Anti-adhesion hemostatic hydrogel as well as preparation method and application thereof

Abstract

The invention discloses anti-adhesion hemostatic hydrogel as well as a preparation method and application thereof. The preparation method of the anti-adhesion hemostatic hydrogel comprises the following steps: dissolving an amino high-molecular polymer in a first solvent to obtain a component A; dissolving a cross-linking agent, a reaction active compound and an anti-tissue adhesion drug in a second solvent to obtain a component B; wherein the cross-linking agent is a dialdehyde compound, and the reaction active compound contains an NHS group; before use, the component A and the component B are mixed, and then in-situ crosslinking can be performed to obtain the anti-adhesion hemostatic hydrogel. The anti-adhesion hemostatic hydrogel disclosed by the invention can form a layer of physical barrier at a wound of an organ, so that the effects of stopping bleeding and preventing tissue adhesion are achieved; in addition, the anti-adhesion drugs uniformly dispersed in the gel network enhance the anti-tissue adhesion effect of the adhesive through the effects of inhibiting tissue surface fibroblast proliferation, promoting fibrin degradation, resisting inflammation and oxidation and the like; the hemostatic hydrogel disclosed by the invention has the advantages of biodegradability and good biocompatibility.

Description

Technical Field

[0001] The present invention belongs to the technical field of hemostatic gels, and particularly relates to an anti-adhesion hemostatic hydrogel, a preparation method thereof, and an application thereof. Background Art

[0002] In the field of medical technology, especially in surgical operations, hemostasis and prevention of postoperative tissue adhesion are two crucial issues (such as liver hemostasis and prevention of postoperative adhesion). This is because bleeding during the operation not only increases the risk to the patient but may also affect the surgical outcome; while postoperative tissue adhesion may lead to serious complications such as chronic pain and intestinal obstruction, bringing long-term pain to the patient and increasing the patient's physiological burden. As a material with good biocompatibility, the adhesive also has adjustable mechanical properties and characteristics similar to those of tissues. It has been widely studied and applied in the fields of life science, clinical medicine, etc. It has been successfully developed as an artificial cornea in tissue engineering and demonstrated the ability of precise control in drug delivery systems. However, in clinical medicine, how to effectively utilize the characteristics of the adhesive to solve the problems of organ hemostasis and postoperative adhesion is an urgent problem to be solved. Summary of the Invention

[0003] In order to solve the above technical problems, the purpose of the present invention is to provide a preparation method that is simple to prepare and can in-situ generate an anti-adhesion hemostatic hydrogel that is biodegradable, has good biocompatibility, and is non-toxic and harmless.

[0004] In order to achieve the above purpose, the technical solution of the present invention is as follows: A preparation method of an anti-adhesion hemostatic hydrogel,

[0005] Dissolve an amino polymer in a first solvent to obtain component A;

[0006] Dissolve a crosslinking agent, a reactive compound, and an anti-tissue adhesion drug in a second solvent to obtain component B;

[0007] Wherein, the crosslinking agent is a dialdehyde compound, and the reactive compound contains an NHS group;

[0008] Before use, mix component A and component B, and then they can be crosslinked in-situ to obtain an anti-adhesion hemostatic hydrogel.

[0009] In the above technical solution, the volume ratio of component A to component B is 10:1 - 100 (it can be any ratio among 10:1, 2:1, 1:1, 1:2, 1:5, 1:10 or the corresponding range between any two ratios. Below or above this ratio, the final crosslinking strength of the hydrogel is low and the adhesion of the hydrogel is low).

[0010] In the above technical solution, the solid content of the anti-adhesion hemostatic hydrogel is 0.5-35 wt% (it can be any value among 0.5 wt%, 5 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt% and 35 wt% or the corresponding range between any two values. If the concentration is too low, the prepared hydrogel has no adhesion to the wound surface. If the concentration is too high, the hydrogel is too hard, has no adhesion and is fragile).

