CN103766351B - A kind of nano pesticide composition and method of making the same - Google Patents
A kind of nano pesticide composition and method of making the same Download PDFInfo
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- CN103766351B CN103766351B CN201410052118.9A CN201410052118A CN103766351B CN 103766351 B CN103766351 B CN 103766351B CN 201410052118 A CN201410052118 A CN 201410052118A CN 103766351 B CN103766351 B CN 103766351B
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- 239000005760 Difenoconazole Substances 0.000 claims description 2
- IWDQPCIQCXRBQP-UHFFFAOYSA-M Fenaminosulf Chemical compound [Na+].CN(C)C1=CC=C(N=NS([O-])(=O)=O)C=C1 IWDQPCIQCXRBQP-UHFFFAOYSA-M 0.000 claims description 2
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- OIPMQULDKWSNGX-UHFFFAOYSA-N bis[[ethoxy(oxo)phosphaniumyl]oxy]alumanyloxy-ethoxy-oxophosphanium Chemical compound [Al+3].CCO[P+]([O-])=O.CCO[P+]([O-])=O.CCO[P+]([O-])=O OIPMQULDKWSNGX-UHFFFAOYSA-N 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 2
- BQYJATMQXGBDHF-UHFFFAOYSA-N difenoconazole Chemical compound O1C(C)COC1(C=1C(=CC(OC=2C=CC(Cl)=CC=2)=CC=1)Cl)CN1N=CN=C1 BQYJATMQXGBDHF-UHFFFAOYSA-N 0.000 claims description 2
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- TVLSRXXIMLFWEO-UHFFFAOYSA-N prochloraz Chemical compound C1=CN=CN1C(=O)N(CCC)CCOC1=C(Cl)C=C(Cl)C=C1Cl TVLSRXXIMLFWEO-UHFFFAOYSA-N 0.000 claims description 2
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Abstract
The present invention relates to nano pesticide composition and method of making the same.Described preparation method comprises the following steps: the first solution mixes with the second solution and emulsification by (1), obtains the first emulsion; Described first solution contains amphipathic nature polyalcohol, hydrophobic pesticidal and organic solvent, and described second solution contains hydrophily agricultural chemicals and water; (2) step (1) gained first emulsion is mixed also emulsification with the 3rd solution containing emulsifier and water, obtain the second emulsion; (3) organic solvent in removing step (2) gained second emulsion, is separated and obtains nano pesticide composition.The present invention forms the principle of the nano-micelle of W/O/W by two newborn method according to amphipathic nature polyalcohol, hydrophily agricultural chemicals and hydrophobic pesticidal are wrapped respectively the different cystoblasts being loaded in nanocapsule, thus achieves hydrophily agricultural chemicals and passing altogether of hydrophobic pesticidal is carried.The present invention, by simple and easy to do method, solves the composite problem of hydrophily agricultural chemicals and hydrophobic pesticidal in nano pesticide.
Description
Technical field
The present invention relates to a kind of composition pesticide and preparation method thereof, particularly relate to a kind of nano pesticide composition and method of making the same.
Background technology
In recent years, be solve the problems such as consumption of organic solvent is large, pesticide efficacy is low in Traditional Agricultural pharmaceutically dosage form, the pesticides new formulation that research and development has slow controlled release, target deposition and an environmentally compatible characteristic has become the development trend of formulations of pesticide processing.Agricultural chemicals controlled release system is one of current main novel form, and mainly comprise nanocapsule and micron capsule, nanocapsule is compared with micron capsule, and particle diameter is less, and passive targeting is better; Specific surface area is larger, dispersed and permeability is better.
One of main selection of nanorize pharmaceutical carrier is amphipathic nature polyalcohol, and it has water-wet side and hydrophobic side, easily forms micella in aqueous, and micella is nano-scale normally, and particle size distribution range is narrower.Such as: polyethylene glycol-glycolic, polylactic acid-polyglycolic acid etc.The method that amphipathic nature polyalcohol prepares nanocapsule mainly contains double emulsion solvent volatilization-extraction (abbreviation multi-emulsion method), emulsification mechanism, nanoprecipitation method, and the hydrophilic and hydrophobic according to medicine can select diverse ways.Multi-emulsion method be wherein search time the earliest, the preparation method of a kind of nanocapsule that range of application is the widest, its technique is simple, and the microballoon medicine carrying content of preparation is high, and protein is distribution uniform in microballoon.
