CN1068518C - Wettable powder of niclosamide salt - Google Patents
Wettable powder of niclosamide salt Download PDFInfo
- Publication number
- CN1068518C CN1068518C CN 94112267 CN94112267A CN1068518C CN 1068518 C CN1068518 C CN 1068518C CN 94112267 CN94112267 CN 94112267 CN 94112267 A CN94112267 A CN 94112267A CN 1068518 C CN1068518 C CN 1068518C
- Authority
- CN
- China
- Prior art keywords
- clonitrilide
- wettable powder
- carboxymethyl cellulose
- water
- niclosamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The present invention relates to wettable powder which is composed of niclosamide ethanolamine salt, sodium dodecyl sulfate and carboxymethyl cellulose and has the advantages of high suspending property and long maintaining time. The present invention can ensure the uniform spraying of medicines to kill amphibious oncomelania which is the intermediate host for the propagation of schistosomiasis and inhabits in various complex environments, and the propagation path of schistosomiasis can be blocked accordingly. The present invention is an effective measure for preventing the infection of schistosomiasis.
Description
The present invention relates to compound formulas, relate to snail control with drugs specifically.
Snail control with drugs be the blocking-up schistosomicide propagation by way of, prevent one of effective measures of schistosomiasis infection, searching is gone out the medicine of spiral shell at first by a large amount of chemical compound of screening test, found that therefrom many chemical substances have the effect of spiral shell extremely, but because various factors makes that its overwhelming majority fails to be promoted application.The sixties from the beginning of, chemists have carried out a large amount of research to niclosamide, find that it has significant killing action to oncomelania, and extremely low to the toxicity of mammal, to the person poultry harmless, to all nonhazardous effects such as crops and other plant, in earth, there is not savings.From its effect, toxicity, it is a comparatively ideal molluscicide, but because its chemical constitution determines, niclosamide itself is water insoluble, directly apply to that extremely spiral shell is very undesirable, influenced its positive role greatly, scientists is made amine salt to niclosamide, make its wettable powder again, form a kind of water dispersant, make it can suspend in water equably to spray with soaking and kill spiral shell and use, but it is very low to make the wettable powder suspendability, and the particle requirement of powder is crushed to less than 75 μ m, its suspensibility then reached the sinking principal agent and is no more than 50% in 0.5 hour.And homemade niclosamide 50% paste of China is called Niclosamide, but it very easily dewaters and condense into lump, can not use.External oncomelania; the two umbilicus spiral shells of example, lamnaeid; ramshorn, vesicle spiral shell etc. all inhabit water body and do not inhabit land; and the oncomelania hupensis of China unique propagation Schistosoma japonicum; it both can inhabit water body; can inhabit land again; as careless beach, phragmites communis beach, foot of the hill grove ground, ground such as barren hillside, the volution border of going out is very complicated; extensive or the large tracts of land of the basic unit spiral shell that goes out; generally time, substantially exceed 0.5 hour, press practical situation from preparating liquid to the sprinkling end; the requirement of suspensibility will be kept within 4-8 hour at least, and the principal agent of sinking can not surpass 50%.
Therefore, at present the spiral shell preparation that goes out used of home and abroad has very big shortcoming, can not bring into play better snail killing function effectively and guarantee the go out quality of spiral shell work of the extensive or large tracts of land of basic unit, can influence the schistosomicide radical cure work of China.
Purpose of the present invention; be to utilize the significant snail killing function of niclosamide; and the advantage that has no side effect; overcome its water-fast shortcoming; it is good to be mixed with a kind of suspensibility; the long wettable powder of holding time makes it can more effective performance snail killing function, guarantees the go out quality of spiral shell work of the extensive or large tracts of land of basic unit.
