Preparation method of composite hydrogel based on carboxymethyl chitosan

Abstract

The preparation method of the composite hydrogel based on carboxymethyl chitosan comprises the following steps: based on the dosage of carboxymethyl chitosan, adjusting the mass ratio of sericin to carboxymethyl chitosan to obtain a carboxymethyl chitosan and sericin polymer solution; fixing the molar ratio of sodium pyrrolidone carboxylate to carboxymethyl chitosan, adding sodium pyrrolidone carboxylate into the mixed solution, and carrying out amidation reaction to obtain a carboxymethyl chitosan composite solution; then adding acrylamide, a cross-linking agent and an initiator to carry out polymerization reaction, uniformly mixing, pouring into a glass mold, and heating to obtain composite hydrogel based on carboxymethyl chitosan; the composite hydrogel prepared by the invention has excellent adhesion, biocompatibility, self-healing performance, antibacterial property, conductivity, injectability and mechanical property, not only shows huge potential in wound dressing, but also has huge application prospect in the field of flexible wearable sensors.

Description

Technical Field

[0001] The invention belongs to the technical field of biomass hydrogels, and in particular relates to a method for preparing a carboxymethyl chitosan-based composite hydrogel. The composite hydrogel is used for wound dressings to treat wound infections. Background Art

[0002] Hydrogel is a three-dimensional network composed of cross-linked hydrophilic polymers. Hydrogel materials have a wide range of applications in flexible electronics, wearable devices, biomedical technology and soft robots due to their excellent adhesion, conductivity, self-healing and other properties. Hydrogels synthesized based on chitosan derivatives have a wide range of applications. Among them, carboxymethyl chitosan obtained by carboxymethylation of chitosan has antibacterial hemostasis, water-soluble moisture retention, biocompatibility and low toxicity. Hydrogels prepared with carboxymethyl chitosan as raw material have the advantages of good hydrophilicity, good conductivity, good biocompatibility, biodegradability and low cost. Traditional dressings (cotton, bandages and gauze) are widely used, but they mainly play an isolation role and cannot provide an antibacterial environment, which limits the repair of wound infections. Therefore, a composite hydrogel dressing based on carboxymethyl chitosan with self-healing, antibacterial, injectable and biocompatible properties is designed to promote the repair of infected wounds. It has great application potential in the field of wound dressings and biomass medical-based wearable sensors. Summary of the invention

[0003] In order to overcome the deficiencies of the above-mentioned prior art, the purpose of the present invention is to develop a new material based on carboxymethyl chitosan composite hydrogel for wound dressing to treat wound infection. The prepared composite hydrogel has good adhesion, self-healing performance, injectability, antibacterial hemostasis and mechanical properties.

[0004] To achieve the above object, the technical solution adopted by the present invention is: The preparation method of carboxymethyl chitosan composite hydrogel comprises the following steps: Step 1, preparing a carboxymethyl chitosan and sericin polymer solution: adjusting the mass ratio of carboxymethyl chitosan and sericin, dissolving them in distilled water respectively and then mixing them, raising the temperature, and using a genipin solution to perform a cross-linking reaction to obtain a carboxymethyl chitosan and sericin polymer solution; Step 2, preparing a sodium pyrrolidone carboxylate-modified carboxymethyl chitosan composite solution: adjusting the amount of sodium pyrrolidone carboxylate according to the amount of carboxymethyl chitosan used, and adding sodium pyrrolidone carboxylate to the carboxymethyl chitosan and sericin polymer solution for amidation reaction; Step 3, preparing a carboxymethyl chitosan-based composite hydrogel: adding acrylamide, a crosslinking agent and an initiator to the carboxymethyl chitosan composite solution obtained in step 2 to carry out a polymerization reaction, mixing evenly and pouring into a glass mold and heating to obtain a carboxymethyl chitosan-based composite hydrogel.

