Oxidized konjac glucomannan and hydrazide hyaluronic acid composite hydrogel as well as preparation method and application thereof

Abstract

The invention discloses oxidized konjac glucomannan and hydrazide hyaluronic acid composite hydrogel. The oxidized konjac glucomannan and hydrazide hyaluronic acid composite hydrogel is prepared from oxidized konjac glucomannan, hydrazide hyaluronic acid, neomycin sulfate, cannabidiol and 2-roots alcohol. The invention further provides a preparation method of the oxidized konjac glucomannan and hydrazide hyaluronic acid composite hydrogel and application of the oxidized konjac glucomannan and hydrazide hyaluronic acid composite hydrogel in preparation of hemostatic materials. The composite hydrogel disclosed by the invention has high adhesion and excellent antibacterial property, is suitable for various wounds, and has excellent effects of stopping bleeding, relieving pain, reducing wound infection and promoting wound healing.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical materials, and particularly relates to an oxidized konjac gum and hydrazide-modified hyaluronic acid composite hydrogel, and a preparation method and application thereof. Background Art

[0002] The hemostasis and healing of tissue wounds, especially hemostasis for severe bleeding, and the demand for related hemostatic materials remain challenges that need to be addressed. Wound healing often presents with complications such as infection and inflammation, which increase the biological and pharmacological requirements for hemostatic materials. Currently, commonly used gauze and wound dressings tend to fall off during wound healing, absorb body fluids, and adhere to the wound, causing secondary damage. They are not highly effective in stopping bleeding and promoting wound healing.

[0003] Hydrogel dressings, as hydrophilic biomaterials, can act as a barrier to wound skin, stopping bleeding and loading various effector molecules to effectively prevent wound infection. However, current hydrogel dressings have several limitations, such as poor mechanical strength and poor adhesion. There is an urgent need for a hydrogel dressing with excellent hemostatic and antibacterial properties that can effectively promote wound healing. Summary of the Invention

[0004] One object of the present invention is to provide a hydrogel dressing with high adhesion and strong antibacterial properties in response to the above technical problems, which is suitable for various traumatic wounds and has the effects of stopping bleeding, relieving pain, reducing wound infection and promoting wound healing.

[0005] Another object of the present invention is to provide a method for preparing the hydrogel dressing.

[0006] Another object of the present invention is to provide applications of the hydrogel dressing.

[0007] In order to achieve the above object of the invention, the present invention provides an oxidized konjac gum and hydrazide hyaluronic acid composite hydrogel, which includes oxidized konjac gum (OKGM), hydrazide hyaluronic acid (ADHHA), neomycin sulfate (NS), cannabidiol (CBD) and 2-camphenol (2B).

[0008] As a preferred embodiment, the oxidized konjac gum is oxidatively modified konjac gum. More preferably, the oxidized konjac gum is a product obtained by oxidizing konjac gum with an oxidant (e.g., sodium periodate).

[0009] As a preferred embodiment, the preparation steps of oxidized konjac glucomannan are as follows: konjac glucomannan is dissolved in water and configured to a solution of 1-5wt%, an oxidant is added under lucifuge, the concentration of the oxidant in the reaction system is 0.1-1wt%, and stirring is continued for 12-24 hours, a terminator is subsequently added at a concentration of 1-5wt%, and stirring is continued for 0.5-2 hours, the reaction is terminated, dialyzed using a dialysis bag, and freeze-dried to obtain oxidized konjac glucomannan.

[0010] As a preferred embodiment, the molecular weight of the konjac gum is 200,000-2,000,000.

[0011] As a preferred embodiment, the hydrazide hyaluronic acid is hydrazide-modified hyaluronic acid. More preferably, the hydrazide hyaluronic acid is adipic acid dihydrazide-modified hyaluronic acid.

