Medical antibacterial repair hydrogel and preparation method thereof

Abstract

The invention discloses medical antibacterial repair hydrogel and a preparation method thereof, and belongs to the technical field of biomedical materials. The hydrogel is prepared by combining a mixed solution of polyvinyl alcohol and sodium carboxymethyl cellulose with modified antibacterial peptide and carrying out freezing-unfreezing circulation. The amino acid sequence of the modified antibacterial peptide is FLWLIPALAGIGKLIK-NH2, and the modified antibacterial peptide has remarkable antibacterial activity, can effectively inhibit growth of gram-negative bacteria, gram-positive bacteria and fungi, and particularly has a strong inhibition effect on escherichia coli, staphylococcus aureus and candida albicans. In addition, the hydrogel containing the antibacterial peptide shows an excellent repairing effect in a wound healing experiment, and the wound healing rate is remarkably increased. Therefore, the hydrogel provided by the invention not only has efficient antibacterial ability, but also can promote wound repair, and has wide clinical application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical materials, and in particular relates to a medical antibacterial repair hydrogel and a preparation method thereof. Background Art

[0002] Medical hydrogel is a hydrophilic polymer network material. Its unique physical and chemical properties, such as good biocompatibility, high water content and air permeability, enable it to provide a moist microenvironment for the wound site, reduce pain caused by external stimulation and dryness, and create favorable conditions for cell migration, proliferation and tissue repair. In view of the above advantages, medical hydrogel has been widely used in biomedical fields such as wound dressings, burn treatment, postoperative rehabilitation, drug delivery, and tissue engineering. It can effectively absorb wound exudate, reduce complications caused by exudate accumulation, and to a certain extent block the invasion of external pathogens, thereby relieving patients' pain, promoting wound healing, and improving healing quality.

[0003] However, traditional medical hydrogels still have certain limitations in wound care, especially in preventing and controlling bacterial infections. Due to their high water content, ordinary hydrogels can easily become a breeding ground for bacteria in a humid environment. If the growth of microorganisms cannot be effectively inhibited, it may cause or aggravate wound infection and delay the healing process. Therefore, the development of new medical hydrogels with excellent antibacterial properties is one of the key issues that need to be solved urgently. Summary of the invention

[0004] The purpose of the present invention is to provide a medical antibacterial repair hydrogel with high-efficiency antibacterial performance and a preparation method thereof.

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] In a first aspect, the present invention provides a method for preparing a medical antibacterial repair hydrogel, the method for preparing the medical antibacterial repair hydrogel comprising the following steps:

[0007] a) dissolving polyvinyl alcohol in a glycerol aqueous solution to obtain a polyvinyl alcohol solution;

[0008] b) dissolving sodium carboxymethyl cellulose in a glycerol aqueous solution to obtain a sodium carboxymethyl cellulose solution;

[0009] c) mixing the polyvinyl alcohol solution and the sodium carboxymethylcellulose solution in a volume ratio of 1:1 to obtain a PVA / Na-CMC solution;

[0010] d) dissolving the modified antimicrobial peptide in deionized water to obtain a modified antimicrobial peptide solution;

[0011] e) mixing the modified antimicrobial peptide solution and the PVA / Na-CMC solution at a volume ratio of 1:10 to obtain a PVA / Na-CMC solution containing the modified antimicrobial peptide;

[0012] f) transferring the PVA / Na-CMC solution containing the modified antimicrobial peptide to a freezing device for initial freezing to obtain a hydrogel containing the modified antimicrobial peptide;

[0013] g) taking out the hydrogel, thawing it at room temperature, and freezing it again to obtain the medical antibacterial repair hydrogel;

[0014] The amino acid sequence of the modified antimicrobial peptide is FLWLIPALAGAIGKLIK-NH2.

