WO2021037269A1 - Method for preparing polyethyleneimine-polyvinyl alcohol hydrogel having self-healing properties - Google Patents

Abstract

Disclosed is a method for preparing a polyethyleneimine-polyvinyl alcohol hydrogel having self-healing properties. In the present invention, the polyethyleneimine-polyvinyl alcohol hydrogel is prepared using polyethyleneimine, polyvinyl alcohol and a molecule containing a benzene boric acid functional group as raw materials, wherein the molecule containing a benzene boric acid functional group is equivalent to a bridging agent and cross-links two hydrophilic polymers together. The amino group of the polyethyleneimine can react with the aldehyde group or carbonyl group of the molecule containing a benzene boric acid functional group to produce a dynamic reversible imine bond; in addition, the alcoholic hydroxyl group of the polyvinyl alcohol can further react with the boric acid group of the molecule containing a benzene boric acid functional group to produce a dynamic reversible boric acid ester bond; in addition, hydrogen bonding interaction is also present between the polyethyleneimine molecule and the polyvinyl alcohol molecule. By means of the above synergistic effect, a hydrogel that can rapidly self-heal is prepared, and the hydrogel can realize excellent self-healing properties without the need for extra stimulation.

Description

Preparation method of polyethyleneimine-polyvinyl alcohol hydrogel with self-healing properties Technical field

The invention belongs to the technical field of high molecular polymers, and specifically relates to a preparation method of a polyethyleneimine-polyvinyl alcohol hydrogel with self-healing properties.

Background technique

Self-healing hydrogel refers to a gel that can recover its original performance and appearance after a certain period of time after the material is destroyed by external force. Because of its reliability and durability, it is widely used in the fields of biomedicine (tissue adhesives, controlled drug release, etc.) and electrochemistry (soft robots, sensors, artificial skin, etc.).

According to the healing conditions, self-healing hydrogels can be divided into self-healing hydrogels and non-self-healing hydrogels. Automatic self-healing hydrogel, that is, without additional stimulation, such as light, electricity, pH, temperature and other stimuli, self-healing can be achieved. This simplifies the self-healing process, which not only reduces energy consumption, but also facilitates the practical application of the gel. Especially in biomedical applications, additional stimuli such as light and electricity can cause damage to cells, so the self-healing hydrogel has greater advantages.

For the construction of self-healing hydrogels, there are two main methods: one is physical cross-linking, such as the use of hydrogen bonds, ionic bonds, superhydrophobic interactions, host-guest interactions, etc.; the second is chemical cross-linking, the rule is Self-healing hydrogels are constructed by dynamic covalent bonds, such as imine bonds, boronic ester bonds, disulfide bonds, acylhydrazone bonds, etc.

Yixi Wang et al. [Wang Y, Niu J, Hou J, et al. A novel design strategy for triple-network structure hydrogels with high-strength, tough and self-healing properties[J].Polymer,2018,135:16-24 .] A PAA/Agar/PVA triple network hydrogel was constructed. The gel system has self-healing ability due to coordination and hydrogen bonding, and its strain self-healing efficiency reaches 84%.

Christopher C. Deng et al. [Deng C C, Brooks W L A, Abboud K A, et al. Boronic Acid-Based Hydrogels Undergo Self-Healing at Neutral and Acidic pH[J].Acs Macro Letters, 2015, 4(2) :220-224.] Using boric acid-containing block copolymers and PVA as raw materials, through dynamic boronic ester bond and hydrogen bond reaction cross-linking to obtain a room temperature self-healing hydrogel, the hydrogel within 60 minutes Achieve complete self-healing.

Bin Yan et al. [Yan B, Huang J, Han L, et al. Duplicating Dynamic Strain-Stiffening Behavior and Nanomechanics of Biological Tissues in A Synthetic Self-Healing Flexible Network Hydrogel[J]. ACS Nano, 2017:05:05. Using aldehyde-terminated polyethylene glycol and polyethyleneimine as raw materials, a self-healing hydrogel is constructed through dynamic imine bonds and hydrogen bonds. The hydrogel has strain hardening and excellent room temperature self-healing ability.

Summary of the invention

The purpose of the present invention is to overcome the defects of the prior art and provide a method for preparing a polyethyleneimine-polyvinyl alcohol hydrogel with self-healing properties.

