Injectable hydrogel for inhibiting abdominal postoperative adhesion and preparation method thereof

Abstract

The invention discloses injectable hydrogel for inhibiting adhesion after an abdominal cavity operation and a preparation method of the injectable hydrogel, and belongs to the cross technical field of biomedical materials and clinical medicine. The honeysuckle plant exosome is prepared from the following raw materials: water-soluble chitosan (CS), hyaluronic acid (HA), an active oxygen responsive chain segment construction macromonomer (Linker), a medicine-loaded honeysuckle plant exosome solution and a cross-linking agent. The raw materials are mixed and subjected to a cross-linking reaction, and the injectable hydrogel is prepared. According to the preparation method, water-soluble chitosan, hyaluronic acid and active oxygen responsive chain segments are used for constructing a macromonomer, genipin is used as a biological cross-linking agent, and the honeysuckle plant exosome containing drugs is loaded into injectable hydrogel, so that the purposes of eliminating postoperative abdominal inflammation and repairing and treating wounds are achieved, and the preparation method is simple and convenient. Therefore, postoperative abdominal cavity tissue adhesion can be synergistically treated and / or prevented.

Description

Technical Field

[0001] The invention belongs to the cross-technical field of biomedical materials and clinical medicine, and in particular relates to an injectable hydrogel for inhibiting postoperative adhesion of the abdominal cavity and a preparation method thereof. Background Art

[0002] Abdominal adhesions refer to abnormal adhesions between the peritoneal surfaces caused by inflammation, surgery, trauma, infection or other pathological processes in the abdominal cavity. These adhesions may occur anywhere in the abdominal cavity, including between organs, between organs and the abdominal wall, or between the peritoneum and other structures. Surgery is the most common cause of abdominal adhesions, especially after abdominal or pelvic surgery. During surgery, prolonged exposure of the intestine, rough movements, large wounds, incomplete hemostasis, postoperative bleeding, exudation, incomplete peritoneal irrigation, or foreign matter left in the abdominal cavity may all cause adhesions, seriously affecting the patient's health.

[0003] To address these problems, laparoscopic surgery and physical isolation materials can be used for treatment. However, laparoscopic surgery has limitations. It cannot completely eliminate adhesions between the abdominal wall and organs, nor can it reduce the incidence of visceral adhesions. In addition, physical isolation materials perform poorly in terms of degradation and anti-swelling properties, which limits their therapeutic effects. Therefore, how to solve these problems has always been a hot topic and difficulty in clinical research. How to treat moderate to severe abdominal adhesions and prevent their recurrence remains an urgent problem to be solved. Summary of the invention

[0004] In view of the above technical problems, the present invention proposes an injectable hydrogel for inhibiting postoperative abdominal adhesion and a preparation method thereof. That is, water-soluble chitosan, hyaluronic acid, and active oxygen responsive segments are used to construct macromolecular monomers, genipin is used as a biocrosslinker, and drug-containing honeysuckle plant exosomes are loaded into the injectable hydrogel, aiming to achieve the removal of postoperative abdominal inflammation and wound repair treatment, so as to synergistically treat and / or prevent postoperative abdominal tissue adhesion.

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] An injectable hydrogel for inhibiting postoperative adhesion of the abdominal cavity, the raw materials comprising:

[0007] Water-soluble chitosan (CS), hyaluronic acid (HA), active oxygen responsive segment-constructed macromolecular monomer (Linker), drug-loaded honeysuckle plant exosome solution and cross-linking agent;

[0008] The structural formula of the macromolecular monomer constructed by the active oxygen responsive segment is:

[0009]

[0010] The synthesis steps of the active oxygen responsive segment to construct the macromolecular monomer are:

[0011] (1) Add 10 mL of thioglycolic acid and 5 mL of acetone, then inject hydrogen chloride gas and react at room temperature for 4 h;

[0012] (2) extracting and evaporating the solution in step (1) to obtain product 1;

[0013] (3) adding the product 1 obtained in step (2) to 10 mL of a tetrahydrofuran solution (1 mol / L) containing lithium aluminum hydride, and reacting at room temperature overnight;

[0014] (4) extracting and evaporating the solution in step (3) to obtain product 2;

