Compound parasite expelling granules for aquaculture as well as preparation method and application of compound parasite expelling granules

Abstract

The invention belongs to the technical field of aquaculture, and discloses compound parasite-expelling granules for aquaculture and a preparation method and application thereof, and the compound parasite-expelling granules are prepared from methylamino abamectin benzoate, novaluron, a surfactant, an antioxidant, a disintegrating agent and a filler. According to the invention, methylamino abamectin benzoate and chlorfenuron are selected as active components to repel and kill crustacean parasites, and at present, an oral anthelmintic compounded by the two components as active components and used for aquaculture does not exist. The methylamino abamectin benzoate death by paralyzing insect bodies, has slow metabolism in vivo, has high toxicity to aquatic animals, and is not easy to use in a large amount or for a long time; the main action mechanism of the novaluron is to inhibit the synthesis of chitin, and the novaluron takes effect slowly, but is relatively safe to aquatic animals, and has a special effect on resistant parasites such as organic phosphorus, pyrethroid and the like. Clinical verifications show that the two components have a synergistic effect, and the killing effect on crustacean parasites is far better than that of an existing aquatic insecticide.

Description

Technical Field

[0001] The invention belongs to the technical field of aquaculture, and particularly relates to a compound anthelmintic granule for aquaculture, and a preparation method and application thereof. Background Art

[0002] my country is a major aquaculture country with an annual output of over 68 million tons, and freshwater aquaculture accounts for about 70% of the global total. In freshwater aquaculture, there are three main types of parasites, namely protozoa, helminths and crustaceans. Among them, crustacean parasites have many types of infections, high infection rates and great harm.

[0003] Crustaceans are relatively primitive species among arthropods. Their main characteristics are that their bodies are segmented irregularly, with three parts: head, thorax, and abdomen. They have chitinous exoskeleton, two pairs of pedipalps, jointed appendages, and an open-tube circulatory system. There are many species of crustaceans, most of which are beneficial to humans, but some of them parasitize on the bodies of aquatic animals, affecting their growth and development, and causing mass deaths in severe cases. The main parasitic crustaceans are copepods, branchioceras, cirripedes, isopods, and decapods. The representative parasites of freshwater aquaculture in my country include Chinese mullet, anchorhead mullet, and silver carp. Crustacean parasites are very harmful to aquatic animals of all ages. They attach to the body surface or gills of aquatic animals, suck the blood and mucus of the host, and seriously affect their healthy growth. In addition, because the parasites cause tissue trauma to the host's parasitic site, bacteria and viruses are more likely to invade the trauma site, causing complications or secondary diseases.

[0004] At present, national standard drugs for the prevention and control of aquaculture crustacean parasites are mainly divided into national standard products and non-national standard products. National standard products include pyrethroids (deltamethrin solution, high-efficiency cypermethrin solution, cypermethrin solution), organophosphates (phoxim solution) and trichlorfon (trichlorfon solution, refined trichlorfon powder). The main ingredients of these products are pesticides, which have poor safety and have certain impacts on the environment and food safety. In addition, since aquatic veterinary drugs have not been updated for many years, drug resistance has become generally serious, which has led to breeders often increasing the dosage during clinical use, which is prone to drug-related accidents. Non-national standard products are usually registered and sold in the form of non-drugs. The ingredients of these products are unknown, and they usually use organic reagents such as isopropyl alcohol, methanol, ethyl acetate, xylene, acetone, etc. as solvents. Their safety and effectiveness need to be further verified.

[0005] Whether they are national standard products or non-national standard products, these insecticides are all external solution preparations, which are diluted with water and then put into the aquaculture water. On the one hand, these insecticides are greatly affected by the environment when used, and they are easy to emulsify and precipitate drug crystals when they come into contact with water, making it difficult to achieve the expected effect; on the other hand, the dosage is difficult to control, which is prone to drug-related accidents and environmental pollution. Summary of the invention

[0006] In order to solve the problems existing in the above-mentioned prior art, the first purpose of the present invention is to provide a compound anthelmintic granule for aquaculture. The compound anthelmintic granule of the present invention is administered orally, has good stability and fast release in vivo, can effectively prevent and treat crustacean parasites when taken orally, is safe for aquatic animals, is friendly to the breeding environment, and can be made into spherical granules of different diameters according to the actual size of feed, which is convenient for clinical mixing use.

