阅读说明：本技术 一种改性壳聚糖-聚乙烯醇复合抗菌水凝胶制法及改性壳聚糖-聚乙烯醇复合抗菌水凝胶 (Preparation method of modified chitosan-polyvinyl alcohol composite antibacterial hydrogel and modified chitosan-polyvinyl alcohol composite antibacterial hydrogel ) 是由 朱弦 万里 曾中良 杜敏 万军 郭伟 于 2021-10-09 设计创作，主要内容包括：本发明涉及抗菌材料技术领域,且公开了一种改性壳聚糖-聚乙烯醇复合抗菌水凝胶,通过化学键的连接,将壳聚糖和聚乙烯醇有机结合,得到化学水凝胶,以壳聚糖作为交联中心,聚乙烯醇形成复杂的三维化学交联互穿网络,当水凝胶收到较大的外力时,化学交联互穿网络可以缓冲局部应力,并且通过化学键的断裂实现外力能力的耗散,氨基甲酸酯基的键能和稳定性,远大于氢键和静电作用,从而使复合水凝胶具有很强的结构稳定性和机械强度,并且通过在水凝胶分子链中引入抗菌性的季铵盐和胍基基团,显著提高了复合水凝胶的抗菌活性。(The invention relates to the technical field of antibacterial materials, and discloses a modified chitosan-polyvinyl alcohol composite antibacterial hydrogel, wherein chitosan and polyvinyl alcohol are organically combined through the connection of chemical bonds to obtain the chemical hydrogel, the chitosan is used as a crosslinking center, the polyvinyl alcohol forms a complex three-dimensional chemical crosslinking interpenetrating network, when the hydrogel receives a larger external force, the chemical crosslinking interpenetrating network can buffer local stress, the dissipation of the external force capability is realized through the breakage of the chemical bonds, and the bond energy and the stability of carbamate are far greater than those of hydrogen bonds and electrostatic action, so that the composite hydrogel has strong structural stability and mechanical strength, and the antibacterial activity of the composite hydrogel is remarkably improved through introducing quaternary ammonium salt and guanidino groups into the molecular chain of the hydrogel.)

1. A preparation method of modified chitosan-polyvinyl alcohol composite antibacterial hydrogel is characterized by comprising the following steps: the preparation method of the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel is as follows:

(1) adding distilled water and a1, 4-dioxane mixed solvent, quaternary ammonium salt chitosan and epoxy chloropropane into a reaction bottle, heating for reaction, cooling to room temperature, adding potassium hydroxide, and performing cyclization reaction to obtain epoxidized chitosan quaternary ammonium salt;

(2) adding distilled water, epoxidized chitosan quaternary ammonium salt and polyhexamethylene biguanide hydrochloride into a reaction bottle for addition reaction, adding distilled water for centrifugal washing until an upper layer liquid is clear, and washing a lower layer product by using distilled water and acetone to obtain guanidino chitosan quaternary ammonium salt;

(3) adding an N, N-dimethylformamide solvent, a guanidyl chitosan quaternary ammonium salt, polyvinyl alcohol and a cross-linking agent into a reaction bottle, then carrying out a cross-linking reaction, adding distilled water for centrifugal washing until the supernatant is clear, washing a precipitation product by using distilled water and ethanol, placing the precipitation product into a dialysis bag, and carrying out dialysis purification to obtain the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel.

2. The preparation method of the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel as claimed in claim 1, wherein the preparation method comprises the following steps: the mass ratio of the epoxy chitosan quaternary ammonium salt to the polyhexamethylene biguanide hydrochloride in the step (2) is 100: 2-10.

3. The preparation method of the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel as claimed in claim 1, wherein the preparation method comprises the following steps: the temperature of the addition reaction in the step (2) is 80-120 ℃, and the reaction time is 2-6 h.

4. The preparation method of the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel as claimed in claim 1, wherein the preparation method comprises the following steps: and (3) the cross-linking agent is toluene diisocyanate or isophorone diisocyanate.

