Wound flushing fluid for surgical operation and preparation method thereof

Abstract

The invention discloses wound flushing fluid for surgical operation and a preparation method of the wound flushing fluid, and belongs to the technical field of medical medicines. The wound flushing fluid for the surgical operation comprises microspheres and sterilized water, the microspheres are prepared by the following steps: S1, dissolving ellagic acid in a polar solvent, and dispersing in deionized water to obtain a dispersion liquid; adding polyethylene polyamine and PEG (Polyethylene Glycol) into the dispersion liquid, carrying out ultrasonic dissolution, and carrying out high-temperature reaction to obtain a reaction liquid; dialyzing, separating and centrifugally freeze-drying the reaction liquid to obtain ellagic acid / polyethylene polyamine / PEG (Polyethylene Glycol); s2, dissolving silk fibroin in deionized water, adding Tween 80, and uniformly stirring to obtain a mixed solution; and S3, adding ellagic acid / polyethylene polyamine / PEG in the step S1 into the mixed solution in the step S2, adding genipin, stirring in a dark place, centrifugally separating, washing and freeze-drying to obtain the microspheres. The microspheres can achieve the effects of penetrating through a biological membrane for sterilization and accelerating wound healing.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical drugs, and particularly relates to a wound irrigation solution for surgical operations and a preparation method thereof. Background Art

[0002] Wound irrigation is an important measure for wound management. Through physical irrigation, wound hydration is achieved, necrotic tissue and foreign bodies are removed, and conditions for intraoperative field observation are provided. Its cleaning efficiency is significantly higher than that of cotton swab wiping, and it can effectively remove cell debris, microorganisms and drug residues. Conventionally in surgery, sterile normal saline is used to maintain tissue homeostasis, but it has limitations in hemostasis, promoting wound healing and long-term antibacterial effects. Currently, the prevention and control of postoperative infections rely on systemic antibiotics, but the problem of drug resistance is severe: more than 1.2 million people die from antimicrobial resistance globally every year, and there are also defects such as liver and kidney toxicity and secondary infections caused by microecological disorders. Traditional irrigation solutions such as normal saline / Ringer's solution can maintain the cleanliness of the incision, but lack multifunctional treatment characteristics.

[0003] The research and development of new irrigation solutions need to integrate multiple mechanisms: ① activating the coagulation pathway to achieve rapid hemostasis; ② degrading the biofilm matrix to enhance antibacterial effects; ③ regulating macrophage polarization to accelerate tissue repair; ④ inhibiting inflammatory mediators to reduce exudation. The cutting-edge directions include temperature-sensitive chitosan hydrogels (maintaining a moist microenvironment at the wound surface), drug-loaded nanoparticles and metal ion composite solutions. These technological breakthroughs will promote the transformation of wound treatment from simple cleaning to functional treatment, and provide new strategies for solving complications such as postoperative infections and delayed wound healing. The patent application with the publication number CN 115634193 A discloses a preparation method, product and application of a surgical irrigation gel. In this application, water-soluble oxidized regenerated cellulose is produced by subjecting plant-derived fibers to controlled oxidation and etherification processes, and is formulated with lentinan, microcrystalline cellulose and injection water to form a surgical irrigation gel. The surgical irrigation gel of this application can be absorbed by tissues and can be used for chronic wound care. When formulated with normal saline in a certain proportion to irrigate the wound surface, it can effectively remove blood stains and tissue residues. However, the intermolecular interactions of different polysaccharides may exacerbate the instability of the system, and the antibacterial and antimicrobial effects are weak, which is likely to cause surgical incision infections. Summary of the Invention

[0004] The purpose of the present invention is to provide a wound irrigation solution for surgical operations and a preparation method thereof, which can penetrate the biofilm to kill bacteria and accelerate wound healing.