The principle of the present invention is as follows:

The invention uses polyethyleneimine, polyvinyl alcohol, and molecules containing phenylboronic acid functional groups as raw materials to prepare polyethyleneimine-polyvinyl alcohol hydrogel. Among them, the molecule containing phenylboronic acid functional group is equivalent to a bridging agent, which cross-links two hydrophilic polymers together. The amino group of polyethyleneimine can react with the aldehyde group or carbonyl group of the molecule containing phenylboronic acid functional group to form a dynamic reversible imine bond; while the alcoholic hydroxyl group of polyvinyl alcohol can react with the boronic acid group of the molecule containing phenylboronic acid functional group to generate dynamic Reversible boron ester bond; at the same time, there is a hydrogen bond between polyethyleneimine and polyvinyl alcohol molecules. Through the above synergistic effects, a hydrogel that can quickly self-heal is prepared, and the hydrogel can achieve excellent self-healing performance without additional stimulation.

The technical scheme of the present invention is as follows:

A preparation method of polyethyleneimine-polyvinyl alcohol hydrogel with self-healing properties, which is characterized in that it comprises the following steps:

(1) Fully mix and dissolve polyvinyl alcohol and solvent at 70-98°C;

(2) After mixing polyethyleneimine and solvent at room temperature, ultrasonic treatment until clear;

(3) After mixing the phenylboronic acid functional group monomer and the solvent at room temperature, ultrasonic treatment until clear;

(4) Mix the material obtained in step (3) with the material obtained in step (2) at room temperature, and ultrasonically treat it until it becomes clear;

(5) Drop the material obtained in step (4) into the material obtained in step (1) at a rate of 0.5-2 drops/s at 70-90°C. After the addition is completed, heat the reaction for 4-8 hours, and then at 50 Heat treatment at ~90°C for 0-9h and cool to obtain the self-healing polyethyleneimine-polyvinyl alcohol hydrogel;

The above-mentioned solvent is made by mixing deionized water and organic solvent in a volume ratio of 1.5-2.5:0.8-1.2, wherein the organic solvent is ethanol, methanol or DMF; the above-mentioned phenylboronic acid functional group monomer is 4-formylphenylboronic acid, 2 -At least one of formylphenylboronic acid and 4-acetylphenylboronic acid.

In a preferred embodiment of the present invention, the polyvinyl alcohol is polyvinyl alcohol 1799 type, with a degree of alcoholysis of 99.8-100%.

In a preferred embodiment of the present invention, the molecular weight of the polyethyleneimine is 600-70,000.

In a preferred embodiment of the present invention, the solvent is formed by mixing deionized water and organic solvent in a volume ratio of 2:1

In a preferred embodiment of the present invention, the mass ratio of the polyethyleneimine to polyvinyl alcohol is 0.5-2:1.

In a preferred embodiment of the present invention, the amount of polyethyleneimine used is 1.0-7.0wt% of the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent.

In a preferred embodiment of the present invention, the amount of the polyvinyl alcohol is 3.0-3.5 wt% of the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent.

In a preferred embodiment of the present invention, the amount of the monomer containing phenylboronic acid functional group is 0-1.0wt% of the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent.

In a preferred embodiment of the present invention, the amount of the solvent is 88.5-96% by weight of the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent.

In a preferred embodiment of the present invention, the amount of polyethyleneimine is 1.0-7.0wt% of the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent. The amount used is 3.0-3.5wt% of the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent, and the amount of the phenylboronic acid functional group-containing monomer is polyethyleneimine, polyvinyl alcohol, benzene The total amount of the boric acid functional group monomer and the solvent is 0-1.0 wt%, and the amount of the solvent is 88.5-96 wt% of the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and the solvent.

The beneficial effects of the present invention are:

1. The polyvinyl alcohol used in the present invention has good biocompatibility, biodegradability, and non-toxicity; and the low-molecular-weight branched polyethyleneimine is a highly cationic water-soluble polymer with low toxicity. It contains a large number of amino groups and is easy to cross-link, and it has been repeatedly shown in the literature to have high drug-carrying capacity.

2. The boronic ester bond in the gel system of the present invention is dynamically reversible and responsive to glucose. The phenylboronic acid group will preferentially react with the o-dihydroxyl group of small molecule glucose, so it can be used for insulin drug release;

3. The active groups (such as amino groups, aldehyde groups, etc.) contained in the gel of the present invention also have a drug-carrying function.

