Application of a polyphenol-polymer composite coating in the preparation of hemostasis-enhanced nanomaterials

Abstract

The invention discloses a kind of application of polyphenol-polymer composite coating in the preparation of hemostasis enhanced nano material, polyphenol hydroxyl substances and hydrophilic non-charged or hydrophilic negatively charged polymer are made into mixed solution, the mass ratio of described polyphenol hydroxyl substances and hydrophilic non-charged or hydrophilic negatively charged polymer is 1:2~8;Nano material base material is soaked in described mixed solution for 0.7~4 hours, the size of described nano material base material is 50~500nm;Separate, wash, dry, obtain hemostasis enhanced nano material;The obtained hemostasis enhanced nano material achieves hemostasis by intravenous administration route.Hydrophilic non-charged or negatively charged polymer regulates the effect between phenolic hydroxyl group and protein in the process of co-deposition with polyphenolic hydroxyl substances, and realizes mild protein adhesion by weakening the hydrogen bonding effect of phenolic hydroxyl group and key coagulation proteins in plasma, and makes protein change into the conformation of easy platelet adhesion, promotes platelet adhesion, and then achieves the effect of promoting blood coagulation.

Description

Technical Field

[0001] The invention belongs to the field of medical hemostatic materials and relates to the application of a polyphenol-polymer composite coating in the preparation of hemostatic enhanced nanomaterials. Background Art

[0002] Uncontrolled excessive bleeding is a significant cause of casualties in traffic accidents, surgical procedures, and natural disasters. Few hemostatic materials are available to stop bleeding at inaccessible internal injury sites, creating an urgent need for effective technologies to treat bleeding that cannot be stopped by external compression. Currently used intravenous hemostatic agents include synthetic polymer-derived hemostatics with limited efficacy and toxic byproducts, which can cause local irritation and tissue necrosis; and biologically derived hemostatics with short shelf life, high cost, stringent storage requirements, batch-to-batch variability, and potential for immune rejection. Therefore, there is a need to develop safe, effective, easily storable, and low-cost hemostatic materials for treating wounds that cannot be stopped by compression. Polyphenol / polymer procoagulant coatings are not affected by surface properties and can be readily coated onto a variety of nanoparticles. These coatings promote platelet adhesion and activation by promoting the conversion of key coagulation proteins to an active conformation, ultimately promoting coagulation. Polyphenol / polymer coatings on nanoparticles can be safely and cost-effectively prepared as hemostatically enhanced nanomaterials. Summary of the Invention

[0003] In view of this, the present invention provides an application of a polyphenol-polymer composite coating in the preparation of a hemostatically enhanced nanomaterial. The present invention specifically provides the following technical solutions:

[0004] The invention discloses an application of a polyphenol-polymer composite coating in the preparation of a hemostasis-enhanced nanomaterial, comprising the following steps: 1) preparing a mixed solution of a polyphenol hydroxyl substance and a hydrophilic non-charged or hydrophilic negatively charged polymer, wherein the mass ratio of the polyphenol hydroxyl substance to the hydrophilic non-charged or hydrophilic negatively charged polymer is 1:2-8; 2) soaking a nanomaterial substrate in the mixed solution for 0.7-4 hours, wherein the size of the nanomaterial substrate is 50-500 nm; 3) separating, washing, and drying to obtain the hemostasis-enhanced nanomaterial; and 4) achieving hemostasis by intravenously administering the hemostasis-enhanced nanomaterial obtained in step 3).

[0005] Furthermore, the mass ratio of the polyphenolic hydroxyl substance in step 1) to the hydrophilic uncharged or hydrophilic negatively charged polymer is 1:2-5, and the soaking time in step 2 is 0.7-1.5 hours.

[0006] Furthermore, the polyphenolic hydroxyl substance described in step 1) is dopamine, tannic acid, gallic acid, catechin, epicatechin, epigallocatechin gallate, theaflavin-3-gallate, 5-hydroxydopamine hydrochloride, or baicalein; the hydrophilic uncharged polymer described in step 1) is dextran, hydroxypropyl cellulose, hydroxyethyl starch, hydroxyethyl cellulose, prolan, pluronic or polyethylene glycol; and the hydrophilic negatively charged polymer is carboxymethyl cellulose or alginic acid, sodium alginate, hyaluronic acid, sodium hyaluronate or carboxymethyl starch.

[0007] Furthermore, the mixed solution in step 1) is an alkaline aqueous solution with an alkaline pH of 8-9.

