacterial agent.
The dosage of the cross-linking agent in the step A1 is 1 to 1.5 percent of the mass of the chitosan.
The molar ratio of the p-carboxyphenol, the potassium carbonate and the 4-nitropyrrole in the step A2 is 1:1.1:1.
The mass ratio of the pretreated chitosan to the modifier in the step A3 is 1:1.5, the mass of the p-toluenesulfonic acid is 3% of the mass of the modifier, and the dosage ratio of the modified chitosan, the silver nitrate, the methanol and the DMF is 5.5g:10.5g:60 mL.
The cross-linking agent is prepared by the following steps:
step B1: uniformly mixing 1, 3-diamino-2-propanol and ethanol, introducing nitrogen for protection, stirring and adding 4-hydroxybenzaldehyde under the conditions of the rotating speed of 200r/min and the temperature of 43 ℃ for reaction for 5 hours to obtain an intermediate 1, uniformly mixing the intermediate 1, acrylic acid, p-toluenesulfonic acid and toluene, and reacting for 7 hours under the conditions of the rotating speed of 150r/min and the temperature of 105 ℃ to obtain an intermediate 2;
step B2: uniformly mixing the intermediate 2, mercaptopropionic acid and DMF, reacting for 1.3 hours under the condition of ultraviolet irradiation at the rotating speed of 60r/min and 365nm to obtain an intermediate 3, uniformly mixing the intermediate 3, 4-aminopyridine, N' -dicyclohexylcarbodiimide and DMF, and reacting for 7 hours under the condition of the rotating speed of 200r/min and the temperature of 28 ℃ to obtain an intermediate 4;
step B3: uniformly mixing the intermediate 4, bromododecane and DMF, reacting for 35min at the rotation speed of 150r/min and the temperature of 120 ℃, adding epoxy chloropropane and benzyl triethyl ammonium chloride, introducing nitrogen for protection, reacting for 3h at the rotation speed of 200r/min and the temperature of 105 ℃, cooling to 73 ℃, adding sodium hydroxide solution, and continuing to react for 18h to obtain the cross-linking agent.
The mol ratio of the 1, 3-diamino-2-propanol to the 4-hydroxybenzaldehyde in the step B1 is 1:2, the mol ratio of the intermediate 1 to the acrylic acid is 1:1, and the dosage of the p-toluenesulfonic acid is the mass of the intermediate 1 to the acrylic acid and 4 percent.
The molar ratio of the intermediate 2 to the mercaptopropionic acid in the step B2 is 1:1, and the molar ratio of the intermediate 3, 4-aminopyridine to the N, N' -dicyclohexyl-carbodiimide is 1:1:1.1.
The mol ratio of the intermediate 4, bromododecane, epichlorohydrin to benzyl triethyl ammonium chloride to the sodium hydroxide solution in the step B3 is 1:1:2:6.75:250, and the mass fraction of the sodium hydroxide solution is 30%.
Example 3
The preparation method of the antibacterial agent for the PGA specifically comprises the following steps:
step A1: dispersing chitosan in deionized water, adding a cross-linking agent, reacting for 6 hours under the conditions of the rotating speed of 150r/min, the temperature of 50 ℃ and the pH value of 10, filtering to remove filtrate, washing a substrate to be neutral, and drying to obtain pretreated chitosan;
step A2: uniformly mixing p-carboxyphenol, potassium carbonate and DMF (dimethyl formamide), stirring for 1.5 hours at the rotation speed of 300r/min and the temperature of 25 ℃, adding 4-nitropyrrole, reacting for 25 hours, and regulating the pH value to be 5 to obtain a modifier;
step A3: uniformly mixing pretreated chitosan, a modifier, p-toluenesulfonic acid and DMF (dimethyl formamide), reacting for 10 hours at the temperature of 120 ℃ at the rotating speed of 150r/min to obtain modified chitosan, mixing the modified chitosan, silver nitrate, methanol and DMF, and reacting for 30 hours at the temperature of 125 ℃ at the rotating speed of 200r/min to obtain the antibacterial agent.
