阅读说明：本技术 一种单宁酸改性双层水凝胶及其制备方法 (Tannic acid modified double-layer hydrogel and preparation method thereof ) 是由 朱晨辉 范代娣 李阳 傅容湛 段志广 于 2020-05-19 设计创作，主要内容包括：本发明公开了一种单宁酸改性双层水凝胶及其制备方法,所述单宁酸改性双层水凝胶的上表面孔径为1μm～30μm,下表面孔径为50μm～300μm。所述制备方法包括在避光条件下,将双层水凝胶于单宁酸溶液中浸泡1h～48h,然后超声振荡,得到单宁酸改性双层水凝胶。本发明的单宁酸改性双层水凝胶结构更为致密,具有良好的皮肤粘合性,能够在受到机械损伤时很快恢复原状,具有良好的自愈和性能,可以有效阻菌、保湿、吸收渗液、防止脱落、抗氧化和促进伤口愈合,在将本发明的单宁酸改性双层水凝胶从皮肤贴合处移除时,不会损伤皮肤,可减少治疗护理工序。(The invention discloses tannic acid modified double-layer hydrogel and a preparation method thereof, wherein the pore diameter of the upper surface of the tannic acid modified double-layer hydrogel is 1-30 mu m, and the pore diameter of the lower surface of the tannic acid modified double-layer hydrogel is 50-300 mu m. The preparation method comprises the steps of soaking the double-layer hydrogel in a tannic acid solution for 1-48 h under a dark condition, and then carrying out ultrasonic oscillation to obtain the tannic acid modified double-layer hydrogel. The tannic acid modified double-layer hydrogel disclosed by the invention is more compact in structure, has good skin adhesiveness, can be quickly restored to the original shape when being mechanically damaged, has good self-healing and performance, can effectively block bacteria, preserve moisture, absorb seepage, prevent falling off and oxidation and promote wound healing, does not damage the skin when being removed from a skin joint, and can reduce treatment and nursing procedures.)

1. The tannin-modified double-layer hydrogel is characterized in that the aperture of the upper surface of the tannin-modified double-layer hydrogel is 1-30 microns, and the aperture of the lower surface of the tannin-modified double-layer hydrogel is 50-300 microns.

2. The tannin-modified bilayer hydrogel according to claim 1, wherein the tannin-modified bilayer hydrogel has an upper surface pore size of 1 to 10 μm and a lower surface pore size of 70 to 120 μm.

3. A method for preparing the tannin-modified bilayer hydrogel of claim 1 or 2, which comprises soaking the bilayer hydrogel in a tannin solution for 1 to 48 hours under a dark condition, and then ultrasonically oscillating to obtain the tannin-modified bilayer hydrogel.

4. The method as claimed in claim 3, wherein the tannic acid solution comprises 1 to 50% by weight of tannic acid.

5. The method according to claim 3, wherein the soaking time is 3 to 12 hours.

6. The method of claim 3, wherein the bilayer hydrogel is prepared by a method comprising the steps of:

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

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

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

step four, mixing the sodium hyaluronate aqueous solution and the polyvinyl alcohol aqueous solution to obtain a sodium hyaluronate-polyvinyl alcohol mixed solution;

step five, dissolving polyethylene glycol into the sodium hyaluronate-polyvinyl alcohol mixed solution obtained in the step four to obtain hydrogel preparation solution;

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

7. The method according to claim 6, wherein the chitosan content in the chitosan aqueous solution in the first step is 4-20% by weight; step one, the mass percentage of polyvinyl alcohol in the polyvinyl alcohol aqueous solution is 10-30%; step one, the temperature of the chitosan-polyvinyl alcohol mixed solution is 70-100 ℃; fourthly, the mass percentage content of the sodium hyaluronate in the sodium hyaluronate aqueous solution is 0.1-4%, and the mass percentage content of the polyvinyl alcohol in the polyvinyl alcohol aqueous solution is 10-30%; fourthly, the temperature of the sodium hyaluronate-polyvinyl alcohol mixed solution is 70-100 ℃.

8. The method according to claim 6, wherein the number average molecular weight of the polyethylene glycol in the second step is 400 to 4000; in the hydrogel preparation liquid in the second step, the mass percentage of the polyethylene glycol is 5-15%; the number average molecular weight of the polyethylene glycol in the step five is 1500-3000, and in the hydrogel preparation liquid in the step five, the mass percentage of the polyethylene glycol is 5% -10%.

