CN113521380B

CN113521380B - Rapid polymerization hydrogel material and preparation method and application thereof

Info

Publication number: CN113521380B
Application number: CN202110742293.0A
Authority: CN
Inventors: 王婷; 蔡成龙; 韩旭; 张译心
Original assignee: Southeast University
Current assignee: Southeast University
Priority date: 2021-06-30
Filing date: 2021-06-30
Publication date: 2022-12-13
Anticipated expiration: 2041-06-30
Also published as: CN113521380A

Abstract

The invention discloses a rapid polymerization hydrogel material and a preparation method and application thereof, wherein the hydrogel is prepared by taking sodium carboxymethylcellulose, glacial acetic acid, glucose and chitosan as raw materials to rapidly obtain an antibacterial and breathable thin-layer hydrogel, and is expected to be used for rapid healing of superficial skin injury. The preparation process is simple, no waste is generated, the rapid film formation of the thin-layer hydrogel can be realized only by simple mixing, and the material shows better physicochemical and biological properties compared with the related materials in the current market, wherein the sodium carboxymethyl cellulose ensures the pharmaceutical activity to the maximum extent, the chitosan ensures the antibacterial property, and the glucose is used as a crosslinking point to promote the material to form a gel structure.

Description

Rapid polymerization hydrogel material and preparation method and application thereof

Technical Field

The invention belongs to biological materials, and particularly relates to a rapid polymerization hydrogel material, and a preparation method and application thereof.

Background

The skin is the largest organ of the human body, is the first line of defense between the human body and the outside, and has the functions of resisting the invasion of outside bacteria, maintaining the balance of body fluid and electrolyte, regulating body temperature and the like. However, in life, the skin is inevitably injured for various reasons, and the structural tissues of the skin are damaged.

The requirements for the superficial skin repair material at present are as follows: 1. can prevent bacterial contamination and infection; 2. can promote wound healing; 3. can reduce the adhesivity of granulation tissues and dressing in the healing process and reduce the secondary damage to the wound. At present, the following types of biological materials are basically adopted in superficial skin repair: 1. biological tissue dressing: primarily in the skin and connective tissue of animals, but the lack of a source of this material has also limited the development of biological tissue dressings. 2. Synthesizing a polymer dressing: the formed film has good barrier effect, but has no defects of bacterial infection resistance, poor moisture retention performance and the like. 3. Film-based synthetic dressing: has certain isolation capacity, but is more easy to cause pathogen invasion after seepage is saturated. 4. Natural polymer: has good biocompatibility and no antigenicity, can adapt to human skin, and can promote cell differentiation. For example, chitosan has good biocompatibility, biodegradability, low immunogenicity, safety, non-toxicity, and other functions. In the process of repairing a wound surface, the wound surface can be subjected to hemostasis, antibiosis and antiphlogosis, the synthesis of wound surface tissue collagen is stimulated, macrophages are rapidly activated, and the healing of the wound surface is accelerated (Arkoun M, daigle F, holley R A, et al. For example, the chitosan solution is added into the scar liquid by Luwangwang people and other people, so that the excessive proliferation of fibroblasts can be well inhibited, the scar formation is further caused, the establishment of a wound granulation tissue circulatory system is accelerated, and the wound granulation tissue circulatory system is closer to normal skin (application research of the Chitosan skin care liquid in skin scar repair [ J ]. Scientific and technical wind 2017 (11): 261 ]). The sodium carboxymethyl cellulose has good biocompatibility and film forming property, has good entrapment capability on active substances, and can be used for releasing carrier drugs. For example, li Van et al added bentonite into sodium carboxymethylcellulose for controlling the release of acetochlor and achieving good slow release effect (Li Van. Carboxymethyl cellulose based gel carrier preparation and its controlled release research [ D ]. Suzhou university, 2007). However, the production process is complex, and a large amount of toxic reagents are required for modification. In conclusion, although there is a breakthrough in preparing a material capable of rapidly polymerizing and repairing superficial skin, each material still has the disadvantages of complex operation and various processes, and thus continuous improvement and optimization are still needed.