The amount of the cross-linking agent in the step A1 is 1.5% of the mass of the chitosan.
The molar ratio of the p-carboxyphenol, the potassium carbonate and the 4-nitropyrrole in the step A2 is 1:1.1:1.
The mass ratio of the pretreated chitosan to the modifier in the step A3 is 1:1.5, the mass of the p-toluenesulfonic acid is 3% of the mass of the modifier, and the dosage ratio of the modified chitosan, the silver nitrate, the methanol and the DMF is 5.5g:10.5g:60 mL.
The cross-linking agent is prepared by the following steps:
step B1: uniformly mixing 1, 3-diamino-2-propanol and ethanol, introducing nitrogen for protection, stirring and adding 4-hydroxybenzaldehyde under the conditions of the rotating speed of 300r/min and the temperature of 45 ℃ for reaction for 6 hours to obtain an intermediate 1, uniformly mixing the intermediate 1, acrylic acid, p-toluenesulfonic acid and toluene, and reacting for 8 hours under the conditions of the rotating speed of 150r/min and the temperature of 110 ℃ to obtain an intermediate 2;
step B2: uniformly mixing the intermediate 2, mercaptopropionic acid and DMF, reacting for 1.5 hours under the condition of ultraviolet irradiation with the rotating speed of 80r/min and 365nm to obtain an intermediate 3, uniformly mixing the intermediate 3, 4-aminopyridine, N' -dicyclohexylcarbodiimide and DMF, and reacting for 8 hours under the condition of the rotating speed of 300r/min and the temperature of 30 ℃ to obtain an intermediate 4;
step B3: uniformly mixing the intermediate 4, bromododecane and DMF, reacting for 40min at the rotation speed of 120-150r/min and the temperature of 125 ℃, adding epoxy chloropropane and benzyl triethyl ammonium chloride, introducing nitrogen for protection, reacting for 4h at the rotation speed of 200r/min and the temperature of 105 ℃, cooling to 75 ℃, adding sodium hydroxide solution, and continuing to react for 20h to obtain the cross-linking agent.
The mol ratio of the 1, 3-diamino-2-propanol and the 4-hydroxybenzaldehyde in the step B1 is 1:2, the mol ratio of the intermediate 1 and the acrylic acid is 1:1, and the dosage of the p-toluenesulfonic acid is 3-5% of the mass of the intermediate 1 and the acrylic acid.
The molar ratio of the intermediate 2 to the mercaptopropionic acid in the step B2 is 1:1, and the molar ratio of the intermediate 3, 4-aminopyridine to the N, N' -dicyclohexyl-carbodiimide is 1:1:1.1.
The mol ratio of the intermediate 4, bromododecane, epichlorohydrin to benzyl triethyl ammonium chloride to the sodium hydroxide solution in the step B3 is 1:1:2:6.75:250, and the mass fraction of the sodium hydroxide solution is 30%.
Comparative example 1
This comparative example uses pretreated chitosan instead of antimicrobial agent as compared to example 1, the rest of the procedure being the same.
Comparative example 2
This comparative example uses chitosan instead of pretreated chitosan as compared to example 1, the rest of the procedure being the same.
The concentration of each of the ideal directions is 10 7 The antibacterial agents prepared in examples 1-3 and comparative examples 1-2 were added to CFU/mLDE staphylococcus aureus bacterial liquid and escherichia coli bacterial liquid at an amount of 0.25mg/mL, 10. Mu.L of bacterial suspension was smeared in a culture medium, and the culture was carried out for 24 hours, and the antibacterial condition was observed, and the detection results were shown in the following table.
As is clear from the above table, the antibacterial agents prepared in examples 1 to 3 have excellent antibacterial effects.
