CN101209043B - Application of sanguinarine or toddaline in prevention and cure of schistosomiasis - Google Patents
Application of sanguinarine or toddaline in prevention and cure of schistosomiasis Download PDFInfo
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Abstract
The invention relates to application of a sanguinarine or a chelerythrine for preventing and curing of schistosomiasis. The invention applies the sanguinarine and the chelerythrine on killing an oncomelania, a snail egg, a Japanese blood fluke cercaria, a schistosome and the prevention and cure of schistosomiasis. The inventor discovers that the sanguinarine or the chelerythrine can kill the oncomelania and the snail egg safely and effectively and can kill the Japanese blood fluke cercaria as well as a schistosomulum and an imago of the schistosome under a lower concentration, which has the functions of preventing and curing the schistosomiasis and does not pollute the environment.
Description
Technical field
The present invention relates to the new application aspect prevention and cure of schistosomiasis of sanguinarine and Chelerythrine and salt thereof---be used to kill oncomelania, spiral shell ovum, schistosoma japonicum cercariae, imago of blood fluke and schistosomulum.
Background technology
Schistosomiasis is commonly called as " pregnant disease ", be since mammalian infections such as people or ox, sheep, pig caused a kind of infectious disease of blood fluke and parasitosis.Total in the world Schistosoma haematobium, Schistosoma mansoni, Schistosoma japonicum, interleave 5 kinds of blood flukes that parasitize human body such as blood fluke, the public blood fluke of river bank.Schistosomiasis endemic in the temperate zone, subtropics, torrid areas.Calendar year 2001 WHO estimates that the population that schistosomiasis is infected in the whole world is about 200,000,000 people, has 600,000,000 populations to be on the hazard, and has 76 countries influenced, and wherein the overwhelming majority is a developing country, this disease serious harm these national people's health and economic development.
The only popular Schistosoma japonicum of China, be called for short blood fluke.Wherein oncomelania (Oncomelaia hupensis, O.hupensis) be Schistosoma japonicum unique intermediate host.Bilharzial miracidium can develop into mother sporocyst after invading breechblock, thereby thousands of times of ground propagation in breechblock, constantly produce cercaria in water or moist soil table, so that infected person and other animals are are so gone round and begun again and facilitated spreading and spreading of schistosomiasis.Killing oncomelania can cut off bilharzial route of transmission.So killing oncomelania is the internationally recognized important measures that prevent schistosomiasis.
The data of announcing according to country shows, blood fluke mainly is distributed in 427 counties (city, district) scope of 12 provinces such as the Jiangsu, Zhejiang, Hunan, Hubei, Anhui, Jiangxi, Sichuan, Yunnan, Guangdong, Guangxi, Fujian, Shanghai of the middle and lower reach of Yangtze River one band and areas to the south, the Yangtze river basin.Schistosomiasis patient is about 1,000,000 people.Though China is the mass control to schistosomiasis through the 50-60 age, the popular of this disease is effectively controlled, in recent years, because factors such as floods, reservoir, dam construction, movements of population, schistosomiasis begins bounce-back.For example, almost all there is oncomelania Dongting Lake lake region, Hunan, and no swimming, and Yueyang along the lake, Changde, Yiyang Prefecture all are severely afflicated areas.Therefore, the control to schistosomiasis becomes one of strategic objective of national sustainable development.
The medicine of prevention and cure of schistosomiasis commonly used mainly contains niclosamidum, penta sodium pentachlorophenate and Australia's second phthalein amine at present.
Wherein the niclosamidum spiral shell prevention and cure of schistosomiasis effect of going out is fine, be universally acknowledged molluscicide, but cost an arm and a leg, use in developing country's large tracts of land to be restricted, also can produce harm when high concentration is used, and also can cause the pesticide resistance of target biology to increase aquatiles such as fish.Penta sodium pentachlorophenate is once used by many countries, and sn ail control effect is good, but to non-target biology, raising fish and shrimp class tool broad spectrum toxicity especially, and cause serious environmental to pollute, classified as the forbidding product by international community already.