More complex preparation is had in Traditional Agricultural pharmaceutically dosage form, there is the complex preparation that report utilizes multi-emulsion method obtained at present, as CN 101617663A discloses a kind of bactericidal composition containing cyprodinil and own azoles alcohol using multi-emulsion method to obtain, CN 101884328A discloses a kind of bactericide containing epoxiconazole and jinggangmeisu prepared by available multi-emulsion method.Composite agricultural chemicals can reduce resistance risk, the increase control spectrum of agricultural chemicals.But, there is no the composite problem that technology solves hydrophilic agricultural chemicals and hydrophobic pesticide in pesticide nano capsule at present.And study the composite of hydrophobic drug and hydrophilic medicament in pesticide nano capsule, more wide application prospect will be provided for nano pesticide composition.
Summary of the invention
The nano pesticide composition that the object of the present invention is to provide a kind of preparation method of nano pesticide composition and obtained by method provided by the invention.The present invention forms the principle of the nano-micelle of W/O/W by two newborn method according to amphipathic nature polyalcohol, hydrophily agricultural chemicals and hydrophobic pesticidal are wrapped respectively the different cystoblasts being loaded in nanocapsule, thus achieve passing altogether of hydrophily agricultural chemicals and hydrophobic pesticidal and carry, solve the composite problem of hydrophily agricultural chemicals and hydrophobic pesticidal in nano pesticide.
In order to achieve the above object, the present invention adopts following technical scheme:
A preparation method for nano pesticide composition, comprises the following steps:
(1) the first solution is mixed also emulsification with the second solution, obtain the first emulsion;
Described first solution contains amphipathic nature polyalcohol, hydrophobic pesticidal and organic solvent, and described second solution contains hydrophily agricultural chemicals and water;
(2) step (1) gained first emulsion is mixed also emulsification with the 3rd solution containing emulsifier and water, obtain the second emulsion;
(3) organic solvent in removing step (2) gained second emulsion, is separated and obtains nano pesticide composition.
According to the present invention, in step (1), described amphipathic nature polyalcohol is can be the selection of general pharmaceutical composition preparation field routine, and such as, described amphipathic nature polyalcohol is the polymer simultaneously containing hydrophilic radical and hydrophobic group; Described hydrophilic radical can be one or more in polyethylene group, polyoxyethylene group and polyisobutene acid groups etc., and described hydrophobic group can be medium one or more of polyoxyethylene group, polylactic acid-glycollic acid group, polystyrene group and polycaprolactone group.It should be noted that, the arrangement mode not requirement especially of the repetitive of described amphipathic nature polyalcohol, in order to improve the result of use of described nano pesticide composition further, under preferable case, can for alternately, block, one or more in random or grafting, most preferably be two blockeds.
Wherein, the not special requirement of molecular weight of described amphipathic nature polyalcohol, in order to improve the result of use of described nano pesticide composition further, under preferable case, can be 10
4-10
5, more preferably 2 × 10
4-4 × 10
4.
According to the present invention, in step (1), described amphipathic nature polyalcohol does not have particular/special requirement, in order to improve the result of use of described nano pesticide composition further, as optimal technical scheme, preparation method of the present invention, amphipathic nature polyalcohol described in step (1) is one or more in MPEG-PLA-glycolic, polyethylene glycol or poly (l-lactic acid), is preferably MPEG-PLA-glycolic.Wherein, the hydrophilic radical of described MPEG-PLA-glycolic is poly glycol monomethyl ether group, hydrophobic grouping is polylactic acid-glycollic acid group, and the arrangement mode of the repetitive of described MPEG-PLA-ethanol copolymer is blocked.
According to the present invention, in step (1), described hydrophobic drug does not have particular/special requirement, the solvability in water can select according to desired drug effect and medicine, such as, the solvability in water can be selected to be less than the medicine of 0.5g/1000g as hydrophobic drug.Preferably, described hydrophobic pesticidal be Prochloraz, Difenoconazole, Tebuconazole, epoxiconazole, own azoles alcohol one or more.
