Hydrogel for preventing postoperative tissue adhesion and preparation method thereof

Abstract

The invention discloses hydrogel for preventing postoperative tissue adhesion and a preparation method thereof, and belongs to the field of medical biological materials. The hydrogel is formed by taking a carboxylated chitin / chitosan derivative with the percentage concentration of 0.5-7% or a low-crosslinking-degree supramolecular derivative of a hydroxyalkylated chitin / chitosan derivative and collagen or gelatin as a solute and water, normal saline, a physiological equilibrium solution, a phosphate buffer solution or a Green's solution as a solvent, the crosslinking degree of the low-crosslinking-degree supramolecular crosslinking derivative is 0.1 to 6 mol percent. The molar ratio of the raw materials to the cross-linking agent is controlled, a small amount of cross-linking agent is used for micro-crosslinking, the prepared low-crosslinking-degree supramolecular derivative can form hydrogel in an aqueous solvent, and the hydrogel has adhesiveness and self-repairing performance, can effectively prolong the residence time and physical barrier time of the hydrogel on the surface of an operative wound, and can be used for preparing the hydrogel. Therefore, the effect of preventing postoperative combined adhesion of the hydrogel is improved, and the hydrogel is an ideal hydrogel material for preventing postoperative abdominal cavity and uterine cavity tissue adhesion.

Description

Technical Field

[0001] The invention relates to a medical biomaterial, and in particular to a hydrogel for preventing postoperative tissue adhesion, and a preparation method and application thereof. Background Art

[0002] Postoperative tissue and organ adhesion is a common complication of abdominal, pelvic, and uterine surgery, with an incidence rate of nearly 80%. Postoperative adhesion can lead to clinical symptoms of varying degrees, such as abdominal pain, pelvic pain, intestinal obstruction, female infertility, etc., causing great pain to patients. Therefore, effectively preventing and blocking postoperative tissue adhesion and reducing complications are urgent issues to be solved in abdominal, pelvic, and uterine surgery. The formation of postoperative tissue adhesion involves complex physiological processes such as inflammatory response, tissue repair, and vascular regeneration. At present, there are three main types of measures to prevent postoperative adhesion in clinical practice: first, using gentle surgical methods to minimize surgical trauma and reduce peritoneal damage; second, postoperative inflammation management, using drugs for auxiliary treatment, and rationally using antibiotics and anti-inflammatory drugs to reduce infection and inflammation; third, using isolation materials for physical isolation, using medical chitosan, hyaluronic acid, dextran, sodium carboxymethyl cellulose, etc., between the surgical wound and the surrounding organs to prevent adhesion biomaterials to form a physical barrier and reduce the contact between the wound tissue and the surrounding organs to form adhesions.

[0003] At present, the main biomaterial products used in clinical practice to prevent adhesion include glue, membrane and other preparations. Glue preparations have good fluidity and can better cover the wound surface to form physical isolation, but the glue barrier material is easily diluted and absorbed by body fluids and has a short retention time on the surgical wound surface, so it is not enough to exert its own barrier effect; while membrane preparations can easily cover the wound surface, but it is difficult to completely cover and isolate wounds of varying depths. Membrane preparations also have the problem of poor adhesion to the wound tissue and movement with intestinal peristalsis and body activities, and all have insufficient efficacy.

[0004] Therefore, as a medical material for preventing postoperative tissue adhesion, it is necessary to increase the adhesion between the material and the tissue and prolong the retention time of the material on the wound surface to increase the physical barrier function of the material and improve the effect of preventing postoperative tissue adhesion. Summary of the invention

[0005] In view of the above problems, the first object of the present invention is to provide a hydrogel for preventing postoperative tissue adhesion, which has good viscosity, adhesion, self-healing properties and can effectively prolong the residence time on the surgical wound surface, so as to make up for the shortcomings of the prior art.

[0006] Another object of the present invention is to provide a method for preparing the hydrogel for preventing postoperative tissue adhesion, and the use of the hydrogel in preparing biomaterials for preventing postoperative abdominal and uterine tissue adhesion.