In view of the drawback of present molluscicide, international community has given very big concern to research and development are plant origin with molluscicide natural products.Therefore, the research and development sn ail control effect is good, cost is lower, hypotoxic novel molluscacide has its necessity and urgency.
Sanguinarine (sanguiranine) chemical name is 13-methyl-[1,3] Ben Bing Er Evil penta [5,6-c]-1,3-Er Evil penta [4,5-i] phenanthridines, and its molecular formula is C
20H
14NO)
4, molecular weight: 332.335.The structure examination is as follows:
It mainly is distributed in Papaveraceae (Argemone, papaver, Sanguinaria, Macleaya, white bending
Belong to angle Foeniculum, favus of the scalp Pittosporum etc.); Fumaraceae (Corydalis, Dicentra etc.) and Rutaceae etc. (Zanthoxylum value thing etc.).The extraction of at present existing sanguinarine separates patent: CN03118201.1 high-purity sanguinarine and Chelerythrine separation preparation; The application in the preparation of high-purity sanguinarine of the preparation method of the polymeric adsorbent of CN200510122488.6 polar functionalities and this resin.
Sanguinarine has resisting pathogenic microbes, antiinflammatory action, insecticidal action, kills the maggot effect, changes disease liver function and enhancing immunity, suppresses cholinesterase activity, antitumor action, weak anti-EC effect etc., be mainly used in veterinary drug at present, feed addictive, daily-use chemical industry, aspects such as agricultural chemicals.United States Patent (USP)s such as existing US4517172, US4590061, US4683133 relate to the treatment that sanguinarine extract etc. is used for mouth diseases such as bacterial plaque developer and periodontosis.In addition, 4689216 of U.S. Pat 4145412 and US have described the situation that the sanguinarine extract is applied to toothpaste that contains.The domestic patent that also has some to relate to sanguinarine at present, CN200410099204.1 mentions a kind of feed addictive that contains sanguinarine,
Chelerythrine (chelerythrine) chemical name is 1,2-dimethoxy-N-methyl-[1,3] Ben Bing Er Evil penta [5,6-c] phenanthridines, and its molecular formula is C
21H
18NO
4, molecular weight: 348.33.Structural formula:
It mainly is distributed in Papaveraceae (Chelidonium, Macleaya, Sanguinaria, angle Foeniculum, papaver etc.); Fumaraceae (Corydalis, Dicentra etc.); Rutaceae (Toddalia, the equivalent thing of Zanthoxylum).The extraction of at present existing Chelerythrine separates patent: CN03118201.1 high-purity Chelerythrine and Chelerythrine separation preparation;
It has resisting pathogenic microbes, antiinflammatory action, insecticidal action, kills the maggot effect.Modern pharmacological research shows that Chelerythrine also has antitumaous effect.Relevant patent CN98804824.8 is with Chelerythrine and tumour is treated in radiation and CN03140103.1 mentions a kind of medicine that contains the treatment cancer of Chelerythrine.
Still be difficult relevant report and the patent application that sanguinarine or Chelerythrine and salt thereof are applied to kill oncomelania, spiral shell ovum, schistosoma japonicum cercariae, blood fluke, inhibition schistosomulum and prevention and cure of snail fever at present both at home and abroad.
Summary of the invention
The objective of the invention is to propose a kind ofly safe and efficiently kill oncomelania, spiral shell ovum, schistosoma japonicum cercariae, blood fluke and schistosomiasis is prevented and treated the application of sanguinarine free from environmental pollution again, non-harmful or Chelerythrine.
The present inventor finds that after deliberation sanguinarine and Chelerythrine and salt thereof can kill unique intermediate host---the oncomelania in the widely popular Japanese schistosomiasis of China effectively, and the effect of spiral shell ovum, can kill schistosoma japonicum cercariae and blood fluke.Can be used for the control of schistosomiasis.
The present invention has opened up the new purposes that sanguinarine and Chelerythrine and salt thereof are killed oncomelania, schistosoma japonicum cercariae and blood fluke, prevented schistosomiasis, also can further prepare the new bio molluscicide and prevent schistosomiasis.
