阅读说明：本技术 一种壳聚糖/海藻酸钠复合水凝胶的制备方法 (Preparation method of chitosan/sodium alginate composite hydrogel ) 是由 周睿 周颖 李明 靳国瑞 程嘉辉 憨勇 于 2020-11-02 设计创作，主要内容包括：本发明公开一种壳聚糖/海藻酸钠复合水凝胶的制备方法,将壳聚糖水溶液和海藻酸钠水溶液混合,得到混合溶液,向混合溶液中加入光引发剂,在紫外光下照射,得到壳聚糖/海藻酸钠复合水凝胶。本发明通过加入海藻酸钠,利用具有良好的塑韧性的海藻酸钠能够改善壳聚糖水凝胶的脆性,优化凝胶的力学性能；通过控制壳聚糖水溶液与海藻酸钠水溶液的混合比例可以调控水凝胶的力学性能,最高可以使壳聚糖的断裂强度从2MPa提升至6MPa。同时使制备的壳聚糖/海藻酸钠复合水凝胶兼具壳聚糖的抗菌性和海藻酸钠的生物活性。该水凝胶负载在种植体表面或内部,有望在抗菌敷料和药物控释领域获得广泛的应用。(The invention discloses a preparation method of chitosan/sodium alginate composite hydrogel, which comprises the steps of mixing a chitosan aqueous solution and a sodium alginate aqueous solution to obtain a mixed solution, adding a photoinitiator into the mixed solution, and irradiating under ultraviolet light to obtain the chitosan/sodium alginate composite hydrogel. According to the invention, sodium alginate is added, and the brittleness of the chitosan hydrogel can be improved by using the sodium alginate with good plasticity and toughness, so that the mechanical property of the hydrogel is optimized; the mechanical property of the hydrogel can be regulated and controlled by controlling the mixing ratio of the chitosan aqueous solution and the sodium alginate aqueous solution, and the breaking strength of the chitosan can be improved from 2MPa to 6MPa to the maximum. Meanwhile, the prepared chitosan/sodium alginate composite hydrogel has the antibacterial property of chitosan and the biological activity of sodium alginate. The hydrogel is loaded on the surface or inside the implant, and is expected to be widely applied in the fields of antibacterial dressings and drug controlled release.)

1. A preparation method of chitosan/sodium alginate composite hydrogel is characterized in that a chitosan aqueous solution and a sodium alginate aqueous solution are mixed to obtain a mixed solution, a photoinitiator is added into the mixed solution, and the chitosan/sodium alginate composite hydrogel is obtained by irradiation under ultraviolet light.

2. The preparation method of the chitosan/sodium alginate composite hydrogel as claimed in claim 1, wherein the mass ratio of chitosan to sodium alginate is 1: 10-10: 1.

3. The method for preparing chitosan/sodium alginate composite hydrogel as claimed in claim 1, wherein the addition amount of the photoinitiator is 0.05-0.2% of the volume of the mixed solution.

4. The preparation method of the chitosan/sodium alginate composite hydrogel as claimed in claim 1, wherein the type of the photoinitiator is I2959.

5. The method for preparing chitosan/sodium alginate composite hydrogel as claimed in claim 1, wherein the irradiation time is 1-10 min.

6. The preparation method of the chitosan/sodium alginate composite hydrogel as claimed in claim 1, wherein the chitosan aqueous solution is prepared by the following processes: dissolving chitosan in water, dropwise adding methacrylic anhydride, adjusting the pH to 8-10 with sodium bicarbonate solution, and uniformly stirring to obtain a chitosan aqueous solution.

7. The preparation method of the chitosan/sodium alginate composite hydrogel as claimed in claim 6, wherein the chitosan concentration in the chitosan aqueous solution is 10-20 g/L, and the addition amount of the methacrylic anhydride is 2-20 times of the amount of the chitosan substance.

8. The preparation method of the chitosan/sodium alginate composite hydrogel as claimed in claim 1, wherein the sodium alginate aqueous solution is prepared by the following processes: dissolving sodium alginate in water, dropwise adding methacrylic anhydride, adjusting pH to 8-10 with sodium hydroxide solution, and stirring to obtain sodium alginate water solution.

9. The preparation method of the chitosan/sodium alginate composite hydrogel as claimed in claim 8, wherein the concentration of sodium alginate in the sodium alginate aqueous solution is 10-20 g/L, and the addition amount of methacrylic anhydride is 2-20 times of the amount of alginic acid substance.