[0007] The technical solution of the present invention, while considering the safety and non-toxicity of the hydrogel as a method for preventing postoperative abdominal and uterine tissue adhesions, improves the viscosity, self-healing properties and tissue adhesion of the hydrogel through micro-crosslinking, so as to obtain a hydrogel with good viscosity, adhesion, self-healing properties, which effectively prolongs its residence time on the surgical trauma wound surface and forms an effective physical barrier for preventing postoperative abdominal and uterine tissue adhesions.

[0008] The hydrogel for preventing postoperative abdominal and uterine tissue adhesion of the present invention is a polysaccharide hydrogel using carboxylated chitosan derivatives or carboxylated chitosan derivatives as raw materials, or using hydroxyalkylated chitosan derivatives or hydroxyalkylated chitosan derivatives and collagen or gelatin as raw materials, and forming a low cross-linking degree supramolecular derivative through micro-crosslinking. The carboxylated chitosan derivatives or carboxylated chitosan derivatives form supramolecular derivatives through hydrogen bonds or ionic interactions between molecules, and the hydroxyalkylated chitosan or hydroxyalkylated chitosan derivatives can also form supramolecular derivatives through intermolecular hydrogen bond interactions with collagen or gelatin. The supramolecular derivatives are further controlled by micro-crosslinking of a crosslinking agent to form a chemical crosslinking network with a low crosslinking degree, which is the main component of the hydrogel. The polysaccharide hydrogel forms supramolecular derivatives through intermolecular interactions, and then the low crosslinking degree polymer chemical crosslinking network formed by micro-crosslinking control, the two are combined with each other, can be dissolved in a water system solvent to form a viscous hydrogel, have good water retention ability, and are easy to cover the surgical wound surface well, protect the wound surface, and form a physical barrier. The low-crosslinked polymer chemical cross-linked network superimposed with hydrogen bonding interactions between molecules makes the hydrogel self-healing and can form hydrogen bonding and self-healing effects with biological macromolecules such as body tissue proteins. It has good adhesion to surgical wounds and is not easy to shift, forming a good protection and physical barrier for surgical wounds. The low-crosslinked supramolecular derivatives in the hydrogel are slowly absorbed in the body tissues due to micro-crosslinking control, and have a strong ability to retain water molecules, which can effectively prolong the time that the hydrogel acts as a physical barrier on the wound surface. Therefore, the carboxylated chitosan derivative or carboxylated chitosan derivative molecules form supramolecular derivatives through hydrogen bonds or ionic interactions, or the hydroxyalkylated chitosan or hydroxyalkylated chitosan derivative can also form supramolecular derivatives with collagen or gelatin through intermolecular hydrogen bond interactions, and further micro-crosslinking with a cross-linking agent can obtain a hydrogel with viscosity, adhesion and self-healing properties. The hydrogel is used for traumatic wounds of abdominal surgery and intrauterine surgery to prevent abdominal and intrauterine adhesions after surgery. The hydrogel can effectively prolong its retention time and physical barrier time in the surgical trauma wound, thereby improving its effect of preventing postoperative combined adhesions and solving the shortcomings of the prior art.

[0009] The specific technical solutions of the present invention are as follows: A hydrogel for preventing postoperative tissue adhesion, characterized in that it is a hydrogel formed by using a low-crosslinking supramolecular derivative formed by micro-crosslinking of 0.5-7% by mass of a carboxylated chitosan derivative or a carboxylated chitosan derivative, or a hydroxyalkylated chitosan derivative and collagen or gelatin as a solute, and water, saline, physiological balance fluid, phosphate buffer or Ringer's solution as a solvent, wherein the crosslinking degree of the low-crosslinking supramolecular derivative is 0.1-6% by mole percentage (calculated as the molar number of polysaccharide).

[0010] The carboxylated chitosan derivatives or carboxylated chitosan derivatives include, but are not limited to, carboxymethyl chitosan, carboxyethyl chitosan, carboxymethyl chitosan, carboxyethyl chitosan, succinyl chitosan, carboxymethyl succinyl chitosan, and carboxyethyl succinyl chitosan.