The objective of the invention is to realize by following manner:
The present invention is used to prepare the medicine of killing oncomelania, spiral shell ovum, blood fluke cercaria, bilharzial prevention and treatment with sanguinarine or Chelerythrine or both mixtures.
Described sanguinarine or Chelerythrine or both mixtures all can be used to prepare medicine by salt form separately.
Sanguinarine or its salt, Chelerythrine or its salt or both mixtures or their salt are used to prepare molluscicide.
Red root alkali salt that the present invention refers to or chelerythrine alkali salt are inorganic acid salt or organic acid salts separately.
Though sanguinarine and Chelerythrine have biologically active preferably to killing oncomelania, spiral shell ovum, schistosoma japonicum cercariae, blood fluke, but its dissolubility in water is very low, and easily change, therefore, exist with salt form and can keep its stability, and be increased in dissolubility in the water with organic acid or inorganic acid salify, help bilharzial control.
The sanguinarine inorganic acid salt of indication of the present invention or the inorganic acid of Chelerythrine inorganic acid salt can be a kind of in hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, boric acid, hydrobromic acid, wolframic acid, phosphorous acid and other inorganic acids.With above-mentioned inorganic acid with from be rich in sanguinarine or Chelerythrine plant, extract or synthesize with the method for chemosynthesis in the sanguinarine inorganic acid salt or the Chelerythrine inorganic acid salt that obtain with sanguinarine or chelerythrine alkali reaction.
The sanguinarine organic acid salt of indication of the present invention or the organic acid of Chelerythrine organic acid salt can be meant a kind of in benzoic acid, salicylic acid, oxalic acid, tartaric acid, malic acid, citric acid, caffeic acid and other organic acids.With above-mentioned organic acid with from the plant that contains sanguinarine or Chelerythrine, extract or synthesize with the method for chemosynthesis in the sanguinarine organic acid salt or the Chelerythrine organic acid salt that obtain with sanguinarine or chelerythrine alkali reaction.
Sanguinarine of the present invention or Chelerythrine be by chemically separated method, from the plant of being rich in sanguinarine or Chelerythrine, extract obtain as: plants such as Papaveraceae.Or, fully utilize reclaiming again in the waste material remaining in extracting process; Or obtain by the method for chemosynthesis.Again further by high performance liquid chroma-tography technology (HPLC) with other correlation analysis technology are analyzed, evaluation and Quality Control.
The medicine of The compounds of this invention uses as molluscicide, also can share with other molluscicides, to strengthen molluscicidal effect or to reduce its toxic and side effect, reduce cost.
Drug prepared of the present invention is can be under low concentration safe and effective safely and efficiently to be killed oncomelania, spiral shell ovum, schistosoma japonicum cercariae, blood fluke and schistosomiasis is prevented and treated, free from environmental pollution again, nuisanceless.
Application mode of the present invention is that sanguinarine or Chelerythrine or their mixture or salt separately are as active component, adding medicine is learned the various pharmaceutical dosage forms that corresponding auxiliary material is made, thereby be applied to kill the generation that oncomelania, spiral shell ovum, schistosoma japonicum cercariae play the prevention schistosomiasis, be applied to drive blood fluke in people's carcass and kill blood fluke cercaria, virgin worm and adult reach the prevention and the therapeutic action of people and animals' schistosomiasis.Application of the present invention can also be made corresponding medicament together by sanguinarine or Chelerythrine or their mixture or salt separately can be killed oncomelania, spiral shell ovum, schistosoma japonicum cercariae, bilharzial active component as active component and other.
Described formulation is pulvis, powder, tablet, capsule or injection etc.
Application of the present invention there is no about report and research.In order better to understand essence of the present invention, below with test explanation more specifically.