[0015] Preferably, the glycerol aqueous solution is a 50% glycerol aqueous solution;

[0016] The polyvinyl alcohol solution is a polyvinyl alcohol solution with a mass concentration of 10%;

[0017] The concentration of the modified antimicrobial peptide solution is greater than or equal to 0.5 mg / mL

[0018] The sodium carboxymethyl cellulose solution is a sodium carboxymethyl cellulose solution with a mass concentration of 1%;

[0019] The conditions for the primary freezing are freezing at -20°C for 8 hours, the thawing time at room temperature is 1 hour, and the conditions for the secondary freezing are freezing at -20°C for 8 hours.

[0020] Preferably, the concentration of the modified antimicrobial peptide solution is 0.5 mg / mL.

[0021] Preferably, the medical antibacterial agent inhibits Gram-negative bacteria, Gram-positive bacteria and fungi;

[0022] The repair is skin damage wound healing repair, and the skin damage includes mechanical damage, physical damage and chemical damage.

[0023] Preferably, the Gram-negative bacteria is Escherichia coli ATCC 25922, the Gram-positive bacteria is Staphylococcus aureus ATCC 25923, and the fungus is Candida albicans ATCC 10231.

[0024] Preferably, the skin injury is a mechanical injury, and the mechanical injury is a cut.

[0025] In a second aspect, the present invention provides a medical antibacterial repair hydrogel, which is prepared by the preparation method described above.

[0026] In a third aspect, the present invention provides an application of a modified antimicrobial peptide in the preparation of an antimicrobial agent or an antimicrobial hydrogel, characterized in that the amino acid sequence of the modified antimicrobial peptide is FLWLIPALAGAIGKLIK-NH2.

[0027] Preferably, the antibacterial agent has an antibacterial spectrum of Gram-negative bacteria, Gram-positive bacteria and fungi.

[0028] Preferably, the Gram-negative bacteria is Escherichia coli ATCC 25922, the Gram-positive bacteria is Staphylococcus aureus ATCC 25923, and the fungus is Candida albicans ATCC 10231.

[0029] Preferably, in the antimicrobial agent or antimicrobial hydrogel, the concentration of the modified antimicrobial peptide is greater than or equal to 50 μg / mL.

[0030] Preferably, in the antibacterial agent or antibacterial hydrogel, the concentration of the modified antimicrobial peptide is 50 μg / mL.

[0031] The present invention has the following significant beneficial effects:

[0032] The present invention significantly improves the antibacterial activity by optimizing the amino acid sequence of the antimicrobial peptide and combining it with acetylation modification. Specifically, the optimized antimicrobial peptide b exhibits significant antibacterial effects on common pathogenic microorganisms such as Escherichia coli, Staphylococcus aureus and Candida albicans, and its antibacterial efficacy is improved by more than 70% compared with traditional antimicrobial peptides. It is particularly noteworthy that the inhibitory effect of antimicrobial peptide b on Candida albicans has made a breakthrough, showing antibacterial activity that the original antimicrobial peptides do not have, thereby showing good broad-spectrum antibacterial properties.

[0033] In addition, the hydrogel prepared by the present invention exhibits high antibacterial activity. In vitro antibacterial experiments show that the growth of Escherichia coli and Staphylococcus aureus can be completely inhibited after incubation with them for 6 hours, and a significant inhibitory effect is shown on Candida albicans, thereby effectively inhibiting pathogenic microorganisms in the wound site and preventing the occurrence of infection.

[0034] In addition, the hydrogel containing antimicrobial peptide b prepared by the present invention (hydrogel c) showed extremely excellent effects in the mouse wound healing experiment. After 12 days of treatment, the wound healing rate of hydrogel c reached 96.05%, which was much higher than hydrogel a (61.57%) without antimicrobial peptides and hydrogel b (76.86%) with antimicrobial peptide Hylin PL. This result shows that the hydrogel containing antimicrobial peptide b not only has significant advantages in antibacterial properties, but also can effectively promote wound healing, and has good clinical application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1The in vitro antibacterial effect of the hydrogel containing antimicrobial peptide b;

[0036] Figure 2 The repairing effect of hydrogel containing antimicrobial peptide b on mouse skin defects. DETAILED DESCRIPTION

[0037] The present invention is further described in detail below in conjunction with examples, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art. The test methods for which specific experimental conditions are not specified in the following examples are usually in accordance with conventional experimental conditions. Unless otherwise specified, the reagents and raw materials used in the present invention can be obtained commercially.

