CN102671199B - Dissolving agent capable of dissolving diclazuril and ethopabate simultaneously and anticoccidial medicinal composition - Google Patents
Dissolving agent capable of dissolving diclazuril and ethopabate simultaneously and anticoccidial medicinal composition Download PDFInfo
- Publication number
- CN102671199B CN102671199B CN 201210011293 CN201210011293A CN102671199B CN 102671199 B CN102671199 B CN 102671199B CN 201210011293 CN201210011293 CN 201210011293 CN 201210011293 A CN201210011293 A CN 201210011293A CN 102671199 B CN102671199 B CN 102671199B
- Authority
- CN
- China
- Prior art keywords
- diclazuril
- coccidiosis
- ethopabate
- dissolving
- ester
- 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.)
- Expired - Fee Related
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a dissolving agent capable of dissolving diclazuril and ethopabate simultaneously and an anticoccidial medicinal composition. The dissolving agent consists of tetrahydrofuran and dimethylfomamide, and can be used for well dissolving diclazuril and ethopabate; and the production problem that diclazuril and ethopabate are dissoluble in water while an ordinary anticoccidial premixing agent is difficult to mix uniformly in a feed is solved. The anticoccidial medicinal composition prepared by using the dissolving agent contains high concentration diclazuril and ethopabate, and has low toxicity; a solution is stable in an environment of which the temperature is over 4 DEG C; crystal substances are precipitated out in a low-temperature environment; and crystal substances can be dissolved by heating to 65 DEG C and preserving heat for 15 minutes or heating to 25 DEG C and preserving heat for 80 minutes, and the solution becomes clear. Due to the adoption of the dissolving agent, diclazuril and ethopabate can be administrated effectively by drinking water; and the dissolving agent is simple, convenient and effective, and has a wide market prospect and high economic benefit.
Description
Technical field
The invention belongs to field of veterinary, relate to a kind of lytic agent and a kind of Anticoccidiosis pharmaceutical composition that can dissolve simultaneously diclazuril and coccidiosis ester.
Background technology
Chicken coccidiosis is the chicken parasitic disease that is caused by Eimeria; it is a kind of global protozoacide; it is one of disease that the intensive poultry husbandry of scale is the most multiple, harm is the most serious and control is difficult, also is one of disease that economic loss is the most serious in all Animal diseases.This disease is classified as one of the most serious disease of birds harm by United States Department of Agriculture (USDA) at present.Chicken coccidiosis is very serious with the harm of breeding chicken to chickling, and the chickling sickness rate of 15-50 age in days is high, and mortality rate is up to more than 80%.The chick growth of anti-mistake is slow, dysplasia; Become chicken mostly to be the carrier, increasing weight and laying eggs is under some influence.Because the raising condition in the intensive chicken farm of scale is well suited for the coccidian oocyst spore development, because egg capsule only to thermo-responsive, has again very strong resistance to disinfectant commonly used, so very difficult generation of stopping chicken coccidiosis with the administration of health means.Therefore the control of chicken coccidiosis is still take chemoprophylaxis as main at present, and annual coccidiostat annual turnover accounts for more than 10% of veterinary drug Total sales volume.Coccidiostat is most active part in the veterinary drug prodution and development.
Diclazuril belongs to triazine benzene acetonitrile chemical compound, for novel, efficient, low toxicity anticoccidial drug, is widely used in the control of chicken coccidiosis.At present, the diclazuril anticoccidial mechanism of action is also not clear.In the peak phase, different with the different genera of coccidiosis to the coccidiosis Main Function.Coccidiosis ester (ethopabate) is the anticoccidial drug synergist, and polygamy becomes compound preparation, is widely used in clinical.The coccidiosis ester is huge to chicken, E.brunetti and other small intestinal coccidiosiss have stronger effect, and is normal with diclazuril and for veterinary clinic, brought into play good effect in the process preventing and treating of coccidiosis.Diclazuril and synergist coccidiosis ester thereof are the splendid medicines of preventing and treating at present chicken coccidiosis, yet the two is all water insoluble, and directly water-soluble chicken is drunk fed; And commercially available diclazuril pre-mixing agent (0.5%, 0.2%) using dosage is few, is not easy and the feedstuff mixing, has reduced drug effect, has limited its use on producing.
