阅读说明：本技术 一种改性羟丙基壳聚糖粘附自愈水凝胶及其制备方法和应用 (Modified hydroxypropyl chitosan adhesive self-healing hydrogel and preparation method and application thereof ) 是由 何广华 宁校庆 陈晓静 陈秀昊 卢昆 樊李红 郭远东 于 2021-08-30 设计创作，主要内容包括：本发明公开了一种改性羟丙基壳聚糖粘附自愈水凝胶及其制备方法和应用,先用咖啡酸对羟丙基壳聚糖进行化学改性,然后复合丙烯酰胺改性,接着通过氧化魔芋葡甘露聚糖和N,N’-亚甲基双丙烯酰胺混合交联剂进行交联,最后保温即得。该水凝胶具有优异的粘附、自愈、力学和溶胀性能。丙烯酰胺的引入使粘附自愈水凝胶的粘附性能提升至2.66倍,力学性能提升至2.4倍。本发明解决了传统羟丙基壳聚糖水凝胶粘附、自愈和力学性能不足的问题。(The invention discloses a modified hydroxypropyl chitosan adhesive self-healing hydrogel and a preparation method and application thereof. The hydrogel has excellent adhesion, self-healing, mechanical and swelling properties. The introduction of the acrylamide improves the adhesion performance of the adhesive self-healing hydrogel to 2.66 times and the mechanical performance to 2.4 times. The invention solves the problems of insufficient adhesion, self-healing and mechanical properties of the traditional hydroxypropyl chitosan hydrogel.)

1. The modified hydroxypropyl chitosan adhesive self-healing hydrogel is characterized in that raw materials of the adhesive self-healing hydrogel comprise caffeic acid modified hydroxypropyl chitosan derivative aqueous solution, acrylamide solution, ammonium persulfate and mixed cross-linking agent, wherein the volume of the acrylamide solution is 33.3% of that of the caffeic acid modified hydroxypropyl chitosan derivative aqueous solution; the dosage of the acrylamide in the acrylamide solution is 10-50% of the mass of the caffeic acid modified hydroxypropyl chitosan derivative;

the dosage of the ammonium persulfate is 4.7 to 7.8 percent of the mass of the caffeic acid modified hydroxypropyl chitosan derivative;

the mixed cross-linking agent consists of oxidized konjac glucomannan and N, N' -methylene bisacrylamide, and the dosage of the mixed cross-linking agent is 3.9-15.3% of the mass of the caffeic acid modified hydroxypropyl chitosan derivative.

2. The modified hydroxypropyl chitosan adhesive self-healing hydrogel according to claim 1, wherein the volume of the acrylamide solution is 33.3% of the volume of the caffeic acid modified hydroxypropyl chitosan derivative aqueous solution, and the concentration of the oxidized konjac glucomannan in the mixed cross-linking agent is 0.06 g-mL^-1The concentration of N, N' -methylenebisacrylamide was 0.01 g/mL^-1。

3. A preparation method of modified hydroxypropyl chitosan adhesion self-healing hydrogel is characterized by comprising the following steps:

(1) dissolving hydroxypropyl chitosan in water to obtain hydroxypropyl chitosan solution;

(2) dissolving caffeic acid in an aqueous solution of ethanol to obtain a caffeic acid solution;

(3) adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into a caffeic acid solution for activation;

(4) adding caffeic acid solution added with 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into hydroxypropyl chitosan solution for reaction;

(5) dialyzing the crude product obtained in the step (4), and drying to obtain the caffeic acid modified hydroxypropyl chitosan derivative;

(6) dissolving the caffeic acid modified hydroxypropyl chitosan derivative in water to obtain a caffeic acid modified hydroxypropyl chitosan derivative solution;

(7) dissolving acrylamide in water, and adding a mixed crosslinking agent of ammonium persulfate, oxidized konjac glucomannan and N, N' -methylene bisacrylamide;

(8) and (4) adding the solution obtained in the step (7) into the solution obtained in the step (6), and carrying out heat preservation and crosslinking to obtain the modified hydroxypropyl chitosan adhesive self-healing hydrogel.

