CN1883266A - A snail-killing medicine-nano suspension concentrate of niclosamide ethanolamine and method for preparing same - Google Patents
A snail-killing medicine-nano suspension concentrate of niclosamide ethanolamine and method for preparing same Download PDFInfo
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- CN1883266A CN1883266A CN 200610088237 CN200610088237A CN1883266A CN 1883266 A CN1883266 A CN 1883266A CN 200610088237 CN200610088237 CN 200610088237 CN 200610088237 A CN200610088237 A CN 200610088237A CN 1883266 A CN1883266 A CN 1883266A
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Abstract
The invention provides a niclosamide nano suspending agent as a medicament for controlling oncomelania hupensis and its preparing process, wherein the basic constituents include (by weight percent) niclosamide 15-25%, water-soluble high polymer 0.05-0.5%, surface active agent 3-15%, defoaming agent 1-10%, and balancing water as dispersion medium.
Description
Technical field
A kind of snail-killing medicine-nano suspension concentrate of niclosamide ethanolamine and preparation method thereof belongs to the nanometer formulation technical field of snail-killing medicine and insoluble medicine.
Background technology
Along with the development of nanometer technology, the nanorize of insoluble drug is the important channel of research and development high-efficiency preparation.The nanometer formulation specific surface of insoluble drug is big, degree of scatter is high, can improve the solvability of medicine, makes that medicine is easier to be absorbed by organism, can better bring into play drug effect; Secondly, nano particle is because its particle diameter is very little, penetrates biomembrane in epidermis and the body easilier, conveniently enters the focus of organism, improves bioavailability of medicament; Simultaneously, nano particle combines with carrier, can also solve active ingredient slowly-releasing and target problem preferably.
Obtain medicament nano-preparation two kinds of methods are arranged usually: a kind of is to select suitable solvent (or additive method) that it is separated into molecule or ionic state earlier, control its cohesion again and form nano particle, methods such as solvent conversion method, solvent evaporation method are arranged usually, also be referred to as " Bottom-up " method; Another kind is with the finished product physical method disperse particlesization of medicine, adds various auxiliary reagents simultaneously and keeps its stability, thereby make nanometer formulation, and methods such as Ball milling, ultrasonic dispersion are arranged usually, is referred to as " Top-down " method.
Niclosamidum: ISO adopted name: niclosamide; Chemical name is 2 ', 5-two chloro-4 '-the nitro salicylanilide.
Structural formula:
Molecular formula: C
13H
8Cl
2N
2O
4Molecular weight: 327.1 (calculating) by international atomic weight table in 2000; Fusing point: 230 ℃; Vapour pressure (20 ℃) :≤1mPa; Solvability (mg/l, 20 ℃): in the water during pH6.4,1.6; During pH9.1,110; Stability: 208 ℃ of decomposition, meet strong acid or highly basic hydrolysis, hard water is to the not influence of its biologically active.
Niclosamidum (Niclosamide) has been the molluscacide that the unique recommendation of WHO is used since 1972, domesticly prepares niclosamidum in generation nineteen sixty.This medicine is insoluble in water, can be dissolved in organic solvent or alkaline solution.Usually niclosamidum can be made into 50% niclosamidum paste (Niclosamide), is used to kill oncomelania.Because its poorly water-soluble, improvement research to Yomesan both at home and abroad never stops, the most frequently used have 70% niclosamide wetting powder or emulsion, 50% a bayluscid wetting powder, also has niclosamidum piperazine salt (as Bayer 9045) and niclosamidum-hyrate (as Mansonil-M) etc. in addition.Because the dissolubility of the various pulvis of niclosamidum is with dispersed undesirable, fritter shape precipitation is easily stopped up drug-spraying instrument, causes use difficulty and liquor strength inhomogeneous, causes sn ail control effect to descend.
Summary of the invention
The purpose of this invention is to provide a kind of snail-killing medicine-nano suspension concentrate of niclosamide ethanolamine and preparation method thereof; adopting the Ball milling method to carry out physics disperses; with the niclosamidum micronize, be prepared into nano suspension concentrate to improve molluscicidal effect, lay the foundation for further developing the niclosamidum nanometer formulation.
