Nanostructure lipid carrier containing fluopyram, preparation method thereof and pesticide preparation

Abstract

The invention relates to the technical field of pesticide preparations, in particular to a nanostructure lipid carrier containing fluopyram, a preparation method of the nanostructure lipid carrier and a pesticide preparation. The nano-structure lipid carrier comprises the following components in percentage by weight: 10%-20% of fluopyram, 10%-20% of a surfactant, 10%-20% of a surfactant, 10%-20% of an emulsifier and the balance of water, 30%-65% of plant essential oil; 3%-30% of triglyceride; and 5%-20% of polyvinyl alcohol. By selecting and matching the plant essential oil, the triglyceride and the polyvinyl alcohol in percentage by weight, the stability of the fluopyram can be remarkably improved, the fluopyram is not easy to degrade in the medication process, the drug effect is better maintained, and the nano-structure lipid carrier has good affinity to plant leaves, so that the effect of improving the stability of the fluopyram is achieved. The fluopyram-containing compound is more beneficial to targeted transportation and permeation of fluopyram, improves the absorptivity, and is also easy to permeate into roots and nematode bodies to improve the effective utilization rate of drugs, so that the fluopyram-containing compound has a very good application prospect.

Description

Technical Field

[0001] The present application belongs to the technical field of pesticide preparations, and in particular relates to a nanostructured lipid carrier containing fluopyram, a preparation method thereof, and a pesticide preparation. Background Art

[0002] Fluopicolide is a new type of highly effective fungicide and nematode control agent, especially in nematode control. It can be widely used in combination with other pesticides to increase control effectiveness and cost-effectiveness. However, due to the low solubility of fluopicolide in organic solvents, it is extremely difficult to make it into small-particle liquid formulations such as traditional microemulsions. Because the distribution of nematode control agents in the soil layer is positively correlated with the solubility of the drug in water and the particle size of the agent, the greater the solubility and the smaller the particle size, the easier it is to leach to the target in the middle and lower layers of the tillage layer. Because the current fluopicolide suspension and water-dispersible granules have relatively large particle sizes, it is difficult to leach downward and it is difficult to exert normal efficacy. It needs to be mixed with vegetable oil adjuvants in a barrel to better exert normal efficacy. This greatly increases the cost of medication and reduces the cost-effectiveness of fluopicolide.

[0003] Nanotechnology is a cutting-edge interdisciplinary subject, which is a system that applies nanotechnology and nanomaterials to the field of pharmaceutical preparations. Among them, nanostructured lipid carriers (NLCs) are the second-generation lipid nanoparticle drug delivery systems developed after 2000. As a new drug delivery system, they are widely used in the pharmaceutical field and cosmetics. The performance of nanostructured lipid carriers is closely related to the selection of auxiliary materials that match the physical and chemical properties of the drug ingredients. At present, there are no reports on the preparation and application of fluopyram nanostructured lipid carriers. Summary of the invention

[0004] The purpose of the present application is to provide a nanostructured lipid carrier containing fluopyram and a preparation method and pesticide formulation thereof, aiming to solve the technical problem of how to improve the stability and effective utilization rate of fluopyram to better improve the efficacy of the drug.

[0005] In order to achieve the above application purpose, the technical solution adopted in this application is as follows: In a first aspect, the present application provides a nanostructured lipid carrier containing fluopyram, which comprises the following components in the following weight percentages, based on the total weight of the nanostructured lipid carrier being 100%: Fluopyram 10%-20%; Plant essential oil 30%-65%; Triglycerides 3%-30%; Polyvinyl alcohol 5%-20%.

[0006] In a second aspect, the present application provides a method for preparing a nanostructured lipid carrier containing fluopyram, comprising: Providing various raw material components of the nanostructured lipid carrier of the first aspect of the present application; Dissolving the fluopyram, the plant essential oil and the triglyceride in an organic solvent to obtain a first solution; Dissolving the polyvinyl alcohol in a water solvent to obtain a second solution; The first solution and the second solution are mixed and then emulsified, and then dried to remove the solvent to obtain the nanostructured lipid carrier.

[0007] In a third aspect, the present application provides a pesticide formulation, comprising the nanostructured lipid carrier of the first aspect of the present application, or the nanostructured lipid carrier prepared by the preparation method of the second aspect of the present application.

[0008] The nanostructured lipid carrier provided in the first aspect of the present application, its components include a certain weight percentage of fluopyram, plant essential oil, triglyceride and polyvinyl alcohol. By selecting and matching the plant essential oil, triglyceride and polyvinyl alcohol of the above-mentioned weight percentage, the stability of fluopyram can be significantly improved, it is not easy to be degraded during medication, and the drug effect is better maintained, and such a nanostructured lipid carrier has a good affinity to plant leaves, which is conducive to the targeted transport and penetration of fluopyram, improves the absorption rate, and is also easy to penetrate into the root and nematode body to improve the effective utilization rate of the drug. In this way, based on the nanostructured lipid carrier containing fluopyram of the present application, there is a good control effect on the basis of improving cost performance, which is conducive to delaying resistance and environmental protection, and therefore has a good application prospect.

