WO2017075777A1 - Method for preparing nanoscale pesticide preparation by using silica aerogel - Google Patents

Abstract

A method for preparing a nanoscale pesticide preparation by using silica aerogel. The present invention relates to the technical field of pesticides, and specifically relates to an application of silica aerogel as a novel carrier in a pesticide processing aid. The technical solution is as follows: the application refers to using the silica aerogel as a carrier to perform nano preparation processing on an insoluble technical material. The processing steps are as follows: dissolving a technical material by a solvent or smashing the technical material; loading the solvent-containing liquid to the silica aerogel by means of absorption or mixing the silica aerogel with the smashed technical material to form a nano-particle pesticide-carrying system having a particle size less than 100 nm; adding water to the nano-particle pesticide-carrying system, stirring or emulsifying to make the nano-particle pesticide-carrying system evenly dispersed; drying to remove the solvent and moisture to obtain the nano pesticide. The present invention has advantages of being environment-friendly and filling in a gap of nanoscale pesticide carrier material both at home and abroad.

Description

Method for preparing nanometer pesticide preparation by using silica aerogel Technical field

The invention belongs to the technical field of pesticides, and specifically relates to the application of silica aerogel as a novel carrier in pesticide processing aids.

Background technique

Pesticides are collectively referred to as a class of drugs used in agricultural production to protect and promote the growth of plants and crops, and to kill insecticides, sterilize, and kill harmful animals (or weeds). Specifically, it is used in agriculture to control pests and diseases, and to regulate plant growth, weeding and other agents. Pesticides play an important role in ensuring the output and quality of agricultural products and ensuring human food security. High-quality, low-toxic, low-residue, economical and easy-to-use pesticide varieties should be the direction of pesticide development.

In the actual production and application of pesticides, although the production and sale of organophosphorus highly toxic pesticides have been banned and restricted, in the current mainstream pesticide varieties, a large amount of organic solvents, especially aromatic hydrocarbons, are still added. Highly toxic organic solvents such as toluene and xylene. With the development of social economy and people's living standards and the enhancement of health awareness, people pay more and more attention to the quality and quality of agricultural products, and pay more and more attention to the impact of pesticide problems on health and even life.

The research and development of pesticide products is an important field of high-tech development. Pesticide researchers have found the problem of adding organic solvents to pesticides. This is the problem of low solubility of pesticides, or that agricultural compounds are difficult to dissolve in water. This problem is prevalent in currently applied biological pesticides, biomimetic pesticides and chemical pesticides. Even new pesticides that have been on the market in recent years have not solved this problem.

Different from human drugs, tablets, capsules, injections, etc., pesticides are usually water as a dispersion medium, the usual method of use is to tens of times to thousands of times in the preparation of water on farmland, vegetable fields Orchard spray application. Therefore, the amount of solubility in water is a key factor in determining the efficacy of pesticides. However, the most important pesticides widely used in today's pesticides are mostly poorly water-soluble drugs, which have to be added in large quantities. Adding organic solvents increases their solubility to achieve the purpose of improving the efficacy and controlling pests and diseases. For example, the avermectin has a solubility in water of about 10 μg/L; the ivermectin has a solubility in water of about 4 mg/L; the emamectin benzoate (a salt) is in the water. Solubility is about 300mg / L; the solubility of azoxystrobin in water is about 6mg / L; the original drug of cyhalothrin is 0.004ppb (at 20 ° C) in solubility water, according to the classification of drug solubility, "almost Insoluble or insoluble refers to the definition that the solute 1 g (ml) cannot be completely dissolved in the solvent 10000 ml, and the original drugs of these drugs are all insoluble and almost insoluble types. Unfortunately, toxic organic solvents such as benzene, toluene and xylene of aromatic hydrocarbons are good solvents for these pesticides. For example, the avermectin has a solubility of up to 350 g/L in toluene, but only in water. 10 μg / L. The avermectin preparation commonly used in pesticides is avermectin ointment, which is an accessory of avermectin refined powder, which is contained in xylene-dissolved emulsifiable concentrate, and the content is between 3 and 7%. The main components of a lambda-cyhalothrin emulsion are: cyhalothrin 2.9%, methanol 20%, xylene 40%.

