Preparation method of ROS (reactive oxygen species) response type wound repair hydrogel and product of ROS response type wound repair hydrogel

Abstract

The invention relates to a preparation method of ROS (reactive oxygen species) response type wound repair hydrogel and a product of the ROS response type wound repair hydrogel. Emodin is loaded on meso-porous silicon, and polyvinyl alcohol emodin is loaded on meso-porous silicon and is integrated with mimic enzyme by active oxygen cross-linking agent N1-(4-bromobenzyl)-N3-(4-bromophenyl)-N1, N1, N3, N3-tetramethylpropane-1, 3-diamine to form the hydrogel. The cross-linking agent TSPBA adopted by the invention contains phenylboronic acid ester bonds and can dynamically respond to ROS (reactive oxygen species) and release loaded drug particles. According to the invention, the emodin is loaded on the meso-porous silicon, so that the solubility and the slow release performance of the emodin are improved. The mimic enzyme loaded on the hydrogel has the capability of scavenging free radicals; the loaded emodin can promote high expression of growth factors related to skin and subcutaneous blood vessels, improve inflammatory response and promote wound healing, and meanwhile, the emodin has an antibacterial effect, so that the prepared hydrogel has a synergistic skin repairing effect.

Description

Technical Field

[0001] The present invention relates to a preparation method and product of a ROS-responsive wound repair hydrogel, and specifically to a polyvinyl alcohol hydrogel that can respond to microenvironmental ROS and is loaded with mesoporous silicon-encapsulated traditional Chinese medicine rhein and nanoenzymes. The present invention belongs to the field of nano-biomedical materials. Background Art

[0002] As a protective barrier, the skin is the largest organ in the human body, preventing damage to the human body from ultraviolet rays, bacteria and other substances. Skin damage repair is a complex process and a continuous reaction. The repair process is mainly divided into four stages: (1) hemostasis; (2) inflammation; (3) proliferation; (4) maturation and remodeling, and the four stages can overlap with each other. After skin injury, platelets immediately begin to aggregate and form thrombi at the damaged blood vessels to stop bleeding. At the same time, various immune cells are activated and aggregate at the wound, and the inflammatory process begins. When immune cells secrete proinflammatory cytokines, inflammatory cells, especially neutrophils, produce a large amount of reactive oxygen species (ROS). A moderate amount of ROS can protect the body from infection, however, excessive ROS can also damage surrounding tissues, and chronic inflammation can further impair the healing of skin wounds.

[0003] Common medical dressings temporarily cover wounds to avoid bacterial infection and other external factors, thereby protecting wounds and wound surfaces. However, during use, medical dressings may cause problems such as wound adhesion, poor mechanical strength, and easy infection. At the same time, frequent dressing changes further cause great pain to patients. Hydrogel dressings are a gel-like substance applied to burn wounds. They can absorb tissue fluid exuded from the wound surface in a timely manner and isolate bacteria, fungi and viruses, thereby controlling infection and promoting wound healing. They are an ideal medical dressing. With the development of materials science, the development of a multi-strategy combined antibacterial hydrogel product that can effectively promote wound healing has become a new research direction for medical dressings. Summary of the invention

[0004] The present invention aims to provide a method for preparing a ROS-responsive wound repair hydrogel.

[0005] Another object of the present invention is to provide a ROS-responsive wound repair hydrogel product prepared by the above method.

[0006] The object of the present invention is achieved by the following scheme: a method for preparing a ROS-responsive wound repair hydrogel, firstly using mesoporous silica to load rheumatoid artemisia (R@MCM), and then using an active oxygen crosslinking agent N1-(4-bromobenzyl)-N3-(4-bromophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diamine (TSPBA) to integrate polyvinyl alcohol (PVA), rheumatoid artemisia loaded mesoporous silica and simulated enzyme to form a hydrogel, comprising the following steps: (1) 0.1-1 g of rhein was fully dissolved in 5 mL of methanol solution, and then the solution was transferred to a beaker containing 1 g of mesoporous silica and stirred to mix thoroughly. The mixture was vacuum dried at 50 °C for 24 hours to remove methanol and obtain R@MCM; (2) 10-50 mg R@MCM and 50-100 mg mimic enzyme were fully dissolved in 1 mL PVA (mass fraction 2-10%) and mixed evenly. Then, 20 μL TSPBA (mass fraction 4%-10%) solution was added and stirred thoroughly. The hydrogel was then allowed to stand to obtain.

[0007] The mesoporous silicon of the present invention has a size of 1-5 μm and a pore size of 2-10 nm.