Test: the sanguinarine that the present invention proposes and the spiral shell that goes out, the spiral shell ovum that goes out of Chelerythrine, kill blood fluke cercaria and schistosomulum, adult effect.Be relatively convenient, institute is useful on the spiral shell that goes out, the spiral shell ovum that goes out, the content of killing the test sample that blood fluke cercaria tests are 98%, in the weight of sanguinarine and chelerythrine alkali salt.
1 material
1.1 sanguinarine (lot number: 060218, Changsha Shiwei Science Co., Ltd provides) is prepared into 200mg/L concentration before Chelerythrine (lot number: 060511, the Changsha Shiwei Science Co., Ltd provides) test, is made into variable concentrations respectively with coubling dilution again.
1.2 preceding the 2～3d of oncomelania test picks up oncomelania from Yueyang Jun Mountain and Fu Jia continent, Xiang River middle reaches and puts laboratory rearing, selecting lives tests into spiral shell.Oncomelania is a rib shell oncomelania.
1.3 cercaria provides positive oncomelania by Hunan Institute of Parasitic Diseases, test ease on the same day is put schistosoma japonicum cercariae.
1.4 Kunming white mouse is used in the mouselet test, purchases the laboratory animal department of the Chinese Academy of Sciences in Hunan University of Traditional Chinese Medicine
One, snail killing test
Method: sanguinarine and Chelerythrine are configured to each 2000ml of soup of variable concentrations, throw in 1 of the Nylon Bag that 10 spiral shells alive are housed in each dosage 100ml soup, establish conventional 50% niclosamidum and clear water control group simultaneously.Soak respectively kill 1d, 2d, 3d after, every day, soup was removed in sampling, after flushing with clean water spiral shell, 24～48h recover to raise, identified the oncomelania death toll and the number of surviving with hammering method.If the control group mortality of snails is greater than 10%, test must be carried out again.Each concentration group is all tested under 20 ℃, 25 ℃ different temperatures.
Computational methods: mortality of snails=oncomelania death toll/test oncomelania sum * 100%
The result: under different temperatures (20 ℃, 25 ℃) and variable concentrations, sanguinarine is different with chelerythrine aqueous slkali molluscicidal effect.In 20 ℃ of sanguinarine of indoor temperature and Chelerythrine variable concentrations group, soak 1-3d, mortality of snails all is lower than 60%.25 ℃ of room temperatures, sanguinarine drug immersion oncomelania 2d, best spiral shell effective dose extremely is 3.25mg/L; Chelerythrine soaks oncomelania 3d, and killing snail rate is 100% in 6.25mg/L.Low concentration soup killing snail rate is relevant with turbidity under 25 ℃ of conditions.See Table one.
Sanguinarine and Chelerythrine are killed the oncomelania result under table one, the different temperatures
Two, go out spiral shell ovum test
Method: select 2d ovum age, the oncomelania ovum that the mud skin is complete, sanguinarine and Chelerythrine are configured to sanguinarine and each 2000ml of Chelerythrine soup of variable concentrations, in each 100ml beaker, respectively put 30 on spiral shell ovum, wherein 3 groups add best spiral shell concentration (3mg/L) totally three each 50ml of concentration liquid up and down that effectively kill, and other establishes the clear water control group.Each soaks and calculated incubation rate in 15 days.Clear water contrast spiral shell ovum nature incubation rate 65%.
Computational methods: spiral shell egg hatching rate=larva of a tapeworm or the cercaria of a schistosome spiral shell is hatched number/test spiral shell ovum sum * 100%
The result: sanguinarine soaks 15d effect 6.25mg/L and the 3.13mg/L group all has notable difference with control group, and hatching has better inhibitory action to the spiral shell ovum.Chelerythrine soaks 7d at 6.25mg/L, and hatching has good inhibitory effect to the spiral shell ovum.See Table two.
