WO2020135600A1

WO2020135600A1 - Nano pesticide formulation and preparation method therefor

Info

Publication number: WO2020135600A1
Application number: PCT/CN2019/128757
Authority: WO
Inventors: 张子勇; 梁冰
Original assignee: 南京善思生物科技有限公司
Priority date: 2018-12-28
Filing date: 2019-12-26
Publication date: 2020-07-02
Also published as: CN113260257A; WO2020135780A1; CN113260257B

Abstract

The present invention relates to the technical field of pesticides. Disclosed are a nano pesticide formulation and a preparation method therefor. The raw materials and auxiliary materials of the preparation comprise an effective amount of a pesticide active ingredient or a raw pesticide, as well as an appropriate amount of a solvent, a high-molecular additive, a small-molecule additive and a dispersant. The formulation has a small nanometer particle size. In addition, disclosed is a new dosage form. The formulation has a wide application prospect and is suitable for popularization.

Description

纳米农药制剂及其制备方法Nano pesticide preparation and preparation method thereof

技术领域Technical field

本发明属于农药技术领域，涉及纳米农药制剂及其制备方法，特别是涉及混溶纳米农药悬浮剂和纳米农药悬浮剂、纳米农药固体粉剂的制备方法。The invention belongs to the technical field of pesticides, and relates to a nano pesticide preparation and a preparation method thereof, in particular to a preparation method of a miscible nano pesticide suspension agent, a nano pesticide suspension agent, and a nano pesticide solid powder.

背景技术Background technique

2018年4月1日，国际纯粹与应用化学联合会(IUPAC)在其成立100周年与门捷列夫元素周期表公布150周年之际，公布了将改变世界的十大化学发明，“纳米农药”位被列于首位。这些新兴技术是IUPAC从工业界和学术界招募的5位权威专家从全球化学家提交的一系列提名中评选出的，具有广泛的代表性和权威性，代表着国际化工领域最前沿的科学技术和发展趋势，有潜力成为21世纪的重大化学突破，有可能改变世界，使地球更可持续发展。On April 1, 2018, the International Union of Pure and Applied Chemistry (IUPAC) announced the top ten chemical inventions that will change the world on the occasion of its 100th anniversary and the 150th anniversary of Mendeleev’s periodic table of elements. "Is listed first. These emerging technologies were selected by a series of nominations submitted by global authors from 5 authoritative experts recruited by IUPAC from industry and academia. They are broadly representative and authoritative, and represent the most cutting-edge science and technology in the international chemical industry. And the development trend has the potential to become a major chemical breakthrough in the 21st century, which may change the world and make the planet more sustainable.

纳米农药入选新兴技术之首是基于世界人口的不断增长。预测到2050年世界人口将接近100亿。为了养活大量的人口，需要大量增加农业产量，并最大限度地减少对土地利用造成的环境影响，包括减少农药污染，减少用水量，以及减少人口数量。纳米农药及其递送***，将是解决传统农药主要问题的很好的工具，这些问题包括环境污染，农药在生物体内的累积和病虫害抗性的大幅增加。纳米农药微粒尺寸小，靶标具有更好的吸收性，虽然不能说它是农业可持续性发展的唯一路径，但可以肯定的是它对生态环境和人类健康的影响更小。Nanopesticides have been selected as the top of emerging technologies based on the growing population of the world. It is predicted that the world’s population will be close to 10 billion by 2050. In order to feed a large number of people, it is necessary to greatly increase agricultural output and minimize the environmental impact on land use, including reducing pesticide pollution, reducing water consumption, and reducing the number of people. Nano pesticides and their delivery systems will be a good tool to solve the main problems of traditional pesticides. These problems include environmental pollution, the accumulation of pesticides in organisms and the substantial increase in resistance to diseases and insect pests. Nano pesticide particles are small in size, and the target has better absorption. Although it cannot be said that it is the only path for sustainable development of agriculture, it is certain that it has less impact on the ecological environment and human health.

纳米(nanometre,nm)亦称毫微米，是长度单位。1nm是十亿分之一米(10 ^-9m)或百万分之一毫米(10 ^-6mm)。简单说来，纳米农药是指农药活性成分的微粒尺寸处于纳米量级的农药制剂。纳米量级通常包括几到几百纳米范围。一般认为，纳米农药术语可用来描述包括下述的任何农药制剂：①制剂的活性成分微粒在纳米尺寸范围内，一般几到几百纳米；②制剂形成的是以指定的“纳米”为前缀的物质，如纳米晶粒、纳米杂化物、纳米复合物、纳米微球、纳米胶囊等；③具有与小尺寸微粒相关的新颖特性的制剂，如巨大的表面积、优异的防效。 Nanometer (nm), also known as nanometer, is a unit of length. 1nm is one billionth of a meter (10 ^-9 m) or one millionth of a millimeter (10 ^-6 mm). Simply put, nano pesticides refer to pesticide preparations whose particle size of pesticide active ingredients is in the nanometer order. The order of nanometers usually includes a few to several hundred nanometers. It is generally believed that the term nanopesticide can be used to describe any pesticide formulation including the following: ① The active ingredient particles of the formulation are in the nanometer size range, generally a few to several hundred nanometers; ② The formulation is formed with the specified "nano" as a prefix Substances, such as nano-grains, nano-hybrids, nano-composites, nano-microspheres, nano-capsules, etc.; ③ preparations with novel characteristics related to small-size particles, such as huge surface area and excellent control effect

研究发现，农药制剂的药效发挥高低，与其活性成分在农药剂型中以及在喷施后最终形成的微粒粒径大小、表面积大小和分散性有关。农药微粒尺寸越小，表面积越大，分散在作物叶面上越均匀，接触生物靶标面积越广，药效的发挥就会越充分。因此，使农药剂型发挥高效最有效的途径，就是尽可能地减小农药活性成分的微粒尺寸。经计算，当农药制剂中活性成分的微粒尺寸从现有的微米尺寸减小至相应的纳米尺寸时，尺寸减小了三个数量级，相同质量的农药微粒数量就会增加10亿倍，表面积增加一千倍，从而农药微粒能够更充分地接触靶标，发挥更好的防治作用，显著提高农药的药效。这样，达到同样对病虫害的防治效果，就可以比传统农药制剂明显减少农药用量，达到农药减量控害的目的，减轻因施用农药对生态环境所造成的影响。这就是为什么要发展纳米农药的根本原因。Studies have found that the effectiveness of pesticide formulations is related to the particle size, surface area, and dispersion of the final active particles in the pesticide formulation and after spraying. The smaller the size of the pesticide particles, the larger the surface area, the more uniformly they are dispersed on the leaf surface of the crop, and the wider the area of contact with the biological target, the more effective the effect will be. Therefore, the most effective way to make pesticide dosage forms effective is to reduce the particle size of pesticide active ingredients as much as possible. It is calculated that when the particle size of the active ingredient in the pesticide formulation is reduced from the existing micron size to the corresponding nano size, the size is reduced by three orders of magnitude, the number of pesticide particles of the same quality will increase by 1 billion times, and the surface area will increase One thousand times, so that the pesticide particles can more fully contact the target, play a better prevention and control role, and significantly improve the efficacy of the pesticide. In this way, to achieve the same effect on the prevention and control of pests and diseases, it is possible to significantly reduce the amount of pesticides compared to traditional pesticide preparations, to achieve the purpose of pesticide reduction and harm control, and to reduce the impact of the application of pesticides on the ecological environment. This is the fundamental reason why the development of nano pesticides.

是否所有农药都能制备成纳米农药呢？这要从农药在水中的溶解性能说起。由于农药大多以水为分散介质进行喷施，所以根据对水的溶解性能，农药大致可以分为三类：一类是可溶于水的农药，这类农药品种的数量不多，大约占8％；第二类是难溶于水或不溶于水，但能溶于某类有机溶剂的农药，这类农药品种约占50％；第三类是既不溶于水又不溶于有机溶剂的农药接近20％。其余农药是性质不明确，或是生物活体、气体类的农药。溶于水的农药在水中是单分子分散，属于真溶液。由于绝大部分农药都是小分子有机化合物，分子尺寸一般都小于1个纳米。由于分子尺寸比纳米尺寸还小，这部分溶于水的农药就无需制备成纳米农药。可见，纳米农药是针对不溶于水的农药品种而言，由于在水中不能溶解，只能聚集，因此希望其在水中的聚集体以尽可能小的尺寸分散，也就是纳米尺寸，从几个纳米，到几十、几百个纳米，这就是纳米农药。这样，并不是所有农药都必须做成纳米农药，水溶性农药就不需要。还有一点就是，也不是所有农药都能做成纳米农药。目前，只有不溶于水但能溶于有机溶剂的农药品种，根据其在溶剂中的溶解性能和溶解情况，才有可能通过分散、沉淀、负载等方式将其制备成纳米农药。这一类农药约占所有农药品种的一半，也是本发明涉及的范围。对于第三类既不溶于水又不溶于有机溶剂的农药品种，将其分散成纳米尺寸聚集体，通常是通过机械力的作用进行粉碎、研磨。按照现有的技术水平，以这种方式全部将其分散成纳米尺寸是基本不可能的，因此这类农药品种难以制备成纳米农药。Can all pesticides be prepared into nano pesticides? This starts with the solubility of pesticides in water. Since most pesticides are sprayed with water as a dispersion medium, pesticides can be roughly divided into three categories according to their solubility in water: one is water-soluble pesticides, and the number of these types of pesticides is not large, accounting for about 8%; the second category is pesticides that are hardly soluble in water or insoluble in water, but can be dissolved in a certain type of organic solvent, this type of pesticide accounts for about 50%; the third category is both insoluble in water and insoluble in organic solvents The pesticide is close to 20%. The remaining pesticides are of unclear nature, or biological or gaseous pesticides. Pesticides soluble in water are monomolecularly dispersed in water and belong to true solutions. Since most pesticides are small molecule organic compounds, the molecular size is generally less than 1 nanometer. Because the molecular size is smaller than the nano size, this part of water-soluble pesticide need not be prepared as a nano pesticide. It can be seen that nano pesticides are for water-insoluble pesticides. Since they cannot be dissolved in water, they can only aggregate. Therefore, it is hoped that the aggregates in water can be dispersed in the smallest possible size, that is, the nano size, from several nanometers. , To tens or hundreds of nanometers, this is nano pesticides. In this way, not all pesticides must be made into nano pesticides, and water-soluble pesticides are not needed. Another point is that not all pesticides can be made into nano pesticides. At present, only pesticide varieties that are insoluble in water but soluble in organic solvents can be prepared into nano pesticides by dispersion, precipitation, loading, etc. according to their solubility and dissolution in solvents. This type of pesticide accounts for about half of all pesticide varieties and is also within the scope of the present invention. For the third category of pesticides that are neither soluble in water nor organic solvents, they are dispersed into nano-sized aggregates, usually crushed and ground by the action of mechanical force. According to the existing technical level, it is basically impossible to disperse them into nano-sizes in this way, so it is difficult to prepare such pesticide varieties into nano-pesticides.

与传统农药制剂相比，纳米农药具有四大明显优势：一是药效提高。由于活性成分微粒尺寸小，同样质量的药物，微粒数量更多，接触作物靶标的面积更大，因而在相同植保效果下，可以显著减少农药用量。二是制剂稳定。分散在水中的纳米农药微粒尺寸越小，制剂的透明性越好，实现表观水溶，热力学稳定。通过性能控制，能够实现兑水稀释不发生农药的析出、沉淀，使农药的使用更加高效便捷。三是绿色环保。利用现有的技术，纳米农药可以研制成以水为分散介质，以天然物质或其衍生物为助剂，不使用高毒的苯类溶剂和助剂的绿色环保型制剂，从而从根本上解决农药施用导致的农业面源污染问题。四是制造安全。研究纳米农药的初衷，就是为了提高农药的药效，减少农药用量，在这一过程中不使用高毒的有机溶剂和助剂，用水取代或部分取代有机溶剂，所有这些举措不仅都标志着纳米农药的高效和环境友好，而且也表明比传统农药剂型如乳油的生产、储存、运输和操作更加安全。正因为如此，纳米农药已成为世界各国竞相研发的热点领域。Compared with traditional pesticide preparations, nano-pesticides have four obvious advantages: One is the improvement of drug efficacy. Due to the small size of the active ingredient particles, the same quality of drugs, the number of particles is greater, and the area contacting the crop target is larger, so under the same plant protection effect, the amount of pesticides can be significantly reduced. Second, the preparation is stable. The smaller the size of the nano pesticide particles dispersed in water, the better the transparency of the preparation, achieving apparent water solubility and thermodynamic stability. Through performance control, it can be diluted with water without precipitation or precipitation of pesticides, which makes the use of pesticides more efficient and convenient. The third is green. Using existing technology, nano pesticides can be developed into green and environmentally friendly formulations that use water as a dispersion medium, natural substances or their derivatives as additives, and do not use highly toxic benzene solvents and additives, thus fundamentally solving Agricultural non-point source pollution caused by pesticide application. The fourth is manufacturing safety. The original intention of studying nano-pesticides is to improve the efficacy of pesticides and reduce the amount of pesticides. In this process, high-toxic organic solvents and additives are not used. Organic solvents are replaced or partially replaced with water. All these measures not only mark nano Pesticides are highly efficient and environmentally friendly, and also show that they are safer than traditional pesticide formulations such as emulsifiable concentrates in production, storage, transportation, and operation. Because of this, nano-pesticides have become a hotspot in which countries around the world are competing in research and development.

目前出现的纳米农药类型，可以归纳为三大类：The types of nano pesticides currently appearing can be grouped into three major categories:

第一类是提高农药表观溶解度的纳米农药。这类纳米农药制剂的目的是为了提高水不溶性农药活性成分的表观溶解度。当分散在水中的农药微粒尺寸小于可见光波长(400～760nm)四分之一时，入射光不产生严重的折射和反射，溶液呈现出表观水溶、外观透明的性能，从而提高了纳米农药在水中的表观溶解度。这类纳米农药包括：微乳剂、纳米乳剂、纳米分散剂等。The first category is nano pesticides that improve the apparent solubility of pesticides. The purpose of this type of nano pesticide formulation is to increase the apparent solubility of the water-insoluble pesticide active ingredient. When the size of pesticide particles dispersed in water is less than one-quarter of the visible light wavelength (400-760nm), the incident light does not cause serious refraction and reflection, and the solution exhibits the properties of apparent water solubility and transparent appearance, thereby improving the Apparent solubility in water. Such nano pesticides include: microemulsion, nanoemulsion, nanodispersant, etc.

第二类是对纳米农药微粒实施保护并赋予缓释或控释性能的纳米农药。发展缓释或控释制剂的初衷，主要是针对农药活性成分过早降解或偏离靶向问题，也有针对低水溶解性活性成分的情况。人们认识到，大多数的农药活性成分在喷施后，受环境因素(紫外光、氧、热)的影响，会发生降解或分解，影响药效发挥。为了实现农药的缓释或控释，就必须对活性成分实施保护，使其免于过早分解。保护的方式，就是使用载体物质。载体物质分为软质载体(高分子、固体脂质体)和硬质载体(多孔中空纳米SiO ₂、层状双金属氢氧化物(LDH)和粘土)。根据载体物质的种类不同，这类纳米农药的类型就有纳米农药微球、纳米农药凝胶、纳米农药纤维、纳米农药脂质体、纳米农药中空多孔SiO ₂、纳米农药LDH、纳米农药粘土等。 The second category is nano-pesticides that protect nano-pesticide particles and impart slow-release or controlled-release properties. The original intention of developing slow-release or controlled-release preparations was mainly to address the problem of premature degradation or deviation from targeting of pesticide active ingredients, and also to the case of active ingredients with low water solubility. It is recognized that after spraying, most of the active ingredients of pesticides will be degraded or decomposed by environmental factors (ultraviolet light, oxygen, heat), which will affect the effectiveness of the drug. In order to achieve slow or controlled release of pesticides, it is necessary to protect the active ingredients from premature decomposition. The way to protect is to use carrier substances. The carrier material is divided into a soft carrier (polymer, solid liposome) and a hard carrier (porous hollow nano-SiO ₂ , layered double metal hydroxide (LDH) and clay). Depending on the type of carrier material, these types of nano pesticides include nano pesticide microspheres, nano pesticide gels, nano pesticide fibers, nano pesticide liposomes, nano pesticide hollow porous SiO ₂ , nano pesticide LDH, nano pesticide clay, etc. .

第三类是纳米金属或纳米金属氧化物农药制剂。纳米金属如银(Ag)和纳米氧化物如二氧化钛(TiO ₂)都是典型的无机物，分别具有各自的特殊性能。它们或单独、或与农药纳米粒子复合在一起，可形成纳米金属或纳米金属氧化物农药制剂。Ag具有大家熟知的抗菌性能。纳米Ag可以一种剂量依赖的方式，显著抑制植物病原体的生长。纳米TiO ₂被称为光触媒，在紫外光的作用下，可催化分解有机物质。这类纳米农药制剂包括两类：一类是单独使用的纳米金属和纳米金属氧化物；另一类是农药活性成分与纳米金属或纳米金属氧化物结合使用的纳米农药。 The third category is nano metal or nano metal oxide pesticide preparations. Nano-metals such as silver (Ag) and nano-oxides such as titanium dioxide (TiO ₂ ) are typical inorganic substances, each with its own special properties. They can be used alone or in combination with pesticide nanoparticles to form nanometal or nanometal oxide pesticide formulations. Ag has well-known antibacterial properties. Nano Ag can significantly inhibit the growth of plant pathogens in a dose-dependent manner. Nano-TiO ₂ is called a photocatalyst, and it can catalyze and decompose organic substances under the action of ultraviolet light. This type of nano pesticide formulation includes two types: one is nano metal and nano metal oxide used alone; the other is nano pesticide used in combination with nano metal or nano metal oxide.

发展纳米农药的就是为了在农业生产中应用，具体地说，就是为了提高药效，减少农药用量，减轻对生态环境的影响。但在纳米农药研发中存在一些问题，包括：(1)缺乏共性技术的研究。多数研发属于孤立、发散性研究探索，通常是针对某一农药品种进行纳米农药的制备和表征；(2)缺乏发展纳米农药研究的方向性和总体性思考与设计，研究不***、不深入。(3)缺乏相关交叉学科的知识，某些研究出现偏差而不自知。(4)缺乏实用性。绝大多数研究仅限于实验室结果，难以实现纳米农药的产业化和商业化。对于后者，主要涉及到纳米农药制备方法的难易、工艺操作流程的控制、纳米农药的性能控制，以及助剂是否易得和性价比等。The development of nano-pesticides is for application in agricultural production, specifically, to improve the efficacy, reduce the amount of pesticides, and reduce the impact on the ecological environment. However, there are some problems in the research and development of nano pesticides, including: (1) The lack of common technology research. Most research and development are isolated and divergent research and exploration, usually for the preparation and characterization of nano pesticides for a certain pesticide variety; (2) Lack of directionality and overall thinking and design for the development of nano pesticide research, the research is not systematic and in-depth. (3) Lack of knowledge of relevant cross-disciplines, and some studies are biased without knowing it. (4) Lack of practicality. The vast majority of research is limited to laboratory results, and it is difficult to realize the industrialization and commercialization of nano pesticides. For the latter, it is mainly related to the difficulty of the preparation method of nano pesticides, the control of process operation flow, the performance control of nano pesticides, and the availability and cost performance of additives.

需要指出的是，纳米农药并不意味着先天就是环境友好。只有在研发过程中树立绿色环保理念，不使用高毒的苯类溶剂和有毒助剂，如壬基酚聚氧乙烯醚类雌性化剂，才能获得绿色环保型纳米农药。It should be pointed out that nano-pesticide does not mean that it is inherently environmentally friendly. Only by establishing the concept of green environmental protection in the research and development process, without using highly toxic benzene solvents and toxic auxiliary agents, such as nonylphenol polyoxyethylene ether feminizing agents, can we obtain green environmentally friendly nano pesticides.

发明内容Summary of the invention

一、术语说明1. Terminology

本发明涉及一些专门术语。在这些专门术语中，其中一些是本专业领域人员熟知的专业术语，另一些是本发明为方便叙述，对一些组分和获得的中间产物进行了专门标注，仅代表所规定的含义。一些术语的说明见表-1。The present invention relates to some specific terms. Among these specialized terms, some of which are well-known to those skilled in the art, and others are for the convenience of the description of the present invention, some components and intermediate products obtained are specifically labeled, and only represent the prescribed meanings. Some terms are described in Table-1.

表-1 本发明涉及的专门术语及说明Table-1 Special terms and descriptions involved in the present invention

二、发明目的2. Purpose of the invention

本发明的首要目的在于克服现有技术的不足，提供新型绿色环保型纳米农药制剂，特别是混溶纳米农药悬浮剂、纳米农药悬浮剂和纳米农药固体粉剂。本发明所述的混溶纳米悬浮剂、纳米悬浮剂和纳米粉剂具有优于现有乳油、悬浮剂、水乳剂、可湿性粉剂、可分散粒剂、水分散粒剂等剂型的特点：⑴农药微粒纳米尺寸分散，比现有的农药剂型微粒的微米尺寸小2～3个数量级，因此同样质量的农药活性成分，就具有更多的微粒数目和更大的比表面积，更有利于提高药效。⑵不使用高毒的苯类溶剂和有毒的助剂，选用天然产物及其衍生物物作为绿色助剂，选用低毒的溶剂，并进行回收。⑶混溶纳米悬浮剂、纳米悬浮剂和纳米粉剂性能稳定，性能指标符合国家相关规定。⑷本发明技术相对并不复杂，有利于纳米农药的产业化。The primary purpose of the present invention is to overcome the shortcomings of the prior art, and to provide new green and environmentally friendly nano pesticide preparations, especially miscible nano pesticide suspension agents, nano pesticide suspension agents and nano pesticide solid powders. The miscible nano-suspending agent, nano-suspending agent and nano-powder described in the present invention have the characteristics of being better than existing emulsifiable concentrates, suspending agents, water emulsions, wettable powders, dispersible granules, water-dispersible granules and other dosage forms: (1) pesticides The nanometer size of the particles is dispersed, which is 2 to 3 orders of magnitude smaller than the micrometer size of the existing pesticide formulation particles. Therefore, the same quality of the pesticide active ingredient has more particles and a larger specific surface area, which is more conducive to improving the efficacy . ⑵Do not use highly toxic benzene solvents and toxic additives, choose natural products and their derivatives as green additives, choose low-toxic solvents, and recycle them. (3) The performance of miscible nano-suspending agent, nano-suspending agent and nano-powder is stable, and the performance index conforms to relevant national regulations. ⑷ The technology of the present invention is relatively uncomplicated, which is beneficial to the industrialization of nano pesticides.

本发明还有一个目的，就是提供绿色环保型纳米农药制剂特别是混溶纳米悬浮剂、纳米悬浮剂和纳米固体粉剂的制备方法。Another object of the present invention is to provide a method for preparing green and environmentally friendly nano pesticide preparations, especially miscible nano suspending agents, nano suspending agents and nano solid powders.

纳米悬浮剂与现有的悬浮剂的区别，除农药活性成分的微粒尺寸要小2～3个数量级外，其制备工艺也不相同。传统悬浮剂的制备需要采用高速剪切机先进行初粉碎，然后再转入连续化砂磨机中与助剂一起进行研磨。因此传统悬浮剂的制备需要购置相应的高速粉碎机、研磨机等机械设备，而且制备操作要经过不同工序。此外，制剂性能不同。由于现有悬浮剂微粒粒径在微米以上，对可见光产生折射和反射，因而不透明，也容易聚集、沉淀；而混溶纳米悬浮剂、纳米悬浮剂的微粒小于可见光波长的四分之一，不产生严重的折射和反射，因而制剂透明、稳定。而本发明制备混溶纳米悬浮剂和纳米悬浮剂的方法和工艺具有如下显著优点：(1)使用的设备简单。所需设备仅是一台搅拌速度可控、具有回流冷凝器、能够在加热条件下进行减压蒸馏操作的搅拌釜。(2)操作并不复杂，包括控制滴加速度、加热和减压回收溶剂。(3)制造过程绿色、节能。制备过程中，虽然使用了一定量的有机溶剂，但选择使用低毒的有机溶剂，而且可通过后续操作环节可进行溶剂回收。(4)提供一个通用普适的制备方法。本发明为众多的农药品种制备混溶纳米悬浮剂、纳米悬浮剂和纳米固体粉剂提供了一个通用有效的方法。The difference between the nano-suspending agent and the existing suspending agent, except that the particle size of the pesticide active ingredient is 2 to 3 orders of magnitude smaller, the preparation process is also different. The preparation of the traditional suspending agent requires the use of a high-speed shearing machine for initial crushing, and then it is transferred to a continuous sand mill for grinding with additives. Therefore, the preparation of traditional suspending agents requires the purchase of corresponding high-speed pulverizers, grinders and other mechanical equipment, and the preparation operations go through different processes. In addition, the performance of the formulation is different. Because the particle size of the existing suspending agent particles is above micrometers, it refracts and reflects the visible light, so it is opaque, and it is easy to aggregate and precipitate; while the particles of the miscible nano-suspending agent and the nano-suspending agent are less than a quarter of the visible light wavelength Severe refraction and reflection occur, so the preparation is transparent and stable. The method and process for preparing the miscible nano-suspending agent and the nano-suspending agent of the present invention have the following significant advantages: (1) The equipment used is simple. The required equipment is only a stirring kettle with a controllable stirring speed, a reflux condenser, and a vacuum distillation operation under heating conditions. (2) The operation is not complicated, including controlling the drop acceleration, heating and decompressing the solvent recovery. (3) The manufacturing process is green and energy-saving. During the preparation process, although a certain amount of organic solvent is used, the low-toxic organic solvent is selected, and the solvent can be recovered through subsequent operations. (4) Provide a universal preparation method. The invention provides a universal and effective method for preparing miscible nano-suspending agents, nano-suspending agents and nano-solid powders for many kinds of pesticides.

三、本发明的技术方案3. The technical solution of the present invention

一种纳米农药制剂，该制剂的原辅料包含有效量的农药活性成分或农药原药，以及适量的溶剂、高分子助剂、小分子助剂和分散剂。A nano pesticide preparation, the raw and auxiliary materials of the preparation contain an effective amount of pesticide active ingredient or pesticide original drug, and an appropriate amount of solvent, high molecular adjuvant, small molecule adjuvant and dispersant.

所述的纳米农药制剂，该制剂的原辅料包含下列质量百分比的物质：In the nano pesticide preparation, the raw and auxiliary materials of the preparation contain the following mass percentage substances:

溶剂8～40％；高分子助剂2～22％；小分子助剂8～25％；分散剂25～56％；余量为农药活性成分或农药原药，各成分总和为100％。Solvents 8-40%; polymer adjuvants 2-22%; small-molecule adjuvants 8-25%; dispersants 25-56%; the balance is pesticide active ingredients or pesticide original drugs, the sum of the ingredients is 100%.

溶剂17～32％；高分子助剂2～7％；小分子助剂12～22％；分散剂35～45％；农药活性成分或农药原药3～18％。Solvents 17 to 32%; high molecular additives 2 to 7%; small molecular additives 12 to 22%; dispersants 35 to 45%; pesticide active ingredients or pesticide original drugs 3 to 18%.

溶剂23～32％；高分子助剂3～6％；小分子助剂16～21％；分散剂38～42％；农药活性成分或农药原药3～12％。Solvents 23 to 32%; high molecular additives 3 to 6%; small molecule additives 16 to 21%; dispersants 38 to 42%; pesticide active ingredients or pesticide original drugs 3 to 12%.

溶剂30％；高分子助剂5％；小分子助剂20％；分散剂40％；农药活性成分或农药原药5％。30% solvent; 5% polymer adjuvant; 20% small molecule adjuvant; 40% dispersant; 5% pesticide active ingredient or pesticide original drug.