[0038] The antimicrobial peptide Hylin PL is a natural antimicrobial peptide derived from a South American tree frog. Its amino acid sequence is: FLGLIPALAGAIGNLIK, SEQ ID NO.1. It has a bactericidal effect on a variety of bacteria, but the inhibitory effect is relatively weak. In order to further improve its antibacterial activity, the present invention modifies its amino acid sequence to obtain a more excellent antibacterial effect and applies it to the preparation of medical hydrogel.

[0039] Antimicrobial peptide a: replace position 5: I (isoleucine) with R (arginine), position 11: A (alanine) with W (tryptophan), and the resulting sequence is as follows: FLGLRPALAGWIGNLIK, SEQ ID NO. 2;

[0040] Antimicrobial peptide b: The 3rd position: G (glycine) is replaced by W (tryptophan), the 14th position: N (aspartic acid) is replaced by K (lysine), and the C-terminus is acetylated. The resulting sequence is as follows: FLWLIPALAGAIGKLIK-NH2, SEQ ID NO.3;

[0041] Antimicrobial peptide c: The 2nd position: L (leucine) is replaced by K (lysine), the 15th position: L (leucine) is replaced by F (phenylalanine), and the C-terminus is acetylated. The resulting sequence is as follows: FKGLIPALAGAIGNFIK-NH2, SEQ ID NO.4.

[0042] The above antimicrobial peptides were synthesized by Shanghai Newpu Biotechnology Co., Ltd.

[0043] Example 1

[0044] Detection of the inhibition zone diameter of different antimicrobial peptides by disc diffusion method

[0045] Escherichia coli and Staphylococcus aureus detection

[0046] (1) picking activated single colonies of Escherichia coli ATCC 25922 or Staphylococcus aureus ATCC 25923, inoculating them into LB liquid culture medium, and culturing them at 37° C. and 120 rpm overnight to obtain Escherichia coli or Staphylococcus aureus suspensions;

[0047] (2) Adjust the suspension of Escherichia coli or Staphylococcus aureus to 1×10 8 CFU / mL, take 200 μL of bacterial suspension and spread it on the prepared LB solid medium;

[0048] (3) The antimicrobial peptides Hylin PL, antimicrobial peptide a, antimicrobial peptide b, and antimicrobial peptide c were prepared into 50 μg / mL solutions, and the solutions were filtered using a 0.22 μm filter membrane to ensure that the solutions were sterile;

[0049] (4) After sterilizing a 5 mm diameter filter disc with high pressure steam, 100 μL of the antimicrobial peptide solution prepared above was added to the center area of ​​the filter disc in portions;

[0050] (5) After standing for 1 hour, the drug-sensitive paper sheet is dried to obtain a drug-sensitive paper sheet loaded with antimicrobial peptides;

[0051] (6) Place the drug-sensitive paper onto a solid culture medium, place it in a constant temperature incubator, and culture at 37°C for 24 h;

[0052] (7) After the incubation period, the diameter of the inhibition zone was measured using a vernier caliper and the cross-cross method. The average value was taken after three measurements and the results were expressed as mean ± standard deviation.

