Active composite gel sealing material as well as preparation method and application thereof

Abstract

The invention discloses an active composite gel sealing material as well as a preparation method and application thereof, and belongs to the technical field of medical materials. The active composite gel sealing material based on multiple crosslinking provided by the invention has excellent tissue adhesion and sealing performance; good in-vivo compatibility, biodegradability, low immunogenicity and high safety are achieved; the mechanical strength is high, the self-repairing capability is good, and the anti-hydrolysis stability is high; the adhesive property and the state of the material can be adjusted by adjusting the proportion of the components and adjusting the adhesive property and the state of the material, so that the requirements on different adhesive properties in practical application are met, irregular wounds are filled, and rapid gelation is performed at the body temperature so as to adapt to the form of a surgical site; the effects of stopping bleeding, resisting inflammation, promoting revascularization and repairing nerves are also achieved.

Description

Technical Field

[0001] This invention relates to the field of medical materials technology, and in particular to an active composite gel sealing material, its preparation method, and its application. Background Technology

[0002] Many neurosurgical and spinal surgeries involve accessing the underlying neural tissue, creating defects in the dura mater, and further leading to cerebrospinal fluid leakage. The dura mater is highly perfused with blood vessels, supporting the transport of immune cells. However, after dural defects, some vascular transport is interrupted. Promoting angiogenesis is essential for restoring the dura mater to its original state. Furthermore, creating a favorable microenvironment is also crucial for promoting rapid tissue repair. Existing tissue sealing materials mostly employ a single cross-linking method (such as Schiff base cross-linking), which suffers from insufficient stability (prone to hydrolysis) and limited functionality (only capable of sealing). Moreover, existing materials struggle to simultaneously achieve a comprehensive combination of rapid sealing, strong adhesion, high stability, and repair promotion. Therefore, there is a need to develop novel dural sealing materials with multi-crosslinking synergy and both hemostatic and bioactive properties.

[0003] Although Schiff base crosslinking forms a gel through a rapid reaction between aldehyde and amino groups, the product is easily hydrolyzed by pH, making it difficult to meet the needs of long-term wound repair. Furthermore, traditional materials lack targeted hemostatic design and cannot effectively address acute dural hemorrhage caused by surgery or trauma (such as cerebrospinal fluid leakage accompanied by vascular rupture and bleeding).

[0004] Crosslinking of hydrogels can be categorized into physical crosslinking and chemical crosslinking. Physical crosslinking is simple and easy to perform, and the resulting hydrogels generally possess reversibility and self-healing properties, but it also suffers from drawbacks such as low strength and uncontrollable mechanical properties. Chemical crosslinking can overcome these shortcomings, endowing hydrogels with excellent mechanical properties and stability. It is typically achieved by triggering monomer polymerization or utilizing chemical reactions between polymer chains. Summary of the Invention

[0005] The purpose of this invention is to provide an active composite gel sealing material, its preparation method, and its application, in order to solve the problems of insufficient stability, limited functionality, insufficient sealing effect, and poor tissue adhesion of existing tissue sealing materials.

[0006] To achieve the above objectives, the present invention provides an active composite gel sealing material, which is prepared from the following components: component A, component B, and active factor; component A is a biocompatible macromolecule containing a carbonyl group, such as an aldehyde or ketone; component B is an amino-terminated macromolecule that is easy to modify structurally; and the active factor is one or more of growth promoters, metal particles, and polyphenols.

[0007] Preferably, the biocompatible macromolecules containing carbonyl groups, such as aldehydes and ketones, are one of oxidized dextran, oxidized hyaluronic acid, oxidized sodium alginate, and NHS-terminated polyethylene glycol derivatives.

[0008] Preferably, the biocompatible macromolecules containing carbonyl groups, such as aldehydes and ketones, are oxidized / modified with sodium periodate.

[0009] Preferably, the amino-terminated macromolecule that is easy to modify is obtained by modifying one of gelatin, chitosan, polyethyleneimine and its derivatives.

[0010] Preferably, the modification is performed using 4-carboxyphenylboronic acid.

[0011] Preferably, the metal particles are divalent cations, specifically Ca. 2+ Mg 2+ Cu 2+ Zn 2+ One of them.

[0012] Preferably, the polyphenol is a natural polyphenol, which is one or two of tannic acid and catechin.