Disclosure of Invention

The purpose of the invention is as follows: aiming at the problems in the prior art, the rapid polymerization hydrogel material and the preparation method thereof have the advantages that compared with the existing natural polymer composite material, the preparation method is simpler, the rapid polymerization hydrogel material can be prepared by simple mixing, and the preparation method is simple, practical and environment-friendly and has the same performance as the existing material.

The invention also provides a hydrogel material prepared by the preparation method and application.

The technical scheme is as follows: in order to achieve the above object, the present invention provides a method for preparing a rapid polymerization hydrogel material for wound repair, comprising the following steps:

a. in deionized water, naHCO was added ₃ Mixing to prepare sodium bicarbonate water solution;

b. adding sodium carboxymethylcellulose into the solution obtained in the step a, and fully stirring to obtain a mixed solution;

c. b, after the solution in the step b is stable, adding glucose, and uniformly stirring to obtain a solution A;

d. adding glacial acetic acid in the deionized water, and uniformly stirring;

e. adding chitosan into the solution obtained in the step d, and uniformly stirring to obtain a solution B;

f. and mixing the two solutions A and B to form the hydrogel.

Wherein, in the step a, 0.005-0.008mol of NaHCO is added into 10mL of deionized water ₃ 。

Preferably, in the step a, 0.005mol of NaHCO is added into 10mL of deionized water ₃ 。

Wherein, in the step b, 0.02-0.09 g of sodium carboxymethyl cellulose is added into the step a, and the mixture is fully stirred to obtain a mixed solution.

Preferably, 0.05g of sodium carboxymethyl cellulose is added in step b to step a.

Wherein, in the step c, 0.08-0.1g of glucose is added after the solution in the step b is stabilized, and the mixture is uniformly stirred to obtain a mixed solution A.

Wherein, in the step d, glacial acetic acid is added into 10mL of deionized water to ensure that the concentration of the glacial acetic acid in the solution reaches 0.01-0.2 mol/L, and the mixture is stirred uniformly.

Preferably, 0.06mL of glacial acetic acid is added to 10mL of deionized water in step d, and the mixture is stirred uniformly.

Wherein, 0.04-0.06g of chitosan is added into the solution in the step d in the step e, and the mixture is stirred uniformly to obtain a mixed solution B.

Preferably, in step e, 0.04g of chitosan is added to the solution in step d, and the mixture is stirred uniformly to obtain a mixed solution B.

Wherein, in the step f, the mixed solution A and the mixed solution B are mixed according to the volume ratio of 1:0.5 to 2 are mixed evenly and then are processed for 10 to 60 seconds.

Preferably, the two solutions A and B are mixed at 37 ℃ in a volume ratio of 1:1, mixing uniformly and then performing 10s to form the hydrogel.

The degradable rapid polymerization hydrogel material prepared by the preparation method of the rapid polymerization hydrogel material for wound repair is provided by the invention.

The application of the rapid polymerization hydrogel material in the preparation of a superficial skin repair medicament can realize superficial skin repair.

The invention constructs the hydrogel with the network structure based on the principle that anionic high polymer sodium carboxymethyl cellulose and natural cationic high polymer chitosan rapidly polymerize at normal temperature. The sodium bicarbonate glucose solution can ensure that the sodium carboxymethyl cellulose can stably exist at normal temperature without agglomeration. In addition, the sodium carboxymethyl cellulose and the chitosan react rapidly to form gel, so that blood can be absorbed and blood vessels can be compressed to achieve the aim of stopping bleeding; the chitosan as a broad-spectrum antibacterial material can effectively inhibit the growth of bacteria, reduce the inflammatory reaction of epidermis and accelerate the healing capacity of the epidermis. Compared with the hydrogel dressing prepared by directly utilizing chitosan or sodium carboxymethylcellulose at present, the hydrogel dressing is more convenient, easier to store and convenient to carry.