According to the present invention, in step (1), the selection of described organic solvent does not have particular/special requirement, it can be the selection of general pharmaceutical composition preparation field routine, but reduce costs in order to the result of use that improves described nano pesticide composition further, preferably, described organic solvent can dissolve described amphipathic nature polyalcohol, but water insoluble, and under emulsification condition not with described amphipathic nature polyalcohol, described hydrophobic pesticidal and described hydrophily agricultural chemicals generation chemical reaction; Be preferably in carrene, chloroform or espeleton one or more, be preferably carrene and/or chloroform.
According to the present invention, in step (1), described hydrophilic medicament does not have particular/special requirement, solvability in water can select according to desired drug effect and medicine, such as, the solvability in water can be selected to be greater than the medicine of 1g/100g as hydrophobic drug, preferably, described hydrophily agricultural chemicals is jinggangmeisu, dislike mould spirit, copper sulphate, fenaminosulf, aliette one or more.
According to the present invention, in step (1), the not special requirement of volume ratio of described first solution and described second solution, but in order to improve the result of use of described nano pesticide composition further, as optimal technical scheme, preparation method of the present invention, described in step (1), the volume ratio of the first solution and described second solution is 500:1-2:1, be such as 5:1,10:1,30:1,60:1,90:1,150:1,250:1,300:1,400:1,490:1 etc., be preferably 100:1-10:1, more preferably 50:1.
According to the present invention, in step (1), in described first solution, the organic solvent relative to every milliliter, the not special requirement of content of described amphipathic nature polyalcohol, but in order to improve the result of use of described nano pesticide composition further, preferably, in described first solution, every milliliter of organic solvent contains described amphipathic nature polyalcohol 10-50 milligram, be such as 12 milligrams, 16 milligrams, 25 milligrams, 30 milligrams, 38 milligrams, 45 milligrams, 48 milligrams etc., be preferably 20 milligrams.
According to the present invention, in step (1), in described first solution, organic solvent relative to every milliliter, the not special requirement of content of described hydrophobic pesticidal, but in order to improve the result of use of described nano pesticide composition further, preferably, in described first solution, every milliliter of organic solvent contains described hydrophobic pesticidal 0.01-50 milligram, be such as 0.05 milligram, 0.2 milligram, 0.8 milligram, 1.5 milligram, 3 milligrams, 5 milligrams, 8 milligrams, 12 milligrams, 16 milligrams, 20 milligrams, 30 milligrams, 38 milligrams, 45 milligrams, 48 milligrams etc., be preferably 5-20 milligram, more preferably 10 milligrams.
According to the present invention, in step (1), in described second solution, organic solvent relative to every milliliter, the not special requirement of content of described hydrophily agricultural chemicals, but in order to improve the result of use of described nano pesticide composition further, preferably, in described second solution, every ml water contains described hydrophily agricultural chemicals 0.01-50 milligram, such as, be 0.05 milligram, 0.2 milligram, 0.8 milligram, 1.5 milligrams, 3 milligrams, 5 milligrams, 8 milligrams, 12 milligrams, 16 milligrams, 20 milligrams, 30 milligrams, 38 milligrams, 45 milligrams, 48 milligrams etc.
As optimal technical scheme, preparation method of the present invention, described in step (1), the mass ratio of amphipathic nature polyalcohol and described hydrophobic pesticidal is 10000:1-2:1, be such as 10:1,50:1,200:1,500:1,1000:1,2000:1,4000:1,6000:1,9000:1 etc., the mass ratio of described amphipathic nature polyalcohol and described hydrophily agricultural chemicals is 10000:1-2:1, such as, be 10:1,50:1,200:1,500:1,1000:1,2000:1,4000:1,6000:1,9000:1 etc.
Preferably, the mass ratio of described hydrophobic pesticidal and described hydrophily agricultural chemicals is 5000:1-1:5000, such as, be 1:4000,1:2000,1:500,1:100,1:1,400:1,1000:1,2000:1,3500:1,4500:1 etc.
