Bromofuranone C-30 sustained-release agent and preparation method and application thereof

Abstract

The application discloses a bromofuranone C-30 slow-release agent and a preparation method and application thereof. The bromofuranone C-30 slow-release agent is prepared by dissolving bromofuranone in ethyl acetate, adding silica to prepare fine particles, and then coating the fine particles with palm wax to obtain the bromofuranone C-30 slow-release agent. The bromofuranone C-30 slow-release agent effectively improves the stability of bromofuranone C-30, avoids the absorption of bromofuranone C-30 in the stomach of animals, prolongs the action time of bromofuranone C-30 in the intestinal tract, and can be applied to livestock, poultry and aquatic animal feed. The preparation method of the bromofuranone C-30 slow-release agent is simple in process and low in production cost.

Description

Technical Field

[0001] This invention belongs to the field of feed additive technology, specifically relating to a bromofuranone C-30 sustained-release agent, its preparation method, and its application. Background Technology

[0002] Bacteria, through their quorum sensing system regulated by signaling molecules, secrete polymers such as polysaccharides, proteins, and DNA, encapsulating themselves within these polymers to form biofilms. Bacteria with well-developed quorum sensing systems can form biofilms that are typically resistant to bactericides. Antibiotics that cannot penetrate biofilms struggle to reach the bacteria within them or achieve the necessary concentrations for antibacterial activity, thus failing to exert their bacteriostatic or bactericidal effects. This poses significant challenges to animal disease control and treatment, indirectly contributing to the overuse of antibiotics in animal disease treatment and the emergence of numerous drug-resistant strains. Therefore, establishing new antimicrobial therapies in animal husbandry is urgently needed. It is estimated that over 60% of refractory microbial infections are related to bacterial biofilm formation. Therefore, inhibiting bacterial biofilm formation by interfering with the quorum sensing system is highly likely to be an effective antimicrobial therapy.

[0003] Halogenated furans are a novel antibacterial agent that has attracted much attention in recent years. Studies have shown that halogenated furans can control bacterial biofilm formation by blocking the signal transduction pathways of the quorum sensing system for most Gram-positive and Gram-negative bacteria, thereby exerting an antibacterial effect without inducing bacterial resistance. They exhibit high biosafety, with no cytotoxicity or genotoxicity. Research has found that natural or synthetic bromofuranones can effectively inhibit the bacterial quorum sensing system and reduce bacterial pathogenicity. Among them, the synthetic bromofuranone C-30 exhibits very high in vitro antibacterial activity, but its in vivo antibacterial activity in animals remains unknown. If bromofuranone C-30 is used directly as a feed additive, it will be rapidly absorbed in the animal's stomach, reducing its efficacy in treating bacterial infections. Furthermore, because bromofuranones are heat-sensitive, they are easily degraded during feed production, resulting in significant losses. The synthetic yield of bromofuranone C-30 is low, with the first-step reaction yield only 40%–66% and the second-step reaction yield only 11%–54%. Therefore, it is urgent to improve the yield of artificial synthesis of bromofuranone C-30, overcome its instability and easy absorption in animal stomachs, and promote its widespread application in animal husbandry as an alternative to antibiotics. Summary of the Invention

[0004] The purpose of this invention is to provide a sustained-release agent of bromofuranone C-30, its preparation method, and its application. This formulation effectively improves the stability of bromofuranone C-30 and avoids its absorption in the animal's stomach, prolonging its action time in the intestine. It can be added to the feed of livestock, poultry, and aquatic animals as a bacterial quorum sensing inhibitor to reduce bacterial pathogenicity. At the same time, the preparation method of this sustained-release agent is simple and has low production cost.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] In a first aspect, the present invention provides a method for preparing bromofuranone C-30, comprising the following steps:

[0007] S1. In the presence of a catalyst and solvent, levulinic acid undergoes a bromination reaction with liquid bromine to give 3,5-dibromo-4-oxopentanoic acid.

[0008] S2. In the presence of a dehydrating agent, the 3,5-dibromo-4-oxovalerate undergoes a cyclization reaction to obtain the bromofuranone C-30.

[0009] The bromofuranone C-30 of this invention has the following structure:

[0010]

[0011] The synthetic route for the above-mentioned bromofuranone C-30 is as follows:

[0012]

[0013] In step S1, the catalyst is selected from one or more of a hydrobromic acid solution, an aqueous solution of hydrogen bromide, and dilute hydrochloric acid; preferably a 40% hydrobromic acid solution.