[0008] Furthermore, the concentration of the polyphenolic hydroxyl substances in step 1) in the mixed solution is 0.25-3 mg / mL.

[0009] Furthermore, the concentration of the polyphenolic hydroxyl substance in the mixed solution of step 1) is 1-1.5 mg / mL, and the concentration of the hydrophilic uncharged or hydrophilic negatively charged polymer in the mixed solution of step 1) is 3-5 mg / mL.

[0010] Furthermore, the polyphenolic hydroxyl substance in step 1) is dopamine, tannic acid or gallic acid, the hydrophilic uncharged polymer is dextran, hydroxypropyl cellulose or polyethylene glycol, and the hydrophilic negatively charged polymer is carboxymethyl cellulose.

[0011] Furthermore, the nanomaterial substrate in step 2) can be silicon dioxide nanoparticles, melanin nanoparticles, prolamin nanoparticles, cellulose nanocrystals or starch nanocrystals.

[0012] Furthermore, the nanomaterial substrate described in step 2) can be silica nanoparticles with a diameter of 50 to 400 nm, melanin nanoparticles with a diameter of 50 to 300 nm, alcohol-soluble protein nanoparticles with a diameter of 50 to 300 nm, cellulose nanocrystals with a long diameter of 50 to 400 nm and a short diameter of 5 to 50 nm, or starch nanocrystals with a diameter of 100 to 400 nm and a thickness of 5 to 50 nm.

[0013] Furthermore, the silica nanoparticles are prepared using tetraethyl orthosilicate as a silicon source, ethanol as a solvent, and ammonia water as a catalyst; the melanin nanoparticles can be obtained by centrifugal extraction from natural cuttlefish juice; and the alcohol-soluble protein nanoparticles can be prepared by dissolving zein in an ethanol-water solution and using deionized water as an antisolvent to cause the nanoparticles to self-assemble and precipitate.

[0014] The beneficial effects of the present invention are:

[0015] The present invention utilizes the oxidative self-polymerization of polyphenolic hydroxyl substances combined with hydrophilic, uncharged or negatively charged polymers to form a pro-coagulant coating on the surface of nanoparticles, thereby obtaining a hemostasis-enhanced nanomaterial. The polyphenolic hydroxyl substances have strong hydrogen bonding interactions with proteins. In the composite coating, they provide a force to key coagulation components in the blood, such as plasma proteins (fibrinogen, etc.), causing them to adhere and aggregate. The hydrophilic, uncharged or negatively charged polymer with anti-protein adhesion regulates the interaction between the phenolic hydroxyl groups and proteins during co-deposition with the polyphenolic hydroxyl substances. By weakening the hydrogen bonding between the phenolic hydroxyl groups and key coagulation proteins in the plasma, mild protein adhesion is achieved, and the proteins are converted into a conformation that is easily adhered to platelets, promoting platelet adhesion and thus achieving a pro-coagulant effect.

[0016] Polyphenols / hydrophilic uncharged or negatively charged polymers form a procoagulant coating, which can be compounded with a variety of existing nanoparticles (such as silica nanoparticles, melanin nanoparticles, zein nanoparticles, cellulose nanocrystals, etc.) through a simple method to form a procoagulant coating on different substrates. This coating can convert key coagulation proteins into an activated conformation through mild plasma protein adhesion, promote platelet adhesion, and thus prepare hemostasis-enhancing nanomaterials.

[0017] The positive charge of positively charged polymers has a strong attraction to negatively charged blood cells in the blood. If positively charged polymers are used for co-deposition (regardless of the polyphenol / polymer ratio and treatment time), the resulting polyphenol / positively charged polymer coating will not significantly reduce the strong protein interaction compared to the strong interaction between pure polyphenol coatings and proteins, and may even enhance it. Therefore, when these two strong interactions exist, they will inhibit the conversion of plasma proteins to an effective conformation that promotes coagulation (i.e., plasma protein adhesion occurs, but the dormant-inactivated conformation is displayed), making it impossible to effectively adhere to platelets, causing the surface to lose its procoagulant effect. Therefore, the present invention can only use hydrophilic, uncharged or negatively charged polymer phases, and cannot use positively charged polymers. DETAILED DESCRIPTION

[0018] The preferred embodiments of the present invention are described in detail below with reference to the accompanying drawings.