[0053] Candida albicans detection

[0054] (1) Pick a single colony of activated Candida albicans ATCC 10231, inoculate it into YPD liquid culture medium, and culture it at 37°C and 120 rpm overnight to obtain a Candida albicans suspension;

[0055] (2) Adjust the concentration of Candida albicans suspension to 1×10 8 CFU / mL, take 200 μL of bacterial suspension and spread it on the prepared Sabouraud solid medium;

[0056] (3) The antimicrobial peptides Hylin PL, antimicrobial peptide a, antimicrobial peptide b, and antimicrobial peptide c were prepared into 50 μg / mL solutions, and the solutions were filtered using a 0.22 μm filter membrane to ensure that the solutions were sterile;

[0057] (4) After sterilizing a 5 mm diameter filter disc with high pressure steam, 100 μL of the antimicrobial peptide solution prepared above was added to the center area of ​​the paper disc in portions;

[0058] (5) After standing for 1 hour, the drug-sensitive paper sheet is dried to obtain a drug-sensitive paper sheet loaded with antimicrobial peptides;

[0059] (6) Place the drug-sensitive paper onto Sabouraud culture medium, place in a constant temperature incubator, and culture at 37°C for 24 h;

[0060] (7) After the incubation period, the diameter of the inhibition zone was measured using a vernier caliper and the cross-cross method. The average value was taken after three measurements and the results were expressed as mean ± standard deviation.

[0061] Table 1 Diameters of inhibition zones of different antimicrobial peptides against Escherichia coli, Staphylococcus aureus and Candida albicans

[0062]

[0063]

[0064] From the results in Table 1, it can be seen that the diameter of the inhibition zone of antimicrobial peptide a against Escherichia coli is 15.87±0.21 mm (an increase of 21.98% relative to Hylin PL), 17.89±0.29 mm (an increase of 11.60% relative to Hylin PL) against Staphylococcus aureus, and 5.11±0.03 mm against Candida albicans; compared with the antimicrobial peptide Hylin PL, its antibacterial ability against Escherichia coli and Staphylococcus aureus has been improved to a certain extent, but the improvement is not particularly significant; and the inhibitory effect on Candida albicans is still weak, similar to that of the antimicrobial peptide Hylin PL, indicating that the replacement of these two amino acids has no significant effect on the inhibitory effect of Candida albicans.

[0065] The diameter of the inhibition zone of antimicrobial peptide b against Escherichia coli reached 22.13±0.24mm (70.09% increase compared to Hylin PL), 29.22±0.23mm (82.28% increase compared to Hylin PL), and 15.13±0.20mm (192.65% increase compared to Hylin PL) against Candida albicans. Compared with the original antimicrobial peptide Hylin PL and antimicrobial peptide a, the diameter of the inhibition zone has been greatly improved. It suggests that the amino acid substitutions and C-terminal acetylation at these positions may significantly change the spatial structure and physicochemical properties of antimicrobial peptides, thereby enhancing their ability to bind to targets such as bacterial or fungal cell membranes, thereby showing strong inhibition against different types of strains (including Gram-positive bacteria, Gram-negative bacteria and fungal Candida albicans), and exerting unexpected antibacterial effects. Therefore, it shows potential application value in the development of new antimicrobial drugs.

[0066] The diameter of the inhibition zone of antimicrobial peptide c against Escherichia coli is 16.41±0.26mm (an increase of 26.13% relative to Hylin PL), 19.30±0.30mm (an increase of 20.40% relative to Hylin PL) against Staphylococcus aureus, and 6.27±0.19mm (an increase of 21.28% relative to Hylin PL) against Candida albicans. Overall, its antibacterial effect is between antimicrobial peptide a and antimicrobial peptide b, indicating that the replacement of these two amino acids and the acetylation of the C-terminus have optimized its antibacterial properties to a certain extent, but the degree of optimization is not as significant as that of antimicrobial peptide b.

