WO2022193613A1 - 一种复合聚丙烯酰胺水凝胶及其制备方法 - Google Patents

一种复合聚丙烯酰胺水凝胶及其制备方法 Download PDF

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WO2022193613A1
WO2022193613A1 PCT/CN2021/121264 CN2021121264W WO2022193613A1 WO 2022193613 A1 WO2022193613 A1 WO 2022193613A1 CN 2021121264 W CN2021121264 W CN 2021121264W WO 2022193613 A1 WO2022193613 A1 WO 2022193613A1
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add
reaction
stirring
rotating speed
necked flask
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刘晓菲
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衡阳市建衡实业有限公司
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0014—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/0066—Medicaments; Biocides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/008—Hydrogels or hydrocolloids
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
    • C08J3/075—Macromolecular gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
    • A61L2300/208—Quaternary ammonium compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2333/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers
    • C08J2333/24—Homopolymers or copolymers of amides or imides
    • C08J2333/26—Homopolymers or copolymers of acrylamide or methacrylamide

Definitions

  • the invention relates to the technical field of hydrogel preparation, in particular to a composite polyacrylamide hydrogel and a preparation method thereof.
  • Hydrogel is a structural gel with a three-dimensional network structure, which is highly hydrophilic and absorbent, can swell rapidly in water, and retain a large amount of water. It can be divided into natural hydrogels and synthetic hydrogels. Such as chitosan hydrogel, sodium alginate hydrogel, polyacrylic acid hydrogel, polyacrylamide hydrogel, etc., can be obtained by chemical cross-linking or physical cross-linking. It has important applications in cosmetic masks, medical drug carriers, tissue engineering, etc., but whether it is a natural hydrogel or a synthetic hydrogel, the biggest disadvantage is low strength and poor toughness, which cannot meet the requirements of practical use.
  • Polyacrylamide hydrogel has good histocompatibility and biological inertness. It has long been used in the field of biomedicine and is expected to be used in the preparation of wound dressings.
  • Chinese patent application CN109513039A discloses an antibacterial containing imidazolium bromide salt. Hydrogel dressing, the antibacterial ingredients imidazolium bromide and acrylamide are evenly dispersed in the initiator into the hydroxyl-containing hydrophilic polymer monomer solution to form a carrier system, and then after heating and repeated freezing-thawing process, it is imidazolium bromide. It is tightly bound to the matrix macromolecules through chemical bonds.
  • Chinese patent applications CN109550073A and CN109481727A disclose that bismuth oxychloride or tungsten disulfide is dispersed in sodium alginate solution, and then mixed with acrylamide, cross-linking agent and initiator to form a gel to prepare an antibacterial hydrogel dressing. It has antibacterial effect only under specific light.
  • organic synthetic drugs or inorganic metal compounds are selected as antibacterial agents. Although the antibacterial effect is good, it has certain potential safety hazards, and the hydrogel has good load performance and mechanical properties.
  • the composite gel carrier has high production cost and complicated process.
  • the technical problem to be solved by the present invention is that the hydrogel material in the prior art has low strength, poor toughness, and has a potential safety hazard.
  • a composite polyacrylamide hydrogel comprising the following raw materials in parts by weight: 100 parts of acrylamide, 0.2-1 part of an antibacterial agent, 0.05-1 part of a crosslinking agent, 220-290 parts of deionized water, and 0.1-0.5 part of an initiator , 0.1-0.5 parts of catalyst;
  • the composite polyacrylamide hydrogel is made by the following steps:
  • antibacterial agent is made by the following steps:
  • Step A1 add dodecyl dimethyl amine and isopropanol into the beaker, under room temperature conditions, the rotating speed is 60-100r/min after stirring and reacting for 10min, then the temperature is raised to 30-50 °C, and epoxy chloride is added to the beaker Propane, control the reaction temperature at 70-90°C, and stir the reaction for 7-9h under the condition of rotating speed 120r/min.
  • After the reaction remove isopropanol under reduced pressure at 0.09MPa and 85°C by rotary evaporation. After cooling to room temperature, dissolve with acetone. Then put it in a 5°C refrigerator for 3-5 hours, take it out, filter with suction, and dry the filter cake at 30-40°C for 12 hours to obtain Intermediate 1;
  • the reaction process is as follows:
  • Step A2 add sulfadiazine and absolute ethanol into the three-necked flask, stir under ice bath conditions for 10min, add triethylamine to the three-necked flask, then control the reaction temperature to 40°C, stir and react for 5min under the condition of rotating speed 100r/min, add Oxalyl chloride, continue to stir and react for 2-4h, after the reaction is over, add 1% sodium hydroxide solution by mass to the three-necked flask dropwise until the precipitation stops dropping, then filter, wash and dry to obtain Intermediate 2;
  • the reaction process is as follows:
  • Step A3 adding potassium carbonate and dimethylformamide to the round-bottomed flask, stirring for 40min at room temperature, adding 4-methyl-2-nitroaniline and 2-chloropropane, stirring the reaction under the condition of rotating speed 100r/min 24h, after the reaction was completed, deionized water was added to the round-bottomed flask, extracted with ethyl acetate 3 times under ice-water bath conditions, the organic phases were combined, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography to obtain the intermediate 3;
  • the reaction process is as follows:
  • Step A4 Add intermediate 3, ethanol and deionized water to the three-necked flask in turn, heat to reflux, and add a 20% mass fraction of sodium hydrosulfite aqueous solution dropwise to the three-necked flask with a constant pressure dropping funnel, and control the rate of addition of 1- 3 drops/sec. After the dropwise addition was completed, the heating was stopped after refluxing and stirring for 30 min. After the solution was cooled to room temperature, it was extracted with ethyl acetate for 3 times. The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated by evaporation to obtain the intermediate. 4. Add intermediate 4, tetrahydrofuran and carbonyldiimidazole into the reaction kettle, and at room temperature, after stirring for 2-4h at a rotating speed of 100-150r/min, intermediate 5 is obtained;
  • the reaction process is as follows:
  • Step A5 add intermediate 5 and dichloromethane to the reaction kettle, add triethylamine after stirring and dissolving, and drip the dichloromethane solution of intermediate 2 into the reaction kettle through a constant pressure dropping funnel at a temperature of 0-5 °C , after the dropwise addition, the temperature was raised to room temperature, and under the condition of rotating speed 100-200r/min, after the reaction for 2h, washed with saturated sodium bicarbonate, water and saturated brine for 3 times each, and finally dried over anhydrous sodium sulfate, silica gel column layer After analysis, intermediate 6 is obtained;
  • the reaction process is as follows:
  • Step A6 add intermediate 6 and dimethyl sulfoxide into the three-necked flask, heat up to 80-100 ° C, add potassium permanganate and a hydrochloric acid solution with a mass fraction of 17% to the three-necked flask, rotating speed 100-200r/min condition
  • deionized water was added, and extracted with ethyl acetate for three times. After drying with sodium sulfate and purification by silica gel column chromatography, the antibacterial agent was obtained.
  • the reaction process is as follows:
  • the dosage ratio of dodecyl dimethyl tertiary amine, isopropanol and epichlorohydrin described in step A1 is 0.1mol:100-200mL:0.1mol;
  • the dosage ratio of ethylamine and oxalyl chloride is 0.1mol:180-220mL:5mL:0.1mol; in step A3, potassium carbonate, dimethylformamide, 4-methyl-2-nitroaniline, 2-chloropropane and
  • the dosage ratio of ionized water is 4g: 20mL: 1.68g: 2.04g: 50mL; in step A4, the dosage ratio of intermediate 3, ethanol, deionized water and sodium hydrosulfite aqueous solution is 8mmol: 10mL: 30mL: 20mL, intermediate 4
  • the dosage ratio of , tetrahydrofuran and carbonyldiimidazole is 1g: 15-20mL: 0.5g; in step A5, the dosage ratio of the dichloromethane solution of intermediate
  • step A3 in the silica gel column chromatography process, the eluent is petroleum ether and ethyl acetate mixed according to a volume ratio of 6:1, and in the step A5 and step A6 in the silica gel column chromatography process, the eluent is petroleum ether. and ethyl acetate in a volume ratio of 7:1.
  • the preparation method of the crosslinking agent is as follows:
  • Aqueous sodium hydroxide solution with a concentration of 0.01mol/mL stirring for 1h at a speed of 100-200r/min, keeping the temperature at 0-5°C, stirring and reacting for 2h, filtering, extracting the filtrate with dichloromethane, and then using anhydrous sodium sulfate After drying for 24 h, the dichloromethane solvent was removed by rotary evaporation, and finally, it was recrystallized in a solvent with a volume ratio of ethyl acetate and heptane of 1:2 to obtain a cross-linking agent.
