Anti-freeze hydrogel and its use in the preparation of a rapid hemostatic product for external wounds

Abstract

The application belongs to the technical field of anti-freezing hydrogel and specifically relates to an anti-freezing hydrogel and application thereof in preparation of a quick hemostatic product for external injury, wherein the anti-freezing hydrogel is prepared by the following steps: 1) configuring a nanocellulose solution; 2) adding a catalyst, a crosslinking agent and dopamine into the nanocellulose solution to react and obtain a first mixed solution; 3) after the first mixed solution is cooled, the first mixed solution is subjected to dialysis and drying to obtain an intermediate solid product; 4) the intermediate solid product is mixed with water to obtain a second mixed solution, glycerol and polyvinyl alcohol are further added, after the intermediate solid product is completely dissolved, a borax solution is added to obtain a third mixed solution; 5) a blood coagulation promoting drug is added into the third mixed solution to obtain a fourth mixed solution, the fourth mixed solution is reacted at 90-92 DEG C for 0.5-1 h, and then cooled to room temperature to form the anti-freezing hydrogel. The material has excellent tissue adhesion, anti-freezing property and quick hemostatic effect.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of antifreeze hydrogel, and particularly relates to an antifreeze hydrogel and application thereof in preparation of a rapid hemostatic product for external injury. BACKGROUND

[0002] Dopamine (DA), also known as 4-(2-ethylamino) benzene-1,2-diol, can be polymerized on the surface of a material to form a polydopamine (PDA) nanofilm containing o-benzene-diol units. The PDA has super-strong tissue adhesion and good biocompatibility. In 2017, a research team of Southwest Jiaotong University in China proposed a glycerol-hydrogel with PDA-modified carbon nanotubes (CNTs) as conductive nanofillers. The hydrogel has antifreeze and heat resistance, long-term stability, good conductivity, super-strong mechanical properties and tissue adhesion. Polyvinyl alcohol (PVA) is a biomedically used polymer material that is widely used, but its mechanical properties are weak, and it lacks effective mechanical protection for a wound surface. In 2020, a research team of Feng Jiang of the University of British Columbia in Canada reported a study on a new type of conductive hydrogel prepared from PVA and cellulose nanofiber (CNF). The team prepared a PVA-CNF organic hydrogel by one-pot sol-gel synthesis method through PVA and TEMPO-oxidized CNF, and used a DMSO / H2O binary solvent system to inhibit the freezing point of water molecules, so as to enhance the mechanical properties and conductivity of the hydrogel while making it have good antifreeze performance. In 2018, the Institute of Physics and Chemistry, Chinese Academy of Sciences disclosed an invention patent (application publication number: CN108359056A) for a self-healing hydrogel of a cellulose-dopamine-polymer composite material as well as a preparation method and application thereof. In addition, glycerol (glycerol) mixed with water forms a binary solvent, which can significantly improve the antifreeze performance of the hydrogel, and the lowest freezing point (-46.5℃) is reached when the mass concentration of glycerol reaches 66.7%.

[0003] In recent years, hydrogels have attracted wide attention in the biomedical field, but the freezing of hydrogels at low temperatures and the poor adhesion limit their application in special environments. The PDA-CNTs hydrogel has the potential to be used as an auxiliary material for frostbite and burn wounds, but it is less effective for the more common acute bleeding wounds in clinical practice, and its application range is limited. The PVA-CNF hydrogel, as a conductive material, has strong mechanical properties but almost no tissue adhesion, and thus cannot be directly used as a wound auxiliary material. The invention patent (CN108359056A) aims to prepare a conductive material that has a repair capacity and can be recycled, but there is no report on the application of biomedical materials, and the hydrogel does not have antifreeze performance. SUMMARY

[0004] In view of the above technical problems, the present application aims to provide an anti-freezing hydrogel and its application in preparing a quick hemostatic product for external injuries to solve the above technical problems.