所述的纳米农药制剂，其中农药活性成分或农药原药主要是不溶于水但能溶于有机溶剂的农药品种；溶剂为能够溶解农药活性成分或农药原药的有机溶剂中的一种或多种；高分子助剂为水溶性天然高分子、水溶性天然高分子衍生物，或者水溶性合成高分子物质；小分子助剂由阴离子助剂和非离子助剂构成的混合助剂，阴离子助剂在小分子助剂中的质量百分比为1～99％，余量为非离子助剂，二者共计为100％，其中阴离子助剂为8～18碳原子的直链或支链烃基或/和芳基的羧酸盐、磺酸盐、硫酸盐或磷酸盐，非离子助剂为聚氧乙烯醚类表面活性剂、多元醇类表面活性剂，或者聚氧乙烯-聚氧丙烯类聚醚型表面活性剂；所述聚氧乙烯醚类表面活性剂不包括壬基酚聚氧乙烯醚类表面活性剂；小分子助剂的HLB值至少为12；分散剂为水。The said nano pesticide preparation, wherein the pesticide active ingredient or pesticide original drug is mainly a kind of pesticide that is insoluble in water but soluble in organic solvents; the solvent is one or more of organic solvents that can dissolve the pesticide active ingredient or pesticide original drug Polymer additives are water-soluble natural polymers, water-soluble natural polymer derivatives, or water-soluble synthetic polymer materials; small molecular additives are mixed additives composed of anionic additives and nonionic additives, anionic additives The mass percentage of the agent in the small molecule adjuvant is 1 to 99%, and the balance is non-ionic adjuvant, the total of the two is 100%, wherein the anionic adjuvant is a linear or branched hydrocarbon group of 8 to 18 carbon atoms or/ And aryl carboxylates, sulfonates, sulfates or phosphates, non-ionic additives are polyoxyethylene ether surfactants, polyol surfactants, or polyoxyethylene-polyoxypropylene polyethers Surfactants; the polyoxyethylene ether surfactants do not include nonylphenol polyoxyethylene ether surfactants; the HLB value of the small molecule adjuvant is at least 12; the dispersant is water.

所述的纳米农药制剂，其中溶剂为包括至少一种可溶于水的溶剂和至少一种不溶于水的溶剂组成混合溶剂，二者比例根据农药及溶剂种类进行预试验确定最佳配比，一般两者质量比在1∶2左右。In the nano pesticide preparation, the solvent includes a mixed solvent composed of at least one water-soluble solvent and at least one water-insoluble solvent, and the ratio between the two is pre-tested according to the pesticide and the type of solvent to determine the optimal ratio. Generally, the mass ratio between the two is about 1:2.

所述的纳米农药制剂，其中高分子助剂选自淀粉及其衍生物(水溶性淀粉、氧化淀粉、羧甲基淀粉、改性淀粉、糊精、环糊精)，纤维素及其衍生物(羧甲基纤维素、羟乙基羟丙基纤维素)，羧甲基壳聚糖，改性瓜尔胶，茶皂素，水溶性腐植酸，木质素磺酸钠，聚乙烯醇，聚丙烯酸，聚丙烯酰胺，聚苯乙烯-马来酸酐共聚物，聚乙烯基吡咯烷酮中的水溶性品种的一种或多种，所述水溶性品种包括上述物质的盐；阴离子助剂选自十二烷基硫酸钠、十二烷基磺酸钠、十二烷基醚硫酸钠、十二烷基单磷酸酯钠、α-烯基磺酸钠、油酸钠、亚油酸钠、亚麻油酸钠、蓖麻油酸钠的一种或多种，非离子助剂选自AEO15、 AEO20、蓖麻油酸聚氧乙烯醚、吐温-80、吐温-40、烷基多糖苷中的一种或多种；小分子助剂的HLB值为13～40，优选13～18。The nano pesticide preparation, wherein the polymer adjuvant is selected from starch and its derivatives (water-soluble starch, oxidized starch, carboxymethyl starch, modified starch, dextrin, cyclodextrin), cellulose and its derivatives (Carboxymethyl cellulose, hydroxyethyl hydroxypropyl cellulose), carboxymethyl chitosan, modified guar gum, tea saponin, water-soluble humic acid, sodium lignosulfonate, polyvinyl alcohol, poly Acrylic acid, polyacrylamide, polystyrene-maleic anhydride copolymer, one or more of water-soluble species in polyvinylpyrrolidone, the water-soluble species include salts of the above substances; the anionic auxiliary agent is selected from twelve Sodium alkyl sulfate, sodium dodecyl sulfonate, sodium dodecyl ether sulfate, sodium dodecyl monophosphate, sodium α-alkenyl sulfonate, sodium oleate, sodium linoleate, linolenic acid One or more of sodium and ricinoleic acid, non-ionic auxiliary selected from one of AEO15, AEO20, ricinoleic acid polyoxyethylene ether, Tween-80, Tween-40, alkyl polyglucoside or Many kinds; the HLB value of the small molecule adjuvant is 13-40, preferably 13-18.

所述的纳米农药制剂，其中该制剂的剂型为适合纳米农药的所有剂型，优选为混溶纳米农药悬浮剂、纳米农药悬浮剂、纳米农药固体粉剂。In the nano pesticide preparation, the dosage form of the preparation is all dosage forms suitable for nano pesticides, preferably a miscible nano pesticide suspension agent, a nano pesticide suspension agent, a nano pesticide solid powder.

所述的纳米农药制剂，其中所述混溶纳米农药悬浮剂是将混溶原药溶液滴加到复合助剂水溶液中形成的有纳米晶粒和增溶胶束共存的水分散液；所述混溶原药溶液是将农药原药溶解在混合溶剂中形成的溶液；所述复合助剂水溶液是将高分子助剂和小分子助剂先后分别溶于水形成的水溶液；所述混合溶剂是由至少两种溶剂按照某种特定的比例混合而成；所述混合溶剂包括至少一种可溶于水的溶剂和至少一种不溶于水的溶剂；每种溶剂都必须能够溶解农药原药。The nano pesticide preparation, wherein the miscible nano pesticide suspension agent is an aqueous dispersion liquid in which nano crystal grains and sol-enriched beam coexist are formed by dropping the miscible prodrug solution into the aqueous solution of the composite auxiliary; the mixture The lyotropic drug solution is a solution formed by dissolving pesticide pesticides in a mixed solvent; the composite auxiliary aqueous solution is an aqueous solution formed by separately dissolving a polymer auxiliary and a small molecule auxiliary in water; the mixed solvent is composed of At least two solvents are mixed according to a certain ratio; the mixed solvent includes at least one water-soluble solvent and at least one water-insoluble solvent; each solvent must be able to dissolve the pesticide pesticide.

所述的混溶纳米农药悬浮剂，其中所述混溶纳米农药悬浮剂中，混溶原药溶液和复合助剂水溶液的质量百分比之和为100％；混溶原药溶液和复合助剂水溶液的质量百分比范围分别为：35％±5％，65％±5％；优选地，混溶原药溶液和复合助剂水溶液的质量百分比范围分别为：35％±3％，65％±3％。The miscible nano pesticide suspension agent, wherein in the miscible nano pesticide suspension agent, the mass percentage of the miscible original drug solution and the composite auxiliary aqueous solution is 100%; the miscible original drug solution and the composite auxiliary aqueous solution The mass percentage ranges are: 35%±5%, 65%±5%; preferably, the mass percentage ranges of the miscible original drug solution and the composite auxiliary solution are: 35%±3%, 65%±3% .

所述的混溶纳米农药悬浮剂，其中所述混溶原药溶液中，所述农药原药和所述混合溶剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：3％～18％，17％～32％；优选地，所述农药原药和所述混合溶剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：3％～12％，23％～32％。The miscible nano pesticide suspension agent, wherein in the miscible original drug solution, the mass percentage of the pesticide pesticide and the mixed solvent in the miscible nano pesticide suspension agent are respectively: 3% to 18 %, 17% to 32%; preferably, the mass percentages of the pesticide original drug and the mixed solvent in the miscible nano pesticide suspension are: 3% to 12% and 23% to 32%, respectively.

所述的混溶纳米农药悬浮剂，其中所述小分子助剂和所述高分子助剂共同组成复合助剂；所述复合助剂水溶液中，所述复合助剂和水占所述混溶纳米农药悬浮剂的质量百分比范围分别为：22％～28％，35％～45％；优选地，所述复合助剂和水占所述混溶纳米农药悬浮剂的质量百分比范围分别为：23％～27％，38％～42％。The miscible nano pesticide suspension agent, wherein the small molecule auxiliary agent and the high molecular auxiliary agent together form a composite auxiliary agent; in the aqueous solution of the composite auxiliary agent, the composite auxiliary agent and water account for the miscibility The range of the mass percentage of the nano pesticide suspension agent is: 22% to 28%, 35% to 45%; preferably, the range of the mass percentage of the composite auxiliary agent and water to the miscible nano pesticide suspension agent is: 23 %～27%, 38%～42%.

所述的混溶纳米农药悬浮剂，其中所述小分子助剂和所述高分子助剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：12％～22％，2％～7％；优选地，所述小分子助剂和所述高分子助剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：16％～21％，3％～6％。The miscible nano pesticide suspension agent, wherein the small molecule adjuvant and the polymer adjuvant account for the mass percentage of the miscible nano pesticide suspension agent are respectively: 12% to 22%, 2% to 7 %; preferably, the mass percentages of the small molecule adjuvant and the polymer adjuvant to the miscible nano pesticide suspension agent are respectively: 16% to 21%, 3% to 6%.

所述的混溶纳米农药悬浮剂，其中所述小分子助剂的HLB值至少为13；优选14以上。The miscible nano pesticide suspension agent, wherein the HLB value of the small molecule adjuvant is at least 13; preferably 14 or more.

所述的混溶纳米农药悬浮剂，其中所述小分子助剂包括阴离子助剂和非离子助剂。The miscible nano pesticide suspension agent, wherein the small molecule auxiliary agent includes an anionic auxiliary agent and a non-ionic auxiliary agent.

所述的混溶纳米农药悬浮剂，其中所述阴离子助剂为8～18碳原子的直链或支链烃基或/和芳基的羧酸盐、磺酸盐、硫酸盐或磷酸盐。The miscible nano pesticide suspension agent, wherein the anionic auxiliary agent is a carboxylate, sulfonate, sulfate or phosphate of a linear or branched hydrocarbon group or/and aryl group with 8 to 18 carbon atoms.

所述的混溶纳米农药悬浮剂，其中所述阴离子助剂为8～18碳原子的直链烷基的羧酸、磺酸、硫酸或磷酸的钠、钾、铵盐。In the miscible nano pesticide suspension agent, the anionic auxiliary agent is a sodium, potassium, or ammonium salt of a linear alkyl carboxylic acid having 8 to 18 carbon atoms, sulfonic acid, sulfuric acid, or phosphoric acid.

所述的混溶纳米农药悬浮剂，其中所述非离子助剂为聚氧乙烯醚类表面活性剂、多元醇类表面活性剂，或者聚氧乙烯-聚氧丙烯类聚醚型表面活性剂；所述聚氧乙烯醚类表面活性剂不包括壬基酚聚氧乙烯醚类表面活性剂。The miscible nano pesticide suspension agent, wherein the non-ionic auxiliary agent is a polyoxyethylene ether surfactant, a polyol surfactant, or a polyoxyethylene-polyoxypropylene polyether surfactant; The polyoxyethylene ether surfactants do not include nonylphenol polyoxyethylene ether surfactants.

所述的混溶纳米农药悬浮剂，其中所述高分子助剂为水溶性天然高分子、水溶性天然高分子衍生物，或者水溶性合成高分子物质。In the miscible nano pesticide suspension agent, the polymer aid is a water-soluble natural polymer, a water-soluble natural polymer derivative, or a water-soluble synthetic polymer substance.

所述的混溶纳米农药悬浮剂，其中所述的水溶性天然高分子、水溶性天然高分子衍生物、水溶性合成高分子物质为容易生物降解的物质。In the miscible nano pesticide suspension agent, the water-soluble natural polymer, the water-soluble natural polymer derivative, and the water-soluble synthetic polymer are easily biodegradable.

所述的混溶纳米农药悬浮剂，其中所述农药原药及其所述混合溶剂中可溶于水的溶剂和不溶于水的溶剂，来自下表：The miscible nano pesticide suspension agent, wherein the pesticide original drug and the mixed solvent thereof are water-soluble and water-insoluble solvents from the following table:

所述的纳米农药制剂的制备方法，该制剂的制备方法包含下列步骤：The preparation method of the nano pesticide preparation includes the following steps:

1)将农药活性成分或农药原药溶于溶剂形成混溶原药溶液；1) Dissolve pesticide active ingredient or pesticide original drug in solvent to form miscible original drug solution;

2)将高分子助剂溶于分散剂形成高分子助剂溶液，将小分子助剂溶于分散剂形成小分子助剂溶液，将小分子助剂溶液加入到高分子助剂溶液中形成复合助剂溶液，或者直接将小分子助剂加入到高分子助剂溶液中形成复合助剂溶液；2) Dissolve the polymer adjuvant in the dispersant to form a polymer adjuvant solution, dissolve the small molecule adjuvant in the dispersant to form a small molecule adjuvant solution, and add the small molecule adjuvant solution to the polymer adjuvant solution to form a compound Auxiliary solution, or directly add small molecule auxiliary to polymer auxiliary solution to form composite auxiliary solution;

3)将混溶原药溶液加入到复合助剂溶液中，控制加入速度及搅拌速度防止产生宏观沉淀，得到混溶纳米农药悬浮剂即可或者在所得到的混溶纳米农药悬浮剂基础上再制备成其他制剂。3) Add the miscible prodrug solution to the compound adjuvant solution, control the addition speed and stirring speed to prevent macro-precipitation, and just obtain the miscible nano pesticide suspension agent or re-based on the obtained miscible nano pesticide suspension agent. Prepared into other preparations.

所述的纳米农药制剂的制备方法，其中所述的其他制剂包括纳米农药悬浮剂、纳米农药固体粉剂。The preparation method of the nano pesticide preparation, wherein the other preparations include a nano pesticide suspension agent and a nano pesticide solid powder.

所述的纳米农药制剂的制备方法，其中所述混溶纳米农药悬浮剂是将某种农药原药制成的混溶原药溶液滴加到复合助剂水溶液中形成的有纳米晶粒和增溶胶束共存的水分散液；所述混溶纳米农药悬浮剂的制备方法包括如下步骤：The method for preparing the nano pesticide preparation, wherein the miscible nano pesticide suspension agent is formed by dropping a miscible original drug solution made of a certain pesticide original drug into an aqueous solution of a composite auxiliary agent, which has nano crystal grains and An aqueous dispersion in which sol beams coexist; the preparation method of the miscible nano pesticide suspension agent includes the following steps:

1)混合溶剂的制备：将至少一种可溶于水的溶剂和至少一种不溶于水的溶剂，在容器中搅拌，生成混合溶剂；所述可溶于水的溶剂和不溶于水的溶剂都能够溶解所述农药原药；1) Preparation of mixed solvent: mixing at least one water-soluble solvent and at least one water-insoluble solvent in a container to produce a mixed solvent; the water-soluble solvent and the water-insoluble solvent Can dissolve the pesticide pesticide;

2)混溶原药溶液的制备：将所述农药原药加入到所述混合溶剂中，经搅拌溶解，得到混溶原药溶液；2) Preparation of miscible original drug solution: add the pesticide original drug to the mixed solvent and dissolve by stirring to obtain a miscible original drug solution;

3)复合助剂水溶液的制备：先将一种或几种高分子助剂在搅拌下加入水中，必要时进行静止溶胀；在所述高分子助剂充分溶胀后，开动搅拌，直到完全溶解，生成透明的高分子水溶液；然后在所述高分子水溶液中再加入一种或几种小分子助剂，经搅拌，溶解，得到复合助剂水溶液；3) Preparation of aqueous solution of compound additives: First, one or several polymer additives are added to water under stirring, and if necessary, static swelling; after the polymer additives are fully swelled, stirring is started until completely dissolved, Generate a transparent polymer aqueous solution; then add one or more small molecule additives to the polymer aqueous solution, stir and dissolve to obtain a composite auxiliary solution;

4)混溶纳米农药悬浮剂的制备：在搅拌速度可控的条件下，将所述混溶原药溶液滴加到所述复合助剂水溶液中；控制滴加速度和搅拌速度，生成分散均匀的纳米农药晶粒，最终完成混溶纳米农药悬浮剂的制备。4) Preparation of miscible nano pesticide suspension agent: Under the condition of controllable agitation speed, the miscible prodrug solution is added dropwise to the aqueous solution of the composite auxiliary; the drop acceleration and the agitation speed are controlled to produce a uniformly dispersed The nano pesticide grains finally complete the preparation of the miscible nano pesticide suspension agent.

所述的制备方法，其中通过控制所述滴加速度和/或搅拌速度，使得体系始终保持透明状态。According to the preparation method, by controlling the drop acceleration and/or stirring speed, the system is always kept in a transparent state.

所述的制备方法，其中，滴加的方式包括单点滴加、多点滴加或者喷雾滴加。According to the preparation method, the method of dropping includes single point dropping, multiple point dropping or spray dropping.

所述的制备方法，其中，所述搅拌速度的优选范围为100～200转/分钟。In the preparation method, the preferred range of the stirring speed is 100-200 rpm.

所述的制备方法，其中，所述混溶纳米农药悬浮剂中，混溶原药溶液和复合助剂水溶液的质量百分比之和为100％；混溶原药溶液和复合助剂水溶液的质量百分比范围分别为：35％±5％，65％±5％；优选地，混溶原药溶液和复合助剂水溶液的质量百分比范围分别为：35％±3％，65％±3％。The preparation method, wherein, in the miscible nano pesticide suspension agent, the sum of the mass percentage of the miscible original drug solution and the composite auxiliary aqueous solution is 100%; the mass percentage of the miscible original drug solution and the composite auxiliary aqueous solution The ranges are: 35%±5%, 65%±5%; preferably, the mass percentage ranges of the miscible original drug solution and the composite auxiliary aqueous solution are: 35%±3%, 65%±3%, respectively.

所述的制备方法，其中，所述混溶原药溶液中，所述农药原药和所述混合溶剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：3％～18％，17％～32％；优选地，所述农药原药和所述混合溶剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：3％～12％，23％～32％。The preparation method, wherein, in the miscible original drug solution, the mass percentage of the pesticide original drug and the mixed solvent in the miscible nano pesticide suspension agent are respectively: 3% to 18%, 17 % To 32%; preferably, the mass percentages of the pesticide original drug and the mixed solvent in the miscible nano pesticide suspension agent are respectively: 3% to 12%, 23% to 32%.

所述的制备方法，其中，所述小分子助剂和所述高分子助剂共同组成复合助剂；所述复合助剂水溶液中，所述复合助剂和水占所述混溶纳米农药悬浮剂的质量百分比范围分别为：22％～28％，35％～45％；优选地，所述复合助剂和水占所述混溶纳米农药悬浮剂的质量百分比范围分别为：23％～27％，38％～42％。The preparation method, wherein the small molecule auxiliary agent and the polymer auxiliary agent together constitute a composite auxiliary agent; in the aqueous solution of the composite auxiliary agent, the composite auxiliary agent and water account for the suspension of the miscible nano pesticide The mass percentage range of the agent is: 22%~28%, 35%~45%; preferably, the mass percentage range of the composite auxiliary agent and water in the miscible nano pesticide suspension agent is: 23%~27 %, 38%～42%.

所述的制备方法，其中，所述小分子助剂和所述高分子助剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：12％～22％，2％～7％；优选地，所述小分子助剂和所述高分子助剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：16％～21％，3％～6％。The preparation method, wherein the mass percentages of the small molecule adjuvant and the polymer adjuvant to the miscible nano pesticide suspension agent are respectively: 12%-22%, 2%-7%; preferably The mass percentages of the small molecule adjuvant and the polymer adjuvant to the miscible nano pesticide suspension agent are respectively: 16%-21%, 3%-6%.

所述的制备方法，其中，所述小分子助剂的HLB值至少为12；优选14以上。According to the preparation method, the HLB value of the small molecule adjuvant is at least 12; preferably 14 or more.

所述的制备方法，其中，所述混合溶剂的制备是在装有回流冷凝器的容器中进行。The preparation method, wherein the preparation of the mixed solvent is carried out in a vessel equipped with a reflux condenser.

所述的制备方法，其中，所述复合助剂水溶液的制备是在装有搅拌、回流冷凝器以及能够加热和减压蒸馏的容器中进行。According to the preparation method, the preparation of the aqueous solution of the composite auxiliary agent is carried out in a vessel equipped with stirring, a reflux condenser, and a vessel capable of heating and vacuum distillation.

所述的纳米农药制剂的制备方法，其中纳米农药悬浮剂的制备方法，在采用上述的方法完成混溶纳米农药悬浮剂的制备后，进一步采用如下两种蒸馏回收溶剂方式之一完成纳米农药悬浮剂的制备：The preparation method of the nano-pesticide preparation, wherein the preparation method of the nano-pesticide suspension agent, after completing the preparation of the miscible nano-pesticide suspension agent by the above method, further adopts one of the following two distillation recovery solvent methods to complete the nano-pesticide suspension Preparation of agent:

1)加热常压蒸馏；1) Heating atmospheric pressure distillation;

2)加热减压蒸馏；2) Heating and vacuum distillation;

当溶剂沸点高于或等于非离子表面活性剂浊点温度时必须采用加热减压蒸馏。When the boiling point of the solvent is higher than or equal to the cloud point temperature of the nonionic surfactant, heating and vacuum distillation must be used.

所述的制备方法，其中，加热温度必须在非离子表面活性剂浊点温度之下。According to the preparation method, the heating temperature must be below the cloud point temperature of the nonionic surfactant.

所述的纳米农药制剂的制备方法，其中纳米固体粉剂的制备方法为将上述的方法制备得到的混溶纳米农药悬浮剂或者将上述的方法制备得到的纳米农药悬浮剂采用喷雾干燥回收部分或全部溶剂后形成纳米农药粉状固体制剂。The preparation method of the nano pesticide preparation, wherein the preparation method of the nano solid powder is the miscible nano pesticide suspension prepared by the above method or the nano pesticide suspension prepared by the above method is spray dried to recover part or all After the solvent, a nanometer pesticide powder solid preparation is formed.

宏观沉淀是指微粒尺寸大于1微米以上的固体粒子。Macro precipitation refers to solid particles with a particle size greater than 1 micron.

四、以下通过具体的混溶纳米悬浮剂、纳米悬浮剂和纳米固体粉剂的制备对本发明作详细的说明。4. The following provides a detailed description of the present invention through the preparation of specific miscible nanosuspension agents, nanosuspension agents and nanosolid powders.

(一)、混溶纳米农药悬浮剂的组成(1) Composition of miscible nano pesticide suspension agent

1、混溶纳米农药悬浮剂的组分选择1. Selection of components of miscible nano pesticide suspension

⑴与农药混溶的混合溶剂⑴ Mixed solvent miscible with pesticide

本发明的第一步是选择能与农药混溶的混合溶剂。混合溶剂是由至少两种溶剂按照某种特定的比例混合而成。选择的原则包括：⑴对农药的溶解性能尽可能要好，使溶剂的使用量不至于太大；⑵溶剂的沸点不能太高，以便利于回收；⑶毒性尽可能要小，在有多种溶剂可供选择时，应选择毒性小的溶剂；⑷在混合溶剂中，每种溶剂都必须能够溶解农药原药；分为两类：一是可溶于水的溶剂；另一是不溶于水的溶剂。⑸混合溶剂至少要包括一种可溶于水的溶剂和一种不溶于水的溶剂。The first step of the present invention is to select a mixed solvent that is miscible with pesticides. The mixed solvent is formed by mixing at least two solvents in a certain ratio. The selection principles include: (1) The solubility of the pesticide should be as good as possible so that the amount of solvent used is not too large; (2) The boiling point of the solvent should not be too high to facilitate recovery; (3) The toxicity should be as small as possible. When choosing, choose a solvent with low toxicity; ⑷ In the mixed solvent, each solvent must be able to dissolve the pesticide pesticide; divided into two categories: one is a solvent soluble in water; the other is a solvent insoluble in water . ⑸ The mixed solvent should include at least a solvent soluble in water and a solvent insoluble in water.

有机溶剂的类型很多，按照结构类型不同，主要分为：苯类溶剂、烷烃溶剂、酮类溶剂、酯类溶剂、醇类溶剂、油类溶剂等。There are many types of organic solvents. According to different structure types, they are mainly divided into: benzene solvents, alkane solvents, ketone solvents, ester solvents, alcohol solvents, and oil solvents.

本发明针对的农药，主要是不溶于水但能溶于有机溶剂的农药品种。在现有的农药手册和文献资料中，一般会列出农药品种的物理性能，其中包括对一些溶剂的溶解性能，但资料并不齐全。这些溶剂的溶解性能可作为供本发明使用的溶剂和混合溶剂的选择。例如，表-2列出了一些重要农药活性成分，包括杀菌剂、杀虫剂和除草剂可选择使用的溶剂，括号中的数据单位为g/L，是每升可溶解农药活性成分的克数，而未标括号的溶剂数据不详，以此作为选择复合溶剂的参考。本发明的方法仅以此作为例子，但并不局限于本表和表中列出的农药品种以及溶解它的溶剂类型。在上述表-2提供的农药活性成分的溶解性能数据中，混合溶剂的选择还存在下述经验规律：The pesticides targeted by the present invention are mainly pesticide varieties that are insoluble in water but soluble in organic solvents. In the existing pesticide manuals and literature, the physical properties of pesticide varieties are generally listed, including the solubility of some solvents, but the information is not complete. The dissolution properties of these solvents can be used as the choice of the solvent and mixed solvent used in the present invention. For example, Table-2 lists some important pesticide active ingredients, including fungicides, insecticides and herbicides. The solvents that can be used are selected. The data unit in parentheses is g/L, which is the grams of soluble pesticide active ingredient per liter. The number of solvents without parentheses is not clear, which is used as a reference for the selection of composite solvents. The method of the present invention is only used as an example, but is not limited to the types of pesticides listed in this table and the tables and the types of solvents that dissolve it. In the solubility performance data of pesticide active ingredients provided in Table 2 above, the following empirical rules still exist for the selection of mixed solvents:

①在农药的溶解性能数据中，出现最多的是丙酮(溶于水)，而与之相复配的不溶于水的酮类溶剂则包括环己酮、甲乙酮、苯乙酮，以及它们的衍生物，具有与丙酮类似的溶解度。①In the dissolution performance data of pesticides, acetone (soluble in water) appears the most, and water-insoluble ketone solvents formulated with it include cyclohexanone, methyl ethyl ketone, acetophenone, and their derivatives It has similar solubility to acetone.

②在可溶于水的甲醇、乙醇、异丙醇、乙腈、四氢呋喃溶剂选择中，与之相复配的不溶于水的溶剂除酮类溶剂外，不溶于水的乙酸乙酯的毒性小，沸点不高，是个可供选择的酯类溶剂，其同系物乙酸丙酯、乙酸异丙酯等，具有与之类似的溶解度。②In the selection of water-soluble solvents for methanol, ethanol, isopropanol, acetonitrile, and tetrahydrofuran, the water-insoluble solvent compounded with it, except ketone solvents, ethyl acetate insoluble in water is less toxic, The boiling point is not high, it is an alternative ester solvent, its homologues propyl acetate, isopropyl acetate, etc., have similar solubility.

③选择原则：溶解度相对较大(可减少溶剂用量)；毒性小；价格相对较低；沸点较低(以利于回收)等。③ Selection principle: relatively high solubility (can reduce the amount of solvent); low toxicity; relatively low price; low boiling point (to facilitate recovery), etc.

表-2 一些不同类型的重要农药品种可供选择的复合溶剂Table-2 Compound solvents that can be selected for some different types of important pesticide varieties

在制备环境有好型纳米农药制剂时尽量避免使用高毒的溶剂，如苯类、甲醇、卤代烷等。Avoid using highly toxic solvents, such as benzenes, methanol, and halogenated alkanes, as far as possible when preparing environmentally friendly nano pesticide formulations.

⑵复合助剂⑵Composite additives

本发明制备的混溶纳米农药悬浮剂、纳米农药悬浮剂，除使用混合溶剂外，还需要复合助剂(体系)。复合助剂包括小分子助剂和高分子助剂。它们的组分、作用分别说明如下。The miscible nano pesticide suspension agent and the nano pesticide suspension agent prepared by the present invention need a compound auxiliary agent (system) in addition to the mixed solvent. Compound additives include small molecule additives and polymer additives. Their components and functions are described below.

①小分子助剂①Small molecule additives

小分子助剂都属于表面活性剂，主要包括阴离子型表面活性剂和非离子型表面活性剂。Small molecule additives are all surfactants, mainly including anionic surfactants and nonionic surfactants.