At present, the main material of the water dressing adopted at home and abroad is a low-molecular-weight rubber material, and an antibacterial and anti-inflammatory material is added, for example, styrene is used as the main material in the US4551490 patent by the American Shi Gui Bao company, so that the service life is prolonged, but the material cannot be degraded, and can only be peeled off in a tearing manner when needing to be replaced, so that secondary damage is caused. The material disclosed by the invention only needs to spray the liquid on the wound in a spraying manner, so that secondary damage is avoided. Furthermore, the rubber articles of interest absorb little water and do not absorb wound exudate completely, resulting in a decrease in the adhesive properties of the material, as proposed in european patent EP0617938 to construct porous discontinuous structures to absorb and channel liquids. The invention adopts sodium carboxymethyl cellulose material, which can absorb wound exudate well and accelerate the repair speed.

In addition, the present invention enables rapid formation of hydrogels. The chitosan is polycation polysaccharide, has active amino and hydroxyl, has good histocompatibility, no toxicity, no sensitization, no blood dissolution, and no residue degradation. The sodium carboxymethyl cellulose is easy to degrade in a human body and can be completely absorbed by the human body, so the invention is a degradable rapid polymerization hydrogel material.

Has the advantages that: compared with the prior art, the invention has the following advantages:

the invention provides a brand-new preparation method of a rapid polymerization hydrogel material for wound repair, the preparation process is simple to operate, and no waste is generated. Compared with the existing chitosan composite material preparation method, the preparation method disclosed by the invention can be realized only by simple mixing, is simple, practical and environment-friendly, and has the advantages of higher film forming speed (10 s film forming), higher wound healing speed (see figure 4), multi-layer ventilation and the like compared with the existing chitosan hydrogel dressing in the market. Compared with other preparation methods, the chitosan serves as an antibacterial natural polymer, inflammatory reaction caused by bacteria invasion can be effectively reduced, the antibacterial performance of the chitosan is guaranteed, the sodium carboxymethyl cellulose serves as an active drug carrier, the drug activity is guaranteed to the maximum extent, long-time continuous drug release of the active drug is guaranteed, the glucose serves as a cross-linking point, the material forms gel with a certain shape, and the material is guaranteed to form a gel structure.

Drawings

FIG. 1 is a graph showing a glacial acetic acid solution of chitosan prepared in example 3, from which it can be seen that chitosan has been completely dissolved in the glacial acetic acid solution, and no layering solution is uniformly mixed;

FIG. 2 is a drawing of the sodium carboxymethylcellulose, sodium hydrogen gluconate carbonate solution prepared in example 3, from which it can be seen that the various components have completely dissolved to form a uniform stable colloidal solution;

FIG. 3 is a gel of the two solutions of example 3 after mixing, and it can be seen that the two solutions crosslink after mixing to form a clear gel;

FIG. 4 shows the healing of a wound after 4 days when the gel prepared in example 3 of the present invention was applied to the wound of a mouse (the left figure shows the gel of the present invention);

FIG. 5 shows the healing of a wound 14 days after the gel prepared in example 3 of the present invention was applied to the wound of a mouse (the left figure shows the gel of the present invention).

Detailed Description

The present invention will be described in detail with reference to specific examples.

The experimental methods described in the examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.

Example 1

Taking deionized water as a solvent, taking 10mL of deionized water, and adding 0.005mol of NaHCO ₃ And stirring fully. Then 0.01g of sodium carboxymethylcellulose is added and fully stirred; after the solution is completely clarified, 0.08g of glucose is added again, and the solution A is obtained after even stirring; adding glacial acetic acid into 10mL of deionized water solution to enable the concentration of the glacial acetic acid solution to reach 0.1mol/L, uniformly stirring, then adding 0.04g of chitosan, and uniformly stirring to obtain a solution B. The volume ratio of the two solutions A and B is 1:1 was mixed homogeneously at 37 ℃ and no gel was formed after 10 s.

Example 2

Taking 10mL of deionized water as a solvent, and adding 0.005mol of NaHCO ₃ And stirring fully. Then adding 0.1g of sodium carboxymethylcellulose, fully stirring, adding 0.08g of glucose again after the solution is completely clarified, and uniformly stirring to obtain a solution A; adding glacial acetic acid into 10mL of deionized water solution to enable the concentration of the glacial acetic acid in the solution to reach 0.1mol/L, uniformly stirring, then adding 0.04g of chitosan, and uniformly stirring to obtain a solution B. The volume ratio of the two solutions A and B is 1:1, mixing uniformly at 37 ℃ for 10s, but the sodium carboxymethyl cellulose solution is layered and still layered after being fully stirred, and the two solutions cannot form gel after being mixed.

