CN1269481C - Continuous release medicine composition and its preparation method - Google Patents
Continuous release medicine composition and its preparation method Download PDFInfo
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- CN1269481C CN1269481C CN 200410001747 CN200410001747A CN1269481C CN 1269481 C CN1269481 C CN 1269481C CN 200410001747 CN200410001747 CN 200410001747 CN 200410001747 A CN200410001747 A CN 200410001747A CN 1269481 C CN1269481 C CN 1269481C
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- medicine composition
- beta cyclodextrin
- praziquantel
- continuous
- pyquiton
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Abstract
The present invention discloses a continuous-release medicine composition and a preparation method thereof. The medicine composition obviously increases a wrapping rate of pyquiton medicine in beta cyclodextrin, and consequently, an injection medicine novel preparation with long effects for stably treating schistosomiasis and taeniasis of livestock is successfully prepared. The medicine composition has the technical scheme that pyquiton and beta cyclodextrin are used as main raw materials and are reasonably optimized and proportioned; moreover, certain technological conditions are matched with the main raw materials; the pyquiton is first dissolved in solvents, and the beta cyclodextrin is ground into paste by adding distilled water; after the pyquiton and the beta cyclodextrin are mixed, stirred, wrapped, dried and pulverized, the continuous-release medicine composition powder is formed; after the powder is packaged, the product of the continuous-release medicine composition is formed. When used, the continuous-release medicine composition is diluted into injections. The continuous-release medicine composition is mainly used for preventing and treating schistosomiasis and taeniasis of livestock such as cattle, sheep, pigs, dogs, etc.
Description
Technical field
The present invention relates to pharmaceutical composition of a kind of lasting release and preparation method thereof, especially relate to pharmaceutical composition of a kind of lasting release that prevents and treats the sick and taeniasis of domestic animal schistosome etc. and preparation method thereof.
Background technology
Schistosomicide, taeniasis are the infecting both domestic animals and human parasitic disease.Especially schistosomicide is on the rise again in recent years, has caused the great attention of country.During the domestic animal severe infections, cause that suffering from poultry becomes thin,, easily cause death, have a strong impact on the sound development of animal husbandry if control is incapable.In order to control above-mentioned parasitic disease, at present still with the oral anthelmintic of common praziquantel medicine, but interim therapeutical effect is only arranged, and do not have long-term preventive effect.Though oral administration is convenient, but medicine is subject to gastric juice to be destroyed, big (the cattle 30mg/kg body weight of dosage, Babalus bubalis L. 25mg/kg body weight, sheep 20mg/kg body weight, pig 60mg/kg body weight, Canis familiaris L. 10mg/kg body weight), short in the gastrointestinal tract time of staying, metabolism is fast, and (total removing half-life of former medicine and metabolite is 2～3 hours.Can not in body, find after 5 days).The once oral therapy of praziquantel has side reaction (mainly show as and ruminate minimizing, loss of appetite, ruminal tympany, sialorrhea is had loose bowels, heart beating speeds, spirit is depressed, can cause miscarriage when serious, death can appear in indivedual cattle).My institute has developed combined sustained-release agent of being made up of praziquantel and two kinds of medicaments of closantel and beta cyclodextrin and preparation method thereof for control domestic animal schistosome, distoma hepaticum, cestode and nematicide, proposed application for a patent for invention (application number is 03143427.4), but only be schistosomicide and taeniasis the main popular parasite in some stock keeping district.If use two kinds of medicament combined sustained-release agent controls of above-mentioned praziquantel and closantel domestic animal, will certainly cause the waste of medicine and production cost to improve, increase the financial burden at stock keeping family.Simultaneously in the process of this slow releasing agent of development, also once run into the low difficult problem of medicine inclusion rate, generally only about 55%, 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 at above-mentioned weak point, find single medicine praziquantel of planting, solvent, process conditions such as reasonably optimizing proportioning between the beta cyclodextrin and enclose procedure of processing and time, temperature, the preparation method of this pharmaceutical composition slow releasing agent is proposed, produce that to be exclusively used in control domestic animal schistosome and taeniasis cost low, inclusion rate height, the product that prevention effect is good, can stablize lasting release medicine.
The objective of the invention is to be achieved by following proposal.