[0011] The hydroxyalkylated chitosan derivative or hydroxyalkylated chitosan derivative includes one or more of hydroxyethyl chitosan, hydroxypropyl chitosan, hydroxybutyl chitosan, hydroxyethyl chitosan, hydroxypropyl chitosan and hydroxybutyl chitosan.

[0012] The low cross-linking supramolecular derivative is prepared by micro-cross-linking of the above carboxylated chitin derivative or carboxylated chitosan derivative, or hydroxyalkylated chitin derivative or hydroxyalkylated chitosan derivative with collagen or gelatin through a cross-linking agent.

[0013] The hydrogel for preventing postoperative tissue adhesion has tissue adhesion and self-repairing properties.

[0014] The method for preparing the hydrogel for preventing postoperative tissue adhesion is characterized by comprising the preparation of a low-crosslinked supramolecular derivative and the preparation of a hydrogel. The specific preparation method comprises the following steps: (1) Preparation of low cross-linking supramolecular derivatives: weigh the raw materials carboxylated chitosan derivatives or carboxylated chitosan derivatives, or hydroxyalkylated chitosan derivatives or hydroxyalkylated chitosan derivatives and collagen or gelatin, wherein the mass ratio of the hydroxyalkylated chitosan derivatives or hydroxyalkylated chitosan derivatives to collagen or gelatin is 1:0.05-0.5, add water and stir to dissolve; calculate the molar number of the polysaccharide raw material, according to the molar ratio of the polysaccharide raw material to the cross-linking agent of 100:0.1-6, add the cross-linking agent, adjust the pH of the solution according to the cross-linking agent's requirements for the reaction pH, and stir to react for 12-24 hours; after the reaction, precipitate with ethanol-water solution, wash, dehydrate with anhydrous ethanol, and dry to obtain a low cross-linking supramolecular derivative.

[0015] (2) Weigh a low-crosslinking supramolecular derivative, dissolve it in water, physiological saline, physiological equilibrium solution, phosphate buffer or Ringer's solution to prepare a hydrogel with a mass percentage concentration of 0.5-7%, put it into an injection bottle or syringe, and sterilize it by wet heat or irradiation to obtain a hydrogel.

[0016] In the above-mentioned method for preparing the hydrogel for preventing postoperative tissue adhesion, the cross-linking agent includes but is not limited to one of glycidyl ether (butylene glycol diglycidyl ether, polyethylene glycol glycidyl ether, ethylene glycol diglycidyl ether, propylene glycol triglycidyl ether, hexanediol diglycidyl ether, etc.), carbodiimide (EDAC, EDC, EDCI, DCC used in combination with NHS, HOBt or HOAt), and DMTMM.

[0017] The above hydrogel for preventing postoperative tissue adhesion is used in the preparation of medical materials for preventing postoperative abdominal and uterine cavity tissue adhesion.

[0018] The raw materials selected by the present invention have excellent biosafety and degradation and absorption, and have no toxic side effects on the human body. By controlling the molar ratio of the raw materials to the cross-linking agent, a small amount of cross-linking agent is used for micro-cross-linking, and the prepared low-cross-linking supramolecular derivative can form a hydrogel in an aqueous solvent. The hydrogel has a polymer chemical cross-linking network with a low cross-linking degree formed by micro-cross-linking control, and a dynamic reversible interaction of intermolecular hydrogen bonds. The hydrogel has adhesion and self-repairing properties, and can effectively prolong its retention time and physical barrier time in the surgical trauma wound surface, thereby improving its prevention of postoperative combined adhesion, and is a relatively ideal hydrogel material for preventing postoperative abdominal and uterine cavity tissue adhesion. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is a self-healing test diagram of the hydrogel 2 of the present invention.

[0020] Among them, the left picture is an orange-dyed hydrogel; the middle picture is an undyed hydrogel; and the right picture shows two parts of hydrogel of different colors healed into a whole.

[0021] Figure 2 This is a self-healing test diagram of hydrogel 4 of the present invention.

[0022] Among them, the left picture is an undyed hydrogel; the middle picture is a blue-dyed hydrogel; and the right picture shows two parts of hydrogel of different colors healed into a whole.

