A hydrogel with a fast formation rate, its preparation method and applications

Abstract

The present invention belongs to the technical field of polymer materials, and discloses a hydrogel with a fast formation rate, a preparation method thereof and an application. The raw materials for preparing the hydrogel include: a polypeptide containing free amino groups, an oxidant, and 2,3,4-trihydroxybenzaldehyde. By using the polypeptide containing free amino groups, the oxidant, and 2,3,4-trihydroxybenzaldehyde as the raw materials for preparing the hydrogel, the present invention greatly improves the formation rate of the hydrogel, and has good biocompatibility, swelling property and antibacterial property, thus having broad application prospects in the field of medical dressings.

Description

Technical Field

[0001] The present invention belongs to the technical field of polymer materials, and particularly relates to a hydrogel with a fast formation rate, a preparation method thereof, and an application thereof. Background Art

[0002] A hydrogel is a polymer with a three-dimensional microstructure. It can not only swell in water without losing the integrity of its structure, but also has excellent softness, biocompatibility, and permeability. It is one of the most promising materials in the current biomedical field. Although there are many existing hydrogel products, they generally have the problems of slow hydrogel reaction speed and long formation time, which greatly restricts the application of hydrogel products in medical dressings. Therefore, the present invention hopes to propose a hydrogel product with a faster formation rate to better meet the actual application needs. Summary of the Invention

[0003] The present invention aims to solve at least one of the technical problems existing in the above-mentioned prior art. For this purpose, the present invention provides a hydrogel with a fast formation rate, a preparation method thereof, and an application thereof. The hydrogel has the characteristics of good swelling property and excellent antibacterial performance, and has a fast formation rate, and has good application prospects in medical materials.

[0004] The present invention provides a hydrogel with a fast formation rate. The raw materials for preparing the hydrogel include: a polypeptide containing free amino groups, an oxidant, and 2,3,4-trihydroxybenzaldehyde.

[0005] Since the aldehyde group on 2,3,4-trihydroxybenzaldehyde (TBH) can directly react with the amino group on the polypeptide to form a Schiff base reaction, that is, preliminary cross-linking can be quickly achieved. And the oxidant will further oxidize the phenolic hydroxyl group at the 4th position of 2,3,4-trihydroxybenzaldehyde into a quinone compound, and the quinone compound contains a carbonyl group, which can also react with the free amino group on the polypeptide to form a Schiff base reaction. In addition, through the hydrogen bond force directly between the phenolic hydroxyl groups at the 2nd and 3rd positions of 2,3,4-trihydroxybenzaldehyde, better and faster cross-linking can be achieved, and finally the hydrogel can be quickly formed. At the same time, 2,3,4-trihydroxybenzaldehyde is a biocompatible reagent and has a certain antibacterial and bacteriostatic effect, which can enhance the antibacterial ability and biocompatibility of the prepared hydrogel.

[0006] Preferably, the polypeptide containing free amino groups is polylysine (EPL). Compared with other types of polypeptides, polylysine contains more free amino groups, which can better undergo Schiff base reaction for better cross-linking. Moreover, polylysine also has good biocompatibility and excellent antibacterial performance, which can make the prepared hydrogel have the characteristics of high safety and strong antibacterial property.

[0007] Preferably, the mass ratio of the polypeptide containing free amino groups to 2,3,4-trihydroxybenzaldehyde is (3-5):1.

[0008] Preferably, the oxidant is hydrogen peroxide.

[0009] Preferably, the raw materials for preparing the hydrogel further include at least one of alkalis and alkaline buffers.

[0010] More preferably, the alkalis include at least one of sodium hydroxide and potassium hydroxide.

[0011] More preferably, the alkaline buffer is Tris-HCl buffer.

[0012] The present invention also provides a preparation method of the above-mentioned hydrogel with a fast formation speed, including the following steps:

[0013] (1) React a polypeptide containing free amino groups and 2,3,4-trihydroxybenzaldehyde under alkaline conditions;

[0014] (2) Then add an oxidant and let it stand to obtain the hydrogel.

[0015] By controlling the reaction conditions to be an alkaline environment, 2,3,4-trihydroxybenzaldehyde can be better dissolved and the occurrence of the Schiff base reaction can be promoted, further accelerating the reaction speed.

[0016] Preferably, the standing time is 4 - 8 min.