[0005] The purpose of the present invention can be achieved through the following technical solutions:

[0006] A wound irrigation solution for surgical operations, comprising microspheres and sterilized water;

[0007] The microspheres are prepared by the following steps:

[0008] S1. Dissolve ellagic acid in a polar solvent and disperse it in deionized water to obtain a dispersion; add polyethylene polyamine and PEG to the dispersion, dissolve it by ultrasonic treatment, and react at high temperature to obtain a reaction solution; separate the reaction solution by dialysis, centrifuge and freeze-dry it to obtain ellagic acid / polyethylene polyamine / PEG;

[0009] S2. Dissolve silk fibroin in deionized water, add Tween 80, and stir evenly to obtain a mixed solution;

[0010] S3. Add the ellagic acid / polyethylene polyamine / PEG in S1 to the mixed solution in S2, add genipin, stir in the dark, centrifuge and separate, wash and freeze-dry to obtain microspheres.

[0011] Furthermore, the microspheres are ellagic acid / polyethylene polyamine / PEG@silk fibroin; the dosage ratio of the microspheres to sterilized water is (5 - 10) g : (90 - 110) mL.

[0012] Furthermore, the dosage ratio of ellagic acid, polar solvent, deionized water, polyethylene polyamine and PEG in S1 is (1 - 2.5) g : (0.5 - 1) mL : (50 - 60) mL : (10 - 15) g : (5 - 7) g.

[0013] Furthermore, the polar solvent is one or a combination of DMSO, acetone, methanol and ethanol.

[0014] Furthermore, the dosage ratio of silk fibroin, deionized water, Tween 80 and genipin in S2 is (3 - 6) g : (90 - 110) mL : (0.05 - 0.2) g : (0.4 - 0.8) g.

[0015] The free radical scavenging ability of ellagic acid is 10 times that of vitamin C. In terms of anti-cancer, it inhibits the proliferation of cancer cells (such as colon cancer HT-29 cells), and at the same time has good anti-inflammatory and antioxidant functions. The main limitation is its poor water solubility and low bioavailability. To solve the problem of poor water solubility, existing technologies have used nano-encapsulation technology for improvement.

[0016] Furthermore, the PEG is one or a combination of PEG400, PEG800 and PEG1500.

[0017] Furthermore, the high-temperature reaction is carried out at 180 - 200 °C for 5 - 6 h.

[0018] Furthermore, the specification of the dialysis bag used for dialysis is 1.2 - 1.5 kDa.

[0019] Furthermore, the centrifugation in S1 is carried out at a rotation speed of 10000 - 12,000 rpm for 10 - 15 min.

[0020] Further, the light-shielding stirring is carried out at room temperature in a light-shielded environment for 12 - 24 h.

[0021] Further, the centrifugal separation in S2 is carried out at a rotation speed of 3000 - 5000 rpm for 5 - 10 min.

[0022] Further, the freeze-drying is carried out at -80 °C for 18 - 24 h.

[0023] A preparation method of a wound irrigation solution for surgical operations, comprising the following steps:

[0024] Mix the microspheres and sterilized water evenly at room temperature, adjust the pH, and store in the dark to obtain a wound irrigation solution for surgical operations.

[0025] Further, the pH is adjusted to 6.5 - 7.5.

[0026] Advantages of the present invention:

[0027] (1) The preparation method of a wound irrigation solution for surgical operations provided by the present invention has a simple preparation process and easily available raw materials; the prepared wound irrigation solution contains microspheres that can penetrate the biofilm to sterilize and accelerate wound healing.

[0028] (2) The microspheres used in the present invention are ellagic acid / polyethylene polyamine / PEG@silk fibroin. The ellagic acid therein can destroy the integrity of the bacterial cell membrane; due to the thermal stability of ellagic acid, ellagic acid can form a polymer with polyethylene polyamine and PEG; the dense amino groups on the polyethylene polyamine molecular chain endow it with a high-density positive charge, which can penetrate the biofilm through electrostatic adsorption and bind to the negatively charged bacterial cell membrane to destroy the membrane integrity; at the same time, it can combine with silk fibroin to form a more stable structure (silk fibroin is negatively charged at normal pH values). In addition, in the wound microenvironment (slightly acidic environment), the serine and glycine released by silk fibroin can promote the migration of fibroblasts and accelerate wound healing. In summary, the microspheres provided by the present invention have the ability to destroy bacterial biofilms and DNA, induce bacteria to produce reactive oxygen species, thereby producing a broad-spectrum antibacterial effect and also having good biocompatibility. In addition, the risk of drug resistance is avoided, and it has a dual mechanism of physical membrane rupture and biological activity repair. Specific embodiments

[0029] The following describes the specific embodiments of the present invention in detail, but it should be understood that the protection scope of the present invention is not limited by the specific embodiments.