Technical scheme of the present invention: a kind of snail-killing medicine-nano suspension concentrate of niclosamide ethanolamine, the mass content of its solvent is: niclosamidum 15%-25%, water soluble polymer 0.05%-0.5%, surfactant 3%-15%, defoamer 1%-10%, all the other are dispersion medium water; The particle diameter of niclosamidum particulate is 50nm-1 μ m.
Water soluble polymer is a polyoxyethylene, polyvinyl alcohol, polyacrylamide, or polyvinylpyrrolidone.
Surfactant is a Tween-80, or neopelex.
Defoamer is a methyl-silicone oil, or organosilicon X-10.
The preparation method of this niclosamidum nano suspension concentrate at first prepares burden by the mass content prescription, niclosamidum 15%-25%, water soluble polymer 0.05%-0.5%, surfactant 3%-15%, defoamer 1%-10%, all the other are dispersion medium water, after the mixing, adopt Ball milling method ball milling, the ball material mass ratio of abrading-ball and material total amount is 10: 1-20: 1, abrading-ball is a zirconia ball, diameter is 1mm-8mm, and rotating speed is 200r/min-1000r/min, ball milling time 40-120h.
The present invention adopts the mechanical lapping technology, is aided with auxiliary agents such as dispersion aids, suspension aid, grinding aid, defoamer, and the insoluble drugs niclosamidum is separated into the nano particle suspending agent.
Water soluble polymer plays stabilization to niclosamidum ultra-fine grain suspension system, and adopting high molecular weight water soluble polymer that the niclosamidum ultra-fine grain is protected is to micron, so that the key of lower particle diameter particle with the niclosamidum ball milling.Adding water soluble high molecular polymer not, form easily and grow to 10 microns acicular crystal, even if long-time the grinding also is difficult to further refinement, this is owing in the suspension system niclosamidum that far exceeds solvability is arranged, and very easily forms new crystal by the dissolution precipitation balance in water.
After adopting the high molecular weight water soluble polymer protection, can just play the effect that improves the ball milling effect at the ball milling initial stage that begins, and after particle forms, protect.With the polyoxyethylene is example, and the polyoxyethylene aqueous solution when 1 ‰ is medium, under the same terms niclosamidum is carried out ball milling and finds after 1 hour that the ratio of granule niclosamidum crystal is obviously more than not adding polyoxyethylated medium system.
Select for use suitable surfactant can disperse the niclosamidum particle preferably.
Add a certain amount of defoamer and can when ball milling, reduce the generation of foam.
Different ratios of grinding media to material are remarkable to the ball milling influential effect.20: 1 ratio of grinding media to material can reach micron particles the fast a few hours than 10: 1, and as ball milling 7 hours, 20: 1 o'clock existing 90% particle of ratio of grinding media to material was less than 5 microns, and ratio of grinding media to material also had the acicular crystal of a large amount of nearly 20 microns to exist at 10: 1 o'clock.
Drum's speed of rotation also has similar influence.Be all 2g material total amount, ratio of grinding media to material 20: 1, when rotating speed was 200r/min, ball milling had the above bulky grain of 20 a large amount of microns to exist after 7 hours in the sample.When rotating speed was 600r/min, particle size was below 5 microns in the sample.
So, when the preparation ultra-fine grain, should select high as far as possible rotating speed for use, big as far as possible ratio of grinding media to material so just can obtain finer particle with the short time.As to select rotating speed for use be 500r/min, ratio of grinding media to material 20: 1, and the ball milling time is 20 hours, can obtain the particles of great majority less than 1 μ m.As seen ratio of grinding media to material is very significant to the influence of ball milling effect.
The influence of abrading-ball size.Select nylon jar and diameter 8mm, 4mm, 1mm abrading-ball for use, to material total amount 2g (25% niclosamidum, 10% Tween 80,1 ‰ polyoxyethylene, methyl-silicone oil 5%, all the other are water), ground 40 hours, find that big abrading-ball makes broad particle distribution, and two peaks appear, two kinds of abrading-balls of 4mm and 1mm all can effectively grind narrow particle size distribution, the less niclosamidum particulate samples of granularity.Table 1 is for grinding back niclosamidum particle size statistics.