阴离子表面活性剂分子是由亲水的极性基团和疏水的烃类基团所构成。在水溶液中离解为离子状态，含负电荷的酸根基团和在其周围的含正电荷的金属离子。从化学结构上分，可以是由8～18碳原子的直链或支链烃基(包括烷烃和烯烃)的羧酸盐、磺酸盐、硫酸盐或磷酸盐，或由8～18碳原子的直链或支链烃基(包括烷烃和烯烃)和芳基构成的羧酸盐、磺酸盐、硫酸盐或磷酸盐。从环境友好性能考虑，环境友好性能从好到差的顺序是，直链烃基的各种盐类>支链烃基的各种盐类>芳基的各种盐类。Anionic surfactant molecules are composed of hydrophilic polar groups and hydrophobic hydrocarbon groups. It dissociates into an ionic state in aqueous solution, with negatively charged acid radicals and positively charged metal ions around it. From the chemical structure, it can be a carboxylate, sulfonate, sulfate or phosphate of 8 to 18 carbon atoms of a linear or branched hydrocarbon group (including alkanes and alkenes), or of 8 to 18 carbon atoms Carboxylates, sulfonates, sulfates or phosphates composed of linear or branched hydrocarbon groups (including alkanes and alkenes) and aryl groups. Considering environmentally friendly performance, the order of environmentally friendly performance from good to poor is: various salts of linear hydrocarbon groups>various salts of branched hydrocarbon groups>various salts of aryl groups.

这些阴离子表面活性剂均具有降低表面张力、乳化和增溶等性能。表征它们有三项性能指标：一是临界胶束浓度(CMC)，即形成胶束的最低乳化剂浓度。CMC值越低，表明阴离子表面活性剂形成胶束的浓度越小，活性越高。所谓胶束，是阴离子表面活性剂在CMC浓度以下，是以单分子分散状态溶解在水中，当超过CMC浓度后，分子则发生聚集，若干个阴离子表面活性剂分子以一种能量最低状态聚集，亲水的极性基团朝向水相，而疏水的非极性基团(亲油基团)则聚集在一起，形成一个直径几纳米的球形胶束，形态结构示意图见图-1。当阴离子表面活性剂的浓度更高时，除球形胶束外，还可能形成棒状胶束。无论是球形胶束还是棒状胶束，其外部是羧酸盐、磺酸盐、硫酸盐或磷酸盐等亲水的基团，而内部都是亲油烃基基团，一种疏水亲油的环境，根据相似相溶的原理，可以容纳不溶于水的农药或它的疏水溶剂的溶液。考察阴离子表面活性剂的CMC时，一般其值越小，表明活性越高。二是克拉夫特(Krafft)温度，是阴离子表面活性剂形成胶束时的温度，也是分子溶解状态、胶束、凝胶三相平衡时的温度。在这一温度以上，阴离子表面活性剂的溶解度剧增，形成胶束。当低于此温度，将以凝胶析出。因此，这一温度越低，表明在水中形成胶束或凝胶析出的温度就越低，使用的温度范围就越宽。三是亲水亲油平衡值(HLB)。表面活性剂都是由亲水和亲油基团所组成，整个分子的亲水和亲油倾向，就用HLB值来衡量，它对于合理选择表面活性剂是一种重要的依据。现在表面活性剂的LHB值的相对标准规定如下：石蜡的HLB＝0，油酸的HLB＝1，油酸钾的HLB＝20，十二烷基硫酸钠的HLB＝40。在1～40，由小到大亲水性增强。一般HLB小于10，则认为亲油性好，大于10则认为亲水性好。根据表面活性剂的HLB值，可以推断作何种用途。表-3列出了各种用途所需要的表面活性剂的HLB值范围。These anionic surfactants have the properties of reducing surface tension, emulsifying and solubilizing. There are three performance indicators to characterize them: One is the critical micelle concentration (CMC), which is the lowest emulsifier concentration to form micelles. The lower the CMC value, the lower the concentration of anionic surfactant to form micelles, the higher the activity. The so-called micelle means that the anionic surfactant is below the CMC concentration and is dissolved in water in a single-molecule dispersed state. When the concentration exceeds the CMC, the molecules aggregate, and several anionic surfactant molecules aggregate in a state with the lowest energy. Hydrophilic polar groups face the water phase, while hydrophobic non-polar groups (lipophilic groups) gather together to form a spherical micelle with a diameter of a few nanometers. The morphological structure is shown in Figure -1. When the concentration of anionic surfactant is higher, rod-shaped micelles may be formed in addition to spherical micelles. Whether it is spherical micelles or rod micelles, the outside is a hydrophilic group such as carboxylate, sulfonate, sulfate or phosphate, while the inside is a lipophilic hydrocarbon group, a hydrophobic and lipophilic environment According to the principle of similar miscibility, it can accommodate solutions of water-insoluble pesticides or its hydrophobic solvents. When examining the CMC of an anionic surfactant, generally the smaller the value, the higher the activity. The second is the Krafft temperature, which is the temperature when the anionic surfactant forms micelles, and is also the temperature when the molecules are dissolved, the micelles, and the gel are in three-phase equilibrium. Above this temperature, the solubility of the anionic surfactant increases dramatically, forming micelles. When it is lower than this temperature, it will precipitate as a gel. Therefore, the lower the temperature, the lower the temperature at which micelles or gels precipitate in water, and the wider the temperature range used. The third is the hydrophilic-lipophilic balance (HLB). Surfactants are composed of hydrophilic and lipophilic groups. The hydrophilic and lipophilic tendency of the entire molecule is measured by the HLB value. It is an important basis for the rational selection of surfactants. The current relative standard of the LHB value of the surfactant is as follows: HLB of paraffin wax = 0, HLB of oleic acid = 1, HLB of potassium oleate = 20, and HLB of sodium lauryl sulfate = 40. From 1 to 40, the hydrophilicity is increased from small to large. Generally, if the HLB is less than 10, the lipophilicity is considered good, and if the HLB is greater than 10, the hydrophilicity is considered good. Based on the HLB value of the surfactant, it can be inferred what kind of use. Table-3 lists the HLB range of surfactants required for various applications.

除阴离子表面活性剂外，小分子助剂还需要使用非离子表面活性剂。这种表面活性剂在水溶液中不离解为离子状态，而是以分子或胶团状态存在于溶液中，故称为非离子表面活性剂。它的亲油基一般是烃链或聚氧丙烯链，亲水部分是聚氧乙烯、羟基或醚基、酰胺基等。非离子表面活性剂产品大部分呈液状或浆状，这是与阴离子表面活性剂不同之处。非离子表面活性剂按其亲水基结构不同，主要包括聚氧乙烯型非离子表面活性剂、多元醇型类离子表面活性剂和烷基醇酰胺型非离子表面活性剂。其中，前者是最重要的一类非离子表面活性剂，尤其是脂肪醇的聚氧乙烯醚品种多，产量大。这类非离子表面活性剂的性能不仅取决于疏水基，而且与聚氧乙烯醚链的长度也有很大的关系。若干个在水中的非离子表面活性剂分子在CMC以上形成球形胶团，胶团的形态结构与胶束类似，亲水的聚氧乙烯链在外部，朝着水相，亲油的烃基结构在内部，尺寸比胶束稍大，见图-3。In addition to anionic surfactants, non-ionic surfactants are required for small molecule additives. This surfactant does not dissociate into an ionic state in an aqueous solution, but exists in the solution in the state of molecules or micelles, so it is called a nonionic surfactant. Its lipophilic group is generally a hydrocarbon chain or a polyoxypropylene chain, and the hydrophilic part is a polyoxyethylene, hydroxyl or ether group, amide group, etc. Most non-ionic surfactant products are liquid or slurry, which is different from anionic surfactants. Nonionic surfactants differ in their hydrophilic group structure and mainly include polyoxyethylene-type nonionic surfactants, polyol-type ionic surfactants, and alkyl alcohol amide-type nonionic surfactants. Among them, the former is the most important type of nonionic surfactant, especially polyoxyethylene ethers of fatty alcohols have many varieties and large output. The performance of this type of nonionic surfactant not only depends on the hydrophobic group, but also has a great relationship with the length of the polyoxyethylene ether chain. Several nonionic surfactant molecules in water form spherical micelles above the CMC. The morphology and structure of the micelles are similar to micelles. The hydrophilic polyoxyethylene chain is on the outside, towards the water phase, and the lipophilic hydrocarbon-based structure is Inside, the size is slightly larger than the micelle, see Figure-3.

表-3 表面活性剂的HLB值范围及其大致应用Table-3 Range of HLB values of surfactants and their approximate applications

非离子表面活性剂的生物降解包括烃链与聚氧乙烯链两部分。烃链部分仍然是直链比支链容易降解，含芳基的降解比脂肪基的降解更为困难。聚氧乙烯链越长，降解性越差。在烷基酚聚氧乙烯醚中，尤其是壬基酚聚氧乙烯醚降解发生在酚基醚上，又生成壬基酚。而壬基酚被证实是具有雌性化毒性的物质，进入环境中尤其是进入水体中，会使水生生物雌性化。人类吃了雌性化的水生生物，也会产生***不育，因此这类非离子表面活性剂虽然乳化性能很好，但已禁用。The biodegradation of nonionic surfactants includes two parts: hydrocarbon chain and polyoxyethylene chain. The part of the hydrocarbon chain is still straight chain which is easier to degrade than branched chain, and the degradation of aromatic group is more difficult than the degradation of fatty group. The longer the polyoxyethylene chain, the worse the degradability. In alkylphenol polyoxyethylene ether, especially degradation of nonylphenol polyoxyethylene ether occurs on phenolic ether, and nonylphenol is generated. Nonylphenol has proved to be a feminine toxic substance, and entering the environment, especially into the water, will feminize aquatic organisms. Humans eat feminized aquatic organisms, and they also have infertility. Therefore, although such nonionic surfactants have good emulsifying properties, they have been banned.

对非离子表面活性剂表征有浊点和HLB值。缓慢加热非离子表面活性剂的透明水溶液，到某一温度后，溶液会发生浑浊，表示表面活性剂开始析出。溶液呈现浑浊的最低温度叫做“浊点”(cloud point)，是其水溶液随温度升高而分相的温度。在亲油基相同的非离子表面活性剂的同系物中，聚氧乙烯链越长，亲水性越强，浊点就越高。从实用化考虑，如果一个体系需要有加热过程，那么一定要考虑所用非离子表面活性剂的浊点，否则会由于出现浊点而使体系的稳定性遭到破坏。The nonionic surfactants are characterized by cloud point and HLB value. Slowly heating the transparent aqueous solution of the non-ionic surfactant, after reaching a certain temperature, the solution will become cloudy, indicating that the surfactant begins to precipitate. The lowest temperature at which a solution appears cloudy is called the "cloud point", which is the temperature at which the aqueous solution separates as the temperature increases. In the homologous series of nonionic surfactants with the same lipophilic group, the longer the polyoxyethylene chain, the stronger the hydrophilicity and the higher the cloud point. From the practical point of view, if a system requires a heating process, then the cloud point of the nonionic surfactant used must be considered, otherwise the stability of the system will be destroyed due to the cloud point.

非离子表面活性剂的HLB值，与阴离子表面活性剂的描述是一样的，都是对亲水亲油性能的一个定性的表征。表面活性剂的HLB值，可以由分析测定和计算多种方法求得，也可在手册和文献资料中查得。根据表面活性剂在水中的溶解状态，可以粗略估计HLB值的范围。例如，表-4列出了估计表面活性剂HLB值范围的一种快速方法。The HLB value of nonionic surfactants is the same as the description of anionic surfactants, and it is a qualitative characterization of the hydrophilic and lipophilic properties. The HLB value of the surfactant can be obtained by various methods of analytical determination and calculation, and can also be found in the manual and literature. According to the dissolution state of the surfactant in water, the range of the HLB value can be roughly estimated. For example, Table-4 lists a quick method for estimating the range of surfactant HLB values.

表-4 由表面活性剂在水中的溶解状态估算HLB值范围Table-4 Estimated HLB value range from the dissolved state of surfactant in water

本发明选择使用的小分子助剂至少由一种阴离子和至少由一种非离子表面活性剂组成，其目的在水溶液中形成具有增溶性能的胶束、胶团。因此对小分子复合助剂选择的原则是：第一，考虑到体系的稳定性，阴离子表面活性剂的krafft温度应尽可能低，最好接近0℃；第二，而非离子表面活性剂的cloud point温度，尽可能高于60℃，以免在减压回收溶剂时加热温度超过浊点温度；第三，溶解农药活性成分的混合溶剂的混溶原药溶液要实现在胶束、胶团中纳米尺寸的增溶，小分子复合助剂的HLB值应在13以上，最好在14以上。因为此时溶液透明，而透明则表明农药微粒尺寸小于可见光波长的四分之一，即100纳米以下。针对某些农药原药，HLB值在12也可以达到透明效果。The small molecule adjuvant selected for use in the present invention is composed of at least one anion and at least one nonionic surfactant, and its purpose is to form micelles and micelles with solubilizing properties in aqueous solution. Therefore, the principle for selecting small molecular compound additives is: first, considering the stability of the system, the krafft temperature of the anionic surfactant should be as low as possible, preferably close to 0 ℃; second, the non-ionic surfactant The cloud point temperature should be higher than 60℃ as much as possible, so as not to heat the temperature above the cloud point temperature when the solvent is recovered under reduced pressure; third, the miscible prodrug solution of the mixed solvent in which the pesticide active ingredient is dissolved must be realized in micelles and micelles For the solubilization of nanometer size, the HLB value of the small molecule compound additive should be above 13 and preferably above 14. Because the solution is transparent at this time, and transparent means that the size of the pesticide particles is less than a quarter of the wavelength of visible light, that is, below 100 nanometers. For some pesticides, the HLB value of 12 can also achieve transparency.

②高分子助剂② Polymer additives

高分子助剂也是高分子表面活性剂，通常是指相对分子质量大于10000、具有表面活性的物质。高分子表面活性剂与小分子表面活性剂相比，降低表面张力的能力不强，但具有其它一些特殊性能，如分散、悬浮、提高粘度等性能。高分子表面活性剂按照来源分类，可分为天然高分子及其衍生物和合成高分子。高分子表面活性剂具有疏水的主链和悬挂的亲水性官能团，如羟基、羧基、羧甲基、磺酸基、硫酸基、磷酸基、氨基等，因此都是水溶性高分子。水溶性天然高分子及其衍生物，包括淀粉、糊精以及各种衍生物，水溶性淀粉、氧化淀粉、羧甲基淀粉、改性淀粉、纤维素及其衍生物，羧甲基纤维素、羟乙基羟丙基纤维素；羧甲基壳聚糖、改性瓜尔胶、茶皂素、水溶性腐植酸、木质素磺酸钠等。合成水溶性高分子，包括聚乙烯醇、聚丙烯酸、聚丙烯酰胺、聚苯乙烯-马来酸酐共聚物、聚乙烯基吡咯烷酮等。由于水溶性合成高分子的主链多为碳链，不易生物降解，从环境友好考虑，应尽量选择水溶性天然高分子及其衍生物，将对生态环境的影响降低到最小。Polymer additives are also polymer surfactants, usually referring to substances with a relative molecular mass greater than 10,000 and having surface activity. Compared with small molecule surfactants, macromolecular surfactants have less ability to reduce surface tension, but have some other special properties, such as dispersion, suspension, and viscosity enhancement. Polymer surfactants can be divided into natural polymers and their derivatives and synthetic polymers according to their source. Polymer surfactants have a hydrophobic main chain and suspended hydrophilic functional groups, such as hydroxyl, carboxyl, carboxymethyl, sulfonate, sulfate, phosphate, and amino groups, so they are all water-soluble polymers. Water-soluble natural polymer and its derivatives, including starch, dextrin and various derivatives, water-soluble starch, oxidized starch, carboxymethyl starch, modified starch, cellulose and its derivatives, carboxymethyl cellulose, Hydroxyethyl hydroxypropyl cellulose; carboxymethyl chitosan, modified guar gum, tea saponin, water-soluble humic acid, sodium lignosulfonate, etc. Synthetic water-soluble polymers, including polyvinyl alcohol, polyacrylic acid, polyacrylamide, polystyrene-maleic anhydride copolymer, polyvinylpyrrolidone, etc. Since the main chain of water-soluble synthetic polymers is mostly carbon chains, it is not easy to biodegrade. From the consideration of environmental friendliness, water-soluble natural polymers and their derivatives should be selected as much as possible to minimize the impact on the ecological environment.

本发明选择高分子助剂的理由，是利用水溶性高分子在水溶液中起到的分散、悬浮等作用。一个相对分子质量在几万、十几万、几十万的水溶性高分子，通常都是线性高分子链结构，可以溶解在水中。当线性高分子溶解在水中时，线性高分子的长径比很大，但并不是以一根伸直的线性状态而呈现，而是由于分子链的柔顺性，呈现出一种卷曲状态，即“无规线团”的形态结构，见图-5。无规线团中的亲水基团尽量朝向水相，而亲油的链结构则卷曲在无规线团的内部。无规线团的尺寸取决于高分子助剂相对分子质量的大小、浓度的高低，以及高分子的聚集态结构。分子量大，单个分子形成的无规线团的体积就大；当水溶性高分子的浓度较高时，不同分子形成的无规线团就会聚集在一起，故而体积也较大。一般，当水溶性高分子的分子量在几万、十几万时，形成的无规线团的尺寸通常在几十至几百纳米。如果体系中有农药纳米晶粒生成时，根据相似相溶的原理，亲油的纳米晶粒倾向于进入亲油的无规线团的内部，掺杂在无规线团的不同部位。当农药纳米晶粒的尺寸较小时，无规线团内部可以分散若干纳米晶粒。事实上，水溶性高分子助剂可以对生成的纳米晶粒起到分散剂和稳定剂的作用。传统农药悬浮剂也是利用这一原理，但它们的农药微粒在微米尺寸，由于微米粒子的尺寸较大，同时具有较大的重力作用，故悬浮剂的稳定性存在较大的不确定性。当农药微粒尺寸降低2～3个数量级时，粒子的重力作用要小得多，同样的水溶性高分子表面活性剂，可以获得更加稳定的悬浮、分散体系，实现表观水溶，外观透明。The reason for selecting the polymer adjuvant in the present invention is to utilize the functions of dispersion and suspension of the water-soluble polymer in the aqueous solution. A water-soluble polymer with a relative molecular mass of tens of thousands, hundreds of thousands, or hundreds of thousands is usually a linear polymer chain structure that can be dissolved in water. When the linear polymer is dissolved in water, the length-to-diameter ratio of the linear polymer is very large, but it is not presented in a straight linear state, but due to the flexibility of the molecular chain, it exhibits a curled state, that is The morphological structure of "random coil" is shown in Figure-5. The hydrophilic groups in the random coil are oriented towards the water phase as much as possible, while the lipophilic chain structure is curled inside the random coil. The size of the random coil depends on the relative molecular mass of the polymer additives, the concentration level, and the aggregation state structure of the polymer. The larger the molecular weight, the larger the volume of random coils formed by a single molecule; when the concentration of water-soluble polymer is higher, the random coils formed by different molecules will gather together, so the volume is also larger. Generally, when the molecular weight of the water-soluble polymer is tens of thousands to hundreds of thousands, the size of the formed random coil is usually tens to hundreds of nanometers. If pesticide nanocrystals are generated in the system, according to the principle of similar miscibility, the oleophilic nanocrystals tend to enter the oleophilic random coil and dope in different parts of the random coil. When the size of the pesticide nanocrystals is small, several nanocrystals can be dispersed inside the random coil. In fact, the water-soluble polymer additives can act as a dispersant and stabilizer for the generated nano-grains. Traditional pesticide suspending agents also use this principle, but their pesticide particles are in the micron size. Because the size of the micron particles is large and at the same time has a large gravitational effect, there is a large uncertainty in the stability of the suspending agent. When the size of pesticide particles is reduced by 2 to 3 orders of magnitude, the gravitational force of the particles is much smaller. The same water-soluble polymer surfactant can obtain a more stable suspension and dispersion system to achieve apparent water solubility and transparent appearance.

2、混溶纳米农药悬浮剂的组分配比2. Composition ratio of miscible nano pesticide suspension agent

本发明的混溶纳米农药悬浮剂、纳米农药悬浮剂涉及到的组分包括：农药活性成分、溶剂(包括可溶于水的溶剂、不溶于水的溶剂)、助剂(包括小分子阴离子助剂、小分子非离子助剂和高分子助剂)和水。进一步归纳后，体系合并成三个组分：一是混溶原药溶液(原药+溶剂S ₁+溶剂S ₂+……)、二是复合助剂(小分子阴离子助剂+小分子非离子助剂+高分子助剂)。三是水。 The components of the miscible nano pesticide suspension agent and the nano pesticide suspension agent of the present invention include: pesticide active ingredients, solvents (including water-soluble solvents and water-insoluble solvents), auxiliary agents (including small molecule anionic auxiliary agents) Agents, small molecule non-ionic additives and polymer additives) and water. After further summarization, the system is combined into three components: one is the miscible drug solution (original drug + solvent S ₁ + solvent S ₂ +...), and the other is the compound auxiliary agent (small molecule anionic agent + small molecule non- Ionic additives + polymer additives). The third is water.

理想情形下，三种组分之间的质量比为：Ideally, the mass ratio between the three components is:

混溶原药溶液∶复合助剂∶水≈35％∶25％∶40％≈0.875∶0.625∶1。Miscible original drug solution: compound adjuvant: water ≈35%:25%:40% ≈0.875:0.625:1.

也就是说，混溶原药溶液、复合助剂分别约为水质量的0.875、0.625倍。That is to say, the miscible drug solution and the compound auxiliary agent are about 0.875 and 0.625 times the mass of water, respectively.

进一步合并后，体系则只存在两组分，即混溶原药溶液和复合助剂水溶液。两者之比约为：After further merging, there are only two components in the system, namely, the miscible drug solution and the aqueous solution of compound additives. The ratio of the two is approximately:

混溶原药溶液∶复合助剂水溶液≈35％∶65％≈7∶13Miscible original drug solution: aqueous solution of compound additives ≈35％:65％≈7:13

它们之间的配比关系论述如下：The matching relationship between them is discussed as follows:

(1)确定混溶原药溶液的质量百分比约为35％。原因分析如下：混溶原药溶液包括原药活性成分质量和混合溶剂质量。原药活性成分的含量有两种不同的表示方法：一是质量百分数，％；二是体积质量数，g/L。前者使用较多，本发明在涉及组分质量时也以质量百分数表示。在传统农药制剂中，尽管农药的活性不同，使用量不一样，但生产厂商在制备农药制剂时往往喜欢追求农药的高活性成分含量。高含量虽然能够减小包装物的体积和运输费用，但由于助剂含量相对较小，将影响农药制剂兑水稀释后药液的分散性能，以及对病虫害的防治效果。事实上，每种不同的农药品种都应该根据农药的活性高低和物理溶解性能不同，具有适合自身的不同活性成分含量。本发明是根据某种农药在某类溶剂体系中的溶解度(St ₁，St ₂……St _i))来制备它的混溶纳米农药悬浮剂和纳米农药悬浮剂(纳米分散剂)。考虑到溶剂的用量有一大致上限，例如30％，因此也就决定了农药活性成分最终在制剂中的含量。例如，序号为4的杀菌剂，苯氧喹啉，它在丙酮中的溶解度为116g/L。也就是10g质量的丙酮(属于可溶于水的溶剂)可以溶解约1.16g农药活性成分，而不溶于水的同系溶剂如甲乙酮、环己酮等具有类似的溶解度。这样，如果使用30g质量的溶剂，就可以溶解3.48g活性成分。考虑到饱和溶液容易析出溶质，混溶原药溶液不能配制成饱和状态，因此在混溶原药溶液中，原药活性成分的质量百分数可以定为3.3％。在体系组分中，混溶原药溶液则为3.3％，其余组分为复合助剂和水。在制剂制备的后期，通过减压蒸馏回收溶剂。假定所用溶剂全部回收，加上水作为共沸物组成被蒸出一部分，最终活性成分的含量可达到约5％。虽然还可以增加溶剂用量溶解更多含量的农药活性成分，但这势必会减少复合助剂和水用量的比例，就有可能影响到农药纳米晶粒生成后的均匀性和稳定性。因此，将混溶原药溶液的上限设定为35％。尽管稍超出这一含量也能制备，但超出太多，将会明显影响其他组分的比例。按照混溶原药溶液质量百分数为35％，混合溶剂的质量比的上限则约为30％，由此反过来，可以查看原药应具有的溶解度，并由此选择原药的品种、混合溶剂。上述例子是原药溶解度约为100g/L的情况。当原药对于某一混合溶剂的溶解度大于100g/L时，使用的溶剂质量可以小于30％，原药活性成分的质量百分数可以适当提高，在3％～12％之间，这样混合溶剂和原药两者之和(即混溶原药溶液)大致为35％，而体系中其它组分的比例在剩余的质量百分数中选择。相反，当原药对于某一混合溶剂的溶解度小于100g/L时，只能得到活性成分含量更低的目标产物。 (1) Determine that the mass percentage of the miscible drug solution is about 35%. The reasons are as follows: The miscible drug solution includes the quality of the active ingredient of the drug and the quality of the mixed solvent. There are two different ways to express the content of active ingredients in the original medicine: one is the mass percentage, %; the other is the volume mass, g/L. The former is often used, and the present invention is also expressed as a mass percentage when referring to the mass of components. In traditional pesticide formulations, although the pesticides have different activities and different usage levels, manufacturers often like to pursue high levels of active ingredients in pesticides when preparing pesticide formulations. Although the high content can reduce the volume and transportation cost of the packaging, due to the relatively small amount of additives, it will affect the dispersion performance of the pesticide solution diluted with water and the prevention and control effect on diseases and insect pests. In fact, each different pesticide variety should have different content of active ingredients suitable for itself according to the level of pesticide activity and physical solubility. The present invention prepares its miscible nano pesticide suspension agent and nano pesticide suspension agent (nano dispersant) according to the solubility (St ₁ , St ₂ ... St _i ) of a pesticide in a certain type of solvent system. Taking into account that the amount of solvent has a rough upper limit, such as 30%, it also determines the final content of pesticide active ingredients in the formulation. For example, the fungicide with serial number 4, phenoxyquinoline, its solubility in acetone is 116g/L. That is, 10g of acetone (a solvent that is soluble in water) can dissolve about 1.16g of the active ingredient of the pesticide, and similar solvents that are insoluble in water, such as methyl ethyl ketone and cyclohexanone, have similar solubility. In this way, if a 30 g mass of solvent is used, 3.48 g of active ingredient can be dissolved. Considering that the saturated solution easily precipitates solute, the miscible drug solution cannot be prepared into a saturated state, so in the miscible drug solution, the mass percentage of the active ingredient of the drug can be set to 3.3%. Among the system components, the miscible original drug solution is 3.3%, and the remaining components are compound additives and water. In the later stage of preparation, the solvent was recovered by distillation under reduced pressure. Assuming that all the solvents used are recovered, and water is distilled as part of the azeotrope composition, the final active ingredient content can reach about 5%. Although it is possible to increase the amount of solvent used to dissolve more pesticide active ingredients, this will inevitably reduce the ratio of the amount of compounding aid and water, which may affect the uniformity and stability of the pesticide nano-grains. Therefore, the upper limit of the miscible drug solution is set to 35%. Although it can be prepared slightly beyond this content, if it exceeds too much, it will obviously affect the proportion of other components. According to the mass percentage of the miscible original drug solution is 35%, the upper limit of the mass ratio of the mixed solvent is about 30%, which in turn can check the solubility of the original drug, and thus select the type of original drug, mixed solvent . The above example is the case where the solubility of the original drug is about 100 g/L. When the solubility of the original drug in a mixed solvent is greater than 100g/L, the mass of the solvent used can be less than 30%, and the mass percentage of the active ingredient of the original drug can be appropriately increased, between 3% and 12%, so that the mixed solvent and the original The sum of the two drugs (that is, the miscible drug solution) is approximately 35%, and the proportion of other components in the system is selected from the remaining mass percentages. On the contrary, when the solubility of the original drug in a mixed solvent is less than 100g/L, only the target product with a lower active ingredient content can be obtained.

