CN103520119A - Preparation method of veterinary long-acting preparation of imidocarb dipropionate - Google Patents
Preparation method of veterinary long-acting preparation of imidocarb dipropionate Download PDFInfo
- Publication number
- CN103520119A CN103520119A CN201310492082.1A CN201310492082A CN103520119A CN 103520119 A CN103520119 A CN 103520119A CN 201310492082 A CN201310492082 A CN 201310492082A CN 103520119 A CN103520119 A CN 103520119A
- Authority
- CN
- China
- Prior art keywords
- preparation
- dipropionate
- imidocard
- emulsifying
- water
- 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.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a preparation method of a veterinary long-acting preparation of imidocarb dipropionate. The preparation method comprises the following steps: (1) dissolving imidocarb dipropionate into water for injection to obtain an internal water phase; (2) dissolving a polylactic acid-glycolic acid copolymer into an organic solvent to obtain an organic phase; (3) adding the internal water phase into the organic phase, and emulsifying to obtain primary emulsion; (4) adding the primary emulsion into a sodium chloride solution of polyvinyl alcohol, and emulsifying to obtain multiple emulsion; (5) adding the multiple emulsion into a sodium chloride solution, removing impurities, and drying, thereby obtaining the long-acting preparation. The veterinary long-acting preparation of imidocarb dipropionate is prepared from poly(DL-lactic acid-glycolic acid) copolymer with the specific mole ratio of monomer polylactic acid and glycolic acid as an auxiliary material and imidocarb dipropionate microspheres prepared by the secondary emulsification method. By adopting the preparation, the defects that an existing medicament for treating bovine babesiosis is short in time of duration, is required to be fed repeatedly, and cannot maintain the prevention effect for a long time are solved.
Description
Technical field
The present invention relates to a kind of preparation method of imidocard dipropionate long-acting veterinary preparation, particularly the preparation method of imidocard dipropionate durative action preparation for a kind of babesiasis, belongs to veterinary drug preparing technical field.
Background technology
Babesiasis (being once called as bovine piroplasmosis) is that the protozoon being belonged to by Babesia parasitizes the hemocyte of cattle and the parasitic disease that reticuloendothelial system causes, by tick-borne blood protozoacide, this disease course of disease is anxious, sickness rate mortality rate is high, is one of parasitic disease that the generally acknowledged harm cattle-raising in countries in the world is the most serious.Primary disease all has popular in a plurality of areas of China, cause larger economic loss.In the situation that there is no at present, can, for the vaccine safely and effectively of large-area applications, primary disease be carried out Drug therapy and prevent just seeming particularly important.But the prevention of the EDD of the treatment Babesia disease of using is at present all shorter, can not be the susceptible season that cattle is ridden out 4 months, the invention therefore with the slow releasing preparation of long-acting just seems particularly important.
Imidocard dipropionate is the dipropionate of the derivant-imidazophenylurea of equal diphenyl urea, is the chemicals of a kind of novel antigens worm of animal specific.Clinically often by muscle or subcutaneous injection, in order to treat and to prevent various babesiosis, giardiasis, african trypanosomiasis, attached erythroderma cytopathy, edge parasitosis and theileriosis etc.After injection, can absorb rapidly and can reach blood peak concentration of drug after 1 hour.This product, as medicine dedicated for animals, has consumption little, easy to use, short treating period, the feature such as drug resistance is low, but babesiasis is ephemeral infectious disease, therefore single administration effective drug duration cannot thoroughly reach the effect of long-time epidemic prevention, adopts multiple dosing greatly to increase cost of labor.