4. The production method according to claim 3, characterized in that: in the step (1), the concentration of hydroxypropyl chitosan solution is 0.01 g/mL^-1The pH value is 5.6;

in the step (2), the ethanol water solution is prepared from deionized water and absolute ethanol according to the volume ratio of 1:1, and the concentration of the caffeic acid solution is 0.025 g/mL^-1。

5. The production method according to claim 3, characterized in that: in the step (3), the dosage of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 200% of the mass of hydroxypropyl chitosan, and the activation time of adding the hydrochloride into the caffeic acid solution is 2 hours;

in the step (4), the reaction needs to be carried out in a dark place under the protection of nitrogen, and the reaction time is 24 hours.

6. The production method according to claim 3, characterized in that: in the step (5), the dialysis time is 3 days, and the drying is drying or freeze drying.

7. The production method according to claim 3, characterized in that: in the step (7), the volume of the acrylamide solution is 33.3% of that of the caffeic acid modified hydroxypropyl chitosan derivative solution; the dosage of the acrylamide is 10 to 50 percent of the mass of the caffeic acid modified hydroxypropyl chitosan derivative.

8. The production method according to claim 3, characterized in that: in the step (7), ammonium persulfate is added firstly, and oxidized konjac glucomannan and N, N' -methylene bisacrylamide are added after 20 minutes, wherein the using amount of the ammonium persulfate is 4.7-7.8% of the mass of the caffeic acid modified hydroxypropyl chitosan derivative;

the mixed cross-linking agent consisting of the oxidized konjac glucomannan and the N, N' -methylene bisacrylamide has the dosage of 3.9 to 15.3 percent of the mass of the caffeic acid modified hydroxypropyl chitosan derivative, and the concentration of the oxidized konjac glucomannan is 0.06 g.mL^-1The concentration of N, N' -methylenebisacrylamide was 0.01 g/mL^-1。

9. The production method according to claim 3, characterized in that: in the step (8), the heat preservation temperature is 45-55 ℃, and the reaction time is 1-3 hours.

10. The application of the modified hydroxypropyl chitosan adhesive self-healing hydrogel in claim 1 in preparing wound repair, tissue adhesion, leak stoppage and sealing materials and object adhesion materials.

Technical Field

The invention relates to the technical field of functional polymers, in particular to modified hydroxypropyl chitosan adhesive self-healing hydrogel and a preparation method and application thereof.

Background

The hydrogel as a functional material has wide application prospect in the fields of biomedical materials, chemical engineering, environmental engineering and agriculture. However, the hydrogel generally has no adhesiveness, so that the hydrogel is inconvenient to use in certain occasions, for example, in surgical operation, the closure and repair of wound surfaces are one of key problems, the traditional suture method has more defects, and the method adopting the adhesive hydrogel is a development direction with potential, thereby arousing wide attention all over the world and having huge market prospect.

In addition, the hydrogel is usually easy to be damaged, causing the functional failure of the material, and needs to be replaced frequently, so that the development of the hydrogel with the self-healing function to prolong the service life thereof has become a research hotspot and frontier of the current functional polymer material.

Hydroxypropyl chitosan is an important chitosan derivative, not only has excellent moisture absorption, moisture retention and biocompatibility, but also has good characteristics of antibiosis, biodegradation and cell proliferation promotion, so that the hydroxypropyl chitosan is very suitable for the growth and repair of wounds or tissues. However, the hydroxypropyl chitosan hydrogel is brittle and easy to break, and has no self-adhesion, so that the development of the modified hydroxypropyl chitosan hydrogel with the functions of adhesion and self-healing has important practical significance.

Disclosure of Invention

The invention aims to solve the defects of the prior art and provides a modified hydroxypropyl chitosan adhesive self-healing hydrogel as well as a preparation method and application thereof. The introduction of acrylamide can simultaneously improve the adhesive property and the mechanical property of the modified hydroxypropyl chitosan hydrogel. The stability of the modified hydroxypropyl chitosan hydrogel can be improved by double crosslinking of oxidized konjac glucomannan and N, N' -methylene bisacrylamide.