这样，在混溶原药溶液中，活性成分的质量百分数，W _a.i.％，设定在3％～12％范围。在理论上，它等于溶剂S ₁的质量百分数S ₁％乘以原药在这种溶剂中的溶解度St ₁，加上溶剂S ₂的质量百分数S ₂％乘以农药在这种溶剂中的溶解度St ₂，如下式所示： In this way, in the miscible drug solution, the mass percentage of the active ingredient, W _ai %, is set in the range of 3% to 12%. In theory, it is equal to the mass percentage S ₁ % of the solvent S ₁ times the solubility of the original drug in this solvent St ₁ , plus the mass percentage S ₂ % of the solvent S ₂ times the solubility of the pesticide in this solvent St ₂ , as shown in the following formula:

W _a.i.％＝S ₁％·St ₁+S ₂％·St ₂+······ W _ai %=S ₁ %·St ₁ +S ₂ %·St ₂ +······

混合溶剂优选的规则总结在表-5。The preferred rules for mixed solvents are summarized in Table-5.

表-5 混合溶剂优选规则Table-5 Preferred rules for mixed solvents

(2)确定复合助剂的组分配比在25％左右。原因分析如下：复合助剂包括小分子助剂和高分子助剂。先讨论小分子助剂的用量。小分子助剂包括阴离子表面活性剂和非离子表面活性剂。对其种类的选择具有不同的考虑。对于阴离子表面活性剂，需要考虑的因素包括：化学结构、临界胶束浓度(CMC)、三相平衡点(krafft)温度、亲憎平衡值(HLB)值；对于非离子表面活性剂，需要考虑的因素包括：化学结构、CMC值、浊点(cloud point)温度、HLB值。两者具有的共同点有：①化学结构。从环境友好考虑，选择可生物降解的表面活性剂类型；②CMC值。从表面活性剂的活性考虑，选择低CMC值的品种，可以减少用量。③HLB值。从表面活性剂的特性和生成透明溶液考虑(透明与否涉及到微粒是否是纳米尺寸)，选择HLB值大于13的表面活性剂品种。两者的不同点在于：阴离子表面活性剂的krafft温度是分子溶解状态、胶束、凝胶三相平衡时的温度，当低于此温度，将以凝胶析出，因此krafft温度应该越低越好，例如接近0℃，可在低温储存。而非离子表面活性剂的cloud point温度，是其水溶液随温度升高而分相的温度。考虑到制备过程的后期需要升温进行减压蒸馏，以回收溶剂。而减压蒸馏的温度须低于非离子表面活性剂的cloud point温度，否则非离子表面活性剂会从水中凝聚析出，体系的稳定性受到破坏。因此cloud point温度应高些为好，最好温度≥60℃。(2) Make sure that the composition ratio of compound additives is around 25%. The reasons are as follows: Compound additives include small molecule additives and polymer additives. First discuss the amount of small molecule additives. Small molecule adjuvants include anionic surfactants and nonionic surfactants. There are different considerations for the choice of its type. For anionic surfactants, factors to be considered include: chemical structure, critical micelle concentration (CMC), three-phase equilibrium point (krafft) temperature, and affinity-phobic balance value (HLB) value; for nonionic surfactants, need to be considered The factors include: chemical structure, CMC value, cloud point temperature, HLB value. The two have in common: ① chemical structure. From environmental considerations, choose the type of biodegradable surfactant; ② CMC value. Considering the activity of the surfactant, choosing a variety with a low CMC value can reduce the dosage. ③ HLB value. Considering the characteristics of the surfactant and generating a transparent solution (transparency or not involves whether the particles are nano-sized), choose a surfactant variety with an HLB value greater than 13. The difference between the two is that the krafft temperature of the anionic surfactant is the temperature at which the molecule dissolves, the micelles, and the gel equilibrate in three phases. Below this temperature, it will precipitate out as a gel, so the lower the krafft temperature, the higher Well, for example, close to 0 ℃, can be stored at low temperature. The cloud point temperature of a nonionic surfactant is the temperature at which the aqueous solution separates as the temperature increases. Considering the need to raise the temperature for vacuum distillation at a later stage of the preparation process to recover the solvent. The temperature of vacuum distillation must be lower than the cloud point temperature of the non-ionic surfactant, otherwise the non-ionic surfactant will condense out from the water and the stability of the system will be destroyed. Therefore, cloud point temperature should be higher, the best temperature ≥ 60 ℃.

对于小分子助剂组分配比的考虑，分析如下：小分子助剂包括阴离子和非离子表面活性剂，在它们溶于水后，在水中分别形成胶束或胶团，见图-1和图-3。当混溶原药溶液滴入小分子助剂的水溶液时，它们起到分散、增溶、稳定农药溶液液滴的作用。混溶原药溶液液滴中含有溶于水和不溶于水的有机溶剂，溶于水的溶剂在进入小分子助剂的水溶液后，立即与水混溶，进入水相，其中它溶解的这一部分农药就会从水中析出，当混溶原药溶液滴加的速度和体系搅拌速度可控，以及其中的可溶于水的溶剂量适当时，农药晶粒析出的速度也可控。这样，控制在体系溶液透明的情况下，农药微粒的尺寸就被控制在100纳米以下。而剩下的不溶于水的农药溶液，在体系中属于油相，与水不能互溶，但根据相似相溶的原理，油溶性的农药溶液就可以进入小分子助剂形成的胶束、胶团中，成为增溶胶束(见图-2)、增溶胶团(图-4)。当增溶胶束、增溶胶团的体积足够小，小于100纳米时，体系是清澈透明的。由于这部分原药溶液形成的增溶胶束、增溶胶团尺寸很小，在热力学上是稳定的。要实现这一目标，就需要众多数目的胶束、胶团，而众多数目的胶束、胶团的形成就需要较大用量的小分子表面活性剂。满足这一需求的小分子助剂的质量百分数应在20％或以上。而阴离子表面活性剂和非离子表面活性剂之间无严格的比例，只是在于两者生成胶束、胶团的形态和数量不同，但它们共同形成的HLB值却一定要控制在13以上，以保证生成O/W乳液。综合考虑，小分子助剂优选的原则总结在表-6。For the consideration of the distribution ratio of small molecule additives, the analysis is as follows: small molecule additives include anionic and nonionic surfactants, and when they are dissolved in water, they form micelles or micelles in water, see Figure -1 and figure -3. When the miscible prodrug solutions are dropped into the aqueous solution of small molecule adjuvants, they function to disperse, solubilize, and stabilize the pesticide solution droplets. The droplets of the miscible prodrug solution contain water-soluble and water-insoluble organic solvents. After entering the aqueous solution of the small molecule adjuvant, the water-soluble solvent is immediately miscible with water and enters the aqueous phase, where it dissolves. A part of the pesticide will be precipitated from the water. When the dropping speed of the miscible drug solution and the stirring speed of the system are controllable, and the amount of water-soluble solvent therein is appropriate, the rate of precipitation of the pesticide grains is also controllable. In this way, when the system solution is controlled to be transparent, the size of the pesticide particles is controlled below 100 nm. The remaining water-insoluble pesticide solution belongs to the oil phase in the system and is not miscible with water, but according to the principle of similar miscibility, the oil-soluble pesticide solution can enter the micelles and micelles formed by small molecule additives In it, it becomes a sol-enhancing beam (see Figure-2) and a sol-enhancing cluster (Figure-4). When the volume of the sol-enhancing beam and sol-enhancing mass is small enough, less than 100 nm, the system is clear and transparent. Because of the small size of the sol-enhancing beam and sol-enhancing mass formed by this part of the original drug solution, it is thermodynamically stable. To achieve this goal, a large number of micelles and micelles are required, and the formation of a large number of micelles and micelles requires a large amount of small molecule surfactants. The mass percentage of small molecule additives to meet this demand should be 20% or more. There is no strict ratio between anionic surfactants and nonionic surfactants, but the form and number of micelles and micelles produced by the two are different, but the HLB value formed by them must be controlled above 13 in order to Ensure the generation of O/W emulsion. Taken together, the principles for the selection of small molecule additives are summarized in Table-6.

表-6 小分子助剂优选的原则Table-6 Principles for selecting small molecule additives

高分子助剂的组分配比。高分子助剂必须水溶，包括天然高分子和合成高分子。选择的原则包括：①性能要环境友好。从有利于生物降解和降解产物的安全性方面考虑，优先选择天然水溶高分子及其衍生物。合成水溶性高分子如果性能优良，对环境影响小，也可作为选择的品种。②溶解性能要好。高分子溶解不同于小分子溶解，溶解过程往往要经过溶胀阶段，比小分子溶解困难，有的需要较长时间。它们的溶解性能受高分子的品种、高分子的聚集态结构和相对分子质量的影响。但从生产的角度考虑，希望这一溶解过程不要影响生产进程，即越易溶解、溶解越快越好。③性价比要好。在满足使用性能的前提下，尽可能选择相对价廉的品种。The proportion of polymer additives. Polymer additives must be soluble in water, including natural polymers and synthetic polymers. The selection principles include: ① performance should be environmentally friendly. From the standpoint of being beneficial to biodegradation and the safety of degradation products, natural water-soluble polymers and their derivatives are preferred. Synthetic water-soluble polymers can also be used as a choice if they have good performance and little impact on the environment. ②The dissolution performance is better. The dissolution of macromolecules is different from the dissolution of small molecules. The dissolution process often goes through the swelling stage, which is more difficult than the dissolution of small molecules, and some takes longer time. Their solubility is affected by the variety of polymers, the aggregate structure of the polymers, and the relative molecular mass. However, from the perspective of production, it is hoped that this dissolution process does not affect the production process, that is, the easier it is to dissolve, the faster the dissolution, the better. ③ The cost performance is better. On the premise of satisfying the use performance, choose relatively cheap varieties as much as possible.

确定高分子助剂的组分比例，要先从添加高分子助剂的目的考虑。前已述及，水溶性高分子助剂在水中溶解后，在水中生成无规线团。当混溶原药溶液在搅拌条件下，以可控的速度滴加到溶解有小分子助剂、高分子助剂的复合助剂水溶液中时，混合溶剂中可溶于水的溶剂就与水互溶，将它溶解的那部分农药就从溶液中以晶粒的形态析出。控制滴加速度和体系的搅拌速度，就可以控制农药晶粒析出的速度以及晶粒尺寸的大小。析出的农药晶粒属于亲油性(疏水性)，就会向高分子助剂形成的无规线团的疏水内部扩散，由于晶粒尺寸较小(保持体系透明，表明小于100纳米)，就会分散进入到悬浮在水中的高分子助剂形成的无规线团之中，见图6。因此，高分子助剂实际上起到了对生成的纳米农药晶粒的悬浮、分散和稳定作用。由于水溶性高分子相对分子质量大，其水溶液的粘度要比同浓度的小分子粘度大很多，这是高分子溶液的基本特征。为了既能悬浮纳米晶粒，又能保持体系比微乳剂稍高的粘度，例如300～500毫帕秒，这一组分的质量百分数应控制在5％左右。To determine the proportion of polymer additives, we must first consider the purpose of adding polymer additives. As mentioned above, after the water-soluble polymer auxiliary is dissolved in water, random coils are formed in the water. When the miscible drug solution is added dropwise to the aqueous solution of compound additives in which small molecule additives and polymer additives are dissolved at a controlled rate, the water-soluble solvent in the mixed solvent is mixed with water Mutually soluble, the part of the pesticide that dissolves it is precipitated from the solution in the form of grains. By controlling the drop acceleration and the stirring speed of the system, the rate of pesticide grain precipitation and the size of the grain size can be controlled. The precipitated pesticide grains are oleophilic (hydrophobic) and will diffuse into the hydrophobic internal formation of random coils formed by polymer additives. Due to the small grain size (keeping the system transparent, indicating less than 100 nm), Disperse into the random coil formed by the polymer additives suspended in water, see Figure 6. Therefore, the polymer additives actually play a role in suspending, dispersing and stabilizing the generated nano pesticide grains. Because the relative molecular mass of a water-soluble polymer is large, the viscosity of its aqueous solution is much higher than that of small molecules of the same concentration. This is the basic feature of polymer solutions. In order to not only suspend nanocrystalline grains, but also maintain a slightly higher viscosity of the system than the microemulsion, for example 300-500 mPas, the mass percentage of this component should be controlled at about 5%.

复合助剂是由小分子助剂(20％)和高分子助剂(5％)共同组成，因此两者之和的质量百分数约为25％。The compound auxiliary is composed of small molecule auxiliary (20%) and high molecular auxiliary (5%), so the mass percentage of the sum of the two is about 25%.

综合考虑，选择高分子助剂优选的原则见表-7。For comprehensive consideration, the principle for selecting the preferred polymer additives is shown in Table-7.

表-7 高分子助剂选择的层级与性能Table-7 Levels and properties of polymer additives

(3)剩余组分是水。水的质量百分比约为40％。水是分散介质，起着维系体系中各组分的分散与稳定作用，其所占组分的比例也非常重要。水的比例太大，体系中活性成分和各组分所占比例相对较小，不利于得到高活性成分含量的纳米农药。水的比例较小，体系粘度较大，不利于纳米农药晶粒的生成、分散与稳定。合适的水的比例是制备纳米农药悬浮剂所必须的。一般，水的质量百分数应在40％左右。(3) The remaining component is water. The mass percentage of water is about 40%. Water is a dispersion medium, which plays a role in maintaining the dispersion and stabilization of each component in the system, and its proportion of components is also very important. The proportion of water is too large, and the proportion of active ingredients and components in the system is relatively small, which is not conducive to obtaining nano pesticides with high content of active ingredients. The proportion of water is small and the viscosity of the system is large, which is not conducive to the formation, dispersion and stability of nano pesticide grains. Proper water ratio is necessary to prepare nano pesticide suspension. Generally, the mass percentage of water should be around 40%.

本发明的混溶纳米农药悬浮剂的组分及合并成的三组分、两组分的质量百分比例见表-8与表-9。The components of the miscible nano pesticide suspension agent of the present invention and the mass percentages of the combined three components and two components are shown in Table-8 and Table-9.

表-8 混溶纳米农药悬浮剂的组分质量比例(理想情形)Table-8 Mass ratio of components of miscible nano pesticide suspension agent (ideal case)

表-9 混溶纳米农药悬浮剂的组分质量比例(可接受情形)Table-9 Mass ratio of components of miscible nano pesticide suspension agent (acceptable situation)

(二)、纳米农药悬浮剂的制备与纳米农药晶粒的形成(2) Preparation of nano pesticide suspension and the formation of nano pesticide grains

1、混合溶剂和混溶农药溶液的制备1. Preparation of mixed solvents and miscible pesticide solutions

根据农药品种，选择可以溶解它的溶剂体系，包括溶于水/不溶于水的混合溶剂体系，包括至少一种溶于水的溶剂和至少一种不溶于水的溶剂。根据表-2中的溶解度，确定农药活性成分的用量和混合溶剂的用量(以质量百分数计)。本方法并不限于表-2中收集的农药品种和溶剂类型。According to the pesticide species, choose a solvent system that can dissolve it, including water-soluble/water-insoluble mixed solvent systems, including at least one water-soluble solvent and at least one water-insoluble solvent. According to the solubility in Table-2, determine the amount of pesticide active ingredient and the amount of mixed solvent (in terms of mass percentage). This method is not limited to the types of pesticides and solvents collected in Table-2.

在装有回流冷凝器的容器中，加入确定质量百分数的溶剂，包括溶于水的溶剂和不溶于水的溶剂，经适当搅拌，配制成混合溶剂。在上述生成的混合溶剂中，加入确定质量百分数的农药活性成分，经适当搅拌，溶解，得到混溶农药活性成分混溶原药溶液。在混溶原药溶液中，农药活性成分是单分子分散在其中，生成的是真溶液，透明稳定。In a container equipped with a reflux condenser, add a certain mass percentage of solvent, including water-soluble and water-insoluble solvents, and mix them into a mixed solvent after proper stirring. To the mixed solvent generated above, a certain mass percentage of the pesticide active ingredient is added, and after proper stirring and dissolution, a miscible pesticide active ingredient miscible original drug solution is obtained. In the miscible prodrug solution, the pesticide active ingredient is a single molecule dispersed in it, resulting in a true solution, transparent and stable.

2、复合助剂水溶液的制备2. Preparation of aqueous solution of compound additives

助剂包括小分子助剂和高分子助剂，小分子助剂又包括阴离子表面活性剂和非离子表面活性剂。考虑到高分子助剂的溶解较为困难，因此复合助剂水溶液的制备应首先溶解高分子助剂，然后再溶解小分子助剂，最后得到复合助剂的水溶液。制备过程如下：Adjuvants include small molecular adjuvants and high molecular adjuvants, and small molecular adjuvants include anionic surfactants and nonionic surfactants. Considering that it is difficult to dissolve the polymer additives, the preparation of the aqueous solution of the compound additives should first dissolve the polymer additives, then the small molecule additives, and finally obtain the aqueous solution of the compound additives. The preparation process is as follows:

在装有搅拌、回流冷凝器以及能够加热和减压蒸馏的容器中，加入确定质量百分数的水，在搅拌下，加入确定质量百分数的一种或几种高分子助剂，必要时进行静止溶胀。在一定时间(几小时或一天)后，开动搅拌，直到完全溶解，生成透明的高分子水溶液。在此溶液中，加入确定质量百分数的一种或几种小分子助剂，搅拌，溶解，得到复合助剂的水溶液。复合助剂水溶液外观透明、稳定。在此溶液中，既有小分子助剂又有高分子助剂，它们在水中形成胶束、胶团，而高分子助剂在水中则形成无规线团。各种助剂在水中的微观形态示意图见图-7。In a container equipped with stirring, reflux condenser and capable of heating and vacuum distillation, add a certain percentage of water, under stirring, add one or more high molecular additives of a certain percentage of mass, if necessary, static swelling . After a certain period of time (a few hours or a day), stirring is started until it is completely dissolved to produce a transparent polymer aqueous solution. In this solution, add one or several small molecular additives with a certain mass percentage, stir and dissolve to obtain an aqueous solution of composite additives. The aqueous solution of compound additives is transparent and stable. In this solution, there are both small molecular additives and high molecular additives. They form micelles and micelles in water, while polymer additives form random coils in water. The microscopic morphology of various additives in water is shown in Figure-7.

3、农药纳米晶粒的生成——混溶纳米农药悬浮剂的制备3. Generation of pesticide nano-grains-preparation of miscible nano pesticide suspension

在上述制备复合助剂水溶液的体系中，在搅拌速度可控的条件下，将混溶原药溶液滴加到复合助剂水溶液中。控制滴加速度和搅拌速度，生成纳米农药晶粒，也是混溶纳米农药悬浮剂。如果不考虑溶剂的回收，这一混溶纳米农药悬浮剂也可以作为纳米农药使用。In the above-mentioned system for preparing an aqueous solution of a compound auxiliary agent, the solution of the miscible prodrug is added dropwise to the aqueous solution of the compound auxiliary agent under conditions of controllable stirring speed. Control the drop acceleration and stirring speed to generate nano pesticide grains, which is also a miscible nano pesticide suspension agent. If solvent recovery is not considered, this miscible nano pesticide suspension can also be used as a nano pesticide.

生成纳米农药晶粒的原理分析如下：在混溶原药溶液中，含有与水互溶的溶剂，例如，可供选择的溶剂有丙酮、甲醇、四氢呋喃、乙腈等。当溶液滴加进入水相时，溶于水的溶剂就迅速与水互溶，进入水相，在水溶液中只剩下不溶于水的原药溶液。由于溶液中溶解原药的溶剂量减少，不足于溶解原来的原药，于是一部分原药就会在水中析出。控制混溶原药溶液的滴加速度，以及控制搅拌速度，就可以控制原药均匀析出的粒径尺寸。而加入不溶于水的溶剂以及比例，事实上，起到控制原药析出速度的重要作用，不至于由于原药析出过快而形成大尺寸的结晶聚集。因此，溶于水/不溶于水溶剂之间的比例也是控制农药纳米晶粒析出快慢的一个重要影响因素。每种原药的化学结构不同，物理性能和溶解性能不同，选择的两种或以上溶剂之间混合的比例不同，一般两者质量比在1∶2～5，但最好通过实验和进行适当调整才能确定。The principle analysis of generating nano pesticide grains is as follows: The miscible prodrug solution contains a solvent that is miscible with water. For example, the available solvents include acetone, methanol, tetrahydrofuran, and acetonitrile. When the solution is added dropwise into the aqueous phase, the solvent soluble in water quickly dissolves with water and enters the aqueous phase, leaving only the original drug solution insoluble in water in the aqueous solution. Since the amount of solvent to dissolve the original drug in the solution is reduced, it is not enough to dissolve the original drug, so a part of the original drug will precipitate out in water. By controlling the dripping acceleration of the miscible drug solution and the stirring speed, the particle size of the drug uniformly precipitated can be controlled. The addition of water-insoluble solvents and proportions, in fact, plays an important role in controlling the rate of precipitation of the original drug, not to mention the formation of large-sized crystal aggregates due to the excessive precipitation of the original drug. Therefore, the ratio of water-soluble/water-insoluble solvents is also an important influencing factor for controlling the precipitation speed of pesticide nanocrystals. The chemical structure of each original drug is different, the physical properties and dissolution properties are different, the mixing ratio between the two or more selected solvents is different, generally the mass ratio between the two is 1: 2 ~ 5, but it is best to experiment and carry out appropriate Adjustment can be determined.

生成的纳米晶粒不能稳定地存在水中。由于自身重力的作用，当静止时会发生晶粒的聚集、长大，以至于以大尺寸的晶粒沉淀析出。为了防止这一现象出现，体系中加入的高分子助剂就起到分散稳定作用。水溶性高分子以无规线团形态结构存在。无规线团是水溶性高分子链自发形成的疏松的球形结构，内部聚集的是亲油疏水的分子主链，外部是亲水的极性基团。此时，当体系生成农药纳米晶粒时，根据“相似相溶”的原理，这些亲油疏水的纳米农药晶粒，就会自发进入到无规线团的内部，被无规线团负载，见图3b。无规线团对与纳米农药晶粒起到了一种悬浮、分散、稳定、保护的作用。由于无规线团是均匀分散在水相，因此，均匀分散在无规线团内部的纳米农药晶粒也均匀分散在水相。当农药纳米晶粒的尺寸在100纳米以下，体系看上去是清澈透明的。The generated nano crystal grains cannot be stably stored in water. Due to its own gravity, when it is at rest, the aggregation and growth of grains will occur, so that large-sized grains will precipitate out. In order to prevent this phenomenon, the polymer additives added to the system play a role of dispersion and stability. Water-soluble polymers exist in the form of random coils. Random coils are loose spherical structures formed spontaneously by water-soluble polymer chains. The inner part is a main chain of lipophilic and hydrophobic molecules, and the outside is a hydrophilic polar group. At this time, when pesticide nanocrystals are generated by the system, according to the principle of "similar miscibility", these lipophilic and hydrophobic nanopesticide crystals will spontaneously enter the interior of the random coil and be loaded by the random coil. See Figure 3b. The random coil plays a role of suspending, dispersing, stabilizing and protecting the nano pesticide grains. Since the random coils are uniformly dispersed in the aqueous phase, the nano pesticide grains uniformly dispersed inside the random coils are also uniformly dispersed in the aqueous phase. When the size of pesticide nanocrystals is below 100 nanometers, the system looks clear and transparent.

混溶原药溶液中只剩下不溶于水的溶剂。这种原药溶液的液滴也是亲油的，它们相对于胶束、胶团、无规线团来说，其体积要大得多。它们最好的去处就是胶束和胶团。根据“相似相溶”原理，它们可以迅速地、自发地进入胶束和胶团内部，成为增溶胶束(见图-2)、增溶胶团。只要胶束、胶团的数量足够多，就可以将剩余的混溶原药溶液全部增溶，而且保持100纳米以下的尺寸，因此体系看上去仍然是清澈透明的。Only miscible solvents remain in the miscible drug solution. The droplets of this original drug solution are also oleophilic, they are much larger than micelles, micelles, and random coils. Their best places are micelles and micelles. According to the principle of "similar miscibility", they can quickly and spontaneously enter the inside of micelles and micelles and become sol-enhancing sols (see Figure-2) and sol-enhancing lumps. As long as the number of micelles and micelles is sufficient, the remaining miscible prodrug solution can be solubilized, and the size below 100 nm can be maintained, so the system still looks clear and transparent.

这样，当混溶农药混合溶剂的溶液不断的滴加进入含有小分子和高分子助剂的水溶液，就不断有纳米农药晶粒生成并不断进入高分子助剂形成的无规线团中，就不断有剩余的混溶原药溶液进入到胶束和胶团中，直到混溶原药溶液滴加完毕。其中，并不排除生成的纳米农药晶粒也可能进入胶束和胶团内部被溶解，也不排除剩余的混溶原药溶液进入无规线团内部。但从体系的稳定性分析，前述描述的分散情况应该是能量最低状态。纳米农药晶粒和混溶原药溶液中各种微粒形态示意图见图-8。In this way, when the solution of the miscible pesticide mixed solvent is continuously dropped into the aqueous solution containing small molecules and polymer additives, nano pesticide particles will continue to be generated and enter into the random coil formed by the polymer additives. The remaining miscible drug solution continues to enter the micelles and micelles until the miscible drug solution is added dropwise. Among them, it is not excluded that the generated nano pesticide grains may also be dissolved inside the micelles and micelles, and it is also not excluded that the remaining miscible prodrug solution enters into the random coils. But from the stability analysis of the system, the dispersion described above should be the lowest energy state. The schematic diagram of various particles in nano pesticide grains and miscible prodrug solution is shown in Figure-8.

4、滴加速度与搅拌速度的控制4. Control of drop acceleration and stirring speed

需要指出的是，在生成纳米农药晶粒的过程中，混溶原药溶液的滴加速度和进入复合助剂水溶液的搅拌速度，涉及到在单位时间内加入到水相的多少和分散的均匀程度，是影响生成的纳米农药晶粒大小的重要因素。对于滴加速度，如果以析出的纳米农药晶粒尺寸小于100纳米为目标，则体系是否清澈透明就是判断标准。它的理论基础是，当微粒尺寸小于可见光波长的四分之一时，不产成严重的折射和反射，因此体系是透明的。可见光的波长是400～760纳米，小于四分之一就是100纳米以下。反过来，如果生成纳米农药晶粒的体系是清澈透明，就表明生成的晶粒尺寸小于100纳米。It should be pointed out that in the process of generating nano pesticide grains, the dripping acceleration of the miscible drug solution and the stirring speed of the aqueous solution of the composite additive are related to the amount of the aqueous phase added and the uniformity of dispersion in a unit time , Is an important factor that affects the grain size of the nano pesticides produced. For the drop acceleration, if the particle size of the precipitated nano pesticides is less than 100 nanometers, whether the system is clear and transparent is the criterion. Its theoretical basis is that when the particle size is less than a quarter of the wavelength of visible light, it does not produce severe refraction and reflection, so the system is transparent. The wavelength of visible light is 400 to 760 nanometers, less than a quarter is less than 100 nanometers. Conversely, if the system for generating nano pesticide grains is clear and transparent, it indicates that the size of the generated grains is less than 100 nanometers.