Microsphere refers to medicine dissolution or is dispersed in the small spherical entity forming in macromolecular material substrate, common particle diameter is generally between 1～500 μ m, belong to matrix type skeleton microgranule, due to its spacetabs type to the targeting of certain organs and tissue and the release of microgranule Chinese medicine, become one of focus of novel medicine-releasing system research in recent years.The preparation technology of microsphere mainly contains multi-emulsion method, solvent evaporation method, phase separation method, spray drying method Precipitation method and coacervation etc., and wherein multi-emulsion method is the preparation method of commonly using the most.Its preparation process is: the aqueous solution of medicine is joined in the organic solvent of polymer, after ultrasonic or high-speed stirred, make colostrum, colostrum is transferred to another and containing in the water of emulsifying agent, make emulsion, constantly stir volatilization organic solvent, macromolecular material is solidified, after collection, washing, lyophilization, obtain microsphere.Preparation technology is simpler for this method, and the particle diameter of colostrum emulsion droplet is easy to control, so medicine is more easily uniformly dispersed in microsphere, and envelop rate is higher, and release is desirable.
As Chinese patent literature CN102793688A(application number 201110149039.6) a kind of preparation method of lactalase nano-microcapsule disclosed, described preparation method is multi-emulsion method, colostric fluid, by the water-soluble surfactant aqueous dispersions adding containing polylactic acid of Lactose enzyme, is made through ultrasonic dispersion by system; Colostric fluid adds the aqueous dispersions through emulsifier tween 80 containing polyvinyl alcohol, through dispersion and emulsion, makes double emulsion; The ethanol acetone soln that adds hydroxypropyl cellulose titanate esters (HP55) in double emulsion, normal temperature and pressure stirs and makes solvent evaporates, and HP55, at nano-microcapsule surface deposition, through high speed centrifugation, washing, lyophilizing, is Lactose enzyme nano-microcapsule.
But not yet there is imidocard dipropionate to adopt multi-emulsion method to make the bibliographical information of durative action preparation at present.
Summary of the invention
The present invention is directed to the deficiencies in the prior art, a kind of preparation method of imidocard dipropionate long-acting veterinary preparation is provided.
Technical solution of the present invention is as follows:
A preparation method for imidocard dipropionate long-acting veterinary preparation, step is as follows:
(1) imidocard dipropionate is dissolved in water for injection, the mass ratio of imidocard dipropionate and water for injection is 1:(3～4), mix homogeneously, makes interior water;
(2) Poly(D,L-lactide-co-glycolide (PLGA) is dissolved in organic solvent, the monomer polylactic acid of Poly(D,L-lactide-co-glycolide: the mol ratio of hydroxyacetic acid is (7～8): (2～3), the mass volume ratio of Poly(D,L-lactide-co-glycolide and organic solvent is 8～20%, unit is g/ml, mix homogeneously, makes organic facies;
(3) interior water step (1) being made is 1:(0.5～1 by volume) ratio join in the organic facies that step (2) makes, mix homogeneously, makes colostrum after emulsifying;
(4) colostrum step (3) being made joins in the sodium chloride solution that polyvinyl alcohol (PVA) mass concentration is 1～4%, and the volume ratio of colostrum and polyvinyl alcohol is 1:(5～15), second emulsifying makes emulsion;
(5) emulsion step (4) being made joins in sodium chloride solution, removes organic solvent, and centrifugal collection microsphere, through water for injection washing, after vacuum lyophilization, makes imidocard dipropionate long-acting veterinary preparation.
Preferred according to the present invention, monomer polylactic acid in described step (2): the mol ratio of hydroxyacetic acid is 3:1.
Preferred according to the present invention, the organic solvent in described step (2) and step (5) be selected from dichloromethane, acetone, ethyl acetate one or both of above arbitrarily than mixed solution;
Preferred according to the present invention, the emulsifying in described step (3) is emulsifying 30～80s under the condition of 5000～20000r/min.
Preferred according to the present invention, the second emulsifying in described step (4) is emulsifying 30～80s under the condition of 5000～20000r/min.
Preferred according to the present invention, in described step (4) and step (5), the mass concentration of sodium chloride solution is 5%.
Preferred according to the present invention, in described step (5), removing organic solvent is under 200～800r/min condition, to stir volatilization to remove organic solvent.
Preferred according to the present invention, in described step (5), the step of vacuum lyophilization is: be first placed in-20 ℃ of refrigerator overnight, be then not more than the vacuum under pressure lyophilization of 0.05mbar.