In order to achieve the purpose, the raw materials of the adhesion self-healing hydrogel comprise caffeic acid modified hydroxypropyl chitosan derivative aqueous solution, acrylamide solution, ammonium persulfate and mixed cross-linking agent, wherein the volume of the acrylamide solution is 33.3% of that of the caffeic acid modified hydroxypropyl chitosan derivative aqueous solution; the dosage of the acrylamide in the acrylamide solution is 10-50% of the mass of the caffeic acid modified hydroxypropyl chitosan derivative;

the dosage of the ammonium persulfate is 4.7 to 7.8 percent of the mass of the caffeic acid modified hydroxypropyl chitosan derivative;

the mixed cross-linking agent consists of oxidized konjac glucomannan and N, N' -methylene bisacrylamide, and the dosage of the mixed cross-linking agent is 3.9-15.3% of the mass of the caffeic acid modified hydroxypropyl chitosan derivative.

Furthermore, the concentration of the oxidized konjac glucomannan in the mixed cross-linking agent is 0.06 g.mL^-1The concentration of N, N' -methylenebisacrylamide was 0.01 g/mL^-1。

The invention also provides a preparation method of the modified hydroxypropyl chitosan adhesive self-healing hydrogel, which comprises the following steps:

(1) dissolving hydroxypropyl chitosan in water to obtain hydroxypropyl chitosan solution;

(2) dissolving caffeic acid in an aqueous solution of ethanol to obtain a caffeic acid solution;

(3) adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into a caffeic acid solution for activation;

(4) adding caffeic acid solution added with 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into hydroxypropyl chitosan solution for reaction;

(5) dialyzing the crude product obtained in the step (4), and drying to obtain the caffeic acid modified hydroxypropyl chitosan derivative;

(6) dissolving the caffeic acid modified hydroxypropyl chitosan derivative in water to obtain a caffeic acid modified hydroxypropyl chitosan derivative solution;

(7) dissolving acrylamide in water, and adding a mixed crosslinking agent of ammonium persulfate, oxidized konjac glucomannan and N, N' -methylene bisacrylamide;

(8) and (4) adding the solution obtained in the step (7) into the solution obtained in the step (6), and carrying out heat preservation and crosslinking to obtain the modified hydroxypropyl chitosan adhesive self-healing hydrogel.

Further, in the step (1), the concentration of the hydroxypropyl chitosan solution as the raw material is 0.01 g/mL^-1The pH value is 5.6;

in the step (2), the ethanol water solution is prepared from deionized water and absolute ethanol according to the volume ratio of 1:1, and the concentration of the caffeic acid solution is 0.025 g/mL^-1。

Further, in the step (3), the amount of the 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 200% of the mass of the hydroxypropyl chitosan, and the activation time of adding the hydrochloride into the caffeic acid solution is 2 hours;

in the step (4), the reaction needs to be carried out in a dark place under the protection of nitrogen, and the reaction time is 24 hours.

Further, in the step (5), the dialysis time is 3 days, and the drying is oven drying or freeze drying.

Further, in the step (7), the volume of the acrylamide solution is 33.3% of that of the caffeic acid modified hydroxypropyl chitosan derivative solution; the dosage of the acrylamide is 10 to 50 percent of the mass of the caffeic acid modified hydroxypropyl chitosan derivative.

Further, in the step (7), ammonium persulfate is firstly added, and oxidized konjac glucomannan and N, N' -methylene bisacrylamide are added after 20 minutes, wherein the using amount of the ammonium persulfate is 4.7% -7.8% of the mass of the caffeic acid modified hydroxypropyl chitosan derivative; the mixed cross-linking agent consisting of the oxidized konjac glucomannan and the N, N' -methylene bisacrylamide has the dosage of 3.9 to 15.3 percent of the mass of the caffeic acid modified hydroxypropyl chitosan derivative, and the concentration of the oxidized konjac glucomannan is 0.06 g.mL^-1The concentration of N, N' -methylenebisacrylamide was 0.01 g/mL^-1。

And (3) further, in the step (8), the heat preservation temperature is 45-55 ℃, and the reaction time is 1-3 hours.

The invention also provides application of the modified hydroxypropyl chitosan adhesive self-healing hydrogel in preparation of wound repair, tissue adhesion, leaking stoppage and sealing materials and object adhesion materials.