4. The gel of the present invention not only has excellent biocompatibility and biodegradability, but also has rapid self-healing properties, and has potential applications in controlled drug release and the like.

5. The synthesis method of the present invention has simple process, easy operation, and relatively mild reaction conditions. The synthesized hydrogel has a rapid room temperature self-healing function, and its strain self-healing efficiency can reach 100% within 2 minutes.

Description of the drawings

Figure 1 is a reaction equation for the preparation of polyethyleneimine-polyvinyl alcohol hydrogels prepared in Examples 1-9 of the present invention.

Figure 2 is an optical picture of the polyethyleneimine-polyvinyl alcohol hydrogel prepared in Example 2 of the present invention;

Fig. 3 is an infrared spectrum diagram of the polyethyleneimine-polyvinyl alcohol hydrogel prepared in Example 2 of the present invention.

4 is an SEM image of the polyethyleneimine-polyvinyl alcohol hydrogel prepared in Example 2 of the present invention, where a is an SEM image at 200 times the cross section, and b is an SEM image at 500 times the cross section.

Fig. 5 is the stress-strain curve of the polyethyleneimine-polyvinyl alcohol hydrogel prepared in Example 5 of the present invention before and after healing.

6 is a diagram of the self-healing process of the polyethyleneimine-polyvinyl alcohol hydrogel prepared in Example 1 of the present invention.

detailed description

The technical solutions of the present invention will be further illustrated and described below through specific implementations in conjunction with the accompanying drawings.

The reaction principle of the following examples is shown in Figure 1. The polyvinyl alcohol is polyvinyl alcohol type 1799, and the degree of alcoholysis is 99.8-100%.

Example 1:

Weigh 2g polyvinyl alcohol (PVA) dissolved in 40mL deionized water and dissolve it at 90℃ for 3.5h; 2g polyethyleneimine (PEI1800) dissolved in 10mL ethanol, ultrasonic for 40min; weigh 0.15g 4-formylphenylboronic acid to dissolve In 10mL ethanol, ultrasonic for 2min; add 4-formylphenylboronic acid to the PEI solution at room temperature, mix and ultrasonic for 30min, drop into the polyvinyl alcohol solution at 80℃, react for 6h to obtain a uniform viscous solution, and then Pour it into a beaker, heat-treat it at 60°C for 5h, and cool to obtain the hydrogel PEI-PVA-1.

Table 1 The amount of each component in the embodiment

(Note: The strain self-healing efficiency is calculated based on the stress-strain curve of the gel, that is, the ratio of the maximum strain of the gel after 2 minutes of healing to the maximum strain of the initial gel sample.)

Control group: Weigh 2g polyvinyl alcohol (PVA) and dissolve it in 40mL deionized water, dissolve it at 95℃ for 1.5h; dissolve 2g polyethyleneimine (PEI1800) in 20mL ethanol, ultrasound for 30min; dissolve the polyethylene at 80℃ The imine solution was dropped into the polyvinyl alcohol solution and reacted for 6 hours to obtain a transparent solution. Then it was poured into a beaker and heat-treated at 70° C. for 8 hours. After cooling, no hydrogel was formed.

Through this control experiment, it can be found that 4-formylphenylboronic acid has a promoting effect on the formation of hydrogel, indicating that the system only relies on hydrogen bonding and cannot form a gel. With the help of the formation of dynamic covalent bonds between the small molecule cross-linking agent and the polymer, the cross-linking between the two polymers is promoted.

Example 2:

Weigh 2g polyvinyl alcohol (PVA) and dissolve it in 40mL deionized water and dissolve it at 90℃ for 3.5h; 2g polyethyleneimine (PEI1800) dissolve in 10mL ethanol and ultrasound for 40min; Weigh 0.30g 4-formylphenylboronic acid to dissolve In 10mL ethanol, ultrasonic for 2min; add 4-formylphenylboronic acid to the PEI solution at room temperature, mix and ultrasonic for 30min, drop into the polyvinyl alcohol solution at 80℃, react for 6h to obtain a uniform viscous solution, and then Pour it into a beaker, heat-treat it at 60°C for 3 hours, and cool to obtain the hydrogel PEI-PVA-2, as shown in Figure 2.

