Ultraviolet-light-responsive pesticide sustained-release preparation, preparation method and application thereof
阅读说明：本技术 一种紫外光响应的农药缓释制剂、制备方法及其应用 (Ultraviolet-light-responsive pesticide sustained-release preparation, preparation method and application thereof ) 是由 何涛 戚士章 夏彬 黄自云 张晓明 孙天赐 方蔚伟 于 2021-07-06 设计创作，主要内容包括：本发明涉及农药制备技术领域,具体涉及一种紫外光响应的农药缓释制剂、制备方法及其应用；将疏水性农药装载入具有紫外光响应的两亲性聚合物胶束中,其粒径在10-1000nm之间,载药量中2-70％之间。本发明公开的紫外光响应负载农药的聚合物胶束农药缓释制剂具有较高的载药量和紫外光缓释效果,实现在避光条件下稳定储存,在自然光/紫外光下缓慢释放。本发明的农药缓释制剂能够提高农药稳定性,可以降低用药量和施药次数,有助于环境保护。(The invention relates to the technical field of pesticide preparation, in particular to an ultraviolet light response pesticide slow release preparation, a preparation method and application thereof; the hydrophobic pesticide is loaded into the ultraviolet-responsive amphiphilic polymer micelle, the particle size of the hydrophobic pesticide is 10-1000nm, and the drug loading amount is 2-70%. The ultraviolet light response pesticide-loaded polymer micelle pesticide slow release preparation disclosed by the invention has higher drug loading capacity and ultraviolet light slow release effect, realizes stable storage under the condition of keeping out of the sun and slowly releases under natural light/ultraviolet light. The pesticide sustained-release preparation can improve the stability of the pesticide, can reduce the dosage and the application frequency, and is beneficial to environmental protection.)
1. The ultraviolet-responsive pesticide slow-release preparation is characterized by comprising a carrier corresponding to ultraviolet rays and a loaded pesticide, wherein the pesticide loading amount of the loaded pesticide is 2-70% of that of the carrier, and the particle size of the pesticide slow-release preparation is 10-1000 nm.
2. A method for preparing the ultraviolet light-responsive pesticide sustained release formulation as set forth in claim 1, comprising the steps of:
s1: preparing an amphiphilic polymer material with ultraviolet response: the hydrophilic chain segment and the hydrophobic chain segment are connected with two ends containing the o-nitrobenzyl alcohol ester through esterification reaction or substitution reaction, or the hydrophilic chain segment is connected with the hydrophobic chain segment consisting of the o-nitrobenzyl alcohol ester through copolymerization;
s2: preparing pesticide-loaded polymer micelles: and (4) dissolving the amphiphilic polymer with the ultraviolet light response and the pesticide obtained in the step (S1) in an organic solvent, then adding a water phase into the organic solvent, stirring for 1-24 h, carrying out reduced pressure distillation or dialysis to remove an organic phase, filtering to remove the unloaded pesticide, and drying to obtain the ultraviolet light response pesticide slow release preparation.
3. The method for preparing a UV-light responsive controlled-release formulation as claimed in claim 2, wherein the UV-light responsive amphiphilic polymer prepared in step S1 has a structural formula of Wherein R is1、R2Is a hydrophilic segment or a hydrophobic segment, R3Is H or CH3，R4Is a hydrophilic segment, n is5～100。
4. The method for preparing a UV-responsive pesticide sustained-release preparation as claimed in claim 3, wherein the hydrophilic segment is polyethylene glycol or polyvinyl alcohol, and the hydrophobic segment is polycaprolactone or polylactic acid.
5. The method for preparing an ultraviolet-responsive pesticide sustained-release preparation according to claim 2, wherein the mass ratio of the amphiphilic polymer to the pesticide in step S2 is 1-5: 1.
6. the method for preparing an ultraviolet-responsive pesticide sustained-release preparation as claimed in claim 2, wherein the organic solvent in the step S2 is any one of methanol, ethanol, tetrahydrofuran and DMSO.
7. The method for preparing an ultraviolet-responsive pesticide sustained-release preparation as claimed in claim 2, wherein the pesticide in the step S2 is any one of acetamiprid, emamectin benzoate and abamectin.
8. The method for preparing an ultraviolet-responsive pesticide sustained-release preparation as claimed in claim 2, wherein the aqueous phase in step S2 is any one of water, a PBS solution, a sodium chloride aqueous solution, and a PVA solution.
9. The method for preparing an ultraviolet-responsive pesticide sustained-release preparation as claimed in claim 2, wherein the volume ratio of the organic phase to the aqueous phase in the step S2 is 1: 1 to 15.
