Self-shedding hemostatic gel as well as preparation method and application thereof

Abstract

The invention provides self-falling hemostatic gel as well as a preparation method and application thereof, and particularly relates to the technical field of biomedical materials. The preparation method specifically comprises the following steps: S1, performing pretreatment on purification of sodium alginate; s2, synthesizing a copolymer of ethyl acrylate and acrylic acid by adopting an RAFT (Reversible Addition-Fragmentation Chain Transfer) controllable polymerization method; s3, preparing hollow particles of the copolymer obtained in S2 by adopting a solvent emulsification method; s4, preparing the bio-based hemostatic gel capable of automatically falling off by adopting a blending cross-linking method. The antibacterial hemostatic gel is good in antibacterial performance and capable of achieving rapid hemostasis, when the pH value of the gel is increased after the gel encounters blood, the gel can automatically fall within about 2-3 h, and secondary damage caused by adhesion to the wound surface is avoided.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and in particular to a self-shedding hemostatic gel and a preparation method and application thereof. Background Art

[0002] In the first aid of open surface trauma, rapid and effective hemostasis is the key to reducing the risk of infection, preventing shock and even saving lives. Traditional in vitro hemostatic materials such as gauze and cotton pads rely on the principle of physical compression, but have significant limitations: poor adhesion to deep or irregular wounds (such as lacerations and gunshot wounds) and low hemostasis efficiency; adhesion caused by blood infiltration during removal will tear new tissue, resulting in a secondary bleeding rate of up to 15-30%. Although the subsequently developed synthetic hemostatic agents (such as gelatin sponges and fibrin patches) have improved adhesion, they are chemically cross-linked and stable, requiring manual peeling or waiting for several days to slowly degrade, resulting in two major clinical pain points: removal of damage and interference with healing. The in vitro clinical dilemma that cannot be safely detached is specifically manifested as follows:

[0003] 1. Tissue adhesion trauma

[0004] Once the gel is tightly bound to the blood clot at the wound surface, forcible removal can damage the delicate granulation tissue. For example, while cyanoacrylate tissue glue can quickly seal wounds, it is very hard after curing, often requiring surgical removal, which can worsen tissue damage.

[0005] 2. Dynamic environment instability

[0006] Wounds in active areas like joints and the neck frequently deform, and conventional gels are prone to breaking and falling apart due to insufficient mechanical strength or compressing tissues due to excessive swelling. Conventional chitosan gels experience a greater than 60% loss of adhesion in moist environments, making them incapable of maintaining a durable seal.

[0007] 3. Functional Singularity Defect

[0008] Most commercially available products focus solely on hemostasis, lacking both antimicrobial and healing-promoting properties. While silver ion dressings have antibacterial properties, their cytotoxicity may delay healing. Furthermore, any residual silver ion dressing after hemostasis hinders oxygen exchange and epithelial regeneration. Summary of the Invention

[0009] To overcome the above-mentioned deficiencies of the prior art, the present invention provides a self-shedding hemostatic gel and its preparation method and application. The specific technical solutions are as follows:

[0010] A method for preparing a self-shedding hemostatic gel comprises the following steps:

[0011] S1 performs pretreatment for the purification of sodium alginate;

[0012] S2 uses RAFT controlled polymerization to synthesize copolymers of ethyl acrylate and acrylic acid;

[0013] S3 prepares hollow microparticles of the copolymer obtained in S2 by solvent emulsification method;

[0014] S4 uses a blending and cross-linking method to prepare a bio-based self-detachable hemostatic gel.

[0015] Preferably, the S1 includes the following sub-steps:

[0016] S1.1 Dissolution: Dissolve sodium alginate in deionized water and stir for 2 h until it is completely dissolved to obtain a sodium alginate solution;

[0017] S1.2 Precipitation purification: Add anhydrous ethanol to the sodium alginate solution to precipitate the sodium alginate, filter the precipitate and wash it with ethanol at least three times;

[0018] S1.3 Drying: Dry the material obtained in S1.2 under vacuum at 40°C for 24 hours to obtain purified sodium alginate for later use;

[0019] Wherein, the concentration of the sodium alginate solution is 0.025 g / mL; the volume of the deionized water is 150 to 400 mL; and the volume of the anhydrous ethanol is 400 to 800 mL.