[0014] In step S1, the solvent is selected from one or more of dichloromethane, trichloromethane, and petroleum ether.

[0015] In step S1, the molar ratio of levulinic acid to the catalyst is 1:(0.01-0.05), preferably 1:(0.04-0.05).

[0016] In step S1, the molar ratio of levulinic acid to liquid bromine is 1:(0.9-1.1), preferably 1:1.

[0017] In step S1, the reaction conditions for the bromination reaction are as follows:

[0018] The temperature is 30–80℃, preferably 45–55℃; specifically, it can be an oil bath.

[0019] The reflux time is 50–120 min, preferably 85–95 min.

[0020] In step S1, after the reaction is completed, the reaction solution is washed with water, extracted, washed with anhydrous sodium sulfite solution, concentrated under reduced pressure, and dried to obtain the 3,5-dibromo-4-oxopentanoic acid.

[0021] In step S2, the dehydrating agent is selected from one or more of concentrated sulfuric acid, phosphorus pentoxide, calcium chloride and magnesium sulfate, preferably concentrated sulfuric acid.

[0022] In step S2, the molar ratio of 3,5-dibromo-4-oxovalerate to the dehydrating agent is 1:(2-40), preferably 1:(30-40).

[0023] In step S2, the reaction conditions for the ring-closing reaction are as follows:

[0024] The temperature is 80–150℃, preferably 95–105℃, such as 100℃;

[0025] The time is 10 to 50 minutes, preferably 15 to 25 minutes.

[0026] In step S2, after the reaction is completed, the reaction solution is cooled, a solid precipitates, is filtered, dissolved in dichloromethane, and an appropriate amount of petroleum ether is added and rotary evaporated to obtain the bromofuranone C-30.

[0027] In a second aspect, the present invention further provides a bromofuranone C-30 sustained-release agent, comprising the following components: a core material and a packaging material covering the outer surface of the core material;

[0028] The core material is composed of nano-silica and bromofuranone C-30 embedded in the pores of the nano-silica;

[0029] The packaging material is made of palm wax.

[0030] In the bromofuranone C-30 sustained-release agent, the mass fraction of bromofuranone C-30 is 40% to 44%, specifically 40%, 42%, or 44%.

[0031] Thirdly, the present invention further provides a method for preparing the bromofuranone C-30 sustained-release agent, comprising the following steps:

[0032] (1) Dissolve the bromofuranone C-30 in a solvent to prepare a saturated solution, add the nano-silica, and obtain the core material;

[0033] (2) The palm wax solution is added to the core material to prepare the bromofuranone C-30 sustained-release agent.

[0034] In step (1), the solvent is selected from one or more of ethyl acetate, dichloromethane and petroleum ether.

[0035] In step (1), the particle size of the nano-silica is 30-500nm, preferably 50-200nm, and specifically can be 50nm, 100nm or 200nm.

[0036] In step (1), the amount of nano-silica added is 20% to 80% of the mass of the bromofuranone C-30, specifically 20%, 50% or 80%.

[0037] In step (1), the stirring temperature is room temperature and the time is 5 to 20 hours, specifically 8 hours, 12 hours or 16 hours.

[0038] In step (1), the nano-silica is added to a saturated solution containing the bromofuranone C-30, and after stirring, filtering, and drying, the core material is obtained.

[0039] In step (2), the mass fraction of palm wax in the palm wax solution is 0.5% to 1.25%, specifically 0.5%, 0.75%, or 1.25%.

[0040] In step (2), the amount of palm wax solution added is 10% to 100% of the mass of the nano silica, specifically 30%, 50% or 100%.

[0041] In step (2), the stirring temperature is room temperature and the time is 10 to 30 minutes, specifically 10 minutes, 20 minutes or 30 minutes.

[0042] In step (2), the palm wax solution is added to the core material, stirred, and dried to obtain the bromofuranone C-30 sustained-release agent.

[0043] Fourthly, the present invention further provides the application of the bromofuranone C-30 sustained-release agent as a bacterial quorum sensing inhibitor in the feed of livestock, poultry and aquatic animals.

[0044] The aquatic animals mentioned are one of zebrafish, tilapia, carp, largemouth bass, and shrimp.

[0045] The amount of the brominated furanone C-30 sustained-release agent added is 0.00001 to 2.27 kg / t of feed, preferably 0.0001 to 0.02 kg / t of feed, and more preferably 0.0001 to 0.0003 kg / t of feed.