A kind of pharmaceutical composition of lasting release is a raw material with praziquantel and beta cyclodextrin, forms by 1: 0.8～1: 1 weight proportion;
A kind of method for preparing the pharmaceutical composition that continues release is prepared from through following machining process:
(1), press 1 gram weight with parasitic medicine praziquantel and etoh solvent or chloroform or dichloromethane such as schistosomicide and cestodes: 15～17 ethanol or 5～7 chloroform or dichloromethane (ml volumes) mixed, jolting to medicine dissolves fully;
(2) beta cyclodextrin and sterile distilled water are pressed 0.8～1 gram weight: 1～6 ml volumes mixed, grind 20～40 minutes one-tenth pasty states;
(3) praziquantel solution is poured in the pasty state beta cyclodextrin, stirred 40～60 minutes, put under 25～40 ℃ of temperature evaporation until drying, after the pulverizing, 80～90 orders sieve, and packing is sealed, a kind of pharmaceutical composition (slow releasing agent) powder product of lasting release.
The concrete using method of this pharmaceutical composition is, with medicine powder compositions and physiological saline solution in 1: 3 ratio, be diluted to liquor, cattle, sheep are pressed the 0.05ml/kg body weight, pig is pressed 0.1ml/kg body weight, Canis familiaris L., rabbit and presses 0.03ml/kg body weight muscle or subcutaneous injection.
Receptor is stablized, slowly discharges the rule of medicine for verifying slow releasing agent of the present invention, prolong drug retaining the time limit in blood, cure the disease thereby reach in the recent period, the effect of medium-term and long-term diseases prevention, with the rabbit is experimental animal, has done the growth and decline rule test of following praziquantel medicine in rabbit anteserum: with bright injection-type slow releasing agent of this law and common praziquantel water preparation, do by the 2mg/kg body weight all that cervical region is subcutaneous injects rabbit respectively, the anti-praziquantel serum of rabbit is made in blood sampling regularly before and after the injection.The anti-praziquantel serum of rabbit is done 6 times of dilutions, do 300 times of dilutions with tested praziquantel rabbit anteserum, use the Dot-ELISA method and detect praziquantel growth and decline situation in the rabbit anteserum, the result shows, strong positive spot reaction (#) appears in the 6th～22 day serum behind the rabbit injection slow releasing agent, and strong positive spot reaction (#) appears in the 6th～9 day serum behind the rabbit injection praziquantel water preparation.Yet along with the prolongation of injection back time, the seropositivity spot reaction in the 30th～90 day behind the rabbit injection slow releasing agent weakens (++ +～++) gradually, turns out cloudy in the 100th day.And the praziquantel water preparation was turned out cloudy at the 19th day; Verified slow releasing agent and delayed pharmaceutical release time prolongation 85 days, seen Table 1 in the former dosage form of rabbit body internal ratio.
Table 1.Dot-ELISA method detects praziquantel growth and decline situation in the rabbit anteserum
| Group | The rabbit number | Natural law and Dot-ELISA response strength before and after the medication | |||||||||||||||
| 0 | 6 | 9 | 12 | 15 | 19 | 22 | 30 | 40 | 50 | 60 | 70 | 80 | 90 | 100 | 110 | ||
| Slow releasing agent | 5 | - | # | # | # | # | # | # | +++ | +++ | +++ | +++ | ++ | ++ | ++ | + | - |
| Water preparation | 5 | - | # | # | +++ | ++ | + | + | - | - | - | - | - | - | - | - | - |
For verifying the effective control phase of slow releasing agent, carried out attacking the worm viewing test, in order to avoid be experimental animal to domestic animal schistosome disease and taeniasis; after injecting slow releasing agent and oral praziquantel powder respectively; attacked the worm result on the 2nd day and show that in the time of 1～3 month, the slow releasing agent protective rate is 100%.And the oral cause of disease of in the time of 1 month, checking of praziquantel powder, the whole rabbits of result are all found pathogen.Confirm that further oral drugs do not have preventive effect, and slow releasing agent has preventive effect, its control phase can reach 3 months (seeing Table 2).