[0007] Another object of the present invention is to provide a method for preparing compound anthelmintic granules for aquaculture. The method is simple and easy to operate. The prepared compound anthelmintic granules have good stability and good water dispersibility. The clinical dosage is much lower than the dosage of existing national standard or non-national standard crustacean parasiticides.

[0008] Another object of the present invention is to provide an application of the compound anthelmintic granules in aquaculture to kill crustacean parasites parasitic on fish.

[0009] The technical solution adopted to achieve the above-mentioned purpose of the present invention is:

[0010] A compound anthelmintic granule for aquaculture, prepared from the following raw materials in percentage by weight:

[0011]

[0012] Furthermore, the surfactant is at least one of heavy alkyl benzene sodium sulfonate, secondary alkyl sodium sulfonate, secondary alkyl sodium sulfate, α-olefin sodium sulfonate, sulfosuccinate, alkylphenol polyoxyethylene ether, and fatty alcohol polyoxyethylene ether.

[0013] Furthermore, the antioxidant is at least one of butylated hydroxyanisole, propyl gallate and butylated hydroxytoluene.

[0014] Furthermore, the disintegrant is at least one of sodium carboxymethyl starch, hydroxypropyl cellulose, and cross-linked polyvinyl pyrrolidone.

[0015] Furthermore, the filler is at least one of corn starch, pregelatinized starch, powdered sugar, lactose, dextrin, microcrystalline cellulose, and calcium carbonate.

[0016] Benzoic acid emamectin methylamino avermectin in the present invention is also called emamectin methylamino avermectin benzoate, emamectin benzoate, emamectin, is a kind of semi-synthetic antibiotic insecticide synthesized from fermentation product avermectin B1, soluble in acetone and methanol, slightly soluble in water, insoluble in hexane. Benzoic acid emamectin methylamino avermectin has stomach poison, contact killing effect, can enhance the effect of neurotic such as glutamic acid and gamma-aminobutyric acid (GABA), so that a large amount of chloride ions enter nerve cells, cell function is lost, nerve conduction is disturbed, irreversible paralysis is caused in the insect body, and the highest lethality is reached in 3-4 days. Benzoic acid emamectin methylamino avermectin is usually made into emulsifiable concentrate, used in cash crops such as vegetables, tobacco, tea, cotton, fruit trees, etc., for driving and killing insects such as mites, Lepidoptera, Coleoptera. At present, the registered emulsifiable concentrates of emamectin benzoate in China have various content specifications such as 0.2%, 0.5%, 0.8%, 1%, 1.5%, 2%, 2.2%, 3%, 5%, 5.7%, etc. There have been studies on the use of emamectin benzoate for deworming marine fish abroad, but there is no insecticide for deworming freshwater aquaculture in China.

[0017] Flubenzuron in the present invention is a phenylformyl urea insecticide, which has stomach poison and contact killing effects, no systemic effect, and is a low-toxic insecticide. It is low-toxic to fish and birds, non-toxic to bees, and safe to crops. The mechanism of action of flubenzuron is mainly to inhibit chitin synthesis. After the insect body contacts, it destroys the formation of insect chitin, thereby preventing the further growth of the insect exoskeleton.

[0018] Accordingly, the present invention also claims a method for preparing the aforementioned compound anthelmintic granules for aquaculture, the steps of which are as follows:

[0019] S1. dispersing a surfactant in water to obtain an aqueous surfactant solution with a mass concentration of 20% to 30%;

[0020] S2, crushing and sieving avermectin benzoate and flubendiamide, and then adding them into the surfactant aqueous solution respectively, stirring evenly to obtain an emulsion;

[0021] S3, uniformly mixing the disintegrant, antioxidant and filler to obtain a mixed excipient, adding 70-85w% of the mixed excipient into a round pot granulator, spraying atomized water, and simultaneously starting spheronization granulation under heating conditions to spheronize the material to form a base core;

[0022] S4. When the diameter of the base core reaches 0.5-1.5 mm, the emulsion is sprayed into a granulator (spraying pressure 0.1-0.2 MPa), and the remaining mixed auxiliary materials are added to the granulator to round the materials into spherical particles, which are the compound anthelmintic particles for aquaculture.