In order to improve the efficacy of the original drug, reduce the damage caused by pests and diseases to agricultural products, adding a large amount of organic solvent to increase the solubility of the original drug is often considered to be difficult to avoid, and is a technical problem that is difficult to solve. The pesticide preparations with a large amount of organic solvents not only endanger people's physical and mental health, damage the ecological environment, are not conducive to environmental protection, but also cause occupational injuries of pesticide farmers. This situation is urgently needed to be solved through advances in science and technology.

At present, researchers of pharmaceutical preparations use the polymer materials such as PEG (polyethylene glycol), cellulose, and dextrin and liposome in the existing pharmaceutical excipients to carry out research on drug-loading system technology. However, there are serious technical defects in the application of such materials, mainly in the following: low drug loading, most not more than 10%, large amount of auxiliary materials or additives; easy to agglomerate, difficult to obtain micro- and nano-structured drug products; stable Poor sex, it is more difficult to adapt to changes in temperature and humidity in pesticide formulations. Liposomes may also leak and degenerate when they are loaded with drugs; they are only suitable for specific individual drugs, which are specific methods, and have no universality; various excipients, which bring more impurities and difficult quality control. The main problem is that no suitable drug carrier has been found. material. For example, the existing traditional excipients are mostly solid granular, and there is no small-scale spatial structure for accommodating drugs. Most of them are loaded with drug molecules on the surface of the fine solid structure, so that a high drug loading amount cannot be achieved, and the formation is often the main Small-scale mixtures with low drug content and large amount of excipients are difficult to meet the basic requirements for high drug loading, large specific surface area and stable quality.

Summary of the invention

In order to solve the above-mentioned problems, the present invention provides a pesticide preparation prepared by using silica aerogel and a preparation method thereof, and the technical problems of the present invention are as follows:

A method for preparing a pesticide preparation by using a silica aerogel, wherein the application refers to a silica aerogel as a carrier for processing a nanometer preparation of a poorly soluble crude drug, and the processing steps are as follows:

1 Solving the original pesticide or pulverizing the original pesticide with a solvent;

2 using a silica aerogel to adsorb a solvent-containing liquid containing a drug solvent or mixing the pulverized original drug to form a nanoparticle drug-loading system having a diameter of less than 100 nm, the silica aerogel being hydrophilic The silica aerogel or the hydrophobic silica aerogel has a hydrophilic silica aerogel after heat treatment, and the mass ratio of the pesticide original drug to the silica aerogel is 1:0.5-20, The silica aerogel encapsulates the drug molecule in its nano-network structure to form a stable nano-solid dispersion of the drug. When applied, the drug aqueous agent formed by the multi-fold water is transparent and has little precipitation, and The comparison of the equivalent water amount of several commercial preparations shows that the pesticide preparation prepared by the method of the invention has the least precipitation and the longest stabilization time;

3 The nanoparticle drug delivery system is uniformly dispersed with water; after this step is completed, a liquid product that can be applied has been formed. The pesticide of the product can be directly diluted with water before application.

4 drying to remove the solvent and water to obtain a nano drug;

5 Preparation of various dosage forms of nanomedicine.

The pesticide is one or more selected from the group consisting of insoluble insecticides, bactericides, and herbicides.

The insecticide is selected from the group consisting of pyrethroids, carbamates, organic phosphorus, organic sulfur, organic choline, silkworm toxin, neonicotinoid, phenyl acyl urea, avermectin, and emamectin benzene. Acid salt, bismuth, cockroach, phenylpyrazole, indoxacarb or dibutyl ether urea insecticide;

The bactericide is selected from the group consisting of anilinopyridine, antibiotics, aromatic hydrocarbons, dinitroaniline, azoxystrobin, allylamine, benzenesulfonamide, benzimidazole, benzisothiazole, benzophenone, benzoyl Pyrimidine, benzotriazine, benzyl carbamate, carbamate, carboxamide, carboxylic acid diamide, chloronitrile, cyanoimidazole, cyclopropanecarboxamide, ethylaminothiazole carboxamide, imidazole, hydroxyanilide , imidazolinone, isobenzofuranone, methoxy acrylate, methoxy carbamate, morpholine, N-phenyl carbamate, oxazolidinedione, phenylacetamide, phenyl Amide, phenylpyrrole, phenylurea, phosphorothioate, o-carbamoylbenzoic acid, phthalimide, piperazine, piperidine, propionamide, pyridine, pyridylmethylamide, toluamide, three Pyrazine or triazole fungicide;