[0023] Figure 3 This is a test diagram of the adhesion of the hydrogel 2 of the present invention.

[0024] Figure 4 This is a test diagram of the adhesion of hydrogel 4 of the present invention. DETAILED DESCRIPTION

[0025] The present invention will be further described in detail below through specific embodiments.

[0026] Example 1: Preparation of carboxylated chitosan derivatives with low cross-linking degree supramolecular derivative 1 Weigh 9.6 g of carboxymethyl chitosan, stir and dissolve in 400 mL of deionized water, add 0.062 g of carbodiimide crosslinker EDC and 0.046 g of NHS at a molar ratio of carboxymethyl chitosan to crosslinker of 100:1, stir and dissolve, adjust the pH to 5.0, and react at room temperature for 24 h. Add about 4 times the volume of anhydrous ethanol to the reaction system to precipitate the reactant, filter, wash with 75% ethanol, dehydrate with anhydrous ethanol, and heat to dry at 60°C to obtain a carboxylated chitosan derivative with a low crosslinking degree supramolecular derivative 1.

[0027] Example 2: Preparation of carboxylated chitosan derivative with low cross-linking degree supramolecular derivative 2 Weigh 11 g of carboxymethyl chitosan, stir and dissolve it in 400 mL of deionized water, add 0.248 g of carbodiimide crosslinker EDC and 0.184 g of NHS at a molar ratio of carboxymethyl chitosan to crosslinker of 100:4, stir and dissolve, adjust the pH to 6.0, and react at room temperature with stirring for 18 h; add about 4 times the volume of anhydrous ethanol to the reaction system to precipitate the reactant, filter, wash with 75% ethanol, dehydrate with anhydrous ethanol, and heat and dry at 60°C to obtain a carboxylated chitosan derivative with a low crosslinking degree supramolecular derivative 2.

[0028] Example 3: Preparation of Hydroxypropylated Chitosan Derivative-Gelatin Low Crosslinking Degree Supramolecular Derivative 3 Weigh 5.2 g of hydroxypropyl chitosan and 2 g of gelatin, stir and dissolve in 400 mL of deionized water, add 0.004 ml of cross-linking agent 1,4-butanediol glycidyl ether at a molar percentage of hydroxypropyl chitosan to cross-linking agent of 100:0.1, stir, adjust the pH to 9.0, and react at room temperature for 24 h; add about 4 times the volume of anhydrous ethanol to the reaction system to precipitate the reactant, filter, wash with 75% ethanol, dehydrate with anhydrous ethanol, and dry at 60°C to obtain hydroxypropyl chitosan derivative-gelatin low cross-linking supramolecular derivative 3.

[0029] Example 4: Preparation of hydroxyethylated chitosan derivative-collagen low cross-linking supramolecular derivative 4 Weigh 12.6 g of hydroxyethyl chitosan and 0.4 g of collagen, stir and dissolve in 500 mL of deionized water, add 0.74 g of carbodiimide crosslinker EDC and 0.56 g of NHS at a molar percentage of hydroxyethyl chitosan to crosslinker of 100:8, stir and dissolve, adjust the pH to 5.0, and react at room temperature for 12 h; add about 4 times the volume of anhydrous ethanol to the reaction system to precipitate the reactant, filter, wash with 80% ethanol, dehydrate with anhydrous ethanol, and heat to dry at 60°C to obtain hydroxyethylated chitosan derivative-collagen low crosslinking supramolecular derivative 4.

