Antibacterial hyaluronic acid wound dressing with core-shell structure and preparation method thereof

Abstract

The invention discloses an antibacterial hyaluronic acid wound dressing with a core-shell structure and a preparation method of the antibacterial hyaluronic acid wound dressing, and belongs to the field of biomedical materials. The core-shell structure nanofiber is prepared by adopting a coaxial electrospinning technology, and the preparation mode is superior to the solid structure nanofiber prepared by common electrospinning. According to the invention, polyvinyl butyral, a polyethylene oxide solution, zein and a modified hyaluronic acid solution are simultaneously sprayed out by using concentrically arranged nozzles, and are drawn into fibers by using electrostatic force, so that drugs wrapped in the fiber structure can realize controlled release and lasting effects; and a new scheme is provided for preparation of wound dressing.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical dressings, and in particular relates to an antibacterial hyaluronic acid wound dressing with a core-shell structure and a preparation method thereof. Background Art

[0002] Electrospinning is a method of producing fibers by placing a polymer solution or molten polymer under a high electric field so that it is subjected to electric charge. In this process, the polymer solution or melt is injected into a nozzle with a high voltage. When the solution is ejected, the charge is distributed on the surface of the droplet, resulting in surface tension and electrostatic interaction, and finally forming fibers. This technology is often used to prepare nanofibers or micro-nanofibers, and has a wide range of applications, including textiles, medical dressings, filter materials, etc. Natural polymer materials such as hyaluronic acid, gelatin, chitosan, protein, etc. have been used to prepare nanofiber membranes for different purposes.

[0003] Three Chinese patents (CN112546295A, CN104013989A, CN103611182A) all focus on using core-shell electrospinning technology to prepare wound dressings with spectral antibacterial capabilities. A common feature of these preparation methods is that they use external antibacterial agents (such as chitosan, silver nitrate, etc.) to achieve antibacterial effects, and these antibacterial agents need to have good compatibility with the original solution system, which to a certain extent limits the configuration of the solution and may increase the complexity of the preparation steps. Summary of the invention

[0004] In order to solve the above-mentioned invention problems, the purpose of the present invention is to provide an antibacterial hyaluronic acid wound dressing with a core-shell structure and a preparation method thereof. The method modifies the hyaluronic acid and adds antibacterial activity without significantly affecting the original solubility, thereby avoiding further restrictions on the properties of the spinning solution by adding chitosan (dissolved in an acidic environment) and coagulation factors (blended and mixed), and avoiding the problem of insufficient mixing in the spinning solution.

[0005] The invention of the present invention is to modify hyaluronic acid to reduce the restrictions of the added substances on the properties of the solvent in the step of preparing the spinning solution, introduce a core-shell structure design, and combine electrospinning technology and coaxial spinning technology to achieve drug sustained release and continuous release. Due to its strong antibacterial properties, it effectively reduces the risk of wound infection and exhibits excellent biocompatibility to promote rapid wound healing. Through the combination of electrospinning and coaxial spinning technology, customized design and production of wound dressings can be achieved to meet personalized treatments for different wound types and treatment needs.

[0006] The invention provides an antibacterial hyaluronic acid wound dressing with a core-shell structure, wherein the core layer of the core-shell structure comprises zein and modified hyaluronic acid, and the shell layer comprises polyvinyl butyral and polyethylene oxide.

[0007] Preferred modified hyaluronic acid includes hemiacetalized hyaluronic acid.

[0008] The present invention also includes the above-mentioned antibacterial hyaluronic acid wound dressing with a core-shell structure, comprising the following steps: (1) Preparation of modified hyaluronic acid Dissolve 10% hyaluronic acid and sodium periodate in an aqueous medium and react fully to obtain a reaction solution. Add an acid solution to the reaction solution to adjust the pH, and add the pH-adjusted reaction solution to a container containing hydroxytyrosol. Fully mix, separate and purify to obtain modified hyaluronic acid.