Table 1 abrading-ball size is to the influence (grinding rate 600r/min) of niclosamidum particle size
| Prescription | Abrading-ball size/ball milling time | DMax | D50 | D90 |
| 25% niclosamidum, 10% Tween 80,1 ‰ polyoxyethylene, methyl-silicone oil 5%, water, sample total amount 2g, ratio of grinding media to material 20: 1 | (every jar is 8 in the big ball of 8mm to 8mm abrading-ball/100h 4mm abrading-ball/100h mixing and ball milling; 50 mixing of 4mm bead)/20h; take out back diameter 1mm, 25 gram abrading-balls grind 80h | 152nm 108nm 71nm | 239nm 106nm 81nm | 787nm 318nm 164nm |
Beneficial effect of the present invention: adopt the Ball milling method that the insoluble medicine niclosamidum further is ground to nanoscale size and kill the oncomelania effect to improve.With ball grinding method niclosamidum is separated into particle diameter and reaches below 100 nanometers, and studied the molluscicidal effect of nanometer niclosamidum suspension, lay the foundation for further developing the niclosamidum nanometer formulation.
Description of drawings
The different abrading-balls of Fig. 1 are to influence (red line is the quad lines of a) the ball radius a:8mm of grinding effect; B:4mm; C: earlier with mixer mill ball milling 20h, again with 1mm abrading-ball mill 80h
Fig. 2 particulate scan electromicroscopic photograph
Embodiment
Embodiment 1: the preparation of niclosamidum nano suspension concentrate
Prescription: niclosamidum 25%, polyoxyethylene 0.1%, Tween-80 10%, methyl-silicone oil 5%, all the other are water, are made into the sample total amount of 20g.
Adopt zirconia ball, ratio of grinding media to material is 20: 1, and rotating speed is 1000r/min, mixes with big ball of diameter 8mm and 4mm bead earlier, and the sizes of balls weight ratio is 1: 2, and abrading-ball ground 5-40 hour, grinds 20-100 hour with diameter 1mm abrading-ball then.
Embodiment 2: the preparation of niclosamidum nano suspension concentrate
Prescription: niclosamidum 15%, polyvinyl alcohol 0.05%, neopelex 15%, methyl-silicone oil 10%, all the other are water, are made into the sample total amount of 20g.
Adopt zirconia ball, ratio of grinding media to material is 10: 1, and rotating speed is 200r/min, grinds 5-40 hour with diameter 4mm abrading-ball earlier, grinds 20-100 hour with diameter 1mm abrading-ball then.
Embodiment 3: the preparation of niclosamidum nano suspension concentrate
Prescription: niclosamidum 20%, polyacrylamide 0.5%, Tween-80 3%, organosilicon X-10 1%, all the other are water, are made into the sample total amount of 20g.
Adopt zirconia ball, ratio of grinding media to material is 15: 1, and rotating speed is 600r/min, grinds 5-40 hour with diameter 8mm abrading-ball earlier, grinds 20-100 hour with diameter 1mm abrading-ball then.
Embodiment 4: oncomelania effect is extremely soaked in the laboratory
25 ℃ of laboratories with 20% niclosamidum nano suspension concentrate preparation niclosamidum effective ingredient concentration be 0.5000,0.2500,0.1250,0.0625 and 0.0313mg/L soak and kill spiral shell 24h, 48h and 72h, use 50% bayluscid wetting powder (WPN) to compare test simultaneously.Niclosamidum nano suspension concentrate effective ingredient concentration 0.125mg/L soaks oncomelania and becomes spiral shell 24h, and killing snail rate can reach 100%, LC
50Be 0.0544mg/L, the LC of 50% bayluscid wetting powder (WPN)
50Be 0.1250mg/L, nano suspension concentrate has molluscicidal effect (table 2) preferably.