[0020] Preferably, the step S2 specifically includes the following sub-steps:

[0021] S2.1 Dissolve purified ethyl acrylate and acrylic acid in anhydrous 1,4-dioxane along with a RAFT chain transfer agent. Deoxygenate the mixture by three freeze-thaw cycles. Add azobisisobutyronitrile under nitrogen and stir in an oil bath at 70°C for 24 hours.

[0022] After the reaction in step S2.2 is completed, the product solution obtained in step S2.1 is poured into cold n-hexane for precipitation;

[0023] S2.3 The precipitate was collected by centrifugation at 10,000 rpm for 15 min and subjected to Soxhlet extraction and dialysis purification.

[0024] S2.4 Dry the product obtained in S2.3 under vacuum at 40°C to a constant weight to obtain a copolymer of ethyl acrylate and acrylic acid.

[0025] Preferably, the step S3 specifically includes the following sub-steps:

[0026] S3.1 Weigh a copolymer of ethyl acrylate and acrylic acid and dissolve it in a pre-cooled mixture of dichloromethane and methanol. Use ultrasound to dissolve the mixture until the solution is completely transparent.

[0027] S3.2 In a 0°C ice-water bath, slowly inject the organic phase obtained in S3.1 into the polyvinylpyrrolidone aqueous solution using a high-speed shear emulsifier at a constant flow rate of 20 mL / min at 8000 rpm. Continue shear emulsification for 60 s to form a stable emulsion.

[0028] S3.3 Transfer the emulsion obtained after emulsification in S3.2 to a magnetic stirrer and gently stir at 300 rpm at room temperature for 12 hours to ensure complete evaporation of the dichloromethane;

[0029] S3.4 Centrifuge the emulsion obtained in S3.3 at 8000 rpm for 10 min, collect the precipitate, and resuspend it in deionized water at least three times to completely remove free polyvinylpyrrolidone;

[0030] S3.5 The precipitate obtained in S3.4 is filtered using a nylon filter membrane with a pore size of 50 μm to remove aggregates in the precipitate, thereby obtaining a uniform hollow microparticle dispersion system of ethyl acrylate and acrylic acid copolymer; it is placed in a vacuum drying environment at a constant temperature of 25°C and a pressure of 0.1 MPa for 24 hours to obtain a white powdery product, which is the hollow microparticles of ethyl acrylate and acrylic acid copolymer.

[0031] Also preferably, the S4 specifically includes the following sub-steps:

[0032] S4.1 Dissolve the purified sodium alginate in phosphate buffer at 50°C and pH 6.0 and stir for 2 h to obtain a purified sodium alginate solution;

[0033] S4.2 preparing an aqueous solution of hollow microparticles of ethyl acrylate and acrylic acid copolymer;

[0034] S4.3: Mix the purified sodium alginate solution obtained in S4.1 with the aqueous solution obtained in S4.2 in a volume ratio of 4:1 and stir at 500 rpm;

[0035] S4.4 Add calcium chloride crosslinker to the mixed solution obtained in S4.3 under ice bath conditions, emulsify at 12,000 rpm for 60 seconds, and immediately inject into a mold. Allow to cure at 4°C for 30 minutes to form a semi-IPN gel.

[0036] S4.5 Wash the semi-IPN gel obtained in S4.4 at least three times with a phosphate buffer having a pH of 7.4 to remove residual substances, thereby obtaining a bio-based self-shedding hemostatic gel.

[0037] Also preferably, in S2.1, the millimolar ratio of ethyl acrylate, acrylic acid, RAFT chain transfer agent and azobisisobutyronitrile is 4:1:0.1:0.02; the volume of anhydrous 1,4-dioxane is 10 to 30 mL; in S2.3, the Soxhlet extraction is continuously performed in methanol solvent for 48 hours; and the dialysis purification uses a membrane with a molecular weight cutoff of 7 kDa for continuous extraction in methanol solvent for 72 hours.