[0009] (2) Preparation of shell spinning solution Dissolving polyvinyl butyral with a mass concentration of 4-10% and polyethylene oxide with a mass concentration of 1-3% in an ethanol aqueous solution, stirring evenly, to obtain a shell spinning solution; (3) Preparation of core layer spinning solution Dissolve zein with a mass concentration of 6-20% in an ethanol aqueous solution, add the modified hyaluronic acid prepared in the above step with a mass concentration of 0.05-0.1% to the above solution, stir evenly, and obtain a nuclear layer spinning solution; (4) Preparation of antibacterial hyaluronic acid wound dressing with core-shell structure Use a syringe to extract the shell layer spinning solution and the core layer spinning solution respectively, and connect them to the coaxial needle. Apply a voltage of 10-25 kV, set the collection distance to 8-20 cm, and push the syringe to spin at a rate of 0.2-1.0 mL / h of the shell layer spinning solution and 0.1-0.3 mL / h of the core layer spinning solution. The collector is the antibacterial hyaluronic acid wound dressing with a core-shell structure.

[0010] Preferably, the acidic solution in step 1 is one of hydrochloric acid, oxalic acid or citric acid.

[0011] Preferably, the molecular weight M of the hyaluronic acid in step 1 is w =10000-1000000 g·mol -1 .

[0012] Preferably, the mass ratio of water to ethanol in the ethanol aqueous solution in step 2 is 1:9-4:6.

[0013] Preferably, the molecular weight M of the polyethylene oxide in step 2 is w=300000-1000000 g·mol -1 .

[0014] Preferably, the mass ratio of water to ethanol in the ethanol aqueous solution in step 3 is 1:9-5:5.

[0015] Preferably, the coaxial needle used in step 4 is of model 25 / 18-19 / 15G.

[0016] The present invention has the following beneficial effects: 1. Modified hyaluronic acid, the solubility is almost unaffected and has bactericidal properties; 2. The above preparation method can obtain a loose and porous structure; 3. Using modified hyaluronic acid to prepare wound dressings through electrospinning technology can help maintain a moist environment for the wound, promote cell migration, accelerate wound healing, and shorten the wound healing cycle; 4. Modified hyaluronic acid has certain antibacterial properties and can replace traditional antibacterial agents, making the preparation process more green; 5. Zein is coated with modified hyaluronic acid and pores are created through polyethylene oxide, so that the fiber membrane has antibacterial sustained-release function and acts on the wound for a long time. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is a physical display picture of wound dressing.

[0018] Figure 2 This is a scanning electron micrograph of a wound dressing. DETAILED DESCRIPTION

[0019] The present invention is further described in detail below in conjunction with the examples, but the implementation method of the present invention is not limited thereto.

[0020] Example 1 (1) Preparation of modified hyaluronic acid Dissolve 10% hyaluronic acid and sodium periodate in an aqueous medium and react fully to obtain a reaction solution. Add an acid solution to the reaction solution to adjust the pH, and add the pH-adjusted reaction solution to a container containing hydroxytyrosol. Fully mix, separate and purify to obtain modified hyaluronic acid. (2) Preparation of shell spinning solution Dissolve polyvinyl butyral with a mass concentration of 4% and polyethylene oxide with a mass concentration of 1% in an ethanol aqueous solution, stir evenly, and obtain a shell spinning solution; (3) Preparation of core layer spinning solution Dissolve zein with a mass concentration of 6% in an ethanol aqueous solution, add the modified hyaluronic acid prepared in the above step with a mass concentration of 0.05% to the above solution, stir evenly, and obtain a nuclear layer spinning solution; (4) Preparation of core-shell structured hyaluronic acid nanofiber materials The shell layer spinning solution and the core layer spinning solution were extracted by syringes respectively, and they were connected to the coaxial needle. A voltage of 10 kV was applied, and the collection distance was 8 cm. The syringe was pushed forward at a rate of 0.2 mL / h of the shell layer spinning solution and 0.1 mL / h of the core layer spinning solution for spinning. The collector obtained was the antibacterial hyaluronic acid wound dressing with a core-shell structure.