Table 2. is attacked worm protection observation after exempting to inject slow releasing agent and oral common praziquantel
| Negative rabbit number | Positive rabbit number | Protective rate (%) | |||||||||||||
| Attack time (moon) | 1 | 2 | 3 | 4 | 5 | 1 | 2 | 3 | 4 | 5 | 1 | 2 | 3 | 4 | 5 |
| The injection-type slow releasing agent | 3/3 | 3/3 | 3/3 | 1/3 | 0/3 | 0/3 | 0/3 | 0/3 | 2/3 | 3/3 | 100 | 100 | 100 | 33.3 | 0 |
| Praziquantel is oral | 3/3 | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 | 3/3 | 3/3 | 3/3 | 3/3 | 100 | 0 | 0 | 0 | 0 |
Annotate: every group of 15 rabbits, analysed 3 rabbits to collect polypide in every month towards the worm method at every turn.
Through to cattle, sheep, pig after domestic animals such as Canis familiaris L. prevent and treat test in batches, all has good prevention effect to suffering from schistosomicide or taeniasis or mixed infection person, and control domestic animal appetite increases, and the growth of livestock takes a turn for the better.And there is not repeated infection (seeing Table 3) in 3 months.
The domestic animal injection slow releasing agent and the oral medicine comparative observation negative conversion rate of table 3. pair natural infection schistosomicide and taeniasis
| Domestic animal | Head (only) | Injection-type slow releasing agent negative conversion rate (%) | The oral negative conversion rate of praziquantel (%) | ||||||||||
| Schistosomicide | Taeniasis | Schistosomicide | Taeniasis | ||||||||||
| 1 month | 2 months | 3 months | 1 month | 2 months | 3 months | 1 month | 2 months | 3 months | 1 month | 2 months | 3 months | ||
| Cattle | 500 | 100 | 100 | 100 | / | / | / | 100 | 0 | 0 | / | / | / |
| Sheep | 20 | / | / | / | 100 | 100 | 100 | / | / | / | 100 | 0 | 0 |
| Pig | 30 | / | / | / | 100 | 100 | 100 | / | / | / | 100 | 0 | 0 |
| Canis familiaris L. | 20 | / | / | / | 100 | 100 | 100 | / | / | / | 100 | 0 | 0 |
Annotate: looked into pathogen 1 time in every month.
Cattle natural infection schistosomicide injection slow releasing agent and oral medicine prevent and treat the back and do not prevent and treat cattle and herd together, carry out excrement and incubate schistosoma miracidium method observation schistosoma miracidium negative conversion rate in every month;
Cattle, sheep, pig, Canis familiaris L. natural infection taeniasis injection slow releasing agent and oral medicine control back are herded the raising of living together together with the domestic animal of not control, observe cestode worm's ovum negative conversion rate in every month.
The invention has the beneficial effects as follows,, reduced a kind of medicament (closantel), increased selection, reduce stock keeping family expenses for prevention and control expenditure 30% pharmaceutical composition at epidemic-stricken area animal infection parasitic disease practical situation.By praziquantel being pressed proper proportion of the present invention and technology enclose in beta cyclodextrin glycosidic bond circulus, form ultra micro cryptomere clathrate, by above-mentioned technological requirement operation, the dose that drops into during the medicament contg in the inclusion rate=slow releasing agent of medicine/preparation, by in the past about 55% bring up to 98.5～99.5%; Because the internal energy accurate quantification of this slow releasing agent ground enclose has the medicament contg index by designing requirement, add slow releasing agent be in carcass internal energy stable, discharge medicine lentamente, sick and taeniasis and clonorchis sinensis, lung fluke, cysticercosis and fasciolopsiasis buski etc. have all been obtained ideal prevention effect to domestic animal schistosome.This injection-type slow releasing agent has following characteristics: the one, and dosage is few, is 1/2 of oral 1 dosage; The 2nd, safe, have no side effect; The 3rd, long-acting, than long 2 months of the effective control of oral medicine time; The 4th, dosage is accurate, and is easy to use, is easy to apply; The 5th, promote the domestic animal growth, weight increase.
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%; Beta cyclodextrin is produced by the limited industrial corporation of Shaanxi Province's Liquan chemical industry and is provided; Ethanol is produced by Long March chemical plant, Hangzhou and is provided, and content is 95%; Chloroform and dichloromethane are produced by the generous chemical reagent in Hangzhou factory and are provided, and content is 99%.