Summary of the invention
The object of the present invention is to provide a kind of lytic agent that can dissolve simultaneously diclazuril and coccidiosis ester.
Purpose of the present invention is to provide a kind of Anticoccidiosis pharmaceutical composition simultaneously.
To achieve these goals, the technical solution used in the present invention is:
A kind of lytic agent that can dissolve simultaneously diclazuril and coccidiosis ester is comprised of the component of following volume parts: 1 part of oxolane, dimethyl formamide 0.25-4.5 part.
A kind of Anticoccidiosis pharmaceutical composition that can dissolve simultaneously as claimed in claim 1 the lytic agent of diclazuril and coccidiosis ester that contains, composed of the following components: lytic agent 1L, diclazuril 5-18g, coccidiosis ester 50-200g.
Doubly can be by the chicken administration of drinking water with Anticoccidiosis pharmaceutical composition dilute with water 500-3000 of the present invention.
The present invention has designed a kind of medicine dissolution agent, this lytic agent can dissolve diclazuril and coccidiosis ester well simultaneously, and dense, solved diclazuril and the coccidiosis ester is water insoluble, and common coccidiosis pre-mixing agent is difficult for this production difficult problem of mixing in feedstuff.With diclazuril and the coccidiosis ester solution of this lytic agent preparation, dense, toxicity is lower, this solution is stable in environment more than 4 ℃, has crystalline solid to separate out in low temperature environment, is heated to 65 ℃ and keeps 15min or place 80min at 25 ℃, crystalline solid is solubilized, and solution becomes must be clarified.This is so that diclazuril and coccidiosis ester can effectively pass through the drinking-water administration, and is simple and convenient and effective, has wide market prospect and economic benefit.
The specific embodiment
Below in conjunction with specific embodiment technical scheme of the present invention is elaborated.
The lytic agent that can dissolve simultaneously diclazuril and coccidiosis ester of embodiment 1. the present embodiment is comprised of 1ml oxolane and 4.5ml dimethyl formamide.
Contain the Anticoccidiosis pharmaceutical composition of above-mentioned lytic agent, composed of the following components: lytic agent 1L, diclazuril 18g, coccidiosis ester 200g.
The preparation method of Anticoccidiosis pharmaceutical composition is: diclazuril, coccidiosis ester are added in the lytic agent, and mixing gets final product.
The lytic agent that can dissolve simultaneously diclazuril and coccidiosis ester of embodiment 2. the present embodiment is comprised of 1ml oxolane and 2ml dimethyl formamide.
Contain the Anticoccidiosis pharmaceutical composition of above-mentioned lytic agent, composed of the following components: lytic agent 1L, diclazuril 12g, coccidiosis ester 160g.
The preparation method of Anticoccidiosis pharmaceutical composition is: diclazuril, coccidiosis ester are added in the lytic agent, and mixing gets final product.
The lytic agent that can dissolve simultaneously diclazuril and coccidiosis ester of embodiment 3. the present embodiment is comprised of 1ml oxolane and 0.25ml dimethyl formamide.
Contain the Anticoccidiosis pharmaceutical composition of above-mentioned lytic agent, composed of the following components: lytic agent 1L, diclazuril 5g, coccidiosis ester 50g.
The preparation method of Anticoccidiosis pharmaceutical composition is: diclazuril, coccidiosis ester are added in the lytic agent, and mixing gets final product.
The test drug source that the present invention adopts is as follows:
Diclazuril crude drug (content 99.9%), the rich female veterinary drug raw material company limited in Qingdao;
Coccidiosis ester (ethopabate) (content 99.7%), the rich female veterinary drug raw material company limited in Qingdao;
Oxolane (analytical pure), Tianjin Da Mao chemical reagent factory;
Dimethyl formamide (analytical pure), Tianjin Bazhou City's chemical industry subsidiary factory of quartzy Clock Factory;
Triple purified water are with the automatic triple pure water distillator self-controls of SZ-97; The automatic triple pure water distillators of SZ-97, Shanghai Yarong Biochemical Instrument Plant.