[0011] In the above technical solution, the component A meets at least one of the following conditions A1-C1:

[0012] A1: The amino polymer is at least one of gelatin, chitosan, carboxymethyl chitosan, 2arm-PEG-NH2, 4arm-PEG-NH2, 8arm-PEG-NH2, linear polyethyleneimine, branched polyethyleneimine, poly-L-lysine, polyamidoamine dendrimer-G1, poly-L-histidine, poly(β-amino ester), poly(N,N-dimethylaminoethyl methacrylate), poly{2-[(2-aminoethyl)amino]ethyl aspartate} and poly(2-aminoethyl vinyl phosphate);

[0013] B1: The first solvent is at least one of deionized water, secondary distilled water, ultrapure water, sodium carbonate-sodium bicarbonate buffer solution, PBS buffer solution, phosphate buffer solution and disodium hydrogen phosphate-citric acid buffer solution;

[0014] C1: The mass concentration of the amino polymer in the component A is 0.1-35.0 wt% (it can be any value among 0.1 wt%, 5 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt% and 35 wt% or the corresponding range between any two values. If the content of the amino polymer is too low, the strength of the formed hydrogel is weak. If the content of the amino polymer is too high, the amount of reactive substances consumed during the reaction process increases, and ultimately the adhesion of the hydrogel may decrease).

[0015] In the above technical solution, the component B meets at least one of the following conditions A2-G2:

[0016] A2: The crosslinking agent is at least one of glyoxal, malonaldehyde, succinaldehyde, glutaraldehyde, adipaldehyde, pimelaldehyde, suberaldehyde, nonanaldehyde, sebacaldehyde, methylmalonaldehyde, dimethylmalonaldehyde and methylbutyraldehyde;

[0017] B2: The reactive compound is at least one of 2arm-PEG-SS, 4arm-PEG-SS, 8arm-PEG-SS, 2arm-PEG-SC, 4arm-PEG-SC, 8arm-PEG-SC, 2arm-PEG-SG, 4arm-PEG-SG, 8arm-PEG-SG, NHS-modified sodium alginate, NHS-modified polypeptide, and NHS-modified sodium hyaluronate;

[0018] C2: The anti-adhesion drug includes at least one of tissue plasminogen activator, heparin, hepatocyte growth factor, anthocyanin, methylene blue, and vitamin E;

[0019] D2 The mass concentration of the reactive compound in the B component is 0.5-35.0 wt% (which can be any value among 0.5 wt%, 1 wt%, 5 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, and 35 wt% or the corresponding range between any two values. If the mass concentration of the reactive compound is too low, the finally formed hydrogel has no adhesiveness; if it is too high, the finally formed hydrogel will be too hard and brittle);

[0020] E2: The mass concentration of the cross-linking agent in the B component is 0.1-10.0 wt% (which can be any value among 0.1 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, and 10 wt% or the corresponding range between any two values. If the content of the cross-linking agent is too low, it has no promoting effect on the gelation time of the hydrogel; if it is too high, the finally formed hydrogel will be either too hard and brittle or will not form a gel);

[0021] F2: The molar concentration of the anti-adhesion drug in the B component is 0.1-200 μM [which can be any value among 0.1 μM, 1 μM, 10 μM, 50 μM, 100 μM, and 200 μM or the corresponding range between any two values. The addition amount of the anti-adhesion drug should not be too high. For example, taking too much vitamin E (300 mg) per day is likely to cause a decline in the body's immune ability];

[0022] G2: The second solvent is at least one of deionized water, secondary distilled water, ultrapure water, sodium carbonate-sodium bicarbonate buffer solution, PBS buffer solution, phosphate buffer solution, and disodium hydrogen phosphate-citric acid buffer solution.

[0023] In the above technical solution, the NHS-modified sodium alginate is obtained by modifying sodium alginate with a compound containing an NHS group in the presence of EDC / EDC I; the NHS-modified polypeptide is obtained by modifying a polypeptide substance with a compound containing an NHS group in the presence of EDC / EDC I; the NHS-modified sodium hyaluronate is obtained by modifying sodium hyaluronate with a compound containing an NHS group in the presence of EDC / EDC I.

[0024] In the above technical solution, the compound containing an NHS group is at least one of N-hydroxysuccinimide, disuccinimidyl glutarate, disuccinimidyl suberate, (+)-biotin-N-succinimidyl ester, N-hydroxysuccinimidyl laurate, N-hydroxysuccinimidyl acetoacetate, N-succinimidyl octanoate, N-succinimidyl hexanoate, N-hydroxysuccinimidyl acetate, and di(N-succinimidyl) sebacate.