[0023] Furthermore, in the step S3, the rotation speed during spheronization is 25-35 rpm and the temperature is 45-60°C.

[0024] Furthermore, the diameter of the base core is 0.5-1.5 mm, and the diameter of the compound anthelmintic granules for aquaculture is 2.0-3.5 mm.

[0025] Both avermectin benzoate and flubenzuron are insoluble in water. In the existing preparation technology, organic solvents such as toluene, xylene, and acetone are usually used to make emulsifiable concentrates. If avermectin benzoate or flubenzuron emulsifiable concentrates are directly used for aquatic insecticide, they are mixed with water to form an emulsion, which is precipitated after being placed for 1-2 hours, and the crustacean parasites in the water body cannot be effective. The dosage is difficult to grasp, and due to the use of more pesticides and organic solvents, the safety is poor and the environment is polluted. The present invention first prepares the base core with mixed auxiliary materials, and then avermectin and flubenzuron are uniformly atomized and sprayed on the surface of the base core with a mixed solution of surfactant, and the water is evaporated by heating at the same time to form drug particles. Compared with common emulsifiable concentrate dosage forms, the drug is more stable in a solid state, and at the same time, due to being wrapped in the outer layer of the particles, it can be released and absorbed more quickly in vivo when it is used for oral deworming of aquatic animals. It is found through clinical verification that its killing effect on crustacean parasites is far superior to existing aquatic insecticides.

[0026] Accordingly, the present invention also claims to protect the use of the aforementioned compound anthelmintic granules in aquaculture, and the use of the compound anthelmintic granules for aquaculture in the preparation of anthelmintics or insecticides for aquaculture.

[0027] Furthermore, the worms are crustacean parasites that parasitize fish.

[0028] Compared with the prior art, the advantages and beneficial effects of the present invention are:

[0029] 1. The present invention selects avermectin benzoate and flubenzuron as active ingredients to kill crustacean parasites. At present, there is no oral anthelmintic for aquaculture using these two ingredients as active ingredients. Emamectin benzoate paralyzes the parasites and metabolizes slowly in the body. It is highly toxic to aquatic animals and is not easy to use in large quantities or for a long time. Flubenzuron has a main mechanism of action of inhibiting chitin synthesis and has a slow onset, but is relatively safe for aquatic animals and has special effects on parasites that are resistant to organophosphorus, pyrethroids, etc. Clinical verification has found that the two have synergistic effects, and the killing effect on crustacean parasites is far better than existing aquatic insecticides.

[0030] 2. The compound anthelmintic granules of the present invention can be orally administered for 3 to 5 days at a clinical dosage of 25 mg / kg bw to effectively kill crustacean parasites on fish. The dosage is much lower than the dosage of the existing national standard anti-crustacean parasite drug (30% trichlorfon solution: per 1m3 Water: 0.33~0.67g; 4.5% highly effective cypermethrin solution: per 1m 3 Water: 0.02~0.03ml; 1% cypermethrin solution: per 1m 3 Water: 15-22 mg; 10% phoxim solution: per 1m 3 Water 0.1-0.12 ml). Due to oral administration, the compound anthelmintic granules of the present invention have no irritation and are safe to aquatic animals and various aquatic organisms. At the same time, since no organic solvent is used, they are environmentally friendly.

