A veterinary antimicrobial peptide sustained-release gel, its preparation method and its application

Abstract

This invention belongs to the field of veterinary drug formulation technology, specifically relating to a veterinary antimicrobial peptide sustained-release gel, its preparation method, and its application. The veterinary antimicrobial peptide sustained-release gel is made from the following materials in the indicated mass percentages: antimicrobial peptide 0.00005%~0.5%; gel matrix 0.25%~2%; excipients 2%~8%; distilled water to make up to 100%; the antimicrobial peptide is antimicrobial peptide Z(WK)2, whose amino acid sequence is shown in SEQ ID NO.1; the gel matrix includes any one or more of carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and carbomer; the excipients include any one or more of propylene glycol, glycerin, sorbitol, and polyethylene glycol. The veterinary antimicrobial peptide sustained-release gel formulation provided by this invention consists of antimicrobial peptide, gel matrix, and excipients, and exhibits significant antibacterial effect, inhibiting the proliferation of bacteria such as methicillin-resistant Staphylococcus aureus.

Description

Technical Field

[0001] This invention belongs to the field of veterinary drug formulation technology, specifically relating to a veterinary antimicrobial peptide sustained-release gel, its preparation method, and its application. Background Technology

[0002] Bacterial infections are a major challenge in livestock farming, affecting not only animal health and productivity but also threatening food safety and public health. However, the irrational use of antibiotics in livestock farming exacerbates antibiotic resistance. Globally, livestock use three times more antibiotics than humans, leading to increased resistance and negatively impacting human society with increased biosecurity threats, environmental pollution, and economic constraints. To address this challenge, the livestock industry is gradually reducing antibiotic use and seeking alternative strategies. The European Union banned the addition of growth promoters to animal feed in 2006, and my country has also launched an action plan to reduce the use of veterinary antibiotics. Therefore, developing green, safe, and efficient alternatives to new veterinary antibiotics is of significant practical importance.

[0003] In recent years, antimicrobial peptides have been found to directly inhibit or kill viruses, fungi, and bacteria in animals, and are among the most studied biological agents in terms of their anti-inflammatory mechanisms. Antimicrobial peptides possess non-specific membrane-breaking mechanisms and broad-spectrum antimicrobial activity, showing great potential as a weapon against drug-resistant bacteria and are considered promising antibiotic alternatives. Although antimicrobial peptides exhibit excellent antimicrobial effects and good antimicrobial activity against multidrug-resistant bacteria, most have limited activity and are unstable in the environment. Therefore, there is a need to develop novel alternatives to veterinary antibiotics using antimicrobial peptides. Summary of the Invention

[0004] To address the problems of limited and unstable activity of antimicrobial peptides in the environment in existing technologies, this invention provides a sustained-release gel for veterinary antimicrobial peptides, its preparation method, and its applications. To achieve the above objectives, this invention adopts the following technical solution.

[0005] This invention provides a veterinary antimicrobial peptide sustained-release gel, made from the following materials in weight percentages:

[0006] Antimicrobial peptides 0.00005%~0.5%.

[0007] The gel matrix is ​​0.25% to 2%.

[0008] Additives: 2%~8%.

[0009] Add distilled water to bring the total to 100%.

[0010] The antimicrobial peptide is antimicrobial peptide Z(WK)2, and its amino acid sequence is shown in SEQ ID NO.1: WKWKCNSKSFCKWKW.

[0011] The gel matrix includes any one or more of carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and carbomer.

[0012] The additives include any one or more of propylene glycol, glycerin, sorbitol, and polyethylene glycol.

[0013] The veterinary antimicrobial peptide sustained-release gel provided by this invention is composed of antimicrobial peptides, a gel matrix, and excipients. It exhibits significant antibacterial effects, inhibiting the proliferation of bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, this veterinary antimicrobial peptide sustained-release gel provides high activity and stability in the environment, which facilitates better exertion of the antimicrobial peptide's antimicrobial effect. The hydrogel, acting as the gel matrix, encapsulates the antimicrobial peptide, protecting it from degradation by environmental proteases and providing sustained release, thus prolonging its in vitro action time. Additionally, excipients such as propylene glycol provide moisturizing effects, preventing moisture loss during prolonged application to the skin. Furthermore, experiments have shown that propylene glycol, as an excipient, can also enhance the antimicrobial effect of the antimicrobial peptide, resulting in a synergistic antimicrobial effect. In summary, the antimicrobial peptide gel complex formulation demonstrates better clinical application results than individual antimicrobial peptide solutions, addressing the problems of limited and unstable activity of antimicrobial peptides in the environment in existing technologies.

