CN111303450B - Injectable composite antibacterial hydrogel and preparation method thereof - Google Patents
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Abstract
The invention provides an injectable composite antibacterial hydrogel and a preparation method thereof, wherein the method comprises the following steps: in the presence of a catalyst, adjusting the pH value of the carboxylated polyvinyl alcohol solution to 3-4, and reacting the carboxylated polyvinyl alcohol solution with epsilon-polylysine to obtain an amino-modified polyvinyl alcohol solution; blending chitosan solution, hydroformylation glucan solution and the amino modified polyvinyl alcohol solution to obtain injectable composite antibacterial hydrogel; the mass ratio of the amino-modified polyvinyl alcohol to the chitosan to the hydroformylated dextran is 4-1: 1: 0.05-0.5. According to the method, amino-modified polyvinyl alcohol with an antibacterial function is blended with chitosan, and then amino groups on molecular chains of the polyvinyl alcohol and the chitosan and aldehyde groups on molecular chains of the chitosan are utilized to construct dynamic Schiff base bonds, so that the hydrogel has reversible crosslinking and is an intrinsic antibacterial material. Also has high antibacterial rate. The hydrogel prepared by the embodiment of the invention has the highest bacteriostasis rate of 99.99% to escherichia coli and staphylococcus aureus.
Description
Technical Field
The invention belongs to the technical field of hydrogel, and particularly relates to injectable composite antibacterial hydrogel and a preparation method thereof.
Background
The hydrogel is a cross-linked body composed of natural or synthetic macromolecules and a certain amount of water, has not only excellent water absorption, but also certain elasticity and excellent biocompatibility, and can be used in the fields of tissue engineering, drug carriers, cell culture and the like (Y.Hao, J.L.He, X.Ma et al, A full soluble and photosslinked polysaccharide-polyphosphate hydrogel for tissue engineering, Carbohydrate Polymers 225(2019) 115257). Hydrogels should have certain antimicrobial properties as Wound dressings, since bacterial infection of wounds can lead to sepsis, increasing the risk of amputation and death (p.g. bowler, bound pathology, infection and therapeutic options, ann.med,34(2002), 419-427.). Chitosan is a natural polymer, has the characteristics of good biocompatibility, degradability and antibacterial property, and is commonly used for constructing hydrogel materials. Another polymer, polyvinyl alcohol, is also widely used to construct hydrogel systems, which is a water-soluble polymer with excellent biocompatibility, however, pure polyvinyl alcohol has no antibacterial effect, and many antibacterial polyvinyl alcohol-based hydrogel materials are prepared by blending metal nanoparticles or oxides. For example, M-Khorasani et al (M.T-Khorasani, A. Joorabloo, A. Moghaddam, et al, incorporated of ZnO nanoparticles in-situ polyvinyl alcohol/chitosan hydrogels for around driving application, International Journal of Biological Macromolecules,114(2018),1203-1215.) produced hydrogel medical dressings with good biocompatibility and mechanical properties by freeze-thaw cycling, with bacteriostatic rates for E.coli and S.aureus of above 70%. Kou et al (S.Bhowmick, V.Koul, Assessment of PVA/silver nanocomposite hydrogel as antimicrobial dressing: Synthesis, chromatography and biological evaluation, Materials Science and Engineering C,59(2016) 109-. Yang et al (W.Yang, E.Fortunati, F.Bertoglio, et al, Polyvinyl alcohol/chitosan hydrogels with enhanced activity and antibacterial properties induced by lignin nanoparticles, Carbohydrate Polymers,181(2018)275-284.) utilize a freeze-thaw cycle to prepare a hydrogel material that can reduce 95% of Escherichia coli and 85% of Staphylococcus aureus, and have potential applications in the fields of drug delivery, food packaging, wound dressing, and the like. Chaturvedi et al (a. Chaturvedi, a.k. bajpal, j. bajpai, et al, Evaluation of Poly (vinyl alcohol) based cryogel-zinc oxide nanocomposites for porous applications as a ground addressing Materials, Materials Science and Engineering C,65(2016)408- & 418.) prepared composite polyvinyl alcohol hydrogel Materials by doping with nano zinc oxide particles using a freeze-thaw cycle, and antibacterial tests showed that the Materials had good antibacterial activity against both gram-negative and gram-positive bacteria.