[0030] Example 1

[0031] This example provides a wound irrigation solution for surgical operations, which is prepared by the following steps:

[0032] S1. Dissolve 1.5 g of ellagic acid in 1 mL of DMSO, and then disperse it in 60 mL of deionized water to obtain a dispersion; add 12 g of polyethylene polyamine and 6 g of PEG400 to the dispersion, ultrasonically dissolve it completely, and react at 180 °C for 6 h to obtain a reaction solution; dialyze and separate the reaction solution with a 1.5 kDa dialysis bag, centrifuge at a rotation speed of 12,000 rpm for 10 min in a centrifuge, and freeze-dry to obtain ellagic acid / polyethylene polyamine / PEG;

[0033] S2. Dissolve 4 g of silk fibroin in 100 mL of deionized water, add 0.1 g of Tween 80, and stir evenly to obtain a mixed solution;

[0034] S3. Add the ellagic acid / polyethylene polyamine / PEG in S1 to the mixed solution in S2, add 0.6 g of genipin, stir for 24 h in a normal temperature and light-proof environment, separate at a rotation speed of 3000 rpm for 10 min, wash, and freeze-dry at -80 °C for 24 h with a freeze dryer to obtain microspheres;

[0035] S4. Mix 8 g of microspheres and 100 mL of sterilized water evenly at normal temperature, adjust the pH to 7.0, and store in the dark to obtain a wound irrigation solution for surgical operations.

[0036] Example 2

[0037] The difference between this example and Example 1 is that "8 g of microspheres and 100 mL of sterilized water" is changed to "10 g of microspheres and 90 mL of sterilized water", and the specific implementation steps are as follows:

[0038] S1. Dissolve 1.5 g of ellagic acid in 1 mL of DMSO, and then disperse it in 60 mL of deionized water to obtain a dispersion; add 12 g of polyethylene polyamine and 6 g of PEG400 to the dispersion, ultrasonically dissolve it completely, and react at 180 °C for 6 h to obtain a reaction solution; dialyze and separate the reaction solution with a 1.5 kDa dialysis bag, centrifuge at a rotation speed of 12,000 rpm for 10 min in a centrifuge, and freeze-dry to obtain ellagic acid / polyethylene polyamine / PEG;

[0039] S2. Dissolve 4 g of silk fibroin in 100 mL of deionized water, add 0.1 g of Tween 80, and stir evenly to obtain a mixed solution;

[0040] S3. Add the ellagic acid / polyethylene polyamine / PEG in S1 to the mixed solution in S2, add 0.6 g of genipin, stir for 24 h in a normal temperature and light-proof environment, separate at a rotation speed of 3000 rpm for 10 min, wash, and freeze-dry at -80 °C for 24 h with a freeze dryer to obtain microspheres;

[0041] S4. Mix 10 g of microspheres and 90 mL of sterilized water evenly at room temperature, adjust the pH to 7.0, and store in the dark to obtain a wound irrigation solution for surgical operations.

[0042] The remaining raw materials and the preparation process are the same as those in Example 1.