[0019] Example 1

[0020] Mix 35.0 mL of anhydrous ethanol, 1.5 mL of ammonia water (25 wt%) and 5.0 mL of deionized water in a flask, stir at 25°C for 5 min, add 1.34 mL of tetraethyl silicate to the mixture, stir at 25°C for 15 min, and centrifuge at 10,000 rpm for 10 min. Wash the precipitate three times with a small amount of deionized water, centrifuging at the same speed each time to obtain silica nanoparticles (diameter 90-200 nm).

[0021] 5 mg of dopamine hydrochloride and 25 mg of dextran were dissolved in 4 mL of Tris buffer solution (10 mM), and the pH was adjusted to 8.5. 1 mL of 30 mg / mL silica nanoparticle dispersion was added to the mixed solution. After stirring at 25°C for 1 hour, the mixture was taken out and washed with deionized water and centrifuged three times to remove the dopamine and dextran that had not formed a coating. The mixture was then dispersed in water and stored to obtain S1.

[0022] In this embodiment, the nanomaterial substrate is silicon dioxide nanoparticles, the polyphenolic hydroxyl substance is dopamine, and the hydrophilic uncharged polymer is dextran, with a mass ratio of 1:5.

[0023] Example 2

[0024] Commercially available cuttlefish juice was centrifuged at 10,000 rpm for 10 min at 4° C., and the precipitate was washed three times with a small amount of deionized water, each time centrifuged at the same speed to obtain melanin nanoparticles (with a diameter of 100 to 200 nm).

[0025] 5 mg of dopamine hydrochloride and 25 mg of dextran were dissolved in 4 mL of Tris buffer solution (10 mM), and the pH was adjusted to 8.5. 1 mL of 30 mg / mL melanin nanoparticle dispersion was added to the mixed solution. After stirring at 25°C for 1 hour, the mixture was taken out and washed with deionized water and centrifuged three times to remove the dopamine and dextran that had not formed a coating. The mixture was then dispersed in water and stored to obtain M1.

[0026] In this embodiment, the nanomaterial substrate is melanin nanoparticles, the polyphenol hydroxyl substance is dopamine, and the hydrophilic uncharged polymer is dextran, with a mass ratio of 1:5.

[0027] Example 3

[0028] 500 mg of zein was weighed and dissolved in 20 mL of 80% ethanol-water solution, 20 mL of water was added thereto to form a zein emulsion, and corn zein nanoparticles (with a diameter of 80-150 nm) were obtained by freeze-drying.

[0029] 5 mg of dopamine hydrochloride and 25 mg of dextran were dissolved in 4 mL of Tris buffer solution (10 mM) and the pH was adjusted to 8.5. 1 mL of 20 mg / mL zein nanoparticle dispersion was added to the mixed solution. After stirring at 25°C for 1 hour, the mixture was taken out and washed with deionized water and centrifuged three times to remove the dopamine and dextran that did not form a coating. The mixture was then dispersed in water and stored to obtain P1.

[0030] In this embodiment, the nanomaterial substrate is zein nanoparticles, the polyphenolic hydroxyl substance is dopamine, and the hydrophilic uncharged polymer is dextran, with a mass ratio of 1:5.

[0031] Example 4

[0032] 5 mg of dopamine hydrochloride and 25 mg of dextran were dissolved in 4 mL of Tris buffer solution (10 mM), and the pH was adjusted to 8.5. 1 mL of 20 mg / mL commercially available cellulose nanocrystal dispersion (long diameter 80-200 nm, short diameter 5-50 nm) was added to the mixed solution. After stirring at 25°C for 1 hour, the mixture was taken out, washed with deionized water, and centrifuged three times to remove the dopamine and dextran that had not formed a coating. The mixture was then dispersed in water and stored to obtain C1.

[0033] In this embodiment, the nanomaterial substrate is cellulose nanocrystals, the polyphenol hydroxyl substance is dopamine, and the hydrophilic uncharged polymer is dextran, with a mass ratio of 1:5.

[0034] Comparative Example 1

[0035] Mix 35.0 mL of anhydrous ethanol, 1.5 mL of ammonia water (25 wt%) and 5.0 mL of deionized water in a flask, stir at 25°C for 5 min, add 1.34 mL of tetraethyl silicate to the mixture, stir at 25°C for 15 min, and centrifuge at 10,000 rpm for 10 min. Wash the precipitate three times with a small amount of deionized water, centrifuging at the same speed each time to obtain silica nanoparticles (diameter 90-200 nm).