  • the dosage ratio of cystamine dihydrochloride, deionized water, dichloromethane solution of acryloyl chloride and sodium hydroxide aqueous solution is 11.5 g: 50 mL: 10 mL: 20 mL.
  • the initiator is amine persulfate.
  • the catalyst is tetramethylethylenediamine.
  • the present invention uses acrylamide, antibacterial agent, cross-linking agent, deionized water, initiator and catalyst as raw materials to prepare composite polyacrylamide hydrogel, wherein the cross-linking agent is cystamine dihydrochloride
  • the cross-linking agent is cystamine dihydrochloride
  • acryloyl chloride Through chemical reaction with acryloyl chloride, a cross-linked molecule containing -C-C-S-S-C-C- long hydrophobic group is obtained, which has a larger molecular distance than ordinary cross-linking agents, and is easier to interpenetrate with each other.
  • the resulting structural entanglement is more complicated, so The movement of the molecular chain during the stretching or compression process is relatively more difficult. The movement of the molecular chain will selectively slip and disentangle to maintain a certain structural integrity.
  • the disulfide bond has self-healing properties, which can further improve the water content.
  • Mechanical properties of gels starting with dodecyldimethylamine tertiary amine, in isopropanol solution with epichlorohydrin to undergo ring-opening reaction to obtain quaternary ammonium salts containing long alkyl chains and alcoholic hydroxyl groups
  • Intermediate 1 taking sulfadiazine as the starting material, chemically reacts with oxalyl chloride in absolute ethanol to obtain the intermediate 2 of the acid chloride structure, and then uses 4-methyl-2-nitroaniline as the substrate to react with 2- Chloropropane reacts to obtain intermediate 3, and intermediate 3 undergoes a reduction reaction in an aqueous solution of sodium dithionite to obtain intermediate 4, and then intermediate 4 is formed under the action of a carbonyldiimidazole condensing agent to form intermediate 5 containing an imidazolone structure.
  • the secondary amine on the intermediate 5 and the intermediate 2 undergo an elimination reaction to obtain the intermediate 6, and the benzyl group of the intermediate 6 is oxidized to a carboxyl group by the acidic potassium permanganate to obtain the intermediate 7, and finally in the concentrated sulfuric acid.
  • intermediate 1 and intermediate 7 undergo esterification reaction, and finally an antibacterial agent is obtained, which contains antibacterial groups such as alkyl long chain of quaternary ammonium salt, imidazolone structure, sulfonamide, etc. It has excellent antibacterial and anti-inflammatory properties, and contains benzene ring and diazide heterocyclic structure, which has high stability and is not easy to volatilize. It contains secondary amine and tertiary amine groups. All materials can interact with each other to enhance the adhesion performance of the hydrogel.
  • the cross-linking agent in the present invention can effectively dissipate the ability and endow the hydrogel with high toughness.
  • the gel has a higher safety of use.
  • a composite polyacrylamide hydrogel comprising the following raw materials in parts by weight: 100 parts of acrylamide, 0.2 part of an antibacterial agent, 0.05 part of a crosslinking agent, 220 parts of deionized water, 0.1 part of an initiator, and 0.1 part of a catalyst;
  • the composite polyacrylamide hydrogel is made by the following steps:
  • the antibacterial agent is made by the following steps:
  • Step A1 add dodecyl dimethyl amine and isopropanol into the beaker, at room temperature, after stirring the reaction for 10 minutes at a rotating speed of 60 r/min, the temperature is raised to 30 ° C, and epichlorohydrin is added to the beaker to control the reaction The temperature was 70°C, and the reaction speed was 120r/min. The reaction was stirred for 7h. After the reaction, the isopropanol was removed by rotary evaporation under reduced pressure at 0.09MPa and 85°C. After cooling to room temperature, it was dissolved in acetone and placed in a 5°C refrigerator for storage. Take out after 3 hours, filter with suction, and dry the filter cake at 30°C for 12 hours to obtain Intermediate 1;
  • Step A2 add sulfadiazine and absolute ethanol into the three-necked flask, stir for 10min under ice bath conditions, add triethylamine to the three-necked flask, then control the reaction temperature to 40°C, stir and react for 5min under the condition of rotating speed 100r/min, add Oxalyl chloride, continue to stir and react for 2h, after the reaction is over, add 1% sodium hydroxide solution by mass to the three-necked flask dropwise until the precipitation stops dropping, then filter, wash and dry to obtain Intermediate 2;
  • Step A3 adding potassium carbonate and dimethylformamide to the round-bottomed flask, stirring for 40min at room temperature, adding 4-methyl-2-nitroaniline and 2-chloropropane, stirring the reaction under the condition of rotating speed 100r/min 24h, after the reaction was completed, deionized water was added to the round-bottomed flask, extracted with ethyl acetate 3 times under ice-water bath conditions, the organic phases were combined, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography to obtain the intermediate 3;
  • Step A4 Add Intermediate 3, ethanol and deionized water to the three-necked flask in turn, heat to reflux, and add a 20% mass fraction of sodium hydrosulfite aqueous solution to the three-necked flask dropwise with a constant pressure dropping funnel, and control the rate of addition to 1 drop After the dropwise addition, the heating was stopped after refluxing for 30 min, the solution was cooled to room temperature, extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated by evaporation to obtain Intermediate 4, Intermediate 4, tetrahydrofuran and carbonyldiimidazole were added to the reaction kettle, and at room temperature, after stirring for 2 h at a rotating speed of 100 r/min, intermediate 5 was obtained;
  • Step A5 add intermediate 5 and dichloromethane to the reaction kettle, add triethylamine after stirring and dissolving, and drip the dichloromethane solution of intermediate 2 into the reaction kettle through a constant pressure dropping funnel at a temperature of 0 ° C, dropwise After the addition, the temperature was raised to room temperature, and the reaction was carried out for 2 h under the condition of rotating speed of 100 r/min, washed three times with saturated sodium bicarbonate, water and saturated brine each, and finally dried over anhydrous sodium sulfate, and after silica gel column chromatography, obtained Intermediate 6;
  • Step A6 add intermediate 6 and dimethyl sulfoxide into the three-necked flask, heat up to 80°C, add potassium permanganate and 17% hydrochloric acid solution by mass to the three-necked flask, and stir the reaction under the condition of rotating speed 100r/min After 20min, filter, transfer the filtrate to the reaction kettle to obtain intermediate 7 solution, then add intermediate 1 to the reaction kettle, add concentrated sulfuric acid dropwise to the reaction kettle through a constant pressure dropping funnel, and the dropwise addition ends within 5min, After the dropwise addition, the temperature was raised to 40 °C, and the reaction was kept under stirring for 2 h. After the reaction was completed, deionized water was added, and extracted with ethyl acetate for 3 times. The organic phases were combined, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography. , to obtain antibacterial agents.
  • the dosage ratio of dodecyl dimethyl tertiary amine, isopropanol and epichlorohydrin described in step A1 is 0.1mol:100mL:0.1mol; in step A2, sulfadiazine, absolute ethanol, triethylamine and oxalyl chloride
  • the dosage ratio is 0.1mol: 180mL: 5mL: 0.1mol; in step A3, the dosage ratio of potassium carbonate, dimethylformamide, 4-methyl-2-nitroaniline, 2-chloropropane and deionized water is 4g : 20mL: 1.68g: 2.04g: 50mL; in step A4, the dosage ratio of intermediate 3, ethanol, deionized water and sodium dithionite aqueous solution is 8mmol: 10mL: 30mL: 20mL, the amount of intermediate 4, tetrahydrofuran and carbonyldiimidazole is The dosage ratio is 1 g: 15 mL: 0.5 g; in step A5, the
  • step A3 in the process of silica gel column chromatography, the eluent is petroleum ether and ethyl acetate mixed according to the volume ratio of 6:1, and in the process of silica gel column chromatography in step A5 and step A6, the eluent is petroleum ether and ethyl acetate.
  • the esters were mixed in a volume ratio of 7:1.
  • the preparation method of the crosslinking agent is as follows:
  • the dosage ratio of cystamine dihydrochloride, deionized water, dichloromethane solution of acryloyl chloride and sodium hydroxide aqueous solution is 11.5 g: 50 mL: 10 mL: 20 mL.
  • the initiator is amine persulfate, and the catalyst is tetramethylethylenediamine.