Example 3:

Weigh 2g polyvinyl alcohol (PVA) and dissolve it in 40mL deionized water, and dissolve it at 90℃ for 3.5h; 2g polyethyleneimine (PEI1800) is dissolved in 10mL ethanol, ultrasonic for 30min; Weigh 0.45g 4-formylphenylboronic acid to dissolve In 10mL ethanol, ultrasonic for 2min; add 4-formylphenylboronic acid to the PEI solution at room temperature, mix and ultrasonic for 20min, drop into the polyvinyl alcohol solution at 80℃, react for 5h to obtain a uniform viscous solution, and then Pour it into a beaker, heat-treat it at 60°C for 1 hour, and cool to obtain the hydrogel PEI-PVA-3.

Example 4:

Weigh 2g polyvinyl alcohol (PVA) and dissolve it in 40mL deionized water, and dissolve it at 90℃ for 3.5h; 2g polyethyleneimine (PEI600) dissolve in 10mL ethanol, ultrasonic for 40min; Weigh 0.15g 4-formylphenylboronic acid to dissolve In 10mL ethanol, ultrasonic for 2min; add 4-formylphenylboronic acid to the PEI solution at room temperature, mix and ultrasonic for 30min, drop into the polyvinyl alcohol solution at 80℃, react for 6h to obtain a uniform viscous solution, and then Pour it into a beaker, heat-treat it at 80°C for 7 hours, and cool to obtain the hydrogel PEI-PVA-4.

Example 5:

Weigh 2g polyvinyl alcohol (PVA) and dissolve it in 40mL deionized water, and dissolve it at 90℃ for 3.5h; 2g polyethyleneimine (PEI10000) dissolve in 10mL ethanol, ultrasound for 60min; Weigh 0.15g 4-formylphenylboronic acid to dissolve In 10mL ethanol, ultrasonic for 2min; add 4-formylphenylboronic acid to the PEI solution at room temperature, mix and ultrasonic for 30min, drop into the polyvinyl alcohol solution at 80℃, react for 6h to obtain a uniform viscous solution, and then Pour it into a beaker, heat-treat it at 60°C for 4h, and cool to obtain the hydrogel PEI-PVA-5.

The steps in Examples 6-11 are the same as in Example 1, and the dosage of each component and its strain self-healing efficiency are shown in Table 1.

3 is an infrared spectrum diagram of the polyethyleneimine-polyvinyl alcohol hydrogel prepared in Example 2. The spectra show: ^-1 -OH, -NH2 vibration absorption peak of 3275cm, 2918,2829cm ^-1 vibration absorption peak of methylene group, the presence of polyvinyl alcohol and polyethyleneimine described above. 1568, 1454 cm ^-1 is the characteristic absorption peak of the benzene ring skeleton, and 811 cm ^-1 is the out-of-plane bending vibration peak of the p-disubstituted aryl CH. The introduction of 4-formylphenylboronic acid molecules is explained above. At 1645 cm ^-1 is the characteristic absorption peak of C=N bond, indicating that the amino group of polyethyleneimine reacts with the aldehyde group of 4-formylphenylboronic acid molecule; in addition, 1371 cm ^-1 is the characteristic peak of BOC bond, indicating that boron The formation of ester bonds.

4 is an SEM image of the polyethyleneimine-polyvinyl alcohol hydrogel prepared in Example 2. It can be seen from the SEM image that the prepared hydrogel has a traditional three-dimensional network structure (Figure 4a); and it has a micron-scale pore structure with a size of about 10 μm (Figure 4b). The porous structure of the hydrogel system is also conducive to drug loading and controlled release.

Fig. 5 is the tensile stress-strain curve of the polyethyleneimine-polyvinyl alcohol hydrogel prepared in Example 5 before and after healing. From the figure, the black line is the stress-strain curve of the initial sample, its strength is about 60kPa, and the elongation at break can reach 1400%; the red line is the stress-strain curve of the sample after 2 minutes of healing, which is the curve of the initial sample Basically agree. According to corresponding calculations, the strain self-healing efficiency of the hydrogel can reach 100%, indicating that it has excellent room temperature self-healing ability.

6 is a diagram of the self-healing process of the polyethyleneimine-polyvinyl alcohol hydrogel prepared in Example 1. Firstly, the hydrogel is made into 3 small balls, and one of the spherical gels is dyed; then the 3 spherical gels are brought into contact with each other, and after 2 minutes, they can be lifted with tweezers, indicating that the hydrogel can withstand Self-respect, and further demonstrated its rapid self-healing behavior.