5. The preparation method of the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel as claimed in claim 1, wherein the preparation method comprises the following steps: in the step (3), the mass ratio of the guanidyl chitosan quaternary ammonium salt to the polyvinyl alcohol to the cross-linking agent is 3-15:100: 0.5-2.

6. The preparation method of the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel as claimed in claim 1, wherein the preparation method comprises the following steps: the temperature of the crosslinking reaction in the step (3) is 40-80 ℃, and the reaction time is 6-12 h.

7. A modified chitosan-polyvinyl alcohol composite antibacterial hydrogel is characterized in that: the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel is obtained according to the preparation method of the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel of any one of claims 1 to 6.

Technical Field

The invention relates to the technical field of antibacterial materials, in particular to a preparation method of modified chitosan-polyvinyl alcohol composite antibacterial hydrogel and the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel.

Background

The hydrogel is a novel functional material, has a three-dimensional network structure and good hydrophilicity and water absorbability, can be formed by physically or chemically crosslinking various hydrophilic natural polymers or synthetic polymers, such as chitosan hydrogel, hyaluronic acid hydrogel, polyacrylic acid hydrogel, polyvinyl alcohol hydrogel, polyethylene glycol hydrogel and the like, is formed by physical acting forces such as electrostatic action, hydrogen bonds and the like, and is formed by chemical bond crosslinking, so that the structural stability and the mechanical property of the chemical hydrogel are far better than those of the physical hydrogel.

The hydrogel is widely applied to analgesic patches, antipyretic patches, artificial cartilages, drug carriers and biomedical engineering, so that development of hydrogel materials with excellent mechanical properties and high antibacterial activity becomes a research hotspot in recent years, polyvinyl alcohol has no toxic or side effect and good biocompatibility and biodegradability, and has wide application in the aspects of wound dressings and medicinal films, but the traditional polyvinyl alcohol hydrogel is physical hydrogel, has poor mechanical properties and poor antibacterial properties, and further development of the polyvinyl alcohol in antibacterial materials and biomedical engineering is hindered.

Technical problem to be solved

Aiming at the defects of the prior art, the invention provides a preparation method and application of a modified chitosan-polyvinyl alcohol composite antibacterial hydrogel, and solves the problem of poor mechanical property and antibacterial property of the traditional polyvinyl alcohol hydrogel.

(II) technical scheme

In order to achieve the purpose, the invention provides the following technical scheme: a preparation method of the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel is as follows:

(1) adding distilled water and a1, 4-dioxane mixed solvent, quaternary ammonium salt chitosan and epoxy chloropropane into a reaction bottle, heating for reaction, cooling to room temperature, adding potassium hydroxide, and performing cyclization reaction to obtain the epoxidized chitosan quaternary ammonium salt.

(2) Adding distilled water, epoxidized chitosan quaternary ammonium salt and polyhexamethylene biguanide hydrochloride into a reaction bottle, carrying out addition reaction, adding distilled water, carrying out centrifugal washing until an upper layer liquid is clear, and washing a lower layer product by using distilled water and acetone to obtain the guanidino chitosan quaternary ammonium salt.

(3) Adding an N, N-dimethylformamide solvent, a guanidyl chitosan quaternary ammonium salt, polyvinyl alcohol and a cross-linking agent into a reaction bottle, then carrying out a cross-linking reaction, adding distilled water for centrifugal washing until the supernatant is clear, washing a precipitation product by using distilled water and ethanol, placing the precipitation product into a dialysis bag, and carrying out dialysis purification to obtain the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel.

Preferably, the mass ratio of the epoxy chitosan quaternary ammonium salt to the polyhexamethylene biguanide hydrochloride in the step (2) is 100: 2-10.

Preferably, the temperature of the addition reaction in the step (2) is 80-120 ℃, and the reaction time is 2-6 h.

Preferably, the crosslinking agent in the step (3) is toluene diisocyanate or isophorone diisocyanate.

Preferably, the mass ratio of the guanidine-based chitosan quaternary ammonium salt, the polyvinyl alcohol and the cross-linking agent in the step (3) is 3-15:100: 0.5-2.