10. The method for preparing chitosan/sodium alginate composite hydrogel as claimed in claim 1, wherein the power of ultraviolet light is 100W, and the ultraviolet intensity is 4800 μ W/cm²。

Technical Field

The invention relates to the technical field of high polymer materials, in particular to a preparation method of chitosan/sodium alginate composite hydrogel.

Background

The chitosan has good biocompatibility, biodegradability and antibacterial property, is often used as medical dressing and drug sustained-release carrier, but has poor mechanical property. Sodium alginate is a good bioactive material, and the hydrogel has certain strength and good toughness. The composite hydrogel prepared by mixing sodium alginate and chitosan solution can improve the mechanical property of chitosan and endow the gel with more biological functions. The prior art can not prepare the chitosan hydrogel with controllable mechanical property.

Disclosure of Invention

The invention aims to solve the problems in the prior art and provides a preparation method of chitosan/sodium alginate composite hydrogel.

In order to achieve the purpose, the invention adopts the following technical scheme:

a preparation method of chitosan/sodium alginate composite hydrogel comprises the steps of mixing a chitosan aqueous solution and a sodium alginate aqueous solution to obtain a mixed solution, adding a photoinitiator into the mixed solution, and irradiating under ultraviolet light to obtain the chitosan/sodium alginate composite hydrogel.

The invention has the further improvement that the mass ratio of the chitosan to the sodium alginate is 1: 10-10: 1.

In a further development of the invention, the photoinitiator is added in an amount of 0.05 to 0.2% by volume of the mixed solution.

A further development of the invention is that the photoinitiator is of type I2959.

The invention is further improved in that the irradiation time is 1-10 min.

In a further improvement of the invention, the aqueous chitosan solution is prepared by the following process: dissolving chitosan in water, dropwise adding methacrylic anhydride, adjusting the pH to 8-10 with sodium bicarbonate solution, and uniformly stirring to obtain a chitosan aqueous solution.

The invention is further improved in that the concentration of chitosan in the chitosan aqueous solution is 10-20 g/L, and the addition amount of methacrylic anhydride is 2-20 times of the amount of the chitosan substance.

The further improvement of the invention is that the sodium alginate aqueous solution is prepared by the following processes: dissolving sodium alginate in water, dropwise adding methacrylic anhydride, adjusting pH to 8-10 with sodium hydroxide solution, and stirring to obtain sodium alginate water solution.

The invention is further improved in that the concentration of the sodium alginate in the sodium alginate aqueous solution is 10-20 g/L, and the addition amount of the methacrylic anhydride is 2-20 times of the amount of the alginic acid substance.

The invention is further improved in that the power of the ultraviolet light is 100W, and the ultraviolet intensity is 4800 mu W/cm²。

Compared with the prior art, the invention has the beneficial effects that: according to the invention, sodium alginate is added, and the brittleness of the chitosan hydrogel can be improved by using the sodium alginate with good plasticity and toughness, so that the mechanical property of the hydrogel is optimized; the mechanical property of the hydrogel can be regulated and controlled by controlling the mixing ratio of the chitosan aqueous solution and the sodium alginate aqueous solution, and the breaking strength of the chitosan can be improved from 2MPa to 6MPa to the maximum. Meanwhile, the prepared chitosan/sodium alginate composite hydrogel has the antibacterial property of chitosan and the biological activity of sodium alginate. The hydrogel is loaded on the surface or inside the implant, and is expected to be widely applied in the fields of antibacterial dressings and drug controlled release.

Drawings

FIG. 1 is a schematic view of a chitosan/sodium alginate mixed solution prepared in the present invention.

FIG. 2 is a schematic diagram of chitosan/sodium alginate composite hydrogel prepared by the present invention.

Detailed Description

The present invention will be described in detail with reference to the accompanying drawings.

The invention comprises the following steps:

1) preparation of aqueous chitosan solution: dissolving chitosan in water, dropwise adding methacrylic anhydride, adjusting the pH to 8-10 with sodium bicarbonate solution, and uniformly stirring to obtain a chitosan aqueous solution. Then, the chitosan water solution is dialyzed for 1 to 3 days by using a dialysis bag with 5 to 8KD, and is frozen and dried for later use.

2) Preparation of sodium alginate aqueous solution: dissolving sodium alginate in water, dropwise adding methacrylic anhydride, adjusting pH to 8-10 with sodium hydroxide solution, and stirring to obtain sodium alginate water solution. And dialyzing the sodium alginate aqueous solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use after dialysis.

