CN1232253C - Combined slow-release agent for preventing and treating domstic aminal schistosome, fascioliasis, cestodiasis and nematodiasis and preparing method thereof - Google Patents
Combined slow-release agent for preventing and treating domstic aminal schistosome, fascioliasis, cestodiasis and nematodiasis and preparing method thereof Download PDFInfo
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- CN1232253C CN1232253C CN 03143427 CN03143427A CN1232253C CN 1232253 C CN1232253 C CN 1232253C CN 03143427 CN03143427 CN 03143427 CN 03143427 A CN03143427 A CN 03143427A CN 1232253 C CN1232253 C CN 1232253C
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- release agent
- praziquantel
- beta cyclodextrin
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- cestodiasis
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Abstract
The present invention discloses a combined slow release agent for preventing and treating domstic animal schistosome, fascioliasis, cestodiasis and nematodiasis and a preparing method thereof. The clathration rate of medicine in beta cyclodextrin is obviously increased. Therefore, a novel medicine preparation which can stably prevent and treat various kinds of trematodiasis, cestodiasis and nematodiasis of domstic animals in a long acting mode is successfully prepared. The present invention has the key point of the technical scheme that praziquantel, chlorocyaniodosalamine and beta cyclodextrin are used as main raw material; the main raw material is reasonably optimized and mixed through certain technical conditions; the praziquantel is dissolved in solvent, the beta cyclodextrin is ground to be pasty in distillation water, and the praziquantel and the beta cyclodextrin are mixed, stirred and covered; some time later, chlorocyaniodosalamine solution dissolved with the solvent is added; through agitation, clathration, dryness and pulverization, combined slow release agent powder is obtained; the combined slow release agent powder is packed, and the combined slow release agent of the present invention is prepared. The combined slow release agent is mainly applied to prevent and treat schistosome, fascioliasis, cestodiasis and nematodiasis of domstic animals, such as cattle, sheep, pigs, rabbits, dogs, etc.
Description
Technical field
The present invention relates to prevent and treat sick medicament of animal parasite and preparation method thereof, especially relate to a kind of combined sustained-release agent of preventing and treating domestic animal schistosome, distoma hepaticum, cestode and nematicide and preparation method thereof.
Background technology
Schistosomicide, distoma hepaticum, cestode and nematicide are the domestic animal common parasitic disease, are widely current in China south, and are ascendant trend year by year.These parasitic disease of the normal mixed infection of domestic animal cause domestic animal to become thin, and meat yield reduces, and milk production of cow reduces, and farm cattle forfeiture farming ability has a strong impact on the sound development of animal husbandry.In order to control above-mentioned parasitic disease, at present still with common single agent praziquantel and the closantel medicine is oral or the anthelmintic of injection medicine.Above-mentioned medicament only has interim therapeutical effect, and does not have long-term preventive effect.Simultaneously, in clinical, it is to have suffered from that a kind of parasitic disease that basic unit also is difficult to diagnose clear and definite actually.So often take continuous a couple of days oral simultaneously or inject above two kinds of medicaments and can reach therapeutic purposes in application, its dosage is bigger, and is time-consuming, increased to prevent and treat cost.At above-mentioned phenomenon, the court has been developed into praziquantel and closantel combined sustained-release agent, and domestic animal only need be injected 1 pin combined sustained-release agent, can prevent and treat schistosomicide, distoma hepaticum, cestode and nematicide simultaneously, therapeutic effect reaches 100%, and effectively the control time reached more than 3 months.But in the process of this combined sustained-release agent of development, a difficult problem that runs into is that the medicine inclusion rate is low, generally only about 58%, and medicine easily crystallization separate out, cause product cure rate instability in application test, phenomenons such as poor effect.
Summary of the invention
The objective of the invention is to find medicine, solvent at above-mentioned difficult point, process conditions such as reasonably optimizing proportioning between the beta cyclodextrin and enclose procedure of processing and time, temperature, propose the preparation method of this combined sustained-release agent, it is low to produce cost, the combined sustained-release agent product that prevention effect is good.
The objective of the invention is to be achieved by following proposal.
Control domestic animal schistosome, distoma hepaticum, cestode and nematicide combined sustained-release agent are raw material with praziquantel and closantel and beta cyclodextrin, form by 1: 0.4: 0.8 weight proportion.