Characteristics of the present invention, be to utilize an end possess hydrophilic property group, the other end has the chemical compound of mercapto aqueous group as the preparation foundation of uphanging the buoyancy wettable powder, select for use the suspending agent and 50% Clonitrilide of good water solubility to be mixed with wettable powder again, it makes through the following steps:
The preparation of niclosamide: with 5-chloro-salicylic acid and 2-chloro-4-nitroaniline, press etc. gram-molecular weight mixed after, in benzene or toluene solution, reflux, drip the phosphorous oxychloride (or Phosphorous chloride .) of amount of calculation, after dropwising, backflow 4-6 hour, the collecting precipitation thing, ethyl alcohol recrystallization gets light yellow crystalline powder.Mp229-232 ℃ (document: Brit.pat., 284,345,1959).
The preparation of Clonitrilide: with above-mentioned niclosamide and ethanolamine in alcoholic solution after the warm-heat effect, the leaching precipitation, behind the recrystallization orange colour acicular crystal, mp219-222 ℃, be insoluble in water (document: Ger.1,126,374,1962)
Sodium lauryl sulphate (Sodicm Laurysulfate SDS) experiment reagent, total alcohol amount>55%, dissolubility and basicity are all qualified, and this product is white powder or crystallization, and m.p is about, and 180 ℃ of branches are situated between, and are dissolved in H
2O is slightly soluble in alcohol, and it is used as wetting agent this experiment, buys from the market.
Sodium carboxymethyl cellulose (Sodium Carboxy Methyl Cellulose) or title carboxymethyl cellulose.This product is a white powder, and is tasteless, harmless, and aqueous solution is neutrality or alkalescence has good dispersion force and adhesion, is used as strong emulsifying agent, and market is buied, and conforms to homemade commercially available specification, this experiment it as diluent or suspending agent, specifically be formulated as follows:
Clonitrilide 50%
Sodium lauryl sulphate 2%-30%
Sodium carboxymethyl cellulose 48%-20% mixes with sodium lauryl sulphate Clonitrilide by different proportion, it is evenly mixed to aequum to add carboxymethyl cellulose again, in dismembyator, grind evenly, be and make Clonitrilide 50% wettable powder
Containing Clonitrilide in Clonitrilide 50% wettable powder is 50 ± 2.5%, get above-mentioned wettable powder an amount of (being equivalent to Clonitrilide 0.5g approximately), add water 50ml, stir and make molten Jie as far as possible, filter, filtrate is evaporated to dried in water-bath, get residue, residue is according to oxygen flask combustion (Chinese Pharmacopoeia 1990 editions, 38 pages of appendix) carry out organic destruction, get residue 100mg and add every liter of solution 10ml that contains 1 mole hydrochloride, add zinc powder 0.2g, heating in water bath 10 minutes, put cold, filter, in filtrate, add 1% sodium nitrite liquid 1mg, placed 10 minutes, add 2% Ammonium sulfamate liquid 4ml, shake up, placed 10 minutes, and added 0.5%N-naphthodiamide dihydrochloride liquid 4ml, promptly show peony.
Suspensibility is measured the accurate this product an amount of (being equivalent to Clonitrilide 0.25g) crossed through thermal stabilization treatment that takes by weighing, put in the conical flask, (dissolving anhydrous calcium chloride 0.304g and Magnesium dichloride hexahydrate 0.139g are in distilled water to add 500ml water or standard hard water, and with distilled water diluting to 1000ml), immediately this conical flask is done the ring shape jolting, reach each 50 commentaries on classics of jolting to the right left, promptly divide in device 100ml or the 250ml graduated cylinder (temperature of liquid during operation be preferably in warm in the big water-bath in the time of 30 ° ± 1 ℃, carry out) to leave standstill 0.5 hour and required various different times immediately, avoid vibration (if produce excessive floccule in the process of the test in the put procedure, be indicated as dissatisfied product), to be about 40cm then, one end internal diameter is that the glass tubing of 5mm is connected to vacuum pump, the other end is that the mouth of pipe of 2-3mm remains just under the suspendible liquid level, at 10-15 suspension of 9/10 in the sucking-off graduated cylinder in second, be 90ml or 225ml, discard this liquid, remaining 1/10 suspension, promptly 10ml or 25ml are provided with down measuring and use.