[0030] In Examples 1 to 4, the carboxylated chitosan derivatives or carboxylated chitosan derivatives include, but are not limited to, carboxymethyl chitosan, carboxyethyl chitosan, carboxymethyl chitosan, carboxyethyl chitosan, succinyl chitosan, carboxymethyl succinyl chitosan, and carboxyethyl succinyl chitosan; the hydroxyalkylated chitosan derivatives or hydroxyalkylated chitosan derivatives include one or more of hydroxyethyl chitosan, hydroxypropyl chitosan, hydroxybutyl chitosan, hydroxyethyl chitosan, hydroxypropyl chitosan, and hydroxybutyl chitosan. The carboxylated chitosan derivative or carboxylated chitosan derivative has carboxyl, amino and hydroxyl groups in its molecular structure; the hydroxyalkylated chitosan derivative or hydroxyalkylated chitosan derivative has amino and hydroxyl groups in its molecular structure; the composition of the hydroxyalkylated chitosan derivative or carboxylated chitosan derivative and collagen or gelatin has amino, hydroxyl and carboxyl groups, wherein the hydroxyalkylated chitosan derivative or hydroxyalkylated chitosan derivative is the main component, and the mass ratio of the hydroxyalkylated chitosan derivative or hydroxyalkylated chitosan derivative to collagen or gelatin is 1:0.05~0.5; the above chemical structure can undergo cross-linking reaction with glycidyl ether cross-linking, and can also undergo cross-linking reaction with carbodiimide carboxyl and amino condensation agents to prepare a low cross-linking supramolecular derivative.

[0031] In the above embodiments 1 to 4, the crosslinking agent includes but is not limited to one of glycidyl ether (butylene glycol diglycidyl ether, polyethylene glycol glycidyl ether, ethylene glycol diglycidyl ether, glycerol triglycidyl ether, hexanediol diglycidyl ether, etc.), carbodiimide (EDAC, EDC, EDCI or DCC used in combination with NHS, HOBt or HOAt), and DMTMM. The molar ratio of the polysaccharide raw material to the crosslinking agent is 100:0.1-6, forming a polymer chemical crosslinking network with a low degree of crosslinking.

[0032] Example 5: Preparation of hydrogel 3 g of the carboxylated chitosan derivative low cross-linking supramolecular derivative 1 prepared in Example 1 was weighed and dissolved in 150 ml of physiological saline, and the pH was adjusted to 7.0 to prepare a hydrogel with a concentration of 2%. After wet heat sterilization, the hydrogel was loaded into a syringe to obtain a hydrogel 1.

[0033] 4.5 g of the low-crosslinked supramolecular derivative 2 of the carboxylated chitosan derivative prepared in Example 2 was weighed and dissolved in 150 ml of physiological saline. The pH was adjusted to 6.5 to prepare a hydrogel with a concentration of 3%. After wet heat sterilization, the hydrogel was loaded into a syringe to obtain a hydrogel 2.

[0034] 0.75 g of the hydroxypropylated chitosan derivative-gelatin low cross-linking supramolecular derivative 3 prepared in Example 3 was weighed and dissolved in 150 ml of water. The pH was adjusted to 8.0 to prepare a hydrogel with a concentration of 0.5%. After wet heat sterilization, the hydrogel was loaded into a syringe to obtain a hydrogel 3.

[0035] 10.5 g of the hydroxyethylated chitosan derivative-collagen low cross-linking supramolecular derivative 4 prepared in Example 4 was weighed and dissolved in 150 ml of phosphate buffer (0.2 M), and the pH was adjusted to 7.6 to prepare a hydrogel with a concentration of 7%. After wet heat sterilization, the hydrogel was loaded into a syringe to obtain hydrogel 4.

[0036] In the preparation of the above hydrogel, the mass percentage of the low cross-linking supramolecular derivative in the hydrogel is 0.5~7%. As the stirring speed increases, the viscosity of the hydrogel shows a significant downward trend and has shear thinning characteristics.

[0037] Example 6: Self-healing test of hydrogel (1) Self-healing test of hydrogel 2: Take 2 portions of hydrogel 2, 4 ml each, add 2 drops of orange neutral pen ink to one portion, stir evenly, and dye the hydrogel orange. Inject the 2 portions of hydrogel of different colors into two five-pointed star-shaped molds respectively. After removing the molds, cut the two five-pointed stars of different colors into two parts from the center line. Put the two parts of different colors side by side and seam together. It can be observed that the two parts of different colors heal into a whole, indicating that hydrogel 2 has self-healing properties. Figure 1 .