[0013] Preferably, the mass ratio of component A: component B: active factor is 1-2:1:0.005-0.02.

[0014] A method for preparing the above-mentioned active composite gel sealing material includes the following steps: S1. Prepare a mixture of component B and active agent; S2. Prepare component A into a solution; S3. Extrude and mix the mixture prepared in S1 and the solution prepared in S2 in equal proportions to form a gel, or form a gel after ultraviolet irradiation.

[0015] The application of an active composite gel sealing material as described above in tissue occlusion and wound closure promotion, wherein the tissue occlusion and wound closure promotion include dural occlusion, spinal dural occlusion, renal hemostasis, pulmonary occlusion, pericardial adhesion and anti-adhesion, gastrointestinal anastomosis, urethral anastomosis, and nerve adhesion.

[0016] The active composite gel sealing material provided by this invention contains tannic acid (TA), which is rich in catechol and phloroglucinol structural units. It can participate in the cross-linking of various components through a variety of non-covalent interactions (such as hydrogen bonding and metal coordination) and dynamic covalent bonds (interacting with each component), thereby forming a dense, multi-crosslinked network structure with a stronger energy dissipation mechanism. This not only significantly enhances the mechanical strength and toughness of the hydrogel, but also gives it excellent self-healing ability. The presence of dynamic multi-crosslinking is conducive to the rapid self-healing and reliable mechanical stability of the hydrogel.

[0017] The adhesion between the gel sealing material and tissue is another extremely important parameter. This invention achieves rapid and robust tissue sealing and repair by adding oxidized dextran, which enables its aldehyde groups to specifically covalently couple with primary amine, carboxylic acid, hydroxyl, and thiols in proteins and / or amino acid residues on the tissue surface. Furthermore, the catechol in the component further promotes these adhesion effects through hydrogen bonding, hydrophobic interactions, and / or covalent bonds, enhancing the tissue adhesion and sealing effect of the tissue sealing material.

[0018] The metal ions in the components can trigger the expression of angiogenic growth factor and exhibit an immunomodulatory M2 polarization effect on macrophages. The TA in the components also has antioxidant, anti-inflammatory, anticancer and antibacterial effects. It can rapidly self-crosslink in water and generate stable metal ion crosslinked tannic acid (MITA) nanostructures through interaction with magnesium and copper ions in the components.

[0019] The aldehyde groups on the surface of the dual-modified hyaluronic acid / oxidized dextran can react with the amino groups on the tissue surface, enhancing the covalent bonding between the gel sealing material and the tissue, achieving rapid tissue sealing and strong chemical adhesion. The dual cross-linking significantly improves the material's mechanical strength, self-healing ability, and hydrolytic stability. Metallic tannic acid nanoparticles act as cross-linking nodes for borate esters, simultaneously chelating metal ions (magnesium, zinc) to achieve controlled release, promoting angiogenesis and nerve repair.

[0020] Phenylboronic acid-modified chitosan forms dynamically reversible borate ester bonds by specifically coordinating its borate groups with the o-dihydroxyl groups on the surface of metal tannic acid nanoparticles. Furthermore, the metal tannic acid nanoparticles can react with amino, carboxyl, or aldehyde groups on macromolecules via their surface o-dihydroxyl groups, or their surface metal ions can form coordination crosslinks with the amino groups of chitosan.

[0021] Polyphenols can react with metal cations such as Ca 2+ Mg 2+ and Cu 2+ The formation of a metal-phenol network (MPN) involves the phenolic hydroxyl groups in the polyphenol molecule donating lone pairs of electrons to metal cations (such as Ca). 2+ Mg 2+ and Cu 2+ Coordinate bonds are formed, and under neutral or weakly alkaline conditions, the phenolic hydroxyl groups of polyphenols, after deprotonation, more readily bind to metal ions, thus forming a stable metal-phenol network. Furthermore, this network structure exhibits a degree of dynamic reversibility; that is, under external stimuli, the metal-phenol bonds can dissociate and reform, thereby enabling the controlled release of metal cations. This allows for the continuous and controlled delivery of metal cations, enabling them to stably exert antibacterial or angiogenesis-promoting effects, while avoiding the toxic effects on tissues or cells caused by concentrated release of metal ions.

