Injectable dextran-based hydrogel, dextran-based hydrogel loaded with polyphyllin I, and preparation method and application thereof

Abstract

The application belongs to the technical field of bio-based hydrogel preparation, and particularly relates to injectable dextran-based hydrogel, dextran-based hydrogel loaded with paris saponin I, and a preparation method and application thereof. The preparation method of the injectable dextran-based hydrogel comprises uniformly mixing an oxidized dextran aqueous solution and a modified hyaluronic acid aqueous solution at a volume ratio of 1:1, and obtaining the dextran-based hydrogel after standing. The preparation method of the injectable dextran-based hydrogel loaded with paris saponin I comprises adding paris saponin I into the oxidized dextran aqueous solution, and obtaining the dextran-based hydrogel loaded with paris saponin I. The dextran-based hydrogel can be injected to adapt to and close a wound in a short time, and can inhibit inflammation at the wound to accelerate wound repair by loading paris saponin 1. It is found through experiments that the hydrogel has excellent self-repairing performance and biocompatibility, and has good tissue adhesion, and is expected to be applied to human bodies in the near future.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of bio-based hydrogel preparation, and particularly relates to an injectable dextran-based hydrogel, a dextran-based hydrogel loaded with Paris saponin I, and a preparation method and application thereof. BACKGROUND

[0002] Hydrogel is a kind of functional polymer material with three-dimensional network structure and hydrophilic, in which water is the dispersion medium. As a new type of biomedical material, hydrogel has attracted widespread attention due to its good biocompatibility, flexibility, high water absorption, water retention and shape adaptability.

[0003] Dextran is a commonly used biomacromolecular material, and the dextran molecular chain contains a large number of hydroxyl groups, which provides favorable conditions for its graft modification. Due to its good biocompatibility and biodegradability, and abundant resources and low price, dextran is also widely used in biomedicine. Functional dextran products can be prepared into widely used hydrogel products by introducing catalysts and crosslinking agents in a chemical crosslinking manner.

[0004] Skin is the first barrier of the human body and the largest organ of the body. As it directly contacts with the outside world, the skin is also the most vulnerable and easily injured tissue. In life, people often use "dry healing" methods such as band-aid and gauze to treat wounds, which is convenient, but it is easy to form scab and tear, and it is also easy to damage the wound and cause secondary infection during the subsequent dressing change. The dynamic process of wound healing is the cooperative result of different systems of our body to repair and replace the inactivated tissue, which is divided into four stages: hemostasis, inflammation, proliferation and maturation. The prolonged inflammation period will seriously hinder the wound healing process. Most of the reported dextran-based compatible hydrogels are based on stable chemical crosslinking and can be used in the field of drug release, but they cannot be injected and do not have anti-inflammatory and wound repair properties. SUMMARY

[0005] The purpose of the present application is to provide an injectable dextran-based hydrogel, a dextran-based hydrogel loaded with Paris saponin I, and a preparation method and application thereof. The present application method uses biocompatible oxidized dextran as the main body, modified hyaluronic acid as the crosslinking agent to prepare the injectable dextran-based hydrogel and the dextran-based hydrogel loaded with Paris saponin I, and by adjusting the crosslinking density of oxidized dextran and modified hyaluronic acid, the obtained dextran-based hydrogel has excellent biocompatibility and drug release performance, and can be applied in the preparation of wound repair materials, controlled release drugs, injectable drugs and anti-inflammatory drugs.

[0006] The implementation process of the present application is as follows:

[0007] An injectable dextran-based hydrogel is spontaneously formed by an aldehyde compound oxidized dextran and modified hyaluronic acid in water.

[0008] A method for preparing the injectable dextran-based hydrogel is to mix an aqueous solution of oxidized dextran and an aqueous solution of modified hyaluronic acid uniformly at a volume ratio of 1:1, and the dextran-based hydrogel can be obtained after standing.

[0009] Further, the preparation process of the oxidized dextran is to dissolve dextran in a solvent to form a solution, then pour the solution into a reaction bottle, add an oxidizing agent to the reaction bottle for oxidation reaction, after the reaction is completed, dialysis and freeze-drying are performed to obtain the oxidized dextran, the solvent is selected from 4-morpholine ethanesulfonic acid aqueous solution or water; and the oxidizing agent is selected from sodium periodate, potassium periodate or lead tetraacetate.