(1) with pyridine 25ml and dimethyl formamide 50ml remaining 25ml suspension is comprised that precipitate quantitatively transfers in the 500ml conical flask, by measure titrimetry (document: WHO/SMF/lR3.1983) carry out, suspensibility must not<50%.This volumetric method is very loaded down with trivial details, time-consuming, needs at CO again
2Carry out in the air-flow, very inconvenience is so can select for use following easy ultraviolet spectrophotometry to carry out.
(2) quantitatively transfer to remaining 1/10 suspension 10ml in the small beaker with suitable quantity of water, add 5% hydrochloric acid solution acidify, with this acid solution of ether extraction, extract altogether 3 times, merge ether extracted liquid, in hot bath, steam and remove ether, residue is quantitatively transferred in the 50ml volumetric flask with the 20ml dehydrated alcohol, add dehydrated alcohol to scale, prepare solution again into about 12.5 μ g/ml concentration, by the method in the ultraviolet spectrophotometry item of following assay, measure trap at 333nm wavelength place, obtain the percent content of niclosamide, calculate the Clonitrilide percent content again after, by formula calculate the suspensibility of Clonitrilide 50% wettable powder.
P
2The percent content of Clonitrilide in=1/10 suspension that records
P
1Clonitrilide total content percentage rate in the=sample.
Assay active volume titrimetry or ultraviolet spectrophotometry record.
(1) volumetric precipitation method
This method is the volumetric precipitation method of WHO/SMF/lR3 (1983).Given this above-mentioned shortcoming of titrimetry existence so set up following ultraviolet spectrophotometry in addition, is carried out the assay of this product.
(2) ultraviolet spectrophotometry
Precision takes by weighing Clonitrilide 50% wettable powder 25mg, adds the 20ml distilled water, after shaking up, adds several dilute hydrochloric acid and makes and be acid.Use this solution of ether extraction 3 times then, merge ether extracted liquid, in hot bath, steam and remove ether, residue quantitatively moves in the 50ml volumetric flask with the 20ml dehydrated alcohol, add dehydrated alcohol to scale, redilution is prepared into about 12.5 μ g/ml solution, measures trap at 333nm wavelength place.When measuring, compare with niclosamide standard solution (concentration is 12.6 μ g/ml).Calculate niclosamide content by following formula, obtain the percentage rate that is equivalent to the Clonitrilide labelled amount again.
Calculate:
The normal concentration of C=reference substance
A
1The trap of=sample
A
2The trap of=reference substance
This wettable powder is the mixture of a homogeneous, is yellow.The water slurry of wettable powder is neutral (pH=7), and additive that is not added and the material of bringing into and cause the variation of color, pH are to principal agent or claim other character of active component also not exert an influence.
The sn ail control effect of this wettable powder is comparatively desirable, indoor snail killing test is for adopting the oncomelania of area, Anqing, Anhui Province beach, every group 30, the medication component is the niclosamide group, the Clonitrilide group, Clonitrilide and sodium lauryl sulphate combined group, Clonitrilide and sodium carboxymethyl cellulose combined group, the sodium lauryl sulphate group, the sodium carboxymethyl cellulose group, sodium lauryl sulphate and sodium carboxymethyl cellulose combined group and not administration clear water matched group, every group of administration 100mg/ liter, 10mg/ liter and 1mg/ rise variable concentrations and soak extremely, soak and kill 24 hours, to test oncomelania takes out, clear water was placed 3 days after cleaning, and observed the oncomelania survival condition.The inertia oncomelania is differentiated anyway with hammering method, the statistics mortality rate.Result of the test shows, except that last 3 groups and clear water matched group do not present the snail killing function, all the other each groups are when 3 kinds of variable concentrations, killing snail rate is 100%, show that list does not all have snail killing function with wetting agent and suspending agent, after principal agent mixes, does not influence the original snail killing function of principal agent yet.