[0005] The specific steps of step 1 are as follows: Carboxymethyl chitosan and sericin in a mass ratio of 1:0.5-2 were dissolved in distilled water and stirred, and mixed after being uniformly dissolved. The temperature was raised to 70°C, and a cross-linking reaction was carried out using a genipin solution. The mixture was stirred for 30 min to obtain a carboxymethyl chitosan and sericin polymer solution.

[0006] The mass ratio of the carboxymethyl chitosan to distilled water is 1:50-100; The mass ratio of the sericin to distilled water is 1:50-100; The mass ratio of the carboxymethyl chitosan to the sericin is 1:0.5, 1:1 or 0.5:1; The concentration of the genipin solution is 1% (w / v); The volume ratio of the carboxymethyl chitosan and sericin polymer solution to the genipin solution is 1:0.333; The temperature for the cross-linking reaction is 70°C.

[0007] The specific steps of step 2 are as follows: Adding sodium pyrrolidone carboxylate to the carboxymethyl chitosan and sericin polymer solution, the molar ratio of carboxymethyl chitosan to sodium pyrrolidone carboxylate being 1:1.2, stirring for 30 minutes to obtain a carboxymethyl chitosan composite solution; The heating temperature of the amidation reaction is 70°C.

[0008] The specific steps of step 3 are as follows: Add acrylamide, N,N'-methylenebisacrylamide and ammonium persulfate to the carboxymethyl chitosan composite solution obtained in step 2, stir thoroughly, mix evenly and pour into a glass mold, put the mold into an oven to heat, take out and cool to obtain a composite hydrogel based on carboxymethyl chitosan; The cross-linking agent is N,N'-methylenebisacrylamide, and its concentration is 0.02 g / mL; The initiator is ammonium persulfate with a concentration of 0.125 g / mL.

[0009] The heating temperature is 70°C; The heating time is 3h.

[0010] The beneficial effects of the present invention are: The present invention uses environmentally friendly carboxymethyl chitosan, sericin and sodium pyrrolidone carboxylate as main raw materials, adds comonomer acrylamide, and undergoes polymerization reaction under the action of a crosslinking agent and an initiator to obtain a multifunctional carboxymethyl chitosan-based composite hydrogel. The preparation method uses the natural crosslinking agent genipin extracted from plants to crosslink carboxymethyl chitosan and sericin, which is non-toxic, biocompatible and environmentally friendly; sodium pyrrolidone carboxylate is a compound present in the stratum corneum of the skin as a natural moisturizing factor, and its correlation with skin hydration has been determined; the amino groups in carboxymethyl chitosan and sericin and the carboxyl groups in sodium pyrrolidone carboxylate undergo amidation reaction; sodium pyrrolidone carboxylate forms a gel network through the interaction between the carboxyl groups and the amino groups in acrylamide. In short, the preparation method is simple and rapid, the raw materials are easy to obtain, and the prepared composite hydrogel has the following advantages: 1) The carboxymethyl chitosan-based composite hydrogel prepared by the present invention has good adhesion, self-healing properties, antibacterial properties, electrical conductivity and mechanical properties; 2) provide a hydrogel wound dressing that effectively coordinates physical, mechanical, biocompatibility, antimicrobial, and motion-related properties to promote healing of infected wounds; 3) The carboxymethyl chitosan-based hydrogel prepared by the present invention has multiple properties and is widely used; The present invention uses environmentally friendly carboxymethyl chitosan, sericin and sodium pyrrolidone carboxylate as main raw materials, adds comonomer acrylamide, and undergoes polymerization reaction under the action of a crosslinking agent and an initiator to obtain a multifunctional carboxymethyl chitosan-based composite hydrogel. The composite hydrogel has excellent conductivity and biocompatibility, and also has good adhesion, self-healing properties, antibacterial hemostasis, injectability and mechanical properties. DETAILED DESCRIPTION

[0011] The present invention is further described in detail below with reference to specific embodiments. Example 1