[0043] Example 3

[0044] Compared with Example 1, the difference in this example is that "8 g of microspheres and 100 mL of sterilized water" is changed to "5 g of microspheres and 110 mL of sterilized water". The specific implementation steps are as follows:

[0045] S1. Dissolve 1.5 g of ellagic acid in 1 mL of DMSO, and then disperse it in 60 mL of deionized water to obtain a dispersion; add 12 g of polyethylene polyamine and 6 g of PEG400 to the dispersion, react at 180 °C for 6 h after ultrasonic dissolution is complete to obtain a reaction solution; dialyze and separate the reaction solution with a 1.5 kDa dialysis bag, centrifuge at a rotation speed of 12,000 rpm for 10 min in a centrifuge, and freeze-dry to obtain ellagic acid / polyethylene polyamine / PEG;

[0046] S2. Dissolve 4 g of silk fibroin in 100 mL of deionized water, add 0.1 g of Tween 80, and stir evenly to obtain a mixed solution;

[0047] S3. Add the ellagic acid / polyethylene polyamine / PEG in S1 to the mixed solution in S2, add 0.6 g of genipin, stir for 24 h in a dark environment at room temperature, separate at a rotation speed of 3000 rpm for 10 min, wash, and freeze-dry at -80 °C for 24 h with a freeze-dryer to obtain microspheres;

[0048] S4. Mix 5 g of microspheres and 110 mL of sterilized water evenly at room temperature, adjust the pH to 7.0, and store in the dark to obtain a wound irrigation solution for surgical operations.

[0049] The remaining raw materials and the preparation process are the same as those in Example 1.

[0050] Example 4

[0051] Compared with Example 1, the difference in this example is mainly to reduce the amount of ellagic acid and increase the amount of silk fibroin at the same time. The specific implementation steps are as follows:

[0052] S1. Dissolve 1 g of ellagic acid in 1 mL of DMSO, and then disperse it in 60 mL of deionized water to obtain a dispersion; add 15 g of polyethylene polyamine and 7 g of PEG400 to the dispersion, ultrasonically dissolve it completely, and react at 180 °C for 6 h to obtain a reaction solution; dialyze and separate the reaction solution with a 1.5 kDa dialysis bag, centrifuge at a rotation speed of 12,000 rpm in a centrifuge for 10 min, and freeze-dry to obtain ellagic acid / polyethylene polyamine / PEG;

[0053] S2. Dissolve 6 g of silk fibroin in 100 mL of deionized water, add 0.15 g of Tween 80, and stir evenly to obtain a mixed solution;

[0054] S3. Add the ellagic acid / polyethylene polyamine / PEG in S1 to the mixed solution in S2, add 0.8 g of genipin, stir in a normal temperature and light-proof environment for 24 h, separate by rotating at a speed of 3000 rpm for 10 min, wash, and freeze-dry at -80 °C for 24 h with a freeze dryer to obtain microspheres;

[0055] S4. Mix 8 g of microspheres and 100 mL of sterilized water evenly at normal temperature, adjust the pH to 7.0, and store in the dark to obtain a wound irrigation solution for surgical operations.

[0056] The remaining raw materials and the preparation process are the same as those in Example 1.

[0057] Example 5

[0058] Compared with Example 1, the difference in this example is mainly to increase the amount of ellagic acid and reduce the amount of silk fibroin at the same time. The specific implementation steps are as follows:

[0059] S1. Dissolve 2.5 g of ellagic acid in 1 mL of DMSO, and then disperse it in 60 mL of deionized water to obtain a dispersion; add 10 g of polyethylene polyamine and 5 g of PEG400 to the dispersion, ultrasonically dissolve it completely, and react at 180 °C for 6 h to obtain a reaction solution; dialyze and separate the reaction solution with a 1.5 kDa dialysis bag, centrifuge at a rotation speed of 12,000 rpm in a centrifuge for 10 min, and freeze-dry to obtain ellagic acid / polyethylene polyamine / PEG;

[0060] S2. Dissolve 3 g of silk fibroin in 100 mL of deionized water, add 0.05 g of Tween 80, and stir evenly to obtain a mixed solution;

[0061] S3. Add the ellagic acid / polyethylene polyamine / PEG in S1 to the mixed solution in S2, add 0.4 g of genipin, stir in a normal temperature and light-proof environment for 24 h, separate by rotating at a speed of 3000 rpm for 10 min, wash, and freeze-dry at -80 °C for 24 h with a freeze dryer to obtain microspheres;

[0062] S4. Mix 8 g of microspheres and 100 mL of sterilized water evenly at room temperature, adjust the pH to 7.0, and store in the dark to obtain a wound irrigation solution for surgical operations.