Preferred according to the present invention, in described step (5), the number of times of water for injection washing is 5～10 times.
Beneficial effect
1, the imidocard dipropionate microsphere that the present invention makes through multi-emulsion method, poly-(DL-LACTIC ACID-hydroxyacetic acid) copolymer that employing monomer polylactic acid and hydroxyacetic acid are specific molar ratio (has another name called for poly lactic-co-glycolic acid, be called for short PLGA) as adjuvant, obtained imidocard dipropionate long-acting veterinary preparation, it is short that said preparation has solved the existing sustained drug time for the treatment of babesiasis, need repeat administration, and can not maintain for a long time the shortcomings such as preventive effect.Through reality, detect, guaranteeing that in the situation that safe and effective for medication, this imidocard dipropionate long-acting veterinary preparation can make medicine discharge more slowly, can guarantee that cattle can ride out the vulnerable period of four months.
2, the present invention gathers (DL-LACTIC ACID-hydroxyacetic acid) copolymer and imidocard dipropionate consumption by adjusting, obtained the optimum balance ratio between cost, action time and epidemic prevention effect, thereby make product that this method makes guarantee to prevent epidemic effect and in the epidemic prevention time, control cost, be conducive to applying of this technology.
The specific embodiment
Below in conjunction with embodiment, technical scheme of the present invention is further elaborated, but institute of the present invention protection domain is not limited to this.
Raw material explanation
Poly-(DL-LACTIC ACID-hydroxyacetic acid) copolymer Guangzhou Su Nuo Chemical Co., Ltd. that it is 3:1 that embodiment 1 adopts monomer polylactic acid and hydroxyacetic acid mol ratio is on sale.
Poly-(DL-LACTIC ACID-hydroxyacetic acid) copolymer Guangzhou Su Nuo Chemical Co., Ltd. that it is 7:3 that embodiment 2 adopts monomer polylactic acid and hydroxyacetic acid mol ratio is on sale.
Poly-(DL-LACTIC ACID-hydroxyacetic acid) copolymer Guangzhou Su Nuo Chemical Co., Ltd. that it is 4:1 that embodiment 3 adopts monomer polylactic acid and hydroxyacetic acid mol ratio is on sale.
Imidocard dipropionate Hubei Yuancheng Pharmaceutical Co., Ltd. is on sale.
Embodiment 1
A preparation method for imidocard dipropionate long-acting veterinary preparation, step is as follows:
(1) take imidocard dipropionate 12.125g, add in 40ml water for injection, stir it is dissolved completely, as interior water;
(2) taking PLGA(molecular weight is 10000 dalton, and monomer polylactic acid and hydroxyacetic acid mol ratio are 3:1) 10g, add 60ml dichloromethane, PLGA is dissolved completely, make organic facies;
(3) interior water step (1) being made joins in the organic facies that step (2) makes, and limit edged stirs, and makes its mix homogeneously, and dispersing emulsification machine is emulsifying 60s under the condition of 5000r/min, obtains colostrum;
(4) ratio that is 1:8 according to the volume ratio of colostrum and poly-vinyl alcohol solution, it is in 2% poly-vinyl alcohol solution (the sodium chloride solution preparation that is 5% by polyvinyl alcohol and mass concentration obtains) that colostrum is joined to mass concentration, under the condition of 5000r/min, stir 30s, batch type 4 times, then second emulsifying 30min under the condition of 5000r/min, obtains emulsion;
(5) volume ratio of the sodium chloride solution that is 5% according to emulsion and mass concentration is 1:20, emulsion is put in sodium chloride solution, 30 ℃ of heating in water bath, low speed (500rpm) stirs, to volatilizing dichloromethane, the centrifugal collection microsphere of 3000rpm, water for injection washing 5 times, is placed in after-20 ℃ of refrigerator overnight, in the vacuum under pressure lyophilization of 0.05mbar, make imidocard dipropionate/PLGA medicine carrying microballoons, be imidocard dipropionate long-acting veterinary preparation.