[0021] Example 2 (1) Preparation of modified hyaluronic acid Dissolve 10% hyaluronic acid and sodium periodate in an aqueous medium and react fully to obtain a reaction solution. Add an acid solution to the reaction solution to adjust the pH, and add the pH-adjusted reaction solution to a container containing hydroxytyrosol. Fully mix, separate and purify to obtain modified hyaluronic acid. (2) Preparation of shell spinning solution Dissolve 8% polyvinyl butyral and 2% polyethylene oxide in an ethanol aqueous solution, stir evenly, and obtain a shell spinning solution; (3) Preparation of core layer spinning solution Dissolve zein with a mass concentration of 14% in an ethanol aqueous solution, add the modified hyaluronic acid prepared in the above step with a mass concentration of 0.05% to the above solution, stir evenly, and obtain a nuclear layer spinning solution; (4) Preparation of antibacterial hyaluronic acid wound dressing with core-shell structure The shell layer spinning solution and the core layer spinning solution were extracted by syringes respectively, and they were connected to the coaxial needle. A voltage of 15 kV was applied, and the collection distance was 10 cm. The syringe was pushed forward at a rate of 0.5 mL / h of the shell layer spinning solution and 0.2 mL / h of the core layer spinning solution for spinning. The collector obtained was the antibacterial hyaluronic acid wound dressing with a core-shell structure.

[0022] Example 3 (1) Preparation of modified hyaluronic acid Dissolve 10% hyaluronic acid and sodium periodate in an aqueous medium and react fully to obtain a reaction solution. Add an acid solution to the reaction solution to adjust the pH, and add the pH-adjusted reaction solution to a container containing hydroxytyrosol. Fully mix, separate and purify to obtain modified hyaluronic acid. (2) Preparation of shell spinning solution Dissolve 8% polyvinyl butyral and 3% polyethylene oxide in an ethanol aqueous solution, stir evenly, and obtain a shell spinning solution; (3) Preparation of core layer spinning solution Dissolve zein with a mass concentration of 20% in an ethanol aqueous solution, add the modified hyaluronic acid prepared in the above step with a mass concentration of 0.05% to the above solution, stir evenly, and obtain a nuclear layer spinning solution; (4) Preparation of antibacterial hyaluronic acid wound dressing with core-shell structure The shell layer spinning solution and the core layer spinning solution were extracted by a syringe and connected to a coaxial needle. A voltage of 25 kV was applied, and the collection distance was 15 cm. The syringe was pushed forward at a rate of 0.8 mL / h of the shell layer spinning solution and 0.2 mL / h of the core layer spinning solution for spinning. The collector obtained was the antibacterial hyaluronic acid wound dressing with a core-shell structure.

[0023] Example 4 (1) Preparation of modified hyaluronic acid Dissolve 10% hyaluronic acid and sodium periodate in an aqueous medium and react fully to obtain a reaction solution. Add an acid solution to the reaction solution to adjust the pH, and add the pH-adjusted reaction solution to a container containing hydroxytyrosol. Fully mix, separate and purify to obtain modified hyaluronic acid. (2) Preparation of shell spinning solution Dissolve polyvinyl butyral with a mass concentration of 10% and polyethylene oxide with a mass concentration of 3% in an ethanol aqueous solution, stir evenly, and obtain a shell spinning solution; (3) Preparation of core layer spinning solution Dissolve zein with a mass concentration of 20% in an ethanol aqueous solution, add the modified hyaluronic acid prepared in the above step with a mass concentration of 0.1% to the above solution, stir evenly, and obtain a nuclear layer spinning solution; (4) Preparation of antibacterial hyaluronic acid wound dressing with core-shell structure The shell layer spinning solution and the core layer spinning solution were extracted by syringes respectively, and they were connected to the coaxial needle. A voltage of 20 kV was applied, and the collection distance was 18 cm. The syringe was pushed forward at a rate of 0.8 mL / h of the shell layer spinning solution and 0.3 mL / h of the core layer spinning solution for spinning. The collector obtained was the antibacterial hyaluronic acid wound dressing with a core-shell structure.

[0024] Example 5 (1) Preparation of modified hyaluronic acid Dissolve 10% hyaluronic acid and sodium periodate in an aqueous medium and react fully to obtain a reaction solution. Add an acid solution to the reaction solution to adjust the pH, and add the pH-adjusted reaction solution to a container containing hydroxytyrosol. Fully mix, separate and purify to obtain modified hyaluronic acid. (2) Preparation of shell spinning solution Dissolve polyvinyl butyral with a mass concentration of 10% and polyethylene oxide with a mass concentration of 3% in an ethanol aqueous solution, stir evenly, and obtain a shell spinning solution; (3) Preparation of core layer spinning solution Dissolve zein with a mass concentration of 20% in an ethanol aqueous solution, add the modified hyaluronic acid prepared in the above step with a mass concentration of 0.1% to the above solution, stir evenly, and obtain a nuclear layer spinning solution; (4) Preparation of antibacterial hyaluronic acid wound dressing with core-shell structure The shell layer spinning solution and the core layer spinning solution were extracted by syringes respectively, and they were connected to the coaxial needle. A voltage of 25 kV was applied, and the collection distance was 20 cm. The syringe was pushed forward at a rate of 1.0 mL / h of the shell layer spinning solution and 0.3 mL / h of the core layer spinning solution for spinning. The collector obtained was the antibacterial hyaluronic acid wound dressing with a core-shell structure.