Oncomelania result is extremely soaked in table 2 laboratory
| Formulation | Time (h) | Different valid density (mg/l) mortality of snails (%) | ||||
| 0.5000 | 0.250 | 0.125 | 0.0625 | 0.0313 | ||
| Nano suspension concentrate WPN | 24 48 24 48 | 100.0 100.0 100.0 100.0 | 100.0 100.0 100.0 100.0 | 100.0 100.0 40.0 60.0 | 70.0 70.0 10.0 10.0 | 0 0 0 0 |
Embodiment 5: oncomelania effect is extremely soaked at the scene
Selecting scene, beach, Dantu District river, Zhengjiang City, Jiangsu Province to soak kills, 20% niclosamidum nano suspension concentrate consumption is 2.0,1.0mg/L (niclosamidum effective ingredient concentration 0.4,0.2mg/L), soak and kill in 1d, 2d, the 3d spiral shell bag and the interior mortality of snails (seeing Table 3,4) of earth in the ditch; Mortality of snails 80.00%, 91.88% and 95.65% in the earth in the mortality of snails 76.00%, 90.00% and 98.00% in WPN 2.0mg/L (effective ingredient concentration 1.0mg/L) the spiral shell bag, ditch.The result shows that working as nano suspension concentrate soaks extremely with 1.0mg/L (niclosamidum effective ingredient concentration 0.2mg/L), its molluscicidal effect and WPN 2.0mg/L (niclosamidum effective ingredient concentration 1.0mg/L) are close, and the niclosamidum nano suspension concentrate soaks extremely that the oncomelania effect is significantly improved than WPN.
The interior oncomelania result of spiral shell bag is extremely soaked at table 3 scene
| Formulation | Valid density (mg/l) | Mortality of snails (%) | ||
| 1d | 2d | 3d | ||
| The contrast of nano suspension concentrate nano suspension concentrate wetting powder clear water | 0.4 0.2 1.0 0 | 94.0 92.0 76.0 0 | 100.0 98.0 90.0 0 | 100.0 100.0 98.0 0 |
The interior oncomelania result of earth is extremely soaked at table 4 scene
| Formulation | Valid density (mg/l) | Mortality of snails (%) | ||
| 1d | 2d | 3d | ||
| The contrast of nano suspension concentrate nano suspension concentrate wetting powder clear water | 0.4 0.2 1.0 0 | 94.78 92.82 80.0 0.67 | 95.52 95.31 91.88 0.96 | 100.0 98.51 95.65 1.9 |
Embodiment 6: the on-the-spot sprinkling killed the oncomelania effect
Select the Dantu District Jiang Tan of Zhengjiang City, Jiangsu Province to carry out on-the-spot spraying molluscicide, with 20% niclosamidum nano suspension concentrate 2.0g/ (Lm
2) (the niclosamidum effective component content is 0.4g/m
2) sprinkling 20m
2, 3d, 7d, 15d mortality of snails are respectively 80.17%, 84.33% and 81.10%, 20% niclosamidum nano suspension concentrate 1.0g/ (Lm
2) (the niclosamidum effective component content is 0.2g/m
2) sprinkling 20m
2, 3d, 7d, 15d mortality of snails are respectively 75.70%, 79.82% and 76.42% (seeing Table 5), and the result shows as nano suspension concentrate 1.0g/ (Lm
2) (niclosamidum effective ingredient concentration 0.2g/m
2) sprinkling molluscicidal effect and WPN 2.0g/ (Lm
2) (effective ingredient concentration 1.0g/m
2) close, the niclosamidum nano suspension concentrate soaks extremely that the oncomelania effect is significantly improved than WPN.