Embodiment 2
A preparation method for imidocard dipropionate long-acting veterinary preparation, step is as follows:
(1) take imidocard dipropionate 13.125g, add in 40ml water for injection, stir it is dissolved completely, as interior water;
(2) taking PLGA(molecular weight is 10000 dalton, and monomer polylactic acid and hydroxyacetic acid mol ratio are 7:3) 10g, add 60ml acetone, PLGA is dissolved completely, make organic facies;
(3) interior water step (1) being made joins in the organic facies that step (2) makes, and limit edged stirs, and makes its mix homogeneously, and dispersing emulsification machine is emulsifying 30s under the condition of 20000r/min, obtains colostrum;
(4) ratio that is 1:5 according to the volume ratio of colostrum and poly-vinyl alcohol solution, it is in 1% poly-vinyl alcohol solution (the sodium chloride solution preparation that is 5% by polyvinyl alcohol and mass concentration obtains) that colostrum is joined to mass concentration, under the condition of 5000r/min, stir 30s, batch type 4 times, then second emulsifying 30min under the condition of 5000r/min, obtains emulsion;
(5) volume ratio of the sodium chloride solution that is 5% according to emulsion and mass concentration is 1:20, emulsion is put in sodium chloride solution, 30 ℃ of heating in water bath, low speed (500rpm) stirs, to volatilizing acetone, the centrifugal collection microsphere of 3000rpm, water for injection washing 5 times, is placed in after-20 ℃ of refrigerator overnight, in the vacuum under pressure lyophilization of 0.05mbar, make imidocard dipropionate/PLGA medicine carrying microballoons, be imidocard dipropionate long-acting veterinary preparation.
Embodiment 3
A preparation method for imidocard dipropionate long-acting veterinary preparation, step is as follows:
(1) take imidocard dipropionate 11.000g, add in 40ml water for injection, stir it is dissolved completely, as interior water;
(2) taking PLGA(molecular weight is 10000 dalton, and monomer polylactic acid and hydroxyacetic acid mol ratio are 4:1) 10g, add 60ml dichloromethane and the acetone mixed solvent of 1:1 by volume, PLGA is dissolved completely, make organic facies;
(3) interior water step (1) being made joins in the organic facies that step (2) makes, and limit edged stirs, and makes its mix homogeneously, and dispersing emulsification machine is emulsifying 80s under the condition of 10000r/min, obtains colostrum;
(4) ratio that is 1:15 according to the volume ratio of colostrum and poly-vinyl alcohol solution, it is in 4% poly-vinyl alcohol solution (the sodium chloride solution preparation that is 5% by polyvinyl alcohol and mass concentration obtains) that colostrum is joined to mass concentration, under the condition of 5000r/min, stir 30s, batch type 4 times, then second emulsifying 30min under the condition of 5000r/min, obtains emulsion;
(5) volume ratio of the sodium chloride solution that is 5% according to emulsion and mass concentration is 1:20, emulsion is put in sodium chloride solution, 30 ℃ of heating in water bath, low speed (500rpm) stirs, to volatilizing mixed solvent, the centrifugal collection microsphere of 3000rpm, water for injection washing 5 times, is placed in after-20 ℃ of refrigerator overnight, in the vacuum under pressure lyophilization of 0.04mbar, make imidocard dipropionate/PLGA medicine carrying microballoons, be imidocard dipropionate long-acting veterinary preparation.