要实现这一目标，必须关注以下几点：①混溶原药溶液的滴加速度不能太快。太快，则生成农药晶粒的速度也快，太多纳米农药晶粒同时在水相产生，就有可能发生纳米晶粒之间的聚集，从而使晶粒尺寸变大。如果体系出现乳光，就说明晶粒尺寸已经在几百纳米，乳光越来越严重甚至不透明，就表明晶粒尺寸已经接近或超过一个微米。因此，滴加速度以保持体系始终透明为准。②溶液的滴加方式也可能影响到晶粒尺寸的大小。为了获得均匀和小尺寸的纳米晶粒，可以采用分散更均匀的方式进行滴加，如多点滴加、喷雾滴加等。滴加的混溶原药溶液的液滴越小越均匀，生成纳米农药晶粒的速度就越均匀，有利于避免晶粒之间的聚集，因此得到的纳米晶粒就越小。③体系的搅拌速度要适当加快。体系的搅拌速度涉及到水相生成的纳米农药晶粒的生成速度和分散速度，搅拌越快，分散越快，越不易发生晶粒之间的聚集和碰撞，越有利于保持较小尺寸晶粒的分散。体系的搅拌速度要大于原药溶解在混合溶剂中的搅拌速度，也要大于高分子助剂和小分子助剂溶解于水中的搅拌速度。它通过与混溶原药溶液的滴加速度相配合，才能获得尺寸较小且均匀的纳米农药晶粒。当混溶原药溶液滴加完毕时，此时已经获得了混溶纳米农药悬浮剂，也可以作为一种纳米农药剂型使用。To achieve this goal, we must pay attention to the following points: ① The drop acceleration of the miscible drug solution should not be too fast. If it is too fast, the speed of generating pesticide grains is also fast. If too many nano pesticide grains are produced in the water phase at the same time, there is a possibility of aggregation between the nano grains, thereby increasing the grain size. If the system has opalescence, it means that the grain size is already in the hundreds of nanometers, and the opalescence becomes more and more serious or even opaque, which means that the grain size is close to or more than one micrometer. Therefore, the drop acceleration is subject to keeping the system always transparent. ② The method of dropping the solution may also affect the grain size. In order to obtain uniform and small-sized nano-crystal grains, it can be added in a more uniformly dispersed manner, such as multi-drop addition, spray drop addition, etc. The smaller and more uniform the droplets of the miscible prodrug solution added, the more uniform the speed of generating nano pesticide grains, which is helpful to avoid the aggregation between the grains, so the smaller the nano grains obtained. ③ The stirring speed of the system should be properly accelerated. The stirring speed of the system involves the generation and dispersion speed of the nano-pesticide grains generated by the aqueous phase. The faster the stirring, the faster the dispersion, the less likely the aggregation and collision between the grains, and the more beneficial it is to keep the grains of a smaller size Of dispersion. The stirring speed of the system is greater than the stirring speed of the original drug dissolved in the mixed solvent, and also higher than the stirring speed of the polymer auxiliary and small molecule auxiliary dissolved in water. Only by matching with the dripping acceleration of the miscible prodrug solution, can the nanometer pesticide grains with smaller size and uniformity be obtained. When the dropping of the miscible prodrug solution is completed, the miscible nano pesticide suspension agent has been obtained at this time, and it can also be used as a nano pesticide formulation.

5、溶剂的回收(加热与减压蒸馏)——纳米农药悬浮剂制备5. Recovery of solvent (heating and vacuum distillation)-preparation of nano pesticide suspension

在上述获得的混溶纳米农药悬浮剂中，还含有确定质量百分数的有机溶剂。溶解在这部分溶剂中农药活性成分并不是以纳米晶粒的方式存在。为此，还需要通过后一过程完成这一转变。The miscible nano pesticide suspension agent obtained above also contains a certain mass percentage of organic solvent. The pesticide active ingredient dissolved in this part of solvent does not exist in the form of nano-grain. To this end, this transition needs to be completed through the latter process.

本发明的后一制备过程是进行减压蒸馏。进行减压蒸馏的目的有以下几点：①完成所有农药活性成分到纳米农药晶粒形态的转变，将体系中的所有农药活性成分全部或大部分都转变为纳米晶粒。②对体系中的有机溶剂进行回收，进一步提高纳米农药悬浮剂的环境友好性能。③通过减压蒸馏对有机溶剂的回收，起到浓缩混溶纳米农药悬浮剂的作用，可提高纳米农药悬浮剂的活性成分含量。The latter preparation process of the present invention is vacuum distillation. The purpose of vacuum distillation is as follows: ①Complete the transformation of all pesticide active ingredients into nano pesticide grains, and convert all or most of the pesticide active ingredients in the system into nano grains. ②Recover the organic solvent in the system to further improve the environmentally friendly performance of the nano pesticide suspension agent. ③ The organic solvent is recovered by vacuum distillation, which plays the role of concentrating and miscible nano pesticide suspension agent, and can increase the active ingredient content of the nano pesticide suspension agent.

前述获得的混溶纳米农药悬浮剂中含有有机溶剂，包括溶于水的溶剂和不溶于水的溶剂。溶于水的有机溶剂混溶在水相中。不溶于水的溶剂溶解活性成分的溶液被增溶在胶束或胶团中。在减压蒸馏过程中，沸点较低的先被蒸出。例如，在丙酮/甲乙酮复合溶剂体系，丙酮与水混溶，沸点较低，最先蒸出的是丙酮，沸点56.12℃。当丙酮蒸出后，开始蒸出甲乙酮-水(组成比88.7/11.3)共沸物，沸点73.41℃。由于甲乙酮还溶解农药活性成分，且存在于胶束或胶团内部，在减压过程中，随着甲乙酮溶剂的蒸出、逐步减少，溶解在溶剂中的农药活性成分在不断地析出，生成农药纳米晶粒。农药纳米晶粒既可能继续留在胶束或胶团内部，也可能从胶束或胶团中析出，转入到高分子助剂形成的无规线团的内部。直至甲乙酮溶剂大部分或全部被蒸出。The miscible nano pesticide suspension agent obtained above contains organic solvents, including water-soluble solvents and water-insoluble solvents. The organic solvent soluble in water is miscible in the aqueous phase. A solution in which the water-insoluble solvent dissolves the active ingredient is solubilized in micelles or micelles. In the vacuum distillation process, the lower boiling point is distilled first. For example, in the acetone/methyl ethyl ketone composite solvent system, acetone is miscible with water and has a low boiling point. The first one to be distilled off is acetone with a boiling point of 56.12°C. After the acetone was distilled off, the methyl ethyl ketone-water (composition ratio 88.7/11.3) azeotrope began to be distilled off, with a boiling point of 73.41°C. Since methyl ethyl ketone also dissolves pesticide active ingredients and exists inside the micelles or micelles, during the decompression process, as the methyl ethyl ketone solvent is distilled off and gradually reduced, the pesticide active ingredients dissolved in the solvent are continuously precipitated to form pesticides Nanocrystalline. Pesticide nanocrystals may either remain inside the micelles or micelles, or they may be precipitated from the micelles or micelles and transferred into the random coils formed by the polymer additives. Until most or all of the methyl ethyl ketone solvent is distilled off.

溶剂蒸出的方式，取决于溶剂的沸点和非离子表面活性剂的浊点温度。常用非离子表面活性剂的浊点温度通常在60℃左右，丙酮的沸点不到60℃，可以常压蒸馏；而甲乙酮-水的共沸点则为74℃，超过了浊点温度，必须在减压下进行蒸馏。对体系中有机溶剂的减压蒸馏，将涉及到有机溶剂的种类、沸点，以及是否与水形成共沸物，包括共沸物的组成、沸点以及沸点与压力之间的关系。为了加快共沸物的蒸出，可以对体系进行加热。这里面有几点需要关注：The method of solvent evaporation depends on the boiling point of the solvent and the cloud point temperature of the nonionic surfactant. The cloud point temperature of commonly used non-ionic surfactants is usually around 60 ℃, the boiling point of acetone is less than 60 ℃, can be distilled at atmospheric pressure; and the azeotropic point of methyl ethyl ketone-water is 74 ℃, exceeding the cloud point temperature, must be reduced Distill under pressure. The vacuum distillation of the organic solvent in the system will involve the type and boiling point of the organic solvent, and whether it forms an azeotrope with water, including the composition, boiling point, and the relationship between boiling point and pressure of the azeotrope. In order to speed up the distillation of the azeotrope, the system can be heated. There are a few points to pay attention to:

①不同溶剂与水组成的共沸物的沸点不同。本发明涉及到的一些溶剂能够形成共沸物的共沸点和组成收集在表-10。在减压蒸馏时，先蒸出共沸点低的溶剂，然后再蒸出共沸点高的溶剂。根据共沸物的组成，可以大致计算出蒸出不同百分数质量的溶剂所携带的水的质量。由此进一步计算出在最后生成的混溶纳米农药悬浮剂中农药活性成分的质量百分数。需要指出的是，并非所有有机溶剂都能完全被蒸出，当某种溶剂沸点较高时，溶剂就很难蒸出，例如二甲基甲酰胺、二甲基亚砜等，故选择这类溶剂时应慎重。①The boiling point of the azeotrope composed of different solvents and water is different. The azeotropes and compositions of some solvents involved in the present invention can form azeotropes are collected in Table-10. In the distillation under reduced pressure, the solvent with a low azeotropic point is distilled off first, and then the solvent with a high azeotropic point is distilled off. According to the composition of the azeotrope, the mass of water carried by the solvent with different percentages of mass can be roughly calculated. From this, the mass percentage of the pesticide active ingredient in the final miscible nano pesticide suspension is further calculated. It should be pointed out that not all organic solvents can be completely distilled off. When the boiling point of a certain solvent is high, the solvent is difficult to be distilled off, such as dimethylformamide, dimethylsulfoxide, etc., so choose this type Be careful when using solvents.

②不同溶剂，或与水也可能形成三元共沸物。②Different solvents may form ternary azeotrope with water.

③不同溶剂与水组成的共沸物的沸点与压力之间的关系不同。当共沸点温度较高时，只有通过减压条件下，才能降低共沸物的沸点。为了达到减压到一定真空度时的沸点温度，对体系适当加热是需要的。③The relationship between boiling point and pressure of the azeotrope composed of different solvents and water is different. When the azeotropic temperature is high, the boiling point of the azeotrope can be lowered only under reduced pressure. In order to achieve the boiling temperature when depressurized to a certain degree of vacuum, proper heating of the system is needed.

④体系加热的最高温度受到限制。体系加热温度必须在非离子表面活性剂浊点cloud point温度之下。否则，由于体系中非离子表面活性剂升高到cloud point温度或以上，将发生浑浊、聚集，使体系的稳定性受到破坏。④ The maximum temperature of system heating is limited. The heating temperature of the system must be below the cloud point temperature of the nonionic surfactant. Otherwise, as the nonionic surfactant in the system rises to the cloud point temperature or above, turbidity and aggregation will occur, and the stability of the system will be destroyed.

⑤减压蒸馏前后农药活性成分的含量发生变化。通过减压蒸馏后，可将体系中有机溶剂尽可能地蒸出，同时也通过共沸物带出来一部分水，使得体系的质量百分数发生变化，从而导致农药活性成分的质量百分数也发生变化。式(1)表示各组分的质量百分数之和为100％。式(2)为减压蒸馏前农药活性成分的质量百分数的表示式；式(3)为减压蒸馏后农药活性成分的质量百分数的表示式。⑤ The content of pesticide active ingredients changes before and after vacuum distillation. After distillation under reduced pressure, the organic solvent in the system can be distilled out as much as possible, and a part of the water is also brought out through the azeotrope, so that the mass percentage of the system changes, resulting in a change in the mass percentage of the pesticide active ingredient. Formula (1) indicates that the sum of the mass percentages of the components is 100%. Equation (2) is an expression for the mass percentage of the pesticide active ingredient before vacuum distillation; Equation (3) is an expression for the mass percentage of the pesticide active ingredient after vacuum distillation.

100％＝W _a.i.％+S ₁％+S ₂％+Ad ₁％+Ad ₂％+W _w％ (1) 100%=W _ai %+S ₁ %+S ₂ %+Ad ₁ %+Ad ₂ %+W _w % (1)

式中，W _a.i.1、W _a.i.2分别为减压蒸馏前后农药活性成分的质量百分数，W _a.i.1<W _a.i.2；W _w1、W _w2分别为减压蒸馏前后的水的质量，W _w1>W _w2。 In the formula, W _ai1 and W _ai2 are the mass percentages of pesticide active ingredients before and after vacuum distillation, W _ai1 <W _ai2 ; W _w1 and W _w2 are the masses of water before and after vacuum distillation, W _w1 >W _w2

可看出，减压蒸馏后农药活性成分的含量增大。It can be seen that the content of pesticide active ingredients increases after vacuum distillation.

表-10 溶剂-水的二元共沸物的组成与沸点(压力101.3kPa)Table-10 Composition and boiling point of solvent-water binary azeotrope (pressure 101.3kPa)

(三)纳米农药固体粉剂的制备(3) Preparation of Nano Pesticide Solid Powder

纳米农药固体粉剂是在混溶纳米悬浮剂(纳米悬浮剂)或者纳米悬浮剂的基础上，通过喷雾干燥回收部分或全部溶剂后最终形成的纳米农药粉状固体制剂。也可以采用其他制备粉剂的方法。The nano-pesticide solid powder is based on the miscible nano-suspending agent (nano-suspending agent) or nano-suspending agent, and finally forms a nano-pesticide powdery solid preparation after spray drying to recover part or all of the solvent. Other methods for preparing powders can also be used.

在一种实施例中，本发明提供一种环境友好型丙硫菌唑纳米粉剂,包括活性成分A，所述活性成分A为丙硫菌唑，还包括溶剂12～28wt％、小分子助剂10～25wt％、高分子助剂小于10～15wt％和分散剂水35～45wt％。In one embodiment, the present invention provides an environmentally friendly prothioconazole nanopowder, including an active ingredient A, the active ingredient A is prothioconazole, and further includes a solvent 12 to 28% by weight, a small molecule adjuvant 10-25 wt%, polymer auxiliary less than 10-15 wt% and dispersant water 35-45 wt%.

在一种实施例中，本发明提供一种环境友好型吡噻菌胺纳米粉剂,包括活性成分A，所述活性成分A为吡噻菌胺，还包括溶剂15～35wt％、小分子助剂8～20wt％、高分子助剂小于5～12wt％和分散剂水40～50wt％。In one embodiment, the present invention provides an environmentally friendly pyrithapyr nanopowder, including active ingredient A, the active ingredient A is pyrithapyr, and further includes a solvent 15 to 35 wt%, a small molecule adjuvant 8-20wt%, polymer auxiliary less than 5-12wt% and dispersant water 40-50wt%.

在一种实施例中，本发明提供一种环境友好型苯并烯氟菌唑纳米粉剂，包括活性成分A，所述活性成分A为苯并烯氟菌唑，还包括溶剂10～30wt％、小分子助剂10～25wt％、高分子助剂小于10wt％和分散剂水40～50wt％。In one embodiment, the present invention provides an environmentally friendly benzoene fluconazole nanopowder, including an active ingredient A, the active ingredient A is benzoene fluconazole, and further includes a solvent 10-30 wt%, Small molecular additives 10-25 wt%, polymer additives less than 10 wt% and dispersant water 40-50 wt%.

在一种实施例中，本发明提供一种环境友好型氟虫苯甲酰胺纳米粉剂，包括活性成分A，所述活性成分A为氟虫苯甲酰胺，还包括溶剂8～23wt％、小分子助剂10～25wt％、高分子助剂小于9～17wt％和分散剂水35～52wt％。In one embodiment, the present invention provides an environmentally friendly fipronil nanopowder, including an active ingredient A, the active ingredient A is fipronil, and also includes a solvent 8 to 23% by weight, small molecules The additive is 10-25 wt%, the polymer additive is less than 9-17 wt%, and the dispersant water is 35-52 wt%.

在一种实施例中，本发明提供一种环境友好型氟虫双酰胺纳米粉剂,包括活性成分A，所述活性成分A为氟虫双酰胺，还包括溶剂14～32wt％、小分子助剂10～25wt％、高分子助剂小于5～22wt％和分散剂水25～40wt％。In one embodiment, the present invention provides an environmentally friendly fipronil nanopowder, including an active ingredient A, the active ingredient A is fipronil, and further includes a solvent 14 to 32% by weight, a small molecule adjuvant 10-25wt%, polymer auxiliary less than 5-22wt% and dispersant water 25-40wt%.

在一种实施例中，本发明提供一种环境友好型螺螨双酯纳米粉剂，包括活性成分A，所述活性成分A为螺螨双酯，还包括溶剂12～21wt％、小分子助剂10～25wt％、高分子助剂小于5～14wt％和分散剂水31～46wt％。In one embodiment, the present invention provides an environmentally friendly snail acaride nanopowder, including an active ingredient A, the active ingredient A is a snail acaride, and also includes a solvent 12 to 21% by weight, a small molecule adjuvant 10 to 25 wt%, polymer additives less than 5 to 14 wt% and dispersant water 31 to 46 wt%.

在一种实施例中，本发明提供一种环境友好型双丙环虫酯纳米粉剂，包括活性成分A，所述活性成分A为双丙环虫酯，还包括溶剂9～26wt％、小分子助剂10～25wt％、高分子助剂小于8～16wt％和分散剂水32～56wt％。In one embodiment, the present invention provides an environmentally friendly dipropanate nanopowder, which includes an active ingredient A, the active ingredient A is dipropanate, and further includes a solvent 9 to 26% by weight, a small molecule The additive is 10-25 wt%, the polymer additive is less than 8-16 wt%, and the dispersant water is 32-56 wt%.

在一种实施例中，本发明提供一种环境友好型缬菌胺纳米粉剂，包括活性成分A，所述活性成分A为缬菌胺，还包括溶剂15～25wt％、小分子助剂10～25wt％、高分子助剂小于5～15wt％和分散剂水40～50wt％。In one embodiment, the present invention provides an environmentally friendly valoxamide nanopowder, including an active ingredient A, the active ingredient A is valoxamide, and further includes a solvent 15-25 wt%, a small molecule adjuvant 10 ~ 25wt%, polymer additives less than 5-15wt% and dispersant water 40-50wt%.

在一种实施例中，本发明提供一种环境友好型精苯霜灵纳米粉剂，包括活性成分A，所述活性成分A为精苯霜灵，还包括溶剂13～27wt％、小分子助剂10～25wt％、高分子助剂小于8～15wt％和分散剂水33～48wt％。In one embodiment, the present invention provides an environmentally friendly nanometer powder of fine benzepine, including active ingredient A, the active ingredient A is fine benzepine, and also includes a solvent 13 to 27% by weight, a small molecule adjuvant 10-25 wt%, polymer auxiliary less than 8-15 wt% and dispersant water 33-48 wt%.

在一种实施例中，本发明提供一种环境友好型氯氟醚菌唑纳米粉剂，包括活性成分A，所述活性成分A为氯氟醚菌唑，还包括溶剂8～26wt％、小分子助剂10～25wt％、高分子助剂小于11～18wt％和分散剂水37～52wt％。In one embodiment, the present invention provides an environmentally friendly clotrifloxazole nanopowder, including an active ingredient A, the active ingredient A is clofluconazole, and also includes a solvent 8 to 26 wt%, small molecules The additive is 10-25 wt%, the polymer additive is less than 11-18 wt% and the dispersant water is 37-52 wt%.

优选的，所述溶剂选用丙酮或环己酮中的一种或两种。Preferably, the solvent is one or two of acetone or cyclohexanone.

优选的，所述小分子助剂选用可生物降解的小分子助剂，包括阴离子型表面活性剂或非离子型表面活性剂。Preferably, the small molecule adjuvant is selected from biodegradable small molecule adjuvants, including anionic surfactants or nonionic surfactants.

优选的，所述离子型表面活性剂包括不同碳原子数构成的直链烷基的羧酸盐、磺酸盐、硫酸盐，所述非离子型表面活性剂包括不同碳原子数构成的直链烷基醚、酯、酰胺的聚氧乙烯醚，所述可生物降解的小分子助剂选用上述表面活性剂中的至少两种的混合物，所述小分子助剂的HLB值位12～15，用量为10～25％、8～20％。Preferably, the ionic surfactants include carboxylates, sulfonates, and sulfates of linear alkyl groups composed of different carbon atoms, and the nonionic surfactants include linear chains composed of different carbon atoms Polyoxyethylene ethers of alkyl ethers, esters, and amides. The biodegradable small molecule adjuvant is a mixture of at least two of the above surfactants. The HLB value of the small molecule adjuvant is 12-15. The dosage is 10-25%, 8-20%.

优选的，所述高分子助剂选用水溶性高分子助剂，包括天然水溶性高分子及其衍生物或合成高分子。Preferably, the polymer adjuvant is selected from water-soluble polymer adjuvants, including natural water-soluble polymers and their derivatives or synthetic polymers.

优选的，所述天然水溶性高分子及其衍生物包括糊精、环糊精、水溶性淀粉、氧化淀粉、羧甲基淀粉、改性淀粉、羧甲基纤维素、羟乙基羟丙基纤维素；羧甲基壳聚糖、改性瓜尔胶、茶皂素，所述合成高分子选用聚乙烯醇、聚丙烯酸钠、聚丙烯酰胺、聚吡咯烷酮、聚苯乙烯-顺丁烯二酸钠，所述水溶性高分子助剂选用其中的一种或几种。Preferably, the natural water-soluble polymer and its derivatives include dextrin, cyclodextrin, water-soluble starch, oxidized starch, carboxymethyl starch, modified starch, carboxymethyl cellulose, hydroxyethyl hydroxypropyl Cellulose; carboxymethyl chitosan, modified guar gum, tea saponin, the synthetic polymer is selected from polyvinyl alcohol, sodium polyacrylate, polyacrylamide, polypyrrolidone, polystyrene-maleic acid Sodium, one or more of the water-soluble polymer additives are selected.

本发明还公开了一种环境友好型丙硫菌唑纳米粉剂制备方法，所述制备方法包括以下步骤，The invention also discloses an environmentally friendly preparation method of prothioconazole nano powder, the preparation method comprises the following steps,

(1)将一定量农药原药溶解在溶剂或混合溶剂中，配制成接近饱和溶液，称为组分A；(1) Dissolve a certain amount of pesticide pesticide in a solvent or mixed solvent to prepare a nearly saturated solution, called component A;

(2)将一定量的高分子助剂溶解在水中，搅拌，配制成一定浓度的水溶液，称为组分B；(2) Dissolve a certain amount of polymer additives in water, stir, and prepare an aqueous solution of a certain concentration, called component B;

(3)将一定量的小分子助剂加入组分B中，搅拌，配制成复合助剂溶液，称为组分C；(3) Add a certain amount of small molecule adjuvant to component B, stir, and prepare a compound adjuvant solution, called component C;

(4)在搅拌条件下，将农药溶液即组分A，滴入复合助剂溶液即组分C中，控制滴加速度，使其不产生沉淀，并保持溶液透明，成为组分D；(4) Under stirring conditions, drip the pesticide solution, component A, into the compound adjuvant solution, component C, control the dripping rate so that it does not cause precipitation, and keep the solution transparent to become component D;

(5)将组分D进行喷雾干燥，得到目标产物。(5) Spray drying component D to obtain the target product.

优选的，所述步骤(1)中的农药原药包括活性成分A，所述活性成分A为丙硫菌唑。Preferably, the pesticide pesticide in the step (1) includes an active ingredient A, and the active ingredient A is prothioconazole.

优选的，所述步骤(2)中的高分子助剂选自糊精、环糊精、水溶性淀粉、氧化淀粉、羧甲基淀粉、改性淀粉、羧甲基纤维素、羟乙基羟丙基纤维素、羧甲基壳聚糖、改性瓜尔胶、茶皂素，所述合成高分子选用聚乙烯醇、聚丙烯酸钠、聚丙烯酰胺、聚吡咯烷酮、聚苯乙烯-顺丁烯二酸钠中的一种或几种。Preferably, the polymer auxiliary in the step (2) is selected from dextrin, cyclodextrin, water-soluble starch, oxidized starch, carboxymethyl starch, modified starch, carboxymethyl cellulose, hydroxyethyl hydroxy Propyl cellulose, carboxymethyl chitosan, modified guar gum, tea saponin, the synthetic polymer is selected from polyvinyl alcohol, sodium polyacrylate, polyacrylamide, polypyrrolidone, polystyrene-cis-butene One or more of sodium diacid.

优选的，所述步骤(3)中的小分子助剂选自羧酸盐、磺酸盐、硫酸盐、不同碳原子数构成的直链烷基醚、酯、酰胺的聚氧乙烯醚中的至少两种，所述小分子助剂的HLB值位12～15，用量为10～25％、8～20％。Preferably, the small molecule adjuvant in the step (3) is selected from the group consisting of carboxylates, sulfonates, sulfates, polyoxyethylene ethers of linear alkyl ethers, esters, and amides composed of different carbon atoms At least two kinds, the HLB value of the small molecule adjuvant is 12-15, and the dosage is 10-25%, 8-20%.

采用上述配方和工艺后，本发明制备的丙硫菌唑纳米粉剂纳米级，同样质量的农药，更多的农药微粒数目，更大的表面积，和靶标接触的面积就更广，发挥的药效就更高，可以用于航空植保专用药剂，不产生沉淀，不会堵塞喷头；选择环境友好的助剂，不选用高毒溶剂(苯，甲苯，二甲苯，甲醇)和助剂(壬基酚聚氧乙烯醚)，更高效、更环保和更安全，改变了以前仅以高效、低毒为首选的状态，要求把药剂对环境安全作为首要条件。上述实施例中其他农药原药固体粉剂的制备方法同丙硫菌唑纳米粉剂的制备方法，不再赘述。After adopting the above formula and process, the prothioconazole nano powder nano-level prepared by the present invention has the same quality of pesticides, more pesticide particles, a larger surface area, and a wider area of contact with the target. Even higher, it can be used as a special agent for aerial plant protection, without precipitation or clogging of the nozzle; choose environmentally friendly additives, do not choose highly toxic solvents (benzene, toluene, xylene, methanol) and additives (nonylphenol Polyoxyethylene ether), more efficient, more environmentally friendly and safer, changed the previous state where only high efficiency and low toxicity were the first choice, and required that the pharmaceuticals be environmentally safe as the primary condition. The preparation method of other solid pesticide powders in the above embodiments is the same as the preparation method of prothioconazole nano powders, which will not be repeated here.

(四)制备工艺流程图与关注事项(4) Preparation process flow chart and concerns

本发明混溶纳米农药悬浮剂和纳米农药悬浮剂的制备工艺流程和注意事项总结在表-11。The preparation process flow and matters needing attention of the miscible nano pesticide suspension agent and the nano pesticide suspension agent of the present invention are summarized in Table-11.

表-11 纳米悬浮剂的制备工艺流程和操作要点Table-11 Preparation process flow and operation points of nano-suspending agent

本发明有益效果：The beneficial effects of the invention:

对现有文件技术的归纳：To summarize the existing file technology:

现有文件一(200780047469.9)：涉及了一种纳米乳剂的制备方法。由水、亲油载体(甘油三酯)、表面活性剂(卵磷脂、聚山梨酯80)，以及活性剂(5-氨基乙酰丙酸)和溶剂(异丙醇)组成，微粒粒径在10～50纳米。Existing document one (200780047469.9): relates to a preparation method of nanoemulsion. It is composed of water, lipophilic carrier (triglyceride), surfactant (lecithin, polysorbate 80), as well as active agent (5-aminolevulinic acid) and solvent (isopropanol), with a particle size of 10 ~50nm.

现有文件二(201210108816.7)：涉及了一种纳米分散体的改进方法。由荷载物药物、一种或多种有机溶剂和高分子载体组成，经喷雾干燥制备而成。微粒粒径在500纳米以下。Existing document two (201210108816.7): relates to an improved method of nanodispersion. It is composed of load medicine, one or more organic solvents and polymer carrier, and is prepared by spray drying. The particle size is below 500 nanometers.

现有文件三(201310550703.7)：涉及了一种纳米乳液的制备。由一种农药原药与一②种合成高分子溶于二氯甲烷的有机相，和另一种合成高分子溶于水中的水相组成。形成的牛奶状(不透明)乳液是将有机相滴入水相制备，微粒粒径在250纳米以上。Existing document three (201310550703.7): relates to the preparation of a nanoemulsion. It is composed of a pesticide pesticide and an organic phase in which a synthetic polymer is dissolved in methylene chloride, and another aqueous phase in which a synthetic polymer is dissolved in water. The formed milky (opaque) emulsion is prepared by dropping the organic phase into the aqueous phase, and the particle size is above 250 nm.

现有文件四(201710462207.4)：涉及了一种嘧菌酯水悬浮剂的制备。在水相、或可溶于水的有机溶剂溶解原药的有机相中，溶解表面活性剂，通过快速射流对冲共混的方法制备农药的悬浮剂，微粒粒径小于100纳米。Existing document 4 (201710462207.4): relates to the preparation of an azoxystrobin aqueous suspension agent. In the water phase or the organic phase in which the water-soluble organic solvent dissolves the original drug, the surfactant is dissolved, and the suspension of the pesticide is prepared by the method of rapid jet hedge blending, and the particle size is less than 100 nanometers.