[0010] Further, the oxidation reaction temperature is 30-50℃, and the reaction time is 12-48h; and the molar ratio of dextran to oxidizing agent is 1:(0.5-2).

[0011] Further, the preparation process of the modified hyaluronic acid is to dissolve hyaluronic acid in a solvent, then add a dehydrating agent and N-hydroxysuccinimide, after dissolution, add adipic acid dihydrazide for hydrazide reaction, and then perform dialysis and freeze-drying to obtain the modified hyaluronic acid; the solvent is selected from 4-morpholine ethanesulfonic acid aqueous solution or water; and the dehydrating agent is 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride, N,N-carbonyldiimidazole or dicyclohexyl carbodiimide.

[0012] Further, the molar ratio of hyaluronic acid to dehydrating agent is 1:2; the molar ratio of the dehydrating agent to N-hydroxysuccinimide is 4:1; the molar ratio of hyaluronic acid to adipic acid dihydrazide is 1:(5-10); the temperature of the hydrazide reaction is 20-50℃, and the reaction time is 24-96h.

[0013] The dextran-based hydrogel obtained by the above method is used for preparing wound repair materials, controlled-release drugs and injectable drugs.

[0014] An injectable dextran-based hydrogel loaded with paris saponin I is obtained by dissolving aldehyde compound oxidized dextran in water to form an aqueous solution, adding paris saponin I to obtain an oxidized dextran aqueous solution containing paris saponin I, and spontaneously forming the oxidized dextran aqueous solution containing paris saponin I and modified hyaluronic acid in water.

[0015] The preparation method of the injectable dioxadecurin I loaded dextran-based hydrogel is characterized in that: the dioxadecurin I is added into the aqueous solution of oxidized dextran in the preparation method of any one of claims 2-6, to obtain an aqueous solution of dioxadecurin I loaded oxidized dextran, and then the aqueous solution of modified hyaluronic acid is mixed with the aqueous solution of dioxadecurin I loaded oxidized dextran at a volume ratio of 1:1, and the dextran-based hydrogel loaded with dioxadecurin I is obtained after standing.

[0016] The dextran-based hydrogel loaded with dioxadecurin I obtained by the method is applied to the preparation of wound repair materials, controlled-release drugs, injectable drugs, inflammation inhibition, and wound repair acceleration drugs.

[0017] The reaction mechanism of the method is as follows:

[0018] (1) Oxidation reaction

[0019] The raw material dextran A is oxidized by an oxidizing agent to obtain oxidized dextran B;

[0020]

[0021] (2) Hydrazination reaction

[0022] The hyaluronic acid C and adipic acid dihydrazide D are synthesized into modified hyaluronic acid E under the condition of a dehydrating agent.

[0023]

[0024] (3) Gelation reaction

[0025] The oxidized dextran B and the modified hyaluronic acid E are dissolved in water respectively, and after being fully dissolved, they are mixed at a volume ratio of 1:1 and then stand, to obtain the dextran-based hydrogel F.

[0026]

[0027] In the gelation reaction, the dioxadecurin I is added into the aqueous solution of oxidized dextran B, and then the aqueous solution of modified hyaluronic acid E is mixed with the aqueous solution of dioxadecurin I at a volume ratio of 1:1, and after standing, the dextran-based hydrogel loaded with dioxadecurin I is obtained.

[0028] The method has the following beneficial effects:

[0029] (1) The dextran-based hydrogel can be injected to adapt to and close a wound in a short time, and the wound repair can be accelerated by inhibiting inflammation at the wound through loading of dioxadecurin I. It is found through experiments that the hydrogel has excellent self-repairing performance and biocompatibility, and has good tissue adhesion, and is expected to be applied to human bodies in the near future.

[0030] (2) The method of the present application can ensure that the obtained hydrogel has excellent biocompatibility and injectability by regulating the crosslinking density of oxidized dextran and modified hyaluronic acid. The prepared dextran-based hydrogel loaded with saponin I of Paris can be applied in the preparation of wound repair materials, controlled-release drugs, injectable drugs, inflammation inhibition, and wound repair acceleration drugs.