[0012] As a preferred embodiment, the preparation steps of hydrazide hyaluronic acid are as follows: dissolving hyaluronic acid in water to prepare a 1~5wt% solution, then adding a hydrazide reagent and an activator, the concentrations of the hydrazide reagent and the activator in the reaction system are both 0.1~1wt%, and adjusting the pH to 4.75, continuously stirring for 12~24 hours, dialyzing using a dialysis bag, and freeze-drying to obtain hydrazide hyaluronic acid.

[0013] As a preferred embodiment, the molecular weight of the hyaluronic acid is 150,000-200,000.

[0014] The present invention utilizes oxidized konjac gum and hydrazide hyaluronic acid to cross-link with Schiff base, loads neomycin sulfate, and wraps cannabidiol and 2-camphenol to form a hydrogel dressing.

[0015] As a preferred embodiment, the mass ratio of oxidized konjac gum to hydrazide hyaluronic acid is (1-5):(1-5), for example (1-3):(1-2).

[0016] As a preferred embodiment, the molar ratio of neomycin sulfate, cannabidiol, and 2-camphenol is neomycin sulfate: cannabidiol: 2-camphenol = (1-5): (1-5): (1-5).

[0017] As a preferred embodiment, the oxidation degree of the oxidized konjac gum is 20%-60%.

[0018] As a preferred embodiment, the hydrazide degree of the hydrazide-modified hyaluronic acid is 10%-50%.

[0019] On the other hand, the present invention also provides a method for preparing the oxidized konjac gum and hydrazide hyaluronic acid composite hydrogel, which comprises the following steps: First, the oxidized konjac gum solution and the neomycin sulfate solution are fully mixed to react, and then the cannabidiol solution and the 2-benzyl alcohol solution are added in sequence, and finally the hydrazide hyaluronic acid solution is added. The mixture is stirred rapidly and allowed to stand to form a gel.

[0020] In the oxidized konjac gum solution, the mass volume concentration of the oxidized konjac gum is 1%-5%, and the solvent is water.

[0021] In the hydrazide hyaluronic acid solution, the mass volume concentration of the hydrazide hyaluronic acid is 1%-5%, and the solvent is water.

[0022] In the neomycin sulfate solution, the concentration of neomycin sulfate is 0.5 mol / L to 1 mol / L, and the solvent is anhydrous ethanol.

[0023] In the cannabidiol solution, the concentration of cannabidiol is 0.5 mol / L to 1 mol / L, and the solvent is anhydrous ethanol.

[0024] In the 2-bromophenol solution, the concentration of 2-bromophenol is 0.5 mol / L to 1 mol / L, and the solvent is anhydrous ethanol.

[0025] The volume ratio of the oxidized konjac gum solution, the hydrazide hyaluronic acid solution, the neomycin sulfate solution, the cannabidiol solution and the 2-benzoyl alcohol solution in the hydrogel dressing is 1:1:0.01:0.01:0.01.

[0026] On the other hand, the present invention also provides use of the composite hydrogel in preparing hemostatic materials.

[0027] Hyaluronic acid is a kind of natural hyaluronic acid, is widely present in human connective tissue, possesses high water retention, no immunity, degradable and product nontoxic, promotes repair effect and adhesion. Konjac glucomannan is the natural konjac glucomannan extracted from konjac tuber, possesses the effects such as high water absorbability, biocompatibility, adhesion. Both possess good biocompatibility, and the characteristics such as degradable are the ideal ingredients for preparing wound hemostasis and promoting healing hydrogel. Hydrogel dressing of the present invention possesses good hemostasis and antibacterial effect, can effectively promote wound healing, and preparation step is simple, and raw material is natural polymer material, nontoxic, easily obtains, and is cheap, has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The frequency and amplitude sweep results of the ADHHA / OKGM / NS / CBD / 2B composite hydrogel according to an embodiment of the present invention are shown. (A) Frequency sweep; (B) Amplitude sweep.

