A method for preparing supramolecular hydrogel materials with intrinsic multifunctionality

Abstract

The present invention provides a method for preparing a supramolecular hydrogel material with intrinsic multifunctionality and its application, belonging to the technical field of medical materials promoting wound healing. The key technical solutions of the present invention are as follows: guanosine nucleoside is first mixed with formylphenylboronic acid and a soluble potassium-containing compound to prepare a guanosine supramolecular hydrogel with boronate bonds. A phenylboronated polysaccharide is then compounded with the guanosine supramolecular hydrogel to enhance the mechanical properties of the supramolecular hydrogel. An aminoglycoside antibiotic is also loaded, and the formation of Schiff base crosslinks and boronate bonds synergistically strengthens the gel network while also imparting excellent antibacterial properties to the supramolecular hydrogel. The supramolecular hydrogel material prepared by this method not only exhibits enhanced mechanical properties but also possesses intrinsic antibacterial, antioxidant, and tissue adhesion properties, and can be used to prepare hydrogel wound dressings that promote wound healing.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical materials for promoting wound healing, and particularly relates to a preparation method and application of a supramolecular hydrogel material with intrinsic antibacterial, antioxidant and tissue adhesion properties. Background Art

[0002] In skin wounds, bacterial infection and oxidative stress can both slow down the rate of wound healing. Traditional wound dressings have a single function, so the development of new wound dressings is of great significance. As a hydrophilic soft material with a three-dimensional network structure, hydrogels are highly similar to living tissues, and thus show great application potential in the biomedical field. In addition, the structure and properties of hydrogels can be easily regulated, making them widely used as wound dressings to promote tissue regeneration. Among the many hydrogel wound dressings, supramolecular hydrogels based on small molecule self-assembly have received much attention due to their easy preparation and responsiveness, but their poor mechanical properties greatly limit their scope of application. Therefore, the design and preparation of multifunctional supramolecular hydrogel dressings with enhanced mechanical properties have important application value. Summary of the Invention

[0003] The present invention aims to address the shortcomings of existing supramolecular hydrogels based on small molecule self-assembly by providing a method for preparing a supramolecular hydrogel material with inherent multifunctionality. The method first selects guanine nucleoside, formsylphenylboronic acid, and a soluble potassium-containing compound to mix to prepare a guanosine supramolecular hydrogel with boronate bonds. Phenylboronated polysaccharides are then compounded with the guanosine supramolecular hydrogel to enhance the mechanical properties of the supramolecular hydrogel. Aminoglycoside antibiotics are also loaded to form Schiff base crosslinks and boronate bonds to synergistically strengthen the gel network while also imparting excellent antibacterial properties to the supramolecular hydrogel. The supramolecular hydrogel material prepared by this method not only has enhanced mechanical properties but also possesses inherent antibacterial, antioxidant, and tissue adhesion properties, and can be used to prepare hydrogel wound dressings that promote wound healing.

[0004] To achieve the above-mentioned object, the present invention adopts the following technical solution, a method for preparing a supramolecular hydrogel material with intrinsic multifunctionality, characterized by the following specific steps:

[0005] Step S1: dissolving a natural polysaccharide containing an amino group and formylphenylboronic acid in deionized water and stirring the mixture to obtain a phenylboronated polysaccharide solution, wherein the natural polysaccharide containing an amino group is one or more of chitosan, quaternized chitosan, carboxymethyl chitosan, carboxyethyl chitosan, hydroxyethyl chitosan, amino sodium alginate, amino sodium hyaluronate, amino chondroitin sulfate, amino xanthan gum, amino konjac gum, amino glucan, amino laminarin, amino bletilla striata polysaccharide, amino gum arabic, or amino gellan gum;

[0006] Step S2: adding the phenylboronated polysaccharide solution obtained in step S1, an aminoglycoside antibiotic, guanosine, formylphenylboronic acid, and a soluble potassium-containing compound to deionized water, heating until completely dissolved, and then standing at room temperature to obtain a supramolecular hydrogel material with intrinsic multifunctionality, wherein the supramolecular hydrogel material not only has enhanced mechanical properties but also has intrinsic antibacterial, antioxidant, and tissue adhesion properties, wherein the aminoglycoside antibiotic is one or more of gentamicin, neomycin sulfate, tobramycin, paromomycin sulfate, ribosomycin sulfate, streptomycin, kanamycin, netilmicin, amikacin, or isopamicin, and the soluble potassium-containing compound is one or more of potassium chloride, potassium sulfate, potassium nitrate, potassium phosphate, potassium carbonate, potassium bicarbonate, or potassium hydroxide;

[0007] The formylphenylboronic acid is one or more of 2-formylphenylboronic acid, 3-formylphenylboronic acid or 4-formylphenylboronic acid.