[0031] (3) The method of the present application solves the problem that the existing hydrogel needs to add a catalyst to realize crosslinking. BRIEF DESCRIPTION OF DRAWINGS

[0032] Figure 1 is the infrared spectrum of dextran and oxidized dextran; wherein Dex is the infrared spectrum of dextran, and ODex is the infrared spectrum of oxidized dextran;

[0033] Figure 2 is the nuclear magnetic resonance spectrum of dextran;

[0034] Figure 3 is the nuclear magnetic resonance spectrum of oxidized dextran;

[0035] Figure 4 is the cell viability assay of the dextran-based injectable hydrogel liquid and L929 cells co-incubated. DETAILED DESCRIPTION

[0036] The present application will be further described below in combination with examples.

[0037] The dextran-based injectable hydrogel and the dextran-based hydrogel loaded with saponin I of Paris obtained by the method of the present application have good stability, good biocompatibility and self-repairing performance, can quickly cover the damaged part when the organism is damaged, can self-repair and restore its use performance when the hydrogel is damaged, prolongs the service life, and the self-repairing process is close to the self-repairing process of the living body, and has a very broad application prospect in the field of biological medicine related to controlled release of drugs.

[0038] In the embodiment of the method of the present application, the molecular weight cut-off (MWCO) of the dialysis bag during the dialysis process is 8000-14000. The amount of saponin I of Paris in the dextran-based hydrogel loaded with saponin I of Paris can be increased according to the reagent demand.

[0039] Example 1 Preparation of dextran-based injectable hydrogel

[0040] (1) Oxidation reaction

[0041] 5 g of dextran (30.86 mmol) was dissolved in 245 mL of 4-morpholinoethanesulfonic acid (MES) aqueous solution (pH = 6.5) to form a 2 wt% solution, which was then added to a 500 mL reaction flask. 3.3 g (15.43 mmol) of sodium periodate was then added, and the mixture was reacted at 30 °C for 24 h. After the reaction was completed, the mixture was dialyzed and freeze-dried to obtain a white solid, which was oxidized dextran, with a yield of 78%.

[0042] (2) Acylhydrazide reaction

[0043] 5 g (12.40 mmol) of hyaluronic acid was dissolved in 245 mL of deionized water at pH 6.5. Then, 4.75 g (24.80 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) and 0.71 g (6.2 mmol) of N-hydroxysuccinimide (NHS) were dissolved in 10 mL of deionized water. All the solutions were added to the reaction flask, and then 10.8 g (62.00 mmol) of adipic acid dihydrazide was added. The reaction was carried out at 30 °C for 36 h. The product was purified by dialysis and freeze-dried to obtain white solid modified hyaluronic acid.

[0044] (3) Gelation reaction

[0045] Dissolve 0.05g of the above-mentioned oxidized dextran in 0.95g of deionized water to obtain a 5wt% solution. Then, dissolve 0.05g of modified hyaluronic acid in 0.95g of deionized water to obtain a 5wt% solution. Mix the two solutions at a volume ratio of 1:1 and let stand for 2 minutes to obtain an injectable dextran-based hydrogel.

[0046] like Figure 1 As shown, the infrared spectrum of oxidized dextran at 1745 cm⁻¹ is... -1 A new peak appeared, proving that an aldehyde group had been formed. For example... Figure 2 and Figure 3 The image shows the NMR spectra of dextran and oxidized dextran. Figure 2 The hydrogen a in the dextran exhibits a disappearing peak at -3.6 ppm in the NMR spectrum due to oxidation, and... Figure 3 A new peak of -5.6 ppm appears at position b in the NMR spectrum.

[0047] The process of cell viability measurement:

[0048] Cell viability assay was performed using mouse fibroblast cells (L929) and DMEM containing 10% fetal bovine serum as cell culture medium. Different concentrations of dextran-based hydrogel solution were prepared using cell culture medium as solvent. Cells were incubated in hydrogel solution for 24h and 48h, 10μL CCK-8 solution was added to each well at the predetermined time, and the cells were incubated at room temperature for another 3h. The absorbance of each well was measured at 450nm using a microplate reader to calculate the cell survival rate, and the average value ± DS (n = 6) was obtained.

[0049] As shown in Figure 4 The injectable dextran-based hydrogel was incubated with L929 cells, and the cell viability assay showed that the cell survival rate was more than 80%, indicating that the dextran-based hydrogel was biocompatible and non-toxic and harmless.