[0046] Compared with the prior art, the present invention has the following characteristics:

[0047] 1) The preparation method of bromofuranone C-30 provided by this invention is simple to operate and has a high yield of bromofuranone C-30. In existing artificial synthesis methods, the yield of the first step reaction is only 40% to 66%, and the yield of the second step reaction is only 11% to 54%; while in the preparation method provided by this invention, the yield of 3,5-dibromo-4-oxopentanoic acid obtained in step S1 reaches 80% to 85%, and the yield of bromofuranone C-30 obtained in step S2 reaches 70% to 80%.

[0048] 2) The bromofuranone C-30 slow-release agent provided by this invention can withstand high-temperature treatment and is suitable for feed pelleting.

[0049] 3) The bromofuranone C-30 sustained-release agent provided by this invention has strong stability and is not easily decomposed during storage.

[0050] 4) The brominated furanone C-30 sustained-release agent provided by this invention has a low release rate in the animal stomach, can be continuously released in the intestine, and has a long duration of action, up to 72 hours.

[0051] 5) The preparation method of the brominated furanone C-30 sustained-release agent provided by the present invention requires simple equipment, has low reagent toxicity, is easy to operate, and is convenient for industrial production.

[0052] 6) The bromofuranone C-30 slow-release agent provided by the present invention can be added to the feed of livestock, poultry and aquatic animals as a bacterial quorum sensing inhibitor to reduce bacterial pathogenicity; the optimal addition amount of the bromofuranone C-30 slow-release agent is 0.0001 to 0.0003 kg / t. At this dosage, the cost is not significantly increased, and the ability of fish and shrimp to resist pathogens can be effectively improved. Attached Figure Description

[0053] Figure 1 The effect of the addition level of the brominated furanone C-30 sustained-release agent provided by the present invention on the mortality rate of zebrafish (48h).

[0054] Figure 2 The effect of the addition level of the brominated furanone C-30 sustained-release agent provided by the present invention on the growth of zebrafish.

[0055] Figure 3 The effect of the addition level of the brominated furanone C-30 sustained-release agent provided by the present invention on the intestinal immunity of zebrafish.

[0056] Figure 4 The effect of the addition level of the brominated furanone C-30 sustained-release agent provided by the present invention on the antioxidant capacity of zebrafish intestine.

[0057] Figure 5 The effect of the addition level of the brominated furanone C-30 sustained-release agent provided by the present invention on the mortality rate of zebrafish (72h). Detailed Implementation

[0058] The present invention will be further described below with reference to specific embodiments, but the present invention is not limited to the following embodiments. Unless otherwise specified, the methods described are conventional methods. Unless otherwise specified, the raw materials are all available from publicly available commercial sources.

[0059] The specifications and sources of the reagents used in the following examples are as follows:

[0060] Acetopropionic acid, dichloromethane, 40% hydrobromic acid solution, liquid bromine, anhydrous sodium sulfite, concentrated sulfuric acid, and ethyl acetate were all purchased from Shanghai Sinopharm Chemical Reagent Co., Ltd., and all were analytical grade reagents.

[0061] Nano silica and palm wax were purchased from Shanghai Maclean Biochemical Technology Co., Ltd., and both were analytical grade reagents.

[0062] Example 1: Preparation of (Z)-4-bromo-5-bromomethylene-2(5H)-furanone C-30

[0063] (1) Weigh 69.6g of levulinic acid (0.6mol) into a 2000mL flask, add 600mL of dichloromethane (9.36mol) and 12 drops of 40% hydrobromic acid solution, stir, add 210g of liquid bromine (0.6mol) and 240mL of dichloromethane (3.74mol) into a constant pressure dropping funnel, slowly add the liquid from the constant pressure funnel into the flask, and after the addition is complete, heat in an oil bath to 50℃ and reflux for 1.5 hours.

[0064] After the reaction was complete, the sample was washed with 800 mL of water, extracted with dichloromethane, washed with anhydrous sodium sulfite solution, extracted with dichloromethane, and the combined organic phases were concentrated to give a white solid with a yield of 80%.

[0065] The specific results of the MRI scan are as follows: 1 ¹H NMR (CHCl₃, TMS, 400MHz): δ=3.05(dd, J=8.0, 20.0Hz, 1H), 3.37(dd, J=8.0, 20.0Hz, 1H), 4.18(d, J=12.0Hz, 1H), 4.38(d, J=12.0Hz, 1H), 5.01(t, J=8.0Hz, 1H). The obtained product was confirmed to be 3,5-dibromo-4-oxopentanoic acid.

