Preparation method of multifunctional hemostatic dressing suitable for multiple external chest injuries

Abstract

The invention discloses a preparation method of a multifunctional hemostatic dressing suitable for multiple external chest injuries. The preparation method comprises the following six steps: preparation of amino modified chitosan, preparation of nanoparticles loaded with blood coagulation factors, preparation of a catechol-sodium alginate composite adhesive, improvement of the performance of a base material through electrode treatment, preparation of a porous hydrophilic layer and composite molding. The method integrates an electrode treatment technology, effectively eliminates the internal stress of the material, and improves the adhesiveness and stability; in combination with core components such as modified chitosan and blood coagulation factor nanoparticles, the dressing is endowed with the functions of quickly stopping bleeding, strongly adhering in a wet state, inhibiting bacteria, resisting infection, promoting healing and the like. The finished dressing is good in biocompatibility, free of sensitization and irritation and excellent in mechanical property, the complex hemostasis requirement for multiple external chest injuries can be met in a targeted mode, the preparation technology is controllable, and the dressing is suitable for large-scale production.

Description

Technical Field

[0001] This invention relates to the field of hemostatic dressing preparation technology, specifically to a method for preparing a multifunctional hemostatic dressing suitable for multiple external chest injuries. Background Technology

[0002] Multiple chest injuries are often accompanied by complex issues such as massive intrapleural hemorrhage, tissue damage, and increased risk of infection, making them one of the types of trauma with a high mortality rate in clinical emergency care. Rapid and effective hemostasis, wound closure, infection control, and promotion of tissue repair are core requirements for improving the success rate of treating multiple chest injuries. Currently used hemostatic dressings mainly include fibrin glue, oxidized regenerated cellulose, chitosan, and zeolite, but they have significant limitations when dealing with the complex scenarios of multiple chest injuries. While fibrin glue can form a clot that adheres to the wound, its adhesive strength is limited. It is prone to detachment in the dynamic environment of the pleural cavity and on moist tissue surfaces, making it unsuitable for rapid massive bleeding such as rupture of a major artery. Oxidized regenerated cellulose, although possessing certain antibacterial properties, suffers from insufficient biocompatibility and potential irritation to nerve tissue, making it unsuitable for sensitive areas such as the mediastinum and pleura involved in external thoracic injuries. Zeolite hemostatic materials exhibit significant water absorption and exothermic effects, with maximum temperatures reaching approximately 100°C, which can easily lead to thermal damage to the soft tissues of the chest wall and internal organs of the pleural cavity. Furthermore, its powdery form can easily remain in blood vessels or wound surfaces, increasing the difficulty of subsequent treatment.

[0003] Existing chitosan-based hemostatic dressings, while exhibiting good biocompatibility, generally suffer from poor wet adhesion, slow hemostasis, and limited functionality, failing to simultaneously meet the multiple demands of frequent chest injuries for rapid hemostasis, secure closure, infection control, and minimizing secondary damage. Furthermore, chest injuries often involve irregular wound shapes, persistent bleeding, and mechanical friction; existing dressings lack sufficient mechanical strength and compliance, making them prone to breakage or displacement, leading to hemostasis failure. Therefore, developing a multifunctional hemostatic dressing that combines rapid and efficient hemostasis, strong wet adhesion, antibacterial and anti-infective properties, excellent mechanical properties, and high biocompatibility is crucial for solving the challenges in treating frequent chest injuries. Summary of the Invention

[0004] In order to solve the problems existing in the background art, the purpose of the present invention is to provide a method for preparing a multifunctional hemostatic dressing suitable for multiple external chest injuries, so as to solve the problems existing in the background art.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: A method for preparing a multifunctional hemostatic dressing suitable for multiple chest injuries, the method being as follows: Step 1: Preparation of amino-modified chitosan Chitosan with a degree of deacetylation of 85%–95% was selected and dissolved in a 1%–2% wt acetic acid solution. The solution was stirred until completely dissolved to form a chitosan solution with a concentration of 2%–5% wt. 3-aminopropyltriethoxysilane was added to the solution at an amount of 10%–20% of the chitosan mass. The solution was stirred at a constant temperature of 40–50°C for 3–5 hours to achieve amino functionalization modification of the chitosan surface. After the reaction was completed, the solution was dialyzed in a dialysis bag with a molecular weight cutoff of 3000–5000 for 24–36 hours to remove unreacted silane reagents and impurities. Finally, the solution was freeze-dried to obtain amino-modified chitosan powder. Step 2: Preparation of Coagulation Factor-Loaded Nanoparticles Polyvinyl alcohol (PVA) was added to deionized water and heated to 80-90°C with stirring for 2-3 hours to form a PVA solution with a mass fraction of 5%-8%. After cooling to 30-40°C, bovine serum albumin (BSA) and coagulation factors were added sequentially, with BSA at a mass fraction of 0.05%-0.1% and coagulation factors at a mass fraction of 0.03%-0.08%. The mixture was stirred continuously for 1-2 hours until completely dissolved. The above mixed solution was slowly injected into a polycaprolactone (PCL) solution in dichloromethane, with PCL at a mass fraction of 2%-4%. The mixture was emulsified using a probe-type ultrasonic homogenizer at 100-150W power for 15-20 minutes to form a stable oil-in-water emulsion. The emulsion was placed in a rotary evaporator and evaporated under reduced pressure at 35-45°C for 1-2 hours to remove dichloromethane, yielding a PVA nanoparticle suspension loaded with coagulation factors. This suspension was then freeze-dried for later use. Step 3: Preparation of Catechol-Sodium Alginate Composite Adhesive Sodium alginate was dissolved in deionized water and stirred until completely dissolved to form a sodium alginate solution with a mass fraction of 3% to 6%. Catechol was added to the solution at a mass ratio of 1:5 to 1:8. The mixture was stirred at 25 to 30°C for 30 to 45 minutes to allow the phenolic hydroxyl groups of the catechin to form hydrogen bonds with the carboxyl groups of the sodium alginate. Subsequently, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride was added at an amount of 20% to 30% of the mass of the catechin. The mixture was stirred for 1 to 2 hours to promote the cross-linking reaction and obtain a catechin-sodium alginate composite adhesive with strong adhesive properties. Step 4: Electrode treatment improves substrate performance The amino-modified chitosan powder prepared in step 1 and the catechol-sodium alginate composite adhesive obtained in step 3 are mixed at a mass ratio of 3:1 to 5:1. An appropriate amount of deionized water is added to adjust the viscosity to 500 to 1000 mPa·s. After stirring evenly, a mixed slurry is formed. The mixed slurry is coated on the surface of a medical nonwoven fabric substrate with a coating thickness controlled at 0.5 to 1.0 mm. The substrate is placed in an electrode treatment device and plasma electrode treatment technology is used. The electrode voltage is set to 10 to 15 kV, the treatment time is 5 to 10 min, and the treatment distance is 5 to 8 cm. The high-energy particles generated by the electrode treatment bombard the coating surface, eliminating the internal stress of the material and introducing active groups to improve the adhesion between the coating and the substrate and the wet adhesion performance. After treatment, the substrate is vacuum dried at 60 to 70 °C for 2 to 3 h. Step 5: Preparation of the porous hydrophilic layer Pumice particles were crushed to a particle size of 0.1-0.3 mm, soaked in 4 mol / L hydrochloric acid for 2-3 hours to remove impurities and soluble salts, washed with water until neutral, and then calcined at 550-600℃ for 2-3 hours to enhance porosity. The calcined pumice particles were dispersed in a 70% ethanol solution, and vinyltriethoxysilane was added at a mass ratio of 10:1-15:1. The mixture was reacted at 60-70℃ for 2-3 hours, followed by the addition of polyethyleneimine for another 1-2 hours to achieve amino modification. The amino-modified pumice was mixed with sodium carboxymethyl cellulose at a mass ratio of 1:2-1:4, and polyethylene glycol 400 was added as a plasticizer at a mass ratio of 5%-10% of the total mass of the mixture. After stirring evenly, the mixture was allowed to stand to defoam, and then freeze-dried at -20 to -30℃ for 12-24 hours to obtain a porous hydrophilic layer material. Step 6: Composite molding of multifunctional dressings The modified substrate after electrode treatment in step 4 is used as the functional bottom layer, the porous hydrophilic layer prepared in step 5 is used as the intermediate layer, and a thermoplastic polyurethane film is selected as the protective layer. The three-layer structure is composited in the order of functional bottom layer, porous hydrophilic layer and protective layer using medical pressure-sensitive adhesive. The pressing temperature is 40~50℃, the pressure is 0.3~0.5MPa, and the pressing time is 15~20min. After composite, it is sterilized by irradiation with Co60 rays at a dose of 25~30kGy, and finally a multifunctional hemostatic dressing suitable for multiple chest injuries is obtained.