According to the present invention, in step (2), described emulsifier does not have particular/special requirement, it can be the selection of general pharmaceutical composition preparation field routine, as optimal technical scheme, preparation method of the present invention, emulsifier described in step (2) is one or more in polyvinyl alcohol, F68, POLYSORBATE 80 or dodecyl sodium sulfate, is preferably polyvinyl alcohol and/or F68.
According to the present invention, in step (2), the volume ratio of described first emulsion and the 3rd solution does not have particular/special requirement, it can be the selection of general pharmaceutical composition preparation field routine, as optimal technical scheme, preparation method of the present invention, in step (2), the volume ratio of the first emulsion and the 3rd solution is 1:2-1:20, be such as 1:5,1:10,1:14,1:18 etc., be preferably 1:3.
According to the present invention, in step (2), in described 3rd solution, the content of emulsifier does not have particular/special requirement, in order to improve the result of use of described nano pesticide composition further, preferably, in described 3rd solution, every ml water contains described emulsifier 1-10 milligram, such as, be 2 milligrams, 5 milligrams, 7 milligrams, 9 milligrams etc., be preferably 1-4 milligram, more preferably 2 milligrams.
According to the present invention, in step (1) and step (2), described emulsification condition does not have particular/special requirement, it can be the selection of general pharmaceutical composition preparation field routine, as optimal technical scheme, preparation method of the present invention, the method of emulsification described in step (1) and step (2) adopt in ultrasonic cell-break machine emulsion process, high-speed shearing machine emulsion process or high pressure homogenizer emulsion process one or more, more preferably ultrasonic emulsification and/or high-speed shearing machine emulsification.
According to the present invention, in step (3), remove process and the not special requirement of method of described solvent, as optimal technical scheme, preparation method of the present invention, in step (3), the method for removing organic solvent is the method removing organic solvent using vacuum rotary steam;
In step (3), be separated and obtain in the process of described nano pesticide composition, the not special requirement of method of described separation, preferably, described is separated into by centrifugal segregation supernatant, obtains pharmaceutical composition.
Another object of the present invention is to provide a kind of nano pesticide composition, and it prepares according to the method in claim 1-8 described in any one.
As optimal technical scheme, nano pesticide composition of the present invention, wherein, described hydrophobic drug is own azoles alcohol, and described hydrophilic medicament is jinggangmeisu, and described amphipathic nature polyalcohol is MPEG-PLA-ethanol copolymer;
Preferably, wherein, the mass ratio of described amphipathic nature polyalcohol and described hydrophobic pesticidal is 10000:1-2:1, and the mass ratio of described amphipathic nature polyalcohol and described hydrophily agricultural chemicals is 10000:1-2:1;
Preferably, wherein, the mass ratio of described hydrophobic pesticidal and described hydrophily agricultural chemicals is 5000:1-1:5000.
Preparation method of the present invention is simple, solve the composite problem of hydrophily agricultural chemicals and hydrophobic pesticidal in nano pesticide composition, and the nano pesticide composition obtained by the inventive method passes through Toxicity Determination, demonstrate good control efficiency, better to the lasting effect of Rhizoctonia cerealis.
Accompanying drawing explanation
Fig. 1 is the image of the nano pesticide composition obtained in bioelectricity Microscopic observation embodiment 1;
Fig. 2 is the grain-size graph that laser particle analyzer records the nano pesticide composition that embodiment 1 obtains.
Embodiment
For ease of understanding the present invention, it is as follows that the present invention enumerates embodiment.Those skilled in the art should understand, described embodiment is only help to understand the present invention, should not be considered as concrete restriction of the present invention.
In the present invention, at the volume of gas and liquid is 20 DEG C, the numerical value of a normal atmosphere pressure.