[0009] The preparation method of the nanostructured lipid carrier provided in the second aspect of the present application comprises dissolving fluopyram, plant essential oil and triglyceride in an organic solvent to obtain a first solution, dissolving polyvinyl alcohol in an aqueous solvent to obtain a second solution, and then mixing the first solution and the second solution, emulsifying, drying and desolventizing to obtain a nanostructured lipid carrier containing fluopyram. In this process, a lipid carrier with a nanostructure encapsulating fluopyram is obtained through a two-phase mixed liquid emulsification process and a desolventizing process, which can significantly improve the stability of fluopyram therein, and the obtained nanostructured lipid carrier is conducive to the targeted transport and penetration of drugs, thereby improving the efficiency of drug utilization.

[0010] The pesticide preparation provided in the third aspect of the present application includes a nanostructured lipid carrier containing fluopyram unique to the present application. By utilizing the efficacy of the nanostructured lipid carrier containing fluopyram, the fluopyram in the pesticide preparation of the present application has good stability and is easy to penetrate into the tillage layer target, and the effective utilization rate of the drug is greatly improved. In addition, the nanostructured lipid carrier containing fluopyram expands the types of pesticide formulations in which fluopyram is compounded with other active ingredients, thereby better improving the prevention effect and cost-effectiveness of the pesticide preparation. DETAILED DESCRIPTION

[0011] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present application more clearly understood, the present application is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0012] In this application, the term "and / or" describes the association relationship of associated objects, indicating that there may be three relationships. For example, A and / or B can mean: A exists alone, A and B exist at the same time, and B exists alone. A and B can be singular or plural. The character " / " generally indicates that the associated objects are in an "or" relationship.

[0013] In this application, "at least one" means one or more, "more than one" means two or more. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single or plural items.

[0014] It should be understood that in the various embodiments of the present application, the size of the serial numbers of the above-mentioned processes does not mean the order of execution, some or all of the steps can be executed in parallel or sequentially, and the execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0015] The terms used in the embodiments of the present application are only for the purpose of describing specific embodiments, and are not intended to limit the present application. The singular forms "a", "said" and "the" used in the embodiments of the present application and the appended claims are also intended to include plural forms, unless the context clearly indicates other meanings.

[0016] The weight of the relevant components mentioned in the embodiment description of the present application can not only refer to the specific content of each component, but also indicate the proportional relationship between the weights of the components. Therefore, as long as the content of the relevant components is proportionally enlarged or reduced according to the embodiment description of the present application, it is within the scope disclosed in the embodiment description of the present application. Specifically, the mass described in the embodiment description of the present application can be a mass unit known in the chemical industry such as µg, mg, g, kg, etc.

[0017] The terms "first" and "second" are used only for descriptive purposes to distinguish objects such as substances from each other, and should not be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features. For example, without departing from the scope of the embodiments of the present application, the first XX may also be referred to as the second XX, and similarly, the second XX may also be referred to as the first XX. Thus, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features.

[0018] Due to the low solubility of fluopyram in organic solvents, it is extremely difficult to make it into small-particle liquid dosage forms such as traditional microemulsions. Currently, it is generally registered for the production of suspensions, water-dispersible granules, etc. Since the particle sizes of commonly used fluopyram suspensions and water-dispersible granules are relatively large and difficult to leach downward, they need to be mixed with vegetable oil adjuvants in a tank to exert normal efficacy, which greatly increases the cost of medication and reduces the cost-effectiveness of fluopyram.

[0019] Compared with other drug delivery systems, nanostructured lipid carriers (NLCs) can improve the stability of drugs that are sensitive to light and moisture and have unstable chemical structures, and have good biocompatibility, making them suitable for large-scale industrial production. Nanostructured lipid carriers have sustained-release function and high drug loading capacity, and can also improve drug stability, dispersibility, use efficiency and efficacy. Based on this, the present application embodiment develops a nanostructured lipid carrier containing fluopyram and a preparation method thereof, and uses this nanostructured lipid carrier to develop a series of pesticide formulations with better performance.

[0020] In the embodiment of the present application, the pesticide preparation processed by the nanostructured lipid carrier containing fluoropyramid has a smaller particle size than the current traditional suspension or water-dispersible granules, and is easier to quickly penetrate into the tillage layer target, and the active ingredients are wrapped in the nanostructured lipid carrier particles of plant essential oils, which are easier to penetrate into the roots and nematodes, and the effective utilization rate of the drug is greatly improved. The nanostructured lipid carrier containing fluoropyramid is not only stable and reliable, but also emits blue light when diluted with water. It can also be diluted twice in a certain proportion. The secondary dilution solution (such as 20-100 times) is not easy to be stratified overnight, and precipitation and crystallization are easy to occur. Fluopyram and plant essential oil are not easy to separate after being diluted with water. Therefore, the nanostructured lipid carrier containing fluoropyramid in the embodiment of the present application can significantly improve the control effect and cost-effectiveness of fluoropyramid on nematodes. Moreover, through the nanostructured lipid carrier containing fluoropyramid, the registered dosage form of fluoropyramid and its compounding with other active ingredients is expanded, and an efficient and cost-effective pesticide formulation is obtained. The specific technical scheme is as follows.