[0063] The remaining raw materials and the preparation process are the same as those in Example 1.

[0064] Example 6

[0065] Compared with Example 1, the difference in this example is that the polar solvent is replaced with methanol. The specific implementation steps are as follows:

[0066] S1. Dissolve 1.5 g of ellagic acid in 1 mL of methanol, and then disperse it in 60 mL of deionized water to obtain a dispersion; add 12 g of polyethylene polyamine and 6 g of PEG400 to the dispersion, react at 180 °C for 6 h after ultrasonic dissolution is complete to obtain a reaction solution; dialyze and separate the reaction solution with a 1.5 kDa dialysis bag, centrifuge at a rotation speed of 12,000 rpm in a centrifuge for 10 min, and freeze-dry to obtain ellagic acid / polyethylene polyamine / PEG;

[0067] S2. Dissolve 4 g of silk fibroin in 100 mL of deionized water, add 0.1 g of Tween 80, and stir evenly to obtain a mixed solution;

[0068] S3. Add the ellagic acid / polyethylene polyamine / PEG in S1 to the mixed solution in S2, add 0.6 g of genipin, stir in the dark at room temperature for 24 h, separate at a rotation speed of 3000 rpm for 10 min, wash, and freeze-dry at -80 °C for 24 h with a freeze-dryer to obtain microspheres;

[0069] S4. Mix 8 g of microspheres and 100 mL of sterilized water evenly at room temperature, adjust the pH to 7.0, and store in the dark to obtain a wound irrigation solution for surgical operations.

[0070] The remaining raw materials and the preparation process are the same as those in Example 1.

[0071] Comparative Example 1

[0072] Compared with Example 1, the difference in this comparative example is that silk fibroin is not added. The specific implementation steps are as follows:

[0073] S1. Dissolve 1.5 g of ellagic acid in 1 mL of DMSO, and then disperse it in 60 mL of deionized water to obtain a dispersion; add 12 g of polyethylene polyamine and 6 g of PEG400 to the dispersion, react at 180 °C for 6 h after ultrasonic dissolution is complete to obtain a reaction solution; dialyze and separate the reaction solution with a 1.5 kDa dialysis bag, centrifuge at a rotation speed of 12,000 rpm in a centrifuge for 10 min, and freeze-dry to obtain ellagic acid / polyethylene polyamine / PEG;

[0074] S2. Mix 8 g of ellagic acid / polyethylene polyamine / PEG and 100 mL of sterilized water evenly at room temperature, adjust the pH to 7.0, and store in the dark to obtain a wound irrigation solution for surgical operations.

[0075] The remaining raw materials and the preparation process are the same as those in Example 1.

[0076] Comparative Example 2

[0077] Compared with Example 1, this comparative example is different in that no polyethylene polyamine is added. The specific implementation steps are as follows:

[0078] S1. Dissolve 1.5 g of ellagic acid in 1 mL of DMSO, and then disperse it in 60 mL of deionized water to obtain a dispersion; add 6 g of PEG400 to the dispersion, ultrasonically dissolve it completely, and react at 180 °C for 6 h to obtain a reaction solution; dialyze and separate the reaction solution with a 1.5 kDa dialysis bag, centrifuge at a rotation speed of 12,000 rpm in a centrifuge for 10 min, and lyophilize to obtain ellagic acid / PEG;

[0079] S2. Dissolve 4 g of silk fibroin in 100 mL of deionized water, add 0.1 g of Tween 80, and stir evenly to obtain a mixed solution;

[0080] S3. Add the ellagic acid / PEG in S1 to the mixed solution in S2, add 0.6 g of genipin, stir in the dark at room temperature for 24 h, separate at a rotation speed of 3000 rpm for 10 min, wash, and lyophilize at -80 °C for 24 h with a lyophilizer to obtain microspheres;

[0081] S4. Mix 8 g of microspheres and 100 mL of sterilized water evenly at room temperature, adjust the pH to 7.0, and store in the dark to obtain a wound irrigation solution for surgical operations.