[0066] (2) Take 100g of 3,5-dibromo-4-oxovalerate (0.37mol) into a 1000mL flask, add 650mL of concentrated sulfuric acid (12.2mol), heat to 100℃ and stir for 20min; let it stand at room temperature, pour it into crushed ice, and a large amount of yellow solid precipitates. Filter, dissolve in dichloromethane, add an appropriate amount of petroleum ether and rotary evaporate, and a large amount of yellow solid precipitates, which is the pure product (Z)-4-bromo-5-bromomethylene-2(5H)-furanone, with a yield of 80%.

[0067] The specific results of the MRI scan are as follows: 1 ¹H NMR (CHCl₃, TMS, 400 MHz): δ = 6.51 (s, 1H), 6.42 (s, 1H). The obtained product was confirmed to be (Z)-4-bromo-5-bromomethylene-2(5H)-furanone C-30.

[0068] Comparative Example 1: Preparation of bromofuranone C-30 by existing methods

[0069] (1) 12.34 g (106.3 mmol) of levulinic acid was dissolved in 100 mL of dichloromethane and placed in a 250 mL three-necked flask. A thermometer was added, and the mixture was stirred magnetically and cooled to 0 °C in an ice bath. Ten drops of 90% hydrogen bromide glacial acetic acid solution were added dropwise. 35.78 g of bromine was dissolved in 20 mL of dichloromethane to prepare a solution, which was added dropwise to the three-necked flask at 0 °C. After the addition was complete, the mixture was stirred at room temperature for 2 h, washed with 50 mL of water, and then washed with 0.5 M Na2S2O3. The aqueous phases were combined and extracted twice with 60 mL of water. The organic phases were combined and dried with anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated by rotary evaporation. Petroleum ether (60–90 °C) was added and stirred to precipitate a large amount of white solid. The solid was filtered, washed with petroleum ether, and 14.01 g of white solid was obtained, with a yield of 48%.

[0070] (2) Dissolve 4.0 g of the above white solid in 20 mL of concentrated sulfuric acid. Stir at room temperature and react at 110 °C for 20 min. After cooling to room temperature, pour into crushed ice and stir vigorously. A yellow insoluble substance precipitates out. Extract with 200 mL of dichloromethane four times. Wash with saturated sodium chloride solution until neutral. Combine the aqueous phases and extract with 100 mL of dichloromethane twice. Combine the organic phases and dry with anhydrous sodium sulfate. Filter and evaporate the filtrate by rotary evaporation to obtain 2.76 g of brownish-yellow solid. Recrystallize twice with dichloromethane and petroleum ether (60–90 °C) to obtain 0.42 g of pale yellow needle-like crystals, with a yield of 11.2%.

[0071] Example 2: Preparation of Bromofuranone C-30 Sustained-Release Agent

[0072] 40g of bromofuranone C-30 (prepared in Example 1) was dissolved in 100mL of ethyl acetate, 8g of 50nm nano-silica was added, the mixture was stirred for 8h, filtered, and dried to obtain fine particles; then 4g of 1.25% palm wax solution was added to the fine particles, stirred for 20min, and dried to obtain bromofuranone C-30 sustained-release agent with a drug loading of 44%.

[0073] Example 3: Preparation of Bromofuranone C-30 sustained-release agent

[0074] 40g of bromofuranone C-30 (prepared in Example 1) was dissolved in 100mL of ethyl acetate, 20g of 100nm nano-silica was added, the mixture was stirred for 12h, filtered, and dried to obtain fine particles; then 10g of 0.5% palm wax solution was added to the fine particles, stirred for 30min, and dried to obtain bromofuranone C-30 sustained-release agent with a drug loading of 42%.

[0075] Example 4: Preparation of Bromofuranone C-30 sustained-release agent

[0076] 40g of bromofuranone C-30 (prepared in Example 1) was dissolved in 100mL of ethyl acetate, 32g of 200nm nano-silica was added, the mixture was stirred for 16h, filtered, and dried to obtain fine particles; then 32g of 0.75% palm wax solution was added to the fine particles, stirred for 10min, and dried to obtain bromofuranone C-30 sustained-release agent with a drug loading of 40%.