[0014] Preferably, it is made of the following materials by weight percentage:

[0015] The antimicrobial peptide Z(WK)2 is 0.1%~0.5%.

[0016] The hydroxypropyl methylcellulose is 0.5% to 2%.

[0017] The propylene glycol content is 6% to 8%.

[0018] The distilled water is replenished to 100%.

[0019] Preferably, it is made of the following materials by weight percentage:

[0020] The antimicrobial peptide Z(WK)2 is 0.5%.

[0021] The hydroxypropyl methylcellulose is 2%.

[0022] The propylene glycol is 8%.

[0023] The distilled water is replenished to 100%.

[0024] The optimal therapeutic concentration of antimicrobial peptide Z(WK)2 at 0.5% by mass was selected through mouse skin anti-infection tests. Hydroxypropyl methylcellulose at 2% by mass, when administered topically, provides good skin adhesion without affecting the antimicrobial efficacy of the peptide, while also offering a 3-day sustained-release effect, reducing the frequency of clinical administration. Propylene glycol at 8% by mass not only provides good gel-moisturizing effects but also, according to antimicrobial tests, significantly enhances the antimicrobial efficacy of the peptide. Therefore, the above materials and concentrations were selected for the final formulation preparation.

[0025] The present invention also provides a method for preparing the aforementioned veterinary antimicrobial peptide sustained-release gel, comprising the following steps:

[0026] Weigh the antimicrobial peptide, gel matrix, and excipients according to the formula, and add distilled water to bring the total to 100%. Mix thoroughly and allow to swell to obtain the veterinary antimicrobial peptide sustained-release gel. The preparation method of the veterinary antimicrobial peptide sustained-release gel prepared by this invention is simple, has good antibacterial activity, good safety, a 3-day sustained-release effect, and good adhesion to the skin, promoting transdermal drug absorption and achieving better drug delivery.

[0027] The present invention also provides the application of the aforementioned veterinary antimicrobial peptide sustained-release gel in the preparation of antimicrobial drugs.

[0028] Preferably, the antibacterial drug uses the veterinary antimicrobial peptide sustained-release gel as its active ingredient.

[0029] Preferably, the antibacterial drug is used against Gram-positive and Gram-negative bacteria.

[0030] Preferably, the Gram-positive bacteria include any one or more of Staphylococcus aureus, Staphylococcus hemolyticus, Streptococcus, and Bacillus cereus.

[0031] Preferably, the Gram-negative bacteria include any one or more of Escherichia coli, Salmonella, Klebsiella pneumoniae, and Proteus.

[0032] The present invention also provides the application of the veterinary antimicrobial peptide sustained-release gel in the preparation of a medicament for treating at least one of bacterial skin diseases, systemic septicemia, and gastrointestinal infections in livestock farming.

[0033] Compared with the prior art, the present invention has the following beneficial effects:

[0034] 1. This invention provides a veterinary antimicrobial peptide sustained-release gel. The veterinary antimicrobial peptide sustained-release gel provided by this invention is composed of antimicrobial peptides, a gel matrix, and excipients. It exhibits significant antibacterial effects, inhibiting the proliferation of bacteria such as methicillin-resistant Staphylococcus aureus. Simultaneously, the veterinary antimicrobial peptide sustained-release gel provided by this invention exhibits high activity and stability in the environment, which is beneficial for the antimicrobial peptides to better exert their antimicrobial effects. The hydrogel, acting as a gel matrix, can encapsulate the antimicrobial peptides, protecting them from degradation by proteases and other environmental factors, while also providing sustained release and prolonging the in vitro action time. Furthermore, excipients such as propylene glycol provide moisturizing effects, preventing moisture loss during prolonged application to the skin. Experiments have also shown that propylene glycol, as an excipient, can enhance the antimicrobial effect of the antimicrobial peptides, resulting in a synergistic antimicrobial effect. In summary, the antimicrobial peptide gel composite formulation has better clinical application effects than individual antimicrobial peptide solutions, solving the problems of limited and unstable activity of antimicrobial peptides in the environment in existing technologies.