[0006] Preferred: In step 1, the pH of the acetic acid solution is adjusted to 4.0~5.0. 3-aminopropyltriethoxysilane is added dropwise to the chitosan solution in 3~5 portions, with an interval of 30 minutes between each addition, to avoid excessive local concentration leading to agglomeration. During dialysis, deionized water is replaced every 6 hours to ensure thorough removal of impurities. The freeze-drying temperature is -40~-50℃, and the drying time is 12~16 hours to ensure the loose and porous structure of the modified chitosan powder.

[0007] Prioritize: In step 2, thrombin is selected as the coagulation factor. It must be stored at -20℃ before addition, and the solution temperature must be strictly controlled below 35℃ during addition to avoid inactivation of the coagulation factor; during ultrasonic emulsification, intermittent operation is adopted, with a 2-minute pause every 5 minutes to prevent excessive temperature from affecting the stability of the nanoparticles; the particle size of the freeze-dried nanoparticles is controlled at 50~200nm, and the particle size is detected by a laser particle size analyzer to ensure uniform dispersion of the particles.

[0008] Prioritize the following: In step 3, sodium alginate with a molecular weight of 100,000 to 200,000 Da should be selected to ensure adhesion and cross-linking effects; catechins should be recrystallized and purified before dissolution to remove impurities that could affect adhesion; magnetic stirring should be used during the cross-linking reaction at a speed of 300 to 500 rpm to avoid damaging the molecular chain structure; the viscosity of the composite adhesive should be monitored in real time using a rotational viscometer to ensure it is within the range of 300 to 800 mPa·s.

[0009] Prioritize: Step 4: The nonwoven fabric for TCM uses a blend of polyester and cotton fibers in a ratio of 7:3 to 6:4 to ensure the breathability and mechanical strength of the substrate; Argon gas is introduced as a protective gas during electrode treatment at a flow rate of 10 to 20 mL / min to prevent coating oxidation; Gradient heating is used during vacuum drying, gradually increasing the temperature from 30°C to 70°C at a rate of 10°C per hour to further eliminate internal stress in the material.

[0010] Prioritize: In step 5, the calcination of the pumice particles adopts a programmed temperature increase, from room temperature to 550~600℃ at a rate of 5℃ / min, to avoid sudden temperature rise that could cause particle breakage; the molecular weight of the polyethyleneimine is selected to be 1000~2000 Da to ensure the amino grafting density; before freeze drying, the mixed system is pre-frozen at -80℃ for 2~3 hours to improve the uniformity of the porous structure, and the porosity of the porous hydrophilic layer is controlled at 70%~85%, as measured by a mercury porosimeter.

[0011] Prioritize: Step 6: Use an acrylic solvent-free pressure-sensitive adhesive for TCM applications to ensure biocompatibility and bonding stability; employ roller pressing during the lamination process with a roller speed of 5-10 r / min to ensure tight adhesion and no air bubbles in the three-layer structure; use a uniform scanning method for Co60 irradiation, placing the dressing flat with a spacing of 5-10 cm during irradiation to ensure uniform sterilization effect; perform sterility testing after irradiation, and the colony count must meet the requirements of GB / T 14233.2-2005 standard.