[0025] The core-shell structure hyaluronic acid nanofibers obtained in Example 1 have a macroscopic morphology as shown in Figure 1 As shown in the figure (below the white fiber is aluminum foil for collection), it was placed under a scanning electron microscope for observation, and the results are as follows Figure 2 As shown, the red circled part shows that the overall morphology of the fiber is regular, and the fiber has an inner and outer layer structure.

[0026] The macroscopic and microscopic morphologies of the fibers obtained in Examples 2 to 5 are similar to those of the fibers in Example 1, and the detailed description is omitted.

Claims

1. A method for preparing an antibacterial hyaluronic acid wound dressing having a core-shell structure, characterized in that: The method comprises the following steps: (1) Preparation of modified hyaluronic acid Dissolve 5-10% hyaluronic acid and sodium periodate in an aqueous medium and react fully to obtain a reaction solution. Add an acid solution to the reaction solution to adjust the pH, and add the pH-adjusted reaction solution to a container containing hydroxytyrosol. Fully mix, separate and purify to obtain modified hyaluronic acid; (2) Preparation of shell spinning solution Dissolving polyvinyl butyral with a mass concentration of 4-10% and polyethylene oxide with a mass concentration of 1-3% in an ethanol aqueous solution, stirring evenly, to obtain a shell spinning solution; (3) Preparation of core layer spinning solution Dissolve zein with a mass concentration of 6-20% in an ethanol aqueous solution, add the modified hyaluronic acid prepared in the above step with a mass concentration of 0.05-0.1% to the above solution, stir evenly, and obtain a nuclear layer spinning solution; (4) Preparation of core-shell structured hyaluronic acid nanofiber materials Use a syringe to extract the shell layer spinning solution and the core layer spinning solution respectively, and connect them to the coaxial needle. Apply a voltage of 10-25kV, set the collection distance to 8-20 cm, and push the syringe to spin at a rate of 0.2-1.0 mL / h of the shell layer spinning solution and 0.1-0.3 mL / h of the core layer spinning solution. The collector is the antibacterial hyaluronic acid wound dressing with a core-shell structure.

2. The method for preparing an antibacterial hyaluronic acid wound dressing with a core-shell structure according to claim 1, characterized in that: The modified hyaluronic acid used in step (1) includes hemiacetalized hyaluronic acid.

3. The method for preparing an antibacterial hyaluronic acid wound dressing with a core-shell structure according to claim 1, characterized in that: The acid solution mentioned in step (1) is one of hydrochloric acid, oxalic acid or citric acid.

4. The method for preparing an antibacterial hyaluronic acid wound dressing with a core-shell structure according to claim 1, characterized in that: The molecular weight M of hyaluronic acid in step (1) w =10000-1000000 g·mol -1 .

5. The method for preparing an antibacterial hyaluronic acid wound dressing with a core-shell structure according to claim 1, characterized in that: The mass ratio of water to ethanol in the ethanol aqueous solution in step (2) is 1:9-4:

6.

6. The method for preparing an antibacterial hyaluronic acid wound dressing with a core-shell structure according to claim 1, characterized in that: The molecular weight M of the polyethylene oxide in step (2) w =300000-1000000 g·mol -1 .

7. The method for preparing an antibacterial hyaluronic acid wound dressing with a core-shell structure according to claim 1, characterized in that: The mass ratio of water to ethanol in the ethanol aqueous solution in step (3) is 1:9-5:

5.

8. The method for preparing an antibacterial hyaluronic acid wound dressing with a core-shell structure according to claim 1, characterized in that: The coaxial needle used in step (4) is 25 / 18-19 / 15G.

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