The preparation mechanism of the modified hydroxypropyl chitosan adhesion self-healing hydrogel comprises the following steps:

the modified hydroxypropyl chitosan adhesive self-healing hydrogel is a novel microstructure, firstly, caffeic acid is bonded to hydroxypropyl chitosan, then acrylamide and the derivatives are compounded, and then crosslinking is carried out through oxidized konjac glucomannan and N, N-methylene bisacrylamide, wherein the oxidized konjac glucomannan crosslinked caffeic acid modified hydroxypropyl chitosan derivative and polyacrylamide, N, N' -methylene bisacrylamide are used for further crosslinking polyacrylamide (namely the compounded caffeic acid modified hydroxypropyl chitosan derivative is single-crosslinked, and the polyacrylamide is double-crosslinked), and finally the caffeic acid modified hydroxypropyl chitosan derivative/polyacrylamide adhesive self-healing hydrogel is generated. In addition, various interactions exist among the oxidized konjac glucomannan, the caffeic acid modified hydroxypropyl chitosan derivative and the polyacrylamide, including covalent bonds, hydrogen bonds and molecular chain winding, so that the stability of the hydrogel is remarkably improved.

The invention has the beneficial effects that:

1. the hydrogel provided by the invention has excellent adhesion and self-healing performance, and solves the problems that the traditional hydroxypropyl chitosan hydrogel has no adhesion and is easy to break.

2. The modified hydroxypropyl chitosan adhesive self-healing hydrogel has physical and chemical adhesive mechanisms at the same time, and is suitable for adhesion of various materials such as skin, metal, high polymers and the like.

3. The modified hydroxypropyl chitosan adhesion self-healing hydrogel has good mechanical properties.

4. The introduction of acrylamide improves the adhesive property of the modified hydroxypropyl chitosan hydrogel to 2.66 times and the mechanical property to 2.4 times.

5. The modified hydroxypropyl chitosan adhesive self-healing hydrogel has good swelling performance.

6. The modified hydroxypropyl chitosan adhesion self-healing hydrogel disclosed by the invention is of a double-crosslinking and double-network structure, and is more stable than a traditional single-crosslinking network.

7. The modified hydroxypropyl chitosan adhesive self-healing hydrogel takes natural polymers as base materials and has good degradability.

8. The preparation process of the modified hydroxypropyl chitosan adhesive self-healing hydrogel is simple and easy to operate, and is easy to industrialize.

Drawings

FIG. 1 shows the adhesion performance of the modified hydroxypropyl chitosan self-healing hydrogel (a: skin, b: stretching, c: steel, d: leaves, e: rubber, f: paper, g: plastic, h: kraft paper);

fig. 2 shows the self-healing performance of the modified hydroxypropyl chitosan adhered self-healing hydrogel.

Detailed Description

The present invention is described in further detail below with reference to specific examples so as to be understood by those skilled in the art.

Example 1

1) Weighing 1g hydroxypropyl chitosan, dissolving in 100mL deionized water, magnetically stirring at room temperature until the hydroxypropyl chitosan is uniformly dissolved, and adjusting the pH value to 5.6.

2) Further, 1g of caffeic acid is weighed and dissolved in 40mL of ethanol aqueous solution (deionized water: absolute ethyl alcohol 1:1), magnetic stirring is carried out until the caffeic acid is dissolved uniformly, then 2g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is added for activation for 2 hours, then the obtained solution is added into the hydroxypropyl chitosan solution, and the obtained solution is reacted for 24 hours in a dark place under the protection of nitrogen.

3) Dialyzing the obtained crude product in deionized water for 3 days, and drying to obtain the caffeic acid modified hydroxypropyl chitosan derivative.

4) 267mg of caffeic acid modified hydroxypropyl chitosan derivative is weighed into a beaker, 3mL of deionized water is added, and the mixture is magnetically stirred until the mixture is dissolved uniformly.

5) Weighing 80mg of acrylamide in another beaker, adding 1mL of deionized water, adding 12.5mg of ammonium persulfate for initiation, and adding 250uL of mixed cross-linking agent oxidized konjac glucomannan and N, N' -methylene bisacrylamide after 20 minutes, wherein the concentration of the oxidized konjac glucomannan is 0.06 g.mL^-1The concentration of N, N' -methylenebisacrylamide was 0.01 g/mL^-1。

6) Adding the mixed solution obtained in the step 5) into the caffeic acid modified hydroxypropyl chitosan derivative solution obtained in the step 4), quickly stirring uniformly, and finally preserving heat at 50 ℃ for 2 hours to obtain the modified hydroxypropyl chitosan adhesive self-healing hydrogel 1.

