CN103550782A - Preparation method and application of water-soluble ethopabate - Google Patents
Preparation method and application of water-soluble ethopabate Download PDFInfo
- Publication number
- CN103550782A CN103550782A CN201310591151.4A CN201310591151A CN103550782A CN 103550782 A CN103550782 A CN 103550782A CN 201310591151 A CN201310591151 A CN 201310591151A CN 103550782 A CN103550782 A CN 103550782A
- Authority
- CN
- China
- Prior art keywords
- water
- ethopabate
- soluble
- cyclodextrin
- preparation
- 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.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention belongs to a preparation method and an application of water-soluble ethopabate, and relates to an anticoccidial veterinary medicine. According to the preparation method, ethopabate and beta-cyclodextrin derivative or water-soluble cyclodextrin polymer are prepared into a clathrate by using an ultrasonic or heating stirring method according to the weight ratio of 1:(10-70); the prepared clathrate can be directly used for preparing a liquid or solid anticoccidial medicine. The solubility of the ethopabate in the water is effectively increased by using the inclusion technology.
Description
Technical field
The present invention relates to a kind of anticoccidial veterinary drug, particularly a kind of preparation method and application thereof of preparing water-soluble ethopabate.
Background technology
Chicken coccidiosis is common a kind of disease important in aviculture, and the harm that it is produced poultry is very serious, and according to statistics, China reaches several hundred million yuans for preventing and treating the expenses for medicine of chicken coccidiosis every year, accounts for nearly 1/3rd of the whole expensess for prevention and control of fowl disease.Long serious hysteresis of chicken all living creatures that coccidiosis is popular, and bring out other diseases thereupon, as colibacillosis, mycoplasma etc.As far back as the 40's, people just find that sulphur limb class medicine can be used for the moon and controls coccidiosis, find successively again that afterwards the other drug medicines such as class, alkaloids, ionophore class of muttering as reflected can be used for preventing and treating coccidiosis.Oneself reaches kind more than 50 by the anticoccidial drug of report, some of them medicine is because toxicity is too large or curative effect is incessantly eliminated, still the anticoccidial drug of application has more than 20 to plant aborning at present, yet drug resistance problem has appearred in most coccidiostat after promoting the use of the several years.
Ethopabate at present most widely used dosage form is mainly pre-tear agent, and because it is insoluble in water, dissolution is lower, causes bioavailability poor, and medicine is difficult to reach the required blood drug level for the treatment of.Cyclodextrin can effectively increase the dissolubility of the relatively low medicine of some water solublity in water and stable ' property, improve the stability of medicine and bioavailability etc.
Summary of the invention
Main purpose of the present invention is to provide a kind of preparation method and application thereof of preparing water-soluble ethopabate, utilizes inclusion technique effectively to increase the dissolubility of ethopabate in water.
In order to realize foregoing invention object, the present invention adopts following technical scheme:
A kind of preparation method of preparing water-soluble ethopabate; by ethopabate and beta-cyclodextrin derivative or water-soluble cyclodextrin by weight being 1:10-70; adopt method ultrasonic or heated and stirred to be prepared into clathrate, the clathrate being prepared into can be directly used in the preparation of liquid or solid coccidiostat; The preparation method of concrete water-soluble ethopabate is as follows:
1), get ethopabate 1.5g-15g and doubly measure dissolve with ethanol with 1.5-3;
2), get beta-cyclodextrin derivative or the water-soluble cyclodextrin that ethopabate 10-65 doubly measures and add 3-6 times of water gaging preparation from cyclodextrin derivative or water-soluble cyclodextrin aqueous solution;
3) when, step 1 being stirred, slowly join in a cyclodextrin derivative or water-soluble cyclodextrin aqueous solution, supersound process 60min or 60 ℃ of heated and stirred are even, be evaporated to after smart thick shape, after the standing 12h of cold preservation is above, filter, filter cake 40-60 ℃ dry, can obtain described water-soluble ethopabate.
The described preparation method of preparing water-soluble ethopabate, wherein said beta-cyclodextrin derivative, comprises HP-β-CD, hydroxyethyl-β-cyclodextrin, dihydroxypropyl-beta-schardinger dextrin-; Water-soluble cyclodextrin comprises alpha-cyclodextrin polymer, beta cyclo dextrin polymer or gamma-cyclodextrin polymer; Preferred HP-β-CD wherein.
The described preparation method of preparing water-soluble ethopabate adds polyvinylpyrrolidone (PVP), Polyethylene Glycol (PEG) water soluble polymer when dissolving ethopabate, and consumption is 1-3g/L.
The described application of preparing water-soluble ethopabate;
The described application of preparing water-soluble ethopabate, described water-soluble ethopabate can be directly and other coccidiostat be prepared into oral administration solid, liquid dosage form.