Embodiment 1
(1) by the amphipathic nature polyalcohol (MPEG-PLA-glycolic of 20mg, mPEG-PLGA, purchased from Dai Gang bio tech ltd, Jinan, the hydrophilic radical of this single methoxypolyethylene glycol-polylactic-co-glycolic acid is poly glycol monomethyl ether group, hydrophobic grouping is polylactic acid-glycollic acid group, the arrangement mode of the repetitive of described MPEG-PLA-ethanol copolymer is blocked, and molecular weight is 2.5 × 10
4) and 2mg hydrophobic drug (own azoles alcohol) be dissolved in 1mL organic solvent (carrene), obtain the first solution; Be the drug solution of 40mg/mL by obtained concentration soluble in water for hydrophilic medicament (jinggangmeisu), obtain the second solution; Joined in the first solution by described 200 μ L second solution, utilize ultrasonic emulsification, power is 3%, and the time is 3 minutes, obtains the first emulsion.
(2) by emulsifier (polyvinyl alcohol, purchased from western Gansu Province chemical industry chemical reagent Co., Ltd, model is PVA-124, and saponification degree is 85mol%; Viscosity at 25 DEG C is 700mPas) be mixed with 2% aqueous solution, obtain the 3rd solution; First emulsion is joined in the 3rd solution of 10ml, utilizes ultrasonic emulsification, power is 5%, and the time is 5 minutes, obtains the second emulsion.
(3), under room temperature, rotary evaporation removing organic solvent, obtains the product after revolving steaming.To revolve the product after steaming under the centrifugal speed of 12000g after centrifugal 10 minutes, collecting precipitation, obtains nano pesticide composition.
According to document (Qing Xu, Deng. biomaterial (Biomaterials), 2012,33, method 1627-1639), in the nano pesticide composition (see figure 1) that bioelectricity Microscopic observation the present embodiment obtains, in typical spheroidal, particle size is about 300nm.
According to document (Qing Xu, Deng. biomaterial (Biomaterials), 2012,33, method 1627-1639), the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is that 257.13 ± 5.61nm(is shown in Fig. 2), dispersity is 0.282.
According to document (Qing Xu, Deng. biomaterial (Biomaterials), 2012,33, method 1627-1639), dissolve with acetonitrile after the nano pesticide composition freeze drying that the present embodiment is obtained, (standard items are purchased from Agilent Technologies to utilize high performance liquid chromatography to detect, trade mark Agilent1200series) medicament contg in composition pesticide, record containing own azoles alcohol 0.02 milligram in every gram of nano pesticide composition, jinggangmeisu 0.076 milligram.
Comparative example 1
The present embodiment prepares nano pesticide composition according to the method identical with embodiment 1, and difference is, in described first solution, the concentration of own azoles alcohol is 0mg/ml.
According to the measuring method identical with embodiment 1, the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is 232nm; Record in every gram of nano pesticide composition containing jinggangmeisu 0.076 milligram.
Comparative example 2
The present embodiment prepares nano pesticide composition according to the method identical with embodiment 1, and difference is, in described second solution, the concentration of jinggangmeisu is 0mg/ml.
According to the measuring method identical with embodiment 1, the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is 244.8nm; Record in every gram of nano pesticide composition containing own azoles alcohol 0.021 milligram.
Embodiment 2
The present embodiment prepares nano pesticide composition according to the method identical with embodiment 1, difference is, by the amphipathic nature polyalcohol (MPEG-PLA-glycolic of 20mg, mPEG-PLGA, purchased from Dai Gang bio tech ltd, Jinan, the hydrophilic radical of this MPEG-PLA-ethanol copolymer is poly glycol monomethyl ether group, hydrophobic grouping is polylactic acid-glycollic acid group, the arrangement mode of the repetitive of described MPEG-PLA-ethanol copolymer is blocked, and molecular weight is 4.5 × 10
4) and 2mg hydrophobic drug (own azoles alcohol) be dissolved in 1ml organic solvent (carrene), obtain the first solution.
According to the measuring method identical with embodiment 1, the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is 260.3nm; Record containing own azoles alcohol 0.021 milligram in every gram of nano pesticide composition, jinggangmeisu 0.077 milligram.
Embodiment 3
The present embodiment prepares nano pesticide composition according to the method identical with embodiment 1, and difference is, described amphipathic nature polyalcohol is poly (l-lactic acid).
According to the measuring method identical with embodiment 1, the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is 2980.3nm; Record containing own azoles alcohol 0.021 milligram in every gram of nano pesticide composition, jinggangmeisu 0.075 milligram.