The adhesion performance of the modified hydroxypropyl chitosan adhesion self-healing hydrogel 1 obtained by the method is shown in fig. 1, and different base materials comprise: fresh leaves, steel, rubber, skin, plastic, kraft paper and the like can be firmly adhered to the surface of an object after being adhered, which shows that the modified hydroxypropyl chitosan adhesive self-healing hydrogel can be adhered to various materials, various adhesive groups exist in the hydrogel, the adhesive mechanism is different, and physical adhesion and chemical adhesion exist simultaneously, so that the hydrogel is suitable for the biomedical and industrial fields.

The self-healing properties of hydrogel 1 are shown in fig. 2, and the obtained dyed gels were diced, cut into the same shape, and the cut gels of different colors were spliced together. After 6 hours, the crack at the spliced part is fuzzy and disappears, and in addition, the methyl blue molecules in the semicircular gel dyed by methyl blue fully diffuse to the semicircular gel dyed by rhodamine B, which indicates that the hydrogel is self-healed.

Two pigskins (simulating human skin) were bonded with hydrogel 1, and the adhesion strength of the hydrogel was characterized by testing the force when the bonded surface between the two pigskins was pulled apart (the same below). The adhesive strength of hydrogel 1 to the skin was 18.12kPa, and without the introduction of acrylamide, the adhesive strength of hydrogel to the skin was only 6.8kPa under the same process conditions, i.e., the adhesive strength increased to 2.66 times after the introduction of acrylamide. The equilibrium swelling ratio of the hydrogel in deionized water was 511%.

Example 2

1) Weighing 1g hydroxypropyl chitosan, dissolving in 100mL deionized water, magnetically stirring at room temperature until the hydroxypropyl chitosan is uniformly dissolved, and adjusting the pH value to 5.6.

2) Further, 1g of caffeic acid is weighed and dissolved in 40mL of ethanol aqueous solution (deionized water: absolute ethyl alcohol 1:1), magnetic stirring is carried out until the caffeic acid is dissolved uniformly, then 2g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is added for activation for 2 hours, then the obtained solution is added into the hydroxypropyl chitosan solution, and the obtained solution is reacted for 24 hours in a dark place under the protection of nitrogen.

3) Dialyzing the obtained crude product in deionized water for 3 days, and drying to obtain the caffeic acid modified hydroxypropyl chitosan derivative.

4) 160mg of caffeic acid modified hydroxypropyl chitosan derivative is weighed into a beaker, 3mL of deionized water is added, and the mixture is magnetically stirred until the mixture is dissolved uniformly.

5) 80mg of acrylamide was weighed into another beaker, and 1mL of deionized water was added, along with 12.5mg of persulfuric acidAmmonium initiation, adding 250uL mixed cross-linking agent oxidized konjac glucomannan and N, N' -methylene bisacrylamide after 20 minutes, wherein the concentration of the oxidized konjac glucomannan is 0.06 g.mL^-1Concentration of N, N' -methylenebisacrylamide 0.01 g/mL^-1。

6) Adding the mixed solution obtained in the step 5) into the caffeic acid modified hydroxypropyl chitosan derivative solution obtained in the step 4), quickly stirring uniformly, and finally preserving heat at 50 ℃ for 2 hours to obtain the modified hydroxypropyl chitosan adhesive self-healing hydrogel 2.

The hydrogel 2 obtained by the method has good mechanical property, and the compressive strength reaches 41.7kPa which is 2.4 times of the compressive strength (17.3kPa) of the hydrogel without acrylamide. Meanwhile, the adhesive strength to the skin was 14.3 kPa.

Example 3

1) Weighing 1g hydroxypropyl chitosan, dissolving in 100mL deionized water, magnetically stirring at room temperature until the hydroxypropyl chitosan is uniformly dissolved, and adjusting the pH value to 5.6.