The described application of preparing water-soluble ethopabate, while wherein preparing liquid oral, solid preparation, when with other coccidiostat coupling, weight ratio is other coccidiostat=1 of ethopabate: 15-35.
The described application of preparing water-soluble ethopabate, other described anticoccidial constituents comprises one or both in amprolium hydrochloride, sulfaquinoxaline or nicarbazine.
The described application of preparing water-soluble ethopabate, oral liquid recommended dose fowl 1L water oral liquid 1ml, 1L water or the 1kg feedstuff soluble powder 1g of preparation.
It should be noted that beta-cyclodextrin derivative of the present invention or water-soluble cyclodextrin are water solublity pharmaceutic adjuvants, utilize beta-cyclodextrin derivative or water-soluble cyclodextrin to carry out enclose to ethopabate, improved the water solublity of ethopabate, make ethopabate directly apply to liquid, solid dosage forms with the form of clathrate, solved the defect that ethopabate water solublity is low, can not directly apply to liquid dosage form.
Owing to having adopted technique scheme, the present invention has following beneficial effect:
It is simple that the present invention prepares water-soluble ethopabate method, easy operating, and the ethopabate after cyclodextrin inclusion compound is soluble in water, during mixed drink, is uniformly dispersed, and is beneficial to the absorption of animal.
The specific embodiment
The preparation of embodiment 1 water-soluble ethopabate:
1) get HP-β-CD 150g and add 6 times of amounts of water, stir, preparation HP-β-CD aqueous solution;
2) get ethopabate 15g and add polyvinylpyrrolidone 0.125g and 25ml dissolve with ethanol;
3) by 2) slowly join in hydroxypropyl--cyclodextrin aqueous solution when stirring, supersound process 60min, be evaporated to thick after, after the standing 12h of cold preservation, filter, 60 ℃ of filter cakes are dry, obtain.Record yield 91.1%, envelop rate is 94.2%.
The preparation of embodiment 2 water-soluble ethopabates:
1) get HP-β-CD 160g and add 3 times of amounts of water, stir, preparation HP-β-CD aqueous solution;
2) get ethopabate 8g 20ml dissolve with ethanol;
3) by 2) slowly join in HP-β-CD aqueous solution when stirring, 60 ℃ of heated and stirred are processed 2 hours, be evaporated to thick after, after the standing 16h of cold preservation, filter, 60 ℃ of filter cakes are dry, obtain.Record yield 93.5%, envelop rate is 95.0%.
Embodiment 3 dissolubility contrast tests
According to < < People's Republic of China (PRC) veterinary drug allusion quotation > > (2005 editions, one), carry out solubility test.
Experimental condition
Test specimen: sample 1: according to the water-soluble ethopabate 500g of embodiment 1 preparation; Sample 2: ethopabate crude drug
Test apparatus and solvent: 200ml beaker, magnetic stirring apparatus
Experimental enviroment: 25 ℃
Process of the test: get purified water 100ml and be placed in 200ml beaker, get overdose of medicine matter sample and join in purified water, be placed on magnetic stirring apparatus and stir, 25 ℃ of temperature, observe the dissolving situation of medicine in solution, until reach capacity, measure drug solution concentration and get final product.
Table 1 dissolubility test result
| Sample | Dissolubility g/1000ml (to dissolve the amount of ethopabate) |
| Sample 1 | 5.2 |
| Sample 2 | 0.058 |
From table 1, can find out, utilize its dissolubility of water-soluble ethopabate prepared by the present invention to improve 89.7 times compared with ethopabate crude drug.
Claims (7)
1. a preparation method of preparing water-soluble ethopabate, it is characterized in that: by ethopabate and beta-cyclodextrin derivative or water-soluble cyclodextrin by weight being 1:10-70, adopt method ultrasonic or heated and stirred to be prepared into clathrate, the clathrate being prepared into can be directly used in the preparation of liquid or solid coccidiostat; The preparation method of concrete water-soluble ethopabate is as follows:
1), get ethopabate 1.5g-15g and doubly measure dissolve with ethanol with 1.5-3;
2), get beta-cyclodextrin derivative or the water-soluble cyclodextrin that ethopabate 10-65 doubly measures and add 3-6 times of water gaging preparation from cyclodextrin derivative or water-soluble cyclodextrin aqueous solution;
3) when, step 1 being stirred, slowly join in beta-cyclodextrin derivative or water-soluble cyclodextrin aqueous solution, supersound process 60min or 60 ℃ of heated and stirred are even, be evaporated to thick after, after the standing 12h of cold preservation is above, filter, filter cake 40-60 ℃ dry, can obtain described water-soluble ethopabate.