[0021] In a first aspect, the present invention provides a nanostructured lipid carrier containing fluopyram. Specifically, based on the total weight of the nanostructured lipid carrier of the present invention as 100%, the nanostructured lipid carrier comprises the following components in the following weight percentages: fluopyram 10%-20%; plant essential oil 30%-65%; triglyceride 3%-30%; polyvinyl alcohol 5%-20%.

[0022] Specifically, in the nanostructured lipid carrier of the embodiment of the present application, the content of fluopyram can be 10%, 12%, 14%, 15%, 16%, 18%, 20%, etc., based on its total weight as 100%. The content of plant essential oil can be 30%, 32%, 35%, 38%, 40%, 42%, 45%, 48%, 50%, 53%, 55%, 58%, 60%, 62%, 65%, etc. Triglyceride can be 3%, 5%, 8%, 10%, 15%, 18%, 20%, 22%, 25%, 28%, 30%, etc. Polyvinyl alcohol can be 5%, 8%, 10%, 12%, 15%, 18%, 20%, etc. The above weight percentages of plant essential oil, triglyceride, polyvinyl alcohol and fluopyram can form a stable and reliable nanolipid carrier.

[0023] In some embodiments, plant essential oils are natural plant essential oils extracted by distilling and pressing the flowers, leaves, roots, barks, fruits, seeds, resins, etc. of herbaceous plants by extracting plant-specific aromatic substances. For example, the plant essential oils in the embodiments of the present application include at least one of peppermint essential oil, citronella oil, cinnamon oil, rose essential oil, wintergreen essential oil, tea tree essential oil, rosemary oil, lemon oil, and lavender oil.

[0024] In some embodiments, triglycerides are triacylglycerols formed by esterification of one glycerol molecule and three fatty acids. The fatty acids can be unsaturated fatty acids. For example, the fatty acids in the triglycerides in the embodiments of the present application can be olefinic acids, such as triglycerides formed by olefinic acids having ten to twenty carbon atoms. In one embodiment of the present application, triolein (also known as oleic acid glyceride) is selected: (Z)-9-octadecenoic acid-1,2,3-propanetriyl ester.

[0025] The nanostructured lipid carrier provided in the embodiment of the present application comprises fluopyram, plant essential oil, triglyceride and polyvinyl alcohol in a certain weight percentage. By selecting and matching the above-mentioned plant essential oil, triglyceride and polyvinyl alcohol in the above weight percentage, the stability of fluopyram can be significantly improved, the stability to ultraviolet light can be greatly improved, the ultraviolet light photolysis during the medication process can be reduced, and the drug efficacy can be better maintained. Moreover, such a nanostructured lipid carrier has a good affinity for plant leaves, which is conducive to the targeted transport and penetration of fluopyram, improves the absorption rate, and is also easy to penetrate into the roots and nematodes to improve the effective utilization rate of the drug.

[0026] In a second aspect, the present invention provides a method for preparing a nanostructured lipid carrier containing fluopyram. Specifically, the preparation method of the present invention comprises: S01: providing the raw material components of the nanostructured lipid carrier of the first aspect of the embodiment of the present application; S02: dissolving fluopyram, plant essential oil and triglyceride in an organic solvent to obtain a first solution; S03: dissolving polyvinyl alcohol in a water solvent to obtain a second solution; S04: The first solution and the second solution are mixed and emulsified, and then dried to remove the solvent to obtain a nanostructured lipid carrier.

[0027] In the embodiment of the present application, fluopyram, plant essential oil and triglyceride are dissolved in an organic solvent to obtain a first solution, polyvinyl alcohol is dissolved in an aqueous solvent to obtain a second solution, and the first solution and the second solution are mixed, emulsified, dried and desolventized to obtain a nanostructured lipid carrier containing fluopyram. In this process, a lipid carrier with a nanostructure encapsulating fluopyram is obtained through a two-phase mixed liquid emulsification process and a desolventization process, which can significantly improve the stability of fluopyram therein, and the obtained nanostructured lipid carrier is conducive to the targeted transport and penetration of drugs, thereby improving the efficiency of drug utilization.

[0028] In step S01, the raw material components of the nanostructured lipid carrier are fluopyram, plant essential oil, triglyceride, and polyvinyl alcohol. Specifically, based on the total weight of the nanostructured lipid carrier finally prepared as 100%, the raw materials include the following components in percentage by weight: fluopyram 10%-20%; plant essential oil 30%-65%; triglyceride 3%-30%; polyvinyl alcohol 5%-20%.

[0029] In step S02, fluopyram, plant essential oil and triglyceride are dissolved in an organic solvent to obtain a first solution. Specifically, fluopyram, plant essential oil and triglyceride can be dissolved in an organic solvent together according to the above proportions.

[0030] In some embodiments, the organic solvent includes at least one of chloroform and ethyl acetate. These organic solvents can disperse the three materials of fluopyram, plant essential oil and triglyceride well.