[0082] The remaining raw materials and the preparation process are the same as those in Example 1.

[0083] Comparative Example 3

[0084] Compared with Example 1, this comparative example is different in that neither polyethylene polyamine nor silk fibroin is added. The specific implementation steps are as follows:

[0085] S1. Dissolve 1.5 g of ellagic acid in 1 mL of DMSO, and then disperse it in 60 mL of deionized water to obtain a dispersion; add 6 g of PEG400 to the dispersion, ultrasonically dissolve it completely, and react at 180 °C for 6 h to obtain a reaction solution; dialyze and separate the reaction solution with a 1.5 kDa dialysis bag, centrifuge at a rotation speed of 12,000 rpm in a centrifuge for 10 min, and lyophilize to obtain ellagic acid / PEG;

[0086] S2. Mix 8 g of ellagic acid / PEG and 100 mL of sterilized water evenly at room temperature, adjust the pH to 7.0, and store in the dark to obtain a wound irrigation solution for surgical operations.

[0087] The remaining raw materials and the preparation process are the same as those in Example 1.

[0088] Comparative Example 4

[0089] Compared with Example 1, this comparative example is characterized in that no polyethylene polyamine and PEG are added. The specific implementation steps are as follows:

[0090] S1. Dissolve 1.5 g of ellagic acid in 1 mL of DMSO, and then disperse it in 60 mL of deionized water to obtain a dispersion;

[0091] S2. Dissolve 4 g of silk fibroin in 100 mL of deionized water, add 0.1 g of Tween 80, and stir evenly to obtain a mixed solution;

[0092] S3. Add the dispersion in S1 to the mixed solution in S2, add 0.6 g of genipin, stir for 24 h in a dark environment at room temperature, centrifuge at a rotation speed of 3000 rpm for 10 min, wash, and freeze-dry at -80 °C for 24 h using a freeze dryer to obtain microspheres;

[0093] S4. Mix 8 g of microspheres and 100 mL of sterilized water evenly at room temperature, adjust the pH to 7.0, and store in the dark to obtain a wound irrigation solution for surgical operations.

[0094] The remaining raw materials and the preparation process are the same as those in Example 1.

[0095] Comparative Example 5

[0096] This comparative example is a blank control, and the irrigation solution used is normal saline with a concentration of 0.9%.

[0097] Performance test

[0098] Perform performance tests on the wound irrigation solutions for surgical operations prepared in Examples 1 - 6 and Comparative Examples 1 - 5 as follows:

[0099] Antibacterial rate (%): Test the antibacterial rate of the wound irrigation solution according to GB 38456-2020 "Hygienic Requirements for Antibacterial and Bacteriostatic Lotions";

[0100] Degree of wound healing (%): Cut a circular wound with a diameter of about 3 cm on the back of mice (3 mice in each group, weighing 22 ± 2 g); irrigate with the irrigation solution once every 24 hours; observe the wound healing situation of diabetic rats, record the degree of wound healing (Table 1 shows the degree of healing on the 14th day), and calculate the average value;

[0101] Hemostasis time (s): After anesthetizing the mice (3 mice per group, body weight 22 ± 2 g) intraperitoneally, cut off 1 cm of the mouse tail. When bleeding, slightly compress the experimental group with absorbent cotton gauze attached with the rinsing solution, and start timing at the same time until the bleeding from the wound stops. Record the bleeding time and calculate the average value.

[0102] The results are shown in Table 1:

[0103] Table 1

[0104]

[0105]

[0106] As can be seen from Table 1, compared with Example 1, the differences in Examples 2 - 6 are only that the raw materials and the replacement and change of the raw material ratio are within a reasonable range. Judging from the test data, the prepared wound rinsing solution has excellent antibacterial properties, with an antibacterial rate > 90.0%; the wound healing degree at 14 days ≥ 82.9%; the hemostasis time ≤ 83 s; and it has excellent hemostasis and wound healing promotion functions.