On-the-spot snail killing test all realizes satisfactory results.
Table 1 Clonitrilide 50% wettable powder
The spraying molluscicide site test results
Medicine | Dosage (g/m 2) | Spray natural law (d) and this day mortality of snails (%) | |||
d1 | d3 | d5 | d7 | ||
Clonitrilide (test group) | 0.25 0.50 1.0 2.0 | 55.9(170)* 59.8(169) 68.0(172) 75.2(165) | 80.3(178) 79.3(150) 70.5(146) 95.1(154) | 50.0(162) 81.3(160) 70.l(174) 76.6(171) | 67.7(167) 75.9(174) 83.4(169) 92.3(194) |
Like product * * (matched group) | 0.25 0.50 1.0 2.0 | 53.6(166) 54.4(180) 70.4(186) 69.1(175) | 69.8(149) 89.1(184) 86.5(171) 90.2(174) | 62.6(163) 70.1(154) 82.6(167) 83.8(148) | 64.8(150) 84.7(176) 84.8(197) 93.4(181) |
Clear water (matched group) | 22.4(174) | 56/4(173) | 13.1(173) | 33.8(198) |
* be in the parantheses and check the spiral shell number.
* simultaneously stirs when implementing, and one side is sprayed.
Time: on April 26th, 1993 to May 3 (fine day on the 29th, 3 are cloudy, and all the other are the rainy day, 28 days and 30 days
Be thunder shower).Temperature: 21 °-28 ℃.
Table 2 Clonitrilide 50% wettable powder
The corrected mortality of on-the-spot spraying molluscicide
Medicine | Dosage (g/m 2) | Spray natural law (d) and this day oncomelania corrected mortality (%) | |||
d1 | d3 | d5 | d7 | ||
Clonitrilide (test group) | 0.25 0.50 1.0 2.0 | 43.2(55.9)* 48.2(59.8) 58.8(68.0) 68.0(75.2) | 54.8(80.3) 52.5(79.3) 32.3(70.5) 88.7(95.1) | 42.5(50.0) 78.5(81.3) 65.6(70.1) 73.1(76.6) | 51.2(67.7) 63.6(75.9) 74.9(83.4) 88.4(92.3) |
Like product (matched group) | 0.25 0.50 1.0 2.0 | 40.2(53.6) 41.2(54.4) 61.8(70.4) 60.2(69.1) | 30.7(69.8) 75.0(89.1) 69.0(86.5) 77.5(90.2) | 57.0(62.6) 65.6(70.1) 80.0(82.6) 81.3(83.8) | 46.8(64.8) 76.9(84.7) 77.0(84.8) 90.0(93.4) |
Clear water (matched group) | (22.4) | (56.4) | (13.1) | (33.8) |
* be mortality of snails in the parantheses.
Table 3 Clonitrilide 50% wettable powder
Soak and kill the spiral shell site test results
Medicine | Concentration (g/m 3Water) | Soak natural law (d) and this day mortality of snails (%) extremely | |||
d1 | d3 | d5 | d7 | ||
Clonitrilide (test group) | 0.25 0.50 1.0 2.0 | 97.0 100 100 100 | 97.0 99.0 100 100 | 98.0 100 100 100 | 100 100 100 100 |
Like product (matched group) | 0.25 0.50 1.0 2.0 | 100 100 99.0 100 | 100 100 100 100 | 100 100 100 100 | 100 100 100 100 |
Clear water (matched group) | 11.0 | 11.0 | 12.0 | 17.0 |
Time: on April 30th, 1993 is to May 6, and except that 30,2,5 and 6 days 4 it rains, all the other are fine.
Temperature: 21 °-23 ℃; Water temperature: 19 °-21.5 ℃.