[0025] In the above technical solution, the polypeptide substance includes plant-derived polypeptides and animal-derived polypeptides; the plant-derived polypeptides include at least one of soy peptide, peanut peptide, corn peptide, pea peptide, rice peptide, flaxseed peptide, corn oligopeptide powder, and wheat oligopeptide powder; the animal-derived polypeptides include at least one of fish collagen peptide, bovine collagen peptide, bone collagen peptide, sea cucumber peptide, oyster peptide, and Antarctic krill peptide.

[0026] The second object of the present invention is to provide an anti-adhesion hemostatic hydrogel prepared by the preparation method as described above, which has good hemostatic effect, can prevent tissue adhesion, and has biocompatibility and biodegradability characteristics.

[0027] The third object of the present invention is to provide an application of the anti-adhesion hemostatic hydrogel as described above in the preparation of products for hemostasis, adhesion sealing, or anti-adhesion.

[0028] The beneficial effects of the present invention are as follows: The mechanism of action of the anti-adhesion hemostatic hydrogel of the present invention is that a Schiff base reaction occurs between a crosslinking agent and an amino polymer, forming a first-layer rapid crosslinking network structure. At the same time, the reactive compound also undergoes an amidation reaction with the amino polymer and the amino groups at the wound site (generating NHS-ester) to form a second-layer adhesion crosslinking network structure. Among them, the second-layer adhesion crosslinking network structure mainly plays a "bridging" role, that is, "bridging" the first-layer rapid crosslinking network structure and the wound tissue, thereby forming a physical barrier at the wound of the organ (and this physical barrier has strong adhesion on the wound surface and is not easy to fall off), thus playing a role in hemostasis and preventing tissue adhesion. The entire crosslinking reaction process lasts for 1-6 seconds. In addition, the anti-adhesion drugs uniformly dispersed in the gel network strengthen the anti-tissue adhesion effect of the adhesive by inhibiting the proliferation of fibroblasts on the tissue surface, promoting fibrin degradation, and having anti-inflammatory and antioxidant effects. The hemostatic hydrogel has biodegradability and good biocompatibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 Schematic diagram of the hemostasis principle of the hemostatic hydrogel of the present invention;

[0030] Figure 2 Pictures of the states of the adhesives prepared in Example 1, Example 2, Example 20, and Example 25 of the present invention;

[0031] Figure 3 Photo of the liver hemostasis of the rat model with liver trauma by the hemostatic hydrogel prepared in Example 5 of the present invention;

[0032] Figure 4 Photo of the liver hemostasis of the rat model with liver trauma by the hemostatic hydrogel prepared in Example 25 of the present invention;

[0033] Figure 5 Test results of the linear viscoelastic range of the hemostatic hydrogel prepared in Example 4 of the present invention;

[0034] Figure 6 Test results of the alternating strain scan of the hemostatic hydrogel prepared in Example 4 of the present invention;

[0035] Figure 7 Test results of H&E section staining of the hemostatic hydrogels prepared in Example 4 and Example 5 of the present invention on the liver of the rat model with liver trauma 55 days after hemostasis;

[0036] Figure 8 In vitro degradation of the hemostatic hydrogel prepared in Example 5 of the present invention;

[0037] Figure 9 In vitro degradation of the hemostatic hydrogel prepared in Example 8 of the present invention;

[0038] Figure 10 Results of the cytotoxicity experiment of the hemostatic hydrogel prepared in Example 5 of the present invention;

[0039] Figure 11 Graph showing the results of the cytotoxicity experiment of the anti-adhesion drug (anthocyanin) in the present invention on cells;

[0040] Figure 12 Electron microscope photographs of the cell adhesion test of the hemostatic hydrogel prepared in Example 12 and Example 33 of the present invention;

[0041] Figure 13 Confocal microscope photographs of the cell adhesion test of the hemostatic hydrogel prepared in Example 12 and Example 33 of the present invention. Detailed implementation manners

[0042] The principles and features of the present invention will be described below in conjunction with examples. The examples given are only for explaining the present invention and are not intended to limit the scope of the present invention. In the following paragraphs, the present invention will be described more specifically by way of example with reference to the accompanying drawings. The advantages and features of the present invention will be more clearly described according to the following description and the claims.