  • a composite polyacrylamide hydrogel comprising the following raw materials in parts by weight: 100 parts of acrylamide, 0.8 parts of antibacterial agents, 0.08 parts of crosslinking agents, 250 parts of deionized water, 0.2 parts of initiators, and 0.2 parts of catalysts;
  • the composite polyacrylamide hydrogel is made by the following steps:
  • the antibacterial agent is made by the following steps:
  • Step A1 add dodecyl dimethyl amine and isopropanol into the beaker, under room temperature conditions, the rotating speed is 80r/min after stirring and reacting for 10min, then the temperature is raised to 40 °C, and epichlorohydrin is added to the beaker to control the reaction The temperature was 80 °C, and the reaction speed was 120 r/min for 8 h. After the reaction, the isopropanol was removed by rotary evaporation under reduced pressure at 0.09 MPa and 85 °C. After cooling to room temperature, it was dissolved in acetone and placed in a 5 °C refrigerator for storage. After 4 hours, it was taken out, filtered with suction, and the filter cake was dried at 35°C for 12 hours to obtain Intermediate 1;
  • Step A2 add sulfadiazine and absolute ethanol into the three-necked flask, stir for 10min under ice bath conditions, add triethylamine to the three-necked flask, then control the reaction temperature to 40°C, stir and react for 5min under the condition of rotating speed 100r/min, add Oxalyl chloride, continue to stir and react for 3h, after the reaction is over, add 1% sodium hydroxide solution by mass to the three-necked flask dropwise until the precipitation stops dropping, then filter, wash and dry to obtain Intermediate 2;
  • Step A3 adding potassium carbonate and dimethylformamide to the round-bottomed flask, stirring for 40min at room temperature, adding 4-methyl-2-nitroaniline and 2-chloropropane, stirring the reaction under the condition of rotating speed 100r/min 24h, after the reaction was completed, deionized water was added to the round-bottomed flask, extracted with ethyl acetate 3 times under ice-water bath conditions, the organic phases were combined, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography to obtain the intermediate 3;
  • Step A4 Add Intermediate 3, ethanol and deionized water to the three-necked flask in turn, heat to reflux, and add a 20% mass fraction of sodium hydrosulfite aqueous solution to the three-necked flask dropwise with a constant pressure dropping funnel, and control the rate of addition to 2 drops After the dropwise addition, the heating was stopped after refluxing for 30 min, the solution was cooled to room temperature, extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated by evaporation to obtain Intermediate 4, Intermediate 4, tetrahydrofuran and carbonyldiimidazole were added to the reaction kettle, and at room temperature, the intermediate 5 was obtained after stirring for 3 hours at a rotating speed of 120 r/min;
  • Step A5 add intermediate 5 and dichloromethane to the reaction kettle, add triethylamine after stirring and dissolving, add the dichloromethane solution of intermediate 2 dropwise to the reaction kettle through a constant pressure dropping funnel at a temperature of 3 °C, dropwise After the addition, the temperature was raised to room temperature, and the reaction was carried out for 2 h under the condition of rotating speed of 150 r/min, washed 3 times with saturated sodium bicarbonate, water and saturated brine each, and finally dried over anhydrous sodium sulfate, and after silica gel column chromatography, obtained Intermediate 6;
  • Step A6 add intermediate 6 and dimethyl sulfoxide into the three-necked flask, heat up to 90°C, add potassium permanganate and 17% hydrochloric acid solution to the three-necked flask, and stir the reaction under the condition of rotating speed 150r/min After 30min, filter, transfer the filtrate to the reaction kettle to obtain Intermediate 7 solution, then add Intermediate 1 to the reaction kettle, add concentrated sulfuric acid dropwise to the reaction kettle through a constant pressure dropping funnel, and the dropwise addition ends within 5min, After the dropwise addition, the temperature was raised to 45°C, and the reaction was kept under stirring for 3 hours. After the reaction was completed, deionized water was added, and extracted with ethyl acetate for three times. The organic phases were combined, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography. , to obtain antibacterial agents.
  • the dosage ratio of dodecyldimethyl tertiary amine, isopropanol and epichlorohydrin described in step A1 is 0.1mol:150mL:0.1mol; in step A2, sulfadiazine, absolute ethanol, triethylamine and oxalyl chloride
  • the dosage ratio is 0.1mol: 200mL: 5mL: 0.1mol; in step A3, the dosage ratio of potassium carbonate, dimethylformamide, 4-methyl-2-nitroaniline, 2-chloropropane and deionized water is 4g : 20mL: 1.68g: 2.04g: 50mL; in step A4, the dosage ratio of intermediate 3, ethanol, deionized water and sodium dithionite aqueous solution is 8mmol: 10mL: 30mL: 20mL, the amount of intermediate 4, tetrahydrofuran and carbonyldiimidazole is The dosage ratio is 1 g: 18 mL: 0.5 g; in step A5,
  • step A3 in the silica gel column chromatography process, the eluent is petroleum ether and ethyl acetate mixed in a volume ratio of 6:1, and in step A5 and step A6 in the silica gel column chromatography process, the eluent is petroleum ether and ethyl acetate.
  • the esters were mixed in a volume ratio of 7:1.
  • the preparation method of the crosslinking agent is as follows:
  • the dosage ratio of cystamine dihydrochloride, deionized water, dichloromethane solution of acryloyl chloride and sodium hydroxide aqueous solution is 11.5 g: 50 mL: 10 mL: 20 mL.
  • the initiator is amine persulfate, and the catalyst is tetramethylethylenediamine.
  • a composite polyacrylamide hydrogel comprising the following raw materials in parts by weight: 100 parts of acrylamide, 1 part of antibacterial agent, 1 part of crosslinking agent, 290 parts of deionized water, 0.5 part of initiator, and 0.5 part of catalyst;
  • the composite polyacrylamide hydrogel is made by the following steps:
  • the antibacterial agent is made by the following steps:
  • Step A1 add dodecyl dimethyl amine and isopropanol into the beaker, under room temperature conditions, after stirring the reaction for 10 minutes at a rotating speed of 100 r/min, the temperature is raised to 50 ° C, and epichlorohydrin is added to the beaker to control the reaction The temperature was 90°C and the reaction speed was 120r/min and the reaction was stirred for 9h. After the reaction, the isopropanol was removed by rotary evaporation under reduced pressure at 0.09MPa and 85°C. After cooling to room temperature, it was dissolved in acetone and placed in a 5°C refrigerator for storage. After 5 hours, it was taken out, filtered with suction, and the filter cake was dried at 40°C for 12 hours to obtain Intermediate 1;
  • Step A2 add sulfadiazine and absolute ethanol into the three-necked flask, stir for 10min under ice bath conditions, add triethylamine to the three-necked flask, then control the reaction temperature to 40°C, stir and react for 5min under the condition of rotating speed 100r/min, add Oxalyl chloride, continue to stir and react for 4h, after the reaction is over, add 1% sodium hydroxide solution by mass to the three-necked flask dropwise until the precipitation stops dropping, then filter, wash and dry to obtain Intermediate 2;
  • Step A3 adding potassium carbonate and dimethylformamide to the round-bottomed flask, stirring for 40min at room temperature, adding 4-methyl-2-nitroaniline and 2-chloropropane, stirring the reaction under the condition of rotating speed 100r/min 24h, after the reaction was completed, deionized water was added to the round-bottomed flask, extracted with ethyl acetate 3 times under ice-water bath conditions, the organic phases were combined, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography to obtain the intermediate 3;
  • Step A4 Add Intermediate 3, ethanol and deionized water to the three-necked flask in turn, heat to reflux, and dropwise add 20% aqueous sodium hydrosulfite solution to the three-necked flask with a constant pressure dropping funnel, and control the rate of addition to 3 drops After the dropwise addition, the heating was stopped after refluxing for 30 min, the solution was cooled to room temperature, extracted three times with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated by evaporation to obtain Intermediate 4, Intermediate 4, tetrahydrofuran and carbonyldiimidazole were added to the reaction kettle, and at room temperature, after stirring for 4 hours at a rotating speed of 150 r/min, intermediate 5 was obtained;
  • Step A5 add intermediate 5 and dichloromethane to the reaction kettle, add triethylamine after stirring and dissolving, and add the dichloromethane solution of intermediate 2 dropwise to the reaction kettle through a constant pressure dropping funnel at a temperature of 5 ° C, dropwise After the addition, the temperature was raised to room temperature, and the reaction was performed for 2 hours under the condition of a rotating speed of 200 r/min, and washed 3 times with saturated sodium bicarbonate, water, and saturated brine each, and finally dried over anhydrous sodium sulfate. After silica gel column chromatography, the obtained Intermediate 6;
  • Step A6 add intermediate 6 and dimethyl sulfoxide into the three-necked flask, heat up to 100°C, add potassium permanganate and 17% hydrochloric acid solution to the three-necked flask, and stir the reaction under the condition of rotating speed 200r/min After 40min, filter, transfer the filtrate to the reaction kettle to obtain intermediate 7 solution, then add intermediate 1 to the reaction kettle, add concentrated sulfuric acid dropwise to the reaction kettle through a constant pressure dropping funnel, and the dropwise addition ends within 5min, After the dropwise addition, the temperature was raised to 50 °C, and the reaction was kept stirring for 4 h. After the reaction was completed, deionized water was added, and extracted with ethyl acetate for three times. The organic phases were combined, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography. , to obtain antibacterial agents.