[0012] Compared with the prior art, the present invention has the following beneficial effects: Rapid and efficient hemostasis: Utilizing the cationic effect of amino-modified chitosan, it quickly captures and activates platelets and red blood cells, accelerating the initiation of coagulation; the loaded coagulation factor nanoparticles can quickly penetrate the wound surface, directly replenishing coagulation components and shortening the coagulation cascade reaction time; the phenolic hydroxyl groups of catechol form covalent bonds with the amino groups on the tissue surface, quickly sealing the bleeding point. The synergistic effect of these three factors shortens the hemostasis time by more than 50% compared to traditional dressings, making it suitable for scenarios involving massive bleeding from multiple external chest injuries.

[0013] Strong wet adhesion and stability: Electrode treatment eliminates internal stress in the material, promotes the exposure of active groups, and enhances the adhesion between the coating and the substrate; the cross-linked structure of catechol-sodium alginate forms a stable adhesive layer in a humid environment with an adhesion strength of over 70 kPa, which can resist the mechanical force generated by dynamic chest cavity activity, prevent dressing displacement, and solve the problem of traditional dressings easily falling off in a wet state.

[0014] Antibacterial and anti-infective properties and biosafety: The quaternary ammonium salt groups of modified chitosan and the silver ions of silver nitrate work synergistically to disrupt the bacterial cell membrane structure, with an antibacterial rate of over 95% against Escherichia coli and Staphylococcus aureus; the material has shown cell viability of over 90% in cytotoxicity tests, with no sensitization or intradermal irritation, meeting medical biosafety standards and reducing the risk of infection in external chest wounds.

[0015] Excellent fluid absorption and retention, and promotes healing: The amino-modified pumice with a porous hydrophilic layer provides strong water absorption capacity, with an absorption rate of over 1500%, quickly absorbing and retaining pleural effusion and preventing fluid accumulation; allantoin and traditional Chinese medicine extracts create a micro-moistening healing environment, promoting epithelial cell proliferation, with a wound healing rate of over 85% in 14 days, and the dressing does not adhere to granulation tissue, reducing secondary damage during dressing changes. Detailed Implementation

[0016] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0017] A method for preparing a multifunctional hemostatic dressing suitable for multiple chest injuries, the method being as follows: Step 1: Preparation of amino-modified chitosan Chitosan with a degree of deacetylation of 85%–95% was selected and dissolved in a 1%–2% wt acetic acid solution. The solution was stirred until completely dissolved to form a chitosan solution with a concentration of 2%–5% wt. 3-aminopropyltriethoxysilane was added to the solution at an amount of 10%–20% of the chitosan mass. The solution was stirred at a constant temperature of 40–50°C for 3–5 hours to achieve amino functionalization modification of the chitosan surface. After the reaction was completed, the solution was dialyzed in a dialysis bag with a molecular weight cutoff of 3000–5000 for 24–36 hours to remove unreacted silane reagents and impurities. Finally, the solution was freeze-dried to obtain amino-modified chitosan powder. The pH of the acetic acid solution was adjusted to 4.0-5.0. 3-aminopropyltriethoxysilane was added dropwise to the chitosan solution in 3-5 portions, with an interval of 30 minutes between each addition, to avoid excessive local concentration that could lead to agglomeration. During dialysis, the deionized water was replaced every 6 hours to ensure thorough removal of impurities. The freeze-drying temperature was -40 to -50°C, and the drying time was 12-16 hours to ensure the loose and porous structure of the modified chitosan powder.

[0018] Analysis of the above technical content: In the preparation of amino-modified chitosan, this scheme precisely selects chitosan with a deacetylation degree of 85%~95% as the substrate, which itself has good biocompatibility. Dissolving it in 1%~2% wt acetic acid solution and adjusting the pH to 4.0~5.0 ensures that the chitosan is fully dissolved to form a stable solution of 2%~5% wt, while also providing a suitable acidic environment for the subsequent amino grafting reaction. The innovative use of 3-aminopropyltriethoxysilane as the modifying agent, added dropwise in 3~5 portions at a ratio of 10%~20% of the chitosan mass with 30-minute intervals, effectively avoids molecular aggregation caused by excessively high local concentrations, ensuring uniform reaction between the silane reagent and chitosan molecules. Amino functionalization of the chitosan surface is achieved by constant temperature stirring at 40~50℃ for 3~5 hours. Subsequently, dialysis was performed for 24-36 hours using dialysis bags with a molecular weight cutoff of 3000-5000, with deionized water replaced every 6 hours to thoroughly remove unreacted silane reagents and impurities. The mixture was then freeze-dried at -40 to -50°C for 12-16 hours, preserving the loose, porous structure of the modified chitosan powder while increasing its surface amino density. The core innovation of this step lies in solving the problems of low amino activity and poor dispersibility of traditional chitosan through precise control of reaction conditions and a step-by-step feeding process. The modified chitosan, with its cationic effect, can rapidly capture and activate platelets and erythrocytes, laying the foundation for the rapid hemostatic function of subsequent dressings. Simultaneously, the porous structure facilitates subsequent compounding with other components and the absorption of wound exudate.

[0019] Step 2: Preparation of Coagulation Factor-Loaded Nanoparticles Polyvinyl alcohol (PVA) was added to deionized water and heated to 80-90°C with stirring for 2-3 hours to form a PVA solution with a mass fraction of 5%-8%. After cooling to 30-40°C, bovine serum albumin (BSA) and coagulation factors were added sequentially, with BSA at a mass fraction of 0.05%-0.1% and coagulation factors at a mass fraction of 0.03%-0.08%. The mixture was stirred continuously for 1-2 hours until completely dissolved. The above mixed solution was slowly injected into a polycaprolactone (PCL) solution in dichloromethane, with PCL at a mass fraction of 2%-4%. The mixture was emulsified using a probe-type ultrasonic homogenizer at 100-150W power for 15-20 minutes to form a stable oil-in-water emulsion. The emulsion was placed in a rotary evaporator and evaporated under reduced pressure at 35-45°C for 1-2 hours to remove dichloromethane, yielding a PVA nanoparticle suspension loaded with coagulation factors. This suspension was then freeze-dried for later use. Thrombin was selected as the coagulation factor and was stored at -20°C before addition. The solution temperature was strictly controlled below 35°C during addition to prevent coagulation factor inactivation. Intermittent operation was used during ultrasonic emulsification, with a 2-minute pause every 5 minutes to prevent excessive temperature from affecting the stability of the nanoparticles. The particle size of the freeze-dried nanoparticles was controlled between 50 and 200 nm and measured by a laser particle size analyzer to ensure uniform particle dispersion.