Research and probe process of the present invention is as follows:
In the time of 25 ℃, take oxolane as solvent, diclazuril, dissolubility and the rate of dissolution of coccidiosis ester under not commensurability dimethyl formamide DMF effect see Table 1.As shown in Table 1, the rate of dissolution of coccidiosis ester in this prescription is higher than diclazuril, and this may be relevant with the physicochemical property of the two, and the coccidiosis ester is crystal state, and diclazuril is cohesive powders.Along with the increase of dimethyl formamide amount, diclazuril and the coccidiosis ester rate of dissolution in this prescription increases, and illustrates that the dimethyl formamide amount has solubilization to diclazuril and coccidiosis ester, and this prescription can dissolve diclazuril and coccidiosis ester well.
The dissolubility of table 1 diclazuril, coccidiosis ester and rate of dissolution (25 ℃)
Diclazuril and coccidiosis ester highly concentrated solution stability test result
Get 24 10mL chloromycetin bottles, after water cleans up, place the baking box inner drying, guarantee a bottle interior anhydrous or foreign body.Be divided at random 8 groups, three every group, labelled.In each bottle, add diclazuril and the coccidiosis ester (diclazuril: 18.18mg/ml for preparing, coccidiosis ester: 200mg/ml) solution 10mL, place respectively-20 ℃ ,-10 ℃ ,-5 ℃, 4 ℃, 25 ℃, 35 ℃, 40 ℃, 60 ℃ environment, place 4h, have or not solid or crystalline material to separate out in the observation solution.
After placing 4h, 8 groups of diclazurils and coccidiosis ester highly concentrated solution sample are taken out from different environment.Found that: the sample in 25 ℃, 35 ℃, 40 ℃, 60 ℃ environment is all separated out without precipitation or crystalline material, is transparent yellow solution; There is a small amount of crystalline solid to separate out in 4 ℃ of environment; The crystalline solid of separating out in the time of-20 ℃ is maximum, mainly is coccidiosis ester composition.
Based on this, 8 groups of samples are all placed-20 ℃ of environment, approximately 4h makes its crystallize out; Be divided at random afterwards three groups, 8 every group, place respectively 25 ℃ indoor, in the water-bath of 35 ℃ and 65 ℃, the bottle that ceaselessly vibrates is simultaneously seen that can crystalline solid dissolve again, and is measured its rate of dissolution.Found that: in 65 ℃ water-bath, crystalline solid is all dissolvings in 15-20min, are transparent yellow solution; In 35 ℃ water-bath, crystalline solid is all dissolvings about 35min, are transparent yellow solution; Indoor at 25 ℃, crystalline solid is all dissolvings about 80min, are transparent yellow solution.Illustrate that temperature is larger on diclazuril and the impact of coccidiosis ester highly concentrated solution of this formulated.Under chicken house was fed environment, this diclazuril and coccidiosis ester solution were very stable.
Diclazuril and coccidiosis ester high concentration (diclazuril: 18.18mg/ml, coccidiosis ester: 200mg/ml) solution with water dilution rear stability test
Under 25 ℃ of conditions, 100 times of diclazuril and coccidiosis ester highly concentrated solution dilute with waters, solution is even milky suspension solution; And the solution that dilutes 500,1000,2000 times is the clear solution of clarification.Room temperature is diluted 100 times solution adularescent Precipitation after placing 4h, is suspended in liquid level, is pasted on a bottle wall; And the SOLUTION PROPERTIES of diluting 500,1000,2000 times is stable, separates out without precipitation or crystalline solid, is clarification, transparent colourless solution.
Toxicity assessment
Oxolane has the characteristics such as low toxicity, low boiling, good fluidity, is a kind of important organic synthesis and fine chemical material and good solvent, has widely purposes.Oxolane has good dissolubility to many Organic substances, and aspect medical, oxolane can be used as the raw material of synthetic carbetapentane citrate, rifamycin, Progesterone and some hormone drugs.Oxolane is micro-virus kind, and per os belongs to lower toxicity.Acute toxicity: LD
50: 1650mg/kg; (rat oral).Subacute and chronic toxicity: this product has to stimulate and anesthetic action, and concentration is greater than 147750mg/m
3The time, animal has corneal edema and muddiness, and sialorrhea, watery nasal discharge and epistaxis have slight stimulation.Cause after the suction that upper respiratory tract stimulates, feels sick, dizzy, headache and central nervous system suppress.Can cause liver, renal damage.Liquid or high concentration steam have zest to eye.Women's Long Term Contact can cause infertile.Mutagenicity: DNA damage.