9. The method according to claim 6, wherein the number of times of the cyclic low-temperature freezing in the step three is 2 to 4, 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 40h, the temperature of the unfreezing is 20 ℃ to 40 ℃, and the time of the unfreezing is 2h to 10 h; and sixthly, the circulation low-temperature freezing is performed for 2-3 times, each circulation low-temperature freezing comprises low-temperature freezing and unfreezing, the low-temperature freezing temperature is-10 ℃ to-40 ℃, the low-temperature freezing time is 2h to 40h, the unfreezing temperature is 20 ℃ to 40 ℃, and the unfreezing time is 2h to 10 h.

10. The method according to claim 6, further comprising placing the hydrogel preparation solution of step two in a room temperature environment for 10min to 30min and placing the hydrogel preparation solution of step five in a room temperature environment for 5min to 20 min.

Technical Field

The invention belongs to the technical field of biomedical materials, and particularly relates to tannic acid modified double-layer hydrogel and a preparation method thereof.

Background

The hydrogel is a soft material with soft texture and water holding capacity, and is widely applied in the medical field. Porous hydrogels have good water absorption properties, which have potential for use as wound dressings. At present, clinically, the hydrogel dressing generally has a single function, and can not simultaneously meet the requirements of the wound dressing for absorbing seepage, ventilating, preventing the excessive rapid loss of water, keeping the wound surface moist, clearing free radicals and preventing bacterial infection; the wound dressing is easy to damage and cannot be applied to dressing change frequency, and the exudate is exposed only to cause that the wound is difficult to heal; poor adhesion, causing skin health problems around the wound; poor convenience and the like, and influences the popularization and application of the hydrogel dressing in clinical medicine.

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 liquid absorption and seepage functions of hydrogel materials and prevent bacteria, researchers in the prior art have constructed double-layer hydrogel, namely a second layer of hydrogel is prepared on the surface of a first layer of hydrogel in situ, and meanwhile, liquid absorption, bacterial invasion prevention and rapid water dissipation are realized, but the double-layer hydrogel has the defects that the double-layer hydrogel is difficult to adhere to the skin and cannot be restored when mechanical damage is received. The adhesive and self-healing performance of the hydrogel dressing are improved on the basis of further optimizing the water retention and bacterium resistance performance of the hydrogel dressing, and the hydrogel dressing is one of effective ways for improving the application range of the hydrogel dressing.

Disclosure of Invention

The invention aims to solve the technical problem of providing a tannic acid modified double-layer hydrogel and a preparation method thereof aiming at the defects of the prior art. The tannic acid modified double-layer hydrogel is more compact in structure, has enhanced bacteria-blocking and water-retaining performances, has good skin adhesiveness and self-healing and performance, can quickly recover when being damaged by machinery, and can effectively block bacteria, retain moisture, absorb seepage, prevent falling, resist oxidation and promote wound healing.

In order to solve the technical problems, the invention adopts the technical scheme that: the tannin-modified double-layer hydrogel is characterized in that the aperture of the upper surface of the tannin-modified double-layer hydrogel is 1-30 microns, and the aperture of the lower surface of the tannin-modified double-layer hydrogel is 50-300 microns.

The tannin-modified double-layer hydrogel is characterized in that the pore diameter of the upper surface of the tannin-modified double-layer hydrogel is 1-10 mu m, and the pore diameter of the lower surface of the tannin-modified double-layer hydrogel is 70-120 mu m.

In addition, the invention also provides a method for preparing the tannic acid modified double-layer hydrogel, which is characterized by comprising the steps of soaking the double-layer hydrogel in a tannic acid solution for 1-48 hours under the condition of keeping out of the sun, and then carrying out ultrasonic oscillation to obtain the tannic acid modified double-layer hydrogel.

The method is characterized in that the mass percentage of the tannic acid in the tannic acid solution is 1-50%.

The method is characterized in that the soaking time is 3-12 hours.