[0031] In step S03, polyvinyl alcohol is dissolved in a water solvent to obtain a second solution.

[0032] In some embodiments, the mass percentage of polyvinyl alcohol in the second solution is 0.1%-10%, such as 0.5%, 1%, 2%, 5%, 8%, 10%, etc. The polyvinyl alcohol is prepared into a second solution with a concentration of 0.1%-10% with water, which can make it dispersed better and facilitate subsequent emulsification.

[0033] In step S04, the final nanostructured lipid carrier is obtained by emulsification, drying and solvent removal.

[0034] In some embodiments, when the first solution and the second solution are mixed and emulsified, the weight ratio of the organic solvent to the aqueous solvent is 1:(3-10). Mixing according to this ratio can better form a two-phase emulsion.

[0035] In some embodiments, the temperature of the emulsification treatment is -5°C to 2°C. For example, after the first solution and the second solution prepared above are mixed in a weight ratio of 1:(3-10), the mixed solution can be emulsified by stirring, oscillating or high-speed shearing at -5°C to 2°C.

[0036] In some embodiments, ultrasonic treatment is further included between the emulsification treatment and the drying and desolvation treatment. For example, ultrasonic micronization is performed after emulsification, stirring for 1-20 hours, and then drying is performed to obtain the final nanostructured lipid carrier.

[0037] In some embodiments, the drying method for removing the solvent may include vacuum drying, freeze drying, and spray drying. These drying methods can effectively remove water solvents and organic solvents.

[0038] The nanostructured lipid carrier containing fluoropyramid prepared by the embodiment of the present application can be called fluoropyramid nanostructured lipid carrier nanoparticles or fluoropyramid nanostructured lipid carrier mother powder. The present embodiment of the present application has found that this nanostructured lipid carrier is a biocompatible lipid carrier matrix with many advantages: such as having good affinity to plant leaves, being conducive to the absorption and transportation of drugs, having good targeting, improving absorption rate, and being used as foliar spraying. The nanostructured lipid carrier containing fluoropyramid slows down the biochemical degradation metabolism under the surface of the leaves, and the storage stability is greatly improved, which prolongs the drug effect period. And because the chemical stability of the drug is improved, the compounding performance is improved, which is conducive to anti-ultraviolet light photolysis, prolongs the drug lasting period, and greatly improves the drug effect. And the nanostructured lipid carrier containing fluoropyramid has the advantages of high stability, low toxicity, simple process, relatively low cost, and large-scale production, which can be used to prepare the pesticide preparation containing fluoropyramid nanostructured lipid carrier.

[0039] In a third aspect, the present invention provides a pesticide formulation. Specifically, the pesticide formulation of the present invention comprises the nanostructured lipid carrier of the first aspect of the present invention, or the nanostructured lipid carrier prepared by the preparation method of the second aspect of the present invention.

[0040] By utilizing the efficacy of the nanostructured lipid carrier containing fluopyram, the fluopyram in the pesticide formulation of the present application has good stability and is easy to penetrate into the tillage layer target, the effective utilization rate of the drug is greatly improved, and the nanostructured lipid carrier containing fluopyram expands the types of pesticide formulations in which fluopyram is compounded with other active ingredients, thereby better improving the prevention effect and cost-effectiveness of the pesticide formulation.

[0041] In some embodiments, the pesticide formulation further includes other active ingredients, which are non-lipid nanostructured active ingredients, and these other active ingredients include at least one of avermectin, chitosan, and chitosan oligosaccharide. These other active ingredients can be compounded with the nanostructured lipid carrier containing fluopyram to obtain a composite formulation. The mass ratio of fluopyram to the other active ingredients can be (1-800): 1. It can be adjusted according to actual needs.

[0042] In some embodiments, the pesticide preparation includes at least one of water dispersible granules, suspensions, emulsions in water, and microemulsions. The nanostructured lipid carrier drug of the embodiment of the present application is compounded with at least one pesticide active ingredient such as avermectin, chitosan, and chitosan oligosaccharides to prepare pesticide preparations such as water dispersible granules, suspensions, emulsions in water, and microemulsions, which have strong compatibility and high transfer efficiency and are suitable for preventing and controlling root-knot nematodes of crops.

[0043] In some embodiments, the pesticide formulation is a water-dispersible granule, which includes the following components based on the total weight of the water-dispersible granules as 100%: 70%-80% of a nanostructured lipid carrier containing fluopyram, 2%-4% of other active ingredients (one of avermectin, chitosan, and chitosan oligosaccharide), 1%-10% of a surfactant, 0%-15% of a disintegrant, 1%-5% of a binder, 0%-5% of other adjuvants, and 1%-20% of a filler carrier. Among them, the surfactant can be one or more selected from lignin sulfonate, sodium dodecyl sulfate, fatty acid sulfate, fatty alcohol polyoxyethylene, sodium dibutylnaphthalene sulfonate, and dodecyl polyoxyethylene ether phosphate; the disintegrant can be one or more selected from bentonite, ammonium sulfate, urea, and magnesium sulfate; the binder can be one or more selected from polyethylene glycol, cyclodextrin, starch, and sodium silicate; other auxiliary agents can be one or more selected from benzylphenol polyoxyethylene ether, tea saponin, and alkylphenol polyoxyethylene ether; the filler carrier can be one or more selected from diatomaceous earth, kaolin, white carbon black, and pearl clay.