[0038] (2) Self-healing test of hydrogel 4: Take 2 portions of hydrogel 4, 4 ml each, add 2 drops of dark blue gel pen ink to one portion, stir evenly, and dye the hydrogel blue. Inject the 2 portions of hydrogel of different colors into two heart-shaped molds respectively. After removing the molds, cut the two hearts of different colors into two parts from the midline position. Put the two parts of different colors side by side and seam together. It can be observed that the two parts of different colors heal into a whole, indicating that hydrogel 4 has self-healing properties. Figure 2 .

[0039] Example 7: Adhesion test of hydrogel like Figure 3 and Figure 4Hydrogel 2 and hydrogel 4 were injected into the middle part of the back of the finger respectively. The finger was bent downward nearly 90 degrees and observed for 10 minutes. It can be seen that the hydrogel still adhered firmly to the original position on the back of the finger, did not flow downward due to gravity, and did not fall off, indicating that the hydrogel has good adhesion and flexibility.

[0040] Example 8: Evaluation of hydrogel in preventing postoperative abdominal adhesions Experimental groups: 30 SD rats, half male and half female, were randomly divided into 3 groups: saline control group, hydrogel 1 test group, and hydrogel 4 test group, with 10 rats in each group.

[0041] Experimental methods: Rats were fasted for 12 hours before surgery, anesthetized with intraperitoneal injection of 30 mg / kg sodium pentobarbital solution, fixed in the supine position, shaved, and the skin disinfected with 0.5% povidone-iodine. A 3 cm longitudinal incision was made in the middle of the abdomen, and the ileocecal part was found. The ileal serosa (about 5 cm long) was repeatedly wiped with dry gauze at about 5 cm from the ileocecal part until a pinpoint bleeding point appeared. Rats in the saline control group were rinsed with saline after ileal injury, and the abdomen was closed after the intestinal tube was returned; rats in the hydrogel 1 test group and the hydrogel 4 test group were evenly applied with hydrogel 1 or hydrogel 4 at the ileal injury site according to the group, and the abdomen was closed after the intestinal tube was returned. Rats were intraperitoneally injected with penicillin to prevent infection after surgery, and were kept normally. Rats were killed on the 14th day after surgery, and the abdominal cavity was opened. The formation of adhesions in the abdominal cavity was observed with the naked eye. Adhesions were scored and graded according to the Nair grading standard, and SPSS13.0 software was used for statistical analysis.

[0042] Experimental results: 14 days after surgery, the rats in the normal saline control group had severe abdominal adhesions, and the ileum of some rats was adhered into a mass and could not be peeled off; in the hydrogel 1 test group and the hydrogel 4 test group, some rats did not have intestinal adhesions, the ileal serosal surface recovered well, and some rats had mesenteric tissue adhesion to the ileum, and the degree of adhesion was lighter than that of the normal saline control group. According to the Nair grading standard, the adhesion scores of the normal saline control group, the hydrogel 1 test group, and the hydrogel 4 test group were 3.2±0.52, 2.0±0.34, and 1.9±0.35, respectively. It can be seen that the adhesion scores of the hydrogel 1 test group and the hydrogel 4 test group were low, and there was a very significant difference compared with the normal saline control group (p<0.01), as shown in Table 1. The experimental results show that the hydrogel of the present invention has the effect of preventing and alleviating postoperative abdominal adhesions.

[0043] Table 1 Nair adhesion scoring results (n=10, 14 days)

[0044] **Compared with the saline control group, p < 0.01.

[0045] The above embodiments show that the present invention uses carboxylated chitosan derivatives or carboxylated chitosan derivatives, or hydroxyalkylated chitosan derivatives and collagen or gelatin, and is micro-crosslinked by a crosslinking agent to prepare a low crosslinking supramolecular derivative, which is further dissolved in an aqueous solvent to form a hydrogel. The low crosslinking supramolecular derivative hydrogel has viscosity, adhesion, and self-repairing properties. The hydrogel is applied to the surgical wound surface to form a good protection and physical barrier for the wound surface. Its adhesion properties, self-repairing properties, and slow absorption by the body due to micro-crosslinking effectively prolong the time of the hydrogel as a physical barrier on the wound surface, thereby improving its role and effect in preventing postoperative combined adhesion. The main mechanism of the hydrogel of the present invention in preventing abdominal adhesion is to form an effective physical barrier on the wound surface of damaged tissues and organs and prolong its time as a physical barrier, isolating the damaged wound surface from surrounding tissues and organs, and this mechanism of preventing postoperative abdominal adhesion by a physical barrier is also applicable to the prevention of tissue adhesion in uterine surgery. Therefore, the hydrogel of the present invention can be used in the preparation of biomaterials for preventing postoperative abdominal and uterine cavity tissue adhesions, and has great application potential.