3) Preparation of composite hydrogel: mixing chitosan water solution and sodium alginate water solution to obtain mixed solution, adding photoinitiator into the mixed solution, and placing in 100W ultraviolet lamp (ultraviolet intensity 4800 μ W/cm)²) Irradiating for 1-10min to obtain chitosan/sodium alginate composite hydrogel.

The concentration of chitosan in the chitosan aqueous solution in the step 1) is 10-20 g/L, and the addition amount of methacrylic anhydride is 2-20 times of the amount of a chitosan substance.

The concentration of the sodium alginate in the sodium alginate aqueous solution in the step 2) is 10-20 g/L, and the addition amount of the methacrylic anhydride is 2-20 times of that of the alginic acid substance.

The mass ratio of the chitosan to the sodium alginate in the step 3) is 1: 10-10: 1.

The modified chitosan and the sodium alginate solution are not crosslinked when being mixed, and are crosslinked and cured under an ultraviolet lamp.

The addition amount of the photoinitiator is 0.05-0.2% of the volume of the mixed solution.

The photoinitiator was type I2959.

The following are specific examples.

Example 1

1) Preparation of aqueous chitosan solution: chitosan was dissolved in water to prepare a solution having a chitosan concentration of 10 g/L. Methacrylic anhydride in an amount 20 times that of the chitosan material was added dropwise, and the pH was adjusted to 8 with a sodium bicarbonate solution, followed by sufficient stirring to obtain a uniform chitosan aqueous solution. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use.

2) Preparation of sodium alginate aqueous solution: dissolving sodium alginate in water to prepare a solution with the concentration of the sodium alginate being 10 g/L. Methacrylic anhydride with the amount 2 times of that of the alginic acid substance is added dropwise, the pH is adjusted to 8 by using sodium hydroxide solution, and the uniform sodium alginate aqueous solution is obtained by fully stirring. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use after dialysis.

3) Preparation of composite hydrogel: mixing the freeze-dried chitosan solution and the sodium alginate solution according to the mass ratio of the chitosan to the sodium alginate of 1:1 to obtain a mixed solution, and adding a photoinitiator I2959. Irradiating the mixed solution under an ultraviolet lamp for 5min to obtain the photo-crosslinking composite hydrogel. Wherein the addition amount of the photoinitiator is 0.1 percent of the volume of the mixed solution.

The gel state was observed, and the solution remained liquid after mixing without curing and crosslinking, as shown in fig. 1. Under a 100W ultraviolet lamp (ultraviolet intensity 4800 mu W/cm)²) The solution was photocured under uv light, as shown in figure 2.

A mechanical testing machine is used for carrying out a compression test on the chitosan hydrogel and the composite hydrogel, and the fracture strength of the chitosan hydrogel is 2MPa, while the fracture strength of the composite hydrogel is 4 MPa.

Example 2

1) Preparation of aqueous chitosan solution: chitosan was dissolved in water to prepare a solution having a chitosan concentration of 15 g/L. Methacrylic anhydride in an amount 20 times that of the chitosan material was added dropwise, and the pH was adjusted to 8 with a sodium bicarbonate solution, followed by sufficient stirring to obtain a uniform chitosan aqueous solution. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use.

2) Preparation of sodium alginate aqueous solution: dissolving sodium alginate in water to prepare a solution with the concentration of the sodium alginate being 10 g/L. Methacrylic anhydride with the amount of 2 times of that of the alginic acid substance is added dropwise, the pH is adjusted to 8 by using sodium hydroxide solution, and the uniform sodium alginate aqueous solution is obtained by fully stirring. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use after dialysis.

3) Preparation of composite hydrogel: mixing the freeze-dried chitosan solution and the sodium alginate solution according to the mass ratio of the chitosan to the sodium alginate of 1:1 to obtain a mixed solution, and adding a photoinitiator I2959. The mixed solution is placed in a 100W ultraviolet lamp (ultraviolet intensity 4800 mu W/cm)²) Irradiating for 6min to obtain the photo-crosslinking composite hydrogel. Wherein the addition amount of the photoinitiator is 0.1 percent of the volume of the mixed solution.

The chitosan hydrogel and the composite hydrogel are subjected to a compression experiment by using a mechanical testing machine, and the fracture strength of the chitosan is 2MPa, while the fracture strength of the composite hydrogel is 3 MPa.

