阅读说明：本技术 一种表面负载纳米银的双层水凝胶及其制备方法 (Double-layer hydrogel with surface loaded with nano-silver and preparation method thereof ) 是由 范代娣 李阳 朱晨辉 段志广 傅容湛 于 2020-05-19 设计创作，主要内容包括：本发明公开了一种表面负载纳米银的双层水凝胶及其制备方法,表面负载纳米银的双层水凝胶的上表面孔径为2μm～10μm,下表面孔径为80μm～130μm,纳米银的尺寸为5nm～110nm。制备方法包括以下步骤：步骤一、将双层水凝胶浸泡于多巴胺溶液中,搅拌,得到多巴胺涂层双层水凝胶；步骤二、将多巴胺涂层双层水凝胶于硝酸银溶液中浸泡5min～1200min,得到表面负载纳米银的双层水凝胶。本发明的表面负载纳米银的双层水凝胶,纳米银颗粒在表面均匀分散,上层孔径较小结构致密,下层孔径较大结构疏松,两层紧密结合,具有优异的生物相容性、阻菌、保湿、抗菌、吸收渗液、粘附皮肤防止敷料脱落以及促进伤口愈合等功能。(The invention discloses a double-layer hydrogel with nano-silver loaded on the surface and a preparation method thereof, wherein the pore diameter of the upper surface of the double-layer hydrogel with nano-silver loaded on the surface is 2-10 mu m, the pore diameter of the lower surface is 80-130 mu m, and the size of the nano-silver is 5-110 nm. The preparation method comprises the following steps: step one, soaking the double-layer hydrogel in a dopamine solution, and stirring to obtain a dopamine coating double-layer hydrogel; and step two, soaking the dopamine coating double-layer hydrogel in a silver nitrate solution for 5-1200 min to obtain the double-layer hydrogel with the surface loaded with the nano-silver. According to the double-layer hydrogel with the nano-silver loaded on the surface, nano-silver particles are uniformly dispersed on the surface, the upper layer is small in pore diameter and compact in structure, the lower layer is large in pore diameter and loose in structure, the two layers are tightly combined, and the double-layer hydrogel has the functions of excellent biocompatibility, bacterium resistance, moisture preservation, antibiosis, seepage absorption, adhesion to skin, prevention of dressing falling, promotion of wound healing and the like.)

1. The double-layer hydrogel with the surface loaded with the nano silver is characterized in that the pore diameter of the upper surface of the double-layer hydrogel with the surface loaded with the nano silver is 2-10 mu m, the pore diameter of the lower surface of the double-layer hydrogel is 80-130 mu m, and the size of the nano silver is 5-110 nm.

2. The bilayer hydrogel with nanosilver supported on the surface thereof as claimed in claim 1, wherein the nanosilver has a size of 5nm to 50 nm.

3. A method for preparing the nanosilver-surface-supported bilayer hydrogel according to claim 1 or 2, comprising the steps of:

step one, soaking the double-layer hydrogel in a dopamine solution, and stirring for 10-30 hours to obtain dopamine coating double-layer hydrogel;

and step two, soaking the dopamine coating double-layer hydrogel in the step one in a silver nitrate solution for 5-1200 min to obtain the double-layer hydrogel with the surface loaded with the nano silver.

4. The method according to claim 3, wherein the pH value of the dopamine solution in the first step is 7-10, and the mass percentage of dopamine in the dopamine solution is 1% -6%.

5. The method as claimed in claim 3, wherein the silver nitrate solution in the second step has a silver nitrate content of 0.5mmol/L to 80 mmol/L.

6. The method as claimed in claim 5, wherein the soaking time in the second step is 10min to 480min, and the amount of silver nitrate in the silver nitrate solution is 1mmol/L to 10 mmol/L.