Comparative example 1
A preparation method for imidocard dipropionate long-acting veterinary preparation, step is as follows:
(1) take imidocard dipropionate 12.125g, add in 40ml water for injection, stir it is dissolved completely, as interior water;
(2) taking PLGA(molecular weight is 10000 dalton, and monomer polylactic acid and hydroxyacetic acid mol ratio are 10:1) 10g, add 60ml dichloromethane, PLGA is dissolved completely, make organic facies;
(3) interior water step (1) being made joins in the organic facies that step (2) makes, and limit edged stirs, and makes its mix homogeneously, and dispersing emulsification machine is emulsifying 60s under the condition of 5000～20000r/min, obtains colostrum;
(4) ratio that is 1:8 according to the volume ratio of colostrum and poly-vinyl alcohol solution, it is in 2% poly-vinyl alcohol solution (the sodium chloride solution preparation that is 5% by polyvinyl alcohol and mass concentration obtains) that colostrum is joined to mass concentration, under the condition of 5000r/min, stir 30s, batch type 4 times, then second emulsifying 30min under the condition of 5000r/min, obtains emulsion;
(5) volume ratio of the sodium chloride solution that is 5% according to emulsion and mass concentration is 1:20, emulsion is put in sodium chloride solution, 30 ℃ of heating in water bath, low speed (500rpm) stirs, to volatilizing dichloromethane, and the centrifugal collection microsphere of 3000rpm, water for injection washing 5 times, be placed in after-20 ℃ of refrigerator overnight, in the vacuum under pressure lyophilization of 0.05mbar, make imidocard dipropionate/PLGA medicine carrying microballoons.
Comparative example 2
A preparation method for imidocard dipropionate long-acting veterinary preparation, step is as follows:
(1) take imidocard dipropionate 12.125g, add in 30ml water for injection, stir it is dissolved completely, as interior water;
(2) taking PLGA(molecular weight is 10000 dalton, and monomer polylactic acid and hydroxyacetic acid mol ratio are 2:1) 10g, add 60ml dichloromethane, PLGA is dissolved completely, make organic facies;
(3) interior water step (1) being made joins in the organic facies that step (2) makes, and limit edged stirs, and makes its mix homogeneously, and dispersing emulsification machine is emulsifying 60s under the condition of 5000～20000r/min, obtains colostrum;
(4) ratio that is 1:8 according to the volume ratio of colostrum and poly-vinyl alcohol solution, it is in 2% poly-vinyl alcohol solution (the sodium chloride solution preparation that is 5% by polyvinyl alcohol and mass concentration obtains) that colostrum is joined to mass concentration, under the condition of 5000r/min, stir 30s, batch type 4 times, then second emulsifying 30min under the condition of 5000r/min, obtains emulsion;
(5) volume ratio of the sodium chloride solution that is 5% according to emulsion and mass concentration is 1:20, emulsion is put in sodium chloride solution, 30 ℃ of heating in water bath, low speed (500rpm) stirs, to volatilizing dichloromethane, and the centrifugal collection microsphere of 3000rpm, water for injection washing 5 times, be placed in after-20 ℃ of refrigerator overnight, in the vacuum under pressure lyophilization of 0.05mbar, make imidocard dipropionate/PLGA medicine carrying microballoons.
Comparative example 3
A preparation method for imidocard dipropionate long-acting veterinary preparation, step is as follows:
(1) take imidocard dipropionate 12.125g, add in 60ml water for injection, stir it is dissolved completely, as interior water;
(2) taking PLGA(molecular weight is 10000 dalton, and monomer polylactic acid and hydroxyacetic acid mol ratio are 2:1) 10g, add 60ml dichloromethane, PLGA is dissolved completely, make organic facies;
(3) interior water step (1) being made joins in the organic facies that step (2) makes, and limit edged stirs, and makes its mix homogeneously, and dispersing emulsification machine is emulsifying 60s under the condition of 5000～20000r/min, obtains colostrum;
(4) ratio that is 1:8 according to the volume ratio of colostrum and poly-vinyl alcohol solution, it is in 2% poly-vinyl alcohol solution (the sodium chloride solution preparation that is 5% by polyvinyl alcohol and mass concentration obtains) that colostrum is joined to mass concentration, under the condition of 5000r/min, stir 30s, batch type 4 times, then second emulsifying 30min under the condition of 5000r/min, obtains emulsion;
(5) volume ratio of the sodium chloride solution that is 5% according to emulsion and mass concentration is 1:20, emulsion is put in sodium chloride solution, 30 ℃ of heating in water bath, low speed (500rpm) stirs, to volatilizing dichloromethane, and the centrifugal collection microsphere of 3000rpm, water for injection washing 5 times, be placed in after-20 ℃ of refrigerator overnight, in the vacuum under pressure lyophilization of 0.05mbar, make imidocard dipropionate/PLGA medicine carrying microballoons.