[0015] (5) The product 2 of step (4) was mixed with 1 g of hydrogenated PMDA, 10 mL of DMF was added, and the mixture was reacted at room temperature for 12 h to obtain a macromolecular monomer for constructing an active oxygen responsive chain segment;

[0016] The synthetic route of the active oxygen responsive segment to construct the macromolecular monomer is as follows:

[0017]

[0018] Beneficial effects: An injectable hydrogel for inhibiting postoperative abdominal adhesion is prepared by the above raw materials defined in the present invention, wherein the function of Linker is to remove reactive oxygen and reduce inflammation; chitosan (CS) has biocompatibility and stability, and can also sterilize, stop bleeding, absorb wound exudate, reduce scar formation and biodegradable and other excellent properties; hyaluronic acid (HA) hydrogel exhibits good biocompatibility, biofunctionality, biodegradability and injectability; the honeysuckle plant exosome solution containing drugs can transfer a variety of bioactive molecules including nucleic acids, proteins and lipids from donor cells to recipient cells, mediate intercellular communication and molecular transport; and the honeysuckle plant exosomes containing drugs have good biocompatibility and can promote the regeneration and repair of damaged tissues. Therefore, the honeysuckle plant exosomes containing drugs of the present invention are loaded into the injectable hydrogel, aiming to achieve the removal of postoperative abdominal inflammation and wound repair treatment, so as to synergistically treat and / or prevent postoperative abdominal tissue adhesion, and have broad clinical application prospects. In addition, the injectable hydrogel for inhibiting postoperative adhesion of the abdominal cavity prepared by the present invention is non-toxic, has good biocompatibility, and has good mechanical properties and viscoelasticity.

[0019] Optionally, the drug includes puerarin, ibuprofen or methyldeferoxamine.

[0020] Furthermore, the drug is puerarin; and the cross-linking agent is genipin.

[0021] Optionally, the preparation process of the honeysuckle plant exosome solution loaded with drugs is:

[0022] Fresh honeysuckle juice is squeezed, and then coarse filtration, centrifugation and fine filtration are performed in sequence to obtain honeysuckle plant exosome solution, and then drugs are added thereto and dialyzed.

[0023] Furthermore, the concentration of the drug in the honeysuckle plant exosome solution is 4 to 10 mg / mL.

[0024] Furthermore, the fine filtration operation is: filtering with a 0.22 um filter.

[0025] Optionally, the mass ratio of the water-soluble chitosan to hyaluronic acid is (3-5):1; preferably 4:1.

[0026] The second technical solution of the present invention:

[0027] A method for preparing an injectable hydrogel for inhibiting postoperative adhesion of the abdominal cavity comprises the following steps:

[0028] Adding the linker solution to the hyaluronic acid solution for a primary reaction, then gradually adding a water-soluble chitosan solution thereto for a secondary reaction, and then performing dialysis, centrifugation and freeze-drying in sequence to prepare HA-Linker-CS powder;

[0029] The HA-Linker-CS powder is dissolved in a honeysuckle plant exosome solution loaded with drugs, a cross-linking agent is added, and the solution is allowed to stand to obtain the injectable hydrogel for inhibiting postoperative adhesion of the abdominal cavity.

[0030] Optionally, the volume ratio of the water-soluble chitosan solution, the hyaluronic acid solution and the active oxygen responsive segment constructing macromolecular monomer solution is: (450-750):150:1;

[0031] Wherein, the concentrations of the water-soluble chitosan solution and the hyaluronic acid solution are both 1 g / 600 mL;

[0032] The concentration of the active oxygen responsive segment constructing macromolecular monomer solution is 200-300 mg / mL.

[0033] Optionally, the dosage ratio of the HA-Linker-CS powder, the drug-loaded honeysuckle plant exosome solution and the cross-linking agent is: (0.01-0.5 g): 1 mL: (50-150 μL), preferably: 0.35 g: 1 mL: 100 μL.

[0034] Optionally, the time of one reaction is 1 h; and / or

[0035] The secondary reaction time was 12 h; the temperatures for both reactions were room temperature.

[0036] Compared with the prior art, the present invention has the following advantages and technical effects:

[0037] The present invention aims to simultaneously achieve the clearance of postoperative abdominal inflammation and wound repair treatment (promoting tissue regeneration and repair) by loading drug-containing honeysuckle plant exosomes into injectable hydrogels, embodying the dual effects of anti-inflammatory and promoting regeneration and repair, so as to synergistically treat and / or prevent postoperative abdominal tissue adhesion.