10. The use of the UV-light responsive pesticide slow release formulation of claim 1 for pest control.
Technical Field
The invention relates to the technical field of pesticide preparation, in particular to an ultraviolet-responsive pesticide sustained-release preparation, a preparation method and application thereof.
Background
The pesticide is widely applied to preventing and controlling crop diseases, insect pests and weeds, plays an important role in protecting the aspects of agricultural production and the like, and is an indispensable agricultural chemical for improving the agricultural yield and the quality of agricultural products. However, for the pesticide dosage forms which are used in large quantities at present, the pesticide dosage forms have the defects of low utilization rate of crops and pest targets, poor solubility and dispersibility, low utilization rate due to the large quantity of organic solvents, loss of most of pesticide active ingredients and the like. As a large population country, China has great demand on agricultural products and great demand on pesticides, the problem that pesticide residues of the agricultural products and water and soil pesticide residues exceed standards is very severe due to excessive pesticide application, non-target organisms and human health are threatened, and the structure and function protection of an ecological system is not facilitated.
In order to meet the market demand of pesticides, the pesticides must be developed in the directions of safety, high efficiency, economy and environmental protection. The pesticide sustained release preparation is a new pesticide formulation with target release, controllable release and long-term release, and becomes a recent research hotspot. For insoluble pesticides, the application of the polymer pesticide sustained-release preparation is beneficial to improving the drug-loading rate and the solubility, and is a pesticide preparation with a good application prospect.
The wavelength range of ultraviolet light (UV) is 10-400 nm, the content of the ultraviolet light in natural light is about 3%, wherein the wavelength range of UVA is 315-400nm, and accounts for 95% of the ultraviolet light reaching the surface. Ultraviolet light can degrade many organic materials, and UVA is also a significant cause of natural aging in many polymeric materials.
In view of the above-mentioned drawbacks, the inventors of the present invention have finally obtained the present invention through a long period of research and practice.
Disclosure of Invention
The invention aims to solve the problems of low utilization rate of crops and pest targets, poor solubility and dispersibility, low utilization rate due to the large amount of organic solvents, loss of most of pesticide active ingredients and the like in the pesticide dosage forms which are used in large quantities at present, and provides an ultraviolet-light-responsive pesticide slow-release preparation, a preparation method and application thereof.
In order to achieve the purpose, the invention discloses an ultraviolet-light-responsive pesticide slow-release preparation which comprises a carrier corresponding to ultraviolet rays and a loaded pesticide, wherein the pesticide-loading amount of the loaded pesticide is 2-70% of that of the carrier, and the particle size of the pesticide slow-release preparation is 10-1000 nm.
The invention also discloses an ultraviolet light response pesticide slow release preparation, which comprises the following steps:
s1: preparing an amphiphilic polymer material with ultraviolet response: the hydrophilic chain segment and the hydrophobic chain segment are connected to two ends of an o-nitrobenzyl alcohol ester structure through esterification reaction or substitution reaction, or the hydrophilic chain segment is copolymerized and connected with the hydrophobic chain segment consisting of the o-nitrobenzyl alcohol ester;
s2: preparing pesticide-loaded polymer micelles: and (4) dissolving the amphiphilic polymer with the ultraviolet light response and the pesticide obtained in the step (S1) in an organic solvent, then adding a water phase into the organic solvent, stirring for 1-24 h, carrying out reduced pressure distillation or dialysis to remove an organic phase, filtering to remove the unloaded pesticide, and drying to obtain the ultraviolet light response pesticide slow release preparation.
The amphiphilic polymer with ultraviolet response prepared in the step S1 has the structural formulaWherein R is1、R2Is a hydrophilic segment or a hydrophobic segment, R3Is H or CH3，R4Is a hydrophilic chain segment, and n is 5-100.
In the step S1, the hydrophilic segment is polyethylene glycol or polyvinyl alcohol, the hydrophobic segment is polycaprolactone or polylactic acid, and the hydrophilic segment and the hydrophobic segment are connected to two ends of the o-nitrobenzyl alcohol ester through esterification reaction or substitution reaction; or copolymerizing the hydrophilic chain segment and the monomer with the o-nitrobenzyl ester structure through controllable free radical polymerization to obtain the amphiphilic block copolymer. The average molecular weight of the hydrophilic chain segment is 1000-40000, and the average molecular weight of the hydrophobic chain segment is 1000-40000.
The mass ratio of the amphiphilic polymer with ultraviolet response to the pesticide in the step S2 is 1-5: 1.
the organic solvent in step S2 is any one of methanol, ethanol, tetrahydrofuran, and DMSO.