[0067] Example 2

[0068] Preparation of hydrogel containing antimicrobial peptide b

[0069] (1) dissolving polyvinyl alcohol (PVA) in a 50% glycerol aqueous solution, heating to 60° C., and stirring for 2 h to ensure that the polyvinyl alcohol is completely dissolved, thereby obtaining a polyvinyl alcohol solution with a mass concentration of 10%;

[0070] (2) Sodium carboxymethyl cellulose (Na-CMC) is dissolved in a 50% glycerol aqueous solution and stirred until completely dissolved to obtain a sodium carboxymethyl cellulose solution with a mass concentration of 1%;

[0071] (3) mixing the polyvinyl alcohol solution and the sodium carboxymethyl cellulose solution in a volume ratio of 1:1 to obtain a PVA / Na-CMC solution;

[0072] (4) dissolving the antimicrobial peptide b in deionized water to obtain a 0.5 mg / mL antimicrobial peptide b solution;

[0073] (5) mixing the antimicrobial peptide b solution and the PVA / Na-CMC solution in a volume ratio of 1:10 to obtain a PVA / Na-CMC solution containing the antimicrobial peptide b;

[0074] (6) The PVA / Na-CMC solution containing antimicrobial peptide b was transferred to a refrigerator and frozen at -20°C for 8 hours. The obtained hydrogel was taken out and thawed at room temperature for 1 hour.

[0075] (7) The hydrogel was placed in a refrigerator again and frozen at -20°C for 8 hours to finally obtain a finished hydrogel containing antimicrobial peptide b.

[0076] Comparative Example 1

[0077] (1) dissolving polyvinyl alcohol (PVA) in a 50% glycerol aqueous solution, heating to 60° C., and stirring for 2 h to ensure that the polyvinyl alcohol is completely dissolved, thereby obtaining a polyvinyl alcohol solution with a mass concentration of 10%;

[0078] (2) Sodium carboxymethyl cellulose (Na-CMC) is dissolved in a 50% glycerol aqueous solution and stirred until completely dissolved to obtain a sodium carboxymethyl cellulose solution with a mass concentration of 1%;

[0079] (3) mixing the polyvinyl alcohol solution and the sodium carboxymethyl cellulose solution in a volume ratio of 1:1 to obtain a PVA / Na-CMC solution;

[0080] (4) The PVA / Na-CMC solution was transferred to a refrigerator and frozen at -20°C for 8 hours. The obtained hydrogel was taken out and thawed at room temperature for 1 hour.

[0081] (5) The hydrogel was placed in a refrigerator again and frozen at -20°C for 8 hours to finally obtain a common hydrogel product.

[0082] Comparative Example 2

[0083] (1) dissolving polyvinyl alcohol (PVA) in a 50% glycerol aqueous solution, heating to 60° C., and stirring for 2 h to ensure that the polyvinyl alcohol is completely dissolved, thereby obtaining a polyvinyl alcohol solution with a mass concentration of 10%;

[0084] (2) Sodium carboxymethyl cellulose (Na-CMC) is dissolved in a 50% glycerol aqueous solution and stirred until completely dissolved to obtain a sodium carboxymethyl cellulose solution with a mass concentration of 1%;

[0085] (3) mixing the polyvinyl alcohol solution and the sodium carboxymethyl cellulose solution in a volume ratio of 1:1 to obtain a PVA / Na-CMC solution;

[0086] (4) dissolving the antimicrobial peptide Hylin PL in deionized water to obtain a 0.5 mg / mL antimicrobial peptide Hylin PL solution;

[0087] (5) mixing the antimicrobial peptide Hylin PL solution and the PVA / Na-CMC solution in a volume ratio of 1:10 to obtain a PVA / Na-CMC solution containing the antimicrobial peptide Hylin PL;

[0088] (6) The PVA / Na-CMC solution containing the antimicrobial peptide Hylin PL was transferred to a refrigerator and frozen at -20°C for 8 hours. The resulting hydrogel was taken out and thawed at room temperature for 1 hour.

[0089] (7) The hydrogel was placed in a refrigerator again and frozen at -20°C for 8 hours to finally obtain a finished hydrogel containing the antimicrobial peptide Hylin PL.