[0022] Boronate esters are used to link the metal-phenol network with the gel network. Boronate ester bonds typically form between boric acid and vicinal diol groups, exhibiting good pH, glucose, and glutathione (GSH) responsiveness. Therefore, the boronate-crosslinked hydrogel can undergo structural dissociation upon stimulation, releasing the metal-phenol network. Through the synergistic effect of multiple components, postoperative adhesions, infections, and secondary injuries can be comprehensively addressed.

[0023] Therefore, the active composite gel sealing material, its preparation method, and its application provided by this invention have the following specific technical effects: (1) The active composite gel sealing material provided by the present invention has excellent tissue adhesion and sealing performance, and can quickly gel or close tissue; it has high stability, good continuous effect, low swelling and certain dynamic reversibility; by adjusting the proportion of each component, the adhesion performance of the material can be adjusted to meet different practical application needs, and the material can also be made into an injectable sol state, which can fill irregular wounds, and can quickly gel at body temperature to adapt to the shape of the surgical site and reduce the risk of leakage; it also has a hemostatic effect and can directly compress the bleeding point by forming a physical barrier. (2) The active composite gel sealing material provided by the present invention has good in vivo compatibility, biodegradability and low immunogenicity, and high safety. The MPN structure therein can not only realize the continuous and controllable release of metal ions to exert antibacterial or angiogenesis-promoting biological effects, but also stabilize the metal-tannic acid complex in the hydrogel matrix through the ester bond, which helps to respond to microenvironment stimulation to realize the slow release of metal ions and avoid the toxic risk to cells or tissues caused by the initial burst release; it can ensure that the material will not cause inflammation or rejection after implantation, and is suitable for long-term in vivo application; (3) The active composite gel sealing material provided by the present invention has the ability to promote angiogenesis. The chelated metal ions can stimulate the formation of new blood vessels by activating the migration and proliferation signaling pathways of endothelial cells; tannic acid protects new blood vessels from oxidative damage through antioxidant effects; the porous scaffold structure in the hydrogel network facilitates the diffusion of oxygen and nutrients and accelerates the reconstruction of the vascular network. (4) The active composite gel sealing material provided by the present invention has the effect of promoting nerve regeneration. The chelated metal particles can promote nerve regeneration by stimulating axonal growth, neural stem cell proliferation and myelin synthesis, and upregulating the release of neurotrophic factors (such as BDNF); Mg 2+ It can effectively promote the proliferation, migration and transformation of Schwann cells to a repair phenotype, and contribute to the regeneration of nerve axons and myelination. (5) The active composite gel sealing material provided by the present invention has anti-inflammatory effects. The polyphenols in the components can scavenge free radicals, inhibit inflammatory signaling pathways, and reduce the release of pro-inflammatory factors. The lubricity of the sealing gel can reduce inflammation caused by mechanical friction. The whole material can continuously release anti-inflammatory factors after implantation, thereby reducing redness, swelling and pain in patients. (6) The active composite gel sealing material provided by the present invention has high mechanical strength, good self-healing ability, strong hydrolysis stability, and also has the ability to load drugs, so that the drugs can be released slowly.

[0024] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0025] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments of the present invention will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0026] Figure 1 This is the FTIR spectrum of the active composite gel sealing material prepared in Example 1; Figure 2 These are the overlap shear analysis results of the active composite gel sealing material prepared in Example 1; Figure 3 This is a rupture pressure diagram of the active composite gel sealing material prepared in Example 1; where A represents materials without Mg@TA nanoparticles and B represents materials containing Mg@TA nanoparticles. Figure 4 The images show the drug release of the active composite gel sealing material prepared in Example 1 under PBS and H2O2 environments. Detailed Implementation

[0027] The technical solution of the present invention will be further described below with reference to the accompanying drawings and embodiments.

[0028] To make the objectives, technical solutions, and advantages of this application clearer, more thorough, and more complete, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings and embodiments. The following detailed descriptions are all illustrations of embodiments, intended to provide further detailed explanation of the present invention. Unless otherwise specified, all technical terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains.

[0029] The instruments, equipment, reagents and materials used in the embodiments were all obtained through commercial means; the methods and steps not described in detail in the embodiments are all conventional techniques in the art.

[0030] Example 1 The specific steps for preparing an active composite gel sealing material are as follows: (1) Preparation of oxidized dextran.