The pesticide in the step S2 is any one of acetamiprid, emamectin benzoate and abamectin.
The water phase in step S2 is any one of water, a PBS solution, a sodium chloride aqueous solution, and a PVA solution.
The volume ratio of the organic phase to the aqueous phase in the step S2 is 1: 1 to 15.
The invention also discloses application of the ultraviolet light response pesticide slow release preparation value in pest control. Under the action of ultraviolet light, the o-nitrobenzyl ester is subjected to hydrolytic breakage, so that the amphiphilic polymer is slowly cracked, and the loaded pesticide is slowly released.
Compared with the prior art, the invention has the beneficial effects that:
(1) according to the invention, by utilizing ultraviolet light in natural light, pesticides such as insoluble acetamiprid, emamectin benzoate and abamectin are loaded in the amphiphilic polymer micelle with ultraviolet response, so that the diffusion and loss of the pesticides in natural environment can be effectively reduced, meanwhile, the effective period of the pesticides is prolonged, the dosage is reduced, and the environment protection is facilitated.
(2) The pesticide slow release agent can slowly release pesticide under natural light conditions, the pesticide effect can be kept for more than 120 hours, the times of spraying the pesticide are reduced, the use amount is reduced, and the pesticide slow release agent is 1/10-1/40 of the conventional use amount.
(3) The pesticide slow release agent disclosed by the invention is simple in preparation process, the use of toxic organic solvents is obviously reduced compared with the conventional pesticide, a stabilizing agent is not added, and the amphiphilic polymer is composed of biodegradable polymers, so that white pollution is not caused, and the pesticide slow release agent is an environment-friendly pesticide preparation.
Drawings
FIG. 1 is a drawing showing the preparation of o-nitrobenzyl methacrylate in example 11H-NMR spectrum;
FIG. 2 is a drawing showing the preparation of o-nitrobenzyl methacrylate in example 113A C-NMR spectrum;
FIG. 3 is a transmission electron micrograph of the drug-loaded polymer micelle in example 1;
FIG. 4 is the acetamiprid-loaded polymer micelle dynamic light scattering test in example 2;
FIG. 5 is a graph of standard acetamiprid concentration-absorbance released from the acetamiprid-loaded polymer micelle of example 1;
FIG. 6 is a comparative photograph of the acetamiprid-loaded polymer micelle of example 1 before and after 120h xenon full spectrum exposure.
Detailed Description
The above and further features and advantages of the present invention are described in more detail below with reference to the accompanying drawings.
Example 1
The preparation method of the ultraviolet light response pesticide slow release preparation comprises the following steps:
s1: preparation of amphiphilic polymers with uv response:
(1) synthesis of O-nitrobenzyl Methacrylate (MANBA): 3.06g (0.2mol) of o-nitrobenzyl alcohol are dissolved in 20mL of dichloromethane, 2.3mL of triethylamine are added, stirring is carried out in an ice bath for 15 minutes, then 1.93mL (0.2mol) of methacryloyl chloride are added dropwise and stirring is carried out at room temperature for 6 hours. After the reaction is finished, the mixture is extracted for four times by deionized water, and dichloromethane is dried in a spinning way to obtain the yellow oily methacrylic acid o-nitrobenzyl alcohol ester.1The H-NMR spectrum is shown in figure 1,13C-NMR, as shown in FIG. 2, demonstrates the successful synthesis of o-nitrobenzyl Methacrylate (MANBA).
(2) Synthesis of mPEG-isobutyl bromide: weighing 4g mPEG4000-OH (1mmol) was dissolved in 20mL of dichloromethane, 0.15mL of triethylamine was added and stirred in an ice bath for 15 minutesThen, 0.13mL (1mmol) of bromoisobutyryl bromide was added, and the mixture was stirred at room temperature for 12 hours. After the reaction is finished, insoluble substances are removed by filtration, and then the insoluble substances are settled for 2 times in ice n-hexane to obtain white mPEG-isobutyl bromide.
(3) Synthesis of PEG-P-MANBA: 2g of mPEG-isobutyl bromide (0.5mmol), 70mg of cuprous bromide (0.5mmol) and 2.21g (10mmol) of MANBA were dissolved in 10mL of ethanol, then deoxygenated and nitrogen-charged by a freeze-pump-vent cycle, 85mg of N, N, N ', N ', N ' -Pentamethyldiethylenetriamine (PMDETA) were added with a microinjection needle and polymerized for 8 hours at room temperature. After the polymerization is finished, the mixture is settled for 2 times in ice hexane to obtain the white amphiphilic polymer PEG-P-MANBA.