Embodiment 4
The present embodiment prepares nano pesticide composition according to the method identical with embodiment 1, and difference is, the volume of described second solution is 2 μ L.
According to the measuring method identical with embodiment 1, the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is 241.2nm; Record containing own azoles alcohol 0.021 milligram in every gram of nano pesticide composition, jinggangmeisu 0.001 milligram.
Embodiment 5
The present embodiment prepares nano pesticide composition according to the method identical with embodiment 1, and difference is, the concentration of described second solution is 10mg/mL, and volume is 500 μ L.
According to the measuring method identical with embodiment 1, the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is 277.2nml; Record containing own azoles alcohol 0.018 milligram in every gram of nano pesticide composition, jinggangmeisu 0.035 milligram.
Embodiment 6
The present embodiment prepares nano pesticide composition according to the method identical with embodiment 1, and difference is, in described first solution, the concentration of own azoles alcohol is 10mg/mL, and in described second solution, the concentration of jinggangmeisu is 0.01mg/mL.
According to the measuring method identical with embodiment 1, the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is 274.2nm; Record containing own azoles alcohol 0.07 milligram in every gram of nano pesticide composition, jinggangmeisu 0.035 microgram.
Embodiment 7
The present embodiment prepares nano pesticide composition according to the method identical with embodiment 1, and difference is, in described first solution, the concentration of own azoles alcohol is 0.01mg/mL, and in described second solution, the concentration of jinggangmeisu is 10mg/mL.
According to the measuring method identical with embodiment 1, the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is 261.3nm; Record containing own azoles alcohol 0.04 microgram in every gram of nano pesticide composition, jinggangmeisu 0.064 milligram.
Embodiment 8
The present embodiment prepares nano pesticide composition according to the method identical with embodiment 1, and difference is, the volume of described 3rd solution is 2.4mL.
According to the measuring method identical with embodiment 1, the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is 256.9nm; Record containing own azoles alcohol 0.018 milligram in every gram of nano pesticide composition, jinggangmeisu 0.073 milligram.
Embodiment 9
The present embodiment prepares nano pesticide composition according to the method identical with embodiment 1, and difference is, the volume of described 3rd solution is 24mL.
According to the measuring method identical with embodiment 1, the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is 258.1nm; Record containing own azoles alcohol 0.019 milligram in every gram of nano pesticide composition, jinggangmeisu 0.073 milligram.
Embodiment 10
The present embodiment prepares nano pesticide composition according to the method identical with embodiment 1, and difference is, in step (1), utilizes high-speed shearing machine emulsification, and frequency is 14000rpm, and emulsification times is 5 minutes.
According to the measuring method identical with embodiment 1, the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is 260nm; Record containing own azoles alcohol 0.02 milligram in every gram of nano pesticide composition, jinggangmeisu 0.073 milligram.
Embodiment 11
The present embodiment prepares nano pesticide composition according to the method identical with embodiment 1, and difference is, in step (2), utilizes high-speed shearing machine emulsification, and frequency is 14000rpm, and emulsification times is 5 minutes.
According to the measuring method identical with embodiment 1, the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is 257.70nm; Record containing own azoles alcohol 0.019 milligram in every gram of nano pesticide composition, jinggangmeisu 0.076 milligram.
Embodiment 12
The present embodiment prepares nano pesticide composition according to the method identical with embodiment 1, and difference is, in step (1) and (2), utilize high-speed shearing machine emulsification, frequency is 14000rpm, and emulsification times is 5 minutes.
According to the measuring method identical with embodiment 1, the particle diameter utilizing laser particle analyzer to record the nano pesticide composition that the present embodiment obtains is 259.0nm; Record containing own azoles alcohol 0.019 milligram in every gram of nano pesticide composition, jinggangmeisu 0.075 milligram.
Toxicity Determination
Embodiment 1 is obtained Nano-particulate medicinal composition as Experimental agents, carries out Toxicity Determination.Under aseptic technique, with micropipettor, from low concentration to high concentration, successively to every bottle of heating and melting containing in quantitative sterilizing PDA medium, inject high concentration mother liquor to be measured (mother liquid concentration is 1000 times of test concentrations), fully shake up, be dispensed in 3 culture dishes, the pastille making respective concentration is dull and stereotyped.