The herbicide is selected from the group consisting of an amide, an aryloxyphenoxypropionate, a phenoxycarboxylic acid, an organophosphorus, a benzamide, a benzofuran, a benzoic acid, a benzothiadiazinone, a carbamate, Chloroacetamide, pyridine carboxylic acid, chlorocarboxylic acid, cyclohexanedione, dinitroaniline, diphenyl ether, isoxazole, isoxazolidinone, N-phenylphthalimide, malignant Azole, oxazolidinedione, oxyacetamide, phenylcarbamate, phenylpyridazine, sulfoaminocarboxytriazolinone, sulfonyltriazolocarbamide, triazolopyrimidine, triketone, Uracil or urea herbicide;

The inventors found through research that silica aerogel is a novel nano-material with three-dimensional network structure, which has a particle size scale of less than 100 nanometers strictly defined by materials science, and an independent spatial structure of less than 100 nanometers. With a thickness of 10,000 nanopores per millimeter, the volume of space (air) that can be used for drug loading is over 90%, which can reach the highest drug loading rate in history. It has a large specific surface area and a stable nano-aperture necessary for improving the bioavailability of the drug to improve the efficacy of the drug, and can be nano-dispersed and loaded with drugs by means of "self-assembly" and "cross-linking". The formation of an independent "nanodispersion" that does not agglomerate can realize the "nano-drug" of the "nano-drug" and the universal multi-drug in the true sense, and directly solve the problem that the agglomeration cannot be established in the nano-drug research. Soluble drugs are difficult to effectively absorb and other formulation problems. The large drug loading, high encapsulation efficiency, large specific surface area and lightest weight are the basic characteristics of silica aerogel as a drug carrier. Silica aerogel is a new type of microstructured porous material. Using this material as a pharmaceutically acceptable carrier can realize the “nanocrystallization” of the original drug from the mesoscale physical level without destroying the molecular structure of the original drug. Because the molecular size of most pharmaceutical compounds is on the angstrom scale. In principle, the silica molecule aerogel encapsulates the drug molecule and physically disperses it to maintain and fully exert its original biological activity. It reflects the characteristics of small scale, high surface activity and high bioavailability, which is difficult to achieve in traditional preparations. Since this principle has universal significance, the inventors believe that a variety of pesticides can be used to prepare new nanomedicine preparations, silica aerogels, which are convenient, fast, high-quality and low-cost. The drug-loading material is a technique of commonality for the nano-treatment of most poorly soluble raw materials.

Further, in step 4, the nanomedicine is passed through a 100 mesh to 200 mesh sieve, and in the nanopesticide final product, it is most suitable to stabilize the properties of the solid nanoformulation in a micron-sized dispersion because the fine particles are too fine. It is easy to cause dusty flying, which is not conducive to field application. It is a good choice to pass the 200 mesh or even 100 mesh mesh particles by the preparation method of this patent, because the drug nanoparticles coated by these coarse particles are in contact with water. It can be quickly decomposed, does not affect the use, and greatly reduces dust during use.

Further, the temperature of the heat treatment is 300 to 1000 °C.

The inventors have found through further research that silica aerogel as a carrier material has unique technical advantages in the processing of nanometer preparations for poorly soluble prodrugs. Silica aerogel as the inorganic material itself has chemical inertness and physical stability, which reflects the high bio-inert and temperature stability of the organic carrier material and the stability of the finished structure. The water-soluble drug is very low in water, but It has good high temperature performance and can be decomposed and deactivated at higher temperatures. For example, the melting point of the original avermectin is: 150-155 ° C; the melting point of the crude salt of the methicillin is 141-146 ° C, suggesting that the preparation process can be carried out at a higher temperature. If the original drug solution is adsorbed by the silica aerogel, it is not necessary to use an expensive high-pressure homogenizer when performing the dispersion treatment, and the ordinary stirring device can be used because the silica aerogel has utilized its own nano-scale. The drug-loading space automatically and highly accurately physically disperses and isolates the contained drug. When the solid nanodispersion is processed, the drug is dried, and it is not necessary to perform low-temperature drying or freeze-drying.