[0035] 2. The preparation method of the veterinary antimicrobial peptide sustained-release gel prepared by the present invention is simple, has good antibacterial activity, good safety, has a sustained-release effect for 3 days, and has good adhesion to the skin, which can promote transdermal drug absorption and achieve better drug delivery effect.

[0036] 3. This invention primarily utilizes hydrogel formulations to overcome the problems of instability, high toxicity, and short-term efficacy of antimicrobial peptides, making them an effective alternative to antibiotics in livestock farming. This invention screened six gel matrices to obtain an optimal matrix that does not affect its antibacterial properties, has high safety, and exhibits a sustained-release effect within 3 days. In clinical applications, its efficacy is superior to that of antimicrobial peptide aqueous solutions and erythromycin ointment. Attached Figure Description

[0037] Figure 1 The results of the in vitro hemolysis test of the gel matrix in this invention are shown; wherein, HPMC: hydroxypropyl methylcellulose; HPC: hydroxypropyl cellulose.

[0038] Figure 2 These are the results of the in vitro release test of the antimicrobial peptide gel formulation in this invention.

[0039] Figure 3 This is a diagram showing the wound healing process after skin antibacterial treatment in this invention; wherein, Figure 3 A in the figure represents the blank control group; Figure 3 B in the model group; Figure 3 C in the figure represents the antimicrobial peptide aqueous solution group; Figure 3 D in the diagram represents the antimicrobial peptide gel group; Figure 3 E in the figure represents the positive drug control group.

[0040] Figure 4This is a statistical diagram of bacterial load in skin tissue in this invention; wherein, Figure 4 A in the figure represents the blank control group; Figure 4 B in the model group; Figure 4 C in the figure represents the antimicrobial peptide aqueous solution group; Figure 4 D in the diagram represents the antimicrobial peptide gel group; Figure 4 E in the figure represents the positive drug control group. Detailed Implementation

[0041] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments, but this should not be construed as limiting the invention. Unless otherwise specified, the technical means used in the following embodiments are conventional means well known to those skilled in the art, and the materials, reagents, etc. used in the following embodiments are commercially available unless otherwise specified.

[0042] The antimicrobial peptide used in the embodiments of the present invention is antimicrobial peptide Z(WK)2, the amino acid sequence of which is shown in SEQ ID NO.1:

[0043] WKWKCNSKSFCKWKW.

[0044] Antimicrobial peptide Z(WK)2 was synthesized by Genscript Chemical, and the content of the synthesized antimicrobial peptide was >95%.

[0045] The gel matrix used in the following examples includes any one or more of carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and carbomer.

[0046] Among them, carboxymethyl cellulose (CMC) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; sodium carboxymethyl cellulose (CMC-Na) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; hydroxyethyl cellulose (HEC) was purchased from Shanghai Maclean Biochemical Technology Co., Ltd.; hydroxypropyl cellulose (HPC) was purchased from Shanghai Maclean Biochemical Technology Co., Ltd.; hydroxypropyl methyl cellulose (HPMC) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; and carbomer was purchased from Shanghai Maclean Biochemical Technology Co., Ltd.

[0047] Example 1: Screening of Gel Matrix

[0048] (1) Take 0.05g of carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose and carbomer respectively, mix with 10mg of antimicrobial peptide Z(WK)2, and add 10mL of distilled water to mix thoroughly to prepare an antimicrobial peptide gel solution. At the same time, prepare an antimicrobial peptide aqueous solution without gel matrix as a control.

[0049] The method for preparing the antimicrobial peptide aqueous solution without gel matrix is ​​as follows: weigh 10 mg of antimicrobial peptide Z(WK)2 and add 10 mL of distilled water and mix thoroughly to prepare the antimicrobial peptide aqueous solution without gel matrix.

[0050] (2) Methicillin-resistant Staphylococcus aureus ATCC 33591 was activated for 3 generations in MHB medium and then cultured continuously at 37℃ and 200 r / min for 12 h. After 12 h, the culture was diluted 100-fold with PBS solution. 20 μL of the diluted bacterial solution was taken and spread evenly on MHA plates with a sterile cotton swab, and then punched with a 6 mm diameter punch. 100 μL of antimicrobial peptide aqueous solution or antimicrobial peptide gel solution was added to the wells, and the plates were cultured overnight. The size of the inhibition zone was measured. The results are shown in Table 1.

[0051] Among them, methicillin-resistant Staphylococcus aureus ATCC 33591 was classified as MRSA and purchased from the China Veterinary Microbiology Culture Collection Center.