[0043] Construction of a liver trauma mouse model: Prepare multiple SD rats at 7 - 8 weeks of age. Anesthetize the SD rats with a 2 wt% sodium pentobarbital solution at a standard injection concentration of 0.2 mL / 100 g by weight. After the SD rats are anesthetized, make a model by transverse incision at the liver site through laparotomy to obtain a liver trauma mouse model. Immediately after the construction of the liver trauma mouse model, inject the corresponding hemostatic hydrogel into the trauma site of the liver to observe the hemostatic ability.

[0044] The double-network structure and hemostatic principle of the hemostatic hydrogel are as Figure 1 shown (the cross-linking agent reacts with the amino polymer to form a Schiff base reaction, cross-linking to form the first layer of rapid cross-linking network structure. At the same time, the reactive compound also undergoes an amidation reaction with the amino polymer and the amino groups at the wound surface (generating NHS-ester) to form the second layer of adhesive cross-linking network structure).

[0045] Example 1

[0046] This example provides a hemostatic hydrogel, and its preparation method is as follows:

[0047] Component A is an aqueous deionized solution of carboxymethyl chitosan (CMC) with a concentration of 3 wt%;

[0048] Component B: glutaraldehyde is dissolved in deionized water to prepare a crosslinker solution with a concentration of 1 wt% (corresponding to the crosslinker concentration in Table 1), an anti-tissue adhesion drug (anthocyanidin) is dissolved in the crosslinker solution, and the concentration of the anti-tissue adhesion drug in the crosslinker solution is 10 μM (corresponding to the anti-tissue adhesion drug concentration in Table 1), 4arm-PEG-SG is dissolved in deionized water to prepare a reactive compound solution with a concentration of 12 wt% (corresponding to the reactive compound concentration in Table 1), and the crosslinker solution containing the anti-tissue adhesion drug is mixed with the reactive compound solution in a volume ratio of 1:1 to obtain component B;

[0049] The component A and the component B are mixed in a volume ratio of 1:1 to obtain an in situ cross-linked hemostatic hydrogel.

[0050] The formulas of Examples 2-33 and Comparative Examples 1-4 are shown in Table 1. Specifically, the process steps of Examples 2-33 and Comparative Examples 1-4 are the same as those of Example 1, and the only difference is the raw material ratio and process parameters. Among them, the volume ratio of component A to component B in Examples 16 to 18 in Table 1 is 1:1, and the volume ratio of component A to component B in the remaining examples and comparative examples is 4:1. Among them, the first solvent of Example 9 is a PBS solution with a pH of 7.4, the first solvent of Example 10 is a PBS solution with a pH of 8.4, and the first solvents of the remaining examples and comparative examples are all deionized water; the second solvent of Example 10 is a PBS solution with a pH of 5.6, and the second solvents of the remaining examples and comparative examples are all deionized water.

[0051] Table 1: Formula table of Example 2-Example 33 and Comparative Example 1-Comparative Example 4

[0052]

[0053]

[0054] Note: "None" in the table means that this item is not added; the serial numbers "Example 2" and "Comparative Example 1" in the table respectively represent "Example 2" and "Comparative Example 1", and the rest of the serial numbers are deduced by analogy; the amino polymer polymer in each example and comparative example is carboxymethyl chitosan (CMC), and the photos of the cross-linked hemostatic hydrogels of Example 1, Example 2, Example 20 and Example 25 coated on transparent glass are shown in FIG. Figure 2 As shown, Examples 2-15, 19-22, 24, 25, 30-33 can all be used for liver hemostasis, Examples 16-18 and 23 can all be used for abdominal adhesion prevention, Examples 26-29 can all be used for abdominal and uterine adhesion prevention, while the hydrogels prepared in Comparative Examples 1-4 are hard and brittle (they cannot be used as hemostatic hydrogels).