[0038] Further preferably, in S3.1, the mass of the copolymer of ethyl acrylate and acrylic acid is weighed to be 1.5 to 3.5 g; the volume of the mixed solvent of dichloromethane and methanol is 25 to 50 mL; in the mixed solvent of dichloromethane and methanol, the volume ratio of dichloromethane solution to methanol solution is 4:1; in S3.2, the concentration of polyvinyl pyrrolidone in water is 5%.

[0039] Further preferably, in S4.1, the mass proportion of the purified sodium alginate in the purified sodium alginate solution is 1 to 5 wt%; in S4.2, the mass proportion of the ethyl acrylate and acrylic acid copolymer hollow particles in the aqueous solution is 3 to 10 wt%; in S4.4, the mass proportion of the calcium chloride crosslinker in the mixed solution obtained in S4.3 is 1.2 to 3 wt%; and the mold cavity of the mold is cylindrical with a cavity diameter of 10 mm and a thickness of 3 mm.

[0040] A self-shedding hemostatic gel is prepared by the above-mentioned preparation method; the hemostatic gel automatically sheds when the pH value of blood rises until the pH value reaches 7.2-7.4; the shedding time is 2-3 hours.

[0041] An application of a self-shedding hemostatic gel, which uses the above-mentioned bio-based self-shedding hemostatic gel and is suitable for high-activity areas, high-risk wounds for infection, and large-scale casualty sites.

[0042] The beneficial effects of the present invention are:

[0043] 1. Compared with traditional external hemostatic materials that rely on physical compression principles, such as gauze and cotton pads, this invention has better antibacterial properties, a shorter hemostatic time, and can also automatically fall off, effectively avoiding secondary trauma caused by adhesion to the tissue wound surface;

[0044] 2. Compared with traditional gels that are prone to breaking and falling off due to insufficient mechanical strength or compressing tissues due to excessive swelling, the present invention can achieve frequent deformation of wounds in active parts such as joints and necks. It is particularly suitable for highly active parts, high-risk wounds for infection, and large-scale casualty scenes that require rapid first aid. DETAILED DESCRIPTION

[0045] To overcome the above-mentioned deficiencies of the prior art, the present invention provides a self-shedding hemostatic gel and its preparation method and application. The specific technical solutions are as follows:

[0046] A method for preparing a self-shedding hemostatic gel comprises the following steps:

[0047] S1 performs pretreatment for the purification of sodium alginate, specifically comprising the following sub-steps:

[0048] S1.1 Dissolution: Dissolve sodium alginate in deionized water and stir for 2 h until it is completely dissolved to obtain a sodium alginate solution;

[0049] S1.2 Precipitation purification: Add anhydrous ethanol to the sodium alginate solution to precipitate the sodium alginate, filter the precipitate and wash it with ethanol at least three times;

[0050] S1.3 Drying: Dry the material obtained in S1.2 under vacuum at 40°C for 24 hours to obtain purified sodium alginate for later use;

[0051] Wherein, the concentration of the sodium alginate solution is 0.025 g / mL; the volume of the deionized water is 150 to 400 mL; and the volume of the anhydrous ethanol is 400 to 800 mL.

[0052] S2 uses RAFT (reversible addition fragmentation chain transfer) controlled polymerization to synthesize a copolymer of ethyl acrylate and acrylic acid (PEA-AA), which specifically includes the following sub-steps:

[0053] S2.1: Dissolve purified ethyl acrylate (EA) and acrylic acid (AA) along with a RAFT chain transfer agent in anhydrous 1,4-dioxane. Deoxygenate the mixture by three freeze-thaw cycles. Add azobisisobutyronitrile under nitrogen and stir in an oil bath at 70°C for 24 hours. The millimolar ratio of ethyl acrylate, acrylic acid, RAFT chain transfer agent, and azobisisobutyronitrile is 4:1:0.1:0.02. The volume of anhydrous 1,4-dioxane is 10-30 mL.