[0008] The loading amount of emodin in the mesoporous silica of the present invention is 0.16-0.2 mg / mg.

[0009] The mimetic enzyme of the present invention has the ability to scavenge free radicals and can be any one of iron-based nanozymes, nanogold, cerium-based metal organic framework materials, manganese-based metal organic framework materials, and the like.

[0010] The size of the nano-gold described in the present invention is 2-10 nm.

[0011] The present invention provides a ROS-responsive wound repair hydrogel, which is characterized by being prepared according to any of the above methods; the hydrogel responds to microenvironmental ROS and is loaded with mesoporous silica-encapsulated traditional Chinese medicine rhein and nanozymes.

[0012] The advantages of the present invention are: (1) The cross-linking agent TSPBA used in the present invention contains a phenylboronic acid ester bond, which can dynamically respond to ROS and release the loaded drug particles.

[0013] (2) Rhein has an anthraquinone structure and is poorly soluble in water. The present invention uses mesoporous silica to load Rhein to improve the solubility and sustained-release properties of Rhein.

[0014] (3) The simulated enzyme attached to the hydrogel of the present invention has the ability to scavenge free radicals; the loaded emodin can promote the high expression of skin and subcutaneous blood vessel-related growth factors, improve inflammatory response, and promote wound healing. At the same time, emodin has an antibacterial effect, so the prepared hydrogel has a synergistic effect of repairing the skin. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Attached Figure 1 Cell activity analysis of the hydrogels prepared in Examples 1-3. DETAILED DESCRIPTION

[0016] The technical scheme of the present invention is further described below through specific examples. The following examples are further explanations of the present invention, but do not limit the scope of the present invention.

[0017] Experimental Example 1 A ROS-responsive wound repair hydrogel is first prepared by using mesoporous silica to load rheumatoid artemisia (R@MCM), and then using a reactive oxygen crosslinking agent N1-(4-bromobenzyl)-N3-(4-bromophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diamine (TSPBA) to integrate polyvinyl alcohol (PVA), rheumatoid artemisia loaded mesoporous silica and a simulated enzyme to form a hydrogel. The preparation is carried out according to the following steps: (1) After 0.2 g of emodin was fully dissolved in 5 mL of methanol solution, the solution was transferred to a beaker containing 1 g of mesoporous silica and stirred to mix thoroughly. The mixture was vacuum dried at 50 °C for 24 hours to remove methanol and obtain R@MCM. (2) 20 mg of R@MCM and 50 mg of enzyme-mimicking ferroferric oxide nanozyme were fully dissolved in 1 mL of PVA (5% by mass). After mixing evenly, 20 μL of TSPBA (7% by mass) solution was added. After stirring thoroughly, the mixture was allowed to stand to obtain a hydrogel.

[0018] The cell viability of the prepared hydrogel was 93%, see attached Figure 1 As shown, the biocompatibility is good.

[0019] Example 2 A ROS-responsive wound repair hydrogel is prepared similar to Example 1 by the following steps: (1) 0.3 g of rhein was fully dissolved in 5 mL of methanol solution, and then the solution was transferred to a beaker containing 1 g of mesoporous silica and stirred to mix thoroughly. The mixture was vacuum dried at 50 °C for 24 hours to remove methanol and obtain R@MCM; (2) 30 mg R@MCM and 60 mg Prussian blue nanozyme were fully dissolved in 1 mL PVA (mass fraction 5%), mixed evenly, and then 20 μL TSPBA (mass fraction 7%) solution was added. After sufficient stirring, the mixture was allowed to stand to obtain a hydrogel. Figure 1 The cell viability of the hydrogel prepared in Example 2 is 89%, and the biocompatibility is good.

[0020] The cell viability of the prepared hydrogel was 90%, see attached Figure 1 As shown, the biocompatibility is good.

[0021] Example 3 A ROS-responsive wound repair hydrogel is prepared similar to Example 1 by the following steps: (1) 0.2 g of rhamnosin was fully dissolved in 5 mL of methanol solution, and then the solution was transferred to a beaker containing 1 g of mesoporous silica and stirred to mix thoroughly. The mixture was vacuum dried at 50 °C for 24 hours to remove methanol and obtain R@MCM; (2) 30 mg of R@MCM and 60 mg of gold nanoparticles were fully dissolved in 1 mL of PVA (mass fraction 5%) and mixed evenly. Then, 20 μL of TSPBA (mass fraction 8%) solution was added and stirred thoroughly. The mixture was allowed to stand to obtain a hydrogel.

[0022] The cell viability of the prepared hydrogel was 95%, see attached Figure 1 As shown, the biocompatibility is good.