[0031] Dissolve 1g of dextran in 10mL of deionized water and stir mechanically until fully dissolved. Then dissolve 746.25mg of sodium periodate in 5mL of deionized water, and add the sodium periodate solution to the dextran solution. Stir in the dark (400rpm) for 6 hours.

[0032] After the reaction was complete, 2 mL of ethylene glycol was added and stirred (400 rpm) for 2 h to allow the ethylene glycol to fully react with the sodium periodate in the reaction system, thereby terminating the reaction between dextran and sodium periodate. The resulting solution was dialyzed (MW 12-14 kDa) and freeze-dried to obtain 800 mg of oxidized dextran.

[0033] (2) Preparation of modified chitosan.

[0034] Add 1g of quaternary ammonium chitosan (QCS) to 200mL of deionized water and stir mechanically until fully dissolved. Dissolve 479.25mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), 287.73mg of N-hydroxysuccinimide (NHS), and 414.85mg of 4-carboxyphenylboronic acid (PBA) in 10mL of dimethyl sulfoxide (DMSO) and activate the solution on a magnetic stirrer for 4 hours.

[0035] The activated solution was then added dropwise to the QCS solution at a rate of 2 mL / min, and the pH was adjusted to approximately 5.5 with 0.1 M NaOH solution. The reaction was carried out at 600 rpm and 25 °C for 24 hours. The resulting solution was transferred to a dialysis bag for dialysis (MW 12-14 kDa), followed by freeze-drying to obtain 750 mg of a pale yellow QCS-PBA product.

[0036] (3) Preparation of tannic acid magnesium ion complex.

[0037] 24 mg MgSO4 and 170 mg tannic acid were dissolved in 40 mL of deionized water and mechanically stirred until fully dissolved. 0.1 M NaOH solution was added to adjust the pH to 8.0, and the solution was stirred at room temperature for 24 hours. The resulting solution was centrifuged (10000 rpm × 20 min) and washed with deionized water. This process was repeated 5 times. After freeze-drying, 40 mg of Mg@TA nanoparticles were obtained.

[0038] (4) Dissolve 100 mg of the oxidized dextran prepared in step (1) in 5 mL of distilled water to obtain solvent A. Dissolve 50 mg of QCS-PBA prepared in step (2) and 2 mg of Mg@TA nanoparticles prepared in step (3) in 5 mL of distilled water to obtain solvent B. Use a double syringe to squeeze solvent A and solvent B in equal proportions onto the tissue to be adhered, and wait for gel formation.

[0039] Example 2 The specific steps for preparing an active composite gel sealing material are as follows: (1) Preparation of double-modified hyaluronic acid.

[0040] 1 g of HA powder was dissolved in 50 mL of deionized water at 55-60 °C. After complete dissolution, the solution was cooled to room temperature, and then 5 mL of sodium periodate aqueous solution (0.05 M-0.25 M) was added dropwise. The reaction was then carried out at 25 °C in the dark for 6 h. To synthesize AHA with different oxidation levels, 1-2 mL of ethylene glycol was added to the reaction solution under stirring, and the reaction was stopped by stirring at 25 °C for 1 h. The resulting solution was dialyzed (MW 12-14 kDa) and freeze-dried to obtain aldehyde-modified AHA.

[0041] Dissolve 1 g of AHA in 100 mL of phosphate-buffered saline (PBS), then add 3.2 mL of methacrylic anhydride (MA). Adjust the pH to approximately 8 by adding 0.1 M NaOH solution dropwise, and react at 4 °C for 24 hours. Dialyze the resulting solution, lyophilize to obtain 765 mg of AHM, and store at -80 °C.

[0042] (2) Preparation of modified chitosan.

[0043] Add 1g of quaternary ammonium chitosan (QCS) to 200mL of deionized water and stir mechanically until fully dissolved. Dissolve 479.25mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), 287.73mg of N-hydroxysuccinimide (NHS), and 414.85mg of 4-carboxyphenylboronic acid (PBA) in 10mL of dimethyl sulfoxide (DMSO) and activate the solution on a magnetic stirrer for 4 hours.

[0044] The activated solution was added dropwise to the QCS solution, and the pH was adjusted to 5.5 with 0.1M NaOH solution. The mixture was mechanically stirred for 24 hours. The resulting solution was transferred to a dialysis bag for dialysis and then freeze-dried to obtain 825 mg of pale yellow QCS-PBA product.