The method for preparing above-mentioned control domestic animal schistosome, distoma hepaticum, cestode and nematicide combined sustained-release agent is prepared from through following machining process:
(1) weighting raw materials praziquantel, closantel and inclusion agents beta cyclodextrin by weight ratio, standby;
(2) with praziquantel and solvent chloroform or the dichloromethane of schistosomicide, cestode, press 1 (gram weight): 2～6 (milliliter volume) mixed, jolting to medicine dissolves fully;
(3) beta cyclodextrin and distilled water are pressed 0.8 (gram weight): 4～8 (milliliter volume) mixed, grind 20～40 minutes one-tenth pasty states;
(4) praziquantel solution (2) is poured in the pasty state beta cyclodextrin (3), stirred 50～70 minutes, put room temperature and continued enclose 30～50 minutes;
(5) will kill medicament closantel and solvent acetone or the ethanol of distoma hepaticum and nematicide, by 0.4 (gram weight): 1～3 milliliter of (milliliter volume) mixed, jolting to medicine dissolves fully;
(6) chlorocyaniosaliamine amine aqueous solution (5) is poured in praziquantel and the beta cyclodextrin clathrate (4), stirred after 40～80 minutes, put under 30～40 ℃ of temperature until drying, after the pulverizing, 80～90 orders sieve, the combined sustained-release agent powder product.
The invention has the beneficial effects as follows, by with praziquantel and these two kinds of medicines of closantel by proper proportion and technology enclose in beta cyclodextrin glycosidic bond circulus, form ultra micro cryptomere clathrate, the inclusion rate of medicine by in the past about 58% bring up to 97.9～99.6%; Because the internal energy accurate quantification of this combined sustained-release agent ground enclose has the medicament contg index by designing requirement, add combined sustained-release agent be in carcass internal energy constant, discharge medicine lentamente, it effectively prevents and treats schistosomicide, distoma hepaticum, cestode and nematicide for up to more than 3 months, has obtained comparatively ideal prevention effect.Warp is to cattle, sheep, pig, Canis familiaris L., domestic animals such as rabbit prevent and treat test in batches, by big domestic animal 0.05ml/kg body weight, 1.0～3.0 milliliters of/dosage injections of hog all have good prevention effect to suffering from schistosomicide, distoma hepaticum, cestode and nematicide single kind disease or mixed infection person, generally inject recovery from illness in 2～7 days, appetite increases, and the growth of livestock takes a turn for the better.And there is not repeated infection in 3～4 months.This combined sustained-release agent has following characteristics: the one, and the anthelmintic spectrum is wide; The 2nd, dosage is few, is 1/2 of oral 1 dosage, can save medication expense 66.7～88.9% one course of treatment than oral anthelmintic; The 3rd, safe, have no side effect; The 4th, long-acting, effectively the control time is grown more than 2 months than oral common drug; Five are to use conveniently, improve 6～13 times of work efficiency than the single anti-method of treatment of parasitosis of planting of tradition, are easy to apply; The 6th, promote the domestic animal growth, weight increase can make domestic animal fur gloss again and bright.Concrete prevention effect sees the following form:
Combined sustained-release agent is to the prevention effect list position % of domestic animal schistosome, distoma hepaticum, cestode stomach function regulating intestinal nematodes disease
| Domestic animal | Schistosomicide | Fascioliasis hepatica | Taeniasis | The gastrointestinal tract nematicide | ||||||||
| January | February | March | January | February | March | January | February | March | January | February | March | |
| Cattle | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
| Sheep | / | / | / | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
| Pig | / | / | / | // | / | / | 100 | 100 | 100 | 100 | 100 | 100 |
| Rabbit | 100 | 100 | 100 | / | / | / | / | / | / | / | / | / |
| Canis familiaris L. | / | / | / | / | / | / | 100 | 100 | 100 | / | / | / |
Annotate: incubate the schistosoma miracidium method as excrement behind the cattle natural infection schistosomicide injection combined sustained-release agent and observe the miracidium negative conversion rate;
Take dissection to look into worm method observation polypide behind sheep natural infection distoma hepaticum, the gastrointestinal tract nematicide injection combined sustained-release agent and drive clean rate;
The Gaster Sus domestica intestinal nematodes adopts excrement inspection worm's ovum method to observe the worm's ovum negative conversion rate;
Attack the schistosoma miracidium method behind the rabbit injection combined sustained-release agent and observe protective rate;
Cattle, sheep, pig, Canis familiaris L. natural infection taeniasis injection combined sustained-release agent are observed the worm's ovum negative conversion rate.
The specific embodiment
The specific embodiment of the present invention is as follows:
Using praziquantel to be produced by Shanghai No.6 Pharmaceutical Factory provides, and content is 99%; Closantel sodium is produced by Huangyan, Zhejiang honor chemical plant and is provided, and content is 99%; Beta cyclodextrin is produced by the limited industrial corporation of Shaanxi Province's Liquan chemical industry and is provided; Chloroform, dichloromethane and acetone are produced by the generous chemical reagent in Hangzhou factory and are provided, and content is followed successively by 99%, 99% and 99.5%; Ethanol is produced by Long March chemical plant, Hangzhou and is provided, and content is 95%.