Preferably, the temperature of the crosslinking reaction in the step (3) is 40-80 ℃, and the reaction time is 6-12 h.

Preferably, the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel is obtained according to the preparation method of the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel, and is applied to the field of antibacterial materials.

(III) advantageous technical effects

Compared with the prior art, the invention has the following chemical mechanism and beneficial technical effects:

according to the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel, epoxy chloropropane is used for carrying out epoxidation modification on chitosan quaternary ammonium salt, an epoxy group is introduced, imino in polyhexamethylene biguanide hydrochloride has good chemical activity and can carry out addition ring-opening reaction with the epoxy group to obtain guanidine chitosan quaternary ammonium salt, chitosan has good biocompatibility and contains rich antibacterial quaternary ammonium salt groups and guanidine groups, so that the chitosan has excellent antibacterial activity, and the application of the chitosan in antibacterial materials and biomedical engineering is widened.

The modified chitosan-polyvinyl alcohol composite antibacterial hydrogel is characterized in that under the action of a cross-linking agent diisocyanate, two isocyanate groups react with hydroxyl groups of quaternary ammonium salt of guanidino chitosan and hydroxyl groups of polyvinyl alcohol respectively to generate carbamate groups, so that the chitosan and the polyvinyl alcohol are organically combined through the connection of chemical bonds to obtain the chemical hydrogel, the chitosan is used as a cross-linking center, the polyvinyl alcohol forms a complex three-dimensional chemical cross-linking interpenetrating network, when the hydrogel receives a large external force, the chemical cross-linking interpenetrating network can buffer local stress, the dissipation of external force capacity is realized through the breakage of the chemical bonds, the bond energy and the stability of the carbamate groups are far greater than those of hydrogen bonds and electrostatic interaction, so that the composite hydrogel has strong structural stability and mechanical strength, and the quaternary ammonium salt and the guanidino groups are introduced into the molecular chain of the hydrogel, the antibacterial activity of the composite hydrogel is obviously improved.

Detailed Description

To achieve the above object, the present invention provides the following embodiments and examples: a modified chitosan-polyvinyl alcohol composite antibacterial hydrogel is prepared by the following steps:

(1) adding distilled water and a1, 4-dioxane mixed solvent, quaternary ammonium salt chitosan and epoxy chloropropane into a reaction bottle, heating for reaction, cooling to room temperature, adding potassium hydroxide, and performing cyclization reaction to obtain the epoxidized chitosan quaternary ammonium salt.

(2) Adding distilled water, epoxidized chitosan quaternary ammonium salt and polyhexamethylene biguanide hydrochloride in a mass ratio of 100:2-10 into a reaction bottle, carrying out addition reaction at the reaction temperature of 80-120 ℃ for 2-6h, adding distilled water, carrying out centrifugal washing until an upper layer solution is clear, and washing a lower layer product by using distilled water and acetone to obtain the guanidino chitosan quaternary ammonium salt.

(3) Adding N, N-dimethylformamide solvent, guanidino chitosan quaternary ammonium salt with the mass ratio of 3-15:100:0.5-2, polyvinyl alcohol and cross-linking agent into a reaction bottle, wherein the cross-linking agent is toluene diisocyanate or isophorone diisocyanate, then carrying out cross-linking reaction at the temperature of 40-80 ℃ for 6-12h, adding distilled water, carrying out centrifugal washing until supernatant is clear, washing a precipitation product by using distilled water and ethanol, placing the precipitation product into a dialysis bag, and carrying out dialysis purification to obtain the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel which is applied to the field of antibacterial materials.

Example 1

(1) Adding distilled water and a1, 4-dioxane mixed solvent, quaternary ammonium salt chitosan and epoxy chloropropane into a reaction bottle, heating for reaction, cooling to room temperature, adding potassium hydroxide, and performing cyclization reaction to obtain the epoxidized chitosan quaternary ammonium salt.