Table two, sanguinarine and Chelerythrine kill spiral shell ovum result
Annotate: the spiral shell ovum that goes out of ovum not, anatomic observation is the ovum embryo of disintegration under the mirror
Three, kill the blood fluke cercaria test
Got the infectious oncomelania ease same day in experiment and put cercaria, with sanguinarine and Chelerythrine by killing oncomelania optimum effective concentration preparating liquid.Get sanguinarine and chelerythrine aqueous slkali 100 microlitres respectively and be placed on the concave slide, live 35～50 of cercarias of every hole picking, anatomical lens observes 1,3,5,10,15,30,45 down, 60min cercaria survival condition.Touch cercaria with dissecting needle, inertia person is judged to death.Establish the clear water control group simultaneously.
Computational methods: different time cercaria lethality=cercaria death toll/observation cercaria sum * 100%
The result: sanguinarine soaks at concentration 6.25mg/L and killed 15 minutes, and 3.125mg/L and 1.563mg/L soak and killed cercaria lethality 100% 60 minutes.Chelerythrine soaks at concentration 6.25mg/L and killed 45 minutes, and 3.125mg/L soaks and killed cercaria lethality 100% 60 minutes.See Table three.
Table three, sanguinarine and Chelerythrine kill the cercaria result
Four, kill the imago of blood fluke test
Sanguinarine and Chelerythrine given the test agent are established not administration control group of 100mg/kg, 200mg/kg, a 300mg/kg3 dosage group and 1 respectively, and every group with 6 of small white mouses, body weight 20～24 grams, male and female half and half.By test requirements document, accurately take by weighing medicine and grind, add 2% starch fluid then and grind that to be made into suspension standby.Get 50 of infectious oncomelanias (conventional ease larva of a tapeworm or the cercaria of a schistosome method is obtained cercaria), every mouse infects 40 of cercarias.Infect back 28 days beginning gastric infusions, every day 1 time, 3 days courses of treatment, the back dissection of 3 weeks is dissected and is seized adult with the method for tearing up (following this method of all using), calculates worm reduction rate, observes and kills the imago of blood fluke effect.
The result: control group imago of blood fluke developmental rate is 77.08%, and sanguinarine and Chelerythrine produce effect to killing imago of blood fluke.See Table four.
Table four, sanguinarine and Chelerythrine are killed the imago of blood fluke result of the test
Five, kill the schistosomulum test
Sanguinarine and Chelerythrine sample are all established not administration control group of 250mg/kg, 333mg/kg, a 500mg/kg3 dosage group and 1, and every group with 6 of small white mouses.Medicine preparation and infection method are the same, infect the back mat woven of fine bamboo strips 1 day, 3 days, 5 days, gastric infusion 1 time every other day, and the back changed the mat woven of fine bamboo strips into 7 days because of 3 administrations of the toxic reaction mat woven of fine bamboo strips.Infect 5 weeks of back and dissect, obtain the inspection adult, calculate worm reduction rate, observe and kill the schistosomulum effect.
The result: control group schistosomulum developmental rate is 75.42%; Sanguinarine and Chelerythrine produce effect to killing schistosomulum.See Table five.
Table five, sanguinarine and Chelerythrine are killed the schistosomulum result of the test
Conclusion: (1) sanguinarine and Chelerythrine have the oncomelania effect of killing preferably.25 ℃ of room temperatures, sanguinarine drug immersion oncomelania 48h, best spiral shell effective dose extremely is 3.25mg/L; 25 ℃ of room temperatures, 6.25mg/L Chelerythrine drug immersion oncomelania 72h, mortality of snails is 100%.
(2) sanguinarine and Chelerythrine have the good spiral shell ovum effect of killing: sanguinarine 3.13～6.25mg/L soaks 15d, the remarkable inhibitory action of spiral shell ovum hatchability; Chelerythrine 6.25mg/L soaks 15d, the remarkable inhibitory action of spiral shell ovum hatchability.。
(3) to kill cercaria effective for sanguinarine and Chelerythrine.
(4) sanguinarine and Chelerythrine produce effect to killing blood fluke.
(5) sanguinarine and Chelerythrine are killed and inhibitory action schistosomulum.
Embodiment
Following examples are intended to illustrate the present invention rather than limitation of the invention further.