Example 3

1) Preparation of aqueous chitosan solution: chitosan was dissolved in water to prepare a solution having a chitosan concentration of 15 g/L. Methacrylic anhydride in an amount 20 times that of the chitosan material was added dropwise, and the pH was adjusted to 8 with a sodium bicarbonate solution, followed by sufficient stirring to obtain a uniform chitosan aqueous solution. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use.

2) Preparation of sodium alginate aqueous solution: dissolving sodium alginate in water to prepare a solution with the concentration of the sodium alginate being 10 g/L. Methacrylic anhydride with 5 times of the amount of the alginic acid substance is added dropwise, the pH is adjusted to 8 by sodium hydroxide solution, and the uniform sodium alginate aqueous solution is obtained by fully stirring. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use after dialysis.

3) Preparation of composite hydrogel: mixing the freeze-dried chitosan solution and the sodium alginate solution according to the mass ratio of the chitosan to the sodium alginate of 1:1 to obtain a mixed solution, and adding a photoinitiator I2959. The mixed solution is placed in a 100W ultraviolet lamp (ultraviolet intensity 4800 mu W/cm)²) Irradiating for 7min under an ultraviolet lamp to obtain the photo-crosslinking composite hydrogel. Wherein the addition amount of the photoinitiator is 0.1 percent of the volume of the mixed solution.

Example 4

1) Preparation of aqueous chitosan solution: chitosan was dissolved in water to prepare a solution having a chitosan concentration of 15 g/L. Methacrylic anhydride in an amount 20 times that of the chitosan material was added dropwise, and the pH was adjusted to 8 with a sodium bicarbonate solution, followed by sufficient stirring to obtain a uniform chitosan aqueous solution. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use.

2) Preparation of sodium alginate aqueous solution: dissolving sodium alginate in water to prepare a solution with the concentration of the sodium alginate being 10 g/L. Methacrylic anhydride with 5 times of the amount of the alginic acid substance is added dropwise, the pH is adjusted to 8 by sodium hydroxide solution, and the uniform sodium alginate aqueous solution is obtained by fully stirring. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use after dialysis.

3) Preparation of composite hydrogel: mixing the freeze-dried chitosan solution and the sodium alginate solution according to the mass ratio of the chitosan to the sodium alginate of 1:2 to obtain a mixed solution, and adding a photoinitiator I2959. The mixed solution is placed in a 100W ultraviolet lamp (ultraviolet intensity 4800 mu W/cm)²) Irradiating under an ultraviolet lamp for 5min to obtain the photo-crosslinking composite hydrogel. Wherein the addition amount of the photoinitiator is 0.1 percent of the volume of the mixed solution.

Example 5

1) Preparation of aqueous chitosan solution: chitosan was dissolved in water to prepare a solution having a chitosan concentration of 15 g/L. Methacrylic anhydride in an amount 20 times that of the chitosan material was added dropwise, and the pH was adjusted to 8 with a sodium bicarbonate solution, followed by sufficient stirring to obtain a uniform chitosan aqueous solution. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use.

2) Preparation of sodium alginate aqueous solution: dissolving sodium alginate in water to prepare a solution with the concentration of sodium alginate being 20 g/L. Methacrylic anhydride with 5 times of the amount of the alginic acid substance is added dropwise, the pH is adjusted to 8 by sodium hydroxide solution, and the uniform sodium alginate aqueous solution is obtained by fully stirring. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use after dialysis.

3) Preparation of composite hydrogel: mixing the freeze-dried chitosan solution and the sodium alginate solution according to the mass ratio of the chitosan to the sodium alginate of 1:2 to obtain a mixed solution, and adding a photoinitiator I2959. The mixed solution is placed in a 100W ultraviolet lamp (ultraviolet intensity 4800 mu W/cm)²) Irradiating for 8min under an ultraviolet lamp to obtain the photo-crosslinking composite hydrogel. Wherein the addition amount of the photoinitiator is 0.1 percent of the volume of the mixed solution.

The chitosan hydrogel and the composite hydrogel are subjected to a compression experiment by using a mechanical testing machine, and the fracture strength of the chitosan is 2MPa, while the fracture strength of the composite hydrogel is 6 MPa.

Example 6

1) Preparation of aqueous chitosan solution: the chitosan is dissolved in water to prepare a solution with the chitosan concentration of 20 g/L. Methacrylic anhydride in an amount 2 times that of the chitosan material was added dropwise, and the pH was adjusted to 9 with a sodium bicarbonate solution, followed by sufficient stirring to obtain a uniform chitosan aqueous solution. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use.