The injectable hydrogel can be injected in a liquid state through an injector and forms solid hydrogel inside and outside a living body, has the characteristics of in-situ drug coating, irregular-shaped wound filling, good adhesion and the like, is widely concerned in recent years, and can prolong the service life of materials and provide better protection for the wound. For example, Chen et al (H.Chen, J.Cheng, L.ran, et al, An injectable hydrogel with adhesive and antibacterial properties active surfaces surrounding the hydrogel, Carbohydrate Polymers,201(2018)522-531.) prepared An injectable hydrogel material that can kill 98% of E.coli and 96% of Staphylococcus aureus by creating Schiff base bonds between chitosan and oxidized konjac glycosides, and animal experiments showed that the material had good wound healing promoting effects. Dong et al (R.Dong, X.ZHao, B.Guo, et al, Self-healing Conductive additives with Antibacterial Activity as Cell Delivery Carrier for card Cell Therapy, ACS Appl.Mater.Interfaces 2016,8, 17138-. Qu et al (J.Qu, X.ZHao, Y.Liang, et al. degradable contained injectable hydrogels as novel additives, inorganic materials for surrounding health, Chemical Engineering Journal 362(2019)548-560.) designed and prepared injectable hydrogels based on oxidized hyaluronic acid grafted aniline tetramers, which had biodegradable, conductive and antioxidant properties, and simultaneously were loaded with amoxicillin to have excellent antibacterial properties, and wound healing experiments proved that the prepared hydrogels had good effects of promoting epithelial tissue healing.
The hydrogel prepared by using the polyvinyl alcohol mostly realizes the cross-linking among molecular chains through a chemical cross-linking agent or a physical means, the cross-linking mode is irreversible, and meanwhile, the hydrogel material prepared by using the polyvinyl alcohol as a raw material mostly adopts the blending and doping of substances with an antibacterial function so as to endow the material with the antibacterial property.
Disclosure of Invention
In view of the above, the present invention is directed to an injectable composite antibacterial hydrogel that is reversibly crosslinkable and is an intrinsic antibacterial material, and a method for preparing the same.
The invention provides a preparation method of injectable composite antibacterial hydrogel, which comprises the following steps:
in the presence of a catalyst, adjusting the pH value of the carboxylated polyvinyl alcohol solution to 3-4, and reacting the carboxylated polyvinyl alcohol solution with epsilon-polylysine to obtain an amino-modified polyvinyl alcohol solution;
blending chitosan solution, hydroformylation glucan solution and the amino modified polyvinyl alcohol solution to obtain injectable composite antibacterial hydrogel;
the mass ratio of the amino-modified polyvinyl alcohol to the chitosan to the hydroformylated dextran is 4-1: 1: 0.05-0.5.
Preferably, the carboxylated polyvinyl alcohol is prepared according to the following method:
dissolving vinyl acetate in azodiisobutyronitrile, reacting with acrylic acid, precipitating the obtained product in deionized water, drying, dissolving again, performing alcoholysis reaction with sodium hydroxide solution, dissolving the obtained colloidal product in water, filtering, precipitating in methanol, and drying to obtain carboxylated polyvinyl alcohol.
Preferably, the reaction temperature of the dissolved vinyl acetate and the acrylic acid is 60-70 ℃ and the reaction time is 6-8 h.
Preferably, the reaction temperature of the carboxylated polyvinyl alcohol solution and epsilon-polylysine is 20-30 ℃ after the pH value of the carboxylated polyvinyl alcohol solution is adjusted to 3-4, and the reaction time is 8-12 hours.
Preferably, the mass fraction of the chitosan solution is 2.0-3.0%; the mass fraction of the hydroformylation glucan solution is 5.5-6.5%; the mass fraction of the amino-modified polyvinyl alcohol solution is 9-11%.
Preferably, the catalyst is selected from a mixture of carbodiimide hydrochloride and N-hydroxysuccinimide;
the catalyst accounts for 5-10% of the mass of the carboxylated polyvinyl alcohol.