[0038] Therefore, by injecting the injectable hydrogel prepared by the present invention into the wound, the risk of postoperative abdominal adhesion can be significantly reduced, providing patients with better treatment effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The accompanying drawings constituting a part of the present invention are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the accompanying drawings:

[0040] Figure 1 This is a SEM image of the CS-Linker-HA powder prepared in Example 1 of the present invention;

[0041] Figure 2 This is a synthetic route diagram of the CS-Linker-HA powder prepared in Example 1 of the present invention;

[0042] Figure 3 This is a degradation diagram of the CS-Linker-HA powder prepared in Example 1 of the present invention in hydrogen peroxide (0.1 mM);

[0043] Figure 4 The degradation comparison diagram (a) and the degradation curve diagram (b) of the CS-Linker-HA powder prepared in Example 1 of the present invention in hydrogen peroxide (0.1 mM) and PBS solution for 7 days;

[0044] Figure 5 The NMR infrared characterization images of CS, HA and CS-Linker-HA powder prepared in Example 1 of the present invention;

[0045] Among them, the left picture is the nuclear magnetic resonance image; the right picture is the infrared image;

[0046] Figure 6 This is a picture of the tissue adhesion between the peritoneum and intestines of mice in the blank control group, blank gel group, and drug-loaded honeysuckle plant exosome hydrogel group 14 days after surgery;

[0047] Among them, (a) is a schematic diagram of tissue adhesion between mouse peritoneum and intestine; (b) is a H&E and Masson staining diagram of tissue adhesion between mouse peritoneum and intestine; (c) is a diagram of the percentage of collagen loss;

[0048] Figure 7 and Figure 8 Immunofluorescence images (a) and relative fluorescence intensity bar graphs (b) of growth factors VEGF, CD31, CD206, IL-4, inflammatory factors CD86, IL-6, TNF-α, α-SMA in the blank control group, blank gel group, and drug-loaded honeysuckle plant exosome hydrogel group;

[0049] Fig. 9 H&E staining of the heart, liver, spleen, lung, and kidney of mice injected with drug-loaded honeysuckle plant exosome hydrogel 14 days after surgery;

[0050] Fig.10 This is the immunofluorescence image of the spleen of mice injected with drug-loaded honeysuckle plant exosome hydrogel 14 days after surgery. DETAILED DESCRIPTION

[0051] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0052] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0053] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0054] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present invention description and examples are exemplary only.

[0055] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0056] The raw materials used in the present invention are all purchased from the market.

[0057] The technical solution of the present invention is further illustrated by the following embodiments.

[0058] Example 1

[0059] A method for preparing an injectable hydrogel capable of inhibiting postoperative adhesion of the abdominal cavity comprises the following steps:

[0060] (1) Preparation of solution:

[0061] 1 g of hyaluronic acid was added into a beaker containing 600 mL of distilled water to dissolve to obtain a hyaluronic acid solution;

[0062] 1 g of water-soluble chitosan was added to another beaker containing 600 mL of distilled water to dissolve to obtain a water-soluble chitosan solution;

[0063] (2) 30 mL of hyaluronic acid solution was added with 0.2 mL of linker aqueous solution (concentration was 250 mg / mL), reacted for 1 h, and then 120 mL of water-soluble chitosan solution was gradually added thereto. After reacting for 12 h, the mixture was dialyzed for 48 days, centrifuged and freeze-dried for 72 hours to form HA-Linker-CS powder;

[0064] The SEM image of CS-Linker-HA powder is shown in Figure 1 , see the synthesis principle diagram Figure 2 ;Depend on Figure 1 It can be seen that it is a porous structure, which gives it a large specific surface area and provides sufficient space for loading active pharmaceutical ingredients;

[0065] Figure 3 This is a degradation diagram of the CS-Linker-HA powder prepared in Example 1 of the present invention in hydrogen peroxide (0.1 mM). It can be seen from the figure that the skeleton structure is severely damaged after being degraded by hydrogen peroxide, indicating that the HA-Linker-CS powder has good degradability;

[0066] Figure 4The degradation comparison diagram (a) and the degradation curve diagram (b) of the CS-Linker-HA powder prepared in Example 1 of the present invention in hydrogen peroxide (0.1 mM) and PBS solution for 7 days show that the degradation rate of HA-Linker-CS powder in hydrogen peroxide is much greater than that in PBS;

[0067] Figure 5 The NMR characterization pictures of CS, HA and CS-Linker-HA powder prepared in Example 1 of the present invention; wherein, the left picture is the NMR picture; the right picture is the IR picture. It can be seen from the pictures that CS-Linker-HA shows unique characteristic peaks compared with the individual CS and HA, which indicates that the Linker has successfully bonded CS and HA together.