(2) Adding distilled water, epoxidized chitosan quaternary ammonium salt and polyhexamethylene biguanide hydrochloride in a mass ratio of 100:2 into a reaction bottle, carrying out addition reaction at the reaction temperature of 80 ℃ for 2h, adding distilled water, carrying out centrifugal washing until an upper layer solution is clear, and washing a lower layer product by using distilled water and acetone to obtain the guanidino chitosan quaternary ammonium salt.

(3) Adding N, N-dimethylformamide solvent, guanidino chitosan quaternary ammonium salt with the mass ratio of 3:100:0.5, polyvinyl alcohol and crosslinking agent toluene diisocyanate into a reaction bottle, then carrying out crosslinking reaction at the temperature of 40 ℃ for 6 hours, adding distilled water for centrifugal washing until supernatant is clear, washing a precipitation product by using distilled water and ethanol, placing the precipitation product into a dialysis bag, and carrying out dialysis purification to obtain the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel.

Example 2

(1) Adding distilled water and a1, 4-dioxane mixed solvent, quaternary ammonium salt chitosan and epoxy chloropropane into a reaction bottle, heating for reaction, cooling to room temperature, adding potassium hydroxide, and performing cyclization reaction to obtain the epoxidized chitosan quaternary ammonium salt.

(2) Adding distilled water, epoxidized chitosan quaternary ammonium salt and polyhexamethylene biguanide hydrochloride in a mass ratio of 100:5 into a reaction bottle, carrying out addition reaction at the reaction temperature of 100 ℃ for 4h, adding distilled water, carrying out centrifugal washing until an upper layer solution is clear, and washing a lower layer product by using distilled water and acetone to obtain the guanidino chitosan quaternary ammonium salt.

(3) Adding N, N-dimethylformamide solvent, guanidino chitosan quaternary ammonium salt with the mass ratio of 8:100:1, polyvinyl alcohol and a crosslinking agent isophorone diisocyanate into a reaction bottle, then carrying out crosslinking reaction at the temperature of 50 ℃ for 10 hours, adding distilled water for centrifugal washing until supernatant is clear, washing a precipitation product with distilled water and ethanol, placing the precipitation product into a dialysis bag, and carrying out dialysis purification to obtain the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel.

Example 3

(1) Adding distilled water and a1, 4-dioxane mixed solvent, quaternary ammonium salt chitosan and epoxy chloropropane into a reaction bottle, heating for reaction, cooling to room temperature, adding potassium hydroxide, and performing cyclization reaction to obtain the epoxidized chitosan quaternary ammonium salt.

(2) Adding distilled water, epoxidized chitosan quaternary ammonium salt and polyhexamethylene biguanide hydrochloride in a mass ratio of 100:7 into a reaction bottle, carrying out addition reaction at the reaction temperature of 120 ℃ for 4h, adding distilled water, carrying out centrifugal washing until an upper layer solution is clear, and washing a lower layer product by using distilled water and acetone to obtain the guanidino chitosan quaternary ammonium salt.

(3) Adding N, N-dimethylformamide solvent, guanidino chitosan quaternary ammonium salt with the mass ratio of 10:100:1.5, polyvinyl alcohol and crosslinking agent toluene diisocyanate into a reaction bottle, then carrying out crosslinking reaction at the temperature of 50 ℃ for 10 hours, adding distilled water for centrifugal washing until supernatant is clear, washing a precipitation product by using distilled water and ethanol, placing the precipitation product into a dialysis bag, and carrying out dialysis purification to obtain the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel.

Example 4

(1) Adding distilled water and a1, 4-dioxane mixed solvent, quaternary ammonium salt chitosan and epoxy chloropropane into a reaction bottle, heating for reaction, cooling to room temperature, adding potassium hydroxide, and performing cyclization reaction to obtain the epoxidized chitosan quaternary ammonium salt.

(2) Adding distilled water, epoxidized chitosan quaternary ammonium salt and polyhexamethylene biguanide hydrochloride in a mass ratio of 100:10 into a reaction bottle, carrying out addition reaction at the reaction temperature of 120 ℃ for 6h, adding distilled water, carrying out centrifugal washing until an upper layer solution is clear, and washing a lower layer product by using distilled water and acetone to obtain the guanidino chitosan quaternary ammonium salt.