Experiment process:
Contrast: sterile water and unloaded nano particle;
Medicament contrasts: well ridge own azoles alcohol wetting powder (seven concentration gradients);
The own azoles alcohol of jinggangmeisu cotransports nano particle (seven concentration gradients);
Each process in triplicate.
Aseptically, be that the card punch of 5mm cuts bacterium cake from colony edge with internal diameter, dislocation is in band medicine medium central authorities, and mycelia faces down and mycelia face is contacted with medium; Place 1 bacterium cake in each culture dish, be placed in incubator, cultivation temperature 28 DEG C.Described mycelia is Rhizoctonia cerealis.
After cultivation 72h (observe every day afterwards and measure colony diameter), measure colony diameter by slide measure right-angled intersection method, get its mean value.Calculate the mycelial growth inhibition rate of each concentration process of each medicament.Embodiments of the invention 1-12 and the obtained composition pesticide of comparative example 1,2 to the result of the test of Rhizoctonia cerealis in table 1.
Developing restraint rate (%)=(contrast bacterium colony diffusion diameter-process bacterium colony diffusion diameter)/(contrast bacterium colony diffusion diameter-5) × 100%
Experimental result confirms, nano pesticide composition illustrates good control efficiency for Rhizoctonia cerealis, and lasting effect is particularly remarkable.Test by same method Rhizoctonia solani, result shows composition pesticide Rhizoctonia solani of the present invention also good control efficiency effect.
Table 1
As can be seen from Table 1:
Drawn with comparing of comparative example 1,2 by embodiment 1: the drug effect of the composite nano particle of well ridge own azoles alcohol is better than the drug effect sum individually using jinggangmeisu nano particle and own azoles alcohol nano particle, and the composite drug effect of visible two kinds of medicines is better;
Embodiment 1 drug effect compared with embodiment 10,11 is almost suitable, utilizes simple preparation technology also can obtain the composite nano particle of drug effect good well ridge own azoles alcohol as seen, high-speed shearing machine can be utilized to be easy to large-scale production.
In addition, although own azoles alcohol drug effect is very high, easily produce chemical injury of crops in actual use, and the adding to reduce and produce the risk of chemical injury of crops of jinggangmeisu, namely both with the use of both good drug effect can be obtained, also can reduce simultaneously and use the side effect that brings of agricultural chemicals as chemical injury of crops.
Applicant states, the present invention illustrates detailed process equipment and process flow process of the present invention by above-described embodiment, but the present invention is not limited to above-mentioned detailed process equipment and process flow process, namely do not mean that the present invention must rely on above-mentioned detailed process equipment and process flow process and could implement.Person of ordinary skill in the field should understand, any improvement in the present invention, to equivalence replacement and the interpolation of auxiliary element, the concrete way choice etc. of each raw material of product of the present invention, all drops within protection scope of the present invention and open scope.
Claims (17)
1. a preparation method for nano pesticide composition, comprises the following steps:
(1) the first solution is mixed also emulsification with the second solution, obtain the first emulsion;
Wherein, the volume ratio of described first solution and described second solution is 500:1-2:1;
Described first solution contains amphipathic nature polyalcohol, hydrophobic pesticidal and organic solvent, and described second solution contains hydrophily agricultural chemicals and water;
(2) step (1) gained first emulsion is mixed also emulsification with the 3rd solution containing emulsifier and water, obtain the second emulsion; Wherein, the volume ratio of the first emulsion and the 3rd solution is 1:2-1:20;
(3) organic solvent in removing step (2) gained second emulsion, is separated and obtains nano pesticide composition;
Described in step (1), the mass ratio of amphipathic nature polyalcohol and described hydrophobic pesticidal is 10000:1-2:1, and the mass ratio of described amphipathic nature polyalcohol and described hydrophily agricultural chemicals is 10000:1-2:1; The mass ratio of described hydrophobic pesticidal and described hydrophily agricultural chemicals is 5000:1-1:5000;
Wherein, described in step (1), organic solvent can dissolve described amphipathic nature polyalcohol, but water insoluble, and under emulsification condition not with described amphipathic nature polyalcohol, described hydrophobic pesticidal and described hydrophily agricultural chemicals generation chemical reaction.