Example 3

Taking 10mL of deionized water as a solvent, and adding 0.005mol of NaHCO ₃ Fully stirring; then 0.05g of sodium carboxymethyl cellulose is added and fully stirred; after the solution is completely clarified, adding 0.08g of glucose again, and uniformly stirring to obtain a solution A; adding glacial acetic acid into 10mL of deionized water solution to enable the concentration of the glacial acetic acid in the solution to reach 0.1mol/L, uniformly stirring, then adding 0.04g of chitosan, and uniformly stirring to obtain a solution B. The volume ratio of the solution A to the solution B is 1:1 at 37 ℃ and forming gel after 10 s. As shown in fig. 1-3, chitosan has been completely dissolved in glacial acetic acid solution, and no layering solution is mixed uniformly; the sodium carboxymethyl cellulose, the glucose and the sodium bicarbonate solution are completely dissolved to form uniform and stable colloidal solution; the two solutions cross-link upon mixing to form a clear gel.

Example 4

Taking deionized water as a solvent, taking 10mL of deionized water, and adding 0.005mol of NaHCO ₃ Stirring fully. Then 0.02g of sodium carboxymethylcellulose is added and fully stirred; after the solution is clarified, adding 0.08g of glucose again, and uniformly stirring to obtain a solution A; adding glacial acetic acid into 10mL of deionized water solution to enable the concentration of the glacial acetic acid in the solution to reach 0.1mol/L, uniformly stirring, then adding 0.04g of chitosan, and uniformly stirring to obtain a solution B. The volume ratio of the two solutions A and B is 1:0.5, mixing evenly at 37 ℃, and forming no gel after 10 s; after 1min, a thin film was formed.

Example 5

Taking 10mL of deionized water as a solvent, and adding 0.005mol of NaHCO ₃ Stirring fully. Then 0.03g of sodium carboxymethylcellulose is added and fully stirred; after the solution is clarified, 0.08g of glucose is added again, and the solution A is obtained after even stirring; adding glacial acetic acid into 10mL of deionized water solution to enable the concentration of the glacial acetic acid in the solution to reach 0.1mol/L, uniformly stirring, then adding 0.04g of chitosan, and uniformly stirring to obtain a solution B. The volume ratio of the two solutions A and B is 1:1, mixing uniformly at 37 ℃, and forming gel after 10 seconds.

Example 6

Taking 10mL of deionized water as a solvent, and adding 0.005mol of NaHCO ₃ And stirring fully. Then 0.09g of sodium carboxymethylcellulose is added and fully stirred; after the solution is clarified, 0.08g of glucose is added again, and the solution A is obtained after even stirring; adding glacial acetic acid into 10mL of deionized water solution to enable the concentration of the glacial acetic acid in the solution to reach 0.1mol/L, uniformly stirring, then adding 0.04g of chitosan, and uniformly stirring to obtain a solution B. The volume ratio of the two solutions A and B is 1:2 mixing at 37 ℃Mixing uniformly, and forming gel after 10 s.

In the examples, the quality of sodium carboxymethylcellulose was used as a variable to prepare degradable rapid polymerization hydrogel materials to obtain the best quality of sodium carboxymethylcellulose for preparing materials. Exceeding the defined ratio cannot be achieved.

Example 7

Taking 10mL of deionized water as a solvent, and adding 0.008mol of NaHCO ₃ Fully stirring; then 0.05g of sodium carboxymethylcellulose is added and fully stirred; after the solution is completely clarified, adding 0.1g of glucose again, and uniformly stirring to obtain a solution A; adding glacial acetic acid into 10mL of deionized water solution to enable the concentration of the glacial acetic acid in the solution to reach 0.2mol/L, uniformly stirring, then adding 0.06g of chitosan, and uniformly stirring to obtain a solution B. The volume ratio of the solution A to the solution B is 1:1 at 25 ℃ for 60s to form a gel.