The method is characterized in that the preparation method of the double-layer hydrogel comprises the following steps:

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

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

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

step four, mixing the sodium hyaluronate aqueous solution and the polyvinyl alcohol aqueous solution to obtain a sodium hyaluronate-polyvinyl alcohol mixed solution;

step five, dissolving polyethylene glycol into the sodium hyaluronate-polyvinyl alcohol mixed solution obtained in the step four to obtain hydrogel preparation solution;

and step six, pouring the hydrogel preparation liquid obtained in the step five onto the upper layer of the double-layer hydrogel obtained in the step three 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 one is 4-20%; step one, the mass percentage of polyvinyl alcohol in the polyvinyl alcohol aqueous solution is 10-30%; step one, the temperature of the chitosan-polyvinyl alcohol mixed solution is 70-100 ℃; fourthly, the mass percentage content of the sodium hyaluronate in the sodium hyaluronate aqueous solution is 0.1-4%, and the mass percentage content of the polyvinyl alcohol in the polyvinyl alcohol aqueous solution is 10-30%; fourthly, the temperature of the sodium hyaluronate-polyvinyl alcohol mixed solution is 70-100 ℃.

The method is characterized in that the number average molecular weight of the polyethylene glycol in the step two is 400-4000; in the hydrogel preparation liquid in the second step, the mass percentage of the polyethylene glycol is 5-15%; the number average molecular weight of the polyethylene glycol in the step five is 1500-3000, and in the hydrogel preparation liquid in the step five, the mass percentage of the polyethylene glycol is 5% -10%.

The method is characterized in that the circulation low-temperature freezing in the step three is performed for 2 to 4 times, each circulation low-temperature freezing comprises low-temperature freezing and unfreezing, the low-temperature freezing temperature is-10 to-40 ℃, the low-temperature freezing time is 2 to 40 hours, the unfreezing temperature is 20 to 40 ℃, and the unfreezing time is 2 to 10 hours; and sixthly, the circulation low-temperature freezing is performed for 2-3 times, each circulation low-temperature freezing comprises low-temperature freezing and unfreezing, the low-temperature freezing temperature is-10 ℃ to-40 ℃, the low-temperature freezing time is 2h to 40h, 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 liquid in the step two in a room temperature environment for 10min to 30min and the step five of placing the hydrogel preparation liquid in the room temperature environment for 5min to 20 min.

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

1. the tannic acid modified double-layer hydrogel disclosed by the invention is more compact in structure, has good skin adhesion and self-healing and performance, can quickly recover to an original state when being mechanically damaged, and can effectively inhibit bacteria, preserve moisture, absorb seepage, prevent falling off, resist oxidation and promote wound healing. When the tannin modified double-layer hydrogel is removed from the skin joint, the skin is not damaged, and treatment and nursing processes can be reduced.

2. According to the method, the tannic acid is used as the modified particle, the double-layer hydrogel is soaked in the tannic acid for modification under the condition of keeping out of the sun, and the aperture is adjusted, so that the bacterium-resistant effect and the water retention performance can be improved.

3. 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 upper surface of the tannic acid-modified bilayer hydrogel of example 1;

FIG. 3 is a scanning electron micrograph of the lower surface of the bilayer hydrogel of example 1;

FIG. 4 is a scanning electron micrograph of the lower surface of the tannic acid-modified bilayer hydrogel of example 1;

FIG. 5 is a scanning electron micrograph of a cross-section of the tannic acid-modified bilayer hydrogel of example 1 at X50 magnification;

FIG. 6 is a scanning electron micrograph of a cross-section of a tannic acid-modified bilayer hydrogel of example 1 at X95 magnification;

FIG. 7 is a graph showing the antibacterial activity of the tannic acid-modified double-layer hydrogel of example 1;

FIG. 8 is a graph comparing the moisturizing performance of the tannic acid-modified bilayer hydrogel of example 1;

FIG. 9 is a comparative bacteriostatic plot of tannin-modified bilayer hydrogel versus bilayer hydrogel of example 1;

FIG. 10 is a graph of the adhesion performance of the tannic acid-modified bilayer hydrogel of example 1;

FIG. 11 is a graph of the tannin modified bilayer hydrogel self-healing and performance of example 1;

FIG. 12 is a scanning electron micrograph of the tannic acid-modified bilayer hydrogel of example 1 after self-healing;

FIG. 13 is a graph of the antioxidant capacity (ABTS) of the tannic acid-modified bilayer hydrogel of example 1;

FIG. 14 is a graph of the antioxidant properties (DPPH) of the tannin-modified bilayer hydrogel of 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 tannic acid-modified bilayer hydrogel refers to the upper surface of the upper layer of the tannic acid-modified bilayer hydrogel, and the lower surface refers to the lower surface of the lower layer of the tannic acid-modified bilayer hydrogel. In the following description, the room temperature is in the range of 20 ℃ to 25 ℃.