In the production of nano-pesticide preparations, it is not necessary to use expensive processing equipment such as freeze dryers, low-temperature dryers, high-pressure homogenizers and other high-end equipment, which will be of great benefit to the production enterprises. The investment and operation and maintenance and energy consumption of high-end equipment will bring about a significant increase in production costs and labor costs. Due to the large-scale production mode of pesticides, the quality requirements of the products can be achieved by using ordinary mixers, dryers and crushing and screening machines. It can save a lot of equipment investment and maintenance costs, and energy consumption can be greatly reduced.

Further, the silica aerogel has a porosity of 95 to 99%, a pore diameter of 10 to 50 nm, a specific surface area of 200 to 1000 m ² /g, a density of 3 to 300 kg/m ³ , and colloidal particles constituting the network. The diameter is 1 to 50 nm.

Further, the solvent is ethanol or ethyl acetate, and since ethanol or ethyl acetate is low in toxicity, it is more environmentally friendly.

Further, the drying method comprises drying, lyophilizing and spray drying, the drying temperature is 60 ° C to 120 ° C; the lyophilization temperature is -50 ° C to -70 ° C, the pressure is 0.1 to 10 Pa; and the drying temperature is 120. °C ~ 220 ° C, the inventors further research found that because the pesticide is poorly soluble original drug and silica aerogel both have good heat resistance, directly use ordinary drying equipment, such as ordinary oven can get nano The bulk precursor of the dried drug body can be obtained by using a common pulverizing and sieving machine to obtain nanometer-sized drug dispersions of different particle sizes, meeting the quality requirements of the pesticide products and meeting the application requirements. The nanomedicine finally obtained by the processing technology can reach a specific surface area of 300 m ² /g. When a spray dryer is used, a microspherical nanosolid dispersion is obtained with a specific surface area of 300 m ² /g.

Further, the pesticide preparation is a nano-scale pesticide solid dispersion, a suspension preparation and a water agent, and there is no difference in stability between the micro-powder and the micro-spherical nano-scale pesticide solid dispersion, and the finished product is bottled or bagged. No desiccant, no reunion for more than three years. There is no difference in the application of the two traits. The carrier material is a hydrophilic silica aerogel, which is a water-soluble carrier. The finished product can be highly uniformly dispersed with a little stirring with water. The liquid solution with high water added before application is water-like transparent. However, in the solid state, the silica aerogel drug delivery system exhibits a high degree of physical stability, and the pesticide nanosolid dispersion is a powder, a tablet, a granule or a microcapsule.

Nano-medicine prepared by using silica aerogel, the nano drug has a drug loading of >50%; encapsulation efficiency of >90%; drug-loaded microsphere specific surface area >300 m ² /g; drug-loaded microspheres The diameter is less than 5μm, which can cover many kinds of original drug particles; stability investigation, no agglomeration time>3 years, there is no precedent for such preparations in international and domestic.

Compared with the prior art, the present invention has the following advantages:

1. The present invention finds a new nano-carrier material for the pesticide preparation, which is not a popular nano-particle material or nano-powder, but truly realizes a nano-scale drug-loading hole new structure. It achieves the physical drug loading standard of less than 100 nanometers that can be realized by any material in today's medicinal materials, and fills the blank of carrier materials for nanometer-level pesticides in the world. It is universally applicable as a formulation innovation for many kinds of pesticides. Sexual meaning.

2. A new pesticide preparation prepared by the present invention which does not contain an organic solvent, particularly benzene. It is of great practical significance to improve the quality of agricultural products, ensure food safety and protect the ecological environment and reduce environmental pollution.

3. The nano pesticide preparation prepared by the invention solves the technical problem that the poorly soluble original drug has to use an organic solvent to disperse the original drug because the solubility is too low. This patent only uses B when preparing nano pesticide formulations. A low-toxic or non-toxic organic solvent such as ethyl acetate or ethanol is used as a drug for dissolving the original drug, and the organic solvent is removed in a subsequent drying process to obtain a commercial drug containing no organic solvent. In the prior art, a large amount of an organic solvent, particularly an aromatic hydrocarbon solvent, is added to the preparation of the preparation. These solvents are sold with commercial drugs and used on crops.