[0052] Both MHA and MHB culture media were purchased from Beijing Aoboxing Biotechnology Co., Ltd., and the specific preparation method is the same as the instruction manual.

[0053] Overnight culture refers to a culture time of ≥12 hours.

[0054] Table 1. Size of the antimicrobial peptide gel inhibition zone

[0055]

[0056] As shown in Table 1, hydroxypropyl cellulose and hydroxypropyl methylcellulose are more suitable as gel matrices for preparing sustained-release veterinary antimicrobial peptide gels without affecting the antimicrobial activity of antimicrobial peptide Z(WK)2.

[0057] Example 2: Hemolytic activity of the gel matrix

[0058] Take 5 mL of fresh defibrinated sheep blood, centrifuge at 1000 × g for 10 min at room temperature, discard the supernatant, collect the lower cell pellet, and wash three times with PBS solution. Resuspend the cell pellet in PBS solution to prepare a 2% v / v red blood cell suspension.

[0059] The prepared red blood cell suspension was added to 96-well cell culture plates at a density of 100 μL / well, followed by 100 μL of gel matrix to each well. PBS solution was used as a negative control, and Triton X-100 (v / v) at 0.1% was used as a positive control. Hydroxypropyl cellulose and hydroxypropyl methylcellulose were prepared at w / v concentrations of 0.25%, 0.5%, 0.75%, and 1%, with three replicates for each concentration. After mixing, the mixture was incubated at 37°C for 1 h and then centrifuged at 3000×g for 10 min. 100 μL of the supernatant was transferred to a new 96-well plate, and the absorbance was measured at OD=576 nm. Finally, the hemolysis rate of the gel matrix was calculated using the formula for cell hemolysis rate. The results are as follows: Figure 1 As shown.

[0060] The formula for calculating cell hemolysis rate is as follows:

[0061] Hemolysis rate = (OD of detection well) 576 - Negative control OD 576 ) / (Positive control OD) 576 - Negative control OD 576 ) × 100%;

[0062] In the above formula, the unit for hemolysis rate is %.

[0063] Defibrinated sheep blood was purchased from Beijing Solarbio Technology Co., Ltd.

[0064] The PBS solution was purchased from Beijing Solarbio Science & Technology Co., Ltd., with a pH of 7.4.

[0065] The gel matrix was obtained by thoroughly mixing hydroxypropyl cellulose and hydroxypropyl methylcellulose in PBS solution.

[0066] Depend on Figure 1 The results showed that, at the same mass percentage concentration, hydroxypropyl methylcellulose had a lower rate of biological hemolysis. Therefore, hydroxypropyl methylcellulose was chosen as the gel matrix.

[0067] Example 3: In vitro time-release curves of antimicrobial peptides in a gel matrix

[0068] Weigh 0.2 g of hydroxypropyl methylcellulose and 10 mg of antimicrobial peptide Z(WK)2, and dissolve them thoroughly in 10 mL of PBS solution to prepare an antimicrobial peptide gel solution. The preparation method is the same as in Example 1.

[0069] The above-mentioned antimicrobial peptide gel solution was placed in a dialysis bag, and an in vitro release assay was performed under physiological conditions of 37°C and PBS solution at pH 7.4. At 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours, 36 hours, 48 ​​hours, and 72 hours, 1 mL of liquid was aspirated from the outside of the dialysis bag, and 1 mL of fresh PBS solution was added. The concentration of the antimicrobial peptide at each sample was determined using a BCA kit. The release curve results are shown below. Figure 2 As shown,

[0070] Among them, the dialysis bag: MwCO: 8000D~14000D.

[0071] The BCA kit was purchased from Beyotime Biotechnology Co., Ltd., and the detection method was the same as the instructions.

[0072] Depend on Figure 2 The results showed that the solution with hydroxypropyl methylcellulose as the gel matrix could release antimicrobial peptides over a period of 3 days, thus prolonging the duration of drug action.

[0073] Example 4: Screening of Additives

[0074] Using hydroxypropyl methylcellulose as the gel matrix, antimicrobial peptide Z(WK)2 was added, along with propylene glycol at v / v concentrations of 0%, 2%, 4%, 6%, and 8%. The mixture was thoroughly mixed in PBS solution to prepare antimicrobial peptide gel solutions with different propylene glycol concentrations. The in vitro antimicrobial effects of the antimicrobial peptide at different propylene glycol concentrations were investigated using minimum inhibitory concentration (MIC) tests. The results are shown in Table 2.