现有文件五(201810614177.9)涉及一种疏水农药组合物的制备。由疏水农药和生物降解聚合物溶于有机溶剂组成的有机相，乳化剂溶于水组成的水相组成，将有机相倒入水相得到乳液，经减压蒸馏得到沉淀(产物)。微粒粒径为220～250纳米。Existing document five (201810614177.9) relates to the preparation of a hydrophobic pesticide composition. The organic phase is composed of a hydrophobic pesticide and a biodegradable polymer dissolved in an organic solvent, an aqueous phase composed of an emulsifier dissolved in water, the organic phase is poured into the aqueous phase to obtain an emulsion, and a precipitate (product) is obtained by distillation under reduced pressure. The particle size is 220-250 nm.

本发明突出的实质性特点(与现有技术的区别特征)The outstanding substantive features of the present invention (distinct features from the prior art)

⑴本发明所述的有机相，是农药原药在至少两种混溶溶剂中生成的溶液。有机相的突出特征是，其中至少一种溶剂是可溶于水的溶剂；而至少另一种溶剂是不能溶于水的溶剂。两者具有一定的比例。(1) The organic phase described in the present invention is a solution formed by pesticide pesticides in at least two miscible solvents. The outstanding feature of the organic phase is that at least one solvent is a solvent that is soluble in water; and at least another solvent is a solvent that is insoluble in water. The two have a certain ratio.

⑵本发明所述的水相，是由高分子助剂和小分子助剂先后分别溶于水中生成的溶液。水相的突出特征是，①高分子助剂先溶于水。因为高分子相对分子质量大，比较难溶，溶解过程往往要经过溶胀阶段。为了尽快得到均匀的水相，最好的顺序是先溶解高分子助剂；②小分子助剂后溶于水。因为小分子助剂易溶于水，因此最好的加入顺序是小分子助剂后加入，且小分子助剂是加到高分子生成的水溶液中，快速生成助剂水溶液；③这样生成的水相，制备时间短，无高分子块状不溶物，有利于生成均相透明的助剂水溶液。⑵ The water phase described in the present invention is a solution formed by polymer additives and small molecule additives dissolved in water respectively. The salient feature of the water phase is that ① the polymer additives are dissolved in water first. Because the relative molecular mass of the polymer is large, it is relatively insoluble, and the dissolution process often goes through the swelling stage. In order to obtain a uniform water phase as soon as possible, the best order is to dissolve the polymer additives first; Because small molecule additives are easily soluble in water, the best order of addition is to add the small molecule additives, and the small molecule additives are added to the aqueous solution generated by the polymer to quickly generate the aqueous solution of the additive; Phase, the preparation time is short, there is no polymer block insoluble matter, which is conducive to the formation of a homogeneous and transparent auxiliary aqueous solution.

⑶本发明所述的制备方法，是将有机相逐步滴加到水相中。其特征包括：①在室温和搅拌下，严格控制有机相的滴加速度，以利于控制纳米晶粒的尺寸；②滴加速度的控制指标是，滴加到水相生成的体系要始终保持透明状态，以确保生成的混溶纳米悬浮剂(即纳米悬乳剂)的微粒粒径保持在100纳米以下。③滴加方式可以是一点滴加、多点滴加、喷雾滴加等，通过控制有机相进入水相的液滴尺寸，从而达到控制生成悬乳剂的微粒尺寸。④控制搅拌速度，要确保滴入水相的有机相液滴能够迅速、均匀地在水相中扩散，从而生成均匀的纳米晶粒。⑶ The preparation method of the present invention is to gradually drop the organic phase into the aqueous phase. Its characteristics include: ① Under room temperature and stirring, strictly control the drop acceleration of the organic phase to facilitate the control of the size of the nanocrystals; ② The control index of the drop acceleration is that the system added to the water phase should always be kept transparent. In order to ensure that the particle size of the generated miscible nanosuspension (ie nanosuspension) is kept below 100 nanometers. ③Drip addition method can be one-drop addition, multi-drop addition, spray-drop addition, etc., by controlling the droplet size of the organic phase into the water phase, so as to achieve the control of the particle size of the suspoemulsion. ④Control the stirring speed to ensure that the organic phase droplets dropped into the water phase can diffuse quickly and evenly in the water phase, thereby generating uniform nano-grains.

⑷通过上述制备步骤和顺序，可以得到≤100纳米，尤其是≤10纳米的纳米农药悬乳剂。⑷Through the above preparation steps and sequence, nano pesticide suspension emulsion ≤100 nm, especially ≤10 nm can be obtained.

本发明的上述区别特征，以及这些特征相结合，带来了显著的效果与意想不到的进步如下：The above distinguishing features of the present invention, and the combination of these features, bring significant effects and unexpected advances as follows:

⑴获得了一种新型的纳米农药类型——纳米农药悬乳剂。虽然传统农药制剂有悬乳剂剂型，但指的是悬浮剂和水乳剂的混合物。而且，无论是悬浮剂还是水乳剂，其农药的微粒尺寸都在几个微米以上，其外观特征是呈现不透明的乳白色。纳米农药悬乳剂则是纳米悬浮剂和微乳剂的混合物，其外观特征是清澈透明，实现了不溶于水的农药的表观水溶。⑴ A new type of nano-pesticide was obtained-nano-pesticide suspension emulsion. Although traditional pesticide formulations have suspension emulsion formulations, they refer to a mixture of suspension and aqueous emulsions. Moreover, whether it is a suspending agent or an aqueous emulsion, the particle size of its pesticide is more than a few microns, and its appearance is characterized by an opaque milky white. Nano-pesticide suspension emulsion is a mixture of nano-suspension and microemulsion. Its appearance is clear and transparent, which achieves the apparent water solubility of water-insoluble pesticides.

⑵纳米悬乳剂的显著特征是微粒尺寸小。微粒尺寸在100纳米以下，尤其是在10纳米以下。与传统悬乳剂相比，尺寸减小了三个数量级。与前述现有技术相比，农药微粒尺寸从几百纳米减小至几个纳米，获得意想不到的效果。⑵ The outstanding feature of nano-suspension is the small particle size. The particle size is below 100 nm, especially below 10 nm. Compared with traditional suspension emulsions, the size is reduced by three orders of magnitude. Compared with the aforementioned prior art, the size of pesticide particles is reduced from several hundred nanometers to several nanometers, and unexpected effects are obtained.

⑶纳米悬乳剂与现有技术制备的纳米药物的生成机理不同，生成的微观形态也不相同。现有技术生成的纳米剂型都是单一的乳剂(微乳剂)，或悬浮剂，而本发明技术既生成纳米悬浮剂，同时又形成微乳剂。生成机理如下：当有机相溶液滴入水相时，有机相溶液中的可溶于水的有机溶剂迅速扩散进入水相，与水互溶。这样有机相溶液的溶剂减少，农药溶液成为过饱和状态，导致农药活性成分从有机相溶液中析出，在水相中沉淀，形成纳米晶粒。生成的纳米晶粒在水相中扩散，其周围到处都有溶解于水中的高分子，高分子在水中以无规线团的形态存在。由于高分子无规线团的体积显著大于水相中由小分子助剂形成的胶束，农药晶粒更容易进入高分子的无规线团之中，成为稳定的纳米晶粒悬浮剂部分。而析出农药后的农药溶液，根据结构相似相溶的原理，会自发地进入数量巨大的胶束内部成为增溶胶束，成为热力学稳定的微乳剂部分。此时体系处于纳米悬浮剂和纳米微乳剂两种剂型的共存状态。(3) The formation mechanism of nanosuspension is different from that of nanomedicines prepared in the prior art, and the generated microscopic morphology is also different. The nano-dosage forms generated in the prior art are all single emulsions (microemulsions), or suspending agents, while the technology of the present invention generates both nano-suspensions and micro-emulsions at the same time. The formation mechanism is as follows: when the organic phase solution is dropped into the aqueous phase, the water-soluble organic solvent in the organic phase solution quickly diffuses into the aqueous phase and is miscible with water. In this way, the solvent of the organic phase solution decreases, and the pesticide solution becomes supersaturated, which causes the pesticide active ingredient to precipitate out of the organic phase solution and precipitate in the aqueous phase to form nano-grains. The generated nano crystals diffuse in the water phase, and there are polymers dissolved in water everywhere around them, and the polymers exist in the form of random coils in the water. Because the volume of polymer random coils is significantly larger than the micelles formed by small molecule additives in the aqueous phase, pesticide grains are more likely to enter the polymer random coils and become a stable nano-grain suspension agent. The pesticide solution after the precipitation of the pesticide, according to the principle of similar structure and miscibility, will spontaneously enter the inside of a large number of micelles to become a sol-enriched beam, and become a thermodynamically stable microemulsion part. At this time, the system is in the state of coexistence of two forms of nano-suspending agent and nano-microemulsion.

⑷纳米悬乳剂的性能优异。表现在：①微粒尺寸小，且分布窄。实施例样品的透射电镜照片显示，微粒粒径小于10纳米，有的小至1纳米。这远远优于现有技术的性能。②制剂外观为均相透明液体，表观水溶，分散均匀，热力学稳定。这一性能源于微粒尺寸小的特征，优于现有技术。按照对现有农药制剂的知识分析，前述专利文件所述的制剂呈牛奶状(不透明)，应属于水乳剂，不具有热力学稳定的性能。③制剂的稀释性能稳定。无论是按照人工喷洒或无人机喷洒的用水量稀释，制剂不会在短期内聚集沉淀。⑷Nano suspension emulsion has excellent performance. The performance is as follows: ① The particle size is small and the distribution is narrow. The TEM photographs of the samples of the examples show that the particle size of the particles is less than 10 nm, and some are as small as 1 nm. This is far superior to the performance of existing technologies. ② The appearance of the preparation is a homogeneous transparent liquid, apparently water soluble, uniformly dispersed and thermodynamically stable. This sexual energy is better than the existing technology due to the small particle size. According to knowledge analysis of existing pesticide formulations, the formulations described in the aforementioned patent documents are milk-like (opaque), should belong to aqueous emulsions, and have no thermodynamically stable properties. ③ The dilution performance of the preparation is stable. Whether it is diluted according to the amount of water used for manual spraying or drone spraying, the preparation will not accumulate in a short time.

⑸纳米悬乳剂还可进一步制备其他纳米农药制剂。纳米悬乳剂中尚存有机溶剂，从环境友好性能考虑，可进一步回收溶剂。将纳米悬乳剂进行减压蒸馏，控制温度和真空度，可以回收有机溶剂，制备成纳米悬浮剂。体系中的有机溶剂存在于两个环境，一是可溶于水的溶剂混溶于水中，另一是不溶于水的溶剂存在于增溶胶束内部。通过减压蒸馏，溶剂得到回收，从而进一步获得不含有机溶剂的纳米悬浮剂。这是一种更为环境友好的纳米农药剂型。纳米悬浮剂和纳米悬乳剂的区别不仅在于前者不含有机溶剂，而且前者只存在纳米晶粒，不存在含有农药溶液的增溶胶束。⑸ Nano-suspension can also be used to prepare other nano pesticide preparations. The organic solvent still exists in the nano-suspension, and the solvent can be further recovered in consideration of environmental friendliness. The nano suspension emulsion is distilled under reduced pressure to control the temperature and vacuum degree, and the organic solvent can be recovered and prepared into a nano suspension emulsion. The organic solvent in the system exists in two environments, one is the water-soluble solvent is miscible in water, and the other is the water-insoluble solvent is present inside the sol-enhancement beam. By distillation under reduced pressure, the solvent is recovered, thereby further obtaining a nano-suspending agent that does not contain an organic solvent. This is a more environmentally friendly nano pesticide formulation. The difference between nano-suspension and nano-suspension is not only that the former does not contain organic solvents, but the former only has nano-crystal grains, and there is no sol-enriched beam containing pesticide solution.

⑹以纳米悬乳剂和纳米悬浮剂为基础，还可以进一步制备纳米固体粉剂。采用常规的喷雾干燥设备剂操作工艺，通过添加容易水溶的天然物质作为固体分散剂，如木质素磺酸盐、黄腐酸盐、茶皂素等，可以制备纳米农药固体粉剂。纳米农药固体粉剂具有农药微粒保持纳米尺寸、不产生团聚、储存运输稳定等优点。⑹Based on nano-suspension and nano-suspension, nano-solid powder can be further prepared. Using the conventional spray drying equipment agent operation process, by adding water-soluble natural substances as solid dispersants, such as lignin sulfonate, xanthate, tea saponin, etc., nano pesticide solid powder can be prepared. The nano-pesticide solid powder has the advantages of maintaining the nanometer size of the pesticide particles, no agglomeration, and stable storage and transportation.

附图说明BRIEF DESCRIPTION

图-1 胶束；Figure-1 Micelles;

图-2 增溶胶束；Figure-2 Increased sol beam;

图-3 胶团；Figure-3 micelle;

图-4 增溶胶团；Figure-4 Adding sol mass;

图-5 无规线团；Figure-5 Random Coils;

图-6 负载纳米晶粒的无规线团；Figure-6 Random coils loaded with nano-grains;

图-7 小分子助剂、高分子助剂在水中微观形态示意图；Figure-7 Schematic diagram of the micro-morphology of small molecule additives and polymer additives in water;

图-8 农药纳米晶粒、农药不溶于水溶液液珠的微观分布形态示意图；Figure-8 Schematic diagram of the microscopic distribution of pesticide nanocrystals and pesticide-insoluble aqueous solution beads;

图-9 混合溶剂的制备；Figure-9 Preparation of mixed solvents;

图-10 混溶原药溶液的制备；Figure-10 Preparation of miscible original drug solution;

图-11 复合助剂水溶液的制备；Figure-11 Preparation of aqueous solution of compound additives;

图-12 混溶纳米悬浮剂的制备；Figure-12 Preparation of miscible nano-suspension agent;

图-13 纳米悬浮剂的制备。Figure-13 Preparation of Nano Suspending Agent.

图-14 实施例1制剂样品用激光纳米粒度仪测定的微粒尺寸和分布图。Figure-14 The particle size and distribution of the sample of the formulation of Example 1 measured by a laser nanoparticle size analyzer.

图-15 实施例1制剂样品透射电镜照片。Figure-15 Transmission electron micrograph of the preparation sample of Example 1.

图-16 实施例2制剂样品用激光纳米粒度仪测定的微粒尺寸和分布图。Figure-16 The particle size and distribution of the sample of the formulation of Example 2 as measured by a laser nanoparticle size analyzer.

图-17 实施例2制剂样品透射电镜照片。Figure-17 Transmission electron micrograph of the preparation sample of Example 2.

图-18 实施例3制剂样品用激光纳米粒度仪测定的微粒尺寸和分布图。Figure-18 The particle size and distribution of the sample of the formulation of Example 3 measured by a laser nanoparticle size analyzer.

图-19 实施例3制剂样品透射电镜照片。Figure-19 Transmission electron micrograph of Example 3 preparation sample.

图-20 实施例4制剂样品用激光纳米粒度仪测定的微粒尺寸和分布图。Figure-20 The particle size and distribution of the sample of the formulation of Example 4 measured with a laser nanoparticle size analyzer.

图-21 实施例4制剂样品透射电镜照片。Figure-21 Transmission electron micrograph of Example 4 preparation sample.

图-22 实施例5制剂样品用激光纳米粒度仪测定的微粒尺寸和分布图。Figure-22 The particle size and distribution of the sample of the formulation of Example 5 measured by a laser nanometer particle size analyzer.

图-23 实施例5制剂样品透射电镜照片。Figure-23 Transmission electron micrograph of the preparation sample of Example 5.

具体实施方式detailed description

下面，通过优选的实施例对本发明剂型详细说明。但本发明并不仅仅限于下述实施例。Hereinafter, the dosage form of the present invention will be described in detail through preferred examples. However, the present invention is not limited to the following embodiments.

实施例中所用的各种原料都是可以通过商业渠道得到的。The various raw materials used in the examples are all commercially available.

本发明中的wt％是指各原料占原料总质量的质量百分比，通常情况下，重量百分数与质量百分数可以等同使用，因为市售原辅料常以重量计量。The wt% in the present invention refers to the mass percentage of each raw material in the total mass of the raw material. Generally, the weight percentage and the mass percentage can be used equally, because commercially available raw materials are often measured by weight.

实施例1 8％丙硫菌唑纳米悬浮剂Example 1 8% Prothioconazole Nano Suspending Agent

原料配比(以质量百分数计)：Raw material ratio (in terms of mass percentage):

通过如下方法制备(以100公斤投料计)：Prepared by the following method (based on 100 kg feed):

Ⅰ.将丙酮和甲乙酮混合，配制成混合溶剂，记作组分A ₁； Ⅰ. Mix acetone and methyl ethyl ketone to prepare a mixed solvent, and record it as component A ₁ ;

Ⅱ.将丙硫菌唑溶于混合溶剂A ₁，得到混溶原药溶液，记作组分B ₁； Ⅱ. Dissolve prothioconazole in the mixed solvent A ₁ to obtain a miscible drug solution, which is recorded as component B ₁ ;

Ⅲ.将羧甲基淀粉和茶皂素溶于水中，得到高分子助剂水溶液，记作组分C ₁； Ⅲ. Dissolve the carboxymethyl starch and the tea saponin in water to obtain an aqueous solution of a polymer additive, and record it as component C ₁ ;

Ⅳ.将十二烷基硫酸钠、油酸钠、AEO ₁₅、AEO ₂₀、溶于组分C ₁中，得到复合助剂水溶液，记作组分D ₁； Ⅳ. Dissolve sodium lauryl sulfate, sodium oleate, AEO ₁₅ , AEO ₂₀ , in component C ₁ to obtain an aqueous solution of compound additives, and record it as component D ₁ ;

Ⅴ.在适当的搅拌速度下，将组分B ₁缓慢地滴加到组分D ₁中。搅拌速度和滴加速度之间的适配，以保持体系透明和不出现沉淀为标准。滴加完毕后，得到混溶纳米农药悬浮剂E ₁； V. Slowly add component B ₁ to component D ₁ at a suitable stirring speed. The adaptation between the stirring speed and the drop acceleration is based on keeping the system transparent and without precipitation. After the dropwise addition, the miscible nano pesticide suspension agent E _{1 is obtained} ;

Ⅵ.进行减压蒸馏，逐渐达到设备的最大真空度。将体系逐渐加热，最高温度不超过55℃，减压蒸馏0.5～1小时，得到纳米农药悬浮剂F ₁，产品重量约为70公斤；进一步地，通过测定丙硫菌唑活性成分含量，补水至活性成分含量为8％，得到丙硫菌唑纳米悬浮剂产品(约为75公斤)。产品外观透明，根据丁达尔现象判断农药活性成分微粒尺寸在100纳米以下。仪器检测结果见图-14、图-15，激光纳米粒度仪结果显示对100％微粒进行检测统计结果表明，其平均粒径为1.308nm，标准偏差为0.3337nm。电镜照片显示纳米微粒粒径很小，只有几纳米，微粒分布均匀。 Ⅵ. Perform vacuum distillation to gradually reach the maximum vacuum of the equipment. Heat the system gradually, the maximum temperature does not exceed 55°C, and distill under reduced pressure for 0.5 to 1 hour to obtain nano pesticide suspension agent F ₁ with a product weight of about 70 kg; further, by measuring the content of prothioconazole active ingredients, make up to The active ingredient content is 8%, and a prothioconazole nano-suspension product (about 75 kg) is obtained. The appearance of the product is transparent, and the particle size of the active ingredient of the pesticide is judged to be below 100 nm according to the Tyndall phenomenon. The test results of the instrument are shown in Figure-14 and Figure-15. The results of the laser nanoparticle size analyzer show that the detection of 100% particles shows that the average particle size is 1.308nm and the standard deviation is 0.3337nm. Electron micrographs show that the particle size of the nanoparticles is very small, only a few nanometers, and the particles are evenly distributed.

Ⅶ.进一步，可以在E ₁或F ₁的基础上通过喷雾干燥的方法回收部分或全部溶剂制备成纳米固体粉剂G ₁。 VII. Further, a part or all of the solvent can be recovered by spray drying on the basis of E ₁ or F ₁ to prepare a nano-solid powder G ₁ .

实施例2 15％环氟菌胺纳米悬浮剂Example 2 15% cyflufenamid nano-suspending agent

Ⅰ.将乙醇和乙酸乙酯混合，配制成混合溶剂，记作组分A ₂； Ⅰ. Mix ethanol and ethyl acetate to make a mixed solvent and record it as component A ₂ ;

Ⅱ.将环氟菌胺溶于混合溶剂A ₂，得到混溶原药溶液，记作组分B ₂； Ⅱ. Dissolve cyflufenamid in the mixed solvent A ₂ to obtain a miscible drug solution, and record it as component B ₂ ;

Ⅲ.将聚乙烯醇、改性瓜尔胶溶于水中，得到高分子助剂水溶液，记作组分C ₂； Ⅲ. Dissolve polyvinyl alcohol and modified guar gum in water to obtain an aqueous solution of polymer additives, and record it as component C ₂ ;

Ⅳ.将十二烷基磺酸钠、亚油酸钠、吐温-40、AEO ₂₀溶于组分C ₂中，得到复合助剂水溶液，记作组分D ₂； Ⅳ. Dissolve sodium dodecyl sulfonate, sodium linoleate, Tween-40, and AEO ₂₀ in component C ₂ to obtain an aqueous solution of a compound additive, which is referred to as component D ₂ ;

Ⅴ.在适当的搅拌速度下，将组分B ₂缓慢地滴加到组分D ₂中。搅拌速度和滴加速度之间的适配，以保持体系透明和不出现沉淀为标准。滴加完毕后，得到混溶纳米农药悬浮剂E ₂； V. Slowly add component B ₂ to component D ₂ under appropriate stirring speed. The adaptation between the stirring speed and the drop acceleration is based on keeping the system transparent and without precipitation. After the dropwise addition, the miscible nano pesticide suspension agent E _{2 is obtained} ;

Ⅵ.进行减压蒸馏，逐渐达到设备的最大真空度。将体系逐渐加热，最高温度不超过55℃，减压蒸馏0.5～1小时，得到纳米农药悬浮剂F ₂，产品重量约为78.5公斤； Ⅵ. Perform vacuum distillation to gradually reach the maximum vacuum of the equipment. Heat the system gradually, the maximum temperature does not exceed 55°C, and distill under reduced pressure for 0.5 to 1 hour to obtain nano pesticide suspension F ₂ with a product weight of about 78.5 kg;

进一步地，测定环氟菌胺活性成分含量约为15％。产品外观透明，根据丁达尔现象判断农药活性成分微粒尺寸在100纳米以下。仪器检测结果见图-16、图-17，激光纳米粒度仪结果显示对100％微粒进行检测统计结果表明，其平均粒径为4.858nm，标准偏差为0.7686nm。电镜照片显示纳米微粒粒径很小，只有几纳米，微粒分布均匀。Further, it was determined that the content of the active ingredient of cyclosporine was about 15%. The appearance of the product is transparent, and the particle size of the active ingredient of the pesticide is judged to be below 100 nm according to the Tyndall phenomenon. The test results of the instrument are shown in Figure-16 and Figure-17. The results of the laser nanoparticle size analyzer show that the statistical results of the detection of 100% particles show that the average particle size is 4.858nm and the standard deviation is 0.7686nm. Electron micrographs show that the particle size of nanoparticles is very small, only a few nanometers, and the particles are evenly distributed.

Ⅶ.进一步，可以在E ₂或F ₂的基础上通过喷雾干燥的方法回收部分或全部溶剂制备成纳米固体粉剂G ₂。 VII. Further, on the basis of E ₂ or F _2, a part or all of the solvent can be recovered by spray drying to prepare a nano-solid powder G ₂ .

实施例3 16％丁氟螨酯纳米悬浮剂的制备Example 3 Preparation of 16% fenfluricide nanosuspension

Ⅰ.将丙酮和乙酸乙酯混合，配制成混合溶剂，得到混合溶剂，记作组分A ₃； Ⅰ. Mix acetone and ethyl acetate to prepare a mixed solvent to obtain a mixed solvent, and record it as component A ₃ ;

Ⅱ.将丁氟螨酯溶于混合溶剂A ₃，得到混溶原药溶液，记作组分B ₃； Ⅱ. Dissolve diflufenican in the mixed solvent A ₃ to obtain a mixed original drug solution, which is recorded as component B ₃ ;

Ⅲ.将羧甲基纤维素、木质素磺酸钠和茶皂素溶于水中，得到高分子助剂水溶液，记作组分C ₃； Ⅲ. Dissolve carboxymethyl cellulose, sodium lignin sulfonate and tea saponin in water to obtain an aqueous solution of polymer additives, and record it as component C ₃ ;

Ⅳ.将十二烷基醚硫酸钠、亚油酸钠、蓖麻油聚氧乙烯醚、吐温-80溶于组分C ₃中，得到复合助剂水溶液，记作组分D ₃； Ⅳ. Dissolve sodium lauryl ether sulfate, sodium linoleate, castor oil polyoxyethylene ether, and Tween-80 in component C ₃ to obtain an aqueous solution of a composite additive, which is referred to as component D ₃ ;

Ⅴ.在适当的搅拌速度下，将组分 ₃B缓慢地滴加到组分D ₃中。搅拌速度和滴加速度之间的适配，以保持体系透明和不出现沉淀为标准。滴加完毕后，得到混溶纳米农药悬浮剂E ₃； Ⅴ. Under the appropriate stirring speed, slowly add component ₃ B to component D ₃ dropwise. The adaptation between the stirring speed and the drop acceleration is based on keeping the system transparent and without precipitation. After the dropwise addition, the miscible nano pesticide suspension agent E _{3 is obtained} ;

Ⅵ.进行减压蒸馏，逐渐达到设备的最大真空度。将体系逐渐加热到56℃，减压蒸馏0.5～1小时，产品重量约为73公斤，得到纳米农药悬浮剂F ₃； Ⅵ. Perform vacuum distillation to gradually reach the maximum vacuum of the equipment. The system was gradually heated to 56°C, and vacuum distillation was performed for 0.5 to 1 hour. The weight of the product was about 73 kg, and nano pesticide suspension F _{3 was obtained} ;

进一步地，测定丁氟螨酯活性成分含量，补水至活性成分为16％，得到丁氟螨酯纳米农药悬浮剂约为75公斤。产品外观透明，根据丁达尔现象判断农药活性成分的微粒尺寸在100纳米以下。仪器检测结果见图-18、图-19，激光纳米粒度仪结果显示对100％微粒进行检测统计结果表明，其平均粒径为1.282nm，标准偏差为0.3182nm。电镜照片显示纳米微粒粒径很小，只有几纳米，微粒分布均匀。Further, the content of the active ingredient of fenfluricide is determined, and the water is replenished until the active ingredient is 16%, to obtain a fenfluricide nano pesticide suspension agent of about 75 kg. The appearance of the product is transparent, and the particle size of the pesticide active ingredient is judged to be below 100 nm according to the Tyndall phenomenon. The test results of the instrument are shown in Figure -18 and Figure -19. The results of the laser nanoparticle size analyzer show that the statistical results of the detection of 100% particles show that the average particle size is 1.282nm and the standard deviation is 0.3182nm. Electron micrographs show that the particle size of the nanoparticles is very small, only a few nanometers, and the particles are evenly distributed.

Ⅶ.进一步，可以在E ₃或F ₃的基础上通过喷雾干燥的方法回收部分或全部溶剂制备成纳米固体粉剂G ₃。 VII. Further, a part or all of the solvent can be recovered by spray drying on the basis of E ₃ or F ₃ to prepare a nano-solid powder G ₃ .