[0090] Example 3

[0091] Testing the antibacterial effect of the finished hydrogel containing antimicrobial peptide b

[0092] (1) Cut the finished ordinary hydrogel (hereinafter referred to as hydrogel a), the finished hydrogel containing the antimicrobial peptide Hylin PL (hereinafter referred to as hydrogel b), and the finished hydrogel containing the antimicrobial peptide b (hereinafter referred to as hydrogel c) into 5 mm small discs (thickness 0.5 mm);

[0093] (2) using ultraviolet light to irradiate hydrogel a, hydrogel b, and hydrogel c for 20 minutes to ensure that there is no microbial contamination on the surface of the hydrogel;

[0094] (3) Prepare bacterial suspensions of Escherichia coli, Staphylococcus aureus, and Candida albicans, and adjust the concentration of the bacterial suspension to 1×10 6 CFU / mL;

[0095] (4) Add 5 mL of sterile PBS to a sterile test tube, add 100 μL of bacterial solution to the test tube, and mix well;

[0096] (5) Add one piece of hydrogel a, hydrogel b or hydrogel c to the test tube, respectively, and incubate at 37°C and 200 r / min for 6 h. Meanwhile, set up a blank control group without hydrogel, containing only PBS and bacterial suspension;

[0097] (6) After the incubation, 100 μL of the mixture was taken from each test tube and evenly spread on the pre-prepared agar plate using a sterile applicator, and then placed in a 37°C constant temperature incubator for 24 hours;

[0098] (7) After the incubation, count the number of colonies on each plate and calculate the inhibition rate (the number of colonies in the blank control group - the number of colonies in the experimental group / the number of colonies in the blank control group). The inhibition rate results are as follows: Figure 1 shown.

[0099] from Figure 1 The results show that the antibacterial rate of hydrogel b with the original antimicrobial peptide is 34.73% for Escherichia coli, 45.72% for Staphylococcus aureus, and low for Candida albicans, close to 0. The hydrogel c with the modified antimicrobial peptide b of the present invention almost completely inhibits Escherichia coli and Staphylococcus aureus, and also has a new function of inhibiting Candida albicans. Its antibacterial rate after incubation for 6 hours reaches 75.19%, which has an excellent effect.

[0100] Example 4

[0101] Testing the effect of hydrogel products containing antimicrobial peptide b on wound repair

[0102] (1) Eighteen 10-week-old BALB / c mice were selected and randomly divided into three groups (6 mice in each group) after one week of adaptive feeding. The mice were fasted for 12 hours before the experiment to prevent the risk of food reflux.

[0103] (2) The experimental mice were anesthetized by intraperitoneal injection of 1% sodium pentobarbital. After confirming that the anesthesia was effective, the hair in the surgical area on the back of the mice was carefully shaved with an electric shaver, and then the remaining hair was removed with 8% sodium sulfide solution;

[0104] (3) Fix the depilated and cleaned mice on the operating board, disinfect them twice with iodine tincture, and then deiodinate them with 75% alcohol;

[0105] (4) After disinfection, a sterilized puncher (1 cm in diameter) was used to punch a hole in the back skin of the mouse, and a circular skin was removed to form a full-thickness skin defect wound;

[0106] (5) After cleaning the wound surface with sterile saline, equal amounts of hydrogel a, hydrogel b and hydrogel c prepared by the present invention were used to cover the entire wound surface;

[0107] (6) The hydrogel dressing was changed every 3 days. On the 12th day, photos were taken and the wound healing rate was calculated. The results were as follows: Figure 2 shown.

[0108] from Figure 2 The data showed that after 12 days of treatment, the wound healing of mice treated with different hydrogels was different. Specifically, the wound healing rate of mice treated with hydrogel a was 61.57%, the wound healing rate of mice treated with hydrogel b was 76.86%, and the wound healing rate of mice treated with hydrogel c was significantly higher, reaching 96.05%.