[0050] Example 2 Preparation of injectable dextran-based hydrogel loaded with saponin I from Paris polyphylla

[0051] In this example, steps (1) and (2) are the same as in Example 1. The difference is in step (3):

[0052] (3) Gelation reaction

[0053] 0.05g of the above oxidized dextran was dissolved in 0.95g of deionized water to form a 5wt% concentration solution, and 10mg of saponin I was added to the solution to obtain an oxidized dextran solution containing saponin I. Then 0.05g of modified hyaluronic acid was dissolved in 0.95g of deionized water to form a 5wt% solution, and the two solutions were mixed uniformly at a volume ratio of 1:1, and then left to stand for 2min to obtain a dextran-based hydrogel loaded with saponin I.

[0054] Example 3 Preparation of injectable dextran-based hydrogel

[0055] (1) Oxidation reaction

[0056] 5g (30.86mmol) of dextran was dissolved in 245mL of deionized water to form a 2wt% concentration solution, which was then added to a 500mL reaction bottle, followed by the addition of 13.2g (61.72mmol) of potassium periodate. The reaction was carried out at 50°C for 12h. After the reaction was completed, the mixture was dialyzed and freeze-dried to obtain a white solid, which was the oxidized dextran with a yield of 67%.

[0057] (2) Hydrazination reaction

[0058] Dissolve 5 g (12.40 mmol) of hyaluronic acid in 245 mL of 4-morpholine ethanesulfonic acid (MES) aqueous solution (pH = 6.5), then dissolve 4.02 g (24.80 mmol) of N,N-carbonyldiimidazole (CDI) and 0.71 g (6.2 mmol) of N-hydroxysuccinimide (NHS) in 10 mL of deionized water, add the above solutions to the reaction bottle, and then add 10.8 g (62.00 mmol) of adipic acid dihydrazide, and react at 20°C for 96 h. The obtained product is purified by dialysis and freeze-dried to obtain a white solid, which is modified hyaluronic acid.

[0059] (3) Gelation reaction

[0060] Dissolve 0.15 g of the above oxidized dextran in 0.85 g of deionized water to form a 15 wt% solution, and then add 20 mg of Paris saponin I to obtain an oxidized dextran solution containing Paris saponin I. Then, dissolve 0.15 g of modified hyaluronic acid in 0.85 g of deionized water to form a 15% concentration solution. Mix the two solutions uniformly at a volume ratio of 1:1, and stand for 8 min to obtain a dextran-based hydrogel loaded with Paris saponin I.

[0061] Preparation of injectable dextran-based hydrogel loaded with Paris saponin I according to Example 4

[0062] Steps (1) and (2) in this example are the same as in Example 3. The difference is in step (3):

[0063] (3) Gelation reaction

[0064] Dissolve 0.15 g of the above oxidized dextran in 0.85 g of deionized water to form a 15 wt% solution, and then add 20 mg of Paris saponin I to obtain an oxidized dextran solution containing Paris saponin I. Then, dissolve 0.15 g of modified hyaluronic acid in 0.85 g of deionized water to form a 15% concentration solution. Mix the two solutions uniformly at a volume ratio of 1:1, and stand for 8 min to obtain a dextran-based hydrogel loaded with Paris saponin I.

[0065] Preparation of injectable dextran-based hydrogel according to Example 5

[0066] (1) Oxidation reaction

[0067] Dissolve 10 g (24.80 mmol) of dextran in 490 mL of deionized water to form a 2 wt% solution, and add it to a 1 L reaction bottle, then add 10.1 g (22.78 mmol) of lead tetraacetate, and react at 40°C for 36 h. After the reaction is completed, the mixture is dialyzed and freeze-dried to obtain a white solid, which is oxidized dextran, with a yield of 75%.

[0068] (2) Hydrazination reaction

[0069] Dissolve 5 g (12.40 mmol) of hyaluronic acid in 245 mL of 4-morpholine ethanesulfonic acid (MES) aqueous solution (pH = 6.5), then dissolve 4.756.25 g (24.80 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC-HCl) and 0.71 g (6.2 mmol) of N-hydroxysuccinimide (NHS) in 10 mL of deionized water, add the above solutions to the reaction bottle, and then add 21.6 g (124.00 mmol) of adipic dihydrazide, and react at 40°C for 46 h. The resulting product is purified by dialysis and freeze-dried to obtain a white solid, which is modified hyaluronic acid.