  • the dosage ratio of dodecyl dimethyl tertiary amine, isopropanol and epichlorohydrin described in step A1 is 0.1mol:200mL:0.1mol; in step A2, sulfadiazine, absolute ethanol, triethylamine and oxalyl chloride
  • the dosage ratio is 0.1mol: 220mL: 5mL: 0.1mol; in step A3, the dosage ratio of potassium carbonate, dimethylformamide, 4-methyl-2-nitroaniline, 2-chloropropane and deionized water is 4g : 20mL: 1.68g: 2.04g: 50mL; in step A4, the dosage ratio of intermediate 3, ethanol, deionized water and sodium dithionite aqueous solution is 8mmol: 10mL: 30mL: 20mL, the amount of intermediate 4, tetrahydrofuran and carbonyldiimidazole is The dosage ratio is 1 g: 20 mL: 0.5 g; in step A5,
  • step A3 in the process of silica gel column chromatography, the eluent is petroleum ether and ethyl acetate mixed according to the volume ratio of 6:1, and in the process of silica gel column chromatography in step A5 and step A6, the eluent is petroleum ether and ethyl acetate.
  • the esters were mixed in a volume ratio of 7:1.
  • the preparation method of the crosslinking agent is as follows:
  • the dosage ratio of cystamine dihydrochloride, deionized water, dichloromethane solution of acryloyl chloride and sodium hydroxide aqueous solution is 11.5 g: 50 mL: 10 mL: 20 mL.
  • the initiator is amine persulfate, and the catalyst is tetramethylethylenediamine.
  • This comparative example is a common composite polyacrylamide hydrogel on the market.
  • hydrogels of Examples 1-3 and Comparative Examples were tested for performance, and the test criteria were as follows:
  • Tensile performance test use a universal testing machine to test the tensile performance.
  • the sample is cut into a cylinder with a diameter of 4mm and a height of 45mm.
  • the initial length gauge length is 15mm, and the loading speed is 100mm/min.
  • the clip of the testing instrument is stuck with a layer of rough paper. , preventing the hydrogel from slipping during testing.
  • Hemolytic performance test Take 5mL of fresh anticoagulated rabbit red blood cells in a centrifuge tube, centrifuge at 2000r/min for 5min, then take out 0.2mL of centrifuged anticoagulant red blood cells into the test tube, slowly add 10mL of normal saline, and then take 5g The composite gel sample was placed in it, shaken slightly, mixed evenly, placed in a 37°C water bath for 60 minutes, and 10 mL of normal saline plus rabbit red blood cells was used as a negative control.
  • Antibacterial property test The antibacterial properties of Examples 1-3 and Comparative Examples were quantitatively characterized by the film method GB/T 21866-2008 standard. The test results are shown in the following table:
  • Example 1 0.117 830 1.80 99.8
  • Example 2 0.120 850 1.72 99.5
  • Example 3 0.119 870 1.77 99.7 Comparative ratio 0.080 1100 6 82.1
  • the composite gels of Examples 1-3 performed better than the comparative examples in the tests of tensile strength, swelling ratio, hemolysis rate and Escherichia coli bacteriostatic rate, indicating that the composite gels prepared by the present invention were Adhesive has high mechanical properties and antibacterial properties, and has great application value in the medical field.

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Abstract

一种复合聚丙烯酰胺水凝胶，包括以下重量份原料：丙烯酰胺100份、抗菌剂0.2-1份、交联剂0.05-1份、去离子水220-290份、引发剂0.1-0.5份、催化剂0.1-0.5份；由以下步骤制成：将丙烯酰胺和去离子水加入圆底烧瓶中，搅拌溶解，然后向反应釜中加入交联剂，提高转速至300-500r/min，将圆底烧瓶置于冰水浴中通氮气5min后，加入引发剂和催化剂、抗菌剂，搅拌5min后，吸到注射器中，密封于4℃环境中48h形成水凝胶，再将产物放入于蒸馏水中透析48h，每12h换水一次，得到复合聚丙烯酰胺水凝胶，具有较高的力学性能和抗菌性能，在医用领域具有很大的应用价值。