[0044] In some embodiments, the pesticide formulation is a suspension, which includes the following components based on the total weight of the suspension as 100%: 45%-55% of a nanostructured lipid carrier containing fluopyram, 2%-4% of other active ingredients (one of avermectin, chitosan, and chitosan oligosaccharide), 1%-10% of a surfactant, 1%-5% of an antifreeze agent, 0.1%-1% of a thickener, 0.1%-1% of a defoamer, and 20%-40% of an aqueous solvent. Among them, the surfactant can be selected from one or more of JFC, 603#, 600#, alkylphenol polyoxyethylene ether or its phosphate ester, fatty alcohol polyoxyethylene ether, lignin sulfonate, and naphthalene sulfonate formaldehyde condensate; the antifreeze agent can be selected from ethylene glycol, the thickener can be selected from xanthan gum, and the defoamer can be selected from silicone.

[0045] In some embodiments, the pesticide formulation is an aqueous emulsion, which includes the following components based on the total weight of the aqueous emulsion as 100%: 45%-55% of a nanostructured lipid carrier containing fluopyram, 2%-4% of other active ingredients (one of avermectin, chitosan, and chitosan oligosaccharide), 1%-10% of a surfactant, 10%-30% of an oil solvent, and 10%-30% of a water solvent. Among them, the surfactant can be selected from one or a combination of two or more of lignin sulfonate, sodium lauryl sulfate, fatty acid sulfate, fatty alcohol polyoxyethylene, sodium dibutylnaphthalene sulfonate, benzylphenol polyoxyethylene ether, alkylphenol polyoxyethylene ether, and pull-open powder; the oil solvent can be selected from one or a combination of two or more of peppermint essential oil, citronella oil, cinnamon oil, rose essential oil, wintergreen essential oil, tea tree essential oil, rosemary oil, lemon oil, and lavender oil.

[0046] In some embodiments, the pesticide formulation is a microemulsion, which includes the following components based on the total weight of the microemulsion as 100%: 25%-42% of a nanostructured lipid carrier containing fluopyram, 2%-4% of other active ingredients (one of avermectin, chitosan, and chitosan oligosaccharide), 5%-25% of a surfactant, 30%-40% of an oil solvent, and 1%-10% of an aqueous solvent. Among them, the surfactant can be selected from one or a combination of two or more of calcium dodecylbenzene sulfonate, sodium dodecyl sulfate, fatty acid sulfate, fatty alcohol polyoxyethylene, sodium dibutylnaphthalene sulfonate, benzylphenol polyoxyethylene ether, and alkylphenol polyoxyethylene ether; the oil solvent can be selected from one or a combination of two or more of peppermint essential oil, citronella oil, cinnamon oil, rose essential oil, wintergreen essential oil, tea tree essential oil, rosemary oil, lemon oil, and lavender oil.

[0047] In the embodiments of the present application, the pesticide formulation is processed using a nanostructured lipid carrier containing fluopyram, which has a smaller particle size than traditional suspensions or water-dispersible granules and can more quickly penetrate into the target crop layer. In addition, the active ingredients are encapsulated in the plant essential oil lipid carrier particles, which can more easily penetrate into the roots and nematodes, greatly improving the effective utilization rate of the drug.

[0048] The following is a description of the specific examples. The active ingredients of pesticides used in the following examples are all calculated as 100% pure unless otherwise specified. In actual operation, the actual purity of the original pesticide used is converted, and the difference is adjusted with fillers or water.

[0049] Example A A nanostructured lipid carrier mother powder containing fluopyram, comprising the following components based on 100% total weight: Fluopyram 10%; Peppermint essential oil 64.5%; Olein 9%; Polyvinyl alcohol 16.5%.

[0050] The preparation method of the nanostructured lipid carrier mother powder comprises: weighing the above raw material components, dissolving the fluopyram original drug together with 90 grams of oleic acid glyceride and 645 grams of peppermint essential oil according to 100 grams of pure fluopyram in 100 grams of chloroform, then mixing with 2200 grams of 7.5% polyvinyl alcohol aqueous solution by weight, stirring the mixed solution at 2°C to make the mixed solution uniformly emulsified, then micronizing with ultrasound, stirring for 2 hours, and finally freeze-drying to obtain the nanostructured lipid carrier mother powder containing 10% fluopyram by weight.

[0051] Example B A nanostructured lipid carrier mother powder containing fluopyram, comprising the following components based on 100% total weight: Fluopyram 15%; Citronella oil 63%; Olein 6%; Polyvinyl alcohol 16%.