[0070] (3) Gelation reaction

[0071] Dissolve 0.2 g of the above oxidized dextran in 0.8 g of deionized water to form a 20 wt% concentration solution, and then add 20 mg of Paris saponin I to obtain an oxidized dextran solution containing Paris saponin I. Then, dissolve 0.2 g of modified hyaluronic acid in 0.8 g of deionized water to form a 20 wt% solution. Mix the two solutions uniformly at a volume ratio of 1:1, and stand for 5 min to obtain a dextran-based hydrogel loaded with Paris saponin I.

[0072] Preparation of injectable dextran-based hydrogel loaded with Paris saponin I according to Example 6

[0073] In this example, steps (1) and (2) are the same as in Example 5. The difference is in step (3):

[0074] (3) Gelation reaction

[0075] Dissolve 0.2 g of the above oxidized dextran in 0.8 g of deionized water to form a 20 wt% concentration solution, and then add 20 mg of Paris saponin I to obtain an oxidized dextran solution containing Paris saponin I. Then, dissolve 0.2 g of modified hyaluronic acid in 0.8 g of deionized water to form a 20 wt% solution. Mix the two solutions uniformly at a volume ratio of 1:1, and stand for 5 min to obtain a dextran-based hydrogel loaded with Paris saponin I.

[0076] Preparation of injectable dextran-based hydrogel according to Example 7

[0077] (1) Oxidation reaction

[0078] Dissolve 5 g (30.86 mmol) of dextran in 245 mL of deionized water to form a 2 wt% concentration solution, and add it to a 500 mL reaction bottle. Then, add 6.6 g (30.86 mmol) of sodium periodate, and react at 30°C for 48 h. After the reaction is completed, the mixture is dialyzed and freeze-dried to obtain a white solid, which is oxidized dextran, with a yield of 77%.

[0079] (2) Hydrazination reaction

[0080] Dissolve 5 g (12.40 mmol) of hyaluronic acid in 245 mL of deionized water, then dissolve 5.12 g (24.80 mmol) of dicyclohexyl carbodiimide (DCC) and 0.71 g (6.2 mmol) of N-hydroxysuccinimide (NHS) in 10 mL of deionized water, add both solutions to a reaction bottle, then add 10.8 g (62.00 mmol) of adipic acid dihydrazide, and react at 50°C for 24 h. The resulting product is purified by dialysis and freeze-dried to obtain a white solid, which is modified hyaluronic acid.

[0081] (3) Gelation reaction

[0082] Dissolve 0.03 g of the above oxidized dextran in 0.97 g of deionized water to form a 3 wt% solution, and then dissolve 0.03 g of the modified hyaluronic acid in 0.97 g of deionized water to form a 3 wt% solution. Mix the two solutions uniformly at a volume ratio of 1:1, and let stand for 2 min to obtain a dextran-based hydrogel loaded with Paris saponin I.

[0083] Preparation of injectable dextran-based hydrogel loaded with Paris saponin I

[0084] In this example, steps (1) and (2) are the same as in Example 7. The difference is in step (3):

[0085] (3) Gelation reaction

[0086] Dissolve 0.03 g of the above oxidized dextran in 0.97 g of deionized water to form a 3 wt% solution, and then add 15 mg of Paris saponin I to obtain an oxidized dextran solution containing Paris saponin I. Dissolve 0.03 g of the modified hyaluronic acid in 0.97 g of deionized water to form a 3 wt% solution. Mix the two solutions uniformly at a volume ratio of 1:1, and let stand for 2 min to obtain a dextran-based hydrogel loaded with Paris saponin I.

[0087] Preparation of injectable dextran-based hydrogel

[0088] (1) Oxidation reaction

[0089] Dissolve 5 g (30.86 mmol) of dextran in 245 mL of deionized water to form a 2 wt% solution, and add it to a 500 mL reaction bottle. Then add 6.6 g (30.86 mmol) of sodium periodate, and react at 30°C for 24 h. After the reaction is completed, the mixture is dialyzed and freeze-dried to obtain a white solid, which is oxidized dextran, with a yield of 72%.

[0090] (2) Hydrazination reaction

[0091] Dissolve 5 g (12.40 mmol) of hyaluronic acid in 245 mL of deionized water with pH 6.5, then dissolve 4.75 g (24.80 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC-HCl) and 0.71 g (6.2 mmol) of N-hydroxysuccinimide (NHS) in 10 mL of deionized water, add the above solutions to the reaction bottle, and then add 10.8 g (62.00 mmol) of adipic acid dihydrazide, and react at 30°C for 48 h. The obtained product is purified by dialysis and freeze-dried to obtain modified hyaluronic acid as a white solid.