7. The method of claim 3, wherein step one of the preparation of the bilayer hydrogel comprises the steps of:

step 101, mixing a chitosan aqueous solution and a polyvinyl alcohol aqueous solution to obtain a chitosan-polyvinyl alcohol mixed solution;

102, dissolving polyethylene glycol into the chitosan-polyvinyl alcohol mixed solution in the step 101 to obtain a hydrogel preparation solution;

103, pouring the hydrogel preparation liquid obtained in the step 102 into a template for circulating low-temperature freezing to obtain an upper layer of the double-layer hydrogel;

step 104, mixing a sodium alginate aqueous solution and a polyvinyl alcohol aqueous solution to obtain a sodium alginate-polyvinyl alcohol mixed solution;

105, dissolving polyethylene glycol in the sodium alginate-polyvinyl alcohol mixed solution obtained in the step 104 to obtain a hydrogel preparation solution;

and 106, pouring the hydrogel preparation liquid obtained in the step 105 onto the upper layer of the double-layer hydrogel obtained in the step 103 at room temperature, and performing circulating low-temperature freezing to obtain the double-layer hydrogel.

8. The method according to claim 3, wherein the chitosan content in the chitosan aqueous solution in step 101 is 8-14% by mass, and the polyvinyl alcohol content in the polyvinyl alcohol aqueous solution in step 101 is 16-28% by mass; the mass percentage of the sodium alginate in the sodium alginate aqueous solution in the step 104 is 2-6%, and the mass percentage of the polyvinyl alcohol in the polyvinyl alcohol aqueous solution in the step 104 is 16-22%; in the step 101, the temperature of the chitosan-polyvinyl alcohol mixed solution is 70-100 ℃; in step 104, the temperature of the sodium alginate-polyvinyl alcohol mixed solution is 70-100 ℃.

9. The method according to claim 3, wherein the number of times of the cyclic low-temperature freezing in the steps 103 and 106 is 2 to 3, each cyclic low-temperature freezing comprises low-temperature freezing and unfreezing, the temperature of the low-temperature freezing is-10 ℃ to-40 ℃, the time of the low-temperature freezing is 2h to 30h, the temperature of the unfreezing is 20 ℃ to 40 ℃, and the time of the unfreezing is 2h to 10 h.

10. The method according to claim 3, further comprising allowing the hydrogel preparation solution of step 102 to stand at room temperature for 2min to 40min and allowing the hydrogel preparation solution of step 105 to stand at room temperature for 2min to 40 min.

Technical Field

The invention belongs to the technical field of biomedical materials, and particularly relates to a double-layer hydrogel with nano-silver loaded on the surface and a preparation method thereof.

Background

The hydrogel is a water-insoluble soft material with water holding capacity, which is soft in texture, can keep a certain shape and absorbs a large amount of water. The hydrogel has the potential in the aspect of wound dressing application due to good water absorption, wound exudate is a problem which is difficult to avoid for wound healing, the wound exudate is liquid leaked from a wound, the main component of the wound exudate liquid is water, and the wound exudate liquid also contains electrolytes, nutrient substances, proteins, inflammatory media, enzymes, growth factors, metabolic waste, various cells and the like, the exudate liquid is transparent and light amber, has uniform viscosity and no odor, and for chronic wounds, the exudate liquid can delay wound healing, damage a wound bed, degrade extracellular matrix and cause skin problems around the wound, so that effective exudate treatment is necessary.

The hydrogel dressing clinically applied at present can only be used as a moisturizing and isolating protective material, and cannot meet the clinical requirements of absorbing seepage, maintaining moisture for a long time and preventing bacterial infection when being used as a wound dressing. The functions of absorbing the exudate and maintaining water for a long time and preventing bacterial infection are contradictory, because the hydrogel needs to have a large pore size for absorbing the exudate and a small pore size for preventing bacteria. In order to balance the function of absorbing exudate and preventing bacteria of hydrogel materials, researchers in the prior art have constructed a hydrogel with a double-layer structure, namely a hydrogel with a second layer is prepared on the surface of a hydrogel with a first layer in situ, and simultaneously, the absorption of exudate and the prevention of bacterial invasion and rapid water dissipation are realized, but bacteria are small and have strong reproductive capacity, and the improvement of the structure of the hydrogel with the double layer is expected to improve the capability of the hydrogel for preventing exudate absorption and bacterial invasion, so that the hydrogel is one of effective ways for reducing inflammation and even death caused by wound infection.