2) Further, 1g of caffeic acid is weighed and dissolved in 40mL of ethanol aqueous solution (deionized water: absolute ethyl alcohol 1:1), magnetic stirring is carried out until the caffeic acid is dissolved uniformly, then 2g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is added for activation for 2 hours, then the obtained solution is added into the hydroxypropyl chitosan solution, and the obtained solution is reacted for 24 hours in a dark place under the protection of nitrogen.

3) Dialyzing the obtained crude product in deionized water for 3 days, and drying to obtain the caffeic acid modified hydroxypropyl chitosan derivative.

4) 160mg of caffeic acid modified hydroxypropyl chitosan derivative is weighed into a beaker, 3mL of deionized water is added, and the mixture is magnetically stirred until the mixture is dissolved uniformly.

5) Weighing 120mg of acrylamide in another beaker, adding 1mL of deionized water, adding 12.5mg of ammonium persulfate for initiation, and adding 250uL of mixed cross-linking agent oxidized konjac glucomannan and N, N' -methylene bisacrylamide after 20 minutes, wherein the concentration of the oxidized konjac glucomannan is 0.06 g.mL^-1The concentration of N, N' -methylenebisacrylamide was 0.01 g/mL^-1。

6) Adding the mixed solution obtained in the step 5) into the caffeic acid modified hydroxypropyl chitosan derivative solution obtained in the step 4), quickly stirring uniformly, and finally preserving heat at 50 ℃ for 2 hours to obtain the modified hydroxypropyl chitosan adhesive self-healing hydrogel 3.

The hydrogel 3 obtained by the method has good mechanical properties, the compression strength reaches 61.2kPa, the equilibrium swelling ratio in deionized water is 645%, and the adhesion strength to the skin is 17.92 kPa.

Example 4

1) Weighing 1g hydroxypropyl chitosan, dissolving in 100mL deionized water, magnetically stirring at room temperature until the hydroxypropyl chitosan is uniformly dissolved, and adjusting the pH value to 5.6.

2) Further, 1g of caffeic acid is weighed and dissolved in 40mL of ethanol aqueous solution (deionized water: absolute ethyl alcohol 1:1), magnetic stirring is carried out until the caffeic acid is dissolved uniformly, then 2g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is added for activation for 2 hours, then the obtained solution is added into the hydroxypropyl chitosan solution, and the obtained solution is reacted for 24 hours in a dark place under the protection of nitrogen.

3) Dialyzing the obtained crude product in deionized water for 3 days, and drying to obtain the caffeic acid modified hydroxypropyl chitosan derivative.

4) 160mg of caffeic acid modified hydroxypropyl chitosan derivative is weighed into a beaker, 3mL of deionized water is added, and the mixture is magnetically stirred until the mixture is dissolved uniformly.

5) Weighing 80mg of acrylamide in another beaker, adding 1mL of deionized water, adding 12.5mg of ammonium persulfate for initiation, and adding 350uL of mixed cross-linking agent oxidized konjac glucomannan and N, N' -methylene bisacrylamide after 20 minutes, wherein the concentration of the oxidized konjac glucomannan is 0.06 g/mL^-1The concentration of N, N' -methylenebisacrylamide was 0.01 g/mL^-1。

6) Adding the mixed solution obtained in the step 5) into the caffeic acid modified hydroxypropyl chitosan derivative solution obtained in the step 4), quickly stirring uniformly, and finally preserving heat at 50 ℃ for 2 hours to obtain the modified hydroxypropyl chitosan adhesive self-healing hydrogel 4.

The compression strength of the hydrogel 4 obtained by the method is 51.6kPa, the adhesion strength to the skin is 17.8kPa, the equilibrium swelling ratio in deionized water reaches 284%, and if the dosage of the mixed cross-linking agent is changed to 150uL, the equilibrium swelling ratio in deionized water is increased to 578% under the same other process conditions, namely the swelling can be increased to 2.04 times.

Other parts not described in detail are prior art. Although the present invention has been described in detail with reference to the above embodiments, it is only a part of the embodiments of the present invention, not all of the embodiments, and other embodiments can be obtained without inventive step according to the embodiments, and the embodiments are within the scope of the present invention.