S2: preparing acetamiprid-loaded polymer micelle: 1g of PEG-P-MANBA and 0.6g of acetamiprid were dissolved in 8mL of tetrahydrofuran, sonicated for 10 minutes to completely dissolve as an oil phase, and then added dropwise to 30mL of water using a syringe pump, and stirred at 500rpm for 8 hours to form a polymer micelle. The tetrahydrofuran was then dried by spinning at 25 ℃ and the resulting aqueous phase was filtered to remove insoluble material and dried for use. The transmission electron microscope detection shows that the morphology of the drug-loaded polymer micelle is as shown in FIG. 3, the size of the drug-loaded polymer micelle is about 80nm, and the polymer micelle is spherical with uniform monodisperse size, thereby proving the successful preparation of the drug-loaded polymer micelle.
Example 2
The preparation method of the ultraviolet light response pesticide slow release preparation comprises the following steps:
s1: preparation of amphiphilic polymers with uv response:
(1) synthesis of O-nitrobenzyl Methacrylate (MANBA): 6.12g (0.4mol) of o-nitrobenzyl alcohol are dissolved in 40mL of dichloromethane, 5mL of triethylamine are added, stirring is carried out in an ice bath for 15 minutes, 4mL (0.42mol) of methacryloyl chloride are subsequently added dropwise and stirring is carried out at room temperature for 6 hours. After the reaction is finished, the mixture is extracted for four times by deionized water, and dichloromethane is dried in a spinning way to obtain the yellow oily methacrylic acid o-nitrobenzyl alcohol ester.
(2) Synthesis of mPEG-isobutyl bromide: weighing 8g of mPEG4000-OH (2mmol) in 50mL of dichloromethane, 0.3mL of triethylamine added, stirring in an ice bath for 15 minutes followed by 0.3mL (2.2mmol) of bromo-bromideIsobutyryl bromide, stirred at room temperature for 12 hours. After the reaction is finished, insoluble substances are removed by filtration, and then the insoluble substances are settled for 2 times in ice n-hexane to obtain white mPEG-isobutyl bromide.
(3) Synthesis of PEG-P-MANBA: 2g mPEG-isobutyl bromide (0.5mmol), 70mg cuprous bromide (0.5mmol) and 4.42g (20mmol) MANBA were dissolved in 10mL ethanol, then deoxygenated and nitrogen charged by a freeze-pump-vent cycle, 85mg N, N, N ', N', Pentamethyldiethylenetriamine (PMDETA) was added with a microinjection needle and polymerized for 8 hours at room temperature. After the polymerization is finished, the mixture is settled for 2 times in ice hexane to obtain the white amphiphilic polymer PEG-P-MANBA.
S2: preparing acetamiprid-loaded polymer micelle: 2g of PEG-P-MANBA and 2g of acetamiprid were dissolved in 20mL of tetrahydrofuran, sonicated for 10 minutes to completely dissolve as an oil phase, and then added dropwise to 60mL of water using a syringe pump, and stirred at 500rpm for 8 hours to form a polymer micelle. The tetrahydrofuran was then dried by spinning at 25 ℃ and the resulting aqueous phase was filtered to remove insoluble material and dried for use. Dynamic light scattering tests show that the hydrated particle size of the polymer micelle loaded with the acetamiprid is about 150nm, as shown in FIG. 4.
The acetamiprid-loaded polymer micelle prepared in example 1 was subjected to release measurement under a full-spectrum xenon lamp: dissolving polymer micelle with effective acetamiprid content of 0.5g in 100mL of water, irradiating for 120h under a full-spectrum xenon lamp at a power of 100W for 1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h, 72h, 96h and 120h, and sampling. Placing 2mL of the taken sample in a dialysis bag, dialyzing in the dark for 48h, testing the absorption value at 278nm by a visible ultraviolet absorption spectrometer after dialysis is finished, calculating the content of acetamiprid according to the standard concentration-absorption value curve of acetamiprid, and drawing a release curve as shown in FIG. 5. As can be seen from the figure, the release rate increases with increasing exposure time. FIG. 6 is a comparison photograph before and after 120h irradiation by a full-spectrum xenon lamp, and it can be seen from the picture that after the o-nitrobenzyl ester is broken, the solution is changed from light yellow to yellow.
The foregoing is merely a preferred embodiment of the invention, which is intended to be illustrative and not limiting. It will be understood by those skilled in the art that various changes, modifications and equivalents may be made therein without departing from the spirit and scope of the invention as defined in the appended claims.