[0092] (3) Gelation reaction

[0093] Dissolve 0.02 g of the above oxidized dextran in 0.98 g of deionized water to form a 2 wt% solution, and then dissolve 0.02 g of the modified hyaluronic acid in 0.98 g of deionized water to form a 2 wt% solution. Mix the two solutions uniformly at a volume ratio of 1:1, and stand for 10 min to obtain the dextran-based hydrogel loaded with Paris saponin I.

[0094] Preparation of injectable dextran-based hydrogel loaded with Paris saponin I

[0095] In this example, steps (1) and (2) are the same as in Example 9. The difference is in step (3):

[0096] (3) Gelation reaction

[0097] Dissolve 0.02 g of the above oxidized dextran in 0.98 g of deionized water to form a 2 wt% solution, and then dissolve 0.02 g of the modified hyaluronic acid in 0.98 g of deionized water to form a 2 wt% solution. Mix the two solutions uniformly at a volume ratio of 1:1, and stand for 10 min to obtain the dextran-based hydrogel loaded with Paris saponin I.

[0098] Performance test of dextran-based hydrogel and injectable dextran-based hydrogel loaded with Paris saponin I

[0099] I. Determination of swelling rate and water content

[0100] Determination of swelling rate: weigh the hydrogel as M0, immerse it in pure water, and after complete swelling for 24 h, remove and dry the surface water to obtain the wet weight Mw. The swelling rate (SR) is calculated according to the following formula: SR (%) = (Mw- M0) / M0 s s ​M0) x 100 / M0

[0101] Water content determination: The hydrogel was weighed as M0, and after freeze-drying, the mass was weighed as M d Water content (WR): WR (%) = (M0- M d ) x 100 / M0

[0102] The measured swelling rate of the dextran-based hydrogel prepared in Example 1 was 30-100%.

[0103] The measured water content of the dextran-based hydrogel prepared in Example 1 was 40-90%.

[0104] The measured swelling rate of the dextran-based hydrogel loaded with saponin I prepared in Example 2 was 32-100%.

[0105] The measured water content of the dextran-based hydrogel loaded with saponin I prepared in Example 2 was 41-90%.

[0106] II. Bacteriostatic experiment test

[0107] Each of E. coli and S. aureus was inoculated with 100 μL of bacterial suspension with a bacterial number turbidity of 0.5 mcf onto a corresponding agar plate, uniformly spread, and then each of the dextran-based hydrogel of Example 1 and the dextran-based hydrogel loaded with saponin I prepared in Example 2 was added, with 3 repeated plates for each bacterium, 37°C culture for 24 h, and the results were observed. The diameter of the bacteriostatic ring was measured, repeated 3 times, and the average value was taken.

[0108] Table 1 Bacteriostatic performance of different samples

[0109]

[0110] The above data show that the bacteriostatic performance of the dextran-based hydrogel loaded with saponin I is better than that of the dextran-based hydrogel.

[0111] III. Wound healing experiment test

[0112] 30 rats with a body weight of 220-240 g were randomly divided into 3 groups, 10 rats in each group, and the rats were routinely fed for 3 days. After successful anesthesia, the rats were shaved, and a circular full-thickness skin with a diameter of 1 cm was cut to form an open wound, which reached the fascia. After the establishment of the wound model, the first group was a blank control group, the second group was applied with the dextran-based hydrogel prepared in Example 1, and the third group was applied with the dextran-based hydrogel loaded with saponin I prepared in Example 2. Then the gauze was fixed and the rats were fed in a single cage. The dressing gel was changed every 2 days for groups 2 and 3 until the wound completely healed, and the number of days was recorded and the change in wound area was counted. The results are as follows:

[0113] Table 2 Effect of different dressing samples on wound healing in rats

[0114] Time / Days 1 3 5 10 15 Group 1 Wound Area / cm 2 ]] 3.1 3.1 2.8 2.4 2.3 Group 2 Wound Area / cm 2 ]] 3.1 3.0 2.8 2.6 2.0 Group 3 Wound Area / cm 2 ]] 3.0 2.5 1.7 0.8 0

[0115] The above data show that the hydrogel prepared using the present application has a faster wound healing time, i.e. promotes wound healing.