Following pulvis is by behind sanguinarine or Chelerythrine and salt and water soluble starch (100 order) stirring and evenly mixing, crosses 100 mesh sieves, makes pulvis.
Embodiment 1
Get 98% sanguinarine, be dissolved in 90% ethanol, stir adding sulfuric acid down, leave standstill crystallization, refining, drying promptly gets and is not less than 98% sanguinarine sulfate; Get gained 98% Chelerythrine, be dissolved in 90% ethanol, stir adding sulfuric acid down, leave standstill crystallization, refining, drying promptly gets and is not less than 98% chelerythrine alkali sulfate.
Sampling is killed oncomelania, the spiral shell ovum that goes out, is killed blood fluke cercaria and test by the routine method of test.
98% sanguinarine sulfate:
Killing the oncomelania test is 3.13mg/L in concentration, and temperature is 25 ℃, soaks 48～72h, mortality of snails 99-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 72h, and spiral shell ovum hatchability is 0-5%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
98% Chelerythrine:
Killing the oncomelania test is 6.25mg/L in concentration, and temperature is 25 ℃, soaks 48～72h, mortality of snails 99-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 5d, and spiral shell ovum hatchability is 0-7%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
Embodiment 2
Get gained 98% sanguinarine, be dissolved in 90% ethanol, stir adding boric acid down, leave standstill crystallization, refining, drying promptly gets and is not less than 98% sanguinarine borate, promptly obtains 60% sanguinarine borate pulvis with the quantitative adjusting of water soluble starch.Get gained 98% Chelerythrine, be dissolved in 90% ethanol, stir adding boric acid down, leave standstill crystallization, refining, drying promptly gets and is not less than 98% Chelerythrine borate, promptly obtains 60% Chelerythrine borate pulvis with the quantitative adjusting of water soluble starch.
Getting above-mentioned two kinds of pulvis kills oncomelania, the spiral shell ovum that goes out, kills blood fluke cercaria and test by the routine method of test.
60% sanguinarine borate pulvis:
Killing the oncomelania test is 3.13mg/L in concentration, and temperature is 25 ℃, soaks 72～96h, mortality of snails 99-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 72h, and spiral shell ovum hatchability is 0-4%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
60% Chelerythrine borate pulvis:
Killing the oncomelania test is 6.25mg/L in concentration, and temperature is 25 ℃, soaks 72～96h, mortality of snails 99-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 5d, and spiral shell ovum hatchability is 0-4%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/l solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
Embodiment 3
Get 98% sanguinarine, be dissolved in 90% ethanol, stir adding salicylic acid down, leave standstill crystallization, refining, drying promptly gets and is not less than 98% sanguinarine salicylate, promptly obtains 98% sanguinarine salicylate pulvis with the quantitative adjusting of water soluble starch.Get 98% Chelerythrine, be dissolved in 90% ethanol, stir adding salicylic acid down, leave standstill crystallization, refining, drying promptly gets and is not less than 98% Chelerythrine salicylate, promptly obtains 98% Chelerythrine salicylate pulvis with the quantitative adjusting of water soluble starch.
Getting above-mentioned two kinds of pulvis kills oncomelania, the spiral shell ovum that goes out, kills blood fluke cercaria and test by the routine method of test.
98% sanguinarine salicylate pulvis:
Killing the oncomelania test is 3.13mg/L in concentration, and temperature is 25 ℃, soaks 72～96h, mortality of snails 95-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 72h, and spiral shell ovum hatchability is 0-3%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
98% Chelerythrine salicylate pulvis:
Killing the oncomelania test is 6.25mg/L in concentration, and temperature is 25 ℃, soaks 72～96h, mortality of snails 99-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 5d, and spiral shell ovum hatchability is 0-5%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
Embodiment 4
Get 98% sanguinarine, be dissolved in 90% ethanol, stir adding tartaric acid down, leave standstill crystallization, refining, drying promptly gets and is not less than 98% sanguinarine tartrate, promptly obtains 60% sanguinarine tartrate pulvis with the quantitative adjusting of water soluble starch.Get 98% Chelerythrine, be dissolved in 90% ethanol, stir adding tartaric acid down, leave standstill crystallization, refining, drying promptly gets and is not less than 98% Chelerythrine tartrate, promptly obtains 60% Chelerythrine tartrate pulvis with the quantitative adjusting of water soluble starch.