[0017] More preferably, the standing time is 5 min.

[0018] The present invention also provides an application of the above-mentioned hydrogel in the preparation of medical dressings.

[0019] The present invention also provides a medical dressing, including the above-mentioned hydrogel.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0021] The present invention uses a polypeptide containing free amino groups, an oxidant and 2,3,4-trihydroxybenzaldehyde as raw materials for preparing the hydrogel, greatly improving the formation speed of the hydrogel, and having good biocompatibility, swelling property and antibacterial property, thus having a broad application prospect in the field of medical dressings. Description of the Drawings

[0022] Figure 1 It is the test result of the formation speed of the hydrogel in Example 1 and Comparative Example 1.

[0023] Figure 2 It is the test result of the swelling degree of the hydrogel in Example 1 at different temperatures.

[0024] Figure 3Antibacterial zone test results of the hydrogel in Example 1; among them, (a) is the antibacterial zone of Staphylococcus aureus, (b) is the antibacterial zone of Escherichia coli, (c) is the antibacterial zone of methicillin-resistant Staphylococcus aureus, and (d) is the antibacterial zone of Pseudomonas aeruginosa.

[0025] Figure 4 Colony counting experiment results of the hydrogel in Example 1; among them, (a) is the comparison chart of Staphylococcus aureus colony counting, and (b) is the comparison chart of Escherichia coli colony counting. Detailed implementation manners

[0026] To make the technical solutions described in the present invention clearer and more understandable to those skilled in the art, the following examples are listed for illustration. It should be noted that the following examples are only the preferred examples of the present invention and do not limit the scope of protection required by the present invention. Any modifications, substitutions, and combinations made without departing from the spirit and principle of the present invention are included in the protection scope of the present invention.

[0027] Unless otherwise specified, the raw materials, reagents, or devices used in the following examples can be obtained from conventional commercial channels or can be obtained by existing known methods.

[0028] Example 1

[0029] This example provides a hydrogel (named EPL-TBH), and its preparation method includes the following steps:

[0030] (1) Add 360 mg of 2,3,4-trihydroxybenzaldehyde to 4 mL of Tris-HCl solution and shake to dissolve.

[0031] (2) Continue to add 400 mg of sodium hydroxide and stir to dissolve.

[0032] (3) Then continue to add 1400 mg of polylysine (manufactured by Zhengzhou Bionovo Biotechnology Co., Ltd.) and dissolve it by ultrasound.

[0033] (4) Finally, add 200 μL of 30% hydrogen peroxide and shake to dissolve; after standing at room temperature, the hydrogel (EPL-TBH) can be obtained.

[0034] Tests show that when standing at room temperature for about 5 minutes in step (4), a hydrogel with good crosslinking can be obtained.

[0035] Comparative Example 1

[0036] This comparative example provides a hydrogel, and its preparation method includes the following steps:

[0037] (1) Add 120 mg of catechol to 2 mL of Tris-HCl solution and shake to dissolve.

[0038] (2) Continue to add 120 mg of sodium hydroxide and stir for dissolution;

[0039] (3) Then continue to add 600 mg of polylysine and dissolve it by ultrasonic treatment;

[0040] (4) Finally, add 200 μL of hydrogen peroxide with a concentration of 30% and dissolve it by shaking; After standing at room temperature, a hydrogel can be obtained.

[0041] Tests show that in step (4), it is necessary to stand at room temperature for at least 10 h to obtain a hydrogel with good cross-linking.

[0042] Comparative Example 2

[0043] This comparative example provides a hydrogel, and its preparation method includes the following steps:

[0044] (1) Weigh 10.0 g of chitosan and place it in a 50 mL round-bottom flask, then add 10 mL of 0.3% (volume fraction) acetic acid aqueous solution to the reaction flask and stir to fully dissolve the chitosan;

[0045] (2) Then add 33.33 mg of 2,4,5-trihydroxybenzaldehyde to the reaction flask respectively and stir at room temperature for 1 h; After standing at room temperature, a hydrogel can be obtained.

[0046] Tests show that in step (2), it is necessary to stand at room temperature for 24 h to obtain a hydrogel with good cross-linking. Even if hydrogen peroxide is added in step (2) to increase the formation rate, it still takes about 10 h to obtain a hydrogel with good cross-linking.