[0020] Analysis of the above technical content: This step uses polyvinyl alcohol as a carrier matrix, preparing a 5%~8% wt polyvinyl alcohol solution by heating and stirring at 80~90℃ for 2~3 hours. Its good biocompatibility and film-forming properties provide a stable loading environment for coagulation factors. Innovatively, bovine serum albumin is introduced as a protective agent, added at a mass fraction of 0.05%~0.1%, and synergistically dissolved with thrombin (preferably a coagulation factor) at a mass fraction of 0.03%~0.08% in a polyvinyl alcohol solution cooled to 30~40℃. The solution temperature is strictly controlled below 35℃ to avoid inactivation of coagulation factors. Simultaneously, bovine serum albumin can reduce the degradation of coagulation factors in subsequent processes. The mixed solution was injected into a dichloromethane solution containing 2%–4% wt polycaprolactone, and intermittently emulsified for 15–20 minutes using a 100–150W probe-type ultrasonic homogenizer (with a 2-minute pause after every 5 minutes of operation). This ensured the formation of a stable oil-in-water emulsion while preventing excessive temperature from damaging the nanoparticle structure. After removing the dichloromethane by vacuum evaporation at 35–45°C, the nanoparticles were freeze-dried to obtain uniform nanoparticles of 50–200 nm. The key innovation of this step lies in the use of nanoparticle drug delivery technology and intermittent ultrasonic emulsification process, which solves the problems of easy inactivation and low efficacy of traditional coagulation factors. The nanoparticles loaded with coagulation factors can quickly penetrate the wound surface, directly replenish coagulation components, shorten the coagulation cascade reaction time, and form a synergistic hemostatic effect with amino-modified chitosan, significantly improving the hemostasis speed.

[0021] Step 3: Preparation of Catechol-Sodium Alginate Composite Adhesive Sodium alginate was dissolved in deionized water and stirred until completely dissolved to form a sodium alginate solution with a mass fraction of 3% to 6%. Catechol was added to the solution at a mass ratio of 1:5 to 1:8. The mixture was stirred at 25 to 30°C for 30 to 45 minutes to allow the phenolic hydroxyl groups of the catechin to form hydrogen bonds with the carboxyl groups of the sodium alginate. Subsequently, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride was added at an amount of 20% to 30% of the mass of the catechin. The mixture was stirred for 1 to 2 hours to promote the cross-linking reaction and obtain a catechin-sodium alginate composite adhesive with strong adhesive properties. Sodium alginate with a molecular weight of 100,000 to 200,000 Da is selected to ensure adhesion and cross-linking effects. Catechol needs to be recrystallized and purified before dissolution to remove the influence of impurities on adhesion performance. Magnetic stirring is used during the cross-linking reaction at a speed of 300 to 500 rpm to avoid high-speed stirring from damaging the molecular chain structure. The viscosity of the composite adhesive is monitored in real time by a rotational viscometer to ensure it is within the range of 300 to 800 mPa·s.

[0022] Analysis of the above technical content: This scheme uses sodium alginate with a molecular weight of 100,000 to 200,000 Da, dissolved in deionized water to form a solution of 3% to 6% wt. Its high molecular weight characteristics ensure the basic adhesive properties and cross-linking effect of the adhesive. Innovatively, catechins are mixed with sodium alginate at a mass ratio of 1:5 to 1:8 and stirred at 25 to 30°C for 30 to 45 minutes, allowing the phenolic hydroxyl groups of catechins to form hydrogen bonds with the carboxyl groups of sodium alginate, thus initially constructing the adhesive system. Subsequently, 20% to 30% by weight of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride is added as a cross-linking agent, and the reaction is carried out at a magnetic stirring speed of 300 to 500 rpm for 1 to 2 hours to avoid high-speed stirring damaging the molecular chain structure. Simultaneously, a rotational viscometer is used for real-time monitoring to ensure that the viscosity of the adhesive is within the range of 300 to 800 mPa·s. The pretreatment step of recrystallization and purification of catechins removes impurities that interfere with adhesive properties. The core innovation of this step lies in the construction of a cross-linked adhesive system with synergistic hydrogen and covalent bonds, which solves the problem of insufficient wet adhesive strength of traditional adhesives. The phenolic hydroxyl groups of catechins can form covalent bonds with amino groups on the tissue surface, and the carboxyl groups of sodium alginate interact with wound cells. The composite adhesive can maintain stable adhesion even in a moist environment, ensuring the firm fixation of the dressing in the dynamic environment of the thoracic cavity.

[0023] Step 4: Electrode treatment improves substrate performance The amino-modified chitosan powder prepared in step 1 and the catechol-sodium alginate composite adhesive obtained in step 3 are mixed at a mass ratio of 3:1 to 5:1. An appropriate amount of deionized water is added to adjust the viscosity to 500 to 1000 mPa·s. After stirring evenly, a mixed slurry is formed. The mixed slurry is coated on the surface of a medical nonwoven fabric substrate with a coating thickness controlled at 0.5 to 1.0 mm. The substrate is placed in an electrode treatment device and plasma electrode treatment technology is used. The electrode voltage is set to 10 to 15 kV, the treatment time is 5 to 10 min, and the treatment distance is 5 to 8 cm. The high-energy particles generated by the electrode treatment bombard the coating surface, eliminating the internal stress of the material and introducing active groups to improve the adhesion between the coating and the substrate and the wet adhesion performance. After treatment, the substrate is vacuum dried at 60 to 70 °C for 2 to 3 h. The medical nonwoven fabric is made of a blend of polyester and cotton fibers in a ratio of 7:3 to 6:4 to ensure the breathability and mechanical strength of the substrate. Argon gas is introduced as a protective gas during the electrode treatment process at a flow rate of 10 to 20 mL / min to prevent coating oxidation. Gradual heating is used during the vacuum drying process, gradually increasing the temperature from 30°C to 70°C at a rate of 10°C per hour to further eliminate internal stress in the material.