[0005] To achieve the above object, the present application adopts the following technical solutions:

[0006] In the first aspect, the present application provides a dopamine-nanocellulose-polyvinyl alcohol composite anti-freezing hydrogel, which is prepared by the following steps:

[0007] 1) configuring a nanocellulose solution;

[0008] 2) adding a catalyst, a crosslinking agent and dopamine to the nanocellulose solution, and reacting at 75-80℃ under nitrogen atmosphere for 20-24h to obtain a first mixed solution; the mass ratio of the nanocellulose, dopamine, catalyst and crosslinking agent is 1:0.9-1:0.5-0.6:0.9-1;

[0009] 3) after the first mixed solution is cooled, it is dialyzed and dried to obtain an intermediate solid product;

[0010] 4) mixing the intermediate solid product with water to obtain a second mixed solution, and then adding glycerol and polyvinyl alcohol, and after the intermediate solid product is completely dissolved, adding a borax solution to obtain a third mixed solution; the mass-volume ratio of the intermediate solid product, water, glycerol, polyvinyl alcohol and borax solution is 0.1-0.3g:3-5ml:10-12ml:0.3-0.4g:3-5ml;

[0011] 5) adding a blood coagulation promoting drug to the third mixed solution to obtain a fourth mixed solution, and reacting at 90-92℃ for 0.5-1h, and then cooling to room temperature to form a dopamine-nanocellulose-polyvinyl alcohol composite anti-freezing hydrogel; the mass ratio of the blood coagulation promoting drug to the intermediate solid product is 3-4:10.

[0012] The dopamine-nanocellulose-polyvinyl alcohol composite anti-freezing hydrogel material of the present application is prepared by mixing nanocellulose, dopamine, catalyst and crosslinking agent in a mass ratio of 1:0.9-1:0.5-0.6:0.9-1, combining part of the nanocellulose containing carboxyl and dopamine by amide reaction to form a new polymer (i.e. the intermediate solid product), then mixing the intermediate solid product, water, glycerol, polyvinyl alcohol and borax solution in a mass-volume ratio of 0.1g-0.3g:3ml-5ml:10ml-12ml:0.3g-0.4g:3ml-5ml to react, combining the intermediate solid product and polyvinyl alcohol to form a hydrogel, and mixing glycerol and water to form a binary solvent, which enhances the anti-freezing performance of the hydrogel and makes it better adapt to extreme environmental conditions such as high coldness, and further loading a common coagulant in clinical treatment into the hydrogel in a mass ratio of 3-4:10, which has a more advantageous hemostatic effect than ordinary wound dressings.

[0013] Further, in step 1), the nanocellulose solution is prepared as follows:

[0014] The nanocellulose is added to water and stirred to dissolve at room temperature to obtain a uniformly dispersed nanocellulose solution.

[0015] Further, the mass ratio of the nanocellulose to water is 1:99-500.

[0016] Further, the nanocellulose is selected from one of carboxymethyl cellulose and nanocellulose oxidized by 2,2,6,6-tetramethylpiperidine N-oxide.

[0017] Further, in step 2), the catalyst is N-hydroxysuccinimide, and the crosslinking agent is 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride.

[0018] Further, in step 4), the mass percentage concentration of the borax solution is 0.5%-4%.

[0019] Further, in step 5), the coagulant is selected from one or any combination of phenol sulfonethimide, carbazochrome and aminomethylbenzoic acid.

[0020] In a specific embodiment of the present application, the coagulant is phenol sulfonethimide powder with CAS number: 2624-44-4. Phenol sulfonethimide is an internal hemostatic drug, but its hemostatic effect is very weak when used externally. The present application uses the hydrogel to load phenol sulfonethimide to achieve remarkable effect in external wound hemostasis, thereby expanding the application range of phenol sulfonethimide.

[0021] Further, in step 5), the fourth mixed solution is shaped in a mold to form the dopamine-nanocellulose-polyvinyl alcohol composite anti-freezing hydrogel, and the thickness of the dopamine-nanocellulose-polyvinyl alcohol composite anti-freezing hydrogel is 0.5 cm-1 cm.

[0022] In a second aspect, the present application provides application of the dopamine-nanocellulose-polyvinyl alcohol composite anti-freezing hydrogel in preparation of a rapid hemostatic product for external injury.

[0023] In a third aspect, the present application provides application of the dopamine-nanocellulose-polyvinyl alcohol composite anti-freezing hydrogel in preparation of a skin injury repair product.

[0024] The present application has the following beneficial effects:

[0025] The dopamine-nanocellulose-polyvinyl alcohol composite anti-freezing hydrogel of the present application has excellent tissue adhesion, anti-freezing and rapid hemostatic effects, and can be used alone without relying on other adhesive substances; it is suitable for use in high-altitude and low-temperature areas; it is suitable for use in the face of wounds of different shapes; in the case of acute trauma, the hydrogel releases drugs after loading, and then directly contacts blood, which is extremely similar to the principle of intravenous infusion in terms of drug efficacy, and has a high local concentration, and has more advantages than ordinary wound dressings in terms of hemostatic effect. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 FIG. 1 is a Fourier transform infrared (FT-IR) spectrum of the hydrogel of the present application.

[0027] Figure 2 FIG. 2 is a thermogravimetric experiment result of the hydrogel of the present application.

[0028] Figure 3 FIG. 3 is an electron microscope photograph of the hydrogel of the present application after freeze-drying of a sample without glycerol.

[0029] Figure 4 FIG. 4 is an in vitro release curve of phenylsulfonethylamine.

[0030] Figure 5 FIG. 5 is the adhesive property of the hydrogel, A is a morphological diagram of the hydrogel, B is the adhesive condition of the hydrogel and a latex glove, C is the adhesive condition of the hydrogel and human skin, and D is the adhesive condition of the hydrogel and pig skin.

[0031] Figure 6 FIG. 6 is a mouse skin wound healing curve. DETAILED DESCRIPTION

[0032] The present application will be described in detail below with reference to the accompanying drawings and specific embodiments, but should not be understood as limiting the present application. If not specifically stated, the technical means used in the following embodiments are conventional means familiar to those skilled in the art, and the materials, reagents, etc. used in the following embodiments, if not specifically stated, can be obtained from commercial channels.

[0033] Nomenclature:

[0034] CNF: nanocellulose, purchased from Beifang Century (Jiangsu) Cellulose Material Co., Ltd., product code 202407291003.

[0035] TEMPO: 2,2,6,6-tetramethylpiperidine N-oxide.

[0036] NaBr: sodium bromide.

[0037] NaCIO: sodium hypochlorite.

[0038] NaOH: sodium hydroxide.

[0039] EDC: 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride.

[0040] NHS: N-hydroxysuccinimide.

[0041] PVA: polyvinyl alcohol.

[0042] CMC: carboxymethyl cellulose.

[0043] Example 1: Preparation of dopamine-nanocellulose-polyvinyl alcohol composite anti-freezing hydrogel

[0044] Under ice water bath, 1 g CNF was dispersed in 90 mL water and ultrasonically mixed, then 10 mL of a mixed solution of TEMPO (0.0156 g) and NaBr (0.103 g) fully dissolved in pure water was added, and 10 mL of 10% NaCIO solution was added. After stirring for 2 h at pH = 10.3-10.5 by adding NaOH, 10 mL of ethanol was added to quench the reaction. After centrifugation, the lower solid mixture was obtained, 200 mL of pure water was added to redissolve and dialyze (molecular weight cut-off 70 kDa) for 3 days, and the dialyzed liquid was frozen (temperature -40°C) and dried, then a 1% nanocellulose solution was prepared with pure water.

[0045] Under oil bath, 50 mL of the above nanocellulose solution and 0.48 g of EDC were added to a beaker, and the solution was stirred and dissolved at 80°C and 500 rpm for 1 h. To the dissolved solution, 0.29 g of NHS and 0.475 g of DA were added, and the pH value was adjusted to 5.0 with dilute hydrochloric acid (concentration 0.1 mol / L). The prepared mixture was continuously reacted at 500 rpm and 80°C for 24 h under N2 protection, and the solution was cooled to room temperature (20-24°C) to obtain a first mixed solution.

[0046] The first mixed solution was dialyzed using pure water (molecular weight cut-off 70 KDa) for 5 days. The conductivity of the dialysate was measured every day, and the dialysate was replaced with pure water to continue dialysis. The conductivity of the dialysate was measured to be 51.6, 11.2, 1.8, and 1.8 Siemens / m (S / m) on the 1st, 2nd, 3rd, and 4th days, respectively. The conductivity of the dialysate did not change after the 3rd day and was consistent with the conductivity of pure water under the same conditions. The dialysis was completed. The dialysate was dried at 60°C for 8h to obtain an intermediate solid product (0.46g).

[0047] Next, the intermediate solid product (0.2g) was added to pure water (4ml) to obtain a second mixed solution, and then glycerol (12ml) and PVA (0.4g) were added. After stirring at 130°C for 24h, it was observed that the solution was completely dissolved. A 2% borax solution (4ml) was added and the temperature was adjusted to 90°C to obtain a third mixed solution. Phenolsulfonethimide (75mg) was added to the third mixed solution to obtain a fourth mixed solution. Stirring was continued for 0.5h, and then the solution was placed in a mold and cooled to room temperature (20°C-24°C) to obtain a brown transparent hydrogel with a thickness of 0.5cm, which was a dopamine-nanocellulose-polyvinyl alcohol composite anti-freezing hydrogel (hereinafter referred to as hydrogel).

[0048] Product performance evaluation:

[0049] To better evaluate the performance of the dopamine-nanocellulose-polyvinyl alcohol composite anti-freezing hydrogel of the present application and further verify the synergistic effect between the functional components, the following verification was performed.

[0050] I. Infrared spectroscopy

[0051] The infrared spectroscopy detection results of the intermediate solid product of Example 1 are shown in Figure 1 The N-H bending vibration was detected at 1577cm -1 The formation of amide bonds between the amino group in dopamine and the carboxyl group in nanocellulose through amide reaction (reference doi: 10.1016 / j.carbpol.2020.117188) increased the crosslinking degree of the hydrogel, which helped to improve its mechanical strength and stability. In addition, the catechol group in dopamine has adhesion, and the formation of amide bonds can enhance the adhesion between dopamine and nanocellulose, so that the hydrogel can better adhere to the wound or tissue surface.

[0052] II. Thermogravimetric analysis

[0053] The thermogravimetric analysis results of the hydrogel of Example 1 are shown in Figure 2The hydrogel mainly had weight loss at 108.852℃ and 253.388℃, and the weight loss percentages were 25.812% and 68.346%, respectively. In combination with the composition and proportion of the hydrogel, it was considered that the weight loss was caused by water and glycerol, respectively. The results indicated that the hydrogel had good thermal stability.

[0054] III. Scanning electron microscope analysis

[0055] The hydrogel of Example 1 (without glycerol and blood coagulation drugs) was taken by scanning electron microscope (SEM) after freeze-drying treatment, and the results are shown in Figure 3 , which shows the structural characteristics of the hydrogel at the microscale. The porous network arranged in various ways is conducive to drug loading of the hydrogel and maintains good water absorption performance and mechanical strength.

[0056] IV. Drug release analysis

[0057] 0.5g of the hydrogel of Example 1 was placed in 20ml of PBS solution, and in vitro drug release experiment was performed at a centrifuge speed of 120rpm. The drug concentration of phenolsulfonphthalein in the solution was measured at 0.5h, 5h, 24h, 48h and 72h, respectively. The results are shown in Figure 4 , which shows that the drug is rapidly released in the early stage (0.5-24h), and the drug is basically completely released in the late stage (after 24h), and the drug concentration in the solution remains stable.

[0058] V. Skin adhesion test

[0059] The adhesion of the hydrogel obtained in Example 1 to latex gloves, human skin and pig skin was tested in the experimental environment, and the test results are shown in Figure 5 , which shows that the hydrogel obtained in Example 1 has ideal adhesion to latex gloves, human skin and pig skin at room temperature, and can maintain adhesion without easily falling off when the skin shape changes or the subject moves.

[0060] VI. Anti-freezing performance test

[0061] The anti-freezing performance of the hydrogel obtained in Example 1 and the hydrogel obtained without adding glycerol in the proportion was tested. The hydrogels were placed in 25℃, 4℃ and -20℃ environments, respectively, and observed for 24 hours. The hydrogel of Example 1 was in a colloidal state, and the hydrogel without glycerol in the -20℃ environment turned into a solid and lost the adhesion ability.

[0062] VII. Skin damage repair effect test

[0063] The hydrogel obtained in Example 1 was subjected to a skin damage repair test, and the test method was as follows: (1) Establishment of a mouse skin defect wound model: C57BL / 6 male mice were anesthetized by intraperitoneal injection of 0.5% chloral hydrate solution, the hair on the back of the mice was removed with a depilatory cream, and the skin on the back of the mice was disinfected with a cotton ball containing 75% ethanol solution by volume. After the ethanol has completely evaporated, a full-thickness skin defect wound is created on each side of the back using a circular punch with a diameter of 0.6 cm. The maximum and minimum diameters are measured with a vernier caliper to estimate the initial wound area. (2) Drug administration: The hydrogel obtained in Example 1 is cut into pieces and placed in a 75% ethanol solution for disinfection for 30 minutes. After being irradiated under an ultraviolet lamp for 2 hours, it is washed 5 times with a PBS solution. After the excess water on the surface of the hydrogel is absorbed with sterile filter paper, it is applied to the surface of the mouse skin wound and protected with sterile gauze and adhesive tape. (3) Mouse skin defect healing time detection: The mouse wound is observed and measured regularly. The maximum and minimum diameters of the wound are measured with a vernier caliper, and the wound area is estimated to evaluate the wound healing.

[0064] The test results are as follows Figure 6 As shown in Table 1, the hydrogel provided by the present invention has an excellent skin damage repair effect. The hydrogel obtained in Example 1 was used as experimental group 1, the hydrogel without ethidium sulfonate was used as experimental group 2, the wound was smeared with a PBS solution containing 3 mg / ml ethidium sulfonate and then covered with sterile gauze as experimental group 3, and the wound was covered with sterile gauze alone as a control group. Comparison of the hydrogel obtained in Example 1 with the other groups showed that the present invention improves the skin damage repair speed of the hydrogel by adding a hemostatic drug to the hydrogel.

[0065] Table 1 Results of two-way ANOVA

[0066]

[0067] Note: *** and ** represent significance levels of 1% and 5%, respectively.

[0068] VII. Test of hemostasis effect of tail-cut bleeding in mice

[0069] The hydrogel obtained in Example 1 was subjected to mouse tail hemostasis effect test, and the test method was as follows: (1) Establishment of mouse tail bleeding model: C57BL / 6 male mice were intraperitoneally injected with 0.5% chloral hydrate solution for anesthesia, and the tail end 1 / 2 area of the mouse was disinfected with 75% ethanol solution on a cotton ball. After the ethanol completely evaporated, the mouse was fixed and the mouse tail was cut off at the tail end 1 / 3 with a sterile scissors, and the mouse tail stump had obvious bleeding, and the bleeding start time was recorded; (2) Drug treatment: the wound was covered with the hydrogel obtained in Example 1 for 20 seconds, and the mouse tail bleeding was observed with sterile filter paper, the hemostasis time was recorded, and the control group without hemostasis drug hydrogel was compared; (3) The bleeding time of each group of mouse tail was calculated and statistically analyzed, and the test results were shown in Table 2:

[0070] Table 2 Independent sample T test analysis result table

[0071]

[0072]

[0073] Note: ***, ** represent 1%, 5% significance level respectively, / indicates that the item is not contained.

[0074] Eight, mouse liver bleeding model test hemostasis effect

[0075] The brown transparent hydrogel obtained in Example 1 was subjected to mouse liver bleeding model hemostasis effect test, and the test method was as follows: (1) Establishment of mouse liver bleeding model: C57BL / 6 male mice were intraperitoneally injected with 0.5% chloral hydrate solution for anesthesia, and the skin area of the mouse chest and abdomen was disinfected with 75% ethanol solution on a cotton ball. After the ethanol completely evaporated, the mouse was fixed and the chest and abdomen area was dissected, and the mouse liver was exposed. The mouse liver was carefully placed on a sterile filter paper under the condition of retaining blood vessels, and the serum around the liver was carefully removed. A 16G sterile syringe needle was used to pierce the liver at the midpoint of the lower end of the front edge of the liver to induce liver bleeding, and the bleeding start time was recorded; (2) Drug treatment: the wound was covered with the hydrogel obtained in Example 1, the liver bleeding was observed with sterile filter paper, the hemostasis time was recorded, and the control group without hemostasis drug hydrogel was compared; (3) The bleeding time of each group of mouse liver was calculated, the bleeding amount was measured by measuring the pre-weighed sterile filter paper, and statistical analysis was performed respectively, and the test results were as follows:

[0076] Table 3 Independent sample T test analysis result table

[0077]

[0078] Note: ***, ** represent 1%, 5% significance level respectively, / indicates that the item is not contained.

[0079] The above data show that the hydrogel provided by the present application has excellent hemostatic effect; compared with the hydrogel provided by comparative example 1 and the hydrogel without hemostatic drugs, the present application improves the hemostatic effect of the hydrogel by adding hemostatic drugs in the hydrogel.

[0080] It should be noted that when the present application claims involve numerical ranges, both endpoints of each numerical range and any number between the two endpoints can be selected, and in order to prevent repetition, the present application describes preferred embodiments.

[0081] Although the preferred embodiments of the present application have been described, those skilled in the art can make further changes and modifications to these embodiments once they know the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications falling within the scope of the present application.

[0082] Obviously, those skilled in the art can make various modifications and variations to the present application without departing from the spirit and scope of the present application. Thus, if these modifications and variations of the present application fall within the scope of the claims of the present application and their equivalents, the present application also intends to include these modifications and variations.

Claims

1. A dopamine-nanocellulose-polyvinyl alcohol composite antifreeze hydrogel, characterized in that: Prepared by the following steps: 1) Prepare nanocellulose solution; 2) adding N-hydroxysuccinimide, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, and dopamine to the nanocellulose solution, and reacting at 75° C. to 80° C. under a nitrogen atmosphere for 20 to 24 hours to obtain a first mixed solution; wherein the mass ratio of the nanocellulose, dopamine, N-hydroxysuccinimide, and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride is 1:0.9 to 1:0.5 to 0.6:0.9 to 1; 3) The first mixed solution is cooled, dialyzed, and dried to obtain an intermediate solid product; 4) mixing the intermediate solid product with water to obtain a second mixed solution, then adding glycerol and polyvinyl alcohol, and after the intermediate solid product is completely dissolved, adding borax solution to obtain a third mixed solution; the mass volume ratio of the intermediate solid product, water, glycerol, polyvinyl alcohol, and borax solution is 0.1 g to 0.3 g: 3 ml to 5 ml: 10 ml to 12 ml: 0.3 g to 0.4 g: 3 ml to 5 ml; 5) adding a procoagulant drug to the third mixed solution to obtain a fourth mixed solution, reacting the solution at 90° C. to 92° C. for 0.5 h to 1 h, and then cooling the solution to room temperature to form a dopamine-nanocellulose-polyvinyl alcohol composite antifreeze hydrogel; the mass ratio of the procoagulant drug to the intermediate solid product is 3 to 4:10; the procoagulant drug is selected from one of sulfonamide, carbazochrome, and aminomethylbenzoic acid, or any combination thereof.

2. The dopamine-nanocellulose-polyvinyl alcohol composite antifreeze hydrogel according to claim 1, characterized in that In step 1), the nanocellulose solution is prepared as follows: Nanocellulose is added to water and stirred to dissolve at room temperature to obtain a uniformly dispersed nanocellulose solution.

3. The dopamine-nanocellulose-polyvinyl alcohol composite antifreeze hydrogel according to claim 2, characterized in that: The mass ratio of the nanocellulose to water is 1:99-500.

4. The dopamine-nanocellulose-polyvinyl alcohol composite antifreeze hydrogel according to claim 3, characterized in that The nanocellulose is selected from carboxymethyl cellulose and nanocellulose oxidized by 2,2,6,6-tetramethylpiperidinium nitrogen oxide.

5. The dopamine-nanocellulose-polyvinyl alcohol composite antifreeze hydrogel according to claim 4, characterized in that: In step 4), the mass percentage concentration of the borax solution is 0.5% to 4%.

6. The dopamine-nanocellulose-polyvinyl alcohol composite antifreeze hydrogel according to claim 5, characterized in that In step 5), the fourth mixed solution is placed in a mold for molding, and the thickness of the dopamine-nanocellulose-polyvinyl alcohol composite antifreeze hydrogel is 0.5 cm-1 cm.

7. Use of the dopamine-nanocellulose-polyvinyl alcohol composite antifreeze hydrogel according to any one of claims 1 to 6 in the preparation of a rapid hemostasis product for trauma.

8. Use of the dopamine-nanocellulose-polyvinyl alcohol composite antifreeze hydrogel according to any one of claims 1 to 6 in the preparation of skin damage repair products.

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