[0054] After the reaction in step S2.2 is completed, the product solution obtained in step S2.1 is poured into cold n-hexane for precipitation;

[0055] S2.3 The precipitate was collected by centrifugation at 10,000 rpm for 15 min and subjected to Soxhlet extraction and dialysis purification in sequence; it is worth noting here that the Soxhlet extraction was performed continuously in methanol solvent for 48 hours; the dialysis purification was performed continuously in methanol solvent for 72 hours using a membrane with a molecular weight cutoff of 7 kDa.

[0056] S2.4 Dry the product obtained in S2.3 under vacuum at 40°C to a constant weight to obtain a copolymer of ethyl acrylate and acrylic acid.

[0057] S3 uses a solvent emulsification method to prepare hollow microparticles of the copolymer obtained in S2, which specifically includes the following sub-steps:

[0058] S3.1 Weigh a copolymer of ethyl acrylate and acrylic acid and dissolve it in a precooled mixed solvent of dichloromethane and methanol. Use ultrasound to assist in dissolution until the solution becomes completely transparent. The weight of the copolymer of ethyl acrylate and acrylic acid is 1.5 to 3.5 g. The volume of the mixed solvent of dichloromethane and methanol is 25 to 50 mL. The volume ratio of the dichloromethane solution to the methanol solution in the mixed solvent of dichloromethane and methanol is 4:1.

[0059] S3.2 In a 0°C ice-water bath, slowly inject the organic phase obtained in S3.1 into the aqueous polyvinylpyrrolidone solution at a constant flow rate of 20 mL / min using a high-speed shear emulsifier at 8000 rpm. Continue shear emulsification for 60 s to form a stable emulsion; the concentration of polyvinylpyrrolidone in water is 5%.

[0060] S3.3 Transfer the emulsion obtained after emulsification in S3.2 to a magnetic stirrer and gently stir at 300 rpm at room temperature for 12 hours to ensure complete evaporation of the dichloromethane;

[0061] S3.4 Centrifuge the emulsion obtained in S3.3 at 8000 rpm for 10 min, collect the precipitate, and resuspend it in deionized water at least three times to completely remove free polyvinylpyrrolidone;

[0062] S3.5 The precipitate obtained in S3.4 is filtered using a nylon filter membrane with a pore size of 50 μm to remove aggregates in the precipitate, thereby obtaining a uniform hollow microparticle dispersion system of ethyl acrylate and acrylic acid copolymer; it is placed in a vacuum drying environment at a constant temperature of 25°C and a pressure of 0.1 MPa for 24 hours to obtain a white powdery product, which is the hollow microparticles of ethyl acrylate and acrylic acid copolymer.

[0063] S4 uses a blending and cross-linking method to prepare a bio-based self-shedding hemostatic gel, which specifically includes the following sub-steps:

[0064] S4.1 dissolving purified sodium alginate in a phosphate buffer solution at 50° C. and pH 6.0 and stirring for 2 hours to obtain a purified sodium alginate solution; wherein the purified sodium alginate accounts for 1 to 5 wt % of the purified sodium alginate solution;

[0065] S4.2 preparing an aqueous solution of hollow microparticles of ethyl acrylate and acrylic acid copolymer; wherein the mass proportion of the hollow microparticles of ethyl acrylate and acrylic acid copolymer in the aqueous solution is 3 to 10 wt %;

[0066] S4.3: Mix the purified sodium alginate solution obtained in S4.1 with the aqueous solution obtained in S4.2 in a volume ratio of 4:1 and stir at 500 rpm;

[0067] S4.4, in an ice bath, adding a calcium chloride crosslinker to the mixed solution obtained in S4.3, emulsifying the mixture at 12,000 rpm for 60 seconds, and immediately injecting the mixture into a mold. The mixture was allowed to stand and cure at 4°C for 30 minutes to form a semi-IPN gel. The calcium chloride crosslinker accounted for 1.2 to 3 wt% of the mixed solution obtained in S4.3. The mold cavity was cylindrical, with a diameter of 10 mm and a thickness of 3 mm.