[0024] Analysis of the above technical content: In this step, amino-modified chitosan powder and catechin-sodium alginate composite adhesive are mixed at a mass ratio of 3:1 to 5:1, and the viscosity is adjusted to 500 to 1000 mPa·s. This mixture is then coated onto the surface of a medical nonwoven fabric made of a blend of polyester and cotton fibers (7:3 to 6:4), with a coating thickness controlled at 0.5 to 1.0 mm. The blended substrate balances breathability and mechanical strength, providing stable support for the dressing. Innovatively, plasma electrode treatment technology is used, treating the surface at a voltage of 10 to 15 kV and a treatment distance of 5 to 8 cm for 5 to 10 minutes. Argon gas is introduced at a rate of 10 to 20 mL / min as a protective gas to prevent coating oxidation. High-energy particles bombard the coating surface, eliminating internal stress and introducing active groups, significantly improving the adhesion between the coating and the substrate and its wet adhesion performance. Subsequent vacuum drying using a gradient temperature increase from 30°C to 70°C (10°C increase per hour) further eliminates internal stress. The key innovation of this step lies in integrating electrode treatment technology into the dressing preparation process, which breaks through the limitations of traditional substrate modification methods. Through the synergistic effect of physical and chemical processes, it simultaneously solves problems such as poor coating adhesion, easy detachment in wet conditions, and poor stability caused by internal stress in the material. This gives the modified substrate excellent mechanical properties and conformability, and it can resist the mechanical forces generated by dynamic chest cavity movements.

[0025] Step 5: Preparation of the porous hydrophilic layer Pumice particles were crushed to a particle size of 0.1-0.3 mm, soaked in 4 mol / L hydrochloric acid for 2-3 hours to remove impurities and soluble salts, washed with water until neutral, and then calcined at 550-600℃ for 2-3 hours to enhance porosity. The calcined pumice particles were dispersed in a 70% ethanol solution, and vinyltriethoxysilane was added at a mass ratio of 10:1-15:1. The mixture was reacted at 60-70℃ for 2-3 hours, followed by the addition of polyethyleneimine for another 1-2 hours to achieve amino modification. The amino-modified pumice was mixed with sodium carboxymethyl cellulose at a mass ratio of 1:2-1:4, and polyethylene glycol 400 was added as a plasticizer at a mass ratio of 5%-10% of the total mass of the mixture. After stirring evenly, the mixture was allowed to stand to defoam, and then freeze-dried at -20 to -30℃ for 12-24 hours to obtain a porous hydrophilic layer material. The calcination of the pumice particles was carried out using a programmed temperature increase, from room temperature to 550~600℃ at a rate of 5℃ / min, to avoid sudden temperature rise that could cause particle breakage. The molecular weight of the polyethyleneimine was selected to be 1000~2000 Da to ensure the amino grafting density. Before freeze-drying, the mixed system was pre-frozen at -80℃ for 2~3 hours to improve the uniformity of the porous structure. The porosity of the porous hydrophilic layer was controlled at 70%~85%, as measured by a mercury porosimeter.

[0026] Analysis of the above technical content: This scheme involves crushing pumice particles to 0.1~0.3mm, soaking them in 4mol / L hydrochloric acid for 2~3h to remove impurities and soluble salts, washing them with water until neutral, and then calcining them at a programmed heating rate of 5℃ / min to 550~600℃ for 2~3h to avoid particle breakage caused by sudden temperature rise and to enhance porosity. The innovative method involves stepwise modification with vinyltriethoxysilane (pumice particles to silane mass ratio 10:1~15:1) and polyethyleneimine (molecular weight 1000~2000Da), reacting sequentially at 60~70℃ for 2~3h and 1~2h, to achieve amino functionalization of the pumice particles, improving their compatibility with other components and water absorption capacity. Amino-modified pumice and sodium carboxymethyl cellulose were mixed at a ratio of 1:2 to 1:4, and 5% to 10% of polyethylene glycol 400 was added as a plasticizer. After pre-freezing at -80℃ for 2 to 3 hours, the mixture was freeze-dried at -20 to -30℃ for 12 to 24 hours to obtain a porous hydrophilic layer with a porosity of 70% to 85%. The core innovation of this step lies in the construction of an amino-modified high-porosity hydrophilic system, which solves the problems of slow absorption rate and insufficient liquid retention capacity of traditional absorbent layers. The synergistic effect of amino-modified pumice and sodium carboxymethyl cellulose results in an absorption rate of over 1500%, which can quickly absorb and retain pleural effusion and prevent fluid accumulation. At the same time, the porous structure provides a breathable environment for the wound, promoting healing.

[0027] Step 6: Composite molding of multifunctional dressings The modified substrate after electrode treatment in step 4 is used as the functional bottom layer, the porous hydrophilic layer prepared in step 5 is used as the intermediate layer, and a thermoplastic polyurethane film is selected as the protective layer. The three-layer structure is composited in the order of functional bottom layer, porous hydrophilic layer and protective layer using medical pressure-sensitive adhesive. The pressing temperature is 40~50℃, the pressure is 0.3~0.5MPa, and the pressing time is 15~20min. After composite, it is sterilized by irradiation with Co60 rays at a dose of 25~30kGy, and finally a multifunctional hemostatic dressing suitable for multiple chest injuries is obtained. The medical pressure-sensitive adhesive uses an acrylic solvent-free pressure-sensitive adhesive to ensure biocompatibility and bonding stability. During the lamination process, a roller pressing method is used with a roller speed of 5-10 r / min to ensure a tight, bubble-free three-layer structure. Co60 irradiation employs a uniform scanning method, with the dressing laid flat at 5-10 cm intervals during irradiation to ensure uniform sterilization. After irradiation, sterility testing is performed, and the colony count must meet the requirements of GB / T 14233.2-2005 standard.

[0028] Analysis of the above technical content: This solution adopts a three-layer composite structure design. The modified substrate after electrode treatment serves as the functional bottom layer (responsible for hemostasis and adhesion), the porous hydrophilic layer as the middle layer (responsible for liquid absorption and promoting healing), and the thermoplastic polyurethane film as the protective layer (preventing external contamination). These layers are sequentially laminated using an acrylic solvent-free pressure-sensitive adhesive. The lamination temperature is 40-50℃, the pressure is 0.3-0.5MPa, and the time is 15-20min. The roller speed is controlled at 5-10r / min to ensure a tight, bubble-free bond between the three layers. After lamination, sterilization is achieved by uniform scanning irradiation with a dose of 25-30kGy of Co60 radiation. The dressing is laid flat with a spacing of 5-10cm to ensure uniform sterilization. The final colony count meets the requirements of GB / T 14233.2-2005 standard. The key innovation of this step lies in the integrated use of multiple layers for hemostasis, adhesion, fluid absorption, anti-infection, and healing promotion, which solves the problem of single function in traditional dressings. Through precise control of composite process parameters, the synergistic effect of each layer is ensured. The protective layer prevents external bacterial invasion, the functional bottom layer quickly stops bleeding and adheres firmly, the middle layer efficiently absorbs fluid and creates a healing environment, and Co60 radiation sterilization ensures the biosafety of the dressing and avoids the risk of wound infection. The overall structure is adapted to the complex treatment needs of multiple chest injuries.

[0029] Working principle: This solution primarily utilizes the synergistic effects of multiple components, optimized integration of multiple processes, and functional division of labor in a multi-layered structure to construct a hemostatic dressing that combines rapid hemostasis, strong adhesion, anti-infection, and healing promotion, precisely adapting to the complex treatment scenarios of multiple chest injuries. Its core working principle revolves around the entire process of "rapid coagulation initiation - firm wound closure - efficient exudate management - safe healing promotion": In terms of hemostasis mechanism, amino-modified chitosan, with its abundant amino groups on the surface forming a cationic effect, can rapidly capture platelets and red blood cells in the blood, accelerate platelet activation and aggregation to form primary blood clots, and simultaneously activate the intrinsic coagulation pathway. Coagulation factors (preferably thrombin) loaded in nanoparticles can quickly penetrate deep into the wound, directly replenishing extrinsic coagulation components, shortening the coagulation cascade reaction time, and forming a highly efficient hemostasis system with modified chitosan through "synergistic effect of intrinsic and extrinsic coagulation." The catechol-sodium alginate composite adhesive forms covalent bonds with the amino groups on the tissue surface through phenolic hydroxyl groups, rapidly sealing bleeding points and preventing continuous blood leakage. These three components synergistically construct a quadruple hemostasis mechanism of "capture-activation-replenishment-closure."

[0030] Regarding the adhesion stabilization mechanism, the electrode treatment technology eliminates internal stress in the material by bombarding the coating surface with high-energy particles, while introducing active groups to enhance the bonding force between the coating and the medical non-woven fabric substrate. The cross-linked structure formed by catechol and sodium alginate can maintain a stable adhesive layer in a humid environment, and its adhesion strength is sufficient to resist the mechanical force generated by dynamic chest cavity movements, preventing the dressing from shifting or falling off, thus solving the problem of insufficient wet adhesion of traditional dressings.

[0031] In the exudate management and anti-infection mechanism, the amino-modified pumice with a porous hydrophilic layer, with its high porosity of 70%~85% and amino functionalization modification, forms a strong water absorption force, which can quickly absorb and lock in pleural effusion and exudate, avoiding the risk of infection caused by effusion accumulation. The quaternary ammonium salt group of modified chitosan works synergistically with silver ions to destroy the bacterial cell membrane structure, inhibit the reproduction of common pathogenic bacteria such as Escherichia coli and Staphylococcus aureus, and reduce the probability of wound infection.

[0032] Regarding the healing mechanism, the porous hydrophilic layer creates a micro-moistened environment that reduces wound dryness and damage. Allantoin and traditional Chinese medicine extracts promote epithelial cell proliferation and tissue repair. Furthermore, all components of the dressing exhibit excellent biocompatibility, do not adhere to granulation tissue, and avoid secondary damage during dressing changes, thus accelerating the wound healing process. The entire system, through the complementary functions and synergistic processes of its components, effectively addresses the core issues of common external thoracic injuries, such as massive bleeding, a moist environment, susceptibility to infection, and slow healing.

[0033] The core innovation of this solution lies in: A multi-component synergistic design of "amino-modified chitosan + coagulation factor-loaded nanoparticles + catechol-sodium alginate composite adhesive" solves the problems of slow hemostasis, poor wet adhesion, and limited functionality of traditional chitosan dressings. By combining electrode treatment technology with gradient drying processes, the background technical problems of insufficient mechanical properties and easy coating detachment caused by internal stress in the material are resolved. Nanoparticle drug delivery technology is used to encapsulate coagulation factors, solving the problems of easy inactivation and low efficacy of traditional coagulation factors. A three-layer composite structure of "functional bottom layer + porous hydrophilic layer + protective layer" is constructed, addressing the multiple requirements of existing dressings that cannot simultaneously achieve rapid hemostasis, firm sealing, efficient fluid absorption, anti-infection, and healing promotion.

[0034] Simultaneously, for the first time, plasma electrode treatment technology was applied to the substrate modification of hemostatic dressings for external chest injuries. By introducing active groups through high-energy particle bombardment, the coating adhesion and wet adhesion performance were simultaneously improved, achieving a synergistic enhancement of "physical modification-chemical adhesion". For the first time, amino-modified calcite was applied to the preparation of the porous hydrophilic layer of hemostatic dressings. Through silanization and polyethyleneimine modification, the absorbent layer was endowed with high absorbency and biocompatibility, achieving an integrated function of "rapid absorption-locking-promoting healing". For the first time, a triple hemostatic system of "cationic coagulation activation + nano-factor supplementation + covalent bond adhesion and sealing" was constructed, achieving a breakthrough effect of shortening the hemostasis time by more than 50% compared with traditional dressings, filling the technological gap in multifunctional hemostatic dressings for multiple external chest injuries.

[0035] Technical effects of implementing this solution: Implementing this solution yields a multifunctional hemostatic dressing suitable for the complex needs of multiple chest injuries. Its technical advantages are reflected in multiple dimensions, including hemostatic efficiency, adhesive stability, anti-infection ability, absorbency, healing promotion, and biocompatibility, comprehensively surpassing existing technologies. In terms of hemostasis, the synergistic effect of amino-modified chitosan in activating coagulation, the coagulation replenishment of nanoparticles loaded with coagulation factors, and the sealing of bleeding points by catechol adhesives shortens the hemostasis time by more than 50% compared to traditional chitosan dressings and fibrin glue dressings. It can quickly control massive intrathoracic hemorrhage, and is especially suitable for critical scenarios such as ruptured aortas, significantly improving the success rate of emergency treatment. Clinical simulation trials have verified that, in a canine model of ruptured chest wall arteries, the average hemostasis time of this dressing is ≤3 minutes, which is far superior to traditional oxidized regenerated cellulose dressings (average 8 minutes) and zeolite dressings (average 6 minutes), and there is no subsequent bleeding.

[0036] Regarding adhesion stability, the synergistic effect of electrode treatment technology and the catechol-sodium alginate composite adhesive enables the dressing to achieve an adhesion strength of over 70 kPa in a moist environment. This resists the mechanical forces generated by thoracic respiratory movements and changes in body position, with a dressing displacement rate of ≤5%. This solves the core problem of traditional dressings easily falling off in moist wounds. Even on external chest injuries with continuous bleeding and irregular tissue, it can maintain firm adhesion for more than 24 hours, avoiding hemostasis failure due to dressing displacement.

[0037] In terms of anti-infection and biosafety, the quaternary ammonium salt groups of modified chitosan work synergistically with silver ions to achieve an antibacterial rate of over 95% against Escherichia coli and Staphylococcus aureus, significantly reducing the risk of infection in external chest wounds. The material has shown cell viability of over 90% in cytotoxicity tests, with no sensitization or intradermal irritation, meeting the GB / T 14233.2-2005 medical biosafety standards. It can be safely applied to sensitive areas such as the mediastinum and pleura, avoiding the potential stimulation of nerve tissue by oxidized regenerated cellulose dressings.

[0038] In terms of fluid absorption and healing promotion, the porous hydrophilic layer has an absorption rate of over 1500%, which can quickly absorb and lock in pleural effusion and prevent tissue edema and infection caused by fluid accumulation. The fluid absorption speed is more than 3 times faster than traditional dressings. By creating a micro-moistening healing environment, it promotes epithelial cell proliferation, with a wound healing rate of over 85% in 14 days. Moreover, the dressing does not adhere to granulation tissue, and the incidence of secondary injury during dressing changes is ≤3%, significantly shortening the patient's recovery period.

[0039] Furthermore, the preparation process is highly controllable, with precise quantification of parameters for each step (such as reaction temperature, time, and material ratio), making it suitable for large-scale production. The finished dressing exhibits excellent mechanical properties, with a breaking strength ≥5MPa and an elongation at break ≥30%. It can withstand shear and tensile forces during clinical operations and is not easily damaged, further ensuring its reliability in the treatment process. This comprehensively solves the problems of existing hemostatic dressings in the treatment of multiple chest injuries, such as limited functionality, poor adaptability, and insufficient safety.

[0040] The above examples illustrate the present invention only to aid in understanding it and are not intended to limit the scope of the invention. Those skilled in the art can make various simple deductions, modifications, or substitutions based on the principles of this invention.

Claims

1. A method for preparing a multifunctional hemostatic dressing suitable for multiple chest injuries, characterized in that: The preparation method is as follows: Step 1: Preparation of amino-modified chitosan Chitosan with a degree of deacetylation of 85%–95% was selected and dissolved in a 1%–2% wt acetic acid solution. The solution was stirred until completely dissolved to form a chitosan solution with a concentration of 2%–5% wt. 3-aminopropyltriethoxysilane was added to the solution at an amount of 10%–20% of the chitosan mass. The solution was stirred at a constant temperature of 40–50°C for 3–5 hours to achieve amino functionalization modification of the chitosan surface. After the reaction was completed, the solution was dialyzed in a dialysis bag with a molecular weight cutoff of 3000–5000 for 24–36 hours to remove unreacted silane reagents and impurities. Finally, the solution was freeze-dried to obtain amino-modified chitosan powder. Step 2: Preparation of Coagulation Factor-Loaded Nanoparticles Polyvinyl alcohol (PVA) was added to deionized water and heated to 80-90°C with stirring for 2-3 hours to form a PVA solution with a mass fraction of 5%-8%. After cooling to 30-40°C, bovine serum albumin (BSA) and coagulation factors were added sequentially, with BSA at a mass fraction of 0.05%-0.1% and coagulation factors at a mass fraction of 0.03%-0.08%. The mixture was stirred continuously for 1-2 hours until completely dissolved. The above mixed solution was slowly injected into a polycaprolactone (PCL) solution in dichloromethane, with PCL at a mass fraction of 2%-4%. The mixture was emulsified using a probe-type ultrasonic homogenizer at 100-150W power for 15-20 minutes to form a stable oil-in-water emulsion. The emulsion was placed in a rotary evaporator and evaporated under reduced pressure at 35-45°C for 1-2 hours to remove dichloromethane, yielding a PVA nanoparticle suspension loaded with coagulation factors. This suspension was then freeze-dried for later use. Step 3: Preparation of Catechol-Sodium Alginate Composite Adhesive Sodium alginate was dissolved in deionized water and stirred until completely dissolved to form a sodium alginate solution with a mass fraction of 3% to 6%. Catechol was added to the solution at a mass ratio of 1:5 to 1:

8. The mixture was stirred at 25 to 30°C for 30 to 45 minutes to allow the phenolic hydroxyl groups of the catechin to form hydrogen bonds with the carboxyl groups of the sodium alginate. Subsequently, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride was added at an amount of 20% to 30% of the mass of the catechin. The mixture was stirred for 1 to 2 hours to promote the cross-linking reaction and obtain a catechin-sodium alginate composite adhesive with strong adhesive properties. Step 4: Electrode treatment improves substrate performance The amino-modified chitosan powder prepared in step 1 and the catechol-sodium alginate composite adhesive obtained in step 3 are mixed at a mass ratio of 3:1 to 5:

1. An appropriate amount of deionized water is added to adjust the viscosity to 500 to 1000 mPa·s. After stirring evenly, a mixed slurry is formed. The mixed slurry is coated on the surface of a medical nonwoven fabric substrate with a coating thickness controlled at 0.5 to 1.0 mm. The substrate is placed in an electrode treatment device and plasma electrode treatment technology is used. The electrode voltage is set to 10 to 15 kV, the treatment time is 5 to 10 min, and the treatment distance is 5 to 8 cm. The high-energy particles generated by the electrode treatment bombard the coating surface, eliminating the internal stress of the material and introducing active groups to improve the adhesion between the coating and the substrate and the wet adhesion performance. After treatment, the substrate is vacuum dried at 60 to 70 °C for 2 to 3 h. Step 5: Preparation of the porous hydrophilic layer Pumice particles were crushed to a particle size of 0.1-0.3 mm, soaked in 4 mol / L hydrochloric acid for 2-3 hours to remove impurities and soluble salts, washed with water until neutral, and then calcined at 550-600℃ for 2-3 hours to enhance porosity. The calcined pumice particles were dispersed in a 70% ethanol solution, and vinyltriethoxysilane was added at a mass ratio of 10:1-15:

1. The mixture was reacted at 60-70℃ for 2-3 hours, followed by the addition of polyethyleneimine for another 1-2 hours to achieve amino modification. The amino-modified pumice was mixed with sodium carboxymethyl cellulose at a mass ratio of 1:2-1:4, and polyethylene glycol 400 was added as a plasticizer at a mass ratio of 5%-10% of the total mass of the mixture. After stirring evenly, the mixture was allowed to stand to defoam, and then freeze-dried at -20 to -30℃ for 12-24 hours to obtain a porous hydrophilic layer material. Step 6: Composite molding of multifunctional dressings The modified substrate after electrode treatment in step 4 is used as the functional bottom layer, the porous hydrophilic layer prepared in step 5 is used as the intermediate layer, and a thermoplastic polyurethane film is selected as the protective layer. The three-layer structure is composited in the order of functional bottom layer, porous hydrophilic layer and protective layer using medical pressure-sensitive adhesive. The pressing temperature is 40~50℃, the pressure is 0.3~0.5MPa, and the pressing time is 15~20min. After composite, it is sterilized by irradiation with Co60 rays at a dose of 25~30kGy, and finally a multifunctional hemostatic dressing suitable for multiple chest injuries is obtained.

2. The method for preparing a multifunctional hemostatic dressing suitable for multiple external chest injuries according to claim 1, characterized in that: In step 1, the pH of the acetic acid solution is adjusted to 4.0-5.

0. 3-aminopropyltriethoxysilane is added dropwise to the chitosan solution in 3-5 portions, with an interval of 30 minutes between each addition to avoid excessive local concentration that could lead to agglomeration. During dialysis, the deionized water is replaced every 6 hours to ensure thorough removal of impurities. The freeze-drying temperature is -40 to -50°C, and the drying time is 12-16 hours to ensure the loose and porous structure of the modified chitosan powder.

3. The method for preparing a multifunctional hemostatic dressing suitable for multiple external chest injuries according to claim 1, characterized in that: In step 2, thrombin is selected as the coagulation factor. It must be stored at -20℃ before addition, and the solution temperature must be strictly controlled below 35℃ during addition to avoid inactivation of the coagulation factor. During ultrasonic emulsification, intermittent operation is adopted, with a 2-minute pause every 5 minutes to prevent the temperature from being too high and affecting the stability of the nanoparticles. The particle size of the freeze-dried nanoparticles is controlled at 50~200nm and is detected by a laser particle size analyzer to ensure uniform dispersion of the particles.

4. The method for preparing a multifunctional hemostatic dressing suitable for multiple external chest injuries according to claim 1, characterized in that: In step 3, sodium alginate with a molecular weight of 100,000 to 200,000 Da is selected to ensure adhesion and cross-linking effects. Catechol needs to be recrystallized and purified before dissolution to remove the influence of impurities on adhesion performance. Magnetic stirring is used during the cross-linking reaction at a speed of 300 to 500 rpm to avoid high-speed stirring from damaging the molecular chain structure. The viscosity of the composite adhesive is monitored in real time by a rotational viscometer to ensure it is within the range of 300 to 800 mPa·s.

5. The method for preparing a multifunctional hemostatic dressing suitable for multiple external chest injuries according to claim 1, characterized in that: Step 4: The non-woven fabric for TCM uses a blend of polyester and cotton fibers in a ratio of 7:3 to 6:4 to ensure the breathability and mechanical strength of the substrate. Argon gas is introduced as a protective gas during electrode treatment at a flow rate of 10 to 20 mL / min to prevent coating oxidation. Gradual heating is used during vacuum drying, gradually increasing the temperature from 30°C to 70°C at a rate of 10°C per hour to further eliminate internal stress in the material.

6. The method for preparing a multifunctional hemostatic dressing suitable for multiple external chest injuries according to claim 1, characterized in that: In step 5, the calcination of the pumice particles is carried out using a programmed temperature increase, from room temperature to 550~600℃ at a rate of 5℃ / min, to avoid sudden temperature rise that could cause particle breakage; the molecular weight of the polyethyleneimine is selected to be 1000~2000 Da to ensure the amino grafting density. Before freeze drying, the mixed system is pre-frozen at -80℃ for 2-3 hours to improve the uniformity of the porous structure. The porosity of the porous hydrophilic layer is controlled at 70%-85%, and the results are measured by mercury porosimetry.

7. The method for preparing a multifunctional hemostatic dressing suitable for multiple external chest injuries according to claim 1, characterized in that: Step 6: For the pressure-sensitive adhesive used in traditional Chinese medicine, an acrylic solvent-free pressure-sensitive adhesive is selected to ensure biocompatibility and bonding stability. During the lamination process, a roller pressing method is used with a roller speed of 5~10 r / min to ensure that the three-layer structure is tightly bonded without air bubbles. Co60 irradiation adopts a uniform scanning method. During the irradiation process, the dressing is laid flat with a spacing of 5~10 cm to ensure uniform sterilization effect. After irradiation, sterility testing is performed, and the colony count must meet the requirements of GB / T 14233.2-2005 standard.