[0068] (3) Weigh 0.35 g of HA-Linker-CS powder, add 1 mL of distilled water, stir evenly, add 100 μL (active ingredient content 0.01 g / mL) of genipin, stir evenly, and let stand to obtain an injectable hydrogel that can inhibit postoperative adhesions in the abdominal cavity.

[0069] Example 2

[0070] A method for preparing an injectable hydrogel capable of inhibiting postoperative adhesion of the abdominal cavity comprises the following steps:

[0071] Steps (1) and (3) are the same as in Example 1;

[0072] (2) 30 mL of hyaluronic acid solution was added with 0.2 mL of linker solution and reacted for 1 h. Then, 90 mL of water-soluble chitosan solution was gradually added thereto. After reacting for 12 h, the solution was dialyzed for 48 days, centrifuged and freeze-dried for 72 hours to form HA-Linker-CS powder.

[0073] Example 3

[0074] A method for preparing an injectable hydrogel capable of inhibiting postoperative adhesion of the abdominal cavity comprises the following steps:

[0075] Steps (1) and (3) are the same as in Example 1;

[0076] (2) 30 mL of hyaluronic acid solution was added with 0.2 mL of linker solution and reacted for 1 h. Then 150 mL of water-soluble chitosan solution was gradually added thereto. After reacting for 12 h, the solution was dialyzed for 48 days, centrifuged and freeze-dried for 72 hours to form HA-Linker-CS powder.

[0077] Example 4

[0078] A method for preparing a drug-loaded honeysuckle plant exosome injectable hydrogel comprises the following steps:

[0079] Steps (1) and (2) are the same as in Example 1;

[0080] (3) The distilled water was replaced with an equal volume of the drug-loaded honeysuckle plant exosome solution, and the preparation process of the solution was as follows:

[0081] First, squeeze the fresh honeysuckle into juice, then filter it coarsely, extract the upper liquid, and then centrifuge it in a high-power centrifuge (the speed is 10000rpm, the centrifugation time is 10min), take the supernatant, and then filter it with a 0.22um filter to obtain a relatively pure honeysuckle extract (i.e., honeysuckle plant exosome solution). Add puerarin (added amount 5mg / mL) to the honeysuckle extract and dialyze it for 1 day.

[0082] Effect verification

[0083] The injectable hydrogels prepared in Example 1 and Example 4 were used to evaluate the anti-adhesion effect of the injectable hydrogels in an animal model of abdominal cavity injury in Kunming mice. The detailed steps are as follows:

[0084] Fifteen female Kunming mice of similar size were selected (Henan Sikebes Biotechnology Co., Ltd., weighing 20 g to 25 g, and all operations on animals were in accordance with NIH guidelines).

[0085] The mice were fed for 5 days before surgery and randomly divided into three groups, with 5 mice in each group, namely, the first group was a blank control group, the second group was a blank gel group (Example 1), and the third group was a drug-loaded honeysuckle plant exosome hydrogel group (Example 4).

[0086] The materials needed for the experiment must be exposed to ultraviolet light for half an hour. Animal experiments were conducted in a sterile experimental environment: first, 0.25-0.35 mL of chloral hydrate solution (5% w / v) was injected into the mouse's peritoneal cavity, the mouse was weighed and anesthetized, the abdomen was depilated and disinfected with ethanol, and then the mouse's abdomen was opened, a small hole with a diameter of 1 cm was cut in the mouse's peritoneum, and the materials needed for the experiment were loaded when the abdomen was sutured (i.e., the materials were injected into the wound surface with a syringe, and the injection volume was 0.5 mL). The blank group did not receive any intervention; the peritoneum and skin were sutured with a 5-0 suture needle.