Description

一种复合聚丙烯酰胺水凝胶及其制备方法 技术领域
本发明涉及水凝胶制备技术领域，尤其指一种复合聚丙烯酰胺水凝胶及其制备方法。
背景技术
水凝胶是一种具有三维网络结构的结构凝胶，亲水性和吸水性很强，在水中可以快速溶胀，并包保有大量的水，可以分为天然水凝胶和合成水凝胶，如壳聚糖水凝胶、海藻酸钠水凝胶、聚丙烯酸水凝胶、聚丙烯酰胺水凝胶等，可以通过化学交联或物理交联得到，水凝胶的高吸水高保水特性，使其在化妆品面膜、医疗药物载体、组织工程等方面具有重要的应用，但是无论是天然水凝胶，还是合成水凝胶，最大的缺点就是强度低，韧性差，无法满足实际使用的要求。
聚丙烯酰胺水凝胶具有良好的组织相容性和生物学上的惰性，早已在生物医用领域得到应有，有望用于制备创面敷料，中国专利申请CN109513039A公开了一种含有咪唑溴盐的抗菌水凝胶敷料，将抗菌成分咪唑溴盐、丙烯酰胺于引发剂均匀分散到含羟基亲水性聚合物单体溶液中形成载体体系，再经过加热及反复的冷冻-解冻过程，是咪唑溴盐通过化学键与基体大分子紧密结合。中国专利申请CN109550073A和CN109481727A公开了将氯氧化秘或二硫化钨分散于海藻酸钠溶液中，再将其与丙烯酰胺、交联剂、引发剂混合成胶，制得抗菌水凝胶敷料，其需在特定的光照下才具有抗菌效果。上述专利公开选用有机合成药物或无机金属化合物作为抗菌剂，虽抗菌效果好，但具有一定的安全隐患，而且使水凝胶有良好的负载性能、力学性能等，需选用多种材料结合成一个复合凝胶载体，制作成本高，过程复杂。
发明内容
本发明所要解决的技术问题是现有技术中水凝胶材料强度低，韧性差， 具有安全隐患。
本发明解决上述技术问题所采用的技术方案为：
一种复合聚丙烯酰胺水凝胶，包括以下重量份原料：丙烯酰胺100份、抗菌剂0.2-1份、交联剂0.05-1份、去离子水220-290份、引发剂0.1-0.5份、催化剂0.1-0.5份；
该复合聚丙烯酰胺水凝胶由以下步骤制成：
将丙烯酰胺和去离子水加入圆底烧瓶中，转速60r/min条件下搅拌溶解，然后向反应釜中加入交联剂，提高转速至300-500r/min，将圆底烧瓶置于冰水浴中通氮气5min后，加入引发剂和催化剂、抗菌剂，搅拌5min后，吸到注射器中，密封于4℃环境中48h形成水凝胶，再将产物放入于蒸馏水中透析48h，每12h换水一次，得到复合聚丙烯酰胺水凝胶。
进一步地，所述抗菌剂由以下步骤制成：
步骤A1、将十二烷基二甲基叔胺和异丙醇加入烧杯中，室温条件下，转速60-100r/min搅拌反应10min后，升温至30-50℃，向烧杯中加入环氧氯丙烷，控制反应温度70-90℃，转速120r/min条件下搅拌反应7-9h，反应结束后，在0.09MPa、85℃下减压旋蒸去除异丙醇，冷却至室温后，用丙酮溶解后放入5℃冰箱中保持3-5h后取出，抽滤，滤饼于30-40℃条件下干燥12h，得到中间体1；
反应过程如下：
Figure PCTCN2021121264-appb-000001
步骤A2、将磺胺嘧啶和无水乙醇加入三口烧瓶中，冰浴条件下搅拌10min， 向三口烧瓶中加入三乙胺，然后控制反应温度40℃，转速100r/min条件下搅拌反应5min后，加入草酰氯，继续搅拌反应2-4h，反应结束后，向三口烧瓶中滴加质量分数1％的氢氧化钠溶液，直到沉淀析出停止滴加，然后进行过滤洗涤烘干，得到中间体2；
反应过程如下：
Figure PCTCN2021121264-appb-000002
步骤A3、向圆底烧瓶中加入碳酸钾和二甲基甲酰胺，室温条件下，搅拌40min后加入4-甲基-2-硝基苯胺和2-氯丙烷，转速100r/min条件下搅拌反应24h，反应结束后，向圆底烧瓶中加入去离子水，冰水浴条件下，用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，硅胶柱层析纯化后，得到中间体3；
反应过程如下：
Figure PCTCN2021121264-appb-000003
步骤A4、向三口烧瓶中依次加入中间体3、乙醇和去离子水，加热至回流，用恒压滴液漏斗向三口烧瓶中滴加质量分数20％的连二亚硫酸钠水溶液，控制滴加速度1-3滴/秒，滴加结束后，回流搅拌30min后停止加热，待溶液冷却至室温，用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，再经过蒸发浓缩，得到中间体4，将中间体4、四氢呋喃和羰基二咪唑加入反应釜中，室温条件下，转速100-150r/min搅拌2-4h后，得到中间体5；
反应过程如此：
Figure PCTCN2021121264-appb-000004
步骤A5、向反应釜中加入中间体5和二氯甲烷，搅拌溶解后加入三乙胺，温度0-5℃下通过恒压滴液漏斗向反应釜中滴加中间体2的二氯甲烷溶液，滴加结束后，升温至室温，转速100-200r/min条件下，反应2h后，用饱和碳酸氢钠、水、饱和食盐水各洗涤3次，最后经无水硫酸钠干燥，硅胶柱层析后，得到中间体6；
反应过程如下：
Figure PCTCN2021121264-appb-000005
步骤A6、将中间体6、二甲基亚砜加入三口烧瓶中，升温至80-100℃，向三口烧瓶中加入高锰酸钾和质量分数17％的盐酸溶液，转速100-200r/min条件下，搅拌反应20-40min后，过滤，将滤液转移至反应釜中，得到中间体7溶液，然后向反应釜中加入中间体1，通过恒压滴液漏斗向反应釜中滴加浓硫酸， 5min内滴加结束，滴加结束后，升温至40-50℃，保温搅拌反应2-4h，反应结束后，加入去离子水，再用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，硅胶柱层析纯化后，得到抗菌剂。
反应过程如下：
Figure PCTCN2021121264-appb-000006
进一步地，步骤A1中所述十二烷基二甲基叔胺、异丙醇和环氧氯丙烷的用量比为0.1mol：100-200mL:0.1mol；步骤A2中磺胺嘧啶、无水乙醇、三乙胺和草酰氯的用量比为0.1mol：180-220mL：5mL：0.1mol；步骤A3中碳酸钾、二甲基甲酰胺、4-甲基-2-硝基苯胺、2-氯丙烷和去离子水的用量比为4g：20mL：1.68g：2.04g：50mL；步骤A4中中间体3、乙醇、去离子水和连二亚硫酸钠水溶液的用量比为8mmol：10mL：30mL：20mL,中间体4、四氢呋喃和羰基 二咪唑的用量比为1g：15-20mL：0.5g；步骤A5中中间体5、二氯甲烷、三乙胺、中间体2的二氯甲烷溶液的用量比为1mmol：20mL：300μL：3-5mL；中间体1的二氯甲烷溶液由中间体1和二氯甲烷按照1g：3-5mL混合而成；步骤A6中中间体6、二甲基亚砜、高锰酸钾和质量分数17％的盐酸溶液的用量比为1g：20-30mL：0.1g：1-3mL，中间体6、中间体1和浓硫酸的用量比为0.1mol：0.1mol：0.1mL，浓硫酸的质量分数为95％。
进一步地，步骤A3中硅胶柱层析过程中洗脱剂为石油醚和乙酸乙酯按照体积比6:1混合而成，步骤A5和步骤A6中硅胶柱层析过程中洗脱剂为石油醚和乙酸乙酯按照体积比7:1混合而成。
进一步地，所述交联剂的制备方法如下：
将胱胺二盐酸盐和去离子水加入四口烧瓶中，在冰水浴中冷却至0-5℃，同时向四口烧瓶中滴加浓度0.01mol/mL的丙烯酰氯的二氯甲烷溶液和浓度0.01mol/mL的氢氧化钠水溶液，转速100-200r/min条件下搅拌1h，温度保持在0-5℃，搅拌反应2h后，过滤，用二氯甲烷萃取滤液，再用无水硫酸钠干燥24h，旋蒸去除二氯甲烷溶剂，最后于乙酸乙酯和庚烷体积比1：2溶剂中重结晶，得到交联剂。
进一步地，所述胱胺二盐酸盐、去离子水、丙烯酰氯的二氯甲烷溶液和氢氧化钠水溶液的用量比为11.5g：50mL：10mL：20mL。
进一步地，所述引发剂为过硫酸胺。
进一步地，所述催化剂为四甲基乙二胺。
进一步地，一种复合聚丙烯酰胺水凝胶的制备方法，步骤如下：
将丙烯酰胺和去离子水加入圆底烧瓶中，转速60r/min条件下搅拌溶解，然后向反应釜中加入交联剂，提高转速至300-500r/min，将圆底烧瓶置于冰水浴中通氮气5min后，加入引发剂和催化剂、抗菌剂，搅拌5min后，吸到注射器中，密封于4℃环境中48h形成水凝胶，再将产物放入于蒸馏水中透析48h， 每12h换水一次，得到复合聚丙烯酰胺水凝胶。