[0052] The preparation method of the nanostructured lipid carrier mother powder comprises: weighing the above raw material components, dissolving the fluopyram original drug in 200 grams of chloroform according to 150 grams of pure fluopyram, 60 grams of oleic acid glyceride and 630 grams of citronella oil, and then mixing with 2000 grams of 8% by weight polyvinyl alcohol aqueous solution, stirring the mixture at 2°C to make it uniformly emulsified, then micronizing with ultrasound, stirring for 3.5 hours and then freeze-drying to obtain the nanostructured lipid carrier mother powder containing 15% by weight of fluopyram.

[0053] Example C A nanostructured lipid carrier mother powder containing fluopyram, comprising the following components based on 100% total weight: Fluopyram 20%; Wintergreen essential oil 58.5%; Olein glyceride 3.5%; Polyvinyl alcohol 18%.

[0054] The preparation method of the nanostructured lipid carrier mother powder comprises: weighing the above raw material components, dissolving the fluopyram original drug in 300 grams of chloroform according to 200 grams of pure fluopyram, 35 grams of oleic acid glyceride and 585 grams of wintergreen essential oil, and then mixing with 2000 grams of 9% by weight polyvinyl alcohol aqueous solution, stirring the mixture at 2°C to make it uniformly emulsified, then micronizing with ultrasound, stirring for 5 hours and then freeze-drying to obtain the nanostructured lipid carrier mother powder containing 20% ​​by weight of fluopyram.

[0055] Example 1 A water dispersible granule, based on 100% total weight, comprises the following components: Chitosan oligosaccharide 2%; The nanostructured lipid carrier containing fluopyram prepared in Example C was 75%; Sodium lignin sulfonate 5%; Sodium lauryl sulfate 5%; Urea 5%; Polyethylene glycol 1%; Diatomaceous earth 7%.

[0056] The preparation method of the water-dispersible granules comprises: weighing the water-dispersible granule components in the above weight percentages, uniformly mixing the components, crushing them by air flow, then adding water accounting for about 1% to 3% of the components and kneading them, granulating and drying the obtained mixture to obtain a water-dispersible granule product, wherein the water-dispersible granule product contains 2% chitosan oligosaccharide and 15% fluopyram.

[0057] Example 2 A suspension concentrate, based on 100% total weight, comprises the following components: 50% of the nanostructured lipid carrier containing fluopyram prepared in Example C; Avermectin 4%; Ethylene glycol 5%; Xanthan gum 0.5%; Alkylphenol polyoxyethylene ether 10%; Silicone 0.5%; Water 30%.

[0058] The preparation method of the suspension comprises: weighing the above-mentioned suspension composition components in weight percentage, mixing the components evenly, and then ball milling them in a ball mill for 2 to 3 hours to make the particle sizes all below 5 μm, thus forming a suspension product, which contains 4% avermectin and 10% fluopyram.

[0059] Example 3 An aqueous emulsion, based on 100% total weight, comprises the following components: 50% of the nanostructured lipid carrier containing fluopyram prepared in Example A; Avermectin 2%; Peppermint essential oil 20%; Alkylphenol polyoxyethylene ether 3%; Benzylphenol polyoxyethylene ether 3%; Water 22%.

[0060] The preparation method of the aqueous emulsion comprises: weighing the aqueous emulsion components in the above weight percentages, mixing the oil phases of the first three components, adding them into the mixture of the last three components at a uniform speed while high shearing, and high shearing for 30 minutes to obtain an aqueous emulsion product containing 2% avermectin and 5% fluopyram.

[0061] Example 4 A microemulsion, based on 100% total weight, comprises the following components: The nanostructured lipid carrier containing fluopyram prepared in Example B was 33.3%; Chitosan oligosaccharide 2%; Citronella oil 35%; Calcium dodecylbenzenesulfonate 10%; Alkylphenol polyoxyethylene ether 8%; Benzylphenol polyoxyethylene ether 5%; Water 6.7%.

[0062] The preparation method of the microemulsion comprises: weighing the microemulsion components in the above weight percentages, mixing the oil phases of the first six components and stirring them into a homogeneous transparent liquid, and adding the remaining water while stirring to obtain a microemulsion product containing 2% chitosan oligosaccharide and 5% fluopyram.

[0063] Comparative Example 1 Conventional water dispersible granules containing 2% chitosan oligosaccharide and 15% fluopyram (conventional means that the difference from Example 1 is that there is no nanostructured lipid carrier, and the others are the same); Comparative Example 2 A conventional suspension concentrate containing 4% avermectin and 10% fluopyram (the conventional suspension concentrate is different from Example 2 in that the nanostructured lipid carrier is not present, and the other aspects are the same); Comparative Example 3 A conventional aqueous emulsion containing 2% avermectin and 10% fluopyram (the conventional emulsion is different from Example 3 in that the nanostructured lipid carrier is not present, and the others are the same); Comparative Example 4 A conventional microemulsion containing 2% chitosan and 5% fluopyram (the conventional microemulsion is different from Example 4 in that there is no nanostructured lipid carrier, and the others are the same).

[0064] Performance Testing 1. Stability of water dispersible granules The water dispersible granules provided in Example 1 and Comparative Example 1 were subjected to cold and hot storage tests simultaneously to compare the stability.