[0077] Comparative Example 2: Preparation of Bromofuranone C-30 Sustained-Release Agent using Talc Carrier

[0078] 40g of bromofuranone C-30 (prepared in Example 1) was dissolved in 100mL of ethyl acetate, 20g of talc was added, the mixture was stirred for 12h, filtered, and dried to obtain a powder sample; then 32g of 0.75% palm wax solution was added to the powder sample, stirred for 10min, and dried to obtain bromofuranone C-30 sustained-release agent with a drug loading of 10%.

[0079] The results showed that the drug loading of the obtained sustained-release agent was low, which indicates that using nano-silica as a carrier has the advantage of high drug loading capacity.

[0080] Comparative Example 3: Preparation of Bromofuranone C-30 Sustained-Release Agent using Sodium Alginate Coating Material

[0081] 40g of bromofuranone C-30 (prepared in Example 1) was dissolved in 100mL of ethyl acetate, 8g of 50nm nano-silica was added, the mixture was stirred for 8h, filtered, and dried to obtain fine particles; then 4g of 1.25% sodium alginate solution was added to the fine particles, stirred for 20min, and dried to obtain bromofuranone C-30 sustained-release agent with a drug loading of 44%.

[0082] The results showed that the obtained sustained-release agent exhibited severe clumping and poor coating uniformity, indicating that using palm wax as a coating material has the advantages of high uniformity and dispersibility.

[0083] Example 5: Effect of Bromofuranone C-30 Slow-Release Additive Level on Zebrafish Mortality

[0084] Two-month-old zebrafish were fed a basal diet with 0, 0.227 μg / g, 2.27 μg / g, and 22.7 μg / g of bromofuranone C-30 sustained-release agent (prepared in Example 2, with a drug loading of 44%), respectively. The zebrafish were then challenged with Vibrio parahaemolyticus ZB-1 for 14 days, and the mortality rate was calculated.

[0085] like Figure 1 As shown, adding bromofuranone C-30 slow-release agent to feed can effectively reduce the mortality rate of zebrafish and improve their resistance to Vibrio parahaemolyticus ZB-1 infection. Specifically, without the addition of bromofuranone C-30 slow-release agent, the mortality rate of zebrafish is very high, reaching over 40% after 20 hours. Adding 0.227 μg / g can effectively reduce the mortality rate of zebrafish; adding 2.27 μg / g can significantly reduce the mortality rate, but the feed cost is high; adding 22.7 μg / g actually increases the mortality rate of zebrafish. Furthermore, the experiment also confirmed that when the dosage of bromofuranone C-30 slow-release agent prepared in this invention is below 0.00001 kg / t (0.01 μg / g), the improvement in the resistance of fish and shrimp to pathogens is not significant. Taking all factors into consideration, the optimal addition amount of bromofuranone C-30 slow-release agent is between 0.0001 and 0.0003 kg / t (0.1 to 0.3 μg / g), which neither significantly increases costs nor significantly reduces the ability of fish and shrimp to resist pathogens.

[0086] Example 6: Effects of Bromofuranone C-30 Sustained-Release Agent on Zebrafish Growth and Intestinal Health

[0087] 0, 0.227 μg / g, 22.7 μg / g, and 2270 μg / g of bromofuranone C-30 sustained-release agent (prepared in Example 2, with a drug loading of 44%) were added to the basal diet, respectively. One-month-old zebrafish were fed for 4 weeks, and samples were collected to analyze the effects of adding bromofuranone C-30 sustained-release agent to the diet on the growth and intestinal health of zebrafish.

[0088] like Figure 2As shown, without the addition of bromofuranone C-30 slow-release agent, the weight gain rate of zebrafish was approximately 175%. When the addition amount was 0.227 μg / g, the weight gain rate significantly increased, exceeding 200%. However, when the addition amount was 22.7 μg / g, the weight gain rate decreased. Finally, when the addition amount was 2270 μg / g, the weight gain rate remained essentially unchanged. Therefore, it can be concluded that adding 0.227 μg / g of bromofuranone C-30 slow-release agent to the feed can significantly improve the growth performance of zebrafish, resulting in the highest weight gain rate.

[0089] like Figure 3 As shown, the relative expression level of immunoglobulins was 1.0 when no bromoxynil C-30 sustained-release agent was added; the relative expression level of immunoglobulins was significantly increased when the added amount was 0.227 μg / g, 22.7 μg / g, and 2270 μg / g. This indicates that when the added amount of bromoxynil C-30 sustained-release agent in the feed is 0.227 μg / g, 22.7 μg / g, and 2270 μg / g, it can significantly improve the intestinal immunity of zebrafish.