Comparative example 1

Taking 10mL of deionized water as a solvent, and adding 0.008mol of NaHCO ₃ Fully stirring; then 0.05g of sodium carboxymethylcellulose is added and fully stirred; after the solution is completely clarified, uniformly stirring to obtain a solution A; adding glacial acetic acid into 10mL of deionized water solution to enable the concentration of the glacial acetic acid in the solution to reach 0.2mol/L, uniformly stirring, then adding 0.06g of chitosan, and uniformly stirring to obtain a solution B. The volume ratio of the two solutions A and B is 1:1 at 25 ℃ and after 60s, no gel could be formed.

Test example 1

The gel prepared in example 3 of the present invention was sprayed on the wounds of mice, and the healing effect was observed for 4 days and 14 days, and it was found that the wounds were remarkably healed (fig. 4, fig. 5). Compared with the similar dressing (Chuangyushu compound amino acid liposome nutritional dressing and the like) in the current market, the auxiliary material prepared by the invention has more obvious effect of promoting wound healing by using the same dosage for treatment, and the wound is obviously drier without secretion, so that the skin dressing prepared by the invention can be used for treating the skin in the following ways: 1. the blood is absorbed and the blood vessel is pressed to achieve the aim of stopping bleeding; 2. the wound exudate can be well absorbed, and the repair speed is accelerated; 3. the hydrogel can be directly sprayed to form a film, so that the hydrogel is more convenient to use, store and carry.

Claims

1. A preparation method of a rapid polymerization hydrogel material for wound repair is characterized by comprising the following steps:

a. to 10mL of deionized water, 0.005mol NaHCO was added ₃ Mixing to prepare sodium bicarbonate water solution;

b. b, adding 0.05g of sodium carboxymethylcellulose into the solution obtained in the step a, and fully stirring to obtain a mixed solution;

c. after the solution in the step b is stable, adding 0.08g of glucose, and uniformly stirring to obtain a solution A;

d. adding glacial acetic acid into 10mL of deionized water to ensure that the concentration of the glacial acetic acid in the solution reaches 0.1mol/L, and uniformly stirring;

e. adding 0.04g of chitosan into the solution obtained in the step d, and uniformly stirring to obtain a solution B;

f. and (3) mixing the two solutions A and B according to a volume ratio of 1:1, mixing uniformly at 37 ℃, and forming gel after 10 seconds.

2. A preparation method of a rapid polymerization hydrogel material for wound repair is characterized by comprising the following steps:

b. adding 0.03g of sodium carboxymethylcellulose into the solution obtained in the step a, and fully stirring to obtain a mixed solution;

3. A preparation method of a rapid polymerization hydrogel material for wound repair is characterized by comprising the following steps:

b. adding 0.09g of sodium carboxymethylcellulose into the solution obtained in the step a, and fully stirring to obtain a mixed solution;

f. and (3) mixing the two solutions A and B according to a volume ratio of 1:2, mixing uniformly at 37 ℃, and forming gel after 10 seconds.

4. A method for preparing a rapid polymerization hydrogel material for wound repair, comprising the steps of:

a. to 10mL of deionized water, 0.008mol NaHCO was added ₃ Mixing to prepare sodium bicarbonate water solution;

b. adding 0.05g of sodium carboxymethylcellulose into the solution obtained in the step a, and fully stirring to obtain a mixed solution;

c. after the solution in the step b is stable, adding 0.1g of glucose, and uniformly stirring to obtain a solution A;

d. adding glacial acetic acid into 10mL of deionized water to ensure that the concentration of the glacial acetic acid in the solution reaches 0.2mol/L, and uniformly stirring;

e. adding 0.06g of chitosan into the solution obtained in the step d, and uniformly stirring to obtain a solution B;

f. and (3) mixing the two solutions A and B according to a volume ratio of 1:1 at 25 ℃ and forming a gel after 60s.

5. A rapidly polymerizing hydrogel material for wound repair prepared by the method for preparing a rapidly polymerizing hydrogel material for wound repair of any one of claims 1 to 4.

6. Use of the rapidly polymerizing hydrogel material of claim 5 in the preparation of a superficial skin repair material.