[0036] 5 mg of dopamine hydrochloride and 50 mg of dextran were dissolved in 4 mL of Tris buffer solution (10 mM), and the pH was adjusted to 8.5. 1 mL of 30 mg / mL silica nanoparticle dispersion was added to the mixed solution. After stirring at 25°C for 1 hour, the mixture was taken out and washed with deionized water and centrifuged three times to remove the dopamine and dextran that had not formed a coating. The mixture was then dispersed in water and stored to obtain S2.

[0037] In this comparative example, the nanomaterial substrate is multi-silica nanoparticles, the phenolic hydroxyl substance is dopamine, and the hydrophilic uncharged polymer is dextran, with a mass ratio of 1:10.

[0038] Comparative Example 2

[0039] Mix 35.0 mL of anhydrous ethanol, 1.5 mL of ammonia water (25 wt%) and 5.0 mL of deionized water in a flask, stir at 25°C for 5 min, add 1.34 mL of tetraethyl silicate to the mixture, stir at 25°C for 15 min, and centrifuge at 10,000 rpm for 10 min. Wash the precipitate three times with a small amount of deionized water, centrifuging at the same speed each time to obtain silica nanoparticles (diameter 90-200 nm).

[0040] 5 mg of dopamine hydrochloride and 5 mg of dextran were dissolved in 4 mL of Tris buffer solution (10 mM), and the pH was adjusted to 8.5. 1 mL of 30 mg / mL silica nanoparticle dispersion was added to the mixed solution. After stirring at 25°C for 1 hour, the mixture was taken out and washed with deionized water and centrifuged three times to remove the dopamine and dextran that had not formed a coating. The mixture was then dispersed in water and stored to obtain S3.

[0041] In this comparative example, the nanomaterial substrate is multi-silica nanoparticles, the polyphenolic hydroxyl substance is dopamine, and the hydrophilic uncharged polymer is dextran, and the mass ratio is 1:1.

[0042] Comparative Example 3

[0043] Mix 35.0 mL of anhydrous ethanol, 1.5 mL of ammonia water (25 wt%) and 5.0 mL of deionized water in a flask, stir at 25°C for 5 min, add 1.34 mL of tetraethyl silicate to the mixture, stir at 25°C for 15 min, and centrifuge at 10,000 rpm for 10 min. Wash the precipitate three times with a small amount of deionized water, centrifuging at the same speed each time to obtain silica nanoparticles (diameter 90-200 nm).

[0044] 5 mg of dopamine hydrochloride was dissolved in 4 mL of Tris buffer solution (10 mM), and the pH was adjusted to 8.5. 1 mL of 30 mg / mL silica nanoparticle dispersion was added to the mixed solution. After stirring at 25°C for 1 hour, the mixture was taken out and washed with deionized water and centrifuged three times to remove the dopamine that did not form a coating. The mixture was then dispersed in water and stored to obtain S4.

[0045] In this comparative example, the nanomaterial substrate is multi-silicon dioxide nanoparticles, the polyphenolic hydroxyl substance is dopamine, and no polymer component is added.

[0046] Comparative Example 4

[0047] 35.0 mL of anhydrous ethanol, 1.5 mL of ammonia (25 wt%), and 5.0 mL of deionized water were mixed in a flask and stirred at 25°C for 5 min. 1.34 mL of tetraethyl silicate was added to the mixture, stirred at 25°C for 15 min, and then centrifuged at 10,000 rpm for 10 min. The precipitate was washed three times with a small amount of deionized water, each time centrifuged at the same speed to obtain silica nanoparticles (S, with a diameter of 90 to 200 nm) without any modification.

[0048] Comparative Example 5

[0049] Commercially available cuttlefish ink was centrifuged at 10,000 rpm for 10 min at 4°C, and the precipitate was washed three times with a small amount of deionized water, each time at the same centrifugation speed to obtain melanin nanoparticles (M, diameter of 100-200 nm) without any modification.

[0050] Comparative Example 6

[0051] 500 mg of zein was weighed and dissolved in 20 mL of 80% ethanol-water solution, to which 20 mL of water was added to form a zein emulsion, which was then freeze-dried to obtain zein nanoparticles (P, size 80-150 nm) without any modification.

[0052] Comparative Example 7

[0053] The commercially available cellulose nanocrystals (C) have a long diameter of 80 to 200 nm and a short diameter of 5 to 50 nm without any modification.

[0054] Test Example 1 In vitro coagulation effect test

[0055] Detection method: The materials obtained in each embodiment and comparative example were subjected to a coagulation effect comparison experiment. The blood used for detection was fresh sodium citrate anticoagulated blood taken from rat hearts.

[0056] Test steps: Take 10 μL of 20 mg / mL physiological saline dispersion of the nanoparticles of Example 1 and Comparative Examples 1-4, and take 10 μL of 10 mg / mL physiological saline dispersion of Examples 2-4 and Comparative Examples 5-7. Take 100 μL of fresh anticoagulated blood and mix it thoroughly with 10 μL of 0.2M CaCl2 solution, then quickly mix it with the nanoparticle dispersion, and place the tube in a constant temperature water bath at 37°C for incubation for 1 minute. Then, use 10 mL of deionized water to fully lyse the excess blood that has not formed a blood clot, and place it in a constant temperature water bath at 37°C for incubation for 3 minutes. Pipette 1 mL of the lysed liquid and centrifuge (2500 rpm, 3 minutes). Take 100 μL of the supernatant after centrifugation and add it to a 96-well plate, and test the absorbance (Abs) at 545 nm using an enzyme-linked immunosorbent assay (ELISA) instrument. For the blank control group, 100 μL of fresh anticoagulated blood was added to 10 mL of deionized water and incubated in a 37°C water bath for 3 minutes. 100 μL of the sample was then added to a 96-well plate and the absorbance at 545 nm was measured. The blood coagulation index (BCI) was calculated using the following formula.

[0057] Blood coagulation index% (BCI) = (Abs 样品 / Abs 空白 )×100%...................Formula 1

[0058] Where: Abs 样品 is the absorbance of the embodiment and the comparative example at 545 nm; Abs 空白 is the absorbance of the blank group at 545 nm.

[0059] Table 1 In vitro coagulation effect test

[0060]

[0061]

[0062] BCI (Blood clotting index) can characterize the coagulation effect of a material. Generally, the smaller the BCI value, the better the coagulation effect of the material.

[0063] As can be seen from Table 1, the BCI index of the materials coated with the polyphenol / polymer procoagulant coating under the preferred preparation parameters obtained in Examples 1 to 4 of the present invention is as low as 16.3% and as high as 61.1%. Compared with the corresponding unmodified substrates (Comparative Examples 4-7) and the materials coated with the polyphenol / polymer coating using non-preferred preparation parameters (Comparative Examples 1-3), the BCI of the Examples is significantly lower, indicating that the nanoparticles modified with the polyphenol / polymer procoagulant coating have more excellent procoagulant properties. Thus, using the preparation method of the present invention, adding an uncharged or negatively charged polymer to the polyphenol for co-deposition can prepare hemostatically enhanced nanomaterials. The reasons why the comparative examples have poor hemostatic effects are as follows:

[0064] Comparative Example 1, in which the glucan dosage in Example 1 was increased from 5 mg / mL to 10 mg / mL, achieved a BCI of 12.7% for Example 1, compared to 24.5% for Comparative Example 1. The results indicate that increasing the glucan dosage resulted in a higher BCI for the polyphenol / polymer composite coating and a poorer procoagulant effect. This is because increasing the glucan content in the composite coating enhances the shielding effect of the polyphenol groups on the strong interaction between the coagulation proteins, weakening the surface's effective interaction with the proteins and making platelet adhesion difficult, thus impairing the coagulation process.

[0065] Comparative Example 2 reduced the amount of glucan added in Example 1 from 5 mg / mL to 1 mg / mL. The BCI for Example 1 was 12.7%, while that for Comparative Example 2 was 18.0%. The results showed that reducing the amount of glucan added resulted in a higher BCI for the polyphenol / polymer composite material, resulting in a poorer procoagulant effect. This is because the reduced glucan content in the composite coating weakens the shielding effect of the strong interaction between the polyphenol groups and coagulation proteins, making them less likely to activate. This results in an inability for platelets to effectively adhere to the surface, which in turn affects coagulation.

[0066] Comparative Example 3 removed the uncharged polymer from Example 1 and directly formed a polyphenol coating. The BCI for Example 1 was 12.7%, while that for Comparative Example 3 was 29.7%. The results show that coating with polyphenol alone, without the uncharged polymer, results in a higher BCI and poorer procoagulant effect. This is because the phenolic hydroxyl groups in the pure polyphenol coating interact strongly with coagulation proteins, inhibiting their activation and preventing them from transitioning to a conformation that effectively adheres to platelets. This inhibits platelet adhesion and, in turn, affects coagulation.

[0067] Comparative Examples 4-7 correspond to the unmodified substrates of Examples 1-4. The BCI of the silica nanoparticles was 28.5%, which decreased to 12.7% after modification; the BCI of the melanin nanoparticles was 81.5%, which decreased to 61.1% after modification; the BCI of the zein nanoparticles was 61.3%, which decreased to 38.4% after modification; and the BCI of the cellulose nanocrystals was 69.5%, which decreased to 43.4% after modification. This indicates that coating the substrate with the polyphenol / polymer coating of the present invention significantly reduces the BCI index and enhances the procoagulant effect.

[0068] Test Example 2: Rat Femoral Artery Hemostasis Effect Test

[0069] Detection method: Example 1 and Comparative Example 4 were injected intravenously into rats to compare their blood loss control effects on femoral artery injury.

[0070] Test steps: SD rats weighing 160-190g were selected and anesthetized by intraperitoneal injection of chloral hydrate (10% deionized water, 0.5mL / 100g body weight). 0.5mL of 20mg / mL nanoparticle dispersion was injected into the rat through the tail vein using a 1mL syringe (0.5mL of normal saline was selected as the control group), and the material was allowed to circulate in the rat for 5 minutes before the experiment. The epithelial tissue of the left hind limb was cut open with surgical scissors to expose the femoral artery and vein of the rat. The femoral artery was quickly cut off with a scalpel (together with the vein and peripheral nerves that were difficult to separate from the artery). After cutting the femoral artery, it was allowed to bleed freely for 10 seconds; thereafter, the blood flowed out freely, and no pressure was applied to the wound surface. The spilled blood was promptly wiped off with filter paper (to accurately observe the time when bleeding stopped, which was recorded as the bleeding time).

[0071] Table 2 Average hemostasis time of femoral artery hemostasis in rats

[0072] sample S1 (Example 1) S (Comparative Example 4) NS (blank control) T(min) 3 5 7

[0073] The rat femoral artery hemostasis test evaluates the hemostatic effect of the material in real application scenarios by measuring the hemostasis time when the material treats the injury site in a rat femoral artery injury model. Generally, the better the procoagulant effect of the material, the shorter the time required for hemostasis during the treatment process.

[0074] As can be seen from Table 2, the nanoparticles coated with a polyphenol / polymer coagulant coating under the preferred preparation parameters obtained in Example 1 of the present invention have an average hemostasis time (3 min) in rat femoral artery trauma hemostasis that is lower than that of the untreated normal saline control group NS (7 min) and the unmodified nanoparticles S (Comparative Example 4, 5 min), indicating that the nanoparticles modified with a polyphenol / polymer coagulant coating have better therapeutic effects in the treatment of rat femoral artery injury model.

[0075] Finally, it should be noted that the above preferred embodiments are only used to illustrate the technical solutions of the present invention and are not limiting. Although the present invention has been described in detail through the above preferred embodiments, those skilled in the art should understand that various changes can be made in form and details without departing from the scope defined by the claims of the present invention.

Claims

1. Application of a polyphenol-polymer composite coating in the preparation of hemostasis-enhanced nanomaterials, characterized in that: The method comprises the following steps: 1) preparing dopamine and glucan into a mixed solution, wherein the mass ratio of dopamine to glucan is 1:5; 2) soaking a nanomaterial substrate in the mixed solution for 0.7 to 4 hours, wherein the size of the nanomaterial substrate is 50 to 500 nm; 3) separating, washing, and drying to obtain a hemostasis-enhanced nanomaterial; 4) achieving hemostasis by intravenously administering the hemostasis-enhanced nanomaterial obtained in step 3; and the nanomaterial substrate in step 2) is silicon dioxide nanoparticles, melanin nanoparticles, zein nanoparticles, or cellulose nanocrystals.

2. The use of a polyphenol-polymer composite coating according to claim 1 in preparing a hemostasis-enhanced nanomaterial, characterized in that: The soaking time in step 2) is 0.7 to 1.5 hours.

3. The use of a polyphenol-polymer composite coating according to claim 1 in preparing a hemostasis-enhanced nanomaterial, characterized in that: The mixed solution in step 1) is an alkaline aqueous solution with an alkaline pH of 8-9.

4. The use of a polyphenol-polymer composite coating according to claim 1 in preparing a hemostasis-enhanced nanomaterial, characterized in that: The concentration of dopamine in the mixed solution of step 1) is 0.25-3 mg / mL.

5. Use of a polyphenol-polymer composite coating according to claim 1 in preparing a hemostasis-enhanced nanomaterial, characterized in that: The concentration of dopamine in the mixed solution of step 1) is 1-1.5 mg / mL, and the concentration of glucan in the mixed solution of step 1) is 3-5 mg / mL.

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