本发明的有益效果：本发明以丙烯酰胺、抗菌剂、交联剂、去离子水、引发剂和催化剂作为原料制备出复合聚丙烯酰胺水凝胶，其中交联剂是胱胺二盐酸盐和丙烯酰氯通过化学反应，得到含有-C-C-S-S-C-C-长疏水基团的交联分子，比一般的交联剂相比具有更大的分子间距，更容易互相穿插，形成的结构缠结更加复杂，因此在拉伸或压缩过程中分子链的运动相对更加困难，分子链的运动会发生选择性滑移、解缠结以保持一定的结构完整性，另外二硫键具有自修复性能，能够进一步地提高水凝胶的机械性能，以十二烷基二甲基叔胺为起始物，在异丙醇溶液中与环氧氯丙烷发生开环反应，得到含有烷基长链和醇羟基的季铵盐中间体1，以磺胺嘧啶为起始物，在无水乙醇中与草酰氯发生化学反应，得到酰氯结构的中间体2，进而以4-甲基-2-硝基苯胺为底物与2-氯丙烷反应得到中间体3，使中间体3在连二亚硫酸钠水溶液发生还原反应，得到中间体4，进而使中间体4在羰基二咪唑缩合剂的作用下，形成含有咪唑酮结构的中间体5，中间体5上的仲胺与中间体2发生消去反应，得到中间体6，通过酸性高锰酸钾使中间体6的苯甲基被氧化成羧基，得到中间体7，最后在浓硫酸的催化作用下，使中间体1和中间体7发生酯化反应，最终得到抗菌剂，该抗菌剂含有季铵盐的烷基长链、咪唑酮结构、磺胺等抗菌基团，能够赋予水凝胶优异的抗菌消炎性能，并且含有苯环、二氮杂环结构，具有较高的稳定性，不易挥发，含有仲胺、叔胺基团，这些基团与含有极性基材和非极性基材均可发生相互作用，增强水凝胶的粘附性能，本发明中的交联剂能够有效的耗散能力，赋予水凝胶较高的韧性，抗菌剂含有多种抗菌基团，赋予水凝胶较高的使用安全性。
本发明的具体实施方式
下面将对本发明实施例中的技术方案进行清楚、完整地描述，显然，所 描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其它实施例，都属于本发明保护的范围。
实施例1
一种复合聚丙烯酰胺水凝胶，包括以下重量份原料：丙烯酰胺100份、抗菌剂0.2份、交联剂0.05份、去离子水220份、引发剂0.1份、催化剂0.1份；
该复合聚丙烯酰胺水凝胶由以下步骤制成：
将丙烯酰胺和去离子水加入圆底烧瓶中，转速60r/min条件下搅拌溶解，然后向反应釜中加入交联剂，提高转速至300r/min，将圆底烧瓶置于冰水浴中通氮气5min后，加入引发剂和催化剂、抗菌剂，搅拌5min后，吸到注射器中，密封于4℃环境中48h形成水凝胶，再将产物放入于蒸馏水中透析48h，每12h换水一次，得到复合聚丙烯酰胺水凝胶。
所述抗菌剂由以下步骤制成：
步骤A1、将十二烷基二甲基叔胺和异丙醇加入烧杯中，室温条件下，转速60r/min搅拌反应10min后，升温至30℃，向烧杯中加入环氧氯丙烷，控制反应温度70℃，转速120r/min条件下搅拌反应7h，反应结束后，在0.09MPa、85℃下减压旋蒸去除异丙醇，冷却至室温后，用丙酮溶解后放入5℃冰箱中保持3h后取出，抽滤，滤饼于30℃条件下干燥12h，得到中间体1；
步骤A2、将磺胺嘧啶和无水乙醇加入三口烧瓶中，冰浴条件下搅拌10min，向三口烧瓶中加入三乙胺，然后控制反应温度40℃，转速100r/min条件下搅拌反应5min后，加入草酰氯，继续搅拌反应2h，反应结束后，向三口烧瓶中滴加质量分数1％的氢氧化钠溶液，直到沉淀析出停止滴加，然后进行过滤洗涤烘干，得到中间体2；
步骤A3、向圆底烧瓶中加入碳酸钾和二甲基甲酰胺，室温条件下，搅拌40min后加入4-甲基-2-硝基苯胺和2-氯丙烷，转速100r/min条件下搅拌反应 24h，反应结束后，向圆底烧瓶中加入去离子水，冰水浴条件下，用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，硅胶柱层析纯化后，得到中间体3；
步骤A4、向三口烧瓶中依次加入中间体3、乙醇和去离子水，加热至回流，用恒压滴液漏斗向三口烧瓶中滴加质量分数20％的连二亚硫酸钠水溶液，控制滴加速度1滴/秒，滴加结束后，回流搅拌30min后停止加热，待溶液冷却至室温，用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，再经过蒸发浓缩，得到中间体4，将中间体4、四氢呋喃和羰基二咪唑加入反应釜中，室温条件下，转速100r/min搅拌2h后，得到中间体5；
步骤A5、向反应釜中加入中间体5和二氯甲烷，搅拌溶解后加入三乙胺，温度0℃下通过恒压滴液漏斗向反应釜中滴加中间体2的二氯甲烷溶液，滴加结束后，升温至室温，转速100r/min条件下，反应2h后，用饱和碳酸氢钠、水、饱和食盐水各洗涤3次，最后经无水硫酸钠干燥，硅胶柱层析后，得到中间体6；
步骤A6、将中间体6、二甲基亚砜加入三口烧瓶中，升温至80℃，向三口烧瓶中加入高锰酸钾和质量分数17％的盐酸溶液，转速100r/min条件下，搅拌反应20min后，过滤，将滤液转移至反应釜中，得到中间体7溶液，然后向反应釜中加入中间体1，通过恒压滴液漏斗向反应釜中滴加浓硫酸，5min内滴加结束，滴加结束后，升温至40℃，保温搅拌反应2h，反应结束后，加入去离子水，再用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，硅胶柱层析纯化后，得到抗菌剂。
步骤A1中所述十二烷基二甲基叔胺、异丙醇和环氧氯丙烷的用量比为0.1mol：100mL:0.1mol；步骤A2中磺胺嘧啶、无水乙醇、三乙胺和草酰氯的用量比为0.1mol：180mL：5mL：0.1mol；步骤A3中碳酸钾、二甲基甲酰胺、4-甲基-2-硝基苯胺、2-氯丙烷和去离子水的用量比为4g：20mL：1.68g：2.04g： 50mL；步骤A4中中间体3、乙醇、去离子水和连二亚硫酸钠水溶液的用量比为8mmol：10mL：30mL：20mL,中间体4、四氢呋喃和羰基二咪唑的用量比为1g：15mL：0.5g；步骤A5中中间体5、二氯甲烷、三乙胺、中间体2的二氯甲烷溶液的用量比为1mmol：20mL：300μL：3mL；中间体1的二氯甲烷溶液由中间体1和二氯甲烷按照1g：3mL混合而成；步骤A6中中间体6、二甲基亚砜、高锰酸钾和质量分数17％的盐酸溶液的用量比为1g：20mL：0.1g：1mL，中间体6、中间体1和浓硫酸的用量比为0.1mol：0.1mol：0.1mL，浓硫酸的质量分数为95％。
步骤A3中硅胶柱层析过程中洗脱剂为石油醚和乙酸乙酯按照体积比6:1混合而成，步骤A5和步骤A6中硅胶柱层析过程中洗脱剂为石油醚和乙酸乙酯按照体积比7:1混合而成。
所述交联剂的制备方法如下：
将胱胺二盐酸盐和去离子水加入四口烧瓶中，在冰水浴中冷却至0℃，同时向四口烧瓶中滴加浓度0.01mol/mL的丙烯酰氯的二氯甲烷溶液和浓度0.01mol/mL的氢氧化钠水溶液，转速100r/min条件下搅拌1h，温度保持在0℃，搅拌反应2h后，过滤，用二氯甲烷萃取滤液，再用无水硫酸钠干燥24h，旋蒸去除二氯甲烷溶剂，最后于乙酸乙酯和庚烷体积比1：2溶剂中重结晶，得到交联剂。
所述胱胺二盐酸盐、去离子水、丙烯酰氯的二氯甲烷溶液和氢氧化钠水溶液的用量比为11.5g：50mL：10mL：20mL。
所述引发剂为过硫酸胺，所述催化剂为四甲基乙二胺。
实施例2
一种复合聚丙烯酰胺水凝胶，包括以下重量份原料：丙烯酰胺100份、抗菌剂0.8份、交联剂0.08份、去离子水250份、引发剂0.2份、催化剂0.2份；
该复合聚丙烯酰胺水凝胶由以下步骤制成：
将丙烯酰胺和去离子水加入圆底烧瓶中，转速60r/min条件下搅拌溶解， 然后向反应釜中加入交联剂，提高转速至400r/min，将圆底烧瓶置于冰水浴中通氮气5min后，加入引发剂和催化剂、抗菌剂，搅拌5min后，吸到注射器中，密封于4℃环境中48h形成水凝胶，再将产物放入于蒸馏水中透析48h，每12h换水一次，得到复合聚丙烯酰胺水凝胶。
所述抗菌剂由以下步骤制成：
步骤A1、将十二烷基二甲基叔胺和异丙醇加入烧杯中，室温条件下，转速80r/min搅拌反应10min后，升温至40℃，向烧杯中加入环氧氯丙烷，控制反应温度80℃，转速120r/min条件下搅拌反应8h，反应结束后，在0.09MPa、85℃下减压旋蒸去除异丙醇，冷却至室温后，用丙酮溶解后放入5℃冰箱中保持4h后取出，抽滤，滤饼于35℃条件下干燥12h，得到中间体1；