Claims

1. A hydrogel for preventing postoperative tissue adhesion, characterized in that: The hydrogel is formed by using carboxylated chitosan / chitosan derivatives or hydroxyalkylated chitosan / chitosan derivatives with a concentration of 0.5-7% and low-crosslinked supramolecular derivatives of collagen or gelatin as solutes and water, physiological saline, physiological equilibrium solution, phosphate buffer or Ringer's solution as solvents. The crosslinking degree of the low-crosslinked supramolecular cross-linked derivative is 0.1-6% by mole percentage.

2. The hydrogel for preventing postoperative tissue adhesion according to claim 1, characterized in that: The carboxylated chitosan derivatives or carboxylated chitosan derivatives include carboxymethyl chitosan, carboxyethyl chitosan, carboxymethyl chitosan, carboxyethyl chitosan, succinyl chitosan, carboxymethyl succinyl chitosan and carboxyethyl succinyl chitosan.

3. The hydrogel for preventing postoperative tissue adhesion according to claim 1, characterized in that: The hydroxyalkylated chitosan derivative or hydroxyalkylated chitosan derivative includes one or more of hydroxyethyl chitosan, hydroxypropyl chitosan, hydroxybutyl chitosan, hydroxyethyl chitosan, hydroxypropyl chitosan and hydroxybutyl chitosan.

4. A method for preparing the hydrogel for preventing postoperative tissue adhesion according to claim 1, characterized in that: The following steps are involved: (1) Preparation of low cross-linking supramolecular derivatives: weigh the raw materials carboxylated chitosan derivatives or carboxylated chitosan derivatives, or hydroxyalkylated chitosan derivatives or hydroxyalkylated chitosan derivatives and collagen or gelatin, wherein the mass ratio of the hydroxyalkylated chitosan derivatives or hydroxyalkylated chitosan derivatives to collagen or gelatin is 1:0.05-0.5, add water and stir to dissolve; calculate the molar number of the polysaccharide raw material, according to the molar ratio of the polysaccharide raw material to the cross-linking agent being 100:0.1-6, add the cross-linking agent, adjust the pH of the solution, and stir to react for 12-24 hours; after the reaction, ethanol precipitation, washing, dehydration with anhydrous ethanol, and drying are performed to obtain the low cross-linking supramolecular derivatives; (2) Weigh a low-crosslinking supramolecular derivative, dissolve it in water, physiological saline, physiological equilibrium solution, phosphate buffer or Ringer's solution to prepare a hydrogel with a mass percentage concentration of 0.5-7%, put it into an injection bottle or syringe, and sterilize it by wet heat or irradiation to obtain a hydrogel.

5. The method for preparing a hydrogel for preventing postoperative tissue adhesion according to claim 4, characterized in that: The cross-linking agent is one of glycidyl ether, carbodiimide and DMTMM.

6. The method for preparing a hydrogel for preventing postoperative tissue adhesion according to claim 5, characterized in that: The glycidyl ether is one of butanediol diglycidyl ether, polyethylene glycol glycidyl ether, ethylene glycol diglycidyl ether, glycerol triglycidyl ether and hexanediol diglycidyl ether.

7. The method for preparing a hydrogel for preventing postoperative tissue adhesion according to claim 5, characterized in that: The carbodiimide is EDAC, EDC, EDCI or DCC used in combination with NHS, HOBt or HOAt.

8. Use of the hydrogel for preventing postoperative tissue adhesion according to claim 1 in the preparation of medical materials for preventing postoperative abdominal and uterine tissue adhesion.

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