[0087] After the experiment, the mice were placed in a clean cage and waited for them to wake up. The mice were disinfected with iodine every day. All mice were killed 14 days after the operation, and the small holes and adhesions cut from the abdominal cavity were dissected and rinsed with PBS, then immersed in tissue cell fixative (4% PFA), and finally embedded in paraffin to make paraffin sections with a thickness of 4.0 μm. The sections were then stained with eosin H&E and Masson, and the histopathology and adhesion formation were analyzed respectively. And VEGF, CD31, CD206, CD86, IL-6, TNF-α, α-SMA, and IL-4 were determined by immunofluorescence staining.

[0088] Figure 6 The figures are the tissue adhesion between the peritoneum and intestines of mice in the blank control group, blank gel group, and drug-loaded honeysuckle plant exosome hydrogel group 14 days after surgery, where (a) is the tissue adhesion between the peritoneum and intestines of mice; (b) is the H&E and Masson staining of the tissue adhesion between the peritoneum and intestines of mice; (c) is the percentage of collagen loss.

[0089] like Figure 6 As shown, the blank control group had a large area of ​​tissue adhesion between the peritoneum and the intestine. In the blank gel group, the collagen tissue was well separated, with a small area of ​​adhesion. The drug-loaded honeysuckle plant exosome hydrogel group showed the best anti-adhesion effect, with almost no adhesion and the most collagen tissue. This shows that the drug-loaded honeysuckle plant exosome hydrogel group can resist inflammation and promote tissue regeneration, preventing the occurrence of abdominal adhesion.

[0090] All groups were marked by immunofluorescence for inflammation assessment, such as VEGF, CD31, CD206, CD86, IL-6, TNF-α, α-SMA, IL-4. Figure 7 and Figure 8 VEGF, CD31, CD206, CD86, IL-6, TNF-α, α-SMA, and IL-4 in the blank control group, blank gel group, and drug-loaded honeysuckle plant exosome hydrogel group. Figure 7 and Figure 8As shown, in the blank control group, a large number of inflammatory factors CD86, TNF-α, IL-6, and α-SMA were observed in the wound tissue. In the blank gel group, inflammatory factors decreased significantly. In the drug-loaded honeysuckle plant exosome hydrogel group, there were almost no inflammatory factors CD86, TNF-α, IL-6, and α-SMA, which indicates that the anti-inflammatory effect of the drug-loaded honeysuckle plant exosome injectable hydrogel prepared by the present invention is the best. In addition, a large number of growth factors VEGF, CD31, CD206, and IL-4 were observed in the drug-loaded honeysuckle plant exosome hydrogel group, only a small amount of growth factors VEGF, CD31, CD206, and IL-4 in the blank gel group, and almost no growth factors VEGF, CD31, CD206, and IL-4 in the blank control group, which indicates that the drug-loaded honeysuckle plant exosome injectable hydrogel prepared by the present invention has a better effect of promoting tissue regeneration.

[0091] The relative fluorescence intensity of the above growth factors and inflammatory factors was calculated using Image software.

[0092] Figure 7 and Figure 8 Figure (b) shows that the VEGF, CD31, CD206, and IL-4 in the drug-loaded honeysuckle plant exosome hydrogel group were significantly higher than those in the blank gel group and the blank control group. This indicates that the content of growth factors VEGF, CD31, CD206, and IL-4 in the drug-loaded honeysuckle plant exosome hydrogel group was significantly higher than that in the blank gel group and the blank control group. In addition, the CD86, TNF-α, IL-6, and α-SMA in the honeysuckle plant exosome hydrogel group were significantly lower than those in the blank gel group and the blank control group. This indicates that the content of inflammatory factor TNF-α in the honeysuckle plant exosome hydrogel group was significantly lower than that in the blank gel group and the blank control group.

[0093] Fig. 9 This is the H&E staining of the heart, liver, spleen, lung, and kidney of mice 14 days after surgery; it can be seen from the figure that there is no significant fluctuation in the indicators of the blank gel group and the drug-loaded honeysuckle plant exosome hydrogel group, indicating that liver and kidney function is not affected. No obvious pathological abnormalities or damage were found in the main organs of mice in each group.