[0029] Figure 2The results show that the ADHHA / OKGM / NS / CBD / 2B composite hydrogel according to the embodiment of the present invention has an effect on Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ) has an inhibitory effect.

[0030] Figure 3 Figure 2 shows the bacterial colony count and antibacterial rate of Escherichia coli and Staphylococcus aureus coated with the ADHHA / OKGM / NS / CBD / 2B composite hydrogel according to an embodiment of the present invention. (A) Bacterial growth on the plate; (B) Bacterial inhibition rate.

[0031] Figure 4 The figure shows the cell compatibility of the ADHHA / OKGM / NS / CBD / 2B composite hydrogel at different concentrations according to an embodiment of the present invention.

[0032] Figure 5 Figure 2 shows the blood compatibility of the ADHHA / OKGM / NS / CBD / 2B composite hydrogel according to an embodiment of the present invention. (A) Hemolysis test of the hydrogel; (B) Hemolysis rate.

[0033] Figure 6 Figure 2 shows the blood coagulation index (BCI) of the ADHHA / OKGM / NS / CBD / 2B composite hydrogel according to an embodiment of the present invention. (A) BCI index of the hydrogel; (B) blood coagulation status of the hydrogel.

[0034] Figure 7 Figure 2 shows the hemostatic effect of the ADHHA / OKGM / NS / CBD / 2B composite hydrogel on mouse liver hemostasis according to an embodiment of the present invention. (A) Hemostasis of mouse liver; (B) Hemostasis time of mouse liver; (C) Hemorrhage volume of mouse liver.

[0035] Figure 8 Figure 2 shows the wound healing effects and healing rates of mice treated with the ADHHA / OKGM / NS / CBD / 2B composite hydrogel according to an embodiment of the present invention. (A) Changes in mouse wounds over time after hydrogel application; (B) Wound healing rates on day 10. ***P ≤ 0.001, indicating significant differences. DETAILED DESCRIPTION

[0036] To facilitate understanding of the present invention, the present invention will be described more fully below in conjunction with specific embodiments. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the present disclosure more thorough and comprehensive. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by those skilled in the art to which this invention pertains. The terms used in this specification are for the purpose of describing specific embodiments only and are not intended to limit the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0037] In the present invention, oxidized konjac glucomannan is preferably obtained by oxidizing the ortho-hydroxyl group of konjac glucomannan to an aldehyde group. The oxidation degree of oxidized konjac glucomannan is preferably 20 to 60%. For example, it can be 20%, 30%, 40%, 50%, 60% etc. The molecular weight of konjac glucomannan can be 200,000 to 2,000,000.

[0038] The hydrazide-modified hyaluronic acid of the present invention is preferably prepared by reacting the hydroxyl groups on hyaluronic acid with a hydrazide-modified reagent.

[0039] In the present invention, the degree of hydrazide of the hydrazide hyaluronic acid is preferably 10-50%. For example, it can be 10%, 20%, 30%, 40%, 50%, etc. The molecular weight of the hyaluronic acid can be 150,000-200,000.

[0040] In the neomycin sulfate solution, the concentration of neomycin sulfate is preferably 0.5 mol / L-1 mol / L, and the solvent is water.

[0041] In the cannabidiol solution, the concentration of cannabidiol is preferably 0.5 mol / L-1 mol / L, and the solvent is anhydrous ethanol.

[0042] In the 2-bromophenol solution, the concentration of 2-bromophenol is 0.5 mol / L-1 mol / L, and the solvent is anhydrous ethanol.

[0043] In order to further illustrate the present invention, the technical solutions provided by the present invention are described in detail below with reference to the accompanying drawings and embodiments, but they should not be construed as limiting the scope of patent protection of the present invention.

[0044] Unless otherwise specified, the reagents, methods and equipment used in the practice of the present invention are conventional reagents, methods and equipment in the technical field.

[0045] Unless otherwise specified, all reagents and materials used in the following examples were purchased from the market.