The above are only the preferred embodiments of the present invention, so the scope of implementation of the present invention cannot be limited accordingly. That is, equivalent changes and modifications made according to the scope of the patent of the present invention and the contents of the specification should still be covered by the present invention. In the range.

Industrial applicability

The invention discloses a preparation method of polyethyleneimine-polyvinyl alcohol hydrogel with self-healing properties. In the present invention, polyethyleneimine, polyvinyl alcohol, and molecules containing phenylboronic acid functional groups are used as raw materials to prepare polyethyleneimine-polyvinyl alcohol hydrogel. Among them, the molecule containing phenylboronic acid functional group is equivalent to a bridging agent, which cross-links two hydrophilic polymers together. The amino group of polyethyleneimine can react with the aldehyde group or carbonyl group of the molecule containing phenylboronic acid functional group to form a dynamic reversible imine bond; while the alcoholic hydroxyl group of polyvinyl alcohol can react with the boronic acid group of the molecule containing phenylboronic acid functional group to generate dynamic Reversible boron ester bond; at the same time, there is a hydrogen bond between polyethyleneimine and polyvinyl alcohol molecules. Through the above synergistic effects, a hydrogel that can quickly self-heal is prepared, and the hydrogel can achieve excellent self-healing performance without additional stimulation, and has industrial practicability.

Claims (10)

1. A preparation method of polyethyleneimine-polyvinyl alcohol hydrogel with self-healing properties, which is characterized in that it comprises the following steps:

   (1) Fully mix and dissolve polyvinyl alcohol and solvent at 70-98°C;

   (2) After mixing polyethyleneimine and solvent at room temperature, ultrasonic treatment until clear;

   (3) After mixing the phenylboronic acid functional group monomer and the solvent at room temperature, ultrasonic treatment until clear;

   (4) Mix the material obtained in step (3) with the material obtained in step (2) at room temperature, and ultrasonically treat it until it becomes clear;

   (5) Drop the material obtained in step (4) into the material obtained in step (1) at a rate of 0.5-2 drops/s at 70-90°C. After the addition is completed, heat the reaction for 4-8 hours, and then at 50 Heat treatment at ~90°C for 0-9h and cool to obtain the self-healing polyethyleneimine-polyvinyl alcohol hydrogel;

   The above-mentioned solvent is made by mixing deionized water and organic solvent in a volume ratio of 1.5-2.5:0.8-1.2, wherein the organic solvent is ethanol, methanol or DMF; the above-mentioned phenylboronic acid functional group monomer is 4-formylphenylboronic acid, 2 -At least one of formylphenylboronic acid and 4-acetylphenylboronic acid.
2. The preparation method according to claim 1, wherein the polyvinyl alcohol is polyvinyl alcohol type 1799, with a degree of alcoholysis of 99.8-100%.
3. The preparation method according to claim 1, wherein the molecular weight of the polyethyleneimine is 600-70,000.
4. The preparation method according to claim 1, wherein the solvent is formed by mixing deionized water and organic solvent in a volume ratio of 2:1
5. The preparation method according to any one of claims 1 to 4, wherein the mass ratio of the polyethyleneimine to polyvinyl alcohol is 0.5-2:1.
6. The preparation method according to any one of claims 1 to 4, wherein the amount of polyethyleneimine is the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent 1.0-7.0wt%.
7. The preparation method according to any one of claims 1 to 4, wherein the amount of the polyvinyl alcohol is 3.0 of the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent. -3.5wt%.
8. The preparation method according to any one of claims 1 to 4, wherein the amount of the monomer containing phenylboronic acid functional group is the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent. The amount of 0-1.0wt%.
9. The preparation method according to any one of claims 1 to 4, wherein the amount of the solvent is 88.5-96wt% of the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent. %.
10. The preparation method according to any one of claims 1 to 4, wherein the amount of polyethyleneimine is the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent 1.0-7.0wt%, the amount of the polyvinyl alcohol is 3.0-3.5wt% of the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent, the amount of the phenylboronic acid functional group monomer It is 0-1.0wt% of the total amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent, and the amount of the solvent is the amount of polyethyleneimine, polyvinyl alcohol, phenylboronic acid functional group monomer and solvent 88.5-96wt% of the total.

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