The pharmacokinetic of imidocard dipropionate/PLGA medicine carrying microballoons of experimental example 1 preparation
Control drug: imidocard dipropionate injection, concentration 5g/100ml.
Trial drug: imidocard dipropionate/PLGA medicine carrying microballoons of embodiment 1,2,3 and comparative example 1,2,3 preparations is dissolved in respectively in water for injection, makes the double emulsion that concentration is 5g imidocard dipropionate/100ml.
Test method: 1, get healthy mice, be divided at random seven groups, 48 every group, I group mouse tail vein injection control drug, every kg body weight dosage is 0.05mg imidocard dipropionate; II～VII group mouse tail vein injection Experimental agents (double emulsion of imidocard dipropionate/PLGA medicine carrying microballoons preparation of embodiment 1～3 and comparative example 1～3 preparation), every kg body weight dosage is 0.05mg imidocard dipropionate.After injection 0.5,1,2,4,8,12,24,48,72 hour, choose at random 6 mouse orbits for every group and get blood 0.5ml, centrifugal separation plasma, HPLC method is measured the content of imidocard dipropionate in blood plasma.
Pharmacokinetics result of the test (the blood drug level unit: ug/ml) of table 1 imidocard dipropionate/PLGA medicine carrying microballoons
The double emulsion of imidocard dipropionate/PLGA medicine carrying microballoons preparation of conclusion: embodiment 1～3 preparation can obviously delay drug absorption, prolong drug action time.
The pharmacodynamic study of experimental example 2 imidocard dipropionates/PLGA medicine carrying microballoons
Control drug: imidocard dipropionate injection, concentration 5g/100ml.
Trial drug: imidocard dipropionate/PLGA medicine carrying microballoons of embodiment 1,2,3 and comparative example 1,2,3 preparations is dissolved in respectively in water for injection, makes the double emulsion that concentration is 5g imidocard dipropionate/100ml.
Test period: in June, 2013 to 2013 year JIUYUE, four totally months.
Experimental animal: choose 560, certain farm and suffer from cattle, wherein Adult Bovine is 394,166 of calves.By the object of these Niu Zuowei imidocard dipropionate/PLGA medicine carrying microballoons efficacy of medicine observing tests.160 cattle are divided into seven groups of A, B, C, D, E, F, G at random, and every group of 80 cattle, correspondingly respectively use the trial drug that control drug and embodiment 1～3 and reference examples 1～3 make.Suffer from Niu Caiyong dosage for every group and be 0.2mg imidocard dipropionate/kg, after medication, in original place feeding and management, and observe.
Efficacy determination: face and examine inspection, gather blood, microscopic examination Babesia infection conditions.
The results of pharmacodynamic test of table 2 imidocard dipropionate/PLGA medicine carrying microballoons
The disposable medication of double emulsion of imidocard dipropionate/PLGA medicine carrying microballoons preparation of conclusion: embodiment 1～3 preparation,
Cure rate, up to 95%, belongs to the durative action preparation of Effective Anti babesiasis.
Claims (9)
1. a preparation method for imidocard dipropionate long-acting veterinary preparation, is characterized in that, step is as follows:
(1) imidocard dipropionate is dissolved in water for injection, the mass ratio of imidocard dipropionate and water for injection is 1:(3～4), mix homogeneously, makes interior water;
(2) Poly(D,L-lactide-co-glycolide (PLGA) is dissolved in organic solvent, the monomer polylactic acid of Poly(D,L-lactide-co-glycolide: the mol ratio of hydroxyacetic acid is (7～8): (2～3), the mass volume ratio of Poly(D,L-lactide-co-glycolide and organic solvent is 8～20%, unit is g/ml, mix homogeneously, makes organic facies;
(3) interior water step (1) being made is 1:(0.5～1 by volume) ratio join in the organic facies that step (2) makes, mix homogeneously, makes colostrum after emulsifying;
(4) colostrum step (3) being made joins in the sodium chloride solution that polyvinyl alcohol (PVA) mass concentration is 1～4%, and the volume ratio of colostrum and polyvinyl alcohol is 1:(5～15), second emulsifying makes emulsion;
(5) emulsion step (4) being made joins in sodium chloride solution, removes organic solvent, and centrifugal collection microsphere, through water for injection washing, after vacuum lyophilization, makes imidocard dipropionate long-acting veterinary preparation.