[0068] S4.5 Wash the semi-IPN gel obtained in S4.4 at least three times with a phosphate buffer having a pH of 7.4 to remove residual substances, thereby obtaining a bio-based self-shedding hemostatic gel.

[0069] A self-detachable hemostatic gel is prepared using the above-mentioned preparation method. It is worth noting that the hemostatic gel gradually increases when it encounters blood pH value. When the pH value reaches 7.2-7.4, the hemostatic gel and the wound surface can automatically detach. The detachment time takes about 2-3 hours, thereby avoiding the problem of adhesion to the wound surface and causing secondary damage to the wound.

[0070] An application of a self-shedding hemostatic gel, using the above-mentioned bio-based self-shedding hemostatic gel, is mainly suitable for the following scenarios:

[0071] Scenario 1. Highly mobile areas: such as lacerations on limb joints and neck. The dynamic adhesion of the gel can maintain a seal as the skin stretches and will automatically fall off after healing starts.

[0072] Scenario 2. High-risk wounds: Gels containing natural antimicrobial ingredients can simultaneously inhibit drug-resistant bacteria and reduce the risk of sepsis.

[0073] Scenario 3. Mass casualty scenes requiring rapid first aid: Hydrogels that rapidly form at room temperature are suitable for non-professionals to operate, ensuring golden rescue time.

[0074] When using, place the hemostatic gel on the bleeding wound. The Ca content of sodium alginate in the hemostatic gel 2+ The mesh shrinks and firmly adheres to the wound surface. PEA-AA releases carboxyl groups to activate coagulation factors and promote rapid hemostasis of the wound. When the pH value of the wound healing period reaches 7.2-7.4, the hydrophilic chain segments of PEA-AA swell and the network dissociates. At this time, the hemostatic gel and the wound surface can automatically fall off. The shedding time takes about 2-3 hours.

[0075] The specific coagulation principle of this hemostatic gel: using the Ca in sodium alginate 2+ It plays the role of adhesion, blood absorption and hemostasis; PEA-AA hollow particles have carboxyl groups, which activate coagulation factors to accelerate hemostasis (specifically, the pH value of carboxyl groups increases after encountering blood, and ionization is negatively charged. The negative charge characteristic can activate coagulation factors in the coagulation pathway, thereby further accelerating the hemostasis process); and the wound exudate contacts the wound to exchange Ca-Na ions, forming a moist gel layer to achieve rapid hemostasis, while releasing Ca 2+ Activate coagulation factors to accelerate the coagulation process.

[0076] In summary, the in vitro self-detachable hemostatic gel solves the core contradiction of traditional materials in surface trauma management, namely "sticking firmly but not being able to be removed", through the closed-loop design of "hemostasis-protection-intelligent evacuation", providing a new generation of solutions for battlefield first aid, disaster medicine and daily trauma care.

[0077] In order to better understand the present invention, the following is further explained with reference to specific embodiments:

[0078] S1 pre-treats the purification of sodium alginate:

[0079] S1.1 Dissolve 5 g of sodium alginate in 200 mL of deionized water and stir for 2 h until it is completely dissolved to obtain a sodium alginate solution.

[0080] S1.2 Add 500 mL of anhydrous ethanol to the sodium alginate solution to precipitate sodium alginate, filter the precipitate, and wash it three times with ethanol;

[0081] S1.3 Dry the material obtained in S1.2 under vacuum at 40°C for 24 hours to obtain purified sodium alginate for later use.

[0082] S2 uses RAFT (reversible addition fragmentation chain transfer) controlled polymerization to synthesize copolymers of ethyl acrylate and acrylic acid:

[0083] S2.1: Dissolve purified ethyl acrylate (8.0 mmol) and acrylic acid (2.0 mmol) in 15 mL of anhydrous 1,4-dioxane along with a RAFT chain transfer agent (0.2 mmol). Deoxygenate the mixture by three freeze-thaw cycles. Add azobisisobutyronitrile (0.04 mmol) under nitrogen and stir in an oil bath at 70°C for 24 h.