[0094] Fig.10 This is an immunofluorescence image of the spleen of mice 14 days after surgery; it can be seen from the figure that the content of growth factors VEGF, CD31, CD206, and IL-4 in the drug-loaded honeysuckle plant exosome hydrogel group was significantly higher than that in the blank gel group. In addition, the CD86, TNF-α, IL-6, and α-SMA in the honeysuckle plant exosome hydrogel group were significantly lower than those in the blank gel group. This shows that the inflammatory factors in the honeysuckle plant exosome hydrogel group were significantly lower than those in the blank gel group.

[0095] In summary, the injectable hydrogel prepared by the present invention can quickly release the honeysuckle plant exosomes containing drugs, promote tissue regeneration of wounds, and reduce the inflammatory response of wounds. That is, the present invention aims to achieve the combination of clearing postoperative abdominal inflammation and wound repair treatment by loading the honeysuckle plant exosomes containing drugs into the injectable hydrogel, so as to synergistically treat and / or prevent postoperative abdominal tissue adhesion.

[0096] The above are only preferred specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. An injectable hydrogel for inhibiting postoperative adhesion of abdominal cavity, characterized in that: Ingredients include: Water-soluble chitosan, hyaluronic acid, active oxygen responsive segment-constructed macromonomers, drug-loaded honeysuckle plant exosome solution, and a cross-linking agent; The structural formula of the macromolecular monomer constructed by the active oxygen responsive segment is:

2. The injectable hydrogel for inhibiting postoperative adhesion of abdominal cavity according to claim 1, characterized in that: The drugs include puerarin, ibuprofen or methyldeferoxamine.

3. The injectable hydrogel for inhibiting postoperative adhesion of abdominal cavity according to claim 2, characterized in that: The drug is puerarin.

4. The injectable hydrogel for inhibiting postoperative adhesion of abdominal cavity according to claim 1, characterized in that: The preparation process of the honeysuckle plant exosome solution loaded with drugs is as follows: Fresh honeysuckle juice is squeezed, and then coarse filtration, centrifugation and fine filtration are performed in sequence to obtain a honeysuckle plant exosome solution, and then drugs are added thereto and dialyzed to obtain the honeysuckle plant exosome solution loaded with the drug.

5. The injectable hydrogel for inhibiting postoperative adhesion of abdominal cavity according to claim 4, characterized in that: The concentration of the drug in the honeysuckle plant exosome solution is 4 to 10 mg / mL.

6. The injectable hydrogel for inhibiting postoperative adhesion of abdominal cavity according to claim 1, characterized in that: The mass ratio of the water-soluble chitosan to the hyaluronic acid is (3-5):

1.

7. A method for preparing an injectable hydrogel for inhibiting postoperative adhesion of the abdominal cavity, characterized in that: The following steps are involved: Adding active oxygen responsive segments to construct macromolecular monomer solution to the hyaluronic acid solution for a primary reaction, then gradually adding water-soluble chitosan solution thereto for a secondary reaction, and then performing dialysis, centrifugation and freeze drying in sequence to prepare HA-Linker-CS powder; The HA-Linker-CS powder is dissolved in a honeysuckle plant exosome solution loaded with a drug, a cross-linking agent is added, and the solution is allowed to stand to obtain the injectable hydrogel for inhibiting postoperative adhesion after abdominal surgery according to any one of claims 1 to 6.

8. The method for preparing an injectable hydrogel for inhibiting postoperative adhesion of abdominal cavity according to claim 7, characterized in that: The volume ratio of the water-soluble chitosan solution, the hyaluronic acid solution and the active oxygen responsive segment construction macromolecular monomer solution is: (450-750):150:1; Wherein, the concentrations of the water-soluble chitosan solution and the hyaluronic acid solution are both 1 g / 600 mL; The concentration of the active oxygen responsive segment constructing macromolecular monomer solution is 200-300 mg / mL.

9. The method for preparing an injectable hydrogel for inhibiting postoperative adhesion of abdominal cavity according to claim 7, characterized in that: The dosage ratio of the HA-Linker-CS powder, the drug-loaded honeysuckle plant exosome solution and the cross-linking agent is: (0.01-0.5 g): 1 mL: (50-150 μL).

10. The method for preparing an injectable hydrogel for inhibiting postoperative adhesion of abdominal cavity according to claim 7, characterized in that: The time of the first reaction is 1 hour; and / or The secondary reaction time is 12h.

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