DRAWINGS

Figure 1 is an electron micrograph of a silica aerogel material, from which the nanoscale spatial structure of the silica aerogel can be seen;

2 is a nano-pesticide dispersion prepared by using a silica aerogel as a carrier, and it can be seen that the particle size of the pesticide dispersion prepared by the present invention is 25 nm;

3 is an electron micrograph of drug-loaded microspheres prepared by using silica aerogel as a carrier. It can be seen that the drug-loaded microspheres prepared by the invention have a particle size of less than 2 μm, and the drug-loaded microspheres carry a large number of nano-sized drug particles.

detailed description

Example 1

Nano-average avermectin drying preparation process

1 drug dissolution and adsorption drug loading

1.1 precision weighing avermectin original drug 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Measure the solvent ethyl acetate (analytically pure) 500 ml, dissolve into a light yellow clear liquid, and add 1500 ml of absolute ethanol (analytical purity) to dilute.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loaded body was placed in a beaker, and 2000 ml of absolute ethanol was added.

2.2 High-speed emulsifying machine emulsification, parameters: speed 10,000 rev / min, time 5 minutes.

2.3 The emulsion was dried using a dry box, parameters: temperature 100 ° C, time 12 hours.

2.4 The semi-finished product is pulverized through a 200 mesh sieve to obtain a nano-avermectin powder.

Example 2

Drying preparation process of nano-methyl avermectin benzoate (methyl sulphate)

1 drug dissolution and adsorption drug loading

1.1 Precision Weighing Emamectin Benzoate 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Weigh 7g D902 anti-decomposing agent (Shenzhen Long Ti Biotechnology Co., Ltd.), measure 2000 ml of solvent anhydrous ethanol (analytical grade), and prepare an alcohol solution with a concentration of 0.35%.

1.4 Add the above alcohol solution to dissolve the original drug of emamectin benzoate to a brown clear liquid.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loaded body was placed in a beaker, and 2000 ml of purified water was added and stirred.

2.2 High-speed emulsifier emulsification, parameters: speed 30,000 rev / min, time 5 minutes.

2.3 The emulsion was dried using a dry box, parameters: temperature 120 ° C, time 12 hours.

2.4 The semi-finished product is pulverized through a 200 mesh sieve to obtain a nano-methyl avermectin benzoate powder.

Example 3

Nano ivermectin drying preparation process

1 drug dissolution and adsorption drug loading

1.1 Precision weighing ivermectin original drug 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Measure the solvent anhydrous ethanol (analytically pure) 2000 ml, dissolve to a pale yellow clear liquid.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loaded body was placed in a beaker, and 2000 ml of purified water was added and stirred.

2.2 High-speed emulsifier emulsification, parameters: speed 28000 rev / min, time 5 minutes.

2.3 The emulsion was dried using a dry box, parameters: temperature 120 ° C, time 12 hours.

2.4 The semi-finished product is pulverized through a 200 mesh sieve to obtain nano ivermectin powder.

Example 4

Nano-pyrazine drying preparation process

1 drug dissolution and adsorption drug loading

1.1 Precision weighing azoxystrobin 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Measure the solvent ethyl acetate (analytically pure) 500 ml, dissolve into a milky white liquid, and add 1500 ml of absolute ethanol (analytical purity) to dilute.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loaded body was placed in a beaker, and 2000 ml of absolute ethanol was added.

2.2 High-speed emulsifier emulsification, parameters: speed 28000 rev / min, time 5 minutes.

2.3 The emulsion was dried using a dry box, parameters: temperature 80 ° C, time 12 hours.

2.4 The semi-finished product is pulverized through a 200 mesh sieve to obtain a nanozoxystrobin powder.

Example 5

Nano-methyl avermectin benzoate drying preparation process

1 drug dissolution and adsorption drug loading

1.1 Precision weighing of emamectin benzoate original drug 25g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Weigh 7g D902 anti-decomposing agent (Shenzhen Long Ti Biotechnology Co., Ltd.), measure 2000 ml of solvent anhydrous ethanol (analytical grade), and prepare an alcohol solution with a concentration of 0.35%.

1.4 Add the above alcohol solution to dissolve the original drug of emamectin benzoate to a brown clear liquid.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loaded body was placed in a beaker, and 2000 ml of purified water was added and stirred.

2.2 High-speed emulsifying machine emulsification, parameters: speed 25000 rev / min, time 2 minutes.

2.3 The emulsion was dried using a dry box, parameters: temperature 120 ° C, time 12 hours.

2.4 The semi-finished product is pulverized through a 200 mesh sieve to obtain a nano-methyl avermectin benzoate powder.

Example 5

Nano-efficiency cyfluthrin drying preparation process

1 drug dissolution and adsorption drug loading

1.1 precision weighing high-efficiency cyfluthrin original drug 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Measure the solvent ethyl acetate (analytically pure) 500 ml, dissolve into a milky white liquid, and add 1500 ml of absolute ethanol (analytical purity) to dilute.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loading body was placed in a beaker, and 2000 ml of purified water was added.