Getting above-mentioned two kinds of pulvis kills oncomelania, the spiral shell ovum that goes out, kills blood fluke cercaria and test by the routine method of test.
60% sanguinarine tartrate pulvis:
Killing the oncomelania test is 3.13mg/L in concentration, and temperature is 25 ℃, soaks 72～96h, mortality of snails 98-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 72h, and spiral shell ovum hatchability is 0-5%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
60% Chelerythrine tartrate pulvis:
Killing the oncomelania test is 6.25mg/L in concentration, and temperature is 25 ℃, soaks 72～96h, mortality of snails 98-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 5d, and spiral shell ovum hatchability is 0-6%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
Embodiment 5
Get 98% sanguinarine, be dissolved in 90% ethanol, stir adding citric acid down, leave standstill crystallization, refining, drying promptly gets and is not less than 98% sanguinarine citrate salt, promptly obtains 60% sanguinarine citrate salt pulvis with the quantitative adjusting of water soluble starch.Get 98% Chelerythrine, be dissolved in 90% ethanol, stir adding citric acid down, leave standstill crystallization, refining, drying promptly gets and is not less than 98% Chelerythrine citrate salt, promptly obtains 60% Chelerythrine citrate salt pulvis with the quantitative adjusting of water soluble starch.
Getting above-mentioned both pulvis kills oncomelania, the spiral shell ovum that goes out, kills blood fluke cercaria and test by the routine method of test.
60% sanguinarine citrate salt pulvis:
Killing the oncomelania test is 3.13mg/L in concentration, and temperature is 25 ℃, soaks 72～96h, mortality of snails 97-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 72h, and spiral shell ovum hatchability is 0-4%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
60% Chelerythrine citrate salt pulvis:
Killing the oncomelania test is 6.25mg/L in concentration, and temperature is 25 ℃, soaks 72～96h, mortality of snails 97-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 5d, and spiral shell ovum hatchability is 0-4%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
Embodiment 6
Get 98% sanguinarine, be dissolved in 90% ethanol, stir adding sulfuric acid down, leave standstill crystallization, refining, drying promptly gets and is not less than 98% sanguinarine sulfate, promptly obtains 40% sanguinarine sulfate pulvis with the quantitative adjusting of water soluble starch.Get 98% Chelerythrine, be dissolved in 90% ethanol, stir adding sulfuric acid down, leave standstill crystallization, refining, drying promptly gets and is not less than 98% chelerythrine alkali sulfate, promptly obtains 40% Chelerythrine sulphate pulvis with the quantitative adjusting of water soluble starch.
Getting above-mentioned two kinds of pulvis kills oncomelania, the spiral shell ovum that goes out, kills blood fluke cercaria and test by the routine method of test.
40% sanguinarine sulfate pulvis:
Killing the oncomelania test is 3.13mg/L in concentration, and temperature is 25 ℃, soaks 72～96h, mortality of snails 96-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 72h, and spiral shell ovum hatchability is 0-4%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
40% Chelerythrine sulphate pulvis:
Killing the oncomelania test is 6.25mg/L in concentration, and temperature is 25 ℃, soaks 72～96h, mortality of snails 96-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 5d, and spiral shell ovum hatchability is 0-7%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
Embodiment 7
Get 98% sanguinarine sulfate and 98% chelerythrine alkali sulfate, quantitatively regulate 1% sanguinarine pulvis and 1% Chelerythrine pulvis with water soluble starch.
Getting above-mentioned two kinds of pulvis kills oncomelania, the spiral shell ovum that goes out, kills blood fluke cercaria and test by the routine method of test.