Table 4 Clonitrilide 50% wettable powder
The corrected mortality of killing spiral shell is soaked at the scene
Medicine | Concentration (g/m 3Water) | Soak natural law (d) and this day oncomelania corrected mortality (%) extremely | |||
d1 | d3 | d5 | d7 | ||
Clonitrilide (test group) | 0.25 0.50 1.0 2.0 | 96.6(97.0)* 100(100) 100(100) 100(100) | 96.6(97.0) 98.9(99.0) 100(100) 100(100) | 97.7(98.0) 100(100) 100(100) 100(100) | 100(100) 100(100) 100(100) 100(100) |
Like product (matched group) | 0.25 0.50 1.0 2.0 | 100(100) 100(100) 98.9(99.0) 100(100) | 100(100) 100(100) 100(100) 100(100) | 100(100) 100(100) 100(100) 100(100) | 100(100) 100(100) 100(100) 100(100) |
Clear water (matched group) | (11.0) | (11.0) | (12.0) | (17.0) |
* be mortality of snails in the parantheses.
As seen from last, the effect according to group when the sn ail control effect of this wettable powder with the like product of Clonitrilide import is is consistent, spraying with soak extremely method relatively, be and soak extremely that effect is better than spray effect.
This wettable powder characteristics are higher suspension rate (91%-97%), continue suspension time long (greater than 24 hours), domestic at present, behind outer wettable powder and the water suspendible, left standstill 0.5 hour, promptly there is tangible principal agent to sink, the oncomelania effect is killed in influence, 0.5 hour suspensibility generally only reaches 50%-60%, because the suspensibility of at present domestic and international wettable powder is low and the therefore necessary Drawing upon physical method of suspendability difference, the granule of this powder is crushed to<75 μ m, just can keep this powder and be not less than 50%, and this wettable powder does not need granular size requirement to some extent because suspendability is good at the suspensibility that leaves standstill 0.5 hour, after leaving standstill the long period, still has good suspendability.Therefore, can save the technology of pulverizing aborning.Because this wettable powder suspendability is good, the characteristics that suspension time is long, thus guarantee the homogeneity of dosage in the spraying molluscicide operating process, be particularly suitable for the extensive or large-area spiral shell dispenser work of going out in various complicated place and basic unit that China's oncomelania is perched.
Be the embodiment of preparation below, illustrate further the present invention, and the restriction to inventing anything but.
Embodiment 1:
Clonitrilide 50g
Sodium lauryl sulphate 2g
Sodium carboxymethyl cellulose adds to 100g
After above-mentioned three kinds of chemical compounds grind mixing, to seal, be put in dry shady and cool place stand-by.
Embodiment 2:
Clonitrilide 50g
Sodium lauryl sulphate 5g
Sodium carboxymethyl cellulose adds to 100g
After above-mentioned three kinds of chemical compounds grind mixing, to seal, be put in dry shady and cool place stand-by.
Embodiment 3:
Clonitrilide 50g
Sodium lauryl sulphate 10g
Sodium carboxymethyl cellulose adds to 100g
After above-mentioned three kinds of chemical compounds grind mixing, to seal, be put in dry shady and cool place stand-by
Embodiment 4:
Clonitrilide 50g
Sodium lauryl sulphate 20g
Sodium carboxymethyl cellulose adds to 100g
After above-mentioned three kinds of chemical compounds grind mixing, to seal, be put in dry shady and cool place stand-by
Embodiment 5:
Clonitrilide 50g
Sodium lauryl sulphate 30g
Sodium carboxymethyl cellulose adds to 100g
After above-mentioned three kinds of chemical compounds grind mixing, to seal, be put in dry shady and cool place stand-by.
Claims (2)
1, the wettable powder a kind of by Clonitrilide, that sodium lauryl sulphate and sodium carboxymethyl cellulose are formed is characterized in that the ratio of filling a prescription is
Clonitrilide 50%
Sodium lauryl sulphate 2%-30%
Sodium carboxymethyl cellulose 20-48%
After above-mentioned three kinds of chemical compounds grind mixing, to seal, be put in dry place stand-by.