[0031] 3. The compound anthelmintic granules of the present invention have a reasonable formula design. Since both raw materials are insoluble in water and difficult to disperse in water, suitable surfactants are screened through experiments so that the two raw materials can be evenly dispersed in the surfactant aqueous solution and sprayed with the solution atomization, thereby evenly distributed on the surface of the base core. Since the drug is wrapped in the outer layer of the granules and there is a disintegrant, it can be quickly released in the body. At this time, the surfactant plays the role of an absorption promoter. On the one hand, it can improve the apparent solubility of the drug, thereby improving the oral delivery efficiency of lipophilic drugs, and on the other hand, it can reduce the metabolic effects of various enzymes on the drug, destroy the tight connection of the digestive tract, improve the fluidity of the cell membrane, promote intestinal lymphatic transport and absorption, enhance the affinity of the drug with epithelial cells, and then increase the penetration efficiency of the drug in the digestive tract, thereby improving the oral bioavailability.

[0032] 4. The raw materials of the compound anthelmintic granules of the present invention are easily available and inexpensive, the preparation method is simple and easy to operate, the preparation cost is low, and industrial large-scale production can be carried out. DETAILED DESCRIPTION

[0033] The present invention is described in detail below with reference to specific embodiments, but these embodiments are not to be interpreted as limiting the protection scope of the present invention in any sense.

[0034] Example 1

[0035] A compound anthelmintic granule for aquaculture, prepared from the following raw materials in percentage by weight:

[0036]

[0037] The preparation method of the above-mentioned compound anthelmintic granules for aquaculture is as follows:

[0038] 1. Disperse 8 g of disodium sulfosuccinate in water to obtain a disodium sulfosuccinate aqueous solution with a mass concentration of 22%.

[0039] 2. Grind 0.2 g of avermectin benzoate and 0.25 g of flubenzuron through a 100-mesh sieve, then add them to the aqueous solution of disodium sulfosuccinate, stir to form a uniform emulsion, and set aside.

[0040] 3. Mix 4 g of cross-linked polyvinyl pyrrolidone, 0.1 g of butylated hydroxyanisole and 87.45 g of lactose to obtain a mixed auxiliary material, add 80 w% of the mixed auxiliary material into a round pot granulator, set the speed of the round pot granulator to 30 rpm, and heat the round pot granulator to 55 ° C, then spray an appropriate amount of atomized water, and start spheronization at the same time to make the material spheronize to form a base core.

[0041] 4. When the diameter of the base core reaches 0.5-1.5 mm, the emulsion is atomized and sprayed into a round pot granulator, and the spray pressure is set to 0.2 MPa. At the same time, the remaining 20w% of the mixed auxiliary materials are added to the granulator to round the material into spherical particles of 2.0-3.5 mm (water content below 5%), which are the compound anthelmintic particles for aquaculture.

[0042] Example 2

[0043] A compound anthelmintic granule for aquaculture, prepared from the following raw materials in percentage by weight:

[0044]

[0045]

[0046] The preparation method of the above-mentioned compound anthelmintic granules for aquaculture is as follows:

[0047] 1. Disperse 10 g of sodium secondary alkyl sulfonate SAS-60 in water to obtain a sodium secondary alkyl sulfonate aqueous solution with a mass concentration of 30%.

[0048] 2. Grind 0.05 g of avermectin benzoate and 0.5 g of flubenzuron through a 100-mesh sieve, then add them to the aqueous solution of sodium secondary alkyl sulfonate, stir to form a uniform emulsion, and set aside.

[0049] 3. Mix 4 g of sodium carboxymethyl starch, 0.1 g of butylated hydroxytoluene and 85.45 g of pregelatinized starch evenly to obtain a mixed auxiliary material, add 80 w% of the mixed auxiliary material into a round pot granulator, set the speed of the round pot granulator to 30 rpm, and heat the round pot granulator to 55 ° C, then spray an appropriate amount of atomized water, and start spheronization at the same time to make the material spheronize to form a base core.

[0050] 4. When the diameter of the base core reaches 0.5-1.5 mm, the emulsion is atomized and sprayed into a round pot granulator, and the spray pressure is set to 0.2 MPa. At the same time, the remaining 20w% of the mixed auxiliary materials are added to the granulator to round the material into spherical particles of 2.0-3.5 mm (water content below 5%), which are the compound anthelmintic particles for aquaculture.