[0084] After the reaction in step S2.2 is completed, the product solution obtained in step S2.1 is poured into cold n-hexane for precipitation;

[0085] S2.3 The precipitate was collected by centrifugation at 10,000 rpm for 15 min and subjected to Soxhlet extraction and dialysis purification, wherein the Soxhlet extraction was performed in methanol for 48 hours; and the dialysis purification was performed in methanol for 72 hours using a membrane with a molecular weight cutoff of 7 kDa.

[0086] S2.4 Dry the product obtained in S2.3 after Soxhlet extraction and dialysis purification at 40° C. under vacuum to constant weight to obtain a copolymer of ethyl acrylate and acrylic acid.

[0087] S3 uses solvent emulsification method to prepare hollow microparticles of the copolymer obtained in S2:

[0088] S3.1 Accurately weigh 2 g of a copolymer of ethyl acrylate and acrylic acid and dissolve it in 30 mL of a pre-cooled mixture of dichloromethane and methanol (4:1 by volume). Use ultrasound to dissolve the mixture until the solution is completely transparent.

[0089] S3.2 In a 0°C ice-water bath, slowly inject the organic phase obtained in S3.1 into 80 mL of a 5% aqueous solution of polyvinylpyrrolidone using a high-speed shear emulsifier at a constant flow rate of 20 mL / min at 8000 rpm. Continue shear emulsification for 60 s to form a stable emulsion.

[0090] S3.3 Transfer the emulsion obtained after emulsification in S3.2 to a magnetic stirrer and gently stir at 300 rpm at room temperature for 12 hours to ensure complete evaporation of the dichloromethane;

[0091] S3.4 Centrifuge the emulsion obtained in S3.3 at 8000 rpm for 10 min, collect the precipitate, and resuspend it in deionized water at least three times to completely remove free polyvinylpyrrolidone;

[0092] S3.5 The precipitate obtained in S3.4 is filtered using a nylon filter membrane with a pore size of 50 μm to remove aggregates in the precipitate, thereby obtaining a uniform hollow microparticle dispersion system of ethyl acrylate and acrylic acid copolymer; it is placed in a vacuum drying environment at a constant temperature of 25°C and a pressure of 0.1 MPa for 24 hours to obtain a white powdery product, which is the hollow microparticles of ethyl acrylate and acrylic acid copolymer.

[0093] S4 uses a blending and cross-linking method to prepare a bio-based self-shedding hemostatic gel:

[0094] S4.1 Dissolve 3 wt% purified sodium alginate in phosphate buffer at 50°C and pH 6.0 and stir for 2 h to obtain a purified sodium alginate solution;

[0095] S4.2 preparing an aqueous solution of hollow microparticles of ethyl acrylate and acrylic acid copolymer;

[0096] S4.3: Mix the purified sodium alginate solution obtained in S4.1 with the 5 wt% aqueous solution obtained in S4.2 in a volume ratio of 4:1 and stir at 500 rpm;

[0097] S4.4: Add 1.5 wt% calcium chloride crosslinker to the mixed solution obtained in S4.3 in an ice bath. Emulsify the mixture at 12,000 rpm for 60 s, then immediately inject it into a mold and allow it to cure at 4°C for 30 min to form a semi-IPN gel.

[0098] S4.5 Wash the semi-IPN gel obtained in S4.4 at least three times with a phosphate buffer having a pH of 7.4 to remove residual substances, thereby obtaining a bio-based self-shedding hemostatic gel with a diameter of 10 mm and a thickness of 3 mm.