2. preparation method as claimed in claim 1, is characterized in that, monomer polylactic acid in described step (2): the mol ratio of hydroxyacetic acid is 3:1.
3. preparation method as claimed in claim 1, is characterized in that, the organic solvent in described step (2) and step (5) be selected from dichloromethane, acetone, ethyl acetate one or both of above arbitrarily than mixed solution.
4. preparation method as claimed in claim 1, is characterized in that, the emulsifying in described step (3) is emulsifying 30～80s under the condition of 5000～20000r/min.
5. preparation method as claimed in claim 1, is characterized in that, the second emulsifying in described step (4) is emulsifying 30～80s under the condition of 5000～20000r/min.
6. preparation method as claimed in claim 1, is characterized in that, in described step (4) and step (5), the mass concentration of sodium chloride solution is 5%.
7. preparation method as claimed in claim 1, is characterized in that, in described step (5), removing organic solvent is under 200～800r/min condition, to stir volatilization to remove organic solvent.
8. preparation method as claimed in claim 1, is characterized in that, in described step (5), the step of vacuum lyophilization is: be first placed in-20 ℃ of refrigerator overnight, be then not more than the vacuum under pressure lyophilization of 0.05mbar.
9. preparation method as claimed in claim 1, is characterized in that, in described step (5), the number of times of water for injection washing is 5～10 times.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310492082.1A CN103520119B (en) | 2013-10-21 | 2013-10-21 | The preparation method of imidocard dipropionate long-acting veterinary preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310492082.1A CN103520119B (en) | 2013-10-21 | 2013-10-21 | The preparation method of imidocard dipropionate long-acting veterinary preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103520119A true CN103520119A (en) | 2014-01-22 |
| CN103520119B CN103520119B (en) | 2016-03-02 |
Family
ID=49922710
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310492082.1A Active CN103520119B (en) | 2013-10-21 | 2013-10-21 | The preparation method of imidocard dipropionate long-acting veterinary preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103520119B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104557715A (en) * | 2014-12-23 | 2015-04-29 | 齐鲁晟华制药有限公司 | Preparation method of imidocarb dipropionate sterile APIs (active pharmaceutical ingredients) |
| CN107334731A (en) * | 2017-07-07 | 2017-11-10 | 中国农业科学院饲料研究所 | A kind of ox imidocard dipropionate parenteral solution and its preparation method and application |
| CN108669272A (en) * | 2018-06-01 | 2018-10-19 | 黑龙江福和制药集团股份有限公司 | A kind of dandelion tea bag and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1739795A (en) * | 2005-08-31 | 2006-03-01 | 上海交通大学 | Prepn process of slow release parathyroid hormone microballoon |
-
2013
- 2013-10-21 CN CN201310492082.1A patent/CN103520119B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1739795A (en) * | 2005-08-31 | 2006-03-01 | 上海交通大学 | Prepn process of slow release parathyroid hormone microballoon |
Non-Patent Citations (1)
| Title |
|---|
| 庞天津等: "盐酸咪唑苯脲W/O/W型复乳制剂处方的研制", 《畜牧与兽医》, vol. 41, no. 09, 31 December 2009 (2009-12-31), pages 18 - 21 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104557715A (en) * | 2014-12-23 | 2015-04-29 | 齐鲁晟华制药有限公司 | Preparation method of imidocarb dipropionate sterile APIs (active pharmaceutical ingredients) |
| CN104557715B (en) * | 2014-12-23 | 2017-01-11 | 齐鲁晟华制药有限公司 | Preparation method of imidocarb dipropionate sterile APIs (active pharmaceutical ingredients) |
| CN107334731A (en) * | 2017-07-07 | 2017-11-10 | 中国农业科学院饲料研究所 | A kind of ox imidocard dipropionate parenteral solution and its preparation method and application |