[0051] Example 3

[0052] A compound anthelmintic granule for aquaculture, prepared from the following raw materials in percentage by weight:

[0053]

[0054] The preparation method of the above-mentioned compound anthelmintic granules for aquaculture is as follows:

[0055] 1. Disperse 7.5 g of fatty alcohol polyoxyethylene ether AEO-9 in water to obtain a fatty alcohol polyoxyethylene ether aqueous solution with a mass concentration of 20%.

[0056] 2. Grind 0.1 g of avermectin benzoate and 0.3 g of flubenzuron and pass through a 100-mesh sieve. Then add them to the fatty alcohol polyoxyethylene ether aqueous solution respectively, stir to form a uniform emulsion, and set aside.

[0057] 3. Mix 2 g of hydroxypropyl cellulose, 0.2 g of butyl hydroxyanisole, 39.9 g of microcrystalline cellulose and 50 g of corn starch to obtain a mixed auxiliary material, add 80 w% of the mixed auxiliary material into a round pot granulator, set the speed of the round pot granulator to 30 rpm, and heat the round pot granulator to 55 ° C, then spray an appropriate amount of atomized water, and start spheronization at the same time to make the material spheronize to form a base core.

[0058] 4. When the diameter of the base core reaches 0.5-1.5 mm, the emulsion is atomized and sprayed into a round pot granulator, and the spray pressure is set to 0.2 MPa. At the same time, the remaining 20w% of the mixed auxiliary materials are added to the granulator to round the material into spherical particles of 2.0-3.5 mm (water content below 5%), which are the compound anthelmintic particles for aquaculture.

[0059] Example 4

[0060] A compound anthelmintic granule for aquaculture, prepared from the following raw materials in percentage by weight:

[0061]

[0062] The preparation method of the above-mentioned compound anthelmintic granules for aquaculture is as follows:

[0063] 1. Disperse 5 g of heavy alkylbenzene sulfonate sodium OBS-50 in water to obtain a heavy alkylbenzene sulfonate aqueous solution with a mass concentration of 30%.

[0064] 2. Grind 0.25 g of avermectin benzoate and 0.1 g of flubenzuron through a 100-mesh sieve, then add them to the aqueous solution of sodium heavy alkylbenzene sulfonate, stir to form a uniform emulsion, and set aside.

[0065] 3. Mix 4 g of hydroxypropyl cellulose, 0.01 g of propyl gallate, 60.64 g of powdered sugar and 30 g of dextrin to obtain a mixed auxiliary material. Add 80 w% of the mixed auxiliary material into a round pot granulator. Set the speed of the round pot granulator to 30 rpm and heat the round pot granulator to 55 ° C. Then spray an appropriate amount of atomized water and start spheronization at the same time to spheronize the material to form a base core.

[0066] 4. When the diameter of the base core reaches 0.5-1.5 mm, the emulsion is atomized and sprayed into a round pot granulator, and the spray pressure is set to 0.2 MPa. At the same time, the remaining 20w% of the mixed auxiliary materials are added to the granulator to round the material into spherical particles of 2.0-3.5 mm (water content below 5%), which are the compound anthelmintic particles for aquaculture.

[0067] Example 5

[0068] In June 2024, at a breeding base in Dongxihu District, Wuhan City, the main breeding species was grass carp, and anchor ichthyosis (a kind of crustacean parasite) occurred. The compound anthelmintic granules prepared in Example 1 (divided into A, B, and C groups according to different dosages) were used to treat anchor ichthyosis, and a control group was set up at the same time. The agents used in the control group were 4.5% highly effective cypermethrin solution and 10% phoxim solution. Ten fish were randomly sampled from each group 3 days after administration, and the results are shown in Table 1.

[0069] Table 1 Comparison of the efficacy of different insecticides against anchor flea disease

[0070]

[0071] As can be seen from Table 1, the compound anthelmintic granules prepared in Example 1 were mixed with feed at 25 mg / kg bw and fed to fish for 3 days, which can effectively kill anchor fleas parasitic on the fish body. In the process of medication, it was found that the fish in the compound anthelmintic granule group B and group C had no abnormal phenomena such as death and swimming, there was no death in the compound anthelmintic granule group A and the high-efficiency chlorpyrifos group, a small number of fish swam sideways, and more fish swam sideways in the phoxim solution group and the non-drug group.