Claims

1. A method for preparing a ROS-responsive wound repair hydrogel, characterized in that: First, mesoporous silica loaded with rheum officinale (R@MCM) was used, and then the active oxygen crosslinking agent N1-(4-bromobenzyl)-N3-(4-bromophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diamine (TSPBA) was used to integrate polyvinyl alcohol (PVA), rheum officinale loaded with mesoporous silica and simulated enzyme to form a hydrogel, which includes the following steps: (1) After 0.1-1 g of emodin was fully dissolved in 5 mL of methanol solution, the solution was transferred to a beaker containing 1 g of mesoporous silica and stirred to mix thoroughly. The mixture was vacuum dried at 50 °C for 24 hours to remove methanol and obtain R@MCM. (2) 10-50 mg R@MCM and 50-100 mg mimic enzyme were fully dissolved in 1 mL PVA (mass fraction 2-10%) and mixed evenly. Then, 20 μL TSPBA (mass fraction 4%-10%) solution was added and stirred thoroughly. The hydrogel was then allowed to stand to obtain.

2. A method for preparing a ROS-responsive wound repair hydrogel according to claim 1, characterized in that The mesoporous silicon has a size of 1-5 μm and a pore size of 2-10 nm.

3. A method for preparing a ROS-responsive wound repair hydrogel according to claim 1, characterized in that The loading amount of emodin in the mesoporous silica is 0.16-0.2 mg / mg.

4. A method for preparing a ROS-responsive wound repair hydrogel according to claim 1, characterized in that The simulated enzyme has the ability to scavenge free radicals and is at least any one of iron-based nanozymes, nanogold, cerium-based metal organic framework materials, and manganese-based metal organic framework materials.

5. A method for preparing a ROS-responsive wound repair hydrogel according to claim 1, characterized in that The size of the gold nanoparticles is 2-10 nm.

6. A method for preparing a ROS-responsive wound repair hydrogel according to any one of claims 1 to 5, characterized in that: Prepare as follows: (1) After 0.2 g of emodin was fully dissolved in 5 mL of methanol solution, the solution was transferred to a beaker containing 1 g of mesoporous silica and stirred to mix thoroughly. The mixture was vacuum dried at 50 °C for 24 hours to remove methanol and obtain R@MCM. (2) 20 mg of R@MCM and 50 mg of enzyme-mimicking ferroferric oxide nanozyme were fully dissolved in 1 mL of PVA (5% by mass). After mixing evenly, 20 μL of TSPBA (7% by mass) solution was added. After stirring thoroughly, the mixture was allowed to stand to obtain a hydrogel.

7. A method for preparing a ROS-responsive wound repair hydrogel according to any one of claims 1 to 5, characterized in that: Prepare as follows: (1) 0.3 g of rhein was fully dissolved in 5 mL of methanol solution, and then the solution was transferred to a beaker containing 1 g of mesoporous silica and stirred to mix thoroughly. The mixture was vacuum dried at 50 °C for 24 hours to remove methanol and obtain R@MCM; (2) 30 mg R@MCM and 60 mg Prussian blue nanozyme were fully dissolved in 1 mL PVA (mass fraction 5%), mixed evenly, and then 20 μL TSPBA (mass fraction 7%) solution was added. After sufficient stirring, the hydrogel was allowed to stand to obtain the hydrogel. The cell viability of the hydrogel prepared in Example 2 shown in Figure 1 was 89%, and the biocompatibility was good.

8. A method for preparing a ROS-responsive wound repair hydrogel according to any one of claims 1 to 5, characterized in that: Prepare as follows: (1) 0.2 g of rhamnosin was fully dissolved in 5 mL of methanol solution, and then the solution was transferred to a beaker containing 1 g of mesoporous silica and stirred to mix thoroughly. The mixture was vacuum dried at 50 °C for 24 hours to remove methanol and obtain R@MCM; (2) 30 mg of R@MCM and 60 mg of gold nanoparticles were fully dissolved in 1 mL of PVA (mass fraction 5%) and mixed evenly. Then, 20 μL of TSPBA (mass fraction 8%) solution was added and stirred thoroughly. The mixture was allowed to stand to obtain a hydrogel. The prepared hydrogel cell viability was 95%, as shown in Figure 1, and had good biocompatibility.

9. A ROS-responsive wound repair hydrogel, characterized in that Prepared according to any one of the methods described in claims 1-8; polyvinyl alcohol hydrogel that responds to microenvironmental ROS and is loaded with mesoporous silica-encapsulated traditional Chinese medicine rhein and nanozymes.

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