[0045] (3) Preparation of tannic acid copper ion complex.

[0046] Dissolve copper sulfate pentahydrate and TA in 50 mL of deionized water (TA:Cu). 2+ (Molar ratio 1:1). Add 0.1M NaOH solution to the solution and adjust the pH to 8.0 with vigorous stirring. After stirring at room temperature for 24 hours, centrifuge at 12000 rpm for 20 min to collect the precipitate. Wash five times with deionized water to obtain 10 mg Cu@TA NPs after lyophilization.

[0047] (4) Dissolve 200 mg of AHM prepared in step (1) in 5 mL of distilled water to obtain solvent A. Dissolve 100 mg of QCS-PBA prepared in step (2) and 2 mg of Cu@TA NPs prepared in step (3) in 5 mL of distilled water to obtain solvent B. Use a double syringe to squeeze solvent A and solvent B in equal proportions onto the tissue to be adhered, irradiate with ultraviolet light for 30 s, and wait for gel formation.

[0048] Example 3 The specific steps for preparing an active composite gel sealing material are as follows: (1) A 1% w / v chitosan solution (100 mL) was obtained by dissolving 1 mg of chitosan in 2% v / v acetic acid at room temperature. 2 mL of methacrylic anhydride was slowly added to the chitosan solution, and the mixture was stirred at 600 rpm for 5 min at 40 °C, avoiding light exposure. Then, 1 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and 1 g of N-hydroxysuccinimide (NHS) were dissolved in 2 mg of deionized water. The solution containing NHS and EDC was added dropwise to the chitosan solution, and the mixture was stirred at 40 °C (600 rpm) for 12 h. The pH of the chitosan solution was then adjusted to neutral (pH = 7.0-7.4) with 1 M sodium hydroxide (NaOH). The obtained chitosan solution was then purified by dialysis (MWCO 12-14 kDa), with the water changed six times within 72 h. After freeze-drying, 750 mg of a white product, methacrylated chitosan (CSMA), was obtained.

[0049] (2) Mix 2% (w / v) CSMA and collagen at a certain mass ratio (CSMA: collagen 2-5:1) and stir (600 rpm) or vortex at 37°C.

[0050] (3) Add 0.1% (w / v) of photoinitiator (lithium phenyl-2,4,6-trimethylbenzoylphosphonate) to the mixed solution, and stir under light-protected conditions until completely dissolved and homogeneous. Inject the mixed solution directly into the target site and irradiate with ultraviolet (UV) light to initiate crosslinking. The UV wavelength is 365 nm, and the light intensity is approximately 1 W / cm². 2 The irradiation time is 10 seconds.

[0051] Effect verification (1) The active composite gel sealing material of Example 1 was measured using Fourier transform infrared spectroscopy (FTIR). The results are as follows: Figure 1 As shown, 1636.93cm -1 The characteristic peak of the BO bond is 1636.93 cm⁻¹. -1 The peak represents the Schiff base C=N stretching vibration, indicating that OD underwent a Schiff base reaction with QCS-PBA. (1082 cm⁻¹) -1 The peak may be a weak vibration of the B-O-C borate ester bond, and the fact that this peak does not appear in OQP indicates that Mg... 2+ @TA incorporates borate ester bonds into the hydrogel.

[0052] (2) The tissue adhesion of the materials was tested using an overlap shear test. 200 μL each of the hydrogel precursor solutions (solvent A and solvent B) prepared in Example 1 were mixed and immediately spread onto the overlapping area (1 cm × 1 cm) of the pig skin. A 200 g weight was then placed on the overlapping area at 37°C under humid conditions for 0.5 h. The adhesive strength was measured using a universal testing machine at a speed of 2 mm / min. Three repeated tests were performed for each material.

[0053] The adhesive strength is calculated using the following formula: Adhesive strength = Maximum load (Fmax) / Area of ​​overlapping contact area. The results are as follows: Figure 2 As shown in the figure, the adhesion properties of the hydrogel increase with the increase of Mg@TA, from 6.443±0.125 kPa to 21.773±0.186 kPa. Tannic acid nanoparticles can act as physical crosslinking points, enhancing the toughness of the hydrogel's internal network through reversible bonds (such as metal coordination and hydrogen bonding). This increases the crosslinking density while maintaining the network's energy dissipation capacity, thereby improving the interfacial peel strength.