实施例4 18％吡螨胺纳米悬浮剂Example 4 18% pyridoxamine nano-suspending agent

Ⅰ.将甲醇和甲乙酮混合，配制成混合溶剂，记作组分A ₄； Ⅰ. Methanol and methyl ethyl ketone are mixed to prepare a mixed solvent, which is recorded as component A ₄ ;

Ⅱ.将吡螨胺唑溶于混合溶剂A ₄，得到混溶原药溶液，记作组分B ₄； Ⅱ. Dissolve pyrimidazole in the mixed solvent A ₄ to obtain a miscible drug solution, which is recorded as component B ₄ ;

Ⅲ.将羧甲基淀粉钠和羧甲基纤维素钠溶于水中，得到高分子助剂水溶液，记作组分C ₄； Ⅲ. Dissolve sodium carboxymethyl starch and sodium carboxymethyl cellulose in water to obtain an aqueous solution of polymer additives, and record it as component C ₄ ;

Ⅳ.将十二烷基单磷酸钠、亚麻油酸钠、AEO ₂₀、烷基多糖苷溶于组分C ₄中，得到复合助剂水溶液，记作组分D ₄； Ⅳ. Dissolve sodium dodecyl monophosphate, sodium linoleate, AEO ₂₀ , and alkyl polyglycoside in component C ₄ to obtain an aqueous solution of a compound additive, which is referred to as component D ₄ ;

Ⅴ.在适当的搅拌速度下，将组分B ₄缓慢地滴加到组分D ₄中。搅拌速度和滴加速度之间的适配，以保持体系透明和不出现沉淀为标准。滴加完毕后，得到混溶纳米农药悬浮剂E ₄； Ⅴ. Slowly add component B ₄ to component D ₄ under appropriate stirring speed. The adaptation between the stirring speed and the drop acceleration is based on keeping the system transparent and without precipitation. After the dropwise addition, the miscible nano pesticide suspension agent E _{4 is obtained} ;

Ⅵ.进行减压蒸馏，逐渐达到设备的最大真空度。将体系逐渐加热，最高温度不超过56℃，减压蒸馏0.5～1小时，得到纳米农药悬浮剂F ₄，产品重量约为76.5公斤； Ⅵ. Perform vacuum distillation to gradually reach the maximum vacuum of the equipment. The system is gradually heated, the maximum temperature does not exceed 56°C, and the vacuum distillation is performed for 0.5 to 1 hour to obtain nano pesticide suspension agent F ₄ with a product weight of about 76.5 kg;

进一步地，测定吡螨胺活性成分含量，补水至活性成分含量为18％，得到吡螨胺纳米悬浮剂约为77公斤。产品外观透明，根据丁达尔现象判断农药活性成分微粒尺寸在100纳米以下。仪器检测结果见图-20、图-21，激光纳米粒度仪结果显示对100％微粒进行检测统计结果表明，其平均粒径为3.804nm，标准偏差为0.7440nm。电镜照片显示纳米微粒粒径很小，只有几纳米，微粒分布均匀。Further, the content of the active ingredient of pyrimethanil was determined, and the water was replenished until the content of the active ingredient was 18%, to obtain a pyrithimide nano-suspension of about 77 kg. The appearance of the product is transparent, and the particle size of the active ingredient of the pesticide is judged to be below 100 nm according to the Tyndall phenomenon. The test results of the instrument are shown in Figure-20 and Figure-21. The results of the laser nanoparticle size analyzer show that the statistical results of the detection of 100% particles show that the average particle size is 3.804nm and the standard deviation is 0.7440nm. Electron micrographs show that the particle size of nanoparticles is very small, only a few nanometers, and the particles are evenly distributed.

Ⅶ.进一步，可以在E ₄或F ₄的基础上通过喷雾干燥的方法回收部分或全部溶剂制备成纳米固体粉剂G ₄。 VII. Further, on the basis of E ₄ or F ₄ , part or all of the solvent can be recovered by spray drying to prepare nano-solid powder G ₄ .

实施例5 10％氰氟草酯纳米悬浮剂Example 5 10% cyfluthon nano-suspension

Ⅰ.将甲醇和乙酸乙酯混合，配制成混合溶剂，记作组分A ₅； Ⅰ.Methanol and ethyl acetate are mixed to make a mixed solvent, which is recorded as component A ₅ ;

Ⅱ.将氰氟草酯溶于混合溶剂A ₅，得到混溶原药溶液，记作组分B ₅； Ⅱ. Dissolve halofopin in the mixed solvent A ₅ to obtain a miscible drug solution, which is recorded as component B ₅ ;

Ⅲ.苯乙烯-马来酸酐共聚物和木质素磺酸钠溶于水中，得到高分子助剂水溶液，记作组分C ₅； Ⅲ. The styrene-maleic anhydride copolymer and sodium lignosulfonate are dissolved in water to obtain an aqueous solution of a polymer additive, which is referred to as component C ₅ ;

Ⅳ.将α-烯基磺酸钠、蓖麻油酸钠、吐温-80、蓖麻油聚氧乙烯醚溶于组分C ₅中，得到复合助剂水溶液，记作组分D ₅； Ⅳ. Dissolve sodium α-alkenyl sulfonate, sodium ricinoleate, Tween-80, and polyoxyethylene ether of castor oil in component C ₅ to obtain an aqueous solution of a compound auxiliary agent, and record it as component D ₅ ;

Ⅴ.在适当的搅拌速度下，将组分B ₅缓慢地滴加到组分D ₅中。搅拌速度和滴加速度之间的适配，以保持体系透明和不出现沉淀为标准。滴加完毕后，得到混溶纳米农药悬浮剂E ₅； Ⅴ. Slowly add component B ₅ to component D ₅ with proper stirring speed. The adaptation between the stirring speed and the drop acceleration is based on keeping the system transparent and without precipitation. After the dropwise addition, the miscible nano pesticide suspension agent E _{5 is obtained} ;

Ⅵ.进行减压蒸馏，逐渐达到设备的最大真空度。将体系逐渐加热，最高温度不超过55℃，减压蒸馏0.5～1小时，得到纳米农药悬浮剂F ₅，产品重量约为69公斤； Ⅵ. Perform vacuum distillation to gradually reach the maximum vacuum of the equipment. Heat the system gradually, the maximum temperature does not exceed 55 ℃, vacuum distillation for 0.5 to 1 hour, to obtain nano pesticide suspension agent F ₅ , the product weight is about 69 kg;

进一步地，测定氰氟草酯活性成分含量，补水至活性成分含量为10％，得到氰氟草酯纳米悬浮剂约为70公斤。产品外观透明，根据丁达尔现象判断农药活性成分微粒尺寸在100纳米以下。仪器检测结果见图-22、图-23，激光纳米粒度仪结果显示对100％微粒进行检测统计结果表明，其平均粒径为6.826nm，标准偏差为1.248nm。电镜照片显示纳米微粒粒径很小，只有几纳米，微粒分布均匀。Further, the content of the active ingredient of cyanfluxate is determined, and the water is replenished until the content of the active ingredient is 10%, and the nanofluidate of cyanfluxate is obtained to be about 70 kg. The appearance of the product is transparent, and the particle size of the active ingredient of the pesticide is judged to be below 100 nm according to the Tyndall phenomenon. The test results of the instrument are shown in Figure-22 and Figure-23. The results of the laser nanoparticle size analyzer show that the statistical results of the detection of 100% particles show that the average particle size is 6.826nm and the standard deviation is 1.248nm. Electron micrographs show that the particle size of the nanoparticles is very small, only a few nanometers, and the particles are evenly distributed.

Ⅶ.进一步，可以在E ₅或F ₅的基础上通过喷雾干燥的方法回收部分或全部溶剂制备成纳米固体粉剂G ₅。 Ⅶ. Further, on the basis of E ₅ or F _5, a part or all of the solvent can be recovered by spray drying to prepare a nano-solid powder G ₅ .

实施例6-1(对应申请号为201811618804.2)Example 6-1 (corresponding application number is 201811618804.2)

一种环境友好型丙硫菌唑纳米粉剂，包括活性成分A，所述活性成分A为丙硫菌唑，活性成分18wt％，还包括溶剂12wt％、小分子助剂15wt％、高分子助剂10wt％、分散剂水45wt％。An environmentally friendly prothioconazole nanopowder, including active ingredient A, the active ingredient A is prothioconazole, the active ingredient is 18% by weight, further includes a solvent 12% by weight, a small molecule auxiliary agent 15% by weight, a polymer auxiliary agent 10wt%, dispersant water 45wt%.

其中，溶剂选用丙酮。Among them, the solvent is acetone.

其中，小分子助剂选用可生物降解的小分子助剂，包括阴离子型表面活性剂或非离子型表面活性剂，离子型表面活性剂包括不同碳原子数构成的直链烷基的羧酸盐、磺酸盐，非离子型表面活性剂包括不同碳原子数构成的直链烷基醚、酯、酰胺的聚氧乙烯醚，小分子助剂的HLB值位12～15。Among them, the small molecule additives are biodegradable small molecule additives, including anionic surfactants or nonionic surfactants, and the ionic surfactants include carboxylates of linear alkyl groups composed of different carbon atoms Sulfonate, non-ionic surfactants include polyoxyethylene ethers of linear alkyl ethers, esters, and amides composed of different carbon atoms. The HLB value of small molecule additives is 12-15.

其中，高分子助剂选用水溶性高分子助剂，包括天然水溶性高分子及其衍生物，天然水溶性高分子及其衍生物选用糊精、环糊精和水溶性淀粉。Among them, the water-soluble polymer additives are used as the polymer additives, including natural water-soluble polymers and their derivatives, and the natural water-soluble polymers and their derivatives are selected from dextrin, cyclodextrin and water-soluble starch.

本实施例中的环境友好型丙硫菌唑纳米粉剂制备方法包括以下步骤，The preparation method of the environmentally friendly prothioconazole nano powder in this embodiment includes the following steps,

(1)将农药原药溶解在溶剂或混合溶剂中，配制成接近饱和溶液(农药活性成分的含量将小于最终纳米粉体制剂中的含量)，称为组分A；(1) Dissolve the pesticide pesticide in a solvent or mixed solvent and prepare a nearly saturated solution (the content of the pesticide active ingredient will be less than that in the final nanopowder preparation), which is called component A;

(2)将高分子助剂溶解在水中，搅拌，配制成一定浓度的水溶液，称为组分B；(2) Dissolve the polymer adjuvant in water, stir to prepare an aqueous solution with a certain concentration, called component B;

(3)将小分子助剂加入组分B中，搅拌，配制成复合助剂溶液，称为组分C；(3) Add small molecule adjuvant to component B, stir, and prepare a compound adjuvant solution, called component C;

实施例6-2Example 6-2

一种环境友好型丙硫菌唑纳米粉剂，包括活性成分A，所述活性成分A为丙硫菌唑，活性成分的质量分数为15wt％，还包括溶剂18wt％、小分子助剂12wt％、高分子助剂15wt％和分散剂水40wt％。An environmentally friendly prothioconazole nanopowder, including active ingredient A, the active ingredient A is prothioconazole, the mass fraction of the active ingredient is 15wt%, and also includes a solvent 18wt%, a small molecule adjuvant 12wt%, Polymer additives 15wt% and dispersant water 40wt%.

其中，溶剂选用环己酮。Among them, the solvent is cyclohexanone.

其中，小分子助剂选用可生物降解的小分子助剂，包括阴离子型表面活性剂，离子型表面活性剂包括不同碳原子数构成的直链烷基的羧酸盐、磺酸盐、硫酸盐，小分子助剂的HLB值位12～15。Among them, small molecule additives are biodegradable small molecule additives, including anionic surfactants, and ionic surfactants include carboxylates, sulfonates, and sulfates of linear alkyl groups composed of different carbon atoms , The HLB value of small molecule additives is 12-15.

其中，高分子助剂选用水溶性高分子助剂，包括天然水溶性高分子及其衍生物，天然水溶性高分子及其衍生物包括羧甲基壳聚糖、改性瓜尔胶、茶皂素。Among them, the water-soluble polymer additives are selected as the polymer additives, including natural water-soluble polymers and their derivatives, and the natural water-soluble polymers and their derivatives include carboxymethyl chitosan, modified guar gum and tea soap Prime.

实施例6-3Example 6-3

一种环境友好型丙硫菌唑纳米粉剂，包括活性成分A，所述活性成分A为丙硫菌唑，活性成分占10wt％，还包括溶剂25wt％、小分子助剂16wt％、高分子助剂14wt％和分散剂水35wt％。An environmentally friendly prothioconazole nanopowder, including active ingredient A, the active ingredient A is prothioconazole, the active ingredient accounts for 10wt%, and also includes a solvent 25wt%, a small molecule adjuvant 16wt%, a polymer aid Agent 14wt% and dispersant water 35wt%.

其中，溶剂选用丙酮和环己酮按照体积比1:1混合。Among them, the solvent is selected from acetone and cyclohexanone mixed in a volume ratio of 1:1.

其中，小分子助剂选用可生物降解的小分子助剂，包括非离子型表面活性剂，非离子型表面活性剂包括不同碳原子数构成的直链烷基醚、酯、酰胺的聚氧乙烯醚，小分子助剂的HLB值位12～15。Among them, small molecule additives are biodegradable small molecule additives, including nonionic surfactants, and nonionic surfactants include polyoxyethylene of linear alkyl ethers, esters, and amides composed of different carbon atoms The HLB value of ether and small molecule additives is 12-15.

其中，高分子助剂选用水溶性高分子助剂，包括合成高分子，合成高分子选用聚乙烯醇、聚丙烯酸钠、聚丙烯酰胺、聚吡咯烷酮、聚苯乙烯-顺丁烯二酸钠。Among them, water-soluble polymer additives are used as polymer additives, including synthetic polymers, and polyvinyl alcohol, sodium polyacrylate, polyacrylamide, polypyrrolidone, and polystyrene-sodium maleate are selected as synthetic polymers.

实施例7-1(对应申请号为201811618805.7)Example 7-1 (corresponding application number is 201811618805.7)

一种环境友好型吡噻菌胺纳米粉剂，包括活性成分A，所述活性成分A为吡噻菌胺，活性成分10wt％，还包括溶剂35wt％、小分子助剂10wt％、高分子助剂5wt％、分散剂水40wt％。An environmentally friendly pyrithapyr nanopowder, including active ingredient A, the active ingredient A is pyrithapyr, the active ingredient 10wt%, also includes a solvent 35wt%, small molecule adjuvant 10wt%, polymer adjuvant 5wt%, dispersant water 40wt%.

其中，溶剂选用丙酮。Among them, the solvent is acetone.

其中，小分子助剂选用可生物降解的小分子助剂，包括阴离子型表面活性剂或非离子型表面活性剂，离子型表面活性剂包括不同碳原子数构成的直链烷基的羧酸盐、磺酸盐，非离子型表面活性剂包括不同碳原子数构成的直链烷基醚、酯、酰胺的聚氧乙烯醚，小分子助剂的HLB值位12～15，用量为10％。Among them, the small molecule additives are biodegradable small molecule additives, including anionic surfactants or nonionic surfactants, and the ionic surfactants include carboxylates of linear alkyl groups composed of different carbon atoms Sulfonate, non-ionic surfactants include polyoxyethylene ethers of linear alkyl ethers, esters, and amides composed of different carbon atoms. The HLB value of small molecule additives is 12-15, and the dosage is 10%.

本实施例中的环境友好型吡噻菌胺纳米粉剂制备方法包括以下步骤，The preparation method of the environment-friendly pyrithapyr nanopowder in this embodiment includes the following steps,

实施例7-2Example 7-2

一种环境友好型吡噻菌胺纳米粉剂，包括活性成分A，所述活性成分A为吡噻菌胺，活性成分的质量分数为10wt％，还包括溶剂15wt％、小分子助剂20wt％、高分子助剂10wt％和分散剂水45wt％。An environmentally friendly pyrithapyr nanopowder, including an active ingredient A, the active ingredient A is pyrithapyr, the mass fraction of the active ingredient is 10wt%, also includes a solvent 15wt%, a small molecule adjuvant 20wt%, Polymer additives 10wt% and dispersant water 45wt%.

其中，溶剂选用环己酮。Among them, the solvent is cyclohexanone.

其中，小分子助剂选用可生物降解的小分子助剂，包括阴离子型表面活性剂，离子型表面活性剂包括不同碳原子数构成的直链烷基的羧酸盐、磺酸盐、硫酸盐，小分子助剂的HLB值位12～15，用量为20％。Among them, small molecule additives are biodegradable small molecule additives, including anionic surfactants, and ionic surfactants include carboxylates, sulfonates, and sulfates of linear alkyl groups composed of different carbon atoms The HLB value of small molecule additives is 12-15, and the dosage is 20%.

实施例8-1(对应申请号为201811618956.2)Example 8-1 (corresponding application number is 201811618956.2)

一种环境友好型苯并烯氟菌唑纳米粉剂，包括活性成分A，所述活性成分A为苯并烯氟菌唑，活性成分8wt％，还包括溶剂30wt％、小分子助剂10wt％、高分子助剂2wt％、分散剂水50wt％。An environmentally friendly benzoene fluconazole nanopowder, including an active ingredient A, the active ingredient A is benzoene fluconazole, the active ingredient is 8wt%, and also includes a solvent 30wt%, a small molecule adjuvant 10wt%, Polymer additives 2wt%, dispersant water 50wt%.

其中，溶剂选用丙酮。Among them, the solvent is acetone.

其中，小分子助剂选用可生物降解的小分子助剂，包括阴离子型表面活性剂或非离子型表面活性剂，离子型表面活性剂包括不同碳原子数构成的直链烷基的羧酸盐、磺酸盐，非离子型表面活性剂包括不同碳原子数构成的直链烷基醚、酯、酰胺的聚氧乙烯醚，小分子助剂的HLB值位12～15，用量为10％。Among them, the small molecule additives are biodegradable small molecule additives, including anionic surfactants or nonionic surfactants, and the ionic surfactants include carboxylates of linear alkyl groups composed of different carbon atoms Sulfonate, non-ionic surfactants include linear alkyl ethers, esters, amide polyoxyethylene ethers with different number of carbon atoms, small molecule additives with HLB value of 12-15, and the dosage is 10%.

本实施例中的环境友好型苯并烯氟菌唑纳米粉剂制备方法包括以下步骤，The preparation method of the environmentally friendly benzoene fluconazole nano powder in this embodiment includes the following steps,

实施例8-2Example 8-2

一种环境友好型苯并烯氟菌唑纳米粉剂，包括活性成分A，所述活性成分A为苯并烯氟菌唑，活性成分的质量分数为10wt％，还包括溶剂15wt％、小分子助剂25wt％、高分子助剂5wt％和分散剂水45wt％。An environmentally friendly benzoene fluconazole nanopowder, including an active ingredient A, the active ingredient A is benzoene fluconazole, the mass fraction of the active ingredient is 10wt%, and also includes a solvent 15wt%, small molecule auxiliary Agent 25wt%, polymer additives 5wt% and dispersant water 45%wt.

其中，溶剂选用环己酮。Among them, the solvent is cyclohexanone.

其中，小分子助剂选用可生物降解的小分子助剂，包括阴离子型表面活性剂，离子型表面活性剂包括不同碳原子数构成的直链烷基的羧酸盐、磺酸盐、硫酸盐，小分子助剂的HLB值位12～15，用量为25％。Among them, small molecule additives are biodegradable small molecule additives, including anionic surfactants, and ionic surfactants include carboxylates, sulfonates, and sulfates of linear alkyl groups composed of different carbon atoms The HLB value of small molecule additives is 12-15, and the dosage is 25%.

实施例9-1(对应申请号为201811618803.8)Example 9-1 (corresponding application number is 201811618803.8)

一种环境友好型氟虫苯甲酰胺纳米粉剂，包括活性成分A，所述活性成分A为氟虫苯甲酰胺，活性成分10wt％，还包括溶剂15wt％、小分子助剂16wt％、高分子助剂14wt％、分散剂水45wt％。An environmentally friendly fipronil nanopowder, including active ingredient A, the active ingredient A is fipronil, 10 wt% of the active ingredient, also includes 15 wt% of the solvent, 16 wt% of small molecule additives, polymer Auxiliary agent 14wt%, dispersant water 45%wt.

其中，溶剂选用丙酮。Among them, the solvent is acetone.

其中，高分子助剂选用水溶性高分子助剂，包括天然水溶性高分子及其衍生物，天然水溶性高分子及其衍生物选用糊精、环糊精和水溶性淀粉。Among them, water-soluble polymer additives are used for the polymer additives, including natural water-soluble polymers and their derivatives, and natural water-soluble polymers and their derivatives are selected for dextrin, cyclodextrin and water-soluble starch.

本实施例中的环境友好型氟虫苯甲酰胺纳米粉剂制备方法包括以下步骤，The preparation method of the environmentally friendly fipronil nanopowder in this embodiment includes the following steps,

实施例9-2Example 9-2

一种环境友好型氟虫苯甲酰胺纳米粉剂，包括活性成分A，所述活性成分A为氟虫苯甲酰胺，活性成分的质量分数为9wt％，还包括溶剂21wt％、小分子助剂13wt％、高分子助剂17wt％和分散剂水40wt％。An environmentally friendly fipronil nanopowder, including active ingredient A, the active ingredient A is fipronil, the mass fraction of the active ingredient is 9wt%, and also includes a solvent 21wt%, a small molecule adjuvant 13wt %, polymer additives 17wt% and dispersant water 40wt%.

其中，溶剂选用环己酮。Among them, the solvent is cyclohexanone.

实施例10-1(对应申请号为201811618802.3)Example 10-1 (corresponding application number is 201811618802.3)

一种环境友好型氟虫双酰胺纳米粉剂，包括活性成分A，所述活性成分A为氟虫双酰胺，活性成分14wt％，还包括溶剂14wt％、小分子助剂10wt％、高分子助剂22wt％、分散剂水40wt％。An environmentally friendly fipronil nanopowder, including active ingredient A, the active ingredient A is fipronil, the active ingredient is 14% by weight, the solvent is 14% by weight, the small molecule auxiliary is 10% by weight, and the polymer auxiliary 22wt%, dispersant water 40wt%.

其中，溶剂选用丙酮。Among them, the solvent is acetone.

本实施例中的环境友好型氟虫双酰胺纳米粉剂制备方法包括以下步骤，The preparation method of the environmentally friendly fipronil nanopowder in this embodiment includes the following steps,

实施例10-2Example 10-2

一种环境友好型氟虫双酰胺纳米粉剂，包括活性成分A，所述活性成分A为氟虫双酰胺，活性成分的质量分数为13wt％，还包括溶剂32wt％、小分子助剂25wt％、高分子助剂5wt％和分散剂水25wt％。An environmentally friendly fipronil nanopowder, including active ingredient A, the active ingredient A is fipronil, the mass fraction of the active ingredient is 13wt%, and also includes a solvent 32wt%, a small molecule adjuvant 25wt%, Polymer additives 5wt% and dispersant water 25wt%.

其中，溶剂选用环己酮。Among them, the solvent is cyclohexanone.

实施例11-1(对应申请号为201811632136.9)Example 11-1 (corresponding application number is 201811632136.9)

一种环境友好型螺螨双酯纳米粉剂，包括活性成分A，所述活性成分A为螺螨双酯，活性成分27wt％，还包括溶剂12wt％、小分子助剂10wt％、高分子助剂5wt％、分散剂水46wt％。An environmentally friendly snail mite diester nanopowder, including active ingredient A, the active ingredient A is spirome diester, active ingredient 27wt%, also includes solvent 12wt%, small molecule additives 10wt%, polymer additives 5wt%, dispersant water 46wt%.

其中，溶剂选用丙酮。Among them, the solvent is acetone.

本实施例中的环境友好型螺螨双酯纳米粉剂制备方法包括以下步骤，The preparation method of the environmentally friendly snail mite diester nano powder in this embodiment includes the following steps,

实施例11-2Example 11-2

一种环境友好型螺螨双酯纳米粉剂，包括活性成分A，所述活性成分A为螺螨双酯，活性成分的质量分数为9wt％，还包括溶剂21wt％、小分子助剂25wt％、高分子助剂14wt％和分散剂水31wt％。An environmentally friendly snail mite diester nanopowder, including active ingredient A, the active ingredient A is spirome diester, the mass fraction of the active ingredient is 9wt%, also includes a solvent 21wt%, small molecule adjuvant 25wt%, Polymer additives 14wt% and dispersant water 31wt%.

其中，溶剂选用环己酮。Among them, the solvent is cyclohexanone.

(1)将农药原药溶解在溶剂或混合溶剂中，配制成接近饱和溶液(农药活性成分的含量将微小于最终纳米粉体制剂中的含量)，称为组分A；(1) Dissolve the pesticide pesticide in a solvent or mixed solvent, and prepare a nearly saturated solution (the content of the pesticide active ingredient will be smaller than that in the final nano-powder preparation), which is called component A;

实施例12-1(对应申请号为201811632002.7)Example 12-1 (corresponding application number is 201811632002.7)

一种环境友好型双丙环虫酯纳米粉剂，包括活性成分A，所述活性成分A为双丙环虫酯，活性成分9wt％，还包括溶剂9wt％、小分子助剂10wt％、高分子助剂16wt％、分散剂水56wt％。An environmentally friendly dipropanate nanopowder, including an active ingredient A, the active ingredient A is dipropanate, the active ingredient is 9wt%, and further includes a solvent 9wt%, a small molecule adjuvant 10wt%, a polymer Auxiliary agent 16wt%, dispersant water 56wt%.

其中，溶剂选用丙酮。Among them, the solvent is acetone.

本实施例中的环境友好型双丙环虫酯纳米粉剂制备方法包括以下步骤，The preparation method of the environmentally friendly dipropanate nanopowder in this embodiment includes the following steps,

实施例12-2Example 12-2

一种环境友好型双丙环虫酯纳米粉剂，包括活性成分A，所述活性成分A为双丙环虫酯，活性成分的质量分数为9wt％，还包括溶剂26wt％、小分子助剂25wt％、高分子助剂8wt％和分散剂水32wt％。An environmentally friendly dipropanate nanopowder, including an active ingredient A, the active ingredient A is dipropanate, the mass fraction of the active ingredient is 9wt%, and also includes a solvent 26wt%, a small molecule adjuvant 25wt %, polymer additives 8wt% and dispersant water 32wt%.

其中，溶剂选用环己酮。Among them, the solvent is cyclohexanone.

实施例14-1(对应申请号为201811632003.1)Example 14-1 (corresponding application number is 201811632003.1)

一种环境友好型缬菌胺纳米粉剂，包括活性成分A，所述活性成分A为缬菌胺，活性成分10wt％，还包括溶剂15wt％、小分子助剂10wt％、高分子助剂15wt％、分散剂水50wt％。An environmentally friendly valoxamide nanopowder, including active ingredient A, the active ingredient A is valoxamide, the active ingredient is 10% by weight, the solvent is 15% by weight, the small molecule auxiliary agent is 10% by weight, and the polymer auxiliary agent is 15% by weight. , 50wt% dispersant water.

其中，溶剂选用丙酮。Among them, the solvent is acetone.

本实施例中的环境友好型缬菌胺纳米粉剂制备方法包括以下步骤，The preparation method of the environmentally friendly valoxamide nanopowder in this embodiment includes the following steps,

实施例14-2Example 14-2

一种环境友好型缬菌胺纳米粉剂，包括活性成分A，所述活性成分A为缬菌胺，活性成分的质量分数为5wt％，还包括溶剂25wt％、小分子助剂25wt％、高分子助剂5wt％和分散剂水40wt％。An environmentally friendly valoxamide nanopowder, including an active ingredient A, the active ingredient A is valoxamide, the mass fraction of the active ingredient is 5wt%, and also includes a solvent 25wt%, a small molecule adjuvant 25wt%, a polymer Auxiliaries 5wt% and dispersant water 40wt%.

其中，溶剂选用环己酮。Among them, the solvent is cyclohexanone.

实施例15-1(对应申请号为201811632004.6)Example 15-1 (corresponding application number is 201811632004.6)

一种环境友好型精苯霜灵纳米粉剂，包括活性成分A，所述活性成分A为精苯霜灵，活性成分14wt％，还包括溶剂13wt％、小分子助剂10wt％、高分子助剂15wt％、分散剂水48wt％。An environment-friendly fine benxylamine nano powder, including active ingredient A, the active ingredient A is fine benxylamine, active ingredient 14wt%, solvent 13wt%, small molecule adjuvant 10wt%, polymer adjuvant 15wt%, dispersant water 48wt%.

其中，溶剂选用丙酮。Among them, the solvent is acetone.

本实施例中的环境友好型精苯霜灵纳米粉剂制备方法包括以下步骤，The preparation method of the environmentally friendly fine benxylamine nano powder in this embodiment includes the following steps,

实施例15-2Example 15-2

一种环境友好型精苯霜灵纳米粉剂，包括活性成分A，所述活性成分A为精苯霜灵，活性成分的质量分数为7wt％，还包括溶剂27wt％、小分子助剂25wt％、高分子助剂8wt％和分散剂水33wt％。An environmentally friendly fine benxylamine nanopowder, including active ingredient A, the active ingredient A is fine benxylamine, the mass fraction of the active ingredient is 7wt%, and also includes a solvent 27wt%, a small molecule auxiliary 25wt%, Polymer additives 8wt% and dispersant water 33wt%.

其中，溶剂选用环己酮。Among them, the solvent is cyclohexanone.