The foregoing is merely illustrative and explanatory of the principles of the invention, as various modifications and additions may be made to the specific embodiments described, or similar thereto, by those skilled in the art, without departing from the principles of the invention or beyond the scope of the appended claims.
Claims (9)
1. A method for preparing an antibacterial agent for PGA is characterized by comprising the following steps: the method specifically comprises the following steps:
step A1: dispersing chitosan in deionized water, adding a cross-linking agent, reacting, filtering to remove filtrate, washing a substrate to be neutral, and drying to obtain pretreated chitosan;
step A2: uniformly mixing p-carboxyphenol, potassium carbonate and DMF, stirring, adding 4-nitropyrrole, reacting, and adjusting the pH value to be acidic to prepare a modifier;
step A3: mixing pretreated chitosan, a modifier, p-toluenesulfonic acid and DMF for reaction to prepare modified chitosan, mixing modified chitosan, silver nitrate, methanol and DMF for reaction to prepare the antibacterial agent.
2. The method for producing an antibacterial agent for PGA according to claim 1, wherein: the dosage of the cross-linking agent in the step A1 is 1 to 1.5 percent of the mass of the chitosan.
3. The method for producing an antibacterial agent for PGA according to claim 1, wherein: the molar ratio of the p-carboxyphenol, the potassium carbonate and the 4-nitropyrrole in the step A2 is 1:1.1:1.
4. The method for producing an antibacterial agent for PGA according to claim 1, wherein: the mass ratio of the pretreated chitosan to the modifier in the step A3 is 1:1.5, the mass of the p-toluenesulfonic acid is 3% of the mass of the modifier, and the dosage ratio of the modified chitosan, the silver nitrate, the methanol and the DMF is 5.5g:10.5g:60 mL.
5. The method for producing an antibacterial agent for PGA according to claim 1, wherein: the cross-linking agent is prepared by the following steps:
step B1: uniformly mixing 1, 3-diamino-2-propanol and ethanol, introducing nitrogen for protection, stirring, adding 4-hydroxybenzaldehyde, reacting to obtain an intermediate 1, and mixing the intermediate 1, acrylic acid, p-toluenesulfonic acid and toluene for reacting to obtain an intermediate 2;
step B2: mixing intermediate 2, mercaptopropionic acid and DMF for reaction to obtain intermediate 3, mixing intermediate 3, 4-aminopyridine, N' -dicyclohexylcarbodiimide and DMF for reaction to obtain intermediate 4;
step B3: and (3) mixing the intermediate 4, bromododecane and DMF for reaction, adding epoxy chloropropane and benzyl triethyl ammonium chloride, introducing nitrogen for protection, reacting, cooling, adding sodium hydroxide solution, and continuing the reaction to obtain the cross-linking agent.
6. The method for producing an antibacterial agent for PGA according to claim 7, wherein: the mol ratio of the 1, 3-diamino-2-propanol and the 4-hydroxybenzaldehyde in the step B1 is 1:2, the mol ratio of the intermediate 1 and the acrylic acid is 1:1, and the dosage of the p-toluenesulfonic acid is 3-5% of the mass of the intermediate 1 and the acrylic acid.
7. The method for producing an antibacterial agent for PGA according to claim 7, wherein: the molar ratio of the intermediate 2 to the mercaptopropionic acid in the step B2 is 1:1, and the molar ratio of the intermediate 3, 4-aminopyridine to the N, N' -dicyclohexyl-carbodiimide is 1:1:1.1.
8. The method for producing an antibacterial agent for PGA according to claim 7, wherein: the mol ratio of the intermediate 4, bromododecane, epichlorohydrin to benzyl triethyl ammonium chloride to the sodium hydroxide solution in the step B3 is 1:1:2:6.75:250, and the mass fraction of the sodium hydroxide solution is 30%.
9. An antibacterial agent for PGA, characterized by: the preparation method according to any one of claims 1-8.
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