Disclosure of Invention

The invention aims to solve the technical problem of providing a double-layer hydrogel with nano silver loaded on the surface and a preparation method thereof aiming at the defects of the prior art. The double-layer hydrogel with the surface loaded with the nano silver utilizes an upper layer and a lower layer with the pore diameters of 2-10 mu m and 80-130 mu m respectively, the size of the nano silver loaded on the surface is 80-110 nm, nano silver particles are uniformly dispersed on the surface, the pore diameter of the upper layer is smaller, the structure is compact, the pore diameter of the lower layer is larger, the structure is loose, the two layers are tightly combined, and the double-layer hydrogel with the surface loaded with the nano silver has excellent biocompatibility and has the functions of resisting bacteria, preserving moisture, resisting bacteria, absorbing seepage, adhering skin, preventing dressing from falling off, promoting wound healing and the like.

In order to solve the technical problems, the invention adopts the technical scheme that: the double-layer hydrogel with the surface loaded with the nano silver is characterized in that the pore diameter of the upper surface of the double-layer hydrogel with the surface loaded with the nano silver is 2-10 mu m, the pore diameter of the lower surface of the double-layer hydrogel is 80-130 mu m, and the size of the nano silver is 5-110 nm.

The double-layer hydrogel with the surface loaded with the nano-silver is characterized in that the size of the nano-silver is 5 nm-50 nm.

In addition, the invention also provides a method for preparing the double-layer hydrogel with the surface loaded with the nano silver, which is characterized by comprising the following steps:

step one, soaking the double-layer hydrogel in a dopamine solution, and stirring for 10-30 hours to obtain dopamine coating double-layer hydrogel;

and step two, soaking the dopamine coating double-layer hydrogel in the step one in a silver nitrate solution for 5-1200 min to obtain the double-layer hydrogel with the surface loaded with the nano silver.

The method is characterized in that in the step one, the pH value of the dopamine solution is 7-10, and the mass percentage of dopamine in the dopamine solution is 1% -6%.

The method described above, wherein the amount concentration of the silver nitrate in the silver nitrate solution in the second step is 0.5mmol/L to 80 mmol/L.

The method is characterized in that the soaking time in the second step is 10-480 min, and the mass concentration of silver nitrate in the silver nitrate solution is 1-10 mmol/L.

The method is characterized in that the preparation method of the bilayer hydrogel in the step one comprises the following steps:

step 101, mixing a chitosan aqueous solution and a polyvinyl alcohol aqueous solution to obtain a chitosan-polyvinyl alcohol mixed solution;

102, dissolving polyethylene glycol into the chitosan-polyvinyl alcohol mixed solution in the step 101 to obtain a hydrogel preparation solution;

103, pouring the hydrogel preparation liquid obtained in the step 102 into a template for circulating low-temperature freezing to obtain an upper layer of the double-layer hydrogel;

step 104, mixing a sodium alginate aqueous solution and a polyvinyl alcohol aqueous solution to obtain a sodium alginate-polyvinyl alcohol mixed solution;

105, dissolving polyethylene glycol in the sodium alginate-polyvinyl alcohol mixed solution obtained in the step 104 to obtain a hydrogel preparation solution;

and 106, pouring the hydrogel preparation liquid obtained in the step 105 onto the upper layer of the double-layer hydrogel obtained in the step 103 at room temperature, and performing circulating low-temperature freezing to obtain the double-layer hydrogel.

The method is characterized in that the mass percentage of the chitosan in the chitosan aqueous solution in the step 101 is 8-14%, and the mass percentage of the polyvinyl alcohol in the polyvinyl alcohol aqueous solution in the step 101 is 16-28%; the mass percentage of the sodium alginate in the sodium alginate aqueous solution in the step 104 is 2-6%, and the mass percentage of the polyvinyl alcohol in the polyvinyl alcohol aqueous solution in the step 104 is 16-22%; in the step 101, the temperature of the chitosan-polyvinyl alcohol mixed solution is 70-100 ℃; in step 104, the temperature of the sodium alginate-polyvinyl alcohol mixed solution is 70-100 ℃.