[0054] (3) Connect a 4cm x 4cm piece of pigskin to a 15mm diameter glass tube using a rubber band. Make a 2-3mm hole in the pigskin with a scalpel. Then, allow the hydrogel to repair the defect in an aqueous environment. After repair, place the glass tube containing the dura mater face down and add red ink to the water to check if the dura mater defect is watertight. Then gradually add water until the pigskin defect cannot be watertightly closed, and define the height of the water column when water leaks from the hole as the burst pressure.

[0055] The rupture pressure diagram of the active composite gel sealing material prepared in Example 1 is shown below. Figure 3 As shown, Part A is the hydrogel without Mg@TA nanoparticles, and Part B is the hydrogel with Mg@TA nanoparticles. The results of the experiments are all greater than the normal value of cerebrospinal fluid pressure of 1800 mmH2O, which can meet the requirements of practical applications.

[0056] (4) Metal ion release models under normal and inflammatory microenvironments were constructed using PBS and 1 mmol / L H2O2, respectively. The drug release diagram of the active composite gel sealing material prepared in Example 1 is shown below. Figure 4 As shown, the release amount and rate of the hydrogel under H2O2 conditions were higher than those under PBS conditions. Under H2O2 conditions, the borate ester bonds in the hydrogel break upon encountering H2O2 and reactive oxygen species such as hydroxyl radicals, leading to increased Mg@TA release and thus increased Mg content. 2+ The release amount increased.

[0057] Therefore, the active composite gel sealing material provided by this invention has excellent tissue adhesion and sealing performance; good in vivo compatibility, biodegradability, and low immunogenicity, resulting in high safety; high mechanical strength, good self-healing ability, and strong hydrolytic stability; the adhesion performance and state of the material can be adjusted by changing the proportion of each component to meet the needs of different adhesion performances in practical applications, fill irregular wounds, and rapidly gel at body temperature to adapt to the shape of the surgical site; it also has hemostatic, anti-inflammatory, and angiogenesis-promoting effects.

[0058] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. An active composite gel sealing material, characterized in that, It is prepared from the following components: component A, component B, and active factor; component A is a biocompatible macromolecule containing carbonyl aldehydes or ketones; component B is an amino-terminated macromolecule that is easy to modify; the active factor is one or more of growth promoters, metal particles, and polyphenols.

2. The active composite gel sealing material according to claim 1, characterized in that: The biocompatible macromolecules containing carbonyl groups, such as aldehydes and ketones, are one of oxidized dextran, oxidized hyaluronic acid, oxidized sodium alginate, and NHS-terminated polyethylene glycol derivatives.

3. The active composite gel sealing material according to claim 2, characterized in that: The biocompatible macromolecules, such as carbonyl aldehydes and ketones, are oxidized / modified with sodium periodate.

4. The active composite gel sealing material according to claim 1, characterized in that: The amino-terminated macromolecule that is easy to modify is obtained by modifying one of gelatin, chitosan, polyethyleneimine and its derivatives.

5. The active composite gel sealing material according to claim 4, characterized in that: The modification was performed using 4-carboxyphenylboronic acid.

6. The active composite gel sealing material according to claim 1, characterized in that: The metal particles are divalent cations, specifically Ca. 2+ Mg 2+ Cu 2+ Zn 2+ One of them.

7. The active composite gel sealing material according to claim 1, characterized in that: The polyphenols are natural polyphenols, and are one or two of tannic acid and catechin.

8. The active composite gel sealing material according to claim 1, characterized in that: The mass ratio of component A: component B: active factor is 1-2:1:0.005-0.

02.

9. A method for preparing an active composite gel sealing material as described in any one of claims 1-5, characterized in that, The steps are as follows: S1. Prepare a mixture of component B and active agent; S2. Prepare component A into a solution; S3. Extrude and mix the mixture prepared in S1 and the solution prepared in S2 in equal proportions to form a gel, or form a gel after ultraviolet irradiation.

10. The application of an active composite gel sealing material as described in any one of claims 1-5 in tissue occlusion and wound closure promotion, characterized in that: The tissue closure and wound closure promotion include, but are not limited to, dural closure, spinal closure, renal hemostasis, pulmonary closure, pericardial adhesion to prevent adhesion, gastrointestinal anastomosis, urethral anastomosis, and nerve adhesion.

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