[0055] Performance Test

[0056] Test 1: Demonstration of Hemostatic Ability of Hemostatic Hydrogel

[0057] The hemostatic hydrogels prepared in Example 5 and Example 25 were respectively used to conduct a hemostasis experiment on a rat model with liver trauma (immediately after the establishment of the rat model with liver trauma, the prepared hemostatic hydrogel was injected into the liver wound site through a double-tube syringe to observe the hemostatic ability). The hemostatic photos corresponding to Example 5 are shown in Figure 3 as shown, and the hemostatic photos corresponding to Example 25 are shown in Figure 4 as shown. The hemostasis results of the two are shown in Table 2:

[0058] Table 2 Hemostasis Results of Hemostatic Hydrogels Corresponding to Example 5 and Example 25

[0059]

[0060] From Table 2,[[]] Figure 3 and Figure 4 the results show that the hemostatic hydrogels prepared in Example 5 and Example 25 have a certain ability to stop bleeding in the livers of SD rats, and the hemostatic time is relatively fast, and they can quickly stop bleeding within 4 - 9 s.

[0061] Test 2: Observation of 30-day Degradation Experiment of Hemostatic Hydrogel

[0062] An in vitro degradation experiment was conducted on the hemostatic hydrogels of Examples 1 - 33 and Comparative Examples 1 - 4. 200 mg of the hemostatic hydrogel sample was accurately weighed, and the sample was immersed in PBS aqueous solution with a volume 100 times and pH = 7.4, and placed in a constant temperature shaking water bath at 37 °C. The PBS solution was changed every one to two days, and the in vitro degradation of the hemostatic hydrogel within 30 days was observed. The results are shown in Table 3.

[0063] Table 3 30-day Degradation Conditions of Hemostatic Hydrogels Corresponding to Each Example and Each Control Example

[0064]

[0065] It can be seen from Table 3 that no obvious degradation was found in the hemostatic hydrogels prepared in the examples and the control examples within 30 days. Among them Figure 8 and Figure 9 it can be concluded that the degradation time of the hemostatic hydrogels prepared in Example 8 and Example 5 is greater than 90 days.

[0066] Test 3: Rheological Test of Hemostatic Hydrogel

[0067] Using the Advanced Rheometer AR2000ex from TA Instruments, USA, in air at 25 °C, in parallel plate mode (gap size = 1 mm), the linear viscoelastic region and the results of alternating strain scanning of the hemostatic hydrogel prepared in Example 4 were tested.

[0068] Test method for the linear viscoelastic region: The changes in G′ (storage modulus), G″ (loss modulus), and the viscosity of the hemostatic hydrogel with increasing shear strain were observed when the shear strain was gradually increased from a small shear strain of 0.1% to a shear strain of 1000%. The test results are shown in Figure 5 the figure.

[0069] Test method for alternating strain scanning: The hemostatic hydrogel sample was subjected to alternating strain testing at a frequency of 1 Hz, starting at a small shear strain (0.1%, 100 s), and then increasing to the point where the hemostatic hydrogel ruptured (1000%, 100 s), repeating twice, and recording the test results. The test results are shown in Figure 6 the figure.

[0070] Figure 5 The results show that within the linear viscoelastic region, the storage modulus (G') is greater than the loss modulus (G”), showing the characteristics of a gel; Figure 6 The results show that at a small amplitude strain (0.1%), the storage modulus (G') is greater than the loss modulus (G”), and the hemostatic hydrogel shows a semi-solid state dominated by elasticity; as the strain increases, G' decreases rapidly, while G” first increases, indicating that the gel network is damaged after being subjected to large amplitude strain oscillations, and the state of the fluid changes from being dominated by elasticity to being dominated by viscosity.

[0071] Test Four: H&E Staining

[0072] For the hemostatic hydrogels prepared in Example 4 and Example 5, H&E section staining was performed on the liver of a rat model with liver trauma 55 days after liver hemostasis, and the state of hepatocytes and the presence or absence of inflammation were observed. The results are shown in Figure 7 the figure.

[0073] Figure 7 The results show that the hepatocytes are round and full; the hepatic sinusoids are not significantly dilated or compressed; no obvious infiltration of inflammatory cells is seen.