Embodiment 1:
Control domestic animal schistosome, distoma hepaticum, cestode and nematicide combined sustained-release agent prepare by following processing step, condition:
(1) powdery schistosomicide and 2000 milliliters → jolting of cestode medicament praziquantel 1000 gram+solvent chloroform to medicine are dissolved into transparency liquid fully;
(2) 4000 milliliters of powdery beta cyclodextrin 800 gram+distilled water → grinding was become pasty state in 20 minutes;
(3) praziquantel solution is poured in the pasty state beta cyclodextrin, stirred after 50 minutes, put room temperature and continued enclose 30 minutes;
(4) powdery is killed distoma hepaticum and 1000 milliliters → jolting of nematicide medicament closantel 400 gram+solvent acetone to medicine is dissolved into transparency liquid fully;
(5) the chlorocyaniosaliamine amine aqueous solution is poured in above-mentioned praziquantel and the beta cyclodextrin clathrate, stirred after 40 minutes, put 30～40 ℃ of following solvent evaporates, water evaporates is until drying, pulverized for 20 seconds after, 80～90 orders sieve, the combined sustained-release agent powder product, through packing, seal.
Embodiment 2:
(1) powdery schistosomicide and 6000 milliliters → jolting of cestode medicament praziquantel 1000 gram+methylene chloride to medicine are dissolved into transparency liquid fully;
(2) 8000 milliliters of powdery beta cyclodextrin 800 gram+distilled water → grinding was become pasty state in 40 minutes;
(3) praziquantel solution is poured in the pasty state beta cyclodextrin, stirred after 70 minutes, put room temperature and continued enclose 50 minutes;
(4) powdery is killed distoma hepaticum and 3000 milliliters → jolting of nematicide medicament closantel 400 gram+etoh solvents to medicine is dissolved into transparency liquid fully;
(5) the chlorocyaniosaliamine amine aqueous solution is poured in above-mentioned praziquantel and the beta cyclodextrin clathrate, stirred after 80 minutes, put 30～40 ℃ of following solvent evaporates, water evaporates is until drying, pulverized for 20 seconds after, 80～90 orders sieve, the combined sustained-release agent powder product, through packing, seal.
Claims (2)
1, control domestic animal schistosome, distoma hepaticum, cestode and nematicide combined sustained-release agent is characterized in that with praziquantel and closantel and beta cyclodextrin be raw material, form by 1: 0.4: 0.8 weight proportion.
2, the method for preparing the described combined sustained-release agent of claim 1 is characterized in that being prepared from through following processing technique:
(1) weighting raw materials praziquantel, closantel and inclusion agents beta cyclodextrin by weight ratio, standby;
(2), press 1 (gram weight) with praziquantel and solvent chloroform or dichloromethane: 2～6 (milliliter volume) mixed, jolting to medicine dissolves fully;
(3) beta cyclodextrin and distilled water are pressed 0.8 (gram weight): 4～8 (milliliter volume) mixed, grind 20～40 minutes one-tenth pasty states;
(4) praziquantel solution (2) is poured in the pasty state beta cyclodextrin (3), stirred 50～70 minutes rearmounted room temperatures and continued enclose 30～50 minutes;
(5), press 0.4 (gram weight) with closantel and solvent acetone or ethanol: 1～3 (milliliter volume) mixed, jolting to medicine dissolves fully;
(6) chlorocyaniosaliamine amine aqueous solution (5) is poured in praziquantel and the beta cyclodextrin clathrate (4), stirred after 40～80 minutes, put under 30～40 ℃ of temperature until drying, after the pulverizing, 80～90 orders sieve, the combined sustained-release agent powder product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03143427 CN1232253C (en) | 2003-09-30 | 2003-09-30 | Combined slow-release agent for preventing and treating domstic aminal schistosome, fascioliasis, cestodiasis and nematodiasis and preparing method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03143427 CN1232253C (en) | 2003-09-30 | 2003-09-30 | Combined slow-release agent for preventing and treating domstic aminal schistosome, fascioliasis, cestodiasis and nematodiasis and preparing method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1528310A CN1528310A (en) | 2004-09-15 |
| CN1232253C true CN1232253C (en) | 2005-12-21 |
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| CN 03143427 Expired - Fee Related CN1232253C (en) | 2003-09-30 | 2003-09-30 | Combined slow-release agent for preventing and treating domstic aminal schistosome, fascioliasis, cestodiasis and nematodiasis and preparing method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021198116A1 (en) * | 2020-04-01 | 2021-10-07 | UNION therapeutics A/S | Formulation |
| US11324708B1 (en) | 2020-04-01 | 2022-05-10 | UNION therapeutics A/S | Niclosamide formulations for treating disease |
-
2003
- 2003-09-30 CN CN 03143427 patent/CN1232253C/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021198116A1 (en) * | 2020-04-01 | 2021-10-07 | UNION therapeutics A/S | Formulation |
| US11324708B1 (en) | 2020-04-01 | 2022-05-10 | UNION therapeutics A/S | Niclosamide formulations for treating disease |
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| Publication number | Publication date |
|---|---|
| CN1528310A (en) | 2004-09-15 |
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