2.2 High-speed emulsifying machine emulsification, parameters: speed 28000 rev / min, time 10 minutes.

2.3 The emulsion was dried using a dry box, parameters: temperature 100 ° C, time 12 hours.

2.4 The semi-finished product is pulverized through a 150 mesh sieve to obtain a nanometer high-efficiency cyfluthrin powder.

Example 6

Nano-avermectin freeze-drying preparation process

1 drug dissolution and adsorption drug loading

1.1 precision weighing avermectin original drug 50 grams

1.2 Precision Weighing Silica Aerogel 250g

1.3 Measure the solvent ethyl acetate (analytically pure) 500 ml, dissolve into a light yellow clear liquid, and add 1500 ml of absolute ethanol (analytical purity) to dilute.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loading body was placed in a beaker, and 2000 ml of purified water was added.

2.2 High-speed emulsifier emulsification, parameters: 28,000 rpm, 5 minutes.

2.3 High-pressure homogenizer homogenization, parameters: pressure 800bar, time 10 minutes.

2.4 Freeze the homogenized liquid, parameters: temperature -70 ° C, pressure: 5 pa, time 24 hours.

2.5 The semi-finished product is pulverized through a 200 mesh sieve to obtain a nano-avermectin powder.

Example 7

Preparation process of nano-methylamino avermectin benzoate freeze-drying

1 drug dissolution and adsorption drug loading

1.1 Precision Weighing Emamectin Benzoate 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Weigh 7g D902 anti-decomposing agent (Shenzhen Long Ti Biotechnology Co., Ltd.), measure 2000 ml of solvent anhydrous ethanol (analytical grade), and prepare an alcohol solution with a concentration of 0.35%.

1.4 Add the above alcohol solution to dissolve the original drug of emamectin benzoate to a brown clear liquid.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loaded body was placed in a beaker, and 2000 ml of purified water was added and stirred.

2.2 High-speed emulsifier emulsification, parameters: speed 28000 rev / min, time 5 minutes.

2.3 High-pressure homogenizer homogenization, parameters: pressure 800bar, time 10 minutes.

2.4 Freeze the homogenized liquid, parameters: temperature -70 ° C, pressure: 5 pa, time 24 hours.

2.5 The semi-finished product is pulverized through a 200 mesh sieve to obtain a nano-methyl avermectin benzoate powder.

Example 8

Nano-ivermectin freeze-drying preparation process

1 drug dissolution and adsorption drug loading

1.1 Precision weighing ivermectin original drug 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Measure the solvent anhydrous ethanol (analytically pure) 2000 ml, dissolve to a pale yellow clear liquid.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loaded body was placed in a beaker, and 2000 ml of purified water was added and stirred.

2.2 High-speed emulsifier emulsification, parameters: speed 28000 rev / min, time 5 minutes.

2.3 High-pressure homogenizer homogenization, parameters: pressure 800bar, time 8 minutes.

2.4 Freeze the homogenized liquid, parameters: temperature -50 ° C, pressure: 5 pa, time 24 hours.

2.5 The semi-finished product is pulverized through a 200 mesh sieve to obtain nano ivermectin powder.

Example 9

Nano-efficiency cyfluthrin freeze-drying preparation process

1 drug dissolution and adsorption drug loading

1.1 precision weighing high-efficiency cyfluthrin original drug 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Measure the solvent ethyl acetate (analytically pure) 500 ml, dissolve into a milky white liquid, and add 1500 ml of absolute ethanol (analytical purity) to dilute.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loading body was placed in a beaker, and 2000 ml of purified water was added.

2.2 High-speed emulsifier emulsification, parameters: speed 28000 rev / min, time 5 minutes.

2.3 High-pressure homogenizer homogenization, parameters: pressure 800bar, time 10 minutes.

2.4 Freeze the homogenized liquid, parameters: temperature -70 ° C, pressure: 5 pa, time 24 hours.

2.5 The semi-finished product is pulverized through a 200 mesh sieve to obtain a nanometer high-efficiency cyfluthrin powder.