[0012] The preparation method based on the preparation method of carboxymethyl chitosan composite hydrogel comprises the following steps: Step 1, preparing a carboxymethyl chitosan and sericin polymer solution, the specific method comprises the following steps: Weigh 0.2 g of carboxymethyl chitosan and dissolve it in 10 g of distilled water, stir and dissolve it. Weigh 0.2 g of sericin and dissolve it in 10 g of distilled water, stir and dissolve it. Raise the temperature to 70°C, mix the two solutions, drop 6.66 mL of genipin solution (1% w / v) and stir for 30 min. As the solution polymerizes, the color changes from colorless to light blue and finally to gray-blue over time. Step 2, preparing a sodium pyrrolidonecarboxylate-modified carboxymethyl chitosan composite solution, the specific method of which comprises the following steps: Weigh 0.1335 g of sodium pyrrolidone carboxylate solution into the mixed solution of step 1, and stir at 70° C. for 30 min to obtain a sodium pyrrolidone carboxylate-modified carboxymethyl chitosan composite solution; Step 3, preparing a carboxymethyl chitosan composite hydrogel, the specific method of which comprises the following steps: To the sodium pyrrolidonecarboxylate-modified carboxymethyl chitosan composite solution obtained in step 2, add 5.6 g acrylamide, 0.2 mL (0.02 g / mL) N,N'-methylenebisacrylamide and 0.2 mL (0.125 g / mL) ammonium persulfate and stir thoroughly. After mixing evenly, pour the mixture into a glass mold, place the mold in a 70 °C oven and heat for 3 h, take it out and cool it to obtain a composite hydrogel based on carboxymethyl chitosan. Example 2

[0013] The preparation method based on the preparation method of carboxymethyl chitosan composite hydrogel is characterized in that it comprises the following steps: Step 1, preparing a carboxymethyl chitosan and sericin polymer solution, the specific method comprises the following steps: Weigh 0.2 g of carboxymethyl chitosan and dissolve it in 10 g of distilled water, and stir to dissolve. Weigh 0.1 g of sericin and dissolve it in 10 mg of distilled water, and stir to dissolve. Raise the temperature to 70°C, mix the two solutions, add 6.66 mL of genipin solution (1% w / v) and stir for 30 min. As the solution polymerizes, the color changes from colorless to light blue and finally to gray-blue over time.

[0014] Step 2, preparing a sodium pyrrolidonecarboxylate-modified carboxymethyl chitosan composite solution, the specific method of which comprises the following steps: Weigh 0.1335 g of sodium pyrrolidonecarboxylate solution into the mixed solution of step 1, and stir at 70° C. for 30 min to obtain a sodium pyrrolidonecarboxylate-modified carboxymethyl chitosan composite solution.

[0015] Step 3, preparing a carboxymethyl chitosan composite hydrogel, the specific method of which comprises the following steps: To the sodium pyrrolidonecarboxylate-modified carboxymethyl chitosan composite solution obtained in step 2, add 5.6 g acrylamide, 0.2 mL (0.02 g / mL) N,N'-methylenebisacrylamide and 0.2 mL (0.125 g / mL) ammonium persulfate and stir thoroughly. After mixing evenly, pour the mixture into a glass mold, place the mold in a 70 °C oven and heat for 3 h, take it out and cool it to obtain a composite hydrogel based on carboxymethyl chitosan. Example 3

[0016] The method for preparing a carboxymethyl chitosan and sericin polymer solution comprises the following steps: Step 1, preparing a mixed solution of carboxymethyl chitosan and sericin, the specific method comprises the following steps: Weigh 0.1 g of carboxymethyl chitosan and dissolve it in 10 g of distilled water, and stir to dissolve. Weigh 0.2 g of sericin and dissolve it in 10 g of distilled water, and stir to dissolve. Raise the temperature to 70°C, mix the two solutions, add 6.66 mL of genipin solution (1% w / v) and stir for 30 minutes. As the solution polymerizes, the color changes from colorless to light blue over time, and finally to gray-blue.

[0017] Step 2, preparing a sodium pyrrolidonecarboxylate-modified carboxymethyl chitosan composite solution, the specific method of which comprises the following steps: Weigh 0.0337 g of sodium pyrrolidone carboxylate solution into the mixed solution of step 1, and stir at 70° C. for 30 min to obtain a sodium pyrrolidone carboxylate-modified carboxymethyl chitosan composite solution.