2. according to the preparation method of preparing water-soluble ethopabate described in claim 1, it is characterized in that: wherein said beta-cyclodextrin derivative, comprises HP-β-CD, hydroxyethyl-β-cyclodextrin, dihydroxypropyl-beta-schardinger dextrin-; Water-soluble cyclodextrin comprises alpha-cyclodextrin polymer, beta cyclo dextrin polymer or gamma-cyclodextrin polymer; Preferred HP-β-CD wherein.
3. according to the preparation method of preparing water-soluble ethopabate described in claim 1, it is characterized in that: when dissolving ethopabate, add polyvinylpyrrolidone (PVP), Polyethylene Glycol (PEG) water soluble polymer, consumption is 1-3g/L.
4. according to the arbitrary described application of preparing water-soluble ethopabate of claim 1-3.
5. according to the application of preparing water-soluble ethopabate described in claim 4, it is characterized in that: described water-soluble ethopabate can be directly and other coccidiostat be prepared into oral administration solid, liquid dosage form.
6. according to the application of preparing water-soluble ethopabate described in claim 5, it is characterized in that: while wherein preparing liquid oral, solid preparation, when with other coccidiostat coupling, weight ratio is ethopabate: other coccidiostat=1:15-35.
7. according to the application of preparing water-soluble ethopabate described in claim 6, it is characterized in that: other described anticoccidial constituents comprises one or both in amprolium hydrochloride, sulfaquinoxaline or nicarbazine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310591151.4A CN103550782A (en) | 2013-11-22 | 2013-11-22 | Preparation method and application of water-soluble ethopabate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310591151.4A CN103550782A (en) | 2013-11-22 | 2013-11-22 | Preparation method and application of water-soluble ethopabate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103550782A true CN103550782A (en) | 2014-02-05 |
Family
ID=50005252
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310591151.4A Pending CN103550782A (en) | 2013-11-22 | 2013-11-22 | Preparation method and application of water-soluble ethopabate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103550782A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107422112A (en) * | 2017-07-01 | 2017-12-01 | 河南科技大学 | A kind of immune reagent kit for detecting ethopabate, preparation method and application |
-
2013
- 2013-11-22 CN CN201310591151.4A patent/CN103550782A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107422112A (en) * | 2017-07-01 | 2017-12-01 | 河南科技大学 | A kind of immune reagent kit for detecting ethopabate, preparation method and application |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104323987B (en) | Mequindox injection and preparation method thereof | |
| CN105287607A (en) | Compound doxycycline-hydrochloride florfenicol sustained-release microsphere suspension injection for veterinary use | |
| CN103494929A (en) | Houttuynia cordata injectable in situ gel as well as preparation method thereof | |
| CN104825416B (en) | disulfiram implant and preparation method thereof | |
| CN101317832B (en) | Oral administration nano-drug administration system of resveratrol | |
| CN101416936A (en) | Preparation method of long-acting composite sulfamonomethoxine suspension | |
| CN104644547A (en) | Long-acting cefotaxime sodium injection and preparation method thereof | |
| CN103550782A (en) | Preparation method and application of water-soluble ethopabate | |
| CN113425738A (en) | Tilmicosin gamma-cyclodextrin inclusion compound and preparation method and application thereof | |
| CN101766591B (en) | Method for preparing water-soluble ethopabate and application thereof | |
| CN103816166B (en) | Compound doxycycline hydrochloride injection for animals, and its preparation method | |
| CN108853025A (en) | A kind of Tilmicosin solid dispersions and preparation method thereof | |
| CN103622987A (en) | Veterinary long-acting compound lincomycin hydrochloride injection and preparation method thereof | |
| CN102697725B (en) | Veterinary ciprofloxacin lactate injection and preparation method thereof | |
| TW200800269A (en) | Solid dosage formulation of solubility-enhanced poorly soluble drugs | |
| CN101653448B (en) | Veterinary compound terramycin injection and preparation method thereof | |
| CN107714653B (en) | Stable soluble methotrexate granules | |
| CN114053229B (en) | Sarafloxacin hydrochloride water-soluble granules and preparation method thereof | |
| CN102266329B (en) | Pharmaceutical composition comprising vinpocetine compound and preparation method thereof | |
| CN104906039A (en) | Suspension for injecting tilmicosin and preparation method thereof | |
| CN104706577A (en) | Veterinary baicalin injection liquid and preparing method thereof | |
| KR101601794B1 (en) | Taste Masked and Orally Administered Pharmaceutical Formulation Containing Clomipramine | |
| CN110538155B (en) | Lansoprazole freeze-dried preparation for injection and preparation method thereof | |
| CN102860981A (en) | Schistosomiasis resistant praziquantel transdermal solution for flocks and herds and preparation method | |
| CN117771175B (en) | Enrofloxacin nano suspension and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20140205 |
|
| WD01 | Invention patent application deemed withdrawn after publication |