[0074] Test Five: Cytotoxicity Test

[0075] Take 5 mg of the hemostatic hydrogel prepared in Example 5, expose it to ultraviolet light for 30 minutes, then add it to 50 mL of complete medium, and soak it at 4 °C for 6 hours to obtain an extract. Filter the extract using a 0.22 μm bacterial filter, and the concentration of the extract is 100 mg / L. Further dilute the extract with complete medium to obtain concentrations of 10 mg / L and 1 mg / L for subsequent use. In a 24-well plate at 2×104 Cells / well and 1×10 4 Cells / well were seeded (co-cultured with the hemostatic hydrogel extract for 24 hours and 48 hours respectively). After overnight culture, extracts at different concentrations were added to the wells, and after co-culture for 24 hours and 48 hours, the absorbance was measured at 450 nm using CCK-8 reagent. The test results are shown in Figure 10 as follows.

[0076] It can be seen from the Figure 10 results (CON in the figure is the control group without adding hydrogel) that for the hemostatic hydrogel prepared in Example 5, the cell viability was above 90% after co-culture with cells for 24 hours and above 70% after co-culture for 48 hours, indicating that the hemostatic hydrogel prepared in Example 5 has low cytotoxicity.

[0077] A complete medium containing anthocyanin was prepared with the concentration of anthocyanin being 10 μM. The complete medium was filtered through a 0.22 μm bacterial filter for subsequent use. Cells were seeded in a 24-well plate at a density of 1×10 4 Cells / well. After overnight incubation until the cells were completely adherent, the complete medium containing anthocyanin was added and cultured for 48 hours. Then, it was observed and photographed under a microscope. The test results are shown in Figure 11 as follows.

[0078] It can be seen from the Figure 11 results (where the Control group is the control group without adding anthocyanin) that after co-culture with cells for 48 hours, the cells adhered, had good morphology, and normal proliferation, indicating that anthocyanin has good biocompatibility and can be added to the cross-linked network as an anti-adhesion drug.

[0079] Test Six: Cell Anti-adhesion Test

[0080] L929 cells were cultured in DMEM medium containing 10 wt% bovine serum until the logarithmic growth phase. Before the adhesion experiment on cells L929, the cells were digested with trypsin, the digestion was terminated with serum-containing medium, and then the cells were washed with serum-free medium and resuspended to prepare a cell suspension. The hemostatic hydrogels prepared in Example 12 and Example 33 were injected into a 24-well plate and gelled, sterilized with 365 nm ultraviolet light for 30 minutes. The prepared cell suspension was evenly seeded into the well plate containing the hemostatic hydrogel, an appropriate amount of cell suspension was added to each well, and the cell state was observed under an electron microscope. Then the well plate was placed in an incubator at 37 °C with 5 vol% CO2 for 4 hours. After incubation, the well plate was taken out, the cell adhesion on the surface of the sample was observed using an electron microscope, and then the surface of the sample was gently washed with PBS buffer to remove the non-adherent cells. The cell adhesion on the surface of the sample was observed using an electron microscope. The results are shown inFigure 12 , the cell adhesion was observed using a confocal microscope, and the results are shown in Figure 13 .

[0081] From Figure 12 and Figure 13 's results (where the blank group did not add any hydrogel), it can be concluded that the hemostatic hydrogels prepared in Example 33 and Example 12 showed no cell adhesion, indicating that the hemostatic hydrogels prepared in this example have strong cell anti-adhesion ability without adding anti-tissue adhesion drugs.

[0082] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims

1. A preparation method of an anti-adhesion hemostatic hydrogel, characterized in that: Dissolve an amino polymer in a first solvent to obtain component A; Dissolve a crosslinking agent, a reactive compound and an anti-tissue adhesion drug in a second solvent to obtain component B; Among them, the crosslinking agent is a dialdehyde compound, and the reactive compound contains an NHS group; Before use, mix component A and component B, and then they can be crosslinked in situ to obtain the anti-adhesion hemostatic hydrogel.

2. The preparation method of the anti-adhesion hemostatic hydrogel according to claim 1, characterized in that: The volume ratio of component A to component B is 10:1 - 100.

3. The preparation method of the anti-adhesion hemostatic hydrogel according to claim 1, characterized in that: The solid content of the anti-adhesion hemostatic hydrogel is 0.5 - 35 wt%.