(3) Adding N, N-dimethylformamide solvent, guanidino chitosan quaternary ammonium salt with the mass ratio of 15:100:2, polyvinyl alcohol and a crosslinking agent isophorone diisocyanate into a reaction bottle, then carrying out crosslinking reaction at the temperature of 80 ℃ for 12 hours, adding distilled water for centrifugal washing until supernatant is clear, washing a precipitation product with distilled water and ethanol, placing the precipitation product into a dialysis bag, and carrying out dialysis purification to obtain the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel.

Comparative example 1

(1) Adding distilled water and a1, 4-dioxane mixed solvent, quaternary ammonium salt chitosan and epoxy chloropropane into a reaction bottle, heating for reaction, cooling to room temperature, adding potassium hydroxide, and performing cyclization reaction to obtain the epoxidized chitosan quaternary ammonium salt.

(2) Adding distilled water, epoxidized chitosan quaternary ammonium salt and polyhexamethylene biguanide hydrochloride in a mass ratio of 100:0.5 into a reaction bottle, carrying out addition reaction at the reaction temperature of 120 ℃ for 4h, adding distilled water, carrying out centrifugal washing until an upper layer solution is clear, and washing a lower layer product by using distilled water and acetone to obtain the guanidino chitosan quaternary ammonium salt.

(3) Adding N, N-dimethylformamide solvent, guanidino chitosan quaternary ammonium salt with the mass ratio of 1:100:0.2, polyvinyl alcohol and a crosslinking agent isophorone diisocyanate into a reaction bottle, then carrying out crosslinking reaction at the temperature of 40 ℃ for 12 hours, adding distilled water for centrifugal washing until supernatant is clear, washing a precipitation product by using distilled water and ethanol, placing the precipitation product into a dialysis bag, and carrying out dialysis purification to obtain the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel.

Comparative example 2

(1) Adding distilled water and a1, 4-dioxane mixed solvent, quaternary ammonium salt chitosan and epoxy chloropropane into a reaction bottle, heating for reaction, cooling to room temperature, adding potassium hydroxide, and performing cyclization reaction to obtain the epoxidized chitosan quaternary ammonium salt.

(2) Adding distilled water, epoxidized chitosan quaternary ammonium salt and polyhexamethylene biguanide hydrochloride in a mass ratio of 100:15 into a reaction bottle, carrying out addition reaction at the reaction temperature of 120 ℃ for 2h, adding distilled water, carrying out centrifugal washing until an upper layer solution is clear, and washing a lower layer product by using distilled water and acetone to obtain the guanidino chitosan quaternary ammonium salt.

(3) Adding N, N-dimethylformamide solvent, guanidino chitosan quaternary ammonium salt with the mass ratio of 18:100:2.5, polyvinyl alcohol and crosslinking agent toluene diisocyanate into a reaction bottle, then carrying out crosslinking reaction at the temperature of 60 ℃ for 6 hours, adding distilled water for centrifugal washing until supernatant is clear, washing a precipitation product by using distilled water and ethanol, placing the precipitation product into a dialysis bag, and carrying out dialysis purification to obtain the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel.

Adding an agar culture medium and an escherichia coli suspension liquid into an aseptic culture dish, uniformly oscillating, adding a phosphate buffer salt solution, cutting the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel into slices, taking the antibacterial hydrogel slices added in the examples as experimental groups, taking the antibacterial hydrogel slices added in the comparative examples as control groups, taking the antibacterial hydrogel slices not added in the comparative examples as blank groups, placing the culture dishes of all groups into a constant-temperature constant-humidity incubator, culturing for 24 hours at 37 ℃, observing the number of bacterial colonies, and testing the antibacterial performance of the antibacterial hydrogel.

And (3) detecting the tensile strength of the modified chitosan-polyvinyl alcohol composite antibacterial hydrogel by using an SHK-A101 tensile strength tester.