[0065] The experimental samples were packaged in 6 ampoules, 2 of the packaged samples were stored in a 54°C constant temperature oven, 2 were stored in a 0°C refrigerator, and 2 were placed at room temperature of 25°C. After 14 days, the decomposition rates of the cold-stored samples and the hot-stored samples were measured. The experimental results are shown in Table 1.

[0066] Table 1

[0067] Note: Decomposition rate of cold and hot storage comparison = (content of the component to be detected in the cold storage sample - content of the component to be detected in the hot storage sample) / content of the component to be detected in the cold storage sample * 100%; the cold storage samples were stored at 0℃ for 14 days, and the hot storage samples were stored at 54℃ for 14 days before testing.

[0068] It can be seen from the test results in Table 1 that the cold-hot contrast decomposition rate of the chitosan oligosaccharide of Example 1 is 1.0%, which meets the national standard (effective ingredient decomposition rate ≤ 5%); while the cold-hot contrast decomposition rate of the chitosan oligosaccharide of Comparative Example 1 is 19.5%, which does not meet the national standard (effective ingredient decomposition rate ≤ 5%); Therefore, the embodiments of the present application can significantly improve the stability of product quality.

[0069] 2. Suspension UV photolysis experiment The suspension samples of Example 2 and the comparative example were simultaneously irradiated with two parallel 30 W ultraviolet lamps, the center of the ultraviolet lamp was 40 cm away from the liquid surface of the solution, and the absorbance of each substance was measured at the corresponding ultraviolet absorption peak by ultraviolet spectrophotometer and high performance liquid chromatography, and the residual fluopyram content under different irradiations was calculated. The conclusions are shown in Table 2 below.

[0070] Table 2

[0071] It can be seen from the test results in Table 2 that the nanostructured lipid carrier in Example 2 can reduce the decomposition rate of fluopyram under ultraviolet light.

[0072] 3. Bio-efficacy test Materials and methods: Test reagents: produced by Nopco Research Institute.

[0073] Test crop: Tomato, variety Jiafen 15.

[0074] Test subjects: root-knot nematodes ( Meloidogyne spp.).

[0075] Environmental conditions: The Nopco Hebei test base is located in a semi-hilly terrain with brown loam, medium soil fertility, 1.55% organic matter content, and a pH value of 7.6. Tomatoes were planted on August 19, 2023, with a planting density of 3,000 plants per mu, and field management was carried out according to the actual management process of local agricultural production.

[0076] 3.1 Experimental design and arrangement (1) The dosage scheme of the pesticide formulation prepared in the examples of the present application is shown in Table 3.

[0077] Table 3

[0078] (2) Plot arrangement. Plots are arranged in random blocks. Plot area and repetition: Plot area 25m 2 ; Repeat 4 times.

[0079] (3) Application method: ① Application method: Root irrigation method: After the tomatoes are transplanted and established, root irrigation method is used for application once. The dosage for each treatment is weighed according to the number of plants in the plot area, diluted with water and applied into the pre-opened trench. ② Application time and number of times: The application time is August 29, 2023, and the application is once.

[0080] (4) Information on pesticides for controlling other diseases and pests: No other nematicides were sprayed during the trial.

[0081] 3.2 Survey, recording and measurement methods 3.2.1 Meteorological and soil data (1) Meteorological data: The weather conditions on the day of application were as follows: average temperature 29.0℃, relative humidity 51%, rainfall 0.0mm, wind speed 2.2m / s, sunshine 10.5h / d. (2) Soil data: The soil is brown loam, with medium soil fertility, organic matter content of 1.55%, and pH value of 7.6.

[0082] 3.2.2 Survey methods, time and frequency (1) Investigation time and frequency: The pesticide was applied on August 29, 2023, and the efficacy investigation was conducted 60 days after the application.

[0083] (2) Survey method: Soil samples were collected from five points in each plot from the root circumference (depth 0-20 cm) using a soil drill. After mixing, 100 g of soil was collected and the nematodes were immediately separated. The number of second-instar nematodes was determined. If separation was not possible, Store under moist conditions or at 1℃~7℃ until separation. The modified Behman funnel method was used to separate the nematodes and the nematodes were counted under a stereoscopic dissecting microscope. The 0.3% gentian violet staining method was used to identify the live or dead nematodes.

[0084] (3) Calculation method of drug efficacy: Nematode reduction rate (%) = (number of nematodes before medication - number of live nematodes after medication) / number of nematodes before medication × 100.

[0085] Control effect (%) = (nematode reduction rate in treatment area - nematode reduction rate in blank control area) / (100 - nematode reduction rate in blank control area) × 100.

[0086] 3.2.3 Impact on crop yields Record and total plot yield, in kg / hm 2 (kg / hectare), calculate the yield increase rate, and compare the yield increase effect.

[0087] Yield increase rate (%) = (yield in the area treated with chemical – yield in the area treated with clean water) / yield in the area treated with clean water * 100.