The invention provides an injectable composite antibacterial hydrogel which is prepared by the preparation method of the technical scheme.
The invention provides a preparation method of injectable composite antibacterial hydrogel, which comprises the following steps: in the presence of a catalyst, adjusting the pH value of the carboxylated polyvinyl alcohol solution to 3-4, and reacting the carboxylated polyvinyl alcohol solution with epsilon-polylysine to obtain an amino-modified polyvinyl alcohol solution; blending chitosan solution, hydroformylation glucan solution and the amino modified polyvinyl alcohol solution to obtain injectable composite antibacterial hydrogel; the mass ratio of the amino-modified polyvinyl alcohol to the chitosan to the hydroformylated dextran is 4-1: 1: 0.05-0.5. The method provided by the invention adopts amino modified polyvinyl alcohol with an antibacterial function, and the amino on the molecular chains of the polyvinyl alcohol and the chitosan are mixed to construct a dynamic Schiff base bond by utilizing the amino on the molecular chains of the polyvinyl alcohol and the chitosan and the aldehyde on the molecular chain of the hydroformylation glucan, so that the prepared hydrogel has reversible crosslinking property and is an intrinsic antibacterial material. Also has higher bacteriostasis rate. The experimental results show that: the hydrogel prepared by the embodiment of the invention has the highest bacteriostasis rate of 99.99% to escherichia coli and staphylococcus aureus.
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FIG. 1 is a chart of the infrared characterization of C-PVA and CPVA-EPL-1 prepared in example 1 of the present invention;
FIG. 2 is a liquid nuclear magnetic characterization of C-PVA and CPVA-EPL-1 prepared in example 1 of the present invention;
FIG. 3 is a graph showing the nuclear magnetic solid state characterization of PVA, C-PVA, CPVA-EPL-1 and CPVA-EPL-2 in examples of the present invention.
Detailed Description
The invention provides a preparation method of injectable composite antibacterial hydrogel, which comprises the following steps:
in the presence of a catalyst, adjusting the pH value of a carboxylated polyvinyl alcohol (C-PVA) solution to 3-4, and reacting the solution with epsilon-polylysine (EPL) to obtain an amino modified polyvinyl alcohol solution (CPVA-g-EPL);
blending a Chitosan (CS) solution, a hydroformylation glucan solution and the amino-modified polyvinyl alcohol solution to obtain an injectable composite antibacterial hydrogel;
the mass ratio of the amino-modified polyvinyl alcohol to the chitosan to the hydroformylated dextran is 4-1: 1: 0.05-0.5.
The method provided by the invention adopts amino modified polyvinyl alcohol with an antibacterial function, and the amino on the molecular chains of the polyvinyl alcohol and the chitosan are mixed to construct a dynamic Schiff base bond by utilizing the amino on the molecular chains of the polyvinyl alcohol and the chitosan and the aldehyde on the molecular chain of the hydroformylation glucan, so that the prepared hydrogel has reversible crosslinking property and is an intrinsic antibacterial material. Also has higher bacteriostasis rate. The intrinsic antibacterial hydrogel is formed by high molecules for constructing a hydrogel network, has an antibacterial effect, and does not need to be added or doped with a series of antibacterial agents such as metal nanoparticles, antibiotics and the like.
In the presence of a catalyst, the pH value of the carboxylated polyvinyl alcohol solution is adjusted to 3-4, and then the carboxylated polyvinyl alcohol solution reacts with epsilon-polylysine to obtain the amino-modified polyvinyl alcohol solution. In the present invention, the catalyst is selected from a mixture of carbodiimide hydrochloride and N-hydroxysuccinimide; the catalyst accounts for 5-10% of the mass of the carboxylated polyvinyl alcohol.
In the present invention, the carboxylated polyvinyl alcohol is preferably prepared according to the following method:
dissolving vinyl acetate in azodiisobutyronitrile, reacting with acrylic acid, precipitating the obtained product in deionized water, drying, dissolving again, performing alcoholysis reaction with sodium hydroxide solution, dissolving the obtained colloidal product in water, filtering, precipitating in methanol, and drying to obtain carboxylated polyvinyl alcohol.
In the present invention, the vinyl acetate is dissolved in methanol. Azodiisobutyronitrile as a catalyst; the mass of the azodiisobutyronitrile accounts for 0.1-0.2% of that of the vinyl acetate. The reaction temperature of the dissolved vinyl acetate and acrylic acid is 60-70 ℃, and the reaction time is 6-8 h; in a specific embodiment, the reaction temperature of the dissolved vinyl acetate and the acrylic acid is 65 ℃ and the reaction time is 8 hours.
In the present invention, the mass ratio of sodium hydroxide to carboxylated polyvinyl alcohol is 0.02: 1; the molar concentration of the sodium hydroxide solution is 1 mol/L; the temperature of the alcoholysis reaction is preferably 40-60 ℃, and more preferably 50-55 ℃; the alcoholysis reaction time is preferably 25-35 min, and more preferably 28-32 min; in a specific embodiment, the temperature for alcoholysis is 50 ℃ and the time for alcoholysis is 30 min. Dissolving the colloidal product in water, filtering to remove insoluble impurities, cooling to room temperature, and precipitating in methanol; the methanol is used as a precipitator; preferably 3 times; filtering and drying after precipitation to obtain the carboxylated polyvinyl alcohol.
The carboxylated polyvinyl alcohol solution is prepared by dissolving carboxylated polyvinyl alcohol in water; the dissolving temperature is 95 ℃, and the time is 3 h. According to the invention, nitric acid is preferably adopted to adjust the pH value of the carboxylated polyvinyl alcohol solution to 3-4, and then a catalyst is added to activate for 1.5-2.5 h. And after the pH value of the carboxylated polyvinyl alcohol solution is adjusted to 3-4, the reaction with epsilon-polylysine is carried out at the temperature of 20-30 ℃ for 8-12 h. And precipitating the obtained reaction product in acetone after the reaction, and drying to obtain the amino-modified polyvinyl alcohol. In the specific example, the reaction temperature with epsilon-polylysine is 30 ℃ and the reaction time is 8 h. The mass ratio of the carboxylated polyvinyl alcohol to the epsilon-polylysine is 1:1 or 1: 2. the invention dissolves amino-modified polyvinyl alcohol in water to obtain amino-modified polyvinyl alcohol solution. The mass fraction of the amino-modified polyvinyl alcohol solution is preferably 9-11%; in a specific embodiment, the mass fraction of the amino-modified polyvinyl alcohol solution is 10%.
After the amino-modified polyvinyl alcohol solution is obtained, the chitosan solution, the hydroformylation glucan solution and the amino-modified polyvinyl alcohol solution are blended to obtain the injectable composite antibacterial hydrogel.
In the present invention, the hydroformylated dextran is preferably prepared according to the following method:
mixing dextran solution with NaIO4And stirring the solution for 22-26 h in the dark, dialyzing, and freeze-drying the obtained dialysis product to obtain the hydroformylation glucan.
In the present invention, dextran and NaIO4The mass ratio of (A) to (B) is preferably 0.95 to 1.05, more preferably 1: 1.
In the invention, the mass fraction of the hydroformylation glucan solution is preferably 5.5-6.5%, and more preferably 5.8-6.2%. The mass fraction of the chitosan solution is preferably 2.0-3.0%, and more preferably 2.3-2.8%. In a specific embodiment, the mass fraction of the hydroformylation glucan solution is 6.0%; the mass fraction of the chitosan solution is 2.5%.
The blending temperature of the chitosan solution, the hydroformylation glucan solution and the amino modified polyvinyl alcohol solution is preferably room temperature, and more preferably 20-30 ℃. Mixing uniformly. The mass ratio of the amino-modified polyvinyl alcohol to the chitosan to the hydroformylated dextran is 4-1: 1: 0.05-0.5, more preferably 1.5-4: 1: 0.45-0.5, and most preferably 2-4: 1: 0.48. In a specific embodiment, the mass ratio of chitosan in the chitosan solution, the hydroformylated dextran in the hydroformylated dextran solution, and the amino-modified polyvinyl alcohol in the amino-modified polyvinyl alcohol solution is specifically 1:0.48: 4; or 1:0.48: 2.
The invention provides an injectable composite antibacterial hydrogel which is prepared by the preparation method of the technical scheme.
The injectable composite antibacterial hydrogel has antibacterial effect on gram-negative bacteria and gram-positive bacteria, such as escherichia coli and staphylococcus aureus.
In order to further illustrate the present invention, the following examples are provided to describe an injectable composite antibacterial hydrogel and a method for preparing the same in detail, but they should not be construed as limiting the scope of the present invention.
Example 1
Adding 20mL of refined vinyl acetate into 40mL of methanol, introducing nitrogen to remove oxygen for 30min, then adding 0.02g of AIBN and 3mL of acrylic acid, reacting for 8h at 65 ℃, precipitating a product in deionized water, and naming the product as P (VAc-co-AA); preparing 25 mass percent of P (VAc-co-AA) methanol solution, adding a proper amount of 1mol/L sodium hydroxide methanol solution at normal temperature to enable the mass ratio of NaOH to P (VAc-co-AA) to reach 0.02, uniformly mixing, carrying out alcoholysis reaction in a thermostatic water bath at 50 ℃ for 30min to obtain a colloidal product, heating deionized water to dissolve the colloidal product, filtering to remove insoluble impurities, cooling to room temperature, precipitating for 3 times by using methanol as a precipitator, filtering, and drying to obtain carboxylated polyvinyl alcohol (C-PVA).
Adding 10mL of deionized water into a 100mL two-neck flask, adding 1g C-PVA, adding a proper amount of nitric acid to adjust the pH value to 3-4, dissolving for 3h at 95 ℃, cooling to 30 ℃, adding 0.1g of EDC and NHS, activating for 2h, adding 1g of EPL to react for 8h, precipitating the product in acetone, and drying to obtain the product named CPVA-g-EPL-1.
Dissolving 2g dextran in 20mL deionized water, and collecting 2g NaIO4Dissolving in 20mL deionized water, mixing, stirring in dark for 24 hr, dialyzing for 24 hr, and lyophilizing to obtain hydroformylation dextran (ODEX).
1mL of 10 mass percent CPVA-g-EPL-1 solution is taken, 1mL of 2.5 mass percent chitosan solution and 200 mu L of 6 mass percent ODEX solution are added, and the mixture is uniformly mixed at room temperature to prepare hydrogel, wherein the product number is S1. The antibacterial test result shows that the bacteriostasis rate of S1 to escherichia coli is 99.89%, and the bacteriostasis rate to staphylococcus aureus is 99.90%.
FIG. 1 is a chart of the infrared characterization of C-PVA and CPVA-EPL-1 prepared in example 1 of the present invention;
3300cm in the figure-1Is located at 2900cm of the stretching vibration peak of hydroxyl in the molecular chain of the carboxylated polyvinyl alcohol C-PVA-1The characteristic peak is the stretching vibration peak of-OH in C-PVA carboxyl, 1080cm-1The position is a stretching vibration characteristic peak of a C-O bond; for the epsilon-polylysine modified polyvinyl alcohol CPVA-g-EPL-1,3230cm-1Is the stretching vibration peak of amino group in molecular chain, 1650 and 1550cm-1Is the in-plane vibration peak of the amino group, and the above results show that carboxylated polyvinyl alcohol and epsilon-polylysine modified polyvinyl alcohol are successfully prepared.
FIG. 2 is a liquid nuclear magnetic characterization of C-PVA and CPVA-EPL-1 prepared in example 1 of the present invention;
compared with the original C-PVA, the 8.7ppm is a characteristic peak of amino in CPVA-g-EPL-1;
FIG. 3 is a graph showing the nuclear magnetic solid state characterization of PVA, C-PVA, CPVA-EPL-1 and CPVA-EPL-2 in examples of the present invention. Compared with PVA and C-PVA, the molecular chain has a characteristic peak that 170ppm is carbonyl in the epsilon-polylysine molecular chain, and the results show that the epsilon-polylysine modified polyvinyl alcohol is successfully prepared.