2, a kind of wettable powder of being made up of Clonitrilide, sodium lauryl sulphate and sodium carboxymethyl cellulose is used being used for preparing the medicine of killing oncomelania.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 94112267 CN1068518C (en) | 1994-08-19 | 1994-08-19 | Wettable powder of niclosamide salt |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 94112267 CN1068518C (en) | 1994-08-19 | 1994-08-19 | Wettable powder of niclosamide salt |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1124621A CN1124621A (en) | 1996-06-19 |
CN1068518C true CN1068518C (en) | 2001-07-18 |
Family
ID=5036056
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 94112267 Expired - Fee Related CN1068518C (en) | 1994-08-19 | 1994-08-19 | Wettable powder of niclosamide salt |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN1068518C (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1985813B (en) * | 2006-12-07 | 2010-10-06 | 江苏省血吸虫病防治研究所 | Metronidazole ethanolamine spray as blood flukedisease preventing and treating medicine for farm cattle and its preparing method |
CN102687718A (en) * | 2011-03-21 | 2012-09-26 | 复旦大学 | Depositing molluscicidal method |
CN104430338B (en) * | 2014-12-08 | 2016-08-31 | 江苏艾津农化有限责任公司 | Niclosamide ethanolamine salt wettable powder agent and its preparation method and application |
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 |
CN106614590B (en) * | 2016-12-04 | 2019-01-29 | 九江学院 | A kind of water-snail eradication composition of medicine |
-
1994
- 1994-08-19 CN CN 94112267 patent/CN1068518C/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CN1124621A (en) | 1996-06-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1899361A (en) | Zhenqi medicinal composition and its preparation | |
CN102133190A (en) | Transferrin nanoparticles and preparation method and application thereof | |
CN1068518C (en) | Wettable powder of niclosamide salt | |
CN1177546C (en) | Use of polyphenol compounds or their derivatives as scavengers of free radicals in cigarette filters | |
CN1792162A (en) | Micro-capsule water suspending agent for killing tick | |
CN101066059A (en) | Soluble Wuyiencin powder and its prepn process | |
Qu et al. | A sustainable and smart fungicide release platform through cocrystal nanocapsules for improved utilization rate and environmental safety | |
CN112056329B (en) | Seawater microalgae regulating agent and microalgae phase regulating method using same | |
CN110590463B (en) | Fertilizer and molluscicide double-effect organic fertilizer molluscicide, preparation method and application thereof | |
CN1806544A (en) | Use of ginkgoic acid in preparation of biological pesticide for killing Oncomelania snail and preventing schistosomiasis | |
CN1775039A (en) | Nim oil micro capsule and its preparing method | |
CN102408497A (en) | Pesticide-carrying nano micellar solution as well as preparation method and application thereof | |
CN1850838A (en) | Scutellarin raw material drug preparing method | |
CN104355379B (en) | A kind of algicide based on Alternanthera philoxeroides and its preparation method and application | |
CN1843128A (en) | Method for directly processing pesticide using Camptotheca acuminata | |
CN104273123A (en) | Seedling-stage insect-prevention seed soaking solution for organically producing corns and gramineae grains and preparation method | |
CN1029451C (en) | Root element and its making method | |
CN1448129A (en) | Garlicin and garlic oil cyclodextrin derivatives inclusion compound and method for making same | |
CN107494611A (en) | A kind of Brontispa longissima preventing and treating Pesticidal tablet formulations and preparation method thereof | |
CN106215885A (en) | The preparation method of a kind of chitosan activated sludge compound adsorbent and purposes | |
CN110612984B (en) | Application of cyclopropylimine in oncomelania killing medicine | |
CN1389112A (en) | Niclosamide insecticide and molluscacide suspension and its prepn. process | |
CN1163147C (en) | Oncomelania killer and its preparing process | |
CN1939908A (en) | Practical large ring lactam bactericide | |
CN1781372A (en) | Water dispersion particle agent of abamectin and its producing method |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C19 | Lapse of patent right due to non-payment of the annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |