Composite hemostatic material of PVA-polyphenol derivative and chitosan and preparation method of composite hemostatic material

Abstract

The invention relates to the field of composite hemostatic materials, and discloses a PVA-polyphenol derivative and chitosan composite hemostatic material and a preparation method thereof.The PVA-polyphenol derivative and chitosan composite hemostatic material is prepared from PVA and 3, 5-dihydroxybenzoic acid (DHBA) through esterification reaction, a PVA-DHBA grafted copolymer serving as a wet adhesion component, chitosan serving as a chemical coagulation accelerating component and a chitosan-polyphenol derivative-chitosan composite hemostatic material. A powdery product is prepared by compounding and blending, freeze-drying, crushing and sieving and irradiation sterilization, and the material performance is accurately regulated and controlled by regulating and controlling the mass ratio of PVA to DHBA, the compounding ratio, freeze-drying parameters and the particle size of powder in the preparation process. The material has dual hemostasis mechanisms of mussel bionic wet bonding, physical plugging and chemical coagulation promotion, the bonding strength with a bone tissue interface reaches 1MPa, the whole blood coagulation time is only 60s, the material is remarkably superior to an existing chitosan-based material and a commercial product Rhino Rescue, and the material is good in biocompatibility, degradable, capable of being adapted to irregular and deep wounds and capable of being used as a medical material for treating the wounds. The hemostat is suitable for rapid hemostasis in trauma first-aid, surgical operations and other scenes.

Description

A composite hemostatic material of PVA-polyphenol derivative and chitosan and its preparation method Technical Field

[0001] This invention relates to the field of composite hemostatic materials, and more particularly to a composite hemostatic material of PVA-polyphenol derivative and chitosan and its preparation method. Background Technology

[0002] In medical emergencies, surgical procedures, and trauma management, rapid and efficient hemostasis is crucial for saving lives and reducing complications. As a core medical consumable, the performance of hemostatic materials directly impacts hemostasis and patient prognosis. Therefore, developing hemostatic materials that combine strong adhesion, rapid hemostasis, and good biocompatibility has become an important need in the medical field.

[0003] Existing hemostatic materials are mainly divided into two categories: physical sealing materials (such as gelatin sponges and hemostatic gauze) and chemical coagulation-promoting materials (such as chitosan-based materials). Physical sealing materials use a porous structure to absorb water and swell, forming a physical barrier to compress and stop bleeding. However, these materials have weak wet adhesion to moist tissue surfaces, are easily washed away by blood, and lack active coagulation-promoting function, resulting in limited hemostatic efficiency. Chemical coagulation-promoting materials rely on their own charge to attract blood cells and activate coagulation factors to achieve coagulation. However, they generally suffer from insufficient adhesion to moist wound surfaces, making it difficult to form a stable hemostatic interface. They also lack physical sealing effects, resulting in poor control of active bleeding. Furthermore, some existing hemostatic materials have drawbacks such as limited functionality, poor biocompatibility, and limited applicability to various wound types (e.g., inability to adapt to irregular deep wounds), making it difficult to meet the needs for efficient hemostasis in complex trauma scenarios.

[0004] To address the aforementioned technical challenges, there is an urgent need to develop a composite hemostatic material that can synergistically combine physical adhesion and occlusion with active chemical coagulation. Polyvinyl alcohol (PVA), a recognized biocompatible material, possesses excellent hydrophilicity and biodegradability, but lacks wet adhesion and coagulation-promoting activity. 3,5-Dihydroxybenzoic acid (DHBA), with its catechol groups, provides strong wet adhesion and can form multiple non-covalent bonds with tissue proteins. Chitosan, with its positively charged amino groups, exhibits excellent chemical coagulation properties. Based on this, this invention introduces DHBA into the PVA backbone through chemical grafting to form a PVA-DHBA graft copolymer, which is then combined with chitosan to construct a composite hemostatic material that combines both physical adhesion and occlusion mechanisms with chemical coagulation. This aims to solve the problems of poor wet adhesion, limited hemostatic mechanisms, and insufficient hemostatic efficiency of existing hemostatic materials, meeting the hemostatic needs of different wound surfaces (especially irregular and deep wounds), while ensuring the material's biocompatibility and ease of use, providing a better solution for clinical hemostasis. Summary of the Invention

[0005] The present invention aims to provide a composite hemostatic material of PVA-polyphenol derivative and chitosan and its preparation method, in order to solve the problems of poor adhesion of hemostatic materials on moist tissue surfaces, insufficient active hemostatic efficacy and long clotting time in the prior art.

[0006] To achieve the above objectives, the present invention provides the following method:

[0007] The present invention provides a method for preparing a composite hemostatic material of PVA-polyphenol derivative and chitosan:

[0008] S1: Weigh out PVA with a degree of alcoholysis >98% and add it to the DMSO / deionized water mixture according to a mass-to-volume ratio of PVA to DMSO / deionized water mixture of 20~35 mg / mL. Stir at 80°C until completely dissolved. The volume ratio of DMSO to deionized water in the DMSO / deionized water mixture is 1:1~6:1 to obtain the first solution.

[0009] S2: After the first solution cools to room temperature, 3,5-dihydroxybenzoic acid and sodium bisulfate are added sequentially, and the reaction is carried out at a constant temperature for 24 hours under nitrogen atmosphere protection. The mass ratio of PVA to 3,5-dihydroxybenzoic acid is 1.5:1 to 1.9:1, and the mass ratio of PVA to sodium bisulfate is 0.5:1 to 0.7:1 to obtain the second solution.

[0010] S3: The second solution was placed into a dialysis bag with a molecular weight cutoff of 3500kDa and dialyzed for 5 days with deionized water as the dialysis medium. After dialysis, the solution was concentrated by rotary evaporation and then freeze-dried to obtain the PVA-DHBA graft copolymer.

[0011] S4: Dissolve the PVA-DHBA graft copolymer in deionized water to prepare a PVA-DHBA aqueous solution with a concentration of 200~300mg / mL; prepare a chitosan-acetic acid solution with a mass fraction of 1%; mix them at a volume ratio of 1:1 and stir magnetically for 20~40 minutes to obtain a homogeneous composite sol.

[0012] S5: Inject the homogeneous composite sol into a flat mold and pre-freeze it at -85℃ to -75℃ for 10 to 14 hours. Then, transfer it to a freeze dryer for 48 hours to freeze dry. Crush the freeze-dried sponge-like product with a pulverizer, and pass it through a standard sieve to obtain powder with a particle size of 50 to 300 μm. After sealing and packaging, sterilize it by Co-60 irradiation to obtain a powdered composite hemostatic material.

[0013] Preferably, the volume ratio of DMSO to deionized water is 3:1 to 5:1; and the mass-volume ratio of PVA to the DMSO / deionized water mixture is 28 to 100 mg / mL.

[0014] Preferably, the mass ratio of PVA to 3,5-dihydroxybenzoic acid is 1.7:1 to 1.8:1, and the mass ratio of PVA to sodium bisulfate is 0.6:1.

[0015] Preferably, during the dialysis of the PVA-DHBA graft copolymer, deionized water that has been boiled and cooled to room temperature is used as the dialysis medium every 12 hours. After dialysis, the rotary evaporation conditions are: temperature 40~50℃, pressure 0.09~0.1MPa, concentration time 2~3 hours, and freeze-drying vacuum degree 10~20Pa.

[0016] Preferably, the freeze-drying time in step S3 is 48 hours, which is consistent with the freeze-drying time of the freeze dryer in step S5.

[0017] Preferably, the concentration of the PVA-DHBA aqueous solution is 240~260 mg / mL, and the magnetic stirring time is 30 minutes.

[0018] Preferably, the degree of deacetylation of chitosan in the chitosan-acetic acid solution is 92%~95%, and the mass fraction of acetic acid in the chitosan-acetic acid solution is 1-20%.

[0019] Preferably, the pre-freezing temperature in step S5 is -80°C and the pre-freezing time is 12 hours.

[0020] The present invention provides a composite hemostatic material of PVA-polyphenol derivative and chitosan prepared according to the preparation method of the composite hemostatic material of PVA-polyphenol derivative and chitosan described above.

[0021] The beneficial effects of this invention are reflected in:

[0022] 1. Synergistic Dual Hemostatic Mechanisms: Physical Adhesion and Sealing: The catechol groups in PVA-g-DHBA provide strong wet adhesion, quickly bonding the wound and sealing bleeding points; the porous powder absorbs water and swells, physically compressing the ruptured blood vessel. Chemical Coagulation: Chitosan's positive charge efficiently aggregates blood cells, activating the coagulation cascade reaction; simultaneously, the adhesion interface of PVA-g-DHBA enriches coagulation factors, accelerating prothrombin activation.

[0023] 2. Excellent biocompatibility and biodegradability: PVA and chitosan are both recognized biocompatible materials that can be gradually degraded in vivo.

[0024] 3. Easy to use and highly adaptable: The powder form can adapt to irregular and deep wounds and can adhere closely to bleeding sites.

[0025] 4. Controllable process: By adjusting the grafting rate, the ratio of PVA-g-DHBA to chitosan, freeze-drying parameters, and powder particle size, the adhesion strength, swelling rate, degradation rate, and hemostatic performance of the material can be precisely controlled. Attached Figure Description

[0026] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the accompanying drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. In all the drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, the elements or parts are not necessarily drawn to scale.

[0027] Figure 1 shows the following provided by the embodiments of the present invention: a) PVA-DHBA-CS gel powder and powder SEM image, illustrating the surface morphology and micropores of the material; b) Schematic diagram of various forms of hemostatic plugs; c) Schematic diagram of the gel form of the product; d) UV-Vis spectrum, indicating the successful synthesis of PVA-DHBA-CS; e) Schematic diagram of the overlapping and shearing of the composite hemostatic material with bone fragments, glass slides and plastic substrates.

[0028] Figure 2 shows the following provided by the embodiments of the present invention: a) is a tube inversion test method, which is performed with water and blood respectively, and is compared with simple CS, DHBA and commercial Rhino Rescue; b) is a schematic diagram of coagulation time test.

[0029] Figure 3 shows the following comparisons provided by the embodiments of the present invention: a) is a schematic diagram of rat liver injury experiments; b) is a schematic diagram of pig liver injury and bleeding experiments. Detailed Implementation

[0030] To enable those skilled in the art to better understand the present invention, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. 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 skilled in the art without creative effort are within the scope of protection of the present invention.

[0031] The terms "first," "second," etc., used in the specification, claims, and accompanying drawings of this invention are used to distinguish different objects, not to describe a specific order. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion. For example, a process, method, apparatus, product, or end that includes a series of steps or units is not limited to the listed steps or units, but may optionally include steps or units not listed, or may optionally include other steps or units inherent to these processes, methods, products, or ends.

[0032] In this document, the term "embodiment" means that a particular feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of the invention. The appearance of this phrase in various places throughout the specification does not necessarily refer to the same embodiment, nor is it a separate or alternative embodiment mutually exclusive with other embodiments. It will be explicitly and implicitly understood by those skilled in the art that the embodiments described herein can be combined with other embodiments.

[0033] Existing hemostatic materials are mainly divided into two categories: physical sealing materials (such as gelatin sponges and hemostatic gauze) and chemical coagulation-promoting materials (such as chitosan-based materials). Physical sealing materials use a porous structure to absorb water and swell, forming a physical barrier to compress and stop bleeding. However, these materials have weak wet adhesion to moist tissue surfaces, are easily washed away by blood, and lack active coagulation-promoting function, resulting in limited hemostatic efficiency. Chemical coagulation-promoting materials rely on their own charge to attract blood cells and activate coagulation factors to achieve coagulation. However, they generally suffer from insufficient adhesion to moist wound surfaces, making it difficult to form a stable hemostatic interface. They also lack physical sealing effects, resulting in poor control of active bleeding. Furthermore, some existing hemostatic materials have drawbacks such as limited functionality, poor biocompatibility, and limited applicability to various wound types (e.g., inability to adapt to irregular deep wounds), making it difficult to meet the needs for efficient hemostasis in complex trauma scenarios.

[0034] To address the aforementioned technical challenges, there is an urgent need to develop a composite hemostatic material that can synergistically combine physical adhesion and occlusion with active chemical coagulation. Polyvinyl alcohol (PVA), a recognized biocompatible material, possesses excellent hydrophilicity and biodegradability, but lacks wet adhesion and coagulation-promoting activity. 3,5-Dihydroxybenzoic acid (DHBA), with its catechol groups, provides strong wet adhesion and can form multiple non-covalent bonds with tissue proteins. Chitosan, with its positively charged amino groups, exhibits excellent chemical coagulation properties. Based on this, this invention introduces DHBA into the PVA backbone through chemical grafting to form a PVA-DHBA graft copolymer, which is then combined with chitosan to construct a composite hemostatic material that combines both physical adhesion and occlusion mechanisms with chemical coagulation. This aims to solve the problems of poor wet adhesion, limited hemostatic mechanisms, and insufficient hemostatic efficiency of existing hemostatic materials, meeting the hemostatic needs of different wound surfaces (especially irregular and deep wounds), while ensuring the material's biocompatibility and ease of use, providing a better solution for clinical hemostasis.

[0035] The present invention aims to provide a composite hemostatic material of PVA-polyphenol derivative and chitosan and its preparation method, in order to solve the problems of poor adhesion of hemostatic materials on moist tissue surfaces, insufficient active hemostatic efficacy and long clotting time in the prior art.

[0036] This invention provides a method for preparing a composite hemostatic material of PVA-polyphenol derivatives and chitosan, comprising the following steps:

[0037] S1: Weigh PVA with a degree of alcoholysis >98% and add it to the DMSO / deionized water mixture according to the mass-volume ratio of PVA to DMSO / deionized water mixture of 20~35 mg / mL. Stir at 80℃ until completely dissolved. The volume ratio of DMSO to deionized water in the DMSO / deionized water mixture is 1:1~6:1 to obtain the first solution.

[0038] In this embodiment of the invention, the volume ratio of DMSO to deionized water is 3:1 to 5:1; the mass-volume ratio of PVA to the DMSO / deionized water mixture is 28 to 100 mg / mL.

[0039] S2: After the first solution cools to room temperature, add 3,5-dihydroxybenzoic acid and sodium bisulfate in sequence, and react at a constant temperature for 24 hours under nitrogen atmosphere protection. The mass ratio of PVA to 3,5-dihydroxybenzoic acid is 1.5:1~1.9:1, and the mass ratio of PVA to sodium bisulfate is 0.5:1~0.7:1 to obtain the second solution.

[0040] In this embodiment of the invention, the mass ratio of PVA to 3,5-dihydroxybenzoic acid is 1.7:1 to 1.8:1, and the mass ratio of PVA to sodium bisulfate is 0.6:1.

[0041] S3: The second solution was placed in a dialysis bag with a molecular weight cutoff of 3500 kDa and dialyzed for 5 days with deionized water as the dialysis medium. After dialysis, the solution was concentrated by rotary evaporation and then freeze-dried to obtain the PVA-DHBA graft copolymer.

[0042] In this embodiment of the invention, during the dialysis of the PVA-DHBA graft copolymer, deionized water that has been boiled and cooled to room temperature is replaced as the dialysis medium every 12 hours. After dialysis, the rotary evaporation conditions are: temperature 45~50℃, pressure 0.09~0.1MPa, concentration time 2~3 hours, freeze-drying vacuum degree 10~20Pa, and freeze-drying time 48 hours.

[0043] S4: Dissolve the PVA-DHBA graft copolymer in deionized water to prepare a PVA-DHBA aqueous solution with a concentration of 200~300mg / mL; prepare a chitosan-acetic acid solution with a mass fraction of 1%; mix them at a volume ratio of 1:1 and stir magnetically for 20~40 minutes to obtain a homogeneous composite sol.

[0044] In this embodiment of the invention, the concentration of the PVA-DHBA aqueous solution is 240~260 mg / mL, and the magnetic stirring time is 30 minutes; the degree of deacetylation of chitosan in the chitosan-acetic acid solution is 92%~95%, and the mass fraction of acetic acid in the chitosan-acetic acid solution is 1-20%.

[0045] S5: Inject the homogeneous composite sol into a flat mold and pre-freeze it at -85℃ to -75℃ for 10 to 14 hours. Then, transfer it to a freeze dryer for 48 hours. Crush the freeze-dried sponge-like product with a pulverizer, and pass it through a standard sieve to obtain powder with a particle size of 50 to 300 μm. After sealing and packaging, sterilize it by Co-60 irradiation to obtain powdered composite hemostatic material.

[0046] In this embodiment of the invention, the pre-freezing temperature is -80°C and the pre-freezing time is 12 hours.

[0047] The present invention provides a composite hemostatic material of PVA-polyphenol derivative and chitosan prepared according to the preparation method of the composite hemostatic material of PVA-polyphenol derivative and chitosan described above.

[0048] Example 1

[0049] 1. Take 4.24g of PVA (degree of alcoholysis >98%), dissolve it in 150mL of DMSO / water mixture, and stir at 80℃ until completely dissolved.

[0050] 2. Cool to room temperature, add 2.47g of 3,5-dihydroxybenzoic acid and 7g of sodium bisulfate catalyst, and react for 24 hours under nitrogen protection.

[0051] 3. The reaction solution was placed in a dialysis bag (molecular weight cutoff 3500kDa) and dialyzed for 5 days. The solution was then lyophilized by rotary evaporation to obtain PVA-DHBA (grafting rate of about 5%).

[0052] 4. Prepare a 250 mg / ml PVA-DHBA aqueous solution (solution A). Prepare a 1% (w / v) chitosan (degree of deacetylation > 90%) acetic acid solution (solution B, acetic acid concentration 1%).

[0053] 5. Mix solution A and solution B at a volume ratio of 1:1 and stir magnetically for 30 minutes to obtain a homogeneous composite sol.

[0054] 6. Pour into a flat mold, pre-freeze at -80℃ for 12 hours, then transfer to a freeze dryer for freeze drying for 48 hours.

[0055] 7. Crush the freeze-dried sponge with a pulverizer, sieve it, take powder with a particle size of 150-300μm, seal it in packaging, and sterilize it by Co-60 irradiation.

[0056] The properties of the final product can be controlled by changing the ratio of PVA to DHBA, the concentration of chitosan, and the ratio of physical mixing.

[0057] The ratio of PVA to DHBA is (1-8):1, thereby controlling the grafting rate of the material and affecting its viscosity.

[0058] The concentration of CS should be controlled between 1% and 20%.

[0059] The mixing ratio of PVA-DHBA to CS is 7:3 to 3:7;

[0060] Powder sieving can be performed with different particle sizes: 50-120um, 120-150um, and 150-300um.

[0061] Example 2

[0062] Weigh 4.5g of PVA with a degree of alcoholysis >98% according to the mass-volume ratio of PVA to DMSO / deionized water mixture (DMSO:deionized water = 3:1, volume ratio) of 30mg / mL, add it to 150mL of the mixture, and stir at 80℃ until completely dissolved to obtain the first solution;

[0063] The first solution was cooled to room temperature, and 2.6 g of 3,5-dihydroxybenzoic acid and 7.5 g of sodium bisulfate were added. The mixture was reacted at a constant temperature for 24 hours under nitrogen protection to obtain the second solution.

[0064] The second solution was placed in a 3500 kDa dialysis bag and dialyzed for 5 days with boiled and cooled deionized water as the medium (the water was changed every 12 hours). The solution was concentrated by rotary evaporation at 48°C and 0.1 MPa for 2.5 hours and then freeze-dried under vacuum at 15 Pa for 48 hours to obtain a PVA-DHBA graft copolymer with a grafting rate of 5%.

[0065] Prepare a 250 mg / mL PVA-DHBA aqueous solution and a 1% chitosan-acetic acid solution (acetic acid mass fraction 1%, chitosan deacetylation degree 93%). Mix them at a volume ratio of 1:1 and stir magnetically for 30 minutes to obtain a homogeneous composite sol.

[0066] The composite sol was injected into a plate mold, pre-frozen at -80℃ for 12 hours, freeze-dried for 48 hours, pulverized and screened to obtain powder with a particle size of 150-300μm, and sterilized by Co-60 irradiation to obtain the composite hemostatic material.

[0067] Example 3

[0068] Weigh 4.2 g of PVA according to the mass-to-volume ratio of PVA to DMSO / deionized water mixture (DMSO:deionized water = 5:1, volume ratio) of 28 mg / mL, add it to 150 mL of the mixture, stir at 80 °C to dissolve, and obtain the first solution;

[0069] Add 2.47 g of 3,5-dihydroxybenzoic acid and 7 g of sodium bisulfate, and react under nitrogen protection for 24 hours to obtain the second solution;

[0070] After 5 days of dialysis, PVA-DHBA was obtained by rotary evaporation at 45℃ and 0.09MPa for 3 hours and freeze-drying at 10Pa for 48 hours, with a grafting rate of 4.5%.

[0071] Prepare a 240 mg / mL PVA-DHBA aqueous solution and mix it with a 1% chitosan-acetic acid solution (95% degree of deacetylation) at a 1:1 ratio, and stir for 30 minutes;

[0072] Pre-freeze at -80℃ for 12 hours, freeze-dry, pulverize and screen to obtain powder with a particle size of 50-120μm, and then sterilize to obtain the product.

[0073] As shown in Figure 1, Figure 1 is a schematic diagram of the successful synthesis of PVA-DHBA-CS gel, powder, and sponge multi-dosage forms provided in the embodiments of the present invention, and the adhesion effect with the bone tissue interface, glass section, and plastic interface. It shows that PVA-DHBA-CS was successfully synthesized and can be made into multiple dosage forms while having a certain adhesion strength with the bone tissue interface, glass, and plastic interface. The adhesion strength with the bone tissue interface reaches 1 MPa. PVA-DHBA-CS material was successfully synthesized and can be prepared into multiple dosage forms as needed, while having good adhesion properties with bone tissue.

[0074] As shown in Figure 2, Figure 2 is a schematic diagram comparing the in vitro sealing and hemostasis effect and the coagulation time effect of the material provided in the embodiment of the present invention. It shows that the synthesized material can effectively seal the aqueous solution in the tube inversion experiment. At the same time, in the whole blood coagulation time test experiment, the coagulation time only needs to be 60s, which is less than 120s in the CS group and 180s in the commercial Rhino Rescue. The comparison shows that the present invention has a good sealing effect.

[0075] As shown in Figure 3, Figure 3a shows a rat liver injury experiment, in which the material of the present invention has excellent hemostatic effect compared with the control group, quickly sealing the wound and reducing bleeding; Figure 3b shows a pig liver injury bleeding experiment, in which the material of the present invention has excellent hemostatic effect compared with the control group, and can withstand water flow to achieve efficient sealing and hemostasis.

[0076] The beneficial effects of this invention are reflected in:

[0077] 1. Synergistic Dual Hemostatic Mechanisms: Physical Adhesion and Sealing: The catechol groups in PVA-g-DHBA provide strong wet adhesion, quickly bonding the wound and sealing bleeding points; the porous powder absorbs water and swells, physically compressing the ruptured blood vessel. Chemical Coagulation: Chitosan's positive charge efficiently aggregates blood cells, activating the coagulation cascade reaction; simultaneously, the adhesion interface of PVA-g-DHBA enriches coagulation factors, accelerating prothrombin activation.

[0078] 2. Excellent biocompatibility and biodegradability: PVA and chitosan are both recognized biocompatible materials that can be gradually degraded in vivo.

[0079] 3. Easy to use and highly adaptable: The powder form can adapt to irregular and deep wounds and can adhere closely to bleeding sites.

[0080] 4. Controllable process: By adjusting the grafting rate, the ratio of PVA-g-DHBA to chitosan, freeze-drying parameters, and powder particle size, the adhesion strength, swelling rate, degradation rate, and hemostatic performance of the material can be precisely controlled.

[0081] The above descriptions are merely embodiments of the present invention. Commonly known technical solutions or characteristics are not described in detail here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A method for preparing a composite hemostatic material of PVA-polyphenol derivative and chitosan, characterized in that, The method includes: S1: Weighing PVA with a degree of alcoholysis >98% and adding it to the DMSO / deionized water mixture at a mass-to-volume ratio of 20-35 mg / mL, and stirring at 80°C until completely dissolved, wherein the volume ratio of DMSO to deionized water in the DMSO / deionized water mixture is 1:1-6:1, to obtain a first solution; S2: After the first solution cools to room temperature, adding 3,5-dihydroxybenzoic acid and sodium bisulfate sequentially, and reacting at a constant temperature for 24 hours under a nitrogen atmosphere, wherein the mass ratio of PVA to 3,5-dihydroxybenzoic acid is 1.5:1-1.9:1, and the mass ratio of PVA to sodium bisulfate is 0.5:1-0.7:1, to obtain a second solution; S3: Loading the second solution into a 3500 kDa molecular weight cutoff container. In the first step, the PVA-DHBA graft copolymer was dialyzed for 5 days in a dialysis bag using deionized water as the dialysis medium. After dialysis, the copolymer was concentrated by rotary evaporation and then freeze-dried to obtain the PVA-DHBA graft copolymer. In the second step, the PVA-DHBA graft copolymer was dissolved in deionized water to prepare a PVA-DHBA aqueous solution with a concentration of 200-300 mg / mL. A 1% chitosan-acetic acid solution was prepared. The solutions were mixed at a volume ratio of 1:1 and magnetically stirred for 20-40 minutes to obtain a homogeneous composite sol. In the third step, the homogeneous composite sol was injected into a flat mold and pre-frozen at -85℃ to -75℃ for 10-14 hours, then freeze-dried for 48 hours. The freeze-dried sponge-like product was pulverized using a pulverizer, and powder with a particle size of 50-300 μm was obtained through standard screening. After sealing and packaging, the powder was sterilized by Co-60 irradiation to obtain a powdered composite hemostatic material.

2. The method for preparing a composite hemostatic material of PVA-polyphenol derivative and chitosan according to claim 1, characterized in that: The volume ratio of DMSO to deionized water is 3:1 to 5:1; the mass-volume ratio of PVA to the DMSO / deionized water mixture is 28 to 100 mg / mL.

3. The method for preparing a composite hemostatic material of PVA-polyphenol derivative and chitosan according to claim 1, characterized in that: The mass ratio of PVA to 3,5-dihydroxybenzoic acid is 1.7:1 to 1.8:1, and the mass ratio of PVA to sodium bisulfate is 0.6:

1.

4. The method for preparing a composite hemostatic material of PVA-polyphenol derivative and chitosan according to claim 1, characterized in that: During the dialysis of the PVA-DHBA graft copolymer, deionized water that has been boiled and cooled to room temperature is replaced every 12 hours as the dialysis medium. After dialysis, the rotary evaporation conditions are: temperature 45~50℃, pressure 0.09~0.1MPa, concentration time 2~3 hours, and freeze-drying vacuum degree 10~20Pa.

5. The method for preparing a composite hemostatic material of PVA-polyphenol derivative and chitosan according to claim 1, characterized in that: The freeze-drying time in step S3 is 48 hours, which is consistent with the freeze-drying time of the freeze dryer in step S5.

6. The method for preparing a composite hemostatic material of PVA-polyphenol derivative and chitosan according to claim 1, characterized in that: The concentration of the PVA-DHBA aqueous solution was 240~260 mg / mL, and the magnetic stirring time was 30 minutes.

7. The method for preparing a composite hemostatic material of PVA-polyphenol derivative and chitosan according to claim 1, characterized in that: The degree of deacetylation of chitosan in the chitosan-acetic acid solution is 92%~95%, and the mass fraction of acetic acid in the chitosan-acetic acid solution is 1-20%.

8. The method for preparing a composite hemostatic material of PVA-polyphenol derivative and chitosan according to claim 1, characterized in that: The pre-freezing temperature in step S5 is -80℃, and the pre-freezing time is 12 hours.

9. A composite hemostatic material of PVA-polyphenol derivative and chitosan prepared according to the method for preparing a composite hemostatic material of PVA-polyphenol derivative and chitosan as described in claims 1-8.

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