[0046] Example 1 A novel hydrogel wound dressing is prepared as follows: (1) 5 g of konjac gum (KGM) was added to 500 mL of deionized water and stirred until completely dissolved. Then, 1.32 g of NaIO4 was added, and the mixture was stirred at 30 °C in the dark for 12 h. Subsequently, 10 mL of ethylene glycol was added to terminate the reaction, and the mixture was stirred for another 2 h. The resulting solution was then dialyzed in deionized water using a dialysis bag for 3 days and freeze-dried to obtain oxidized konjac gum (OKGM). Oxidized konjac gum was dissolved in 50 °C deionized water to obtain a 5% oxidized konjac gum solution (5 g oxidized konjac gum: 100 mL deionized water).

[0047] (2) Weigh 5 mmol of neomycin sulfate (NS) into a beaker and add 5 mL of deionized water to dissolve it to obtain a neomycin sulfate solution (concentration of 1 mol / L).

[0048] (3) Weigh 2 mmol of cannabidiol (CBD) into a vial and add anhydrous ethanol to make up to 2 mL to obtain a cannabidiol solution (concentration of 1 mol / L).

[0049] (4) Weigh 2 mmol of 2-bromophenol (2B) into a vial and add anhydrous ethanol to make the volume up to 2 mL to obtain a 2-bromophenol solution (concentration is 1 mol / L).

[0050] (5) Dissolve 2 g of hyaluronic acid (HA) in 200 mL of sterile water. Add 2.3 g of ADH to the solution. While stirring continuously, slowly add 1.84 g of ADH and 1.43 g of HOBT (dissolved in 10 mL of deionized water and then added dropwise to the HA solution) to the HA solution to adjust the pH to 4.75. Continue to slowly add 0.91 g of EDC (dissolved in 10 mL of deionized water and then added dropwise to the mixed solution) to the solution. Adjust the pH with 1 M HCl and 1 M NaOH to maintain pH 4.75 for 4 hours. Continue stirring at room temperature for 24 hours. After the reaction is completed, dialyze with deionized water for 3 days, freeze at -80 ° C, and freeze-dry using a freeze dryer to obtain hydrazide hyaluronic acid (ADHHA). Prepare a 5% hydrazide hyaluronic acid solution according to the ratio.

[0051] (6) Take 1 mL of oxidized konjac gum solution (concentration of 5% w / v) in a container, add 10 μL of neomycin sulfate solution (concentration of 1 mol / L), stir thoroughly, continue to add 10 μL of cannabidiol solution (concentration of 1 mol / L) and 10 μL of 2-benzyl alcohol solution (concentration of 1 mol / L) to the solution, stir thoroughly, and finally add 1 mL of hydrazide hyaluronic acid solution (concentration of 5% w / v) and continue stirring and let it stand for observation; the solution forms a hydrogel in 5 minutes.

[0052] Example 2 A novel hydrogel wound dressing is provided, wherein the preparation method thereof is different from that of Example 1 in that the concentration of oxidized konjac gum is changed; in this embodiment, the concentration of oxidized konjac gum is 3%.

[0053] Example 3 A novel hydrogel wound dressing is provided, wherein the preparation method thereof is different from that of Example 1 in that the concentration of oxidized konjac gum is changed; in this embodiment, the concentration of oxidized konjac gum is 2%.

[0054] Example 4 A method for preparing a novel hydrogel wound dressing comprises the following steps: (1) 5 g of konjac gum (KGM) was added to 500 mL of deionized water and stirred until completely dissolved. Then, 1.32 g of NaIO4 was added, and the mixture was stirred at 30 °C in the dark for 12 h. Subsequently, 10 mL of ethylene glycol was added to terminate the reaction, and the mixture was stirred for another 2 h. The resulting solution was then dialyzed in deionized water using a dialysis bag for 3 days and freeze-dried to obtain oxidized konjac gum (OKGM), which was then prepared into a 3% oxidized konjac gum solution (3 g oxidized konjac gum: 100 mL of deionized water) according to the ratio.