[0088] 3.3 Results and Analysis 3.3.1 Biostatistical analysis methods Data analysis was performed using DPS v9.50 for windows, and multiple comparisons were performed using Duncan's new multiple range method.

[0089] 3.3.2 The results of the efficacy evaluation of the pesticide preparations prepared in the examples of the present application are shown in Table 4.

[0090] Table 4

[0091] 3.3.3 The results of the effect of the pesticide formulation prepared in the examples of the present application on crop yield are shown in Table 5.

[0092] Table 5

[0093] As can be seen from the test results in the above table, after 60 days of investigation, the yield increase rates of Examples 1 to 4 were 15.26%, 14.32%, 19.98% and 24.67%, respectively. There was no significant difference between the treatments of Example 1 and Example 2, and there was a very significant difference between the treatments of Example 1 and Example 2 and Example 3 and Example 4. The yield increase rates of Comparative Examples 1 to 4 were 10.12%, 9.61%, 9.93% and 8.90%, respectively. There was no significant difference between the treatments of Comparative Examples 1 to 4, but there was a very significant difference between the treatments of Comparative Examples 1 to 4 and Examples 1 to 4. Therefore, the yield increase rate of the embodiments of the present application is significantly improved.

[0094] The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present application should be included in the protection scope of the present application.

Claims

1. A nanostructured lipid carrier containing fluopyram, characterized in that: Taking the total weight of the nanostructured lipid carrier as 100%, the following components are included in the following weight percentages: Fluopyram 10%-20%; Plant essential oil 30%-65%; Triglycerides 3%-30%; Polyvinyl alcohol 5%-20%.

2. The nanostructured lipid carrier according to claim 1, characterized in that The plant essential oil includes at least one of peppermint essential oil, citronella oil, cinnamon oil, rose essential oil, wintergreen essential oil, tea tree essential oil, rosemary oil, lemon oil, and lavender oil; And / or, the triglyceride includes a triglyceride formed from olefinic acid having ten to twenty carbon atoms.

3. A method for preparing a nanostructured lipid carrier containing fluopyram, characterized in that: include: Providing raw material components of the nanostructured lipid carrier according to any one of claims 1 to 2; Dissolving the fluopyram, the plant essential oil and the triglyceride in an organic solvent to obtain a first solution; Dissolving the polyvinyl alcohol in a water solvent to obtain a second solution; The first solution and the second solution are mixed and then emulsified, and then dried to remove the solvent to obtain the nanostructured lipid carrier.

4. The preparation method according to claim 3, characterized in that: The mass percentage of the polyvinyl alcohol in the second solution is 0.1%-10%.

5. The preparation method according to claim 3, characterized in that: The weight ratio of the organic solvent to the aqueous solvent is 1:(3-10); And / or, the organic solvent includes at least one of chloroform and ethyl acetate.

6. The preparation method according to any one of claims 3 to 5, characterized in that: The temperature of the emulsification treatment is -5°C to 2°C; And / or, ultrasonic treatment is also included between the emulsification treatment and the drying and desolventizing treatment.

7. A pesticide preparation, characterized in that: The invention comprises the nanostructured lipid carrier according to any one of claims 1 to 2, or the nanostructured lipid carrier prepared by the preparation method according to any one of claims 3 to 6.

8. The pesticide formulation according to claim 7, characterized in that The pesticide preparation further comprises other active ingredients, wherein the other active ingredients comprise at least one of avermectin, chitosan and chitosan oligosaccharide; And / or, the pesticide formulation includes at least one of water dispersible granules, suspensions, aqueous emulsions, and microemulsions.

9. The pesticide formulation according to claim 8, characterized in that The pesticide preparation is a water-dispersible granule, and based on the total weight of the water-dispersible granule being 100%, it comprises the following components: The nanostructured lipid carrier 70%-80%, the other active ingredients 2%-4%, surfactants 1%-10%, disintegrants 0%-15%, binders 1%-5%, other additives 0%-5%, fillers and carriers 1%-20%; Alternatively, the pesticide preparation is a suspension concentrate, which comprises the following components based on the total weight of the suspension concentrate as 100%: The nanostructured lipid carrier comprises 45%-55%, the other active ingredients comprise 2%-4%, a surfactant comprises 1%-10%, an antifreeze agent comprises 1%-5%, a thickener comprises 0.1%-1%, a defoaming agent comprises 0.1%-1%, and an aqueous solvent comprises 20%-40%.

10. The pesticide formulation according to claim 8, characterized in that The pesticide preparation is an aqueous emulsion, and based on the total weight of the aqueous emulsion being 100%, it comprises the following components: The nanostructured lipid carrier is 45%-55%, the other active ingredients are 2%-4%, the surfactant is 1%-10%, the oil solvent is 10%-30%; the water solvent is 10%-30%; Alternatively, the pesticide preparation is a microemulsion, and based on the total weight of the microemulsion being 100%, it comprises the following components: The nanostructured lipid carrier comprises 25%-42%, the other active ingredients comprise 2%-4%, the surfactant comprises 5%-25%, the oil solvent comprises 30%-40%, and the water solvent comprises 1%-10%.

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