[0047] Product Effect Test

[0048] 1. Hydrogel Formation Rate Test

[0049] As Figure 1 can be seen, the hydrogel (EPL-TBH) formed by polylysine and 2,3,4-trihydroxybenzaldehyde in Example 1 can be formed only after five minutes, while the system containing polylysine and catechol in Comparative Example 1 is still in a flowing state at 5 min and has not formed a hydrogel with good cross-linking. Thus, it can be seen that the hydrogel in Example 1 has a significantly faster formation rate than the hydrogel in Comparative Example 1 and can better meet the actual needs.

[0050] 2. Swelling Property Test

[0051] The swelling degree of the hydrogel product prepared in Example 1 was tested at different temperatures (25 °C, 37 °C, 45 °C). The swelling test method: The formed hydrogel was placed in a -80 °C refrigerator overnight and freeze-dried for 24 hours. The initial weight was recorded as W0. After being placed in aqueous solutions at different temperatures, the weight was measured as W1 every 5 minutes. The swelling degree was calculated using the formula: Swelling degree = (W1 ÷ W0) × 100%.

[0052] The test results are as Figure 2 shown. The results show that the hydrogel can have good swelling properties at different temperatures, and the maximum swelling degree at room temperature of 25 °C can reach 379.31%.

[0053] 3. Inhibition zone test

[0054] The hydrogel product prepared in Example 1 was subjected to an inhibition zone test. The Staphylococcus aureus and Escherichia coli were diluted into a bacterial solution of 1×10 6 CFU / mL and spread on a plate. Then, the hydrogel group, the antibiotic group, and the PBS group were placed, and they were cultured in an incubator at 37 °C for 24 hours, and then the diameter of the inhibition zone was observed.

[0055] The test results are as Figure 3 shown. The results show that the hydrogel has better antibacterial ability than conventional antibiotics (such as vancomycin and chloramphenicol), and the antibacterial effect is obvious.

[0056] 4. Colony counting experiment

[0057] The hydrogel product prepared in Example 1 was subjected to a colony counting experiment. Before use, the hydrogel film was immersed in a large amount of deionized (DI) water and PBS was disinfected for 3 days to remove residual H2O2 until there was no inhibition zone. 100 μL of a bacterial solution of 1×10 6 CFU / mL was placed on the surface of the hydrogel and incubated for 4 hours, then rinsed with 1 mL of PBS and ultrasonically recovered. The recovered bacteria were spread on a plate and colony counting was performed.

[0058] The test results are as Figure 4 shown. The results further verify that the hydrogel in Example 1 has good antibacterial performance.

[0059] The above has described the embodiments of the present application in detail with reference to the drawings. However, the present application is not limited to the above embodiments. Within the scope of knowledge possessed by those of ordinary skill in the art, various changes can be made without departing from the purpose of the present application. In addition, without conflict, the embodiments of the present application and the features in the embodiments can be combined with each other.

Claims

1. A hydrogel, characterized in that, The raw materials for preparing the hydrogel include: a polypeptide containing free amino groups, an oxidant, and 2,3,4-trihydroxybenzaldehyde; The hydrogel is prepared by the following preparation method: (1) React a polypeptide containing free amino groups and 2,3,4-trihydroxybenzaldehyde under alkaline conditions; (2) Then add an oxidant and let it stand to obtain the hydrogel; The oxidant is hydrogen peroxide; The standing time is 4 - 8 min.

2. The hydrogel according to claim 1, characterized in that, The polypeptide containing free amino groups is polylysine.

3. The hydrogel according to claim 1, wherein The raw materials for preparing the hydrogel further include at least one of alkalis and alkaline buffers; the alkalis include at least one of sodium hydroxide and potassium hydroxide.

4. The hydrogel according to claim 3, wherein The alkaline buffer is Tris-HCl buffer.

5. The method for preparing the hydrogel according to any one of claims 1-4, characterized in that, It includes the following steps: (1) React a polypeptide containing free amino groups and 2,3,4-trihydroxybenzaldehyde under alkaline conditions; (2) Then add an oxidant and let it stand to obtain the hydrogel.

6. The preparation method according to claim 5, characterized in that, The standing time is 4 - 8 min.

7. The preparation method according to claim 6, characterized in that, The standing time is 5 min.

8. Use of the hydrogel according to any one of claims 1 - 4 in the preparation of a medical dressing.

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