[0008] It is further defined that the molar ratio of the formylphenylboronic acid to the amino group in the amino group-containing natural polysaccharide in step S1 is 0.01-0.4:1.

[0009] It is further defined that the concentration of the phenylboronic acid polysaccharide solution in step S2 is 0.1~50 mg / mL, the mass concentration of guanosine is 10~50 mg / mL, the molar ratio of guanosine, formylphenylboronic acid and potassium ions in the soluble potassium-containing compound is 1:1:0.1~5, the concentration of the aminoglycoside antibiotic is 1~5 mmol / L, the heating temperature is 60~100°C, and the standing time at room temperature is 20~720 min.

[0010] The invention relates to the use of the supramolecular hydrogel material with intrinsic multifunctionality in the preparation of biomedical materials.

[0011] The invention relates to an application of the supramolecular hydrogel material with intrinsic multifunctionality in the preparation of a hydrogel wound dressing for promoting wound healing.

[0012] Compared with the prior art, the present invention has the following advantages and beneficial effects: the supramolecular hydrogel material with intrinsic antibacterial, antioxidant and tissue adhesion provided by the present invention not only enhances the mechanical properties of functional small molecule hydrogels, but also contains antibacterial drugs, antioxidant borate cross-linking and aldehyde groups that are beneficial to tissue adhesion. Compared with traditional wound dressings and existing hydrogel wound dressings, it not only has intrinsic multifunctionality, but also has the advantages of a wide source of raw materials and simple preparation. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 The antibacterial performance test results of the supramolecular hydrogel material with intrinsic multifunctionality prepared in Example 1;

[0014] Figure 2 The antioxidant test results of the supramolecular hydrogel material with intrinsic multifunctionality prepared in Example 1;

[0015] Figure 3 These are the tissue adhesion test results of the supramolecular hydrogel material with intrinsic multifunctionality prepared in Example 1. DETAILED DESCRIPTION

[0016] The above contents of the present invention are further described in detail below through examples, but this should not be understood as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above contents of the present invention fall within the scope of the present invention. Example

[0017] Step S1: 0.5 g of carboxymethyl chitosan was dissolved in 10 mL of water, and 5 mg of 4-formylphenylboronic acid was added and reacted for 12 h to obtain a phenylboronated polysaccharide solution;

[0018] Step S2: 50 μL of the phenylboronated polysaccharide solution obtained in step S1, 44.5 mg of guanosine, 22.5 mg of 2-formylphenylboronic acid, 7.5 mg of potassium bicarbonate, and 2.4 mg of paromomycin sulfate were added to 1.95 mL of deionized water, heated to 90°C, and allowed to stand at room temperature for 30 minutes after complete dissolution to obtain a supramolecular hydrogel material with intrinsic multifunctionality. Example

[0019] Step S1: Dissolve 0.5 g of amino-modified sodium hyaluronate in 5 mL of water, add 7.5 mg of 4-formylphenylboronic acid, and react for 6 h to obtain a phenylboronated polysaccharide solution;

[0020] Step S2: 100 μL of the phenylboronated polysaccharide solution obtained in step S1, 71.2 mg of guanosine, 36 mg of 4-formylphenylboronic acid, 17.5 mg of potassium carbonate, and 2 mg of tobramycin were added to 1.9 mL of deionized water, heated to 90°C, and allowed to stand at room temperature for 30 minutes after complete dissolution to obtain a supramolecular hydrogel material with intrinsic multifunctionality.

[0021] In order to illustrate the various properties of the supramolecular hydrogel material with intrinsic multifunctionality provided by the present invention, the performance test of the supramolecular hydrogel material prepared in Example 1 was carried out, and the test results are shown in FIG. Figures 1 to 3 .

[0022] Figure 1The antibacterial performance test results of the supramolecular hydrogel material with intrinsic multifunctionality prepared in Example 1 are shown in the figure. As shown in the figure, compared with the blank control group and the pure gel group, the supramolecular hydrogel material prepared in Example 1 exhibits excellent antibacterial properties against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli.