[0055] (2) Weigh 5 mmol of neomycin sulfate into a beaker and add 5 mL of deionized water to dissolve it to obtain a neomycin sulfate solution (concentration is 1 mol / L).

[0056] (3) Weigh 2 mmol of cannabidiol into a vial and add anhydrous ethanol to make the volume up to 2 mL to obtain a cannabidiol solution (concentration is 1 mol / L).

[0057] (4) Weigh 2 mmol of 2-bromophenol into a penicillin bottle and add anhydrous ethanol to make the volume up to 2 mL to obtain a 2-bromophenol solution (concentration is 1 mol / L).

[0058] (5) Dissolve 2 g of hyaluronic acid (HA) in 200 mL of sterile water. Add 2.3 g of ADH to the solution. While stirring continuously, slowly add 1.84 g of ADH and 1.43 g of HOBT (dissolved in 10 mL of deionized water and then added dropwise to the HA solution) to the HA solution to adjust the pH to 4.75. Continue to slowly add 0.91 g of EDC (dissolved in 10 mL of deionized water and then added dropwise to the mixed solution) to the solution. Adjust the pH with 1 M HCl and 1 M NaOH to maintain pH 4.75 for 4 hours. Continue stirring at room temperature for 24 hours. After the reaction is completed, dialyze with deionized water for 3 days, freeze at -80 ° C, and freeze-dry using a freeze dryer to obtain hydrazide hyaluronic acid (ADHHA), which is prepared into a 2% hydrazide hyaluronic acid solution according to the ratio.

[0059] (6) Place 1 mL of oxidized konjac gum solution (3% w / v) in a container, add 10 μL of neomycin sulfate solution (1 mol / L), and stir thoroughly. Then, add 10 μL of cannabidiol solution (1 mol / L) and 10 μL of 2-bromophenol solution (1 mol / L) to the solution and stir thoroughly. Finally, add 1 mL of hydrazide hyaluronic acid solution (2% w / v), continue stirring, and then let it stand for observation. The solution forms a hydrogel in 3 minutes.

[0060] Example 5 A novel hydrogel wound dressing, the preparation method of which is different from the preparation method of Example 4 only in that the concentration of oxidized konjac gum is changed; in this example, the concentration of oxidized konjac gum is 4%.

[0061] Example 6 A novel hydrogel wound dressing, the preparation method of which is different from the preparation method of Example 4 only in that the concentration of oxidized konjac gum is changed; in this example, the concentration of oxidized konjac gum is 5%.

[0062] In the present invention, the ortho-hydroxyl groups in the konjac gum structure can be oxidized to aldehyde groups, and the amino groups in the hyaluronic acid hydrazide can undergo Schiff base reaction to generate dynamic Schiff base bonds with reversible characteristics. In addition, the hydrogen bonds formed between the amino groups and hydroxyl groups can strengthen the bonding degree of the hydrogel three-dimensional network, thereby preparing a new hydrogel dressing with fast and strong self-healing properties.

[0063] Performance Testing The antibacterial properties and biocompatibility tests of the hydrogels were conducted according to GB / T 31402-2015 and GB / T16886.5-2003, respectively.

[0064] Biological toxicity scores: no cytotoxicity (0), slight cytotoxicity (1), moderate cytotoxicity (2), severe cytotoxicity (3).

[0065] The hemolysis rate is calculated as follows: Hemolysis rate = (absorbance of experimental group - absorbance of negative control group) / (absorbance of positive control group - absorbance of negative control group) × 100%.

[0066] The gelation time of the hydrogel samples obtained in Examples 1-6 above is shown in Table 1.