[0116] IV. Self-healing experiment

[0117] The dextran-based hydrogel of Example 1 was cut into two long strips, and after being pressed end to end for 24 h, the two strips were bonded together, indicating that the dextran-based hydrogel has self-healing properties.

[0118] The dextran-based hydrogel loaded with Paris saponin I prepared in Example 2 was cut into two long strips, and after being pressed end to end for 24 h, the two strips were bonded together, indicating that the dextran-based hydrogel loaded with Paris saponin I has self-healing properties.

[0119] V. Adhesion experiment

[0120] A lap shear test was performed on a universal testing machine (HY 940F, China) to measure the adhesive strength of the dextran-based hydrogel of Example 1 and the dextran-based hydrogel loaded with Paris saponin I prepared in Example 2. The hydrogel was applied to the surface of pig skin tissue, and the bonding area was 10 mm x 10 mm. Pig skin was selected to simulate adhesion to soft tissue. The stretching rate was 2 mm min -1 A lap shear test was performed to measure the adhesive strength.

[0121] The adhesive strength of the dextran-based hydrogel of Example 1 was measured to be 4.1 kPa. The adhesive strength of the dextran-based hydrogel loaded with Paris saponin I prepared in Example 2 was measured to be 4.3 kPa.

[0122] VI. Controlled release of drugs

[0123] The dextran-based hydrogel loaded with Paris saponin I prepared in Example 2 was placed in pure water, and water samples were taken at 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 20 h, 24 h, 30 h, 36 h, and the absorption of Paris saponin was tested by ultraviolet-visible spectroscopy. The release concentration was determined by comparison with the standard curve.

[0124] The dextran-based hydrogel loaded with Paris saponin I was measured to release 20-50% of Paris saponin I at 12 h, and 40-70% of Paris saponin I at 24 h.

[0125] The above description is further detailed in combination with specific preferred embodiments of the present application, and cannot be deemed as limiting the specific implementation of the present application to these descriptions. For those skilled in the art to which the present application belongs, several simple deductions or replacements can be made without departing from the concept of the present application, and all of them should be deemed as falling within the protection scope of the present application.

Claims

1. A method for preparing injectable glycodendrimer-based hydrogel loaded with sarsasapogenin I, characterized by: The oxidized dextran aqueous solution is obtained by adding Paris saponin I into the oxidized dextran aqueous solution, and then mixed with the modified hyaluronic acid aqueous solution in a volume ratio of 1:1, and the dextran-based hydrogel loaded with Paris saponin I is obtained after standing. The preparation process of the oxidized dextran is as follows: dextran is dissolved in a solvent to form a solution, and then the solution is poured into a reaction bottle, an oxidizing agent is added into the reaction bottle for oxidation reaction, after the reaction is completed, the oxidized dextran is obtained by dialysis and freeze-drying, the solvent is selected from 4-morpholine ethanesulfonic acid aqueous solution or water, and the oxidizing agent is selected from sodium periodate, potassium periodate or lead tetraacetate; the molar ratio of dextran to the oxidizing agent is 1:(0.5-2). The preparation process of the modified hyaluronic acid is as follows: hyaluronic acid is dissolved in a solvent, then a dehydrating agent and N-hydroxysuccinimide are added, after dissolution, hexanedioic acid dihydrazide is added for hydrazide reaction, and the modified hyaluronic acid is obtained by dialysis and freeze-drying; the solvent is selected from 4-morpholine ethanesulfonic acid aqueous solution or water; the dehydrating agent is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N-carbonyldiimidazole or dicyclohexyl carbodiimide; the molar ratio of hyaluronic acid to hexanedioic acid dihydrazide is 1:(5-10); the molar ratio of hyaluronic acid to the dehydrating agent is 1:2; and the molar ratio of the dehydrating agent to N-hydroxysuccinimide is 4:

1.

2. The method for preparing the injectable polysaccharide hydrogel loaded with psorospermin I according to claim 1, characterized in that: The oxidation reaction temperature is 30-50 ℃, and the reaction time is 12-48 h.

3. The method for preparing the injectable dextran-based hydrogel loaded with Paris polyphylla saponin I according to claim 1, characterized in that: The hydrazide reaction temperature is 20-50 ℃, and the reaction time is 24-96 h.

4. The dextran-based hydrogel loaded with Paris saponin I prepared by the method of claim 1 is used for preparing wound repair materials, controlled-release drugs, injectable drugs and drugs for accelerating wound repair.

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