A kind of pharmaceutical composition of lasting release prepares by following processing step:
Embodiment 1:
(1) powdery schistosomicide and 16000 milliliters → jolting of cestode medicament praziquantel 1000 gram+etoh solvents to medicine are dissolved into transparency liquid fully;
(2) 1500 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 45 minutes, put under 30 ℃ of temperature until drying, after the pulverizing, 80～90 orders sieve, the slow releasing agent powder product, through packing, seal.
Embodiment 2:
(1) powdery schistosomicide and 6000 milliliters → jolting of cestode medicament praziquantel 1000 gram+solvent chloroform to medicine are dissolved into transparency liquid fully;
(2) 5500 milliliters of powdery beta cyclodextrin 900 gram+distilled water → grinding was become pasty state in 40 minutes;
(3) praziquantel solution is poured in the pasty state beta cyclodextrin, stirred after 55 minutes, put under 35 ℃ of temperature until drying, after the pulverizing, 80～90 orders sieve, the slow releasing agent powder product, through packing, seal.
Implement 3:
(1) powdery schistosomicide and 7000 milliliters → jolting of cestode medicament praziquantel 1000 gram+methylene chloride to medicine are dissolved into transparency liquid fully;
(2) 3000 milliliters of powdery beta cyclodextrin 1000 gram+distilled water → grinding was become pasty state in 25 minutes;
(3) praziquantel solution is poured in the pasty state beta cyclodextrin, stirred after 45 minutes, put under 40 ℃ of temperature until drying, after the pulverizing, 80～90 orders sieve, the slow releasing agent powder product, through packing, seal.
Claims (2)
1, a kind of pharmaceutical composition of lasting release is characterized in that with praziquantel and beta cyclodextrin be raw material, forms by 1: 0.8～1: 1 weight proportion.
2, a kind of preparation continues the method for the pharmaceutical composition of release according to claim 1, it is characterized in that being prepared from through following machining process:
(1), press 1 gram weight with medicament praziquantel and etoh solvent or chloroform or dichloromethane: 15～17 ethanol or 5～7 chloroform or dichloromethane ml volumes mixed, jolting to medicine dissolves fully;
(2) beta cyclodextrin and distilled water are pressed 0.8～1 gram weight: 1～6 ml volumes mixed, grind 20～40 minutes one-tenth pasty states;
(3) praziquantel solution is poured in the pasty state beta cyclodextrin, stirred 40～60 minutes, put under 25～40 ℃ of temperature evaporation until drying, after the pulverizing, 80～90 orders sieve, product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410001747 CN1269481C (en) | 2004-01-20 | 2004-01-20 | Continuous release medicine composition and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410001747 CN1269481C (en) | 2004-01-20 | 2004-01-20 | Continuous release medicine composition and its preparation method |
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| CN1557318A CN1557318A (en) | 2004-12-29 |
| CN1269481C true CN1269481C (en) | 2006-08-16 |
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| CN 200410001747 Expired - Fee Related CN1269481C (en) | 2004-01-20 | 2004-01-20 | Continuous release medicine composition and its preparation method |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107961277A (en) * | 2016-10-20 | 2018-04-27 | 王腊俊 | A kind of compound medicine for treating swine taeniasis |
| CN109432440B (en) * | 2018-11-30 | 2022-04-26 | 佛山科学技术学院 | Praziquantel hydroxypropyl cyclodextrin inclusion compound and preparation method and application thereof |
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| C14 | Grant of patent or utility model | ||
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Assignee: Zhejiang Rongyao Chemical Co., Ltd. Assignor: Zhejiang Academy of Agricultural Sciences Contract fulfillment period: 2007.8.16 to 2013.8.15 contract change Contract record no.: 2009330001788 Denomination of invention: Continuous release medicine composition and its preparation method Granted publication date: 20060816 License type: Exclusive license Record date: 2009.8.3 |
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| LIC | Patent licence contract for exploitation submitted for record |
Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2007.8.16 TO 2013.8.15; CHANGE OF CONTRACT Name of requester: ZHEJIANG RONGYAO CHEMICAL INDUSTRY CO., LTD. Effective date: 20090803 |
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Granted publication date: 20060816 Termination date: 20140120 |