[0107] Compared with Example 1, after not adding silk fibroin in Comparative Example 1, the wound healing promotion and hemostasis performance decreased significantly; compared with Example 1 in Comparative Example 2, the antibacterial effect decreased due to the non - addition of polyethylene polyamine; combining Comparative Examples 1 - 2 in Comparative Example 3 would lead to a decrease in antibacterial and wound healing promotion performance; compared with Example 1 in Comparative Example 4, after not adding polyethylene polyamine and PEG, the dispersibility of ellagic acid was very poor, which would lead to uneven dispersion in the rinsing solution; in addition, polyethylene polyamine is positively charged and silk fibroin is negatively charged, which is more conducive to binding and improving the stability of the microspheres.

[0108] The above - disclosed are only several specific embodiments of the present invention. However, the embodiments of the present invention are not limited thereto, and any changes that can be thought of by those skilled in the art should fall within the protection scope of the present invention.

Claims

1. A wound irrigation solution for surgical operations, characterized in that, It includes microspheres and sterilized water; The microspheres are prepared by the following steps: S1. Dissolve ellagic acid in a polar solvent, disperse it in deionized water to obtain a dispersion; add polyethylene polyamine and PEG to the dispersion, ultrasonically dissolve it, and react at high temperature to obtain a reaction solution; dialyze and separate the reaction solution, centrifuge and freeze-dry it to obtain ellagic acid / polyethylene polyamine / PEG; S2. Dissolve silk fibroin in deionized water, add Tween 80, and stir evenly to obtain a mixed solution; S3. Add the ellagic acid / polyethylene polyamine / PEG in S1 to the mixed solution in S2, add genipin, stir in the dark, centrifuge and separate, wash and freeze-dry to obtain microspheres.

2. The wound irrigation solution for surgical operations according to claim 1, characterized in that, The microspheres are ellagic acid / polyethylene polyamine / PEG@silk fibroin; the dosage ratio of the microspheres to the sterilized water is (5 - 10) g : (90 - 110) mL.

3. The wound irrigation solution for surgical operations according to claim 1, characterized in that, The dosage ratio of ellagic acid, polar solvent, deionized water, polyethylene polyamine and PEG in S1 is (1 - 2.5) g : (0.5 - 1) mL : (50 - 60) mL : (10 - 15) g : (5 - 7) g.

4. The wound irrigation solution for surgical operations according to claim 1, characterized in that, The polar solvent is one or a combination of DMSO, acetone, methanol and ethanol.

5. The wound irrigation solution for surgical operations according to claim 1, characterized in that, The dosage ratio of silk fibroin, deionized water, Tween 80 and genipin in S2 is (3 - 6) g : (90 - 110) mL : (0.05 - 0.2) g : (0.4 - 0.8) g.

6. The wound irrigation solution for surgical operations according to claim 1, wherein The PEG is one or a combination of PEG400, PEG800 and PEG1500.

7. The wound irrigation fluid for surgical operations according to claim 1, characterized in that, The high-temperature reaction is carried out at 180 - 200 °C for 5 - 6 h; the specification of the dialysis bag used for dialysis is 1.2 - 1.5 kDa; the stirring in the dark is carried out for 12 - 24 h in a normal-temperature dark environment; the freeze-drying is carried out at -80 °C for 18 - 24 h.

8. The surgical wound irrigation solution according to claim 1, characterized in that, The centrifugation in S1 is carried out at a rotation speed of 10000 - 12,000 rpm for 10 - 15 min; the centrifugal separation in S2 is carried out at a rotation speed of 3000 - 5000 rpm for 5 - 10 min.

9. A method for preparing a wound irrigation solution for surgical operations according to any one of claims 1-8, characterized in that, It includes the following steps: Mix the microspheres and the sterilized water evenly at room temperature, adjust the pH, and store in the dark to obtain a wound irrigation solution for surgical operations.

10. The preparation method of a surgical wound irrigation solution according to claim 9, characterized in that, The pH is adjusted to 6.5 - 7.5.

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