[0075] The specific procedure is as follows: Add 100 μL of MRSA bacterial solution to each well of a 96-well plate, at a concentration of 1 × 10⁻⁶. 6 CFU / mL, and then 100 μL of antimicrobial peptide gel solutions containing different concentrations of antimicrobial peptide and different concentrations of propylene glycol were added respectively, wherein the w / v concentration of hydroxypropyl methylcellulose was 0.5%, the final concentration of antimicrobial peptide was 0.5-1024 μg / mL, and the final v / v concentration of propylene glycol was 0%, 2%, 4%, 6% and 8%.

[0076] The minimum inhibitory concentration (MIC) test is abbreviated as MIC and is measured in μg / mL.

[0077] The results showed that the addition of propylene glycol significantly improved the in vitro antibacterial effect of the antimicrobial peptides. The most significant improvement was observed with propylene glycol at a final v / v concentration of 8%, which reduced the MIC to one-eighth of its previous value. Therefore, propylene glycol at a final v / v concentration of 8% was chosen as an adjuvant for the antimicrobial peptide gel formulation.

[0078] Table 2 Minimum inhibitory concentration of antimicrobial peptide gel formulations

[0079]

[0080] Note: MIC stands for minimum inhibitory concentration, in μg / mL.

[0081] Example 5: Anti-infection test of antimicrobial peptide gel formulation in mouse skin

[0082] Female BALB / c mice aged 6-8 weeks were selected and randomly divided into 5 groups: blank control group, model group, antimicrobial peptide aqueous solution group, antimicrobial peptide gel group, and positive drug control group. The positive drug control group used commercially available erythromycin ointment.

[0083] Before modeling, each animal was anesthetized with an intraperitoneal injection of 2.5 mg / animal of salbutamol. After anesthesia, the hair on the back was shaved, and a 10 mm circular wound was cut on the back with scissors. Except for the blank control group, each group was given 100 μL of 10% saline solution. 9 A CFU / mL solution of methicillin-resistant Staphylococcus aureus (ATCC) 33591 was applied to a circular wound. Treatment was administered at the wound site 3 days after infection, every 2 days for 10 consecutive days. The antimicrobial peptide aqueous solution group, antimicrobial peptide gel group, and positive control group were each given 100 μL of their respective drugs applied to the circular wound. The blank control group and model group received no treatment. Photos were taken every 2 days to record changes in the size of the circular wound. On day 10, mice were euthanized, and wound tissue was collected for bacterial load determination. The therapeutic effects of the antimicrobial peptide aqueous solution and antimicrobial peptide gel were compared by assessing wound healing and bacterial load.

[0084] The preparation method and concentration of erythromycin are the same as those in the patent application description.

[0085] Preparation method of antimicrobial peptide aqueous solution: Weigh 50mg of antimicrobial peptide Z(WK)2, add 10mL of distilled water and mix thoroughly to prepare antimicrobial peptide aqueous solution.

[0086] Preparation method of antimicrobial peptide gel solution: Weigh 0.2g of hydroxypropyl methylcellulose and 50mg of antimicrobial peptide Z(WK)2, add 10mL of distilled water and mix thoroughly to prepare antimicrobial peptide gel solution.

[0087] The results of wound healing and bacterial load are shown below. Figure 3 and Figure 4 .

[0088] After euthanasia, tissue samples were taken from the skin wounds on the back of the mice for bacterial load testing.

[0089] The bacterial load detection method is as follows:

[0090] Weigh approximately 1g of tissue and add 1mL of PBS solution for homogenization. Centrifuge the homogenate at 500 rpm for 5 minutes and retain the supernatant. Serially dilute the supernatant 10-fold in PBS solution, and evenly spread 50μL of each dilution onto MHA plates. Incubate the MHA plates upside down at 37℃ for 24 hours, then count the colonies.

[0091] The homogenization conditions were 600 Hz and 10 min.

[0092] The method for calculating bacterial load is as follows:

[0093] log 10 (CFU / g) = log 10 (Colony count / Spread volume / Dilution factor / Tissue weight).

[0094] Depend on Figure 3 The results showed that the wound recovery in the antimicrobial peptide gel group was significantly better than that in the antimicrobial peptide aqueous solution group. The wound began to shrink significantly on the 6th day of treatment and was basically completely recovered on the 10th day of treatment.