[0090] like Figure 4 As shown, the relative expression level of superoxide dismutase (SOD) was 1.0 without the addition of bromofuranone C-30 sustained-release agent. The relative expression level of SOD significantly increased when the added amounts were 0.227 μg / g and 22.7 μg / g. However, the relative expression level of SOD remained unchanged when the added amount was 2270 μg / g. This indicates that the addition of bromofuranone C-30 sustained-release agent to the feed at amounts of 0.227 μg / g and 22.7 μg / g can significantly improve the antioxidant capacity of the zebrafish intestine.

[0091] Example 7: High-temperature resistance of bromofuranone C-30 sustained-release agent

[0092] The specific investigation steps are as follows: 1.0g of bromofuranone C-30 sustained-release agent (prepared from Example 2, with a drug loading of 44%) and 0.44g of bromofuranone C-30 were respectively placed into sealed transparent glass bottles and heated in an oven at 100°C for 10 minutes. Red gas appeared in the bromofuranone C-30 bottle, while no red gas was produced in the sustained-release agent bottle. The test proved that bromofuranone C-30 is easily decomposed to produce elemental bromine at high temperatures, while the bromofuranone C-30 sustained-release agent provided by this invention can withstand high-temperature treatment and is suitable for feed pelleting.

[0093] Example 8: Stability of Bromofuranone C-30 sustained-release formulation

[0094] The specific investigation steps are as follows: 1.0g of bromofuranone C-30 sustained-release agent (prepared from Example 2, with a drug loading of 44%) and 0.44g of bromofuranone C-30 were respectively placed in sealed transparent glass bottles and placed at room temperature for 30 days. A red substance appeared in the bromofuranone C-30 bottle, but no red substance was produced in the sustained-release agent bottle. The test proved that the sustained-release agent has strong stability and is not easily decomposed during storage.

[0095] Example 8: The sustained-release properties of bromofuranone C-30 sustained-release agent

[0096] The specific investigation steps are as follows: 10 μg / g of bromofuranone C-30 and 22.7 μg / g of a slow-release agent (prepared in Example 2, with a drug loading of 44%) were added to the basal diet. Two-month-old zebrafish were fed for 14 days and challenged with Vibrio parahaemolyticus ZB-1. The mortality rate was calculated. Figure 5 As shown, within 72 hours of the challenge, the mortality rate of zebrafish in the sustained-release group was consistently lower than that in the brominated furanone C-30 group, demonstrating that the sustained-release agent has a low release rate in the animal's stomach, can be continuously released in the intestine, and has a long duration of action, up to 72 hours.

[0097] Although the present invention has been described in detail above with general descriptions and specific embodiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. The application of a brominated furanone C-30 sustained-release agent in the preparation of bacterial quorum sensing inhibitors; The bacterial quorum sensing inhibitor is applied to aquatic animal feed; The dosage of the brominated furanone C-30 sustained-release agent is 0.00001–2.27 kg / t of feed; The bromofuranone C-30 sustained-release agent comprises the following components: a core material and a packaging material covering the outer surface of the core material; The core material is composed of nano-silica and bromofuranone C-30 embedded in the pores of the nano-silica; The packaging material is made of palm wax; The mass fraction of bromofuranone C-30 in the bromofuranone C-30 sustained-release agent is 40% to 44%.

2. The application according to claim 1, characterized in that: The preparation method of the bromofuranone C-30 sustained-release agent includes the following steps: (1) Dissolve the bromofuranone C-30 in a solvent to prepare a saturated solution, add the nano-silica, and obtain the core material; (2) The palm wax solution is added to the core material to prepare the bromofuranone C-30 sustained-release agent.

3. The application according to claim 2, characterized in that: In step (1), the solvent is selected from one or more of ethyl acetate, dichloromethane, and petroleum ether; The particle size of the nano-silica is 30–500 nm; The amount of nano-silica added is 20% to 80% of the mass of the bromofuranone C-30.

4. The application according to claim 2 or 3, characterized in that: In step (2), the mass fraction of palm wax in the palm wax solution is 0.5% to 1.25%; The amount of palm wax solution added is 10% to 100% of the mass of the nano-silica.

5. The application according to claim 1, characterized in that: The aquatic animals mentioned are one of zebrafish, tilapia, carp, largemouth bass, and shrimp.

Images