[0023] Figure 2 The antioxidant performance test results of the supramolecular hydrogel material with intrinsic multifunctionality prepared in Example 1 are shown in the figure. + It exhibits excellent free radical scavenging ability.

[0024] Figure 3 The tissue adhesion test results of the supramolecular hydrogel material with intrinsic multifunctionality prepared in Example 1 are shown in the figure. As shown in the figure, compared with pure guanine nucleoside hydrogel, the supramolecular hydrogel material prepared in Example 1 exhibits stronger adhesion to pig skin, which is conducive to the supramolecular hydrogel material to adhere closely to the wound.

[0025] In summary, the supramolecular hydrogel material with intrinsic multifunctionality provided by the present invention exhibits good antibacterial, antioxidant and tissue adhesion properties, showing its application potential as a biomedical material, especially as a hydrogel wound dressing that promotes wound healing.

[0026] The basic principles, main features and advantages of the present invention are shown and described above. Without departing from the spirit and scope of the present invention, the present invention may also undergo various changes and improvements, which are required to fall within the scope of protection of the present invention.

Claims

1. Application of a supramolecular hydrogel material with intrinsic multifunctionality in the preparation of a hydrogel wound dressing for promoting wound healing, characterized in that: Guanosine supramolecular hydrogels with boronate bonds were prepared by mixing guanosine nucleoside with formylphenylboronic acid and a soluble potassium-containing compound. Phenylboronic acid-modified polysaccharides were then composited with the guanosine supramolecular hydrogels to enhance their mechanical properties. Aminoglycoside antibiotics were also loaded, and the formation of Schiff base crosslinks and boronate bonds synergistically enhanced the gel network while also imparting excellent antibacterial properties to the supramolecular hydrogels. The resulting supramolecular hydrogel material has enhanced mechanical properties, as well as intrinsic antibacterial, antioxidant, and tissue adhesion properties, and can be used to prepare hydrogel wound dressings that promote wound healing. The specific preparation steps of the supramolecular hydrogel material with intrinsic multifunctionality are: Step S1: dissolving a natural polysaccharide containing an amino group and formylphenylboronic acid in deionized water and stirring the mixture to obtain a phenylboronated polysaccharide solution, wherein the natural polysaccharide containing an amino group is one or more of chitosan, quaternized chitosan, carboxymethyl chitosan, carboxyethyl chitosan, hydroxyethyl chitosan, amino sodium alginate, amino sodium hyaluronate, amino chondroitin sulfate, amino xanthan gum, amino konjac gum, amino glucan, amino laminarin, amino bletilla striata polysaccharide, amino gum arabic, or amino gellan gum; Step S2: adding the phenylboronated polysaccharide solution obtained in step S1, an aminoglycoside antibiotic, guanosine, formylphenylboronic acid, and a soluble potassium-containing compound to deionized water, heating until completely dissolved, and then standing at room temperature to obtain a supramolecular hydrogel material with intrinsic multifunctionality, wherein the supramolecular hydrogel material not only has enhanced mechanical properties but also has intrinsic antibacterial, antioxidant, and tissue adhesion properties, wherein the aminoglycoside antibiotic is one or more of gentamicin, neomycin sulfate, tobramycin, paromomycin sulfate, ribosomycin sulfate, streptomycin, kanamycin, netilmicin, amikacin, or isopamicin, and the soluble potassium-containing compound is one or more of potassium chloride, potassium sulfate, potassium nitrate, potassium phosphate, potassium carbonate, potassium bicarbonate, or potassium hydroxide; The formylphenylboronic acid is one or more of 2-formylphenylboronic acid, 3-formylphenylboronic acid or 4-formylphenylboronic acid.

2. The use according to claim 1, characterized in that: In step S1, the molar ratio of formylphenylboronic acid to amino groups in the amino group-containing natural polysaccharide is 0.01-0.4:

1.

3. The use according to claim 1, wherein: The concentration of the phenylboronic acid polysaccharide solution in step S2 is 0.1-50 mg / mL, the mass concentration of guanosine is 10-50 mg / mL, the molar ratio of guanosine, formylphenylboronic acid and potassium ions in the soluble potassium-containing compound is 1:1:0.1-5, the concentration of the aminoglycoside antibiotic is 1-5 mmol / L, the heating temperature is 60-100° C., and the standing time at room temperature is 20-720 min.

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