| CN107334731B (en) * | 2017-07-07 | 2021-06-04 | 中国农业科学院饲料研究所 | Cattle imidocarb dipropionate injection and preparation method and application thereof |
| CN108669272A (en) * | 2018-06-01 | 2018-10-19 | 黑龙江福和制药集团股份有限公司 | A kind of dandelion tea bag and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103520119B (en) | 2016-03-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2586306C2 (en) | Risperidone sustained release microsphere composition | |
| CN102302457B (en) | Preparation method of ivermectin sustained-release microspheres | |
| CN101703482B (en) | Galanthamine long-acting release injectable microsphere composite and preparation method thereof | |
| CN107811967B (en) | Antiparasitic in-situ curing slow-release injection and preparation method thereof | |
| CN103520119B (en) | The preparation method of imidocard dipropionate long-acting veterinary preparation | |
| CN102423300A (en) | Acetyl amino abamectin sustained-release microsphere and preparation method as well as sustained-release microsphere injection | |
| US20110104151A1 (en) | Microparticle compositions and methods for treating age-related macular degeneration | |
| CN108912349A (en) | Polylactic acid microsphere and preparation method thereof and the application in medicament slow release | |
| CN103720652B (en) | Prepare containing Avermectins medicine injection with poloxamer and oil medium | |
| CN1723895A (en) | Injectable long-acting microsphere suspension contg. | |
| CN102083742A (en) | Method for manufacturing uniform size polymeric nanoparticles containing poorly soluble drugs | |
| CN105288613A (en) | Nanoparticle vaccine preparation containing recombinant hepatitis B surface antigen and preparation method thereof | |
| CN103721266A (en) | In-situ gelation injection containing avermectin medicine/hydrogenated castor oil | |
| CN102008436B (en) | Nocathiacin antibiotic medicament composition containing emulsifying agent | |
| CN101756909B (en) | Lung-targeting ceftiofur microsphere and preparation method thereof | |
| CN103908659B (en) | P-GLU-HIS-TRP-SER-TYR-D-TRP-LEU-ARG-PRO-GLY-NH2 and ziconotide composition sustained-release microsphere preparation and preparation method thereof | |
| CN103462901A (en) | Method for controlling dichloromethane residue in polymer microsphere preparation | |
| CN1835735A (en) | Drug delivery system for administering fine particle under tenon's capsule | |
| CN101511341A (en) | Sustained release formulations of aromatase inhibitors | |
| CN103932989A (en) | Method used for preparing pharmaceutic adjuvant Eudragit RL100 polymer particulates | |
| CN102652736A (en) | Method for preparing soybean isoflavone sustained-release microspheres | |
| Shenoy et al. | Poly (DL-lactide-co-glycolide) microporous microsphere-based depot formulation of a peptide-like antineoplastic agent | |
| CN101947206B (en) | Method for preparing recombinant pancreotropic hormone secretion peptide medicament microspheres | |
| CN111358934A (en) | Leuprolide acetate long-acting pharmaceutical preparation combination and use method thereof | |
| CN103845296A (en) | Aspirin lipid microsphere preparation and preparation method of aspirin lipid microsphere preparation |
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 | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Wang Haiting Inventor after: Li Youzhi Inventor after: Li Baohua Inventor after: Kong Mei Inventor after: Wu Lianyong Inventor before: Wang Haiting |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20171114 Address after: Industrial Road Licheng District, Ji'nan city of Shandong Province, No. 243 250100 Co-patentee after: SHANDONG PROVINCE VETERINARY DRUG QUALITY INSPECTION Patentee after: Qilu Animal Health Products Co., Ltd. Address before: Industrial Road Licheng District, Ji'nan city of Shandong Province, No. 243 250100 Patentee before: Qilu Animal Health Products Co., Ltd. |