Example 2:
the experimental procedures for the preparation of carboxylated polyvinyl alcohol (C-PVA), amino acid modified polyvinyl alcohol (CPVA-g-EPL-1) and hydroformylated dextran (ODEX) were the same as in example 1.
0.7mL of 10% by mass CPVA-g-EPL-1 solution was added with 1.4mL of 2.5% by mass chitosan solution and 200. mu.L of 6% by mass ODEX solution, and the mixture was mixed uniformly at room temperature to prepare a hydrogel, the product number was S2. The antibacterial test result shows that the bacteriostasis rate of S2 to escherichia coli is 99.96%, and the bacteriostasis rate to staphylococcus aureus is 99.98%.
Example 3:
the experimental procedure for the preparation of carboxylated polyvinyl alcohol (C-PVA) and of hydroformylated dextran (ODEX) was the same as in example 1.
Adding 10mL of deionized water into a 100mL two-neck flask, adding 1g of C-PVA, adding a proper amount of nitric acid to adjust the pH value to 3-4, dissolving for 3h at 95 ℃, cooling to 30 ℃, adding 0.1g of EDC and NHS, activating for 2h, adding 2g of EPL to react for 8h, precipitating a product in acetone, and drying to obtain the product named CPVA-g-EPL-2.
1mL of 10 mass percent CPVA-g-EPL-2 solution is taken, 1mL of 2.5 mass percent chitosan solution and 200 mu L of 6 mass percent ODEX solution are added, and the mixture is uniformly mixed at room temperature to prepare hydrogel, wherein the product number is S3. The antibacterial test result shows that the bacteriostasis rate of S3 to escherichia coli is 99.99%, and the bacteriostasis rate to staphylococcus aureus is 99.92%.
Example 4:
the experimental procedures for the preparation of carboxylated polyvinyl alcohol (C-PVA) and hydroformylated dextran (ODEX) were the same as in example 1. The experimental procedure for the preparation of amino-modified polyvinyl alcohol (CPVA-g-EPL-2) was the same as in example 3.
0.7mL of 10% by mass CPVA-g-EPL-2 solution was added with 1.4mL of 2.5% by mass chitosan solution and 200. mu.L of 6% by mass ODEX solution, and the mixture was mixed uniformly at room temperature to prepare a hydrogel, the product number was S4. The antibacterial test result shows that the bacteriostasis rate of S4 to escherichia coli is 99.98%, and the bacteriostasis rate to staphylococcus aureus is 99.99%.
From the above embodiments, the present invention provides a method for preparing an injectable composite antibacterial hydrogel, comprising the following steps: in the presence of a catalyst, adjusting the pH value of the carboxylated polyvinyl alcohol solution to 3-4, and reacting the carboxylated polyvinyl alcohol solution with epsilon-polylysine to obtain an amino-modified polyvinyl alcohol solution; blending chitosan solution, hydroformylation glucan solution and the amino modified polyvinyl alcohol solution to obtain injectable composite antibacterial hydrogel; the mass ratio of the amino-modified polyvinyl alcohol to the chitosan to the hydroformylated dextran is 4-1: 1: 0.05-0.5. The method provided by the invention adopts amino modified polyvinyl alcohol with an antibacterial function, and the amino on the molecular chains of the polyvinyl alcohol and the chitosan are mixed to construct a dynamic Schiff base bond by utilizing the amino on the molecular chains of the polyvinyl alcohol and the chitosan and the aldehyde on the molecular chain of the hydroformylation glucan, so that the prepared hydrogel has reversible crosslinking property and is an intrinsic antibacterial material. Also has higher bacteriostasis rate. The experimental results show that: the hydrogel prepared by the embodiment of the invention has the highest bacteriostasis rate of 99.99% to escherichia coli and staphylococcus aureus.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (4)
1. A preparation method of injectable composite antibacterial hydrogel comprises the following steps:
in the presence of a catalyst, adjusting the pH value of the carboxylated polyvinyl alcohol solution to 3-4, reacting the carboxylated polyvinyl alcohol solution with epsilon-polylysine, precipitating an obtained reaction product in acetone after reaction, drying to obtain amino-modified polyvinyl alcohol, and dissolving the amino-modified polyvinyl alcohol in water to obtain an amino-modified polyvinyl alcohol solution; the reaction temperature is 20-30 ℃, and the reaction time is 8-12 h;
blending chitosan solution, hydroformylation glucan solution and the amino modified polyvinyl alcohol solution to obtain injectable composite antibacterial hydrogel; the mass fraction of the chitosan solution is 2.0-3.0%; the mass fraction of the hydroformylation glucan solution is 5.5-6.5%; the mass fraction of the amino-modified polyvinyl alcohol solution is 9-11%;
the mass ratio of the amino-modified polyvinyl alcohol to the chitosan to the hydroformylated dextran is 4-1: 1: 0.05-0.5;
the catalyst is selected from a mixture of carbodiimide hydrochloride and N-hydroxysuccinimide;
the catalyst accounts for 5-10% of the mass of the carboxylated polyvinyl alcohol.