1% sanguinarine pulvis:
Killing the oncomelania test is 3.13mg/L in concentration, and temperature is 25 ℃, soaks 72～96h, mortality of snails 96-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 72h, and spiral shell ovum hatchability is 0-4%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
1% Chelerythrine pulvis:
Killing the oncomelania test is 6.25mg/L in concentration, and temperature is 25 ℃, soaks 72～96h, mortality of snails 95-100%.
The spiral shell ovum that goes out test is 3.13mg/L in concentration, soaks 5d, and spiral shell ovum hatchability is 0-5%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
Embodiment 8
Get 98% sanguinarine sulfate and 98% chelerythrine alkali sulfate, mix with 1: 1 ratio.
Getting said mixture kills oncomelania, the spiral shell ovum that goes out, kills blood fluke cercaria and test by the routine method of test.
Mixture:
Killing the oncomelania test is 3.13mg/L at the mixture concentration of sanguinarine sulfate and chelerythrine alkali sulfate, and temperature is 25 ℃, soaks 72～96h, mortality of snails 98-100%.
The spiral shell ovum that goes out test is 3.13mg/L at the mixture concentration of sanguinarine sulfate and chelerythrine alkali sulfate, soaks 72h, and spiral shell ovum hatchability is 0-5%.
Kill the death in 60 minutes 100% of blood fluke cercaria test cercaria contact 3.13mg/L solution.
And schistosomulum there is inhibitory action and has the blood fluke of killing produce effect.
Claims (8)
1. sanguinarine or the Chelerythrine application in prevention and cure of snail fever is characterized in that: sanguinarine or Chelerythrine or both mixtures are used to prepare the medicine of killing oncomelania, oncomelania ovum, blood fluke cercaria, bilharzial prevention and treatment as active component.
2. sanguinarine according to claim 1 or the application of Chelerythrine in prevention and cure of snail fever is characterized in that: described sanguinarine or Chelerythrine or both mixtures are used to prepare medicine with salt form separately.
3. sanguinarine according to claim 1 or the application of Chelerythrine in prevention and cure of snail fever is characterized in that: sanguinarine or its salt, Chelerythrine or its salt or both mixtures or their salt are used to prepare molluscicide.
4. according to claim 2 or 3 described sanguinarine or the application of Chelerythrine in prevention and cure of snail fever, it is characterized in that: red root alkali salt or chelerythrine alkali salt are inorganic acid salt or organic acid salt.
5. sanguinarine according to claim 4 or the application of Chelerythrine in prevention and cure of snail fever is characterized in that: the inorganic acid in sanguinarine inorganic acid salt or the Chelerythrine inorganic acid salt is hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, boric acid, hydrobromic acid, wolframic acid or phosphorous acid.
6. the application in prevention and cure of snail fever according to described sanguinarine of claim 4 or Chelerythrine is characterized in that: the organic acid in sanguinarine organic acid salt or the Chelerythrine organic acid salt is benzoic acid, salicylic acid, oxalic acid, tartaric acid, malic acid, citric acid or caffeic acid.
7. sanguinarine according to claim 1 and 2 or the application of Chelerythrine in prevention and cure of snail fever is characterized in that: described sanguinarine or its salt, Chelerythrine or its salt or both mixtures or their salt and corresponding medicinal auxiliary material are made required formulation.
8. sanguinarine according to claim 7 or the application of Chelerythrine in prevention and cure of snail fever is characterized in that: described formulation is pulvis, powder, tablet, capsule or injection.
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| WO2015027040A3 (en) * | 2013-08-21 | 2015-08-06 | Tufts University | Methods and compositions for treating schistosome infection |
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| CN101069510A (en) * | 2007-06-20 | 2007-11-14 | 湖南师范大学 | Use of chelerythrine extracted from plant for killing snall |
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| CN102631682A (en) * | 2012-02-21 | 2012-08-15 | 中国科学院苏州纳米技术与纳米仿生研究所 | Graphene oxide and sanguinarine compound and preparation method thereof |
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| WO2015027040A3 (en) * | 2013-08-21 | 2015-08-06 | Tufts University | Methods and compositions for treating schistosome infection |
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