4. The preparation method of the anti-adhesion hemostatic hydrogel according to claim 1, characterized in that: Component A meets at least one of the following conditions A1 - C1: A1: The amino polymer is at least one of gelatin, chitosan, carboxymethyl chitosan, 2arm-PEG-NH2, 4arm-PEG-NH2, 8arm-PEG-NH2, linear polyethyleneimine, branched polyethyleneimine, poly-L-lysine, polyamidoamine dendrimer-G1, poly-L-histidine, poly(β-aminoester), poly(N,N-dimethylaminoethyl methacrylate), poly{2-[(2-aminoethyl)amino]ethyl aspartate} and poly(2-aminoethyl vinyl phosphate); B1: The first solvent is at least one of deionized water, secondary distilled water, ultrapure water, sodium carbonate-sodium bicarbonate buffer solution, PBS buffer solution, phosphate buffer solution and disodium hydrogen phosphate-citric acid buffer solution; C1: The mass concentration of the amino polymer in component A is 0.1 - 35.0 wt%.

5. The preparation method of the anti-adhesion hemostatic hydrogel according to claim 1, characterized in that: Component B meets at least one of the following conditions A2 - G2: A2: The crosslinking agent is at least one of glyoxal, malonaldehyde, succinaldehyde, glutaraldehyde, adipic dialdehyde, pimelic dialdehyde, suberic dialdehyde, azelaic dialdehyde, sebacic dialdehyde, methylmalonaldehyde, dimethylmalonaldehyde and methylbutanedial; B2: The reactive compound is at least one of 2arm-PEG-SS, 4arm-PEG-SS, 8arm-PEG-SS, 2arm-PEG-SC, 4arm-PEG-SC, 8arm-PEG-SC, 2arm-PEG-SG, 4arm-PEG-SG, 8arm-PEG-SG, NHS-modified sodium alginate, NHS-modified polypeptide and NHS-modified sodium hyaluronate; C2: The anti-tissue adhesion drug includes at least one of tissue plasminogen activator, heparin, hepatocyte growth factor, anthocyanin, methylene blue and vitamin E; D2: The mass concentration of the reactive compound in component B is 0.5 - 35.0 wt%; E2: The mass concentration of the crosslinking agent in component B is 0.1 - 10.0 wt%; F2: The molar concentration of the anti-tissue adhesion drug in component B is 0.1 - 200 μM; G2: The second solvent is at least one of deionized water, secondary distilled water, ultrapure water, sodium carbonate-sodium bicarbonate buffer solution, PBS buffer solution, phosphate buffer solution and disodium hydrogen phosphate-citric acid buffer solution.

6. The preparation method of the anti-adhesion hemostatic hydrogel according to claim 5, characterized in that: The NHS-modified sodium alginate is obtained by modifying sodium alginate with a compound containing an NHS group in the presence of EDC / EDCI; the NHS-modified polypeptide is obtained by modifying a polypeptide substance with a compound containing an NHS group in the presence of EDC / EDCI; The NHS-modified sodium hyaluronate is obtained by modifying sodium hyaluronate with a compound containing an NHS group in the presence of EDC / EDCI.

7. The preparation method of the anti-adhesion hemostatic hydrogel according to claim 6, characterized in that: The compound containing an NHS group is at least one of N-hydroxysuccinimide, disuccinimidyl glutarate, disuccinimidyl suberate, (+)-biotin-N-succinimidyl ester, N-hydroxysuccinimidyl laurate, N-hydroxysuccinimidyl acetoacetate, N-succinimidyl octanoate, N-succinimidyl hexanoate, N-hydroxysuccinimidyl acetate, and di(N-succinimidyl) sebacate.

8. The preparation method of the anti-adhesion hemostatic hydrogel according to claim 6, wherein: The polypeptide substance includes plant-derived polypeptides and animal-derived polypeptides; the plant-derived polypeptides include at least one of soy peptide, peanut peptide, corn peptide, pea peptide, rice peptide, linseed peptide, corn oligopeptide powder, and wheat oligopeptide powder; the animal-derived polypeptides include at least one of fish collagen peptide, bovine collagen peptide, bone collagen peptide, sea cucumber peptide, oyster peptide, and Antarctic krill peptide.

9. A non-adhesive hemostatic hydrogel, characterized in that, It is prepared by using the preparation method according to any one of claims 1-8.

10. Use of the anti-adhesion hemostatic hydrogel according to claim 9, characterized in that, It is used in the preparation of products for hemostasis, adhesion sealing, or anti-adhesion.

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