2. preparation method according to claim 1, is characterized in that, amphipathic nature polyalcohol described in step (1) is one or more in MPEG-PLA-glycolic, polyethylene glycol or poly (l-lactic acid).
3. preparation method according to claim 1, is characterized in that, hydrophobic pesticidal described in step (1) be Prochloraz, Difenoconazole, Tebuconazole, epoxiconazole, own azoles alcohol one or more.
4. preparation method according to claim 1, is characterized in that, described organic solvent is one or more in carrene, chloroform or espeleton.
5. preparation method according to claim 1, is characterized in that, hydrophily agricultural chemicals described in step (1) is jinggangmeisu, dislike mould spirit, copper sulphate, fenaminosulf, aliette one or more.
6. the method according to any one of claim 1-5, is characterized in that, in the first solution described in step (1), every milliliter of organic solvent contains described amphipathic nature polyalcohol 10-50 milligram.
7. the method according to any one of claim 1-5, is characterized in that, in the first solution described in step (1), every milliliter of organic solvent contains described hydrophobic pesticidal 0.01-50 milligram.
8. the method according to any one of claim 1-5, is characterized in that, in the second solution described in step (1), every ml water contains described hydrophily agricultural chemicals 0.01-50 milligram.
9. the method according to any one of claim 1-5, is characterized in that, emulsifier described in step (2) is one or more in polyvinyl alcohol, F68, POLYSORBATE 80 or dodecyl sodium sulfate.
10. the method according to any one of claim 1-5, is characterized in that, in the 3rd solution described in step (1), every ml water contains described emulsifier 1-10 milligram.
11. methods according to any one of claim 1-5, it is characterized in that, the method for emulsification described in step (1) and step (2) adopt in ultrasonic cell-break machine emulsion process, high-speed shearing machine emulsion process or high pressure homogenizer emulsion process one or more.
12. methods according to any one of claim 1-5, is characterized in that, in step (3), the method for removing organic solvent is the method removing organic solvent using vacuum rotary steam.
13. methods according to any one of claim 1-5, it is characterized in that, being separated into by centrifugal segregation supernatant described in step (3), obtains pharmaceutical composition.
14. 1 kinds of nano pesticide compositions, is characterized in that, prepare according to the method in claim 1-13 described in any one.
15. nano pesticide compositions according to claim 14, is characterized in that, wherein, described hydrophobic drug is own azoles alcohol, and described hydrophilic medicament is jinggangmeisu, and described amphipathic nature polyalcohol is MPEG-PLA-ethanol copolymer.
16. nano pesticide compositions according to claims 14 or 15, it is characterized in that, wherein, the mass ratio of described amphipathic nature polyalcohol and described hydrophobic pesticidal is 10000:1-2:1, and the mass ratio of described amphipathic nature polyalcohol and described hydrophily agricultural chemicals is 10000:1-2:1.
17. nano pesticide compositions according to claims 14 or 15, it is characterized in that, wherein, the mass ratio of described hydrophobic pesticidal and described hydrophily agricultural chemicals is 5000:1-1:5000.
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| CN104255715A (en) * | 2014-09-01 | 2015-01-07 | 李晓枫 | Nano biopesticide composition and preparation method thereof |
| US11172675B2 (en) * | 2014-12-22 | 2021-11-16 | Oro Agri Inc. | Nano particulate delivery system |
| CN106942256A (en) * | 2017-02-20 | 2017-07-14 | 北京林业大学 | A kind of new preparation method for containing thiacloprid and the protein nano ball of pheromones |
| CN107954778A (en) * | 2017-11-27 | 2018-04-24 | 岳西县天泰化工有限责任公司 | A kind of production method of foliar fertilizer |
| CN108245484B (en) * | 2017-12-27 | 2020-02-21 | 国家纳米科学中心 | Nano-medicine composition and preparation method and application thereof |
| CN108684688A (en) * | 2018-06-14 | 2018-10-23 | 国家纳米科学中心 | A kind of nano pesticide composition and preparation method thereof |
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