实施例16-1(对应申请号为201811632005.0)Example 16-1 (corresponding application number is 201811632005.0)

一种环境友好型氯氟醚菌唑纳米粉剂，包括活性成分A，所述活性成分A为氯氟醚菌唑，活性成分12wt％，还包括溶剂8wt％、小分子助剂10wt％、高分子助剂18wt％、分散剂水52wt％。An environmentally friendly clotrifloxazole nanopowder, including active ingredient A, the active ingredient A is clotrifloxazole, the active ingredient is 12wt%, the solvent is also 8wt%, the small molecule adjuvant is 10wt%, the polymer Auxiliary agent 18wt%, dispersant water 52wt%.

其中，溶剂选用丙酮。Among them, the solvent is acetone.

本实施例中的环境友好型氯氟醚菌唑纳米粉剂制备方法包括以下步骤，The preparation method of the environmentally friendly clofluconazole nanopowder in this embodiment includes the following steps,

实施例16-2Example 16-2

一种环境友好型氯氟醚菌唑纳米粉剂，包括活性成分A，所述活性成分A为氯氟醚菌唑，活性成分的质量分数为11wt％，还包括溶剂26wt％、小分子助剂25wt％、高分子助剂11wt％和分散剂水37wt％。An environmentally friendly clotrifloxazole nanopowder, including active ingredient A, the active ingredient A is clofluconazole, the mass fraction of the active ingredient is 11% by weight, and also includes 26% by weight of solvent and 25% by weight of small molecule additives %, polymer additives 11wt% and dispersant water 37wt%.

其中，溶剂选用环己酮。Among them, the solvent is cyclohexanone.

Claims

一种纳米农药制剂，其特征在于该制剂的原辅料包含有效量的农药活性成分或农药原药，以及适量的溶剂、高分子助剂、小分子助剂和分散剂。A nano pesticide preparation, characterized in that the raw and auxiliary materials of the preparation contain an effective amount of pesticide active ingredients or pesticide original drugs, as well as an appropriate amount of solvent, high molecular additives, small molecule additives and dispersants.
根据权利要求1所述的纳米农药制剂，其特征在于该制剂的原辅料包含下列质量百分比的物质：The nano-pesticide preparation according to claim 1, characterized in that the raw and auxiliary materials of the preparation contain the following mass percent substances:

溶剂8～40％；高分子助剂2～22％；小分子助剂8～25％；分散剂25～56％；余量为农药活性成分或农药原药，各成分总和为100％。Solvents 8-40%; polymer adjuvants 2-22%; small-molecule adjuvants 8-25%; dispersants 25-56%; the balance is pesticide active ingredients or pesticide original drugs, the sum of the ingredients is 100%.
根据权利要求2所述的纳米农药制剂，其特征在于该制剂的原辅料包含下列质量百分比的物质：The nano pesticide preparation according to claim 2, characterized in that the raw and auxiliary materials of the preparation contain the following mass percent substances:

溶剂17～32％；高分子助剂2～7％；小分子助剂12～22％；分散剂35～45％；农药活性成分或农药原药3～18％。Solvents 17 to 32%; high molecular additives 2 to 7%; small molecular additives 12 to 22%; dispersants 35 to 45%; pesticide active ingredients or pesticide original drugs 3 to 18%.
根据权利要求3所述的纳米农药制剂，其特征在于该制剂的原辅料包含下列质量百分比的物质：The nano pesticide preparation according to claim 3, characterized in that the raw and auxiliary materials of the preparation contain the following mass percent substances:

溶剂23～32％；高分子助剂3～6％；小分子助剂16～21％；分散剂38～42％；农药活性成分或农药原药3～12％。Solvents 23 to 32%; high molecular additives 3 to 6%; small molecule additives 16 to 21%; dispersants 38 to 42%; pesticide active ingredients or pesticide original drugs 3 to 12%.
根据权利要求4所述的纳米农药制剂，其特征在于该制剂的原辅料包含下列质量百分比的物质：The nano-pesticide preparation according to claim 4, characterized in that the raw and auxiliary materials of the preparation contain the following mass percent substances:

溶剂30％；高分子助剂5％；小分子助剂20％；分散剂40％；农药活性成分或农药原药5％。30% solvent; 5% polymer adjuvant; 20% small molecule adjuvant; 40% dispersant; 5% pesticide active ingredient or pesticide original drug.
根据权利要求1所述的纳米农药制剂，其特征在于农药活性成分或农药原药是不溶于水但能溶于有机溶剂的农药品种；溶剂为能够溶解农药活性成分或农药原药的有机溶剂中的一种或多种；高分子助剂为水溶性天然高分子、水溶性天然高分子衍生物，或者水溶性合成高分子物质；小分子助剂由阴离子助剂和非离子助剂构成的混合助剂，阴离子助剂在小分子助剂中的质量百分比为1～99％，余量为非离子助剂，二者共计为100％，其中阴离子助剂为8～18碳原子的直链或支链烃基或/和芳基的羧酸盐、磺酸盐、硫酸盐或磷酸盐，非离子助剂为聚氧乙烯醚类表面活性剂、多元醇类表面活性剂，或者聚氧乙烯-聚氧丙烯类聚醚型表面活性剂；所述聚氧乙烯醚类表面活性剂不包括壬基酚聚氧乙烯醚类表面活性剂；小分子助剂的HLB值至少为12；分散剂为水。The nano pesticide preparation according to claim 1, characterized in that the pesticide active ingredient or pesticide original drug is a pesticide variety that is insoluble in water but soluble in an organic solvent; the solvent is an organic solvent capable of dissolving the pesticide active ingredient or pesticide original drug One or more of the polymer additives are water-soluble natural polymers, water-soluble natural polymer derivatives, or water-soluble synthetic polymer materials; small molecule additives are composed of anionic additives and nonionic additives Auxiliary agent, the mass percentage of anionic auxiliary agent in small molecule auxiliary agent is 1-99%, the balance is non-ionic auxiliary agent, the total of the two is 100%, of which anionic auxiliary agent is a straight chain of 8-18 carbon atoms or Carboxylates, sulfonates, sulfates or phosphates of branched-chain hydrocarbon groups and/or aryl groups, non-ionic additives are polyoxyethylene ether surfactants, polyol surfactants, or polyoxyethylene-poly Oxypropylene-based polyether surfactants; the polyoxyethylene ether-based surfactants do not include nonylphenol polyoxyethylene ether-based surfactants; the HLB value of the small molecule adjuvant is at least 12; the dispersant is water.
根据权利要求6所述的纳米农药制剂，其特征在于溶剂为包括至少一种可溶于水的溶剂和至少一种不溶于水的溶剂组成的混合溶剂，二者比例根据农药及溶剂种类进行预试验确定最佳配比，一般两者质量比在1∶2左右。The nano pesticide formulation according to claim 6, wherein the solvent is a mixed solvent composed of at least one water-soluble solvent and at least one water-insoluble solvent, and the ratio between the two is pre-determined according to the type of pesticide and solvent Test to determine the best ratio, generally the mass ratio of the two is about 1:2.
根据权利要求6所述的纳米农药制剂，其特征在于高分子助剂选自淀粉及其衍生物(水溶性淀粉、氧化淀粉、羧甲基淀粉、改性淀粉、糊精、环糊精)，纤维素及其衍生物(羧甲基纤维素、羟乙基羟丙基纤维素)，羧甲基壳聚糖，改性瓜尔胶，茶皂素，水溶性腐植酸，木质素磺酸钠，聚乙烯醇，聚丙烯酸，聚丙烯酰胺，聚苯乙烯-马来酸酐共聚物，聚乙烯基吡咯烷酮中的水溶性品种的一种或多种，所述水溶性品种包括上述物质的盐；阴离子助剂选自十二烷基硫酸钠、十二烷基磺酸钠、十二烷基醚硫酸钠、十二烷基单磷酸酯钠、α-烯基磺酸钠、油酸钠、亚油酸钠、亚麻油酸钠、蓖麻油酸钠的一种或多种，非离子助剂选自AEO ₁₅、AEO ₂₀、蓖麻油酸聚氧乙烯醚、吐温-80、吐温-40、烷基多糖苷中的一种或多种；小分子助剂的HLB值为12～40，优选13～18。 The nano pesticide formulation according to claim 6, wherein the polymer adjuvant is selected from starch and its derivatives (water-soluble starch, oxidized starch, carboxymethyl starch, modified starch, dextrin, cyclodextrin), Cellulose and its derivatives (carboxymethyl cellulose, hydroxyethyl hydroxypropyl cellulose), carboxymethyl chitosan, modified guar gum, tea saponin, water-soluble humic acid, sodium lignosulfonate , Polyvinyl alcohol, polyacrylic acid, polyacrylamide, polystyrene-maleic anhydride copolymer, one or more of the water-soluble species in polyvinylpyrrolidone, the water-soluble species including salts of the above substances; anions The auxiliary agent is selected from sodium dodecyl sulfate, sodium dodecyl sulfonate, sodium dodecyl ether sulfate, sodium dodecyl monophosphate, sodium α-alkenyl sulfonate, sodium oleate, linoleic acid One or more of sodium sulfate, sodium linoleate, and sodium ricinoleate, and the non-ionic auxiliary agent is selected from AEO ₁₅ , AEO ₂₀ , ricinoleic acid polyoxyethylene ether, Tween-80, Tween-40, alkyl One or more of the base polyglycosides; the HLB value of the small molecule adjuvant is 12-40, preferably 13-18.
根据权利要求1所述的纳米农药制剂，其特征在于该制剂的剂型为适合纳米农药的水性化剂型和固体剂型，优选为混溶纳米农药悬浮剂、纳米农药悬浮剂、纳米农药固体粉剂。The nano pesticide formulation according to claim 1, characterized in that the dosage form of the formulation is an aqueous formulation and a solid dosage form suitable for nano pesticides, preferably a miscible nano pesticide suspension agent, a nano pesticide suspension agent, a nano pesticide solid powder.
根据权利要求9所述的纳米农药制剂，其特征在于所述混溶纳米农药悬浮剂是将混溶原药溶液滴加到复合助剂水溶液中形成的有纳米晶粒和增溶胶束共存的水分散液；所述混溶原药溶液是将农药原药溶解在混合溶剂中形成的溶液；所述复合助剂水溶液是将高分子助剂和小分子助剂先后分别溶于水形成的水溶液；所述混合溶剂是由至少两种溶剂按照某种特定的比例混合而成；所述混合溶剂包括至少一种可溶于水的溶剂和至少一种不溶于水的溶剂；每种溶剂都必须能够溶解农药原药。The nano pesticide formulation according to claim 9, characterized in that the miscible nano pesticide suspension agent is water in which nano crystal grains and sol-enhanced beams coexist when the miscible prodrug solution is added dropwise to the composite auxiliary aqueous solution Dispersion; the miscible drug solution is a solution formed by dissolving pesticide pesticides in a mixed solvent; the composite auxiliary aqueous solution is an aqueous solution formed by separately dissolving polymer additives and small molecule additives in water; The mixed solvent is formed by mixing at least two solvents in a certain ratio; the mixed solvent includes at least one water-soluble solvent and at least one water-insoluble solvent; each solvent must be capable of Dissolve pesticide pesticides.
如权利要求10所述的混溶纳米农药悬浮剂，其特征在于，所述混溶纳米农药悬浮剂中，混溶原药溶液和复合助剂水溶液的质量百分比之和为100％；混溶原药溶液和复合助剂水溶液的质量百分比范围分别为：35％±5％，65％±5％；优选地，混溶原药溶液和复合助剂水溶液的质量百分比范围分别为：35％±3％，65％±3％。The miscible nano pesticide suspension agent according to claim 10, characterized in that, in the miscible nano pesticide suspension agent, the sum of the mass percentage of the miscible prodrug solution and the composite auxiliary aqueous solution is 100%; the miscible agent The mass percentage ranges of the drug solution and the composite auxiliary aqueous solution are: 35%±5%, 65%±5%; preferably, the mass percentage ranges of the miscible drug solution and the composite auxiliary aqueous solution are: 35%±3, respectively %, 65% ± 3%.
如权利要求10所述的混溶纳米农药悬浮剂，其特征在于，所述混溶原药溶液中，所述农药原药和所述混合溶剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：3％～18％，17％～32％；优选地，所述农药原药和所述混合溶剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：3％～12％，23％～32％。The miscible nano pesticide suspension agent according to claim 10, wherein, in the miscible original drug solution, the pesticide original drug and the mixed solvent account for the mass percentage range of the miscible nano pesticide suspension agent Respectively: 3% to 18%, 17% to 32%; preferably, the mass percentage of the pesticide original drug and the mixed solvent in the miscible nano pesticide suspension agent are respectively: 3% to 12%, 23%～32%.
如权利要求10所述的混溶纳米农药悬浮剂，其特征在于，所述小分子助剂和所述高分子助剂共同组成复合助剂；所述复合助剂水溶液中，所述复合助剂和水占所述混溶纳米农药悬浮剂的质量百分比范围分别为：22％～28％，35％～45％；优选地，所述复合助剂和水占所述混溶纳米农药悬浮剂的质量百分比范围分别为：23％～27％，38％～42％。The miscible nano pesticide suspension agent according to claim 10, wherein the small molecule auxiliary agent and the high molecular auxiliary agent together constitute a composite auxiliary agent; in the aqueous solution of the composite auxiliary agent, the composite auxiliary agent The water and water account for the mass percentage of the miscible nano pesticide suspension agent respectively: 22% to 28%, 35% to 45%; preferably, the composite auxiliary agent and water account for the miscible nano pesticide suspension agent The mass percentage ranges are: 23% to 27%, 38% to 42%.
如权利要求10所述的混溶纳米农药悬浮剂，其特征在于，所述小分子助剂和所述高分子助剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：12％～22％，2％～7％；优选地，所述小分子助剂和所述高分子助剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：16％～21％，3％～6％。The miscible nano pesticide suspension agent according to claim 10, wherein the mass percentage of the small molecule adjuvant and the polymer adjuvant to the miscible nano pesticide suspension agent are respectively: 12%~ 22%, 2% to 7%; preferably, the mass percentages of the small molecule adjuvant and the polymer adjuvant to the miscible nano pesticide suspension are: 16% to 21%, 3% to 6%.
如权利要求10～14任一所述的混溶纳米农药悬浮剂，其特征在于，所述小分子助剂的HLB值至少为12；优选14以上。The miscible nano pesticide suspension agent according to any one of claims 10 to 14, wherein the HLB value of the small molecule adjuvant is at least 12; preferably 14 or more.
如权利要求10～14任一所述的混溶纳米农药悬浮剂，其特征在于，所述小分子助剂包括阴离子助剂和非离子助剂。The miscible nano pesticide suspension agent according to any one of claims 10 to 14, wherein the small molecule adjuvant includes an anionic adjuvant and a non-ionic adjuvant.
如权利要求16所述的混溶纳米农药悬浮剂，其特征在于，所述阴离子助剂为8～18碳原子的直链或支链烃基或/和芳基的羧酸盐、磺酸盐、硫酸盐或磷酸盐。The miscible nano pesticide suspension agent according to claim 16, wherein the anionic auxiliary agent is a carboxylate or sulfonate of a linear or branched hydrocarbon group or/and aryl group having 8 to 18 carbon atoms, Sulfate or phosphate.
如权利要求14所述的混溶纳米农药悬浮剂，其特征在于，所述阴离子助剂为8～18碳原子的直链烷基的羧酸、磺酸、硫酸或磷酸的钠、钾、铵盐。The miscible nano pesticide suspension agent according to claim 14, wherein the anionic auxiliary agent is a sodium, potassium, or ammonium carboxylic acid, sulfonic acid, sulfuric acid, or phosphoric acid of a linear alkyl group having 8 to 18 carbon atoms. salt.
如权利要求14所述的混溶纳米农药悬浮剂，其特征在于，所述非离子助剂为聚氧乙烯醚类表面活性剂、多元醇类表面活性剂，或者聚氧乙烯-聚氧丙烯类聚醚型表面活性剂；所述聚氧乙烯醚类表面活性剂不包括壬基酚聚氧乙烯醚类表面活性剂。The miscible nano pesticide suspension agent according to claim 14, wherein the non-ionic auxiliary agent is a polyoxyethylene ether surfactant, a polyol surfactant, or polyoxyethylene-polyoxypropylene Polyether surfactants; the polyoxyethylene ether surfactants do not include nonylphenol polyoxyethylene ether surfactants.
如权利要求10～14任一所述的混溶纳米农药悬浮剂，其特征在于，所述高分子助剂为水溶性天然高分子、水溶性天然高分子衍生物，或者水溶性合成高分子物质。The miscible nano pesticide suspension agent according to any one of claims 10 to 14, wherein the polymer adjuvant is a water-soluble natural polymer, a water-soluble natural polymer derivative, or a water-soluble synthetic polymer substance .
如权利要求20所述的混溶纳米农药悬浮剂，其特征在于，所述的水溶性天然高分子、水溶性天然高分子衍生物、水溶性合成高分子物质为容易生物降解的物质。The miscible nano pesticide suspension agent according to claim 20, wherein the water-soluble natural polymer, the water-soluble natural polymer derivative, and the water-soluble synthetic polymer substance are substances that are easily biodegradable.
如权利要求10～14任一所述的混溶纳米农药悬浮剂，其特征在于，所述农药原药及其所述混合溶剂中可溶于水的溶剂和不溶于水的溶剂，来自下表：The miscible nano pesticide suspension agent according to any one of claims 10 to 14, characterized in that, in the pesticide original drug and the mixed solvent thereof, the water-soluble solvent and the water-insoluble solvent are from the following table :
如权利要求1所述的纳米农药制剂的制备方法，其特征在于该制剂的制备方法包含下列步骤：The preparation method of the nano pesticide preparation according to claim 1, wherein the preparation method of the preparation comprises the following steps:

1)将农药活性成分或农药原药溶于溶剂形成混溶原药溶液；1) Dissolve pesticide active ingredient or pesticide original drug in solvent to form miscible original drug solution;

2)将高分子助剂溶于分散剂形成高分子助剂溶液，将小分子助剂溶于分散剂形成小分子助剂溶液，将小分子助剂溶液加入到高分子助剂溶液中形成复合助剂溶液，或者直接将小分子助剂加入到高分子助剂溶液中形成复合助剂溶液；2) Dissolve the polymer adjuvant in the dispersant to form a polymer adjuvant solution, dissolve the small molecule adjuvant in the dispersant to form a small molecule adjuvant solution, and add the small molecule adjuvant solution to the polymer adjuvant solution to form a compound Auxiliary solution, or directly add small molecule auxiliary to polymer auxiliary solution to form composite auxiliary solution;

3)将混溶原药溶液加入到复合助剂溶液中，控制加入速度及搅拌速度防止产生宏观沉淀，得到混溶纳米农药悬浮剂即可或者在所得到的混溶纳米农药悬浮剂基础上再制备成其他制剂。3) Add the miscible prodrug solution to the compound adjuvant solution, control the addition speed and stirring speed to prevent macro-precipitation, and just obtain the miscible nano pesticide suspension agent or re-based on the obtained miscible nano pesticide suspension agent. Prepared into other preparations.
根据权利要求23所述的纳米农药制剂的制备方法，其特征在于所述的其他制剂包括纳米农药悬浮剂、纳米农药固体粉剂。The preparation method of the nano pesticide preparation according to claim 23, characterized in that the other preparations include a nano pesticide suspension agent and a nano pesticide solid powder.
根据权利要求23所述的纳米农药制剂的制备方法，其特征在于所述混溶纳米农药悬浮剂是将某种农药原药制成的混溶原药溶液滴加到复合助剂水溶液中形成的有纳米晶粒和增溶胶束共存的水分散液；所述混溶纳米农药悬浮剂的制备方法包括如下步骤：The preparation method of the nano pesticide preparation according to claim 23, characterized in that the miscible nano pesticide suspension is formed by dropping a mixed original drug solution made of a certain pesticide original drug into an aqueous solution of a compound auxiliary agent Aqueous dispersion solution with coexistence of nano crystal grains and sol-enhancing beam; the preparation method of the miscible nano pesticide suspension agent includes the following steps:

1)混合溶剂的制备：将至少一种可溶于水的溶剂和至少一种不溶于水的溶剂，在容器中搅拌，生成混合溶剂；所述可溶于水的溶剂和不溶于水的溶剂都能够溶解所述农药原药；1) Preparation of mixed solvent: mixing at least one water-soluble solvent and at least one water-insoluble solvent in a container to produce a mixed solvent; the water-soluble solvent and the water-insoluble solvent Can dissolve the pesticide pesticide;

2)混溶原药溶液的制备：将所述农药原药加入到所述混合溶剂中，经搅拌溶解，得到混溶原药溶液；2) Preparation of miscible original drug solution: add the pesticide original drug to the mixed solvent and dissolve by stirring to obtain a miscible original drug solution;

3)复合助剂水溶液的制备：先将一种或几种高分子助剂在搅拌下加入水中，必要时进行静止溶胀；在所述高分子助剂充分溶胀后，开动搅拌，直到完全溶解，生成透明的高分子水溶液；然后在所述高分子水溶液中再加入一种或几种小分子助剂，经搅拌，溶解，得到复合助剂水溶液；3) Preparation of aqueous solution of compound additives: First, one or several polymer additives are added to water under stirring, and if necessary, static swelling; after the polymer additives are fully swelled, stirring is started until completely dissolved, Generate a transparent polymer aqueous solution; then add one or more small molecule additives to the polymer aqueous solution, stir and dissolve to obtain a composite auxiliary solution;

4)混溶纳米农药悬浮剂的制备：在搅拌速度可控的条件下，将所述混溶原药溶液滴加到所述复合助剂水溶液中；控制滴加速度和搅拌速度，生成分散均匀的纳米农药晶粒，最终完成混溶纳米农药悬浮剂的制备。4) Preparation of miscible nano pesticide suspension agent: Under the condition of controllable agitation speed, the miscible prodrug solution is added dropwise to the aqueous solution of the composite auxiliary; the drop acceleration and the agitation speed are controlled to produce a uniformly dispersed The nano pesticide grains finally complete the preparation of the miscible nano pesticide suspension agent.
如权利要求25所述的制备方法，其特征在于，通过控制所述滴加速度和/或搅拌速度，使得体系始终保持透明状态。The preparation method according to claim 25, characterized in that, by controlling the drop acceleration and/or the stirring speed, the system is always kept in a transparent state.
如权利要求25所述的制备方法，其特征在于，滴加的方式包括单点滴加、多点滴加或者喷雾滴加。The preparation method according to claim 25, characterized in that the method of dropping includes single-point dropping, multi-point dropping or spray-dropping.
如权利要求25所述的制备方法，其特征在于，所述搅拌速度的优选范围为100～200转/分钟。The preparation method according to claim 25, wherein the preferred range of the stirring speed is 100 to 200 rpm.
如权利要求25所述的制备方法，其特征在于，所述混溶纳米农药悬浮剂中，混溶原药溶液和复合助剂水溶液的质量百分比之和为100％；混溶原药溶液和复合助剂水溶液的质量百分比范围分别为：35％±5％，65％±5％；优选地，混溶原药溶液和复合助剂水溶液的质量百分比范围分别为：35％±3％，65％±3％。The preparation method according to claim 25, characterized in that, in the miscible nano pesticide suspension agent, the sum of the mass percentage of the miscible drug solution and the composite auxiliary aqueous solution is 100%; the miscible drug solution and the compound The mass percentage ranges of the aqueous solution of the additives are: 35%±5%, 65%±5%; preferably, the mass percentage ranges of the miscible drug solution and the composite auxiliary solution are: 35%±3%, 65% ±3%.
如权利要求29所述的制备方法，其特征在于，所述混溶原药溶液中，所述农药原药和所述混合溶剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：3％～18％，17％～32％；优选地，所述农药原药和所述混合溶剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：3％～12％，23％～32％。The preparation method according to claim 29, wherein, in the miscible crude drug solution, the mass percentage range of the pesticide primary drug and the mixed solvent in the miscible nano pesticide suspension agent are: 3 % To 18%, 17% to 32%; preferably, the mass percentages of the pesticide original drug and the mixed solvent in the miscible nano pesticide suspension agent are respectively: 3% to 12%, 23% to 32 %.
如权利要求29所述的制备方法，其特征在于，所述小分子助剂和所述高分子助剂共同组成复合助剂；所述复合助剂水溶液中，所述复合助剂和水占所述混溶纳米农药悬浮剂的质量百分比范围分别为：22％～28％，35％～45％；优选地，所述复合助剂和水占所述混溶纳米农药悬浮剂的质量百分比范围分别为：23％～27％，38％～42％。The preparation method according to claim 29, characterized in that the small molecule auxiliary agent and the high molecular auxiliary agent together constitute a composite auxiliary agent; in the aqueous solution of the composite auxiliary agent, the composite auxiliary agent and water account for The mass percentage range of the miscible nano pesticide suspension agent is respectively: 22% to 28%, 35% to 45%; preferably, the composite auxiliary agent and water account for the mass percentage range of the miscible nano pesticide suspension agent respectively It is: 23% to 27%, 38% to 42%.
如权利要求31所述的制备方法，其特征在于，所述小分子助剂和所述高分子助剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：12％～22％，2％～7％；优选地，所述小分子助剂和所述高分子助剂占所述混溶纳米农药悬浮剂的质量百分比范围分别为：16％～21％，3％～6％。The preparation method according to claim 31, wherein the mass percentages of the small molecule adjuvant and the polymer adjuvant to the miscible nano pesticide suspension agent are respectively: 12% to 22%, 2 % To 7%; preferably, the mass percentages of the small molecule adjuvant and the polymer adjuvant to the miscible nano pesticide suspension agent are respectively: 16% to 21%, 3% to 6%.
如权利要求31所述的制备方法，，其特征在于，所述小分子助剂的HLB值至少为13；优选14以上。The preparation method according to claim 31, characterized in that the HLB value of the small molecule adjuvant is at least 13; preferably 14 or more.
如权利要求25至33任一所述的制备方法，其特征在于，所述混合溶剂的制备是在装有回流冷凝器的容器中进行。The preparation method according to any one of claims 25 to 33, wherein the preparation of the mixed solvent is carried out in a vessel equipped with a reflux condenser.
如权利要求25至33任一所述的制备方法，其特征在于，所述复合助剂水溶液的制备是在装有搅拌、回流冷凝器以及能够加热和减压蒸馏的容器中进行。The preparation method according to any one of claims 25 to 33, characterized in that the preparation of the aqueous solution of the composite auxiliary agent is carried out in a vessel equipped with a stirring, reflux condenser, and capable of heating and vacuum distillation.
根据权利要求23所述的纳米农药制剂的制备方法，其特征在于纳米农药悬浮剂的制备方法，在采用权利要求25所述的方法完成混溶纳米农药悬浮剂的制备后，进一步采用如下两种蒸馏回收溶剂方式之一完成纳米农药悬浮剂的制备：The preparation method of the nano pesticide preparation according to claim 23, characterized in that the preparation method of the nano pesticide suspension agent, after the method of claim 25 is used to complete the preparation of the miscible nano pesticide suspension agent, the following two methods are further used One way to recover the solvent by distillation is to complete the preparation of nano pesticide suspension agent:

1)加热常压蒸馏；1) Heating atmospheric pressure distillation;

2)加热减压蒸馏；2) Heating and vacuum distillation;

当溶剂沸点高于或等于非离子表面活性剂浊点温度时必须采用加热减压蒸馏。When the boiling point of the solvent is higher than or equal to the cloud point temperature of the nonionic surfactant, heating and vacuum distillation must be used.
如权利要求36所述的制备方法，其特征在于，加热温度必须在非离子表面活性剂浊点温度之下。The preparation method according to claim 36, wherein the heating temperature must be below the cloud point temperature of the nonionic surfactant.
根据权利要求23所述的纳米农药制剂的制备方法，其特征在于纳米固体粉剂的制备方法为将权利要求23制备得到的混溶纳米农药悬浮剂或者将权利要求36制备得到的纳米农药悬浮剂采用喷雾干燥回收部分或全部溶剂后形成纳米农药粉状固体制剂。The preparation method of the nano pesticide preparation according to claim 23, characterized in that the preparation method of the nano-solid powder is to adopt the miscible nano pesticide suspension prepared by claim 23 or the nano pesticide suspension prepared by claim 36 After spray drying and recovering part or all of the solvent, a nanometer pesticide powder solid preparation is formed.