[0109] This result shows that hydrogel c containing antimicrobial peptide b shows significant advantages in promoting wound healing, not only better than hydrogel a without antimicrobial peptides, but also significantly better than hydrogel b with antimicrobial peptide Hylin PL. Among them, antimicrobial peptide b in hydrogel c may significantly accelerate the wound healing process through its stronger antimicrobial effect and other properties, further proving its potential and advantages in wound treatment.

Claims

1. A method for preparing a medical antibacterial repair hydrogel, characterized in that: The preparation method of the medical antibacterial repair hydrogel comprises the following steps: a) dissolving polyvinyl alcohol in a glycerol aqueous solution to obtain a polyvinyl alcohol solution; b) dissolving sodium carboxymethyl cellulose in a glycerol aqueous solution to obtain a sodium carboxymethyl cellulose solution; c) mixing the polyvinyl alcohol solution and the sodium carboxymethylcellulose solution in a volume ratio of 1:1 to obtain a PVA / Na-CMC solution; d) dissolving the modified antimicrobial peptide in deionized water to obtain a modified antimicrobial peptide solution; e) mixing the modified antimicrobial peptide solution and the PVA / Na-CMC solution at a volume ratio of 1:10 to obtain a PVA / Na-CMC solution containing the modified antimicrobial peptide; f) transferring the PVA / Na-CMC solution containing the modified antimicrobial peptide to a freezing device for initial freezing to obtain a hydrogel containing the modified antimicrobial peptide; g) taking out the hydrogel, thawing it at room temperature, and freezing it again to obtain the medical antibacterial repair hydrogel; The amino acid sequence of the modified antimicrobial peptide is FLWLIPALAGAIGKLIK-NH2.

2. The preparation method according to claim 1, characterized in that: The glycerol aqueous solution is a 50% glycerol aqueous solution; The polyvinyl alcohol solution is a polyvinyl alcohol solution with a mass concentration of 10%; The concentration of the modified antimicrobial peptide solution is greater than or equal to 0.5 mg / mL The sodium carboxymethyl cellulose solution is a sodium carboxymethyl cellulose solution with a mass concentration of 1%; The conditions for the primary freezing are freezing at -20°C for 8 hours, the thawing time at room temperature is 1 hour, and the conditions for the secondary freezing are freezing at -20°C for 8 hours.

3. The preparation method according to claim 2, characterized in that: The medical antibacterial agent is used to inhibit Gram-negative bacteria, Gram-positive bacteria and fungi; The repair is skin damage wound healing repair, and the skin damage includes mechanical damage, physical damage and chemical damage.

4. The preparation method according to claim 3, characterized in that: The Gram-negative bacteria is Escherichia coli ATCC25922, the Gram-positive bacteria is Staphylococcus aureus ATCC 25923, and the fungus is Candida albicans ATCC10231.

5. The preparation method according to claim 4, characterized in that: The skin injury is a mechanical injury, and the mechanical injury is a cut.

6. A medical antibacterial repair hydrogel, characterized in that: The medical antibacterial repair hydrogel is prepared by the preparation method according to any one of claims 1 to 5.

7. Use of a modified antimicrobial peptide in the preparation of an antimicrobial agent or an antimicrobial hydrogel, characterized in that: The amino acid sequence of the modified antimicrobial peptide is FLWLIPALAGAIGKLIK-NH2.

8. The use according to claim 7, characterized in that: The antibacterial agent has an antibacterial spectrum of Gram-negative bacteria, Gram-positive bacteria and fungi.

9. The use according to claim 8, characterized in that: The Gram-negative bacteria is Escherichia coli ATCC25922, the Gram-positive bacteria is Staphylococcus aureus ATCC 25923, and the fungus is Candida albicans ATCC10231.

10. The use according to claim 9, characterized in that: In the antibacterial agent or antibacterial hydrogel, the concentration of the modified antimicrobial peptide is greater than or equal to 50 μg / mL.

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