Example 10

Semi-pyrrolidone freeze-drying preparation process

1 drug dissolution and adsorption drug loading

1.1 Precision weighing azoxystrobin 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Measure the solvent ethyl acetate (analytically pure) 500 ml, dissolve into a milky white liquid, and add 1500 ml of absolute ethanol (analytical purity) to dilute.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The dried product was placed in a beaker and 2000 ml of purified water was added.

2.2 High-speed emulsifier emulsification, parameters: speed 28000 rev / min, time 5 minutes.

2.3 High-pressure homogenizer homogenization, parameters: pressure 1000bar, time 10 minutes.

2.4 Freeze the homogenized liquid, parameters: temperature -70 ° C, pressure: 5 pa, time 24 hours.

2.5 The semi-finished product is pulverized through a 200 mesh sieve to obtain a nanozoxystrobin powder.

Example 11

Nano avermectin spray drying preparation process

1 drug dissolution and adsorption drug loading

1.1 precision weighing avermectin original drug 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Measure the solvent ethyl acetate (analytically pure) 500 ml, dissolve into a light yellow clear liquid, and add 1500 ml of absolute ethanol (analytical purity) to dilute.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loading body was placed in a beaker, and 2000 ml of purified water was added.

2.2 High-speed emulsifier emulsification, parameters: 28,000 rpm, 5 minutes.

2.3 High-pressure homogenizer homogenization, parameters: pressure 800bar, time 10 minutes.

2.4 Spray the homogenized liquid, parameters: temperature 120 ° C, flow rate 500 ml / hour, nozzle 0.75 mm.

2.5 spray dry product to obtain nano avermectin powder.

Example 12

Preparation process of nano-methylamino Avermectin benzoate spray drying

1 drug dissolution and adsorption drug loading

1.1 Precision Weighing Emamectin Benzoate 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Weigh 7g D902 anti-decomposing agent (Shenzhen Long Ti Biotechnology Co., Ltd.), measure 2000 ml of solvent anhydrous ethanol (analytical grade), and prepare an alcohol solution with a concentration of 0.35%.

1.4 Add the above alcohol solution to dissolve the original drug of emamectin benzoate to a brown clear liquid.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loaded body was placed in a beaker, and 2000 ml of purified water was added and stirred.

2.2 High-speed emulsifier emulsification, parameters: speed 28000 rev / min, time 5 minutes.

2.3 High-pressure homogenizer homogenization, parameters: pressure 500bar, time 10 minutes.

2.4 Spray the homogenized liquid, parameters: temperature 120 ° C, flow rate 500 ml / hour, nozzle 0.75 mm.

2.5 spray dry product to obtain nano-methyl avermectin benzoate powder.

Example 13

Preparation of spray drying process of nano ivermectin

1 drug dissolution and adsorption drug loading

1.1 Precision weighing ivermectin original drug 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Measure the solvent anhydrous ethanol (analytically pure) 2000 ml, dissolve to a pale yellow clear liquid.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loaded body was placed in a beaker, and 2000 ml of purified water was added and stirred.

2.2 High-speed emulsifier emulsification, parameters: speed 28000 rev / min, time 5 minutes.

2.3 High-pressure homogenizer homogenization, parameters: pressure 800bar, time 10 minutes.

2.4 Spray the homogenized liquid, parameters: temperature 120 ° C, flow rate 500 ml / hour, nozzle 0.75 mm.

2.5 spray dry product to obtain nano ivermectin powder.

Example 14

Spraying dry preparation process of Nanzoxystrobin

1 drug dissolution and adsorption drug loading

1.1 Precision weighing azoxystrobin 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Measure the solvent ethyl acetate (analytically pure) 500 ml, dissolve into a milky white liquid, and add 1500 ml of absolute ethanol (analytical purity) to dilute.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The dried product was placed in a beaker and 2000 ml of purified water was added.

2.2 High-speed emulsifier emulsification, parameters: speed 28000 rev / min, time 5 minutes.

2.3 High-pressure homogenizer homogenization, parameters: pressure 800bar, time 10 minutes.

2.4 Spray the homogenized liquid, parameters: temperature 120 ° C, flow rate 500 ml / hour, nozzle 0.75 mm.

2.5 spray dry product to obtain nano-pyrimidal powder.