The method is characterized in that the times of circulating low-temperature freezing in the step 103 and the step 106 are 2-3 times, each circulating low-temperature freezing comprises low-temperature freezing and unfreezing, the temperature of the low-temperature freezing is-10 ℃ to-40 ℃, the time of the low-temperature freezing is 2h to 30h, the unfreezing temperature is 20 ℃ to 40 ℃, and the unfreezing time is 2h to 10 h.

The method is characterized by further comprising the step of placing the hydrogel preparation solution obtained in the step 102 at room temperature for 2min to 40min and the step of placing the hydrogel preparation solution obtained in the step 105 at room temperature for 2min to 40 min.

Compared with the prior art, the invention has the following advantages:

1. the double-layer hydrogel with the nano-silver loaded on the surface of the invention utilizes the double-layer structure of the hydrogel and the nano-silver particles loaded on the surface to realize bacterium resistance, moisture preservation, antibiosis, seepage absorption, adhesion to skin, prevention of dressing falling and promotion of wound healing, the double-layer hydrogel has an upper layer and a lower layer with the pore diameters of 2-10 mu m and 80-130 mu m respectively, the size of the nano-silver loaded on the surface is 80-110 nm, the upper layer hydrogel has a small pore diameter and a compact structure, the lower layer hydrogel has a large pore diameter and a loose structure, the two layers are tightly combined, the nano-silver particles are uniformly dispersed on the surface of the double-layer hydrogel, and the double-layer hydrogel has excellent biocompatibility.

2. The double-layer hydrogel with the surface loaded with the nano silver is cooperated to prevent bacteria from permeating into a wound surface under the action of the double-layer hydrogel and the nano silver loaded on the surface of the double-layer hydrogel.

3. The double-layer hydrogel with the surface loaded with the nano-silver can be directly attached to the skin, so that the treatment and nursing procedures are reduced, and the cell proliferation is promoted to accelerate the wound healing.

4. According to the method, the double-layer hydrogel is placed in the dopamine solution and stirred to coat dopamine on the surface of the double-layer hydrogel, and then the double-layer hydrogel with the dopamine coating is placed in the silver nitrate solution and soaked to obtain the double-layer hydrogel with the surface loaded with the nano-silver, so that the nano-silver can be uniformly loaded on the surface of the double-layer hydrogel and the surface is endowed with viscosity, the method is simple and easy to operate, and the parameters of the preparation process are easy to control.

5. Preferably, the double-layer hydrogel is prepared by adopting two-time circulation low-temperature freezing, a chemical cross-linking agent is not required to be introduced, the double-layer hydrogel is safe, non-toxic and convenient, and molecules between the two layers of hydrogel form hydrogen bonds and are tightly combined.

The technical solution of the present invention is further described in detail below with reference to the embodiments and the accompanying drawings.

Drawings

FIG. 1 is a scanning electron micrograph of the upper surface of a bilayer hydrogel in example 1;

FIG. 2 is a scanning electron micrograph of the lower surface of the bilayer hydrogel of example 1;

FIG. 3 is a scanning electron micrograph of a cross section of the bilayer hydrogel of example 1;

FIG. 4 is a scanning electron micrograph of the double-layer hydrogel with the surface loaded with nano-silver in example 1;

FIG. 5 is a graph showing the antibacterial activity of the double-layered hydrogel having nanosilver loaded on the surface thereof in example 1;

FIG. 6 is a graph showing the moisturizing performance of the bilayer hydrogel having nanosilver loaded surfaces in example 1;

FIG. 7 is a comparison graph of bacteriostatic performance of the double-layer hydrogel with nano-silver loaded on the surface in example 1;

fig. 8 is a graph showing the adhesion performance of the double-layer hydrogel with nano silver loaded on the surface in example 1.

Detailed Description

In the following description, the part directly contacting the skin surface of the human body is referred to as the upper layer of the double-layered hydrogel, and the part away from the skin of the human body is referred to as the lower layer of the double-layered hydrogel. The upper surface of the double-layer hydrogel with the nano-silver loaded on the surface refers to the upper surface of the upper layer of the double-layer hydrogel with the nano-silver loaded on the surface, and the lower surface refers to the lower surface of the lower layer of the double-layer hydrogel with the nano-silver loaded on the surface. In the following description, the room temperature is in the range of 20 ℃ to 25 ℃.