[0067] Table 1: Comparison of hydrogel gelation time in examples

[0068] As shown in Table 1, the gelation time of the hydrogel varies with the concentration and ratio of oxidized konjac gum and hydrazide hyaluronic acid. When the ratio of oxidized konjac gum to hydrazide hyaluronic acid is 2:1, the gelation time of the hydrogel is the shortest, at 10 seconds. This is of great significance for the preparation of fast and self-healing Schiff base hydrogels.

[0069] Various properties of the composite hydrogels of Examples 1-6 were measured. The results showed that the composite hydrogels of Examples 1-6 all had good hydrogel structures, significant antibacterial effects, were harmless and non-toxic to cells, had excellent blood compatibility, and could effectively coagulate and stop bleeding and promote wound healing.

[0070] The following description will be made using the hydrogel performance test results of Example 5 as an example.

[0071] The rheological analysis of the hydrogel of Example 5 was performed. Figure 1 As shown, when the angular frequency of the hydrogel of Example 5 is ≤20, its G' is always greater than G" ( Figure 1 , A), indicating that it is always a hydrogel in this range, which is the elastic range of the hydrogel. When the shear strain is ≤13, G' and G" do not change much with the shear strain and can be regarded as constants ( Figure 1 , B), proving that this region is the linear viscoelastic range of the hydrogel and the hydrogel structure will not change due to strain.

[0072] As a wound dressing, antibacterial properties are essential. Therefore, the antibacterial properties of the hydrogel in Example 5 were tested. Escherichia coli and Staphylococcus aureus were selected as bacterial models and the antibacterial properties were determined by the inhibition zone method. The results are shown in Figure 5. Figure 2 shown. Figure 2In the figure, A shows a hydrogel composed solely of oxidized konjac gum and hydrazide-modified hyaluronic acid (neomycin sulfate, cannabidiol, and 2-camphenol are omitted from the components of Example 5), and B shows the hydrogel of Example 5. As can be seen from the figure, after loading neomycin sulfate, the hydrogel exhibits significant inhibitory effects against Staphylococcus aureus and Escherichia coli. Therefore, the hydrogel prepared by the present invention exhibits antibacterial effects.

[0073] The antibacterial rate was determined by the dilution plate method. The bacterial solution co-cultured with the hydrogel and the two bacteria was diluted to the same multiple and plated for counting. The results are as follows: Figure 3 As shown in the figure, compared with the blank control, the hydrogel exhibited a significant inhibitory effect against Staphylococcus aureus and Escherichia coli, with no bacterial growth on the culture medium, resulting in an inhibition rate of 100%. This result is consistent with the results of the inhibition zone experiment, indicating that the hydrogel prepared by the present invention has an inhibitory effect on both bacteria.

[0074] Wound dressings must be non-toxic to the human body and have no adverse reactions after use. Therefore, 3T3 fibroblasts were selected and the CCK8 method was used to detect the toxicity of hydrogels at different concentrations (0.625 mg / mL, 1.25 mg / mL, 2.5 mg / mL, and 5 mg / mL) on cells. The results are as follows: Figure 4 The results showed that compared with the blank control, the cell survival rate of the hydrogel in Example 5 remained basically unchanged as the concentration increased, maintaining above 90%. When the concentration reached 1 mg / mL, the cell survival rate decreased slightly.

[0075] The hydrogel of Example 5 prepared by the present invention is very important for blood compatibility. Figure 5 It can be seen that the hydrogel of Example 5 has very good blood compatibility compared with the control group (1.8 mL of sterile water was taken and then 36 μL of red blood cell suspension was added, as the positive control group) ( Figure 5 , A). In addition, the hemolysis rate calculated by measuring the ultraviolet absorbance is also below 5%, indicating that the hydrogel has very excellent blood compatibility ( Figure 5 , B).