步骤A2、将磺胺嘧啶和无水乙醇加入三口烧瓶中，冰浴条件下搅拌10min，向三口烧瓶中加入三乙胺，然后控制反应温度40℃，转速100r/min条件下搅拌反应5min后，加入草酰氯，继续搅拌反应3h，反应结束后，向三口烧瓶中滴加质量分数1％的氢氧化钠溶液，直到沉淀析出停止滴加，然后进行过滤洗涤烘干，得到中间体2；
步骤A3、向圆底烧瓶中加入碳酸钾和二甲基甲酰胺，室温条件下，搅拌40min后加入4-甲基-2-硝基苯胺和2-氯丙烷，转速100r/min条件下搅拌反应24h，反应结束后，向圆底烧瓶中加入去离子水，冰水浴条件下，用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，硅胶柱层析纯化后，得到中间体3；
步骤A4、向三口烧瓶中依次加入中间体3、乙醇和去离子水，加热至回流，用恒压滴液漏斗向三口烧瓶中滴加质量分数20％的连二亚硫酸钠水溶液，控制滴加速度2滴/秒，滴加结束后，回流搅拌30min后停止加热，待溶液冷却至室温，用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，再经过蒸发浓缩，得到中间体4，将中间体4、四氢呋喃和羰基二咪唑加入反应釜中，室温条件 下，转速120r/min搅拌3h后，得到中间体5；
步骤A5、向反应釜中加入中间体5和二氯甲烷，搅拌溶解后加入三乙胺，温度3℃下通过恒压滴液漏斗向反应釜中滴加中间体2的二氯甲烷溶液，滴加结束后，升温至室温，转速150r/min条件下，反应2h后，用饱和碳酸氢钠、水、饱和食盐水各洗涤3次，最后经无水硫酸钠干燥，硅胶柱层析后，得到中间体6；
步骤A6、将中间体6、二甲基亚砜加入三口烧瓶中，升温至90℃，向三口烧瓶中加入高锰酸钾和质量分数17％的盐酸溶液，转速150r/min条件下，搅拌反应30min后，过滤，将滤液转移至反应釜中，得到中间体7溶液，然后向反应釜中加入中间体1，通过恒压滴液漏斗向反应釜中滴加浓硫酸，5min内滴加结束，滴加结束后，升温至45℃，保温搅拌反应3h，反应结束后，加入去离子水，再用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，硅胶柱层析纯化后，得到抗菌剂。
步骤A1中所述十二烷基二甲基叔胺、异丙醇和环氧氯丙烷的用量比为0.1mol：150mL:0.1mol；步骤A2中磺胺嘧啶、无水乙醇、三乙胺和草酰氯的用量比为0.1mol：200mL：5mL：0.1mol；步骤A3中碳酸钾、二甲基甲酰胺、4-甲基-2-硝基苯胺、2-氯丙烷和去离子水的用量比为4g：20mL：1.68g：2.04g：50mL；步骤A4中中间体3、乙醇、去离子水和连二亚硫酸钠水溶液的用量比为8mmol：10mL：30mL：20mL,中间体4、四氢呋喃和羰基二咪唑的用量比为1g：18mL：0.5g；步骤A5中中间体5、二氯甲烷、三乙胺、中间体2的二氯甲烷溶液的用量比为1mmol：20mL：300μL：4mL；中间体1的二氯甲烷溶液由中间体1和二氯甲烷按照1g：4mL混合而成；步骤A6中中间体6、二甲基亚砜、高锰酸钾和质量分数17％的盐酸溶液的用量比为1g：25mL：0.1g：2mL，中间体6、中间体1和浓硫酸的用量比为0.1mol：0.1mol：0.1mL，浓硫酸的质量分数为95％。
步骤A3中硅胶柱层析过程中洗脱剂为石油醚和乙酸乙酯按照体积比6:1 混合而成，步骤A5和步骤A6中硅胶柱层析过程中洗脱剂为石油醚和乙酸乙酯按照体积比7:1混合而成。
所述交联剂的制备方法如下：
将胱胺二盐酸盐和去离子水加入四口烧瓶中，在冰水浴中冷却至3℃，同时向四口烧瓶中滴加浓度0.01mol/mL的丙烯酰氯的二氯甲烷溶液和浓度0.01mol/mL的氢氧化钠水溶液，转速150r/min条件下搅拌1h，温度保持在3℃，搅拌反应2h后，过滤，用二氯甲烷萃取滤液，再用无水硫酸钠干燥24h，旋蒸去除二氯甲烷溶剂，最后于乙酸乙酯和庚烷体积比1：2溶剂中重结晶，得到交联剂。
所述胱胺二盐酸盐、去离子水、丙烯酰氯的二氯甲烷溶液和氢氧化钠水溶液的用量比为11.5g：50mL：10mL：20mL。
所述引发剂为过硫酸胺，所述催化剂为四甲基乙二胺。
实施例3
一种复合聚丙烯酰胺水凝胶，包括以下重量份原料：丙烯酰胺100份、抗菌剂1份、交联剂1份、去离子水290份、引发剂0.5份、催化剂0.5份；
该复合聚丙烯酰胺水凝胶由以下步骤制成：
将丙烯酰胺和去离子水加入圆底烧瓶中，转速60r/min条件下搅拌溶解，然后向反应釜中加入交联剂，提高转速至500r/min，将圆底烧瓶置于冰水浴中通氮气5min后，加入引发剂和催化剂、抗菌剂，搅拌5min后，吸到注射器中，密封于4℃环境中48h形成水凝胶，再将产物放入于蒸馏水中透析48h，每12h换水一次，得到复合聚丙烯酰胺水凝胶。
所述抗菌剂由以下步骤制成：
步骤A1、将十二烷基二甲基叔胺和异丙醇加入烧杯中，室温条件下，转速100r/min搅拌反应10min后，升温至50℃，向烧杯中加入环氧氯丙烷，控制反应温度90℃，转速120r/min条件下搅拌反应9h，反应结束后，在0.09MPa、 85℃下减压旋蒸去除异丙醇，冷却至室温后，用丙酮溶解后放入5℃冰箱中保持5h后取出，抽滤，滤饼于40℃条件下干燥12h，得到中间体1；
步骤A2、将磺胺嘧啶和无水乙醇加入三口烧瓶中，冰浴条件下搅拌10min，向三口烧瓶中加入三乙胺，然后控制反应温度40℃，转速100r/min条件下搅拌反应5min后，加入草酰氯，继续搅拌反应4h，反应结束后，向三口烧瓶中滴加质量分数1％的氢氧化钠溶液，直到沉淀析出停止滴加，然后进行过滤洗涤烘干，得到中间体2；
步骤A3、向圆底烧瓶中加入碳酸钾和二甲基甲酰胺，室温条件下，搅拌40min后加入4-甲基-2-硝基苯胺和2-氯丙烷，转速100r/min条件下搅拌反应24h，反应结束后，向圆底烧瓶中加入去离子水，冰水浴条件下，用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，硅胶柱层析纯化后，得到中间体3；
步骤A4、向三口烧瓶中依次加入中间体3、乙醇和去离子水，加热至回流，用恒压滴液漏斗向三口烧瓶中滴加质量分数20％的连二亚硫酸钠水溶液，控制滴加速度3滴/秒，滴加结束后，回流搅拌30min后停止加热，待溶液冷却至室温，用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，再经过蒸发浓缩，得到中间体4，将中间体4、四氢呋喃和羰基二咪唑加入反应釜中，室温条件下，转速150r/min搅拌4h后，得到中间体5；
步骤A5、向反应釜中加入中间体5和二氯甲烷，搅拌溶解后加入三乙胺，温度5℃下通过恒压滴液漏斗向反应釜中滴加中间体2的二氯甲烷溶液，滴加结束后，升温至室温，转速200r/min条件下，反应2h后，用饱和碳酸氢钠、水、饱和食盐水各洗涤3次，最后经无水硫酸钠干燥，硅胶柱层析后，得到中间体6；
步骤A6、将中间体6、二甲基亚砜加入三口烧瓶中，升温至100℃，向三口烧瓶中加入高锰酸钾和质量分数17％的盐酸溶液，转速200r/min条件下，搅 拌反应40min后，过滤，将滤液转移至反应釜中，得到中间体7溶液，然后向反应釜中加入中间体1，通过恒压滴液漏斗向反应釜中滴加浓硫酸，5min内滴加结束，滴加结束后，升温至50℃，保温搅拌反应4h，反应结束后，加入去离子水，再用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，硅胶柱层析纯化后，得到抗菌剂。
步骤A1中所述十二烷基二甲基叔胺、异丙醇和环氧氯丙烷的用量比为0.1mol：200mL:0.1mol；步骤A2中磺胺嘧啶、无水乙醇、三乙胺和草酰氯的用量比为0.1mol：220mL：5mL：0.1mol；步骤A3中碳酸钾、二甲基甲酰胺、4-甲基-2-硝基苯胺、2-氯丙烷和去离子水的用量比为4g：20mL：1.68g：2.04g：50mL；步骤A4中中间体3、乙醇、去离子水和连二亚硫酸钠水溶液的用量比为8mmol：10mL：30mL：20mL,中间体4、四氢呋喃和羰基二咪唑的用量比为1g：20mL：0.5g；步骤A5中中间体5、二氯甲烷、三乙胺、中间体2的二氯甲烷溶液的用量比为1mmol：20mL：300μL：5mL；中间体1的二氯甲烷溶液由中间体1和二氯甲烷按照1g：5mL混合而成；步骤A6中中间体6、二甲基亚砜、高锰酸钾和质量分数17％的盐酸溶液的用量比为1g：30mL：0.1g：3mL，中间体6、中间体1和浓硫酸的用量比为0.1mol：0.1mol：0.1mL，浓硫酸的质量分数为95％。