[0095] Depend on Figure 4 The results showed that the bacterial load on the skin in the antimicrobial peptide gel group was significantly lower than that in the antimicrobial peptide aqueous solution group and the positive drug control group, indicating that the antimicrobial peptide gel group had a better bactericidal effect.

[0096] The above experimental results indicate that the antimicrobial peptide gel group has a better wound healing effect than the antimicrobial peptide aqueous solution group. After 10 days of treatment, the wound healing rate of the antimicrobial peptide gel group is better than that of the positive drug control group. Furthermore, the results of skin tissue bacterial load also show that the bactericidal effect of the antimicrobial peptide gel group is significantly better than that of the antimicrobial peptide aqueous solution group and the positive drug control group. After 10 days of treatment, the bacterial load in the antimicrobial peptide gel group decreased significantly.

[0097] The experimental results above show that the antimicrobial peptide gel solution has better clinical application effects than the antimicrobial peptide aqueous solution, significantly reducing bacterial load and promoting wound healing.

[0098] Antimicrobial peptides are commonly used clinically for in vitro antibacterial applications, such as for skin and vaginal infections, due to their structural characteristics. However, complex environmental changes during infection, such as low pH and various proteases, can still lead to the degradation and loss of activity of antimicrobial peptides. Furthermore, they often exert their rapid antibacterial effect through membrane disruption mechanisms. Therefore, the effective antibacterial time of antimicrobial peptides is relatively short.

[0099] This invention prepares an antimicrobial peptide gel solution by adding a gel matrix and excipients, and compares its therapeutic effect on skin infections in vitro by administering it twice a day. The results show that even with a low-frequency administration of twice a day, the hydrogel formulation still exhibits good wound healing effects, with near-complete recovery within 10 days. In contrast, the wound healing effect and skin bacterial load of the antimicrobial peptide aqueous solution group are significantly worse than those of the gel group, possibly due to the short duration of action of the antimicrobial peptide aqueous solution and degradation by proteases and other components. Therefore, the technical solution of this invention can effectively solve the problems of instability and short duration of action of antimicrobial peptides in clinical applications, significantly improving their clinical application value.

[0100] It should be noted that when numerical ranges are involved in this invention, it should be understood that the two endpoints of each numerical range and any value between the two endpoints can be selected. To avoid redundancy, this invention describes preferred embodiments.

[0101] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments, all of which fall within the scope of the invention.

Claims

1. A veterinary antimicrobial peptide sustained-release gel, characterized in that, Made from the following percentages by mass: Antimicrobial peptides 0.1%~0.5%; Hydroxypropyl methylcellulose 0.5%~1%; Propylene glycol 6%~8%; Replenish with distilled water to 100%; The antimicrobial peptide is antimicrobial peptide Z(WK)2, and its amino acid sequence is shown in SEQ ID NO.1; The veterinary antimicrobial peptide sustained-release gel is used against Staphylococcus aureus.

2. The veterinary antimicrobial peptide sustained-release gel according to claim 1, characterized in that, Made from the following percentages by mass: The antimicrobial peptide Z(WK)2 is 0.5%; The hydroxypropyl methylcellulose is 1%; The propylene glycol is 8%; The distilled water is replenished to 100%.

3. The method for preparing the veterinary antimicrobial peptide sustained-release gel according to claim 1, characterized in that, Includes the following steps: Weigh out the antimicrobial peptide, hydroxypropyl methylcellulose and propylene glycol according to the formula, and add distilled water to make up to 100%. After mixing, the veterinary antimicrobial peptide sustained-release gel is obtained.

4. The application of the veterinary antimicrobial peptide sustained-release gel according to claim 1 in the preparation of antimicrobial drugs, characterized in that, The antibacterial drug is a veterinary drug.

5. The application according to claim 4, characterized in that, The antibacterial drug uses the veterinary antimicrobial peptide sustained-release gel as its active ingredient.

6. The application according to claim 5, characterized in that, The antibacterial drug is used against Staphylococcus aureus.

7. The application of the veterinary antimicrobial peptide sustained-release gel of claim 1 in the preparation of a medicament for treating bacterial skin diseases in livestock farming, characterized in that, The bacterial dermatitis is a skin infection caused by methicillin-resistant Staphylococcus aureus (ATCC) 33591.

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