[0076] The most important property of wound materials is the ability to aggregate platelets to promote blood coagulation. Figure 6 In the hydrogel group, blood can be clearly seen coagulating at the bottom to form dark red blood clots, proving that the hydrogel has a very excellent coagulation effect ( Figure 6 , B). Figure 6 It can be seen that the blood coagulation index (BCI) is below 40%, indicating that the hydrogel has a significant coagulation effect ( Figure 6 , A).

[0077] The Blood Clotting Index (BCI) was calculated using the following formula:

[0078] The OD value was measured by a microplate reader at 540 nm.

[0079] The lower the BCI, the more effectively blood coagulation can be stimulated.

[0080] The hemorrhage effect was created in a mouse liver model, and then the hydrogel was attached to achieve the effect for quantitative analysis. Figure 7 As shown. Figure 7 It can be seen that when the mouse liver was cut open without any treatment, the amount of bleeding was large, reaching 0.2081g. After the hydrogel was attached, the amount of bleeding was greatly reduced to only about 0.04g ( Figure 7 , A, C). The time to stop bleeding is also greatly shortened, and bleeding stops in about 32 seconds ( Figure 7 , B), therefore, the hydrogel of the present invention has a very obvious effect on stopping bleeding from wounds, and when debridement of the mouse liver was performed, it was found that blood clots were obviously formed at the bleeding site, indicating that the hydrogel achieved its effect by promoting coagulation.

[0081] In the mouse wound healing experiment, Figure 8 It was found that when only 3M dressing was applied, white pus appeared on the mouse wound, and this pus lasted from the third day to the tenth day. When hydrogel was applied inside the 3M dressing, the mouse wound did not suppurate and the mouse wound gradually healed. By the tenth day, the healing was obviously good ( Figure 8 , A), the healing rate reached about 98% ( Figure 8 , B).

Claims

1. An oxidized konjac gum and hydrazide hyaluronic acid composite hydrogel, characterized in that Including oxidized konjac gum, hydrazide hyaluronic acid, neomycin sulfate, cannabidiol and 2-camphenol.

2. the oxidized konjac gum and hydrazide hyaluronic acid composite hydrogel according to claim 1, is characterized in that, The mass ratio of oxidized konjac gum to hydrazide hyaluronic acid is (1-5): (1-5).

3. the oxidized konjac gum and hydrazide hyaluronic acid composite hydrogel according to claim 1, is characterized in that, The molar ratio of neomycin sulfate, cannabidiol and 2-camphenol is (1-5): (1-5): (1-5).

4. The method for preparing the oxidized konjac gum and hydrazide hyaluronic acid composite hydrogel according to any one of claims 1 to 3, wherein The method comprises the following steps: First, the oxidized konjac gum solution and the neomycin sulfate solution are fully mixed to react, and then the cannabidiol solution and the 2-benzyl alcohol solution are added in sequence, and finally the hydrazide hyaluronic acid solution is added. After rapid stirring and standing, the mixture can form a gel.

5. The method according to claim 4, characterized in that In the oxidized konjac gum solution, the mass volume concentration of the oxidized konjac gum is 1%-5%, and the solvent is water.

6. The method according to claim 4, characterized in that In the hydrazide hyaluronic acid solution, the mass volume concentration of the hydrazide hyaluronic acid is 1%-5%, and the solvent is water.

7. The method according to claim 4, characterized in that In the neomycin sulfate solution, the concentration of neomycin sulfate is 0.5 mol / L to 1 mol / L, and the solvent is anhydrous ethanol.

8. The method according to claim 4, characterized in that In the cannabidiol solution, the concentration of cannabidiol is 0.5 mol / L to 1 mol / L, and the solvent is anhydrous ethanol.

9. The method according to claim 8, characterized in that In the 2-bromophenol solution, the concentration of 2-bromophenol is 0.5 mol / L to 1 mol / L, and the solvent is anhydrous ethanol.

10. Use of the composite hydrogel of oxidized konjac gum and hydrazide hyaluronic acid according to any one of claims 1 to 3 in the preparation of a hemostatic material.

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