The on-the-spot sprinkling of table 5 killed the spiral shell result of the test
| Formulation | Valid density (mg/l) | Mortality of snails (%) | ||
| 1d | 2d | 3d | ||
| The contrast of nano suspension concentrate nano suspension concentrate wetting powder clear water | 0.4 0.2 1.0 0 | 80.17 75.70 77.94 0.91 | 84.33 79.82 78.45 0.85 | 81.10 76.42 68.66 1.08 |
Above result shows the effective dose calculating by niclosamidum, and nano suspension concentrate (20%) is using 1.0g/m
2The time (effective dose is 0.2g/m
2Or 0.2mg/L) time, can reach 50% bayluscid 2.0g (is effective dose 1.0g/m
2Or 1.0mg/L) molluscicidal effect.
Claims (5)
1. snail-killing medicine-nano suspension concentrate of niclosamide ethanolamine, the mass content of its solvent is: niclosamidum 15%-25%, water soluble polymer 0.05%-0.5%, surfactant 3%-15%, defoamer 1%-10%, all the other are dispersion medium water; The particle diameter of niclosamidum particulate is 50nm-1 μ m.
2. niclosamidum nano suspension concentrate according to claim 1 is characterized in that water soluble polymer is a polyoxyethylene, polyvinyl alcohol, polyacrylamide, or polyvinylpyrrolidone.
3. niclosamidum nano suspension concentrate according to claim 1 is characterized in that surfactant is a Tween-80, or neopelex.
4. niclosamidum nano suspension concentrate according to claim 1 is characterized in that defoamer is a methyl-silicone oil, or organosilicon X-10.
5. as the preparation method of claim 1,2,3 or 4 described niclosamidum nano suspension concentrates, it is characterized in that preparing burden by the mass content prescription, niclosamidum 15%-25%, water soluble polymer 0.05%-0.5%, surfactant 3%-15%, defoamer 1%-10%, all the other are dispersion medium water, after the mixing, adopt Ball milling method ball milling, the ball material mass ratio of abrading-ball and material total amount is 10: 1-20: 1, abrading-ball is a zirconia ball, diameter is 1mm-8mm, and rotating speed is 200r/min-1000r/min, ball milling time 40-120h.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101829061A (en) * | 2010-05-14 | 2010-09-15 | 无锡纳生生物科技有限公司 | Taxol nanoparticle composition and preparation method thereof |
| CN103070195A (en) * | 2012-12-19 | 2013-05-01 | 青岛盛瀚色谱技术有限公司 | Pesticide composition for eucalyptus |
| CN104983680A (en) * | 2015-06-25 | 2015-10-21 | 中国科学院东北地理与农业生态研究所 | Stability nanometer suspension preparation of worm repellent compound for sheep and preparation method thereof |
| CN106070190A (en) * | 2016-06-17 | 2016-11-09 | 杨美玲 | Two-in-one " Lac Bovis seu Bubali shape " pesticide of a kind of efficient stable and the preparation of compounding suspending agent thereof |
| CN107094775A (en) * | 2017-04-25 | 2017-08-29 | 中国农业科学院植物保护研究所 | A kind of composition for preventing and treating agricultural disease and the spiral shell that goes out |
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2006
- 2006-07-05 CN CN 200610088237 patent/CN1883266A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101829061A (en) * | 2010-05-14 | 2010-09-15 | 无锡纳生生物科技有限公司 | Taxol nanoparticle composition and preparation method thereof |
| CN103070195A (en) * | 2012-12-19 | 2013-05-01 | 青岛盛瀚色谱技术有限公司 | Pesticide composition for eucalyptus |
| CN103070195B (en) * | 2012-12-19 | 2015-02-18 | 青岛文创科技有限公司 | Pesticide composition for eucalyptus |
| CN104983680A (en) * | 2015-06-25 | 2015-10-21 | 中国科学院东北地理与农业生态研究所 | Stability nanometer suspension preparation of worm repellent compound for sheep and preparation method thereof |
| CN106070190A (en) * | 2016-06-17 | 2016-11-09 | 杨美玲 | Two-in-one " Lac Bovis seu Bubali shape " pesticide of a kind of efficient stable and the preparation of compounding suspending agent thereof |
| CN107094775A (en) * | 2017-04-25 | 2017-08-29 | 中国农业科学院植物保护研究所 | A kind of composition for preventing and treating agricultural disease and the spiral shell that goes out |
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