[0099] The following is a comparison of the main performance parameters of the hemostatic gel with common hemostatic materials on the market. The results are shown in Table 1 below:

[0100] Table 1. Performance comparison with other common hemostatic materials

[0101]

[0102]

[0103] As can be seen from the above table, the hemostatic gel provided by the present invention not only achieves rapid hemostasis, but also greatly improves the antibacterial performance. It is particularly suitable for wounds in highly active areas (strong conformability), wounds at high risk of infection (better antibacterial properties), and large-scale casualty scenes where rapid first aid is required (good rapid coagulation performance).

[0104] In the present invention, the directions or positional relationships indicated by terms such as "upper", "lower", "bottom", "top", etc. are directions or positional relationships. They are relational words determined only for the convenience of describing the structural relationships of the various parts or elements of the present invention. They do not specifically refer to the present invention or elements and should not be understood as limitations on the present invention. Terms such as "connected" and "connect" should be understood in a broad sense, indicating that they can be fixedly connected, integrally connected, or detachably connected; they can be directly connected or indirectly connected through an intermediate medium. For relevant scientific research or technical personnel in this field, the specific meanings of the above terms in the present invention can be determined according to specific circumstances, and they should not be understood as limitations on the present invention.

[0105] Of course, the above description is not a limitation of the present invention, and the present invention is not limited to the above examples. Changes, modifications, additions or substitutions made by technicians in this technical field within the essential scope of the present invention should also fall within the scope of protection of the present invention.

Claims

1. A method for preparing a self-shedding hemostatic gel, characterized in that: The specific steps include: S1 performs pretreatment for the purification of sodium alginate; S2 uses RAFT controlled polymerization to synthesize copolymers of ethyl acrylate and acrylic acid; S3 prepares hollow microparticles of the copolymer obtained in S2 by solvent emulsification method; S4 uses a blending and cross-linking method to prepare a bio-based self-detachable hemostatic gel.

2. The method for preparing the self-shedding hemostatic gel according to claim 1, wherein: The S1 comprises the following sub-steps: S1.1 Dissolution: Dissolve sodium alginate in deionized water and stir for 2 h until it is completely dissolved to obtain a sodium alginate solution; S1.2 Precipitation purification: Add anhydrous ethanol to the sodium alginate solution to precipitate the sodium alginate, filter the precipitate and wash it with ethanol at least three times; S1.3 Drying: Dry the material obtained in S1.2 under vacuum at 40°C for 24 hours to obtain purified sodium alginate for later use; Wherein, the concentration of the sodium alginate solution is 0.025 g / mL; the volume of the deionized water is 150 to 400 mL; and the volume of the anhydrous ethanol is 400 to 800 mL.

3. The method for preparing the self-shedding hemostatic gel according to claim 2, wherein: The S2 specifically includes the following sub-steps: S2.1 Dissolve purified ethyl acrylate and acrylic acid in anhydrous 1,4-dioxane along with a RAFT chain transfer agent. Deoxygenate the mixture by three freeze-thaw cycles. Add azobisisobutyronitrile under nitrogen and stir in an oil bath at 70°C for 24 hours. After the reaction in step S2.2 is completed, the product solution obtained in step S2.1 is poured into cold n-hexane for precipitation; S2.3 The precipitate was collected by centrifugation at 10,000 rpm for 15 min and subjected to Soxhlet extraction and dialysis purification. S2.4 The product obtained in S2.3 after Soxhlet extraction and dialysis purification was dried at 40°C under vacuum to constant weight to obtain a copolymer of ethyl acrylate and acrylic acid.