[0072] Example 6

[0073] In September 2024, at the same breeding base in Dongxihu District, Wuhan City, anchor ichthyosis broke out again in farmed grass carp. The compound anthelmintic granules prepared in Example 1 were used to treat anchor ichthyosis. At the same time, 0.45wt% benzoic acid emamectin granules (auxiliary materials and preparation method are the same as in Example 1) and 0.45wt% fluorobenzamide granules (auxiliary materials and preparation method are the same as in Example 1) were prepared as control groups. After 3 consecutive days of administration, 10 fish were randomly sampled from each group, and the results are shown in Table 2.

[0074] Table 2 Comparison of the efficacy of different anthelmintics on anchor lice

[0075]

[0076] As shown in Table 2, according to the same dosage, the compound anthelmintic granules prepared by Example 1 can effectively treat anchor lice, without abnormal phenomena such as death and swimming; there is no death in the flubendiamide group and the avermectin benzoate group, and a small amount of fish swims sideways, while the non-administered group has more fish deaths and more fish swim sideways. The anthelmintic effect of the compound anthelmintic granules of Example 1 is better than the anthelmintic prepared by using avermectin benzoate and flubendiamide alone.

Claims

1. A compound anthelmintic granule for aquaculture, characterized in that It is prepared from the following raw materials in weight percentage:

2. The compound anthelmintic granules for aquaculture according to claim 1, characterized in that: The surfactant is at least one of heavy alkyl benzene sodium sulfonate, secondary alkyl sodium sulfonate, secondary alkyl sodium sulfate, α-olefin sodium sulfonate, sulfosuccinate, alkylphenol polyoxyethylene ether and fatty alcohol polyoxyethylene ether.

3. The compound anthelmintic granules for aquaculture according to claim 1, characterized in that: The antioxidant is at least one of butylated hydroxyanisole, propyl gallate and butylated hydroxytoluene.

4. The compound anthelmintic granules for aquaculture according to claim 1, characterized in that: The disintegrant is at least one of sodium carboxymethyl starch, hydroxypropyl cellulose and cross-linked polyvinyl pyrrolidone.

5. The compound anthelmintic granules for aquaculture according to claim 1, characterized in that: The filler is at least one of corn starch, pregelatinized starch, powdered sugar, lactose, dextrin, microcrystalline cellulose and calcium carbonate.

6. A method for preparing the compound anthelmintic granules for aquaculture according to any one of claims 1 to 5, characterized in that The steps include: S1. dispersing a surfactant in water to obtain a surfactant aqueous solution; S2, crushing and sieving avermectin benzoate and flubendiamide, and then adding them into the surfactant aqueous solution respectively, stirring evenly to obtain an emulsion; S3, uniformly mixing the disintegrant, antioxidant and filler to obtain a mixed excipient, adding 70-85wt% of the mixed excipient into a round pot granulator, spraying atomized water, and simultaneously starting spheronization granulation under heating conditions to spheronize the material to form a base core; S4. When the diameter of the base core reaches 0.5-1.5 mm, the emulsion is atomized and sprayed into a granulator, and the remaining mixed auxiliary materials are added into the granulator to round the materials into spherical particles, which are the compound anthelmintic particles for aquaculture.

7. The method for preparing the compound anthelmintic granules for aquaculture according to claim 6, characterized in that: In the step S3, the rotation speed during spheronization is 25-35 rpm and the temperature is 45-60°C.

8. The method for preparing the compound anthelmintic granules for aquaculture according to claim 6, characterized in that: The diameter of the base core is 0.5-1.5 mm, and the diameter of the compound anthelmintic granules for aquaculture is 2.0-3.5 mm.

9. Use of the compound anthelmintic granules for aquaculture according to claim 1 in the preparation of anthelmintics or insecticides for aquaculture.

10. The use of the compound anthelmintic granules for aquaculture according to claim 9, characterized in that: The worms are crustacean parasites that parasitize on fish bodies.

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