2) Preparation of sodium alginate aqueous solution: dissolving sodium alginate in water to prepare a solution with the concentration of the sodium alginate being 12 g/L. Methacrylic anhydride in an amount which is 10 times that of the alginic acid substance is added dropwise, the pH is adjusted to 9 by using sodium hydroxide solution, and the mixture is fully stirred to obtain a uniform sodium alginate aqueous solution. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use after dialysis.

3) Preparation of composite hydrogel: mixing the freeze-dried chitosan solution and the sodium alginate solution according to the mass ratio of the chitosan to the sodium alginate of 1:10 to obtain a mixed solution, and adding a photoinitiator I2959. The mixed solution is placed in a 100W ultraviolet lamp (ultraviolet intensity 4800 mu W/cm)²) Irradiating for 1min under a lamp to obtain the photo-crosslinking composite hydrogel. Wherein the addition amount of the photoinitiator is 0.05 percent of the volume of the mixed solution.

Example 7

1) Preparation of aqueous chitosan solution: chitosan was dissolved in water to prepare a solution having a chitosan concentration of 17 g/L. Methacrylic anhydride in an amount 5 times that of the chitosan material was added dropwise, and the pH was adjusted to 10 with a sodium bicarbonate solution, followed by sufficient stirring to obtain a uniform chitosan aqueous solution. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use.

2) Preparation of sodium alginate aqueous solution: dissolving sodium alginate in water to prepare a solution with the concentration of sodium alginate being 20 g/L. Methacrylic anhydride in an amount which is 20 times that of the alginic acid substance is added dropwise, the pH is adjusted to 10 by using sodium hydroxide solution, and the mixture is fully stirred to obtain a uniform sodium alginate aqueous solution. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use after dialysis.

3) Preparation of composite hydrogel: and (2) mixing the freeze-dried chitosan solution and the sodium alginate solution according to the mass ratio of the chitosan to the sodium alginate of 10:1 to obtain a mixed solution, and adding a photoinitiator I2959. The mixed solution is placed in a 100W ultraviolet lamp (ultraviolet intensity 4800 mu W/cm)²) Irradiating for 3min under a lamp to obtain the photo-crosslinking composite hydrogel. Wherein the addition amount of the photoinitiator is 0.2 percent of the volume of the mixed solution.

The chitosan hydrogel and the composite hydrogel are subjected to a compression experiment by using a mechanical testing machine, and the fracture strength of the chitosan is 2MPa, while the fracture strength of the composite hydrogel is 5 MPa.

Example 8

1) Preparation of aqueous chitosan solution: chitosan was dissolved in water to prepare a solution having a chitosan concentration of 12 g/L. Methacrylic anhydride in an amount 10 times that of the chitosan material was added dropwise, and the pH was adjusted to 8 with a sodium bicarbonate solution, followed by sufficient stirring to obtain a uniform chitosan aqueous solution. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use.

2) Preparation of sodium alginate aqueous solution: dissolving sodium alginate in water to prepare a solution with the concentration of the sodium alginate being 16 g/L. Methacrylic anhydride 15 times of the amount of the alginic acid substance was added dropwise, and the pH was adjusted to 8 with sodium hydroxide solution, followed by sufficient stirring to obtain a uniform sodium alginate aqueous solution. And dialyzing the obtained solution for 1-3 days by using a dialysis bag with 5-8KD, and freeze-drying for later use after dialysis.

3) Preparation of composite hydrogel: mixing the freeze-dried chitosan solution and the sodium alginate solution according to the mass ratio of 5:1 of chitosan to sodium alginate to obtain a mixed solution, and adding a photoinitiator I2959. The mixed solution is placed in a 100W ultraviolet lamp (ultraviolet intensity 4800 mu W/cm)²) Irradiating under lamp for 10min to obtain photo-crosslinking complexAnd (3) hydrating the hydrogel. Wherein the addition amount of the photoinitiator is 0.15 percent of the volume of the mixed solution.

According to the invention, chitosan and sodium alginate solution are modified by methacrylic anhydride and then mixed, and the hydrogel with optimized performance is prepared by an ultraviolet curing method. The composite hydrogel has antibacterial property of chitosan and biological activity of sodium alginate, and the brittleness of the chitosan hydrogel is greatly improved by adding the sodium alginate. The hydrogel is loaded on the surface or inside the implant, and is expected to be widely applied in the fields of antibacterial dressings and drug controlled release.