2. The method of claim 1, wherein the carboxylated polyvinyl alcohol is prepared by the following method:
dissolving vinyl acetate in azodiisobutyronitrile, reacting with acrylic acid, precipitating the obtained product in deionized water, drying, dissolving again, performing alcoholysis reaction with sodium hydroxide solution, dissolving the obtained colloidal product in water, filtering, precipitating in methanol, and drying to obtain carboxylated polyvinyl alcohol.
3. The preparation method according to claim 2, wherein the reaction temperature of the dissolved vinyl acetate and the acrylic acid is 60-70 ℃ and the reaction time is 6-8 hours.
4. An injectable composite antibacterial hydrogel prepared by the preparation method of any one of claims 1 to 3.
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| CN112300420B (en) * | 2020-11-20 | 2021-12-17 | 福州大学 | Injectable antibacterial interpenetrating double-network hydrogel and preparation method and application thereof |
| CN113308137A (en) * | 2021-06-11 | 2021-08-27 | 安徽强邦印刷材料有限公司 | Treatment-free printing plate protective coating and preparation method thereof |
| CN113499472B (en) * | 2021-06-18 | 2022-05-03 | 西北大学 | Method for preparing iron tannate coordination modified molybdenum disulfide hydrogel dressing |
| CN113769157B (en) * | 2021-09-01 | 2022-08-05 | 西北大学 | Injectable hydrogel and preparation method thereof |
| CN115843790A (en) * | 2022-12-04 | 2023-03-28 | 吉林大学 | Preparation and application of perillic acid-loaded antibacterial hydrogel |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109157669A (en) * | 2018-09-18 | 2019-01-08 | 东华大学 | Cellulose enhances glucan base injectable anti-bacterial hydrogel dressing and preparation method thereof |
| CN110124117A (en) * | 2019-06-28 | 2019-08-16 | 北京化工大学 | A kind of injection aquagel and preparation method thereof |
-
2020
- 2020-02-12 CN CN202010088620.0A patent/CN111303450B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109157669A (en) * | 2018-09-18 | 2019-01-08 | 东华大学 | Cellulose enhances glucan base injectable anti-bacterial hydrogel dressing and preparation method thereof |
| CN110124117A (en) * | 2019-06-28 | 2019-08-16 | 北京化工大学 | A kind of injection aquagel and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| (乙酸乙烯酯-co-丙烯酸)共聚物的合成、醇解及产物水溶性研究;杨同禄等;《化学研究与应用》;20090430;第21卷(第4期);第1.2-1.4节 * |
| ε-Poly(L-lysine)-based Hydrogels with Fast-acting and Prolonged Antibacterial Activities;Yi-Jie Zou et al.;《Chinese Journal of POLYMER SCIENCE》;20180611;第36卷(第11期);实验部分，摘要，结论，流程图1，图7 * |
| 基于席夫碱键的可注射糖肽水凝胶的制备及性能;赵麒等;《高等学校化学学报》;20160930;第37卷(第9期);摘要、结果与讨论部分 * |
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