步骤A3中硅胶柱层析过程中洗脱剂为石油醚和乙酸乙酯按照体积比6:1混合而成，步骤A5和步骤A6中硅胶柱层析过程中洗脱剂为石油醚和乙酸乙酯按照体积比7:1混合而成。
所述交联剂的制备方法如下：
将胱胺二盐酸盐和去离子水加入四口烧瓶中，在冰水浴中冷却至5℃，同时向四口烧瓶中滴加浓度0.01mol/mL的丙烯酰氯的二氯甲烷溶液和浓度0.01mol/mL的氢氧化钠水溶液，转速200r/min条件下搅拌1h，温度保持在5℃，搅拌反应2h后，过滤，用二氯甲烷萃取滤液，再用无水硫酸钠干燥24h，旋蒸去除二氯甲烷溶剂，最后于乙酸乙酯和庚烷体积比1：2溶剂中重结晶， 得到交联剂。
所述胱胺二盐酸盐、去离子水、丙烯酰氯的二氯甲烷溶液和氢氧化钠水溶液的用量比为11.5g：50mL：10mL：20mL。
所述引发剂为过硫酸胺，所述催化剂为四甲基乙二胺。
对比例
本对比例为市场上常见的一种复合聚丙烯酰胺水凝胶。
将实施例1-3和对比例的水凝胶进行性能测试，测试标准如下：
拉伸性能测试：采用万能试验机拉伸性能测试，样品裁剪成约直径4mm高45mm的圆柱，初始长度标距长度为15mm，加载速度为100mm/min，测试仪器的夹子粘一层粗糙的纸，防止水凝胶在测试时滑动。
溶胀性能测试：将复合凝胶样品进行自然烘干，待其失去所有水分，称量其干重，而后将样品放置于有磷酸一氢钠和磷酸二氢钠配制的pH＝7.4的缓冲液，浸泡20h后，测试溶胀比，溶胀比公式为SR＝(W s-W d)/W d×100％，W s为吸水后的质量/g，W d为干重质量；
溶血性能测试：取5mL新鲜抗凝兔血红细胞于离心管中，在2000r/min条件下离心5min，然后取出0.2mL离心过的抗凝血红细胞加入试管中，缓慢加入10mL生理盐水，然后取5g复合凝胶样品放入其中，并轻微震荡，混合均匀，置于37℃水浴保温震荡60min，以10mL生理盐水加兔红细胞为阴性对照，分别取上述试管中溶液在转速2000rpm的离心机中离心3min，取上层清液，用UV-vis光谱仪测定上清液在454nm处的吸光度，记录试验结果，并计算溶血率(HR)，HR＝(OD t-OD n)/(OD P-OD n)×100％,其中OD t、OD P、OD n分别为试验组、阳性对照组、阴性对照吸光度值，平行测试三次取其平均值；
抗菌性测试：采用贴膜法GB/T 21866-2008标准定量表征实施例1-3和对比例的抗菌性能。测试结果如下表所示：
项目 拉伸强度/MPa 溶胀比/％ 溶血率/％ 大肠杆菌抑菌率/％
实施例1 0.117 830 1.80 99.8
实施例2 0.120 850 1.72 99.5
实施例3 0.119 870 1.77 99.7
对比例 0.080 1100 6 82.1
由上表可以看出，实施例1-3的复合凝胶在拉伸强度、溶胀比、溶血率和大肠杆菌抑菌率测试过程中，表现均优于对比例，说明本发明制备的复合凝胶具有较高的力学性能和抗菌性能，在医用领域具有很大的应用价值。
以上内容仅仅是对本发明的构思所作的举例和说明，所属本技术领域的技术人员对所描述的具体实施例做各种各样的修改或补充或采用类似的方式替代，只要不偏离发明的构思或者超越本权利要求书所定义的范围，均应属于本发明的保护范围。

Claims (5)

  1. 一种复合聚丙烯酰胺水凝胶，其特征在于，包括以下重量份原料：丙烯酰胺100份、抗菌剂0.2-1份、交联剂0.05-1份、去离子水220-290份、引发剂0.1-0.5份、催化剂0.1-0.5份；
    该复合聚丙烯酰胺水凝胶由以下步骤制成：
    将丙烯酰胺和去离子水加入圆底烧瓶中，转速60r/min条件下搅拌溶解，然后向反应釜中加入交联剂，提高转速至300-500r/min，将圆底烧瓶置于冰水浴中通氮气5min后，加入引发剂和催化剂、抗菌剂，搅拌5min后，吸到注射器中，密封于4℃环境中48h形成水凝胶，再将产物放入于蒸馏水中透析48h，每12h换水一次，得到复合聚丙烯酰胺水凝胶。
  2. 根据权利要求1所述的一种复合聚丙烯酰胺水凝胶，其特征在于，所述抗菌剂由以下步骤制成：
    步骤A1、将十二烷基二甲基叔胺和异丙醇加入烧杯中，室温条件下，转速60-100r/min搅拌反应10min后，升温至30-50℃，向烧杯中加入环氧氯丙烷，控制反应温度70-90℃，转速120r/min条件下搅拌反应7-9h，反应结束后，在0.09MPa、85℃下减压旋蒸去除异丙醇，冷却至室温后，用丙酮溶解后放入5℃冰箱中保持3-5h后取出，抽滤，滤饼于30-40℃条件下干燥12h，得到中间体1；
    步骤A2、将磺胺嘧啶和无水乙醇加入三口烧瓶中，冰浴条件下搅拌10min，向三口烧瓶中加入三乙胺，然后控制反应温度40℃，转速100r/min条件下搅拌反应5min后，加入草酰氯，继续搅拌反应2-4h，反应结束后，向三口烧瓶中滴加质量分数1％的氢氧化钠溶液，直到沉淀析出停止滴加，然后进行过滤洗涤烘干，得到中间体2；
    步骤A3、向圆底烧瓶中加入碳酸钾和二甲基甲酰胺，室温条件下，搅拌 40min后加入4-甲基-2-硝基苯胺和2-氯丙烷，转速100r/min条件下搅拌反应24h，反应结束后，向圆底烧瓶中加入去离子水，冰水浴条件下，用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，硅胶柱层析纯化后，得到中间体3；
    步骤A4、向三口烧瓶中依次加入中间体3、乙醇和去离子水，加热至回流，用恒压滴液漏斗向三口烧瓶中滴加质量分数20％的连二亚硫酸钠水溶液，控制滴加速度1-3滴/秒，滴加结束后，回流搅拌30min后停止加热，待溶液冷却至室温，用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，再经过蒸发浓缩，得到中间体4，将中间体4、四氢呋喃和羰基二咪唑加入反应釜中，室温条件下，转速100-150r/min搅拌2-4h后，得到中间体5；
    步骤A5、向反应釜中加入中间体5和二氯甲烷，搅拌溶解后加入三乙胺，温度0-5℃下通过恒压滴液漏斗向反应釜中滴加中间体2的二氯甲烷溶液，滴加结束后，升温至室温，转速100-200r/min条件下，反应2h后，用饱和碳酸氢钠、水、饱和食盐水各洗涤3次，最后经无水硫酸钠干燥，硅胶柱层析后，得到中间体6；
    步骤A6、将中间体6、二甲基亚砜加入三口烧瓶中，升温至80-100℃，向三口烧瓶中加入高锰酸钾和质量分数17％的盐酸溶液，转速100-200r/min条件下，搅拌反应20-40min后，过滤，将滤液转移至反应釜中，得到中间体7溶液，然后向反应釜中加入中间体1，通过恒压滴液漏斗向反应釜中滴加浓硫酸，5min内滴加结束，滴加结束后，升温至40-50℃，保温搅拌反应2-4h，反应结束后，加入去离子水，再用乙酸乙酯萃取3次，合并有机相，经无水硫酸钠干燥，硅胶柱层析纯化后，得到抗菌剂。
  3. 根据权利要求1所述的一种复合聚丙烯酰胺水凝胶，其特征在于，所述交联剂的制备方法如下：
    将胱胺二盐酸盐和去离子水加入四口烧瓶中，在冰水浴中冷却至0-5℃， 同时向四口烧瓶中滴加浓度0.01mol/mL的丙烯酰氯的二氯甲烷溶液和浓度0.01mol/mL的氢氧化钠水溶液，转速100-200r/min条件下搅拌1h，温度保持在0-5℃，搅拌反应2h后，过滤，用二氯甲烷萃取滤液，再用无水硫酸钠干燥24h，旋蒸去除二氯甲烷溶剂，最后于乙酸乙酯和庚烷体积比1：2溶剂中重结晶，得到交联剂。
  4. 根据权利要求1所述的一种复合聚丙烯酰胺水凝胶，其特征在于，所述引发剂为过硫酸胺，所述催化剂为四甲基乙二胺。
  5. 根据权利要求1所述的一种复合聚丙烯酰胺水凝胶的制备方法，其特征在于，步骤如下：
    将丙烯酰胺和去离子水加入圆底烧瓶中，转速60r/min条件下搅拌溶解，然后向反应釜中加入交联剂，提高转速至300-500r/min，将圆底烧瓶置于冰水浴中通氮气5min后，加入引发剂和催化剂、抗菌剂，搅拌5min后，吸到注射器中，密封于4℃环境中48h形成水凝胶，再将产物放入于蒸馏水中透析48h，每12h换水一次，得到复合聚丙烯酰胺水凝胶。
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