4. The method for preparing the self-shedding hemostatic gel according to claim 3, wherein: The S3 specifically includes the following sub-steps: S3.1 Weigh a copolymer of ethyl acrylate and acrylic acid and dissolve it in a pre-cooled mixture of dichloromethane and methanol. Use ultrasound to dissolve the mixture until the solution is completely transparent. S3.2 In a 0°C ice-water bath, slowly inject the organic phase obtained in S3.1 into the polyvinylpyrrolidone aqueous solution using a high-speed shear emulsifier at a constant flow rate of 20 mL / min at 8000 rpm. Continue shear emulsification for 60 s to form a stable emulsion. S3.3 Transfer the emulsion obtained after emulsification in S3.2 to a magnetic stirrer and gently stir at 300 rpm at room temperature for 12 hours to ensure complete evaporation of the dichloromethane; S3.4 Centrifuge the emulsion obtained in S3.3 at 8000 rpm for 10 min, collect the precipitate, and resuspend it in deionized water at least three times to completely remove free polyvinylpyrrolidone; S3.5 The precipitate obtained in S3.4 is filtered using a nylon filter membrane with a pore size of 50 μm to remove aggregates in the precipitate, thereby obtaining a uniform hollow microparticle dispersion system of ethyl acrylate and acrylic acid copolymer; the system is then placed in a vacuum drying environment at a constant temperature of 25°C and a pressure of 0.1 MPa for 24 hours to obtain a white powdery product, which is the hollow microparticles of ethyl acrylate and acrylic acid copolymer.

5. The method for preparing the self-shedding hemostatic gel according to claim 4, characterized in that: The S4 specifically includes the following sub-steps: S4.1 Dissolve the purified sodium alginate in phosphate buffer at 50°C and pH 6.0 and stir for 2 h to obtain a purified sodium alginate solution; S4.2 preparing an aqueous solution of hollow microparticles of ethyl acrylate and acrylic acid copolymer; S4.3: Mix the purified sodium alginate solution obtained in S4.1 with the aqueous solution obtained in S4.2 in a volume ratio of 4:1 and stir at 500 rpm; S4.4 Add calcium chloride crosslinker to the mixed solution obtained in S4.3 under ice bath conditions, emulsify at 12,000 rpm for 60 seconds, and immediately inject into a mold. Allow to cure at 4°C for 30 minutes to form a semi-IPN gel. S4.5 Wash the semi-IPN gel obtained in S4.4 at least three times with a phosphate buffer having a pH of 7.4 to remove residual substances, thereby obtaining a bio-based self-shedding hemostatic gel.

6. The method for preparing the self-shedding hemostatic gel according to claim 3, characterized in that: In S2.1, the molar ratio of ethyl acrylate, acrylic acid, RAFT chain transfer agent and azobisisobutyronitrile is 4:1:0.1:0.02; The volume of the anhydrous 1,4-dioxane is 10 to 30 mL; In S2.3, the Soxhlet extraction is performed in a methanol solvent for 48 hours; the dialysis purification is performed in a methanol solvent for 72 hours using a membrane with a molecular weight cutoff of 7 kDa.

7. The method for preparing the self-shedding hemostatic gel according to claim 4, characterized in that: In S3.1, weigh 1.5 to 3.5 g of the copolymer of ethyl acrylate and acrylic acid; The volume of the mixed solvent of dichloromethane and methanol is 25 to 50 mL; In the mixed solvent of dichloromethane and methanol, the volume ratio of dichloromethane solution to methanol solution is 4:1; In S3.2, the concentration of the polyvinyl pyrrolidone aqueous solution is 5%.

8. The method for preparing the self-shedding hemostatic gel according to claim 5, characterized in that: In S4.1, the mass proportion of the purified sodium alginate in the purified sodium alginate solution is 1 to 5 wt%; In S4.2, the mass proportion of the ethyl acrylate and acrylic acid copolymer hollow particles in the aqueous solution thereof is 3 to 10 wt %; In S4.4, the mass proportion of the calcium chloride cross-linking agent in the mixed solution obtained in S4.3 is 1.2 to 3 wt%; the mold cavity of the mold is cylindrical with a diameter of 10 mm and a thickness of 3 mm.

9. A self-shedding hemostatic gel, characterized in that: Prepared by the preparation method according to claim 5; The hemostatic gel automatically falls off when the pH value of the blood rises until the pH value reaches 7.2 to 7.4; The shedding time is 2 to 3 hours.

10. An application of a self-shedding hemostatic gel, using the self-shedding hemostatic gel according to claim 9, characterized in that: Suitable for high-mobility areas, high-risk wounds for infection, and mass casualty scenes.

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