[0018] Step 3, preparing a carboxymethyl chitosan composite hydrogel, the specific method of which comprises the following steps: To the sodium pyrrolidonecarboxylate-modified carboxymethyl chitosan composite solution obtained in step 2, add 5.6 g acrylamide, 0.2 mL (0.02 g / mL) N,N'-methylenebisacrylamide and 0.2 mL (0.125 g / mL) ammonium persulfate and stir thoroughly. After mixing evenly, pour the mixture into a glass mold, place the mold in a 70 °C oven and heat for 3 h, take it out and cool it to obtain a composite hydrogel based on carboxymethyl chitosan.

Claims

1. A method for preparing a carboxymethyl chitosan composite hydrogel, characterized in that: The following steps are involved: Step 1, preparing a carboxymethyl chitosan and sericin polymer solution: adjusting the mass ratio of carboxymethyl chitosan and sericin, dissolving them in distilled water respectively and then mixing them, raising the temperature, and using a genipin solution to perform a cross-linking reaction to obtain a carboxymethyl chitosan and sericin polymer solution; Step 2, preparing a sodium pyrrolidone carboxylate-modified carboxymethyl chitosan composite solution: adjusting the amount of sodium pyrrolidone carboxylate according to the amount of carboxymethyl chitosan used, and adding sodium pyrrolidone carboxylate to the carboxymethyl chitosan and sericin polymer solution for amidation reaction; Step 3, preparing a carboxymethyl chitosan-based composite hydrogel: adding acrylamide, a crosslinking agent and an initiator to the carboxymethyl chitosan composite solution obtained in step 2 to carry out a polymerization reaction, mixing evenly and pouring into a glass mold and heating to obtain a carboxymethyl chitosan-based composite hydrogel.

2. The method for preparing a carboxymethyl chitosan composite hydrogel according to claim 1, characterized in that: The specific steps of step 1 are as follows: Carboxymethyl chitosan and sericin in a mass ratio of 1:0.5-2 were dissolved in distilled water and stirred, and mixed after being uniformly dissolved. The temperature was raised to 70°C, and a cross-linking reaction was carried out using a genipin solution. The mixture was stirred for 30 min to obtain a carboxymethyl chitosan and sericin polymer solution.

3. The method for preparing the carboxymethyl chitosan composite hydrogel according to claim 2, characterized in that: The mass ratio of the carboxymethyl chitosan to distilled water is 1:50-100; The mass ratio of the sericin to distilled water is 1:50-100; The mass ratio of the carboxymethyl chitosan to the sericin is 1:0.5, 1:1 or 0.5:1; The concentration of the genipin solution is 1% (w / v); The volume ratio of the carboxymethyl chitosan and sericin polymer solution to the genipin solution is 1:0.333; The temperature for the cross-linking reaction is 70°C.

4. The method for preparing the carboxymethyl chitosan composite hydrogel according to claim 1, characterized in that: The specific steps of step 2 are as follows: Adding sodium pyrrolidone carboxylate to the carboxymethyl chitosan and sericin polymer solution, the molar ratio of carboxymethyl chitosan to sodium pyrrolidone carboxylate being 1:1.2, stirring for 30 minutes to obtain a carboxymethyl chitosan composite solution; The heating temperature of the amidation reaction is 70°C.

5. The method for preparing the carboxymethyl chitosan composite hydrogel according to claim 1, characterized in that: The specific steps of step 3 are as follows: Add acrylamide, N,N'-methylenebisacrylamide and ammonium persulfate to the carboxymethyl chitosan composite solution obtained in step 2, stir thoroughly, mix evenly and pour into a glass mold, put the mold into an oven to heat, take out and cool to obtain a composite hydrogel based on carboxymethyl chitosan; The cross-linking agent is N,N'-methylenebisacrylamide, and its concentration is 0.02 g / mL; The initiator is ammonium persulfate with a concentration of 0.125 g / mL; The heating temperature is 70°C; The heating time is 3h.