Example 15

Nano-efficiency cyfluthrin spray drying preparation process

1 drug dissolution and adsorption drug loading

1.1 precision weighing high-efficiency cyfluthrin original drug 250g

1.2 Precision Weighing Silica Aerogel 250g

1.3 Measure the solvent ethyl acetate (analytically pure) 500 ml, dissolve into a milky white liquid, and add 1500 ml of absolute ethanol (analytical purity) to dilute.

1.4 250 g of aerogel was added until the drug solution was completely absorbed.

2 nanodispersion or microsphere preparation

2.1 The obtained drug-loading body was placed in a beaker, and 2000 ml of purified water was added.

2.2 High-speed emulsifier emulsification, parameters: speed 28000 rev / min, time 5 minutes.

2.3 High-pressure homogenizer homogenization, parameters: pressure 800bar, time 10 minutes.

2.4 Spray the homogenized liquid, parameters: temperature 120 ° C, flow rate 500 ml / hour, nozzle 0.75 mm.

2.5 spray dry product to obtain nano-efficient cyfluthrin powder.

The nano-scale pesticide prepared by the invention has achieved satisfactory results in the field efficacy experiment, and the dosage forms used are all water-dispersible granules without organic solvent, which are obtained by the drying process in the examples provided by the patent. The method of use is to spray after watering.

In the field efficacy test, the nano-grade pesticide of this patent was compared with the commercially available vegetable insecticide Benedict (10% cyanamide sulphonic dispersing oil suspension), which was DuPont in 2015. A new generation of multi-spectrum insecticides launched in China in May.

The field efficacy test was carried out independently by the Jixian Plant Protection Station in Jiangxi Province. The three groups of data are as follows:

Field efficacy test 1

Field efficacy test 2

Field efficacy test 3

Claims (10)

1. A method for preparing a nanometer pesticide preparation by using a silica aerogel, wherein the application refers to a silica aerogel as a carrier for processing a nanometer preparation of a poorly soluble crude drug, and the processing steps are as follows:

   1 Solving the original pesticide or pulverizing the original pesticide with a solvent;

   2 a nanoparticle drug-loading system having a diameter of less than 100 nm formed by adsorbing a drug-containing solvent liquid or mixing the pulverized original drug with silica aerogel, wherein the silica aerogel is hydrophilic silica The aerogel or the hydrophobic silica aerogel has a hydrophilic silica aerogel after heat treatment, and the mass ratio of the original drug to the silica aerogel is 1:0.5-20, the heat treatment The temperature is 300 to 1000 ° C;

   3 adding water to the nanoparticle drug loading system, stirring or emulsification to homogenize the dispersion;

   4 Drying removes solvent and water to obtain a nano drug.
2. The method according to claim 1, wherein in the step 3, the emulsion is emulsified by an emulsifier, and the rotation speed is 10,000 to 30,000 rpm, and the time is 2 to 10 minutes.
3. The method according to claim 1, characterized in that in the step 3, the homogenizer is used for homogenization, the pressure is from 500 bar to 1500 bar, and the time is from 5 to 15 minutes.
4. The method of claim 1 wherein said nanomedicine is passed through a 100 mesh to 200 mesh screen in step 5.
5. The method according to claim 1, wherein the silica aerogel has a porosity of 95 to 99%, a pore diameter of 10 to 50 nm, a specific surface area of 200 to 1000 m ² /g, and a density of 3 to The colloidal particles of the composition network of 300 kg/m ^{3 have a} diameter of 1 to 50 nm.
6. The method of claim 1 wherein said solvent is ethanol or ethyl acetate.
7. The method according to claim 1, wherein the drying method comprises drying, lyophilizing and spray drying, the drying temperature is 60 ° C to 120 ° C; and the lyophilization temperature is -50 ° C to -70 ° C, The pressure is 0.1 to 10 Pa; the spray drying temperature is 120 to 220 °C.
8. The method of claim 1 wherein said nanopharmaceutical comprises various dosage forms comprising a nanoscale pesticide solid dispersion, a suspension formulation and a water formulation.
9. A nanomedicine prepared using silica aerogel.
10. The nanomedicine according to claim 9, wherein the nano drug is loaded with a drug content of >50%; the encapsulation efficiency is >90%; the drug-loaded microsphere specific surface area is >300 m ² /g; and the drug-loaded microspheres are loaded. The diameter is <5 μm.

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