Dimethyl formamide (DMF) can be used for synthetic sulfadiazine, doxycycline, cortisone, vitamin B as important industrial chemicals and the solvent of function admirable in the medical industry
6, idoxuridine, drive clean, pyrantel, chloramphenalan, methoxymerphalan, tranamic acid, doubly minute beautiful pine, megestrol, gallbladder are tieed up chlorphenamine etc.Dimethyl formamide belongs to lower toxicity, acute toxicity LD
50: 4000mg/kg (rat oral).Subacute and chronic toxicity: rat sucks 2500mg/m
3, 6 hours/day, 5 days, 80% death, the liver lung has pathological changes; The people sucks 5.1-49mg/m
3* 3 years, god's syndrome that declines, blood pressure is on the low side, changes of liver function.
With diclazuril and the coccidiosis ester solution of this formulated, dissolubility is respectively up to 18.1818mg/mL, 200.0000mg/mL; The valid density of diclazuril control chicken coccidiosis is 0.5-1 μ g/mL (drinking-water is fed).Every chicken 250mL that drinks water every day, with 1000 times of this highly concentrated solution dilutions of 1mL, i.e. 1000mL, drug level are about 30 times of valid density of control chicken coccidiosis, can satisfy the needs of actual production.The density of oxolane and dimethyl formamide is respectively 0.8992g/mL and 0.9445g/mL, the body weight of Adult Chicken is generally 1-2kg, the amount that chicken is taken in oxolane and dimethyl formamide every day is respectively 7.4917mg and 7.8708mg, reaches far away acute poisoning dosage, is safe.During as for Long-term Feeding, issuable cumulative toxicity effect needs by experiment animal, carries out next step exploration.
Claims (2)
1. oxolane and dimethyl formamide lytic agent dissolve the application in diclazuril and the coccidiosis ester at the same time, it is characterized in that: described lytic agent is comprised of the component of following volume parts: 1 part of oxolane, dimethyl formamide 0.25-4.5 part.
2. application according to claim 1 is characterized in that: diclazuril 5-18g and coccidiosis ester 50-200g are dissolved among the lytic agent 1L.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210011293 CN102671199B (en) | 2012-01-15 | 2012-01-15 | Dissolving agent capable of dissolving diclazuril and ethopabate simultaneously and anticoccidial medicinal composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210011293 CN102671199B (en) | 2012-01-15 | 2012-01-15 | Dissolving agent capable of dissolving diclazuril and ethopabate simultaneously and anticoccidial medicinal composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102671199A CN102671199A (en) | 2012-09-19 |
| CN102671199B true CN102671199B (en) | 2013-09-18 |
Family
ID=46804179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201210011293 Expired - Fee Related CN102671199B (en) | 2012-01-15 | 2012-01-15 | Dissolving agent capable of dissolving diclazuril and ethopabate simultaneously and anticoccidial medicinal composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102671199B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973496B (en) * | 2012-11-22 | 2014-12-17 | 青岛绿曼生物工程有限公司 | Preparation method of diclazuril oral liquid for treating poultry coccidiosis |
-
2012
- 2012-01-15 CN CN 201210011293 patent/CN102671199B/en not_active Expired - Fee Related
Non-Patent Citations (4)
| Title |
|---|
| "地克珠利饮水剂生产工艺研究及临床药效试验";张龙现等;《河南畜牧兽医》;19991231;第20卷(第8期);第7-9页 * |
| "溶剂对静电纺丝聚氨酯纤维仿生涂层的影响";邹迪婧等;《功能材料》;20071231;第38卷(第7期);第7期 * |
| 张龙现等."地克珠利饮水剂生产工艺研究及临床药效试验".《河南畜牧兽医》.1999,第20卷(第8期),第7-9页. |
| 邹迪婧等."溶剂对静电纺丝聚氨酯纤维仿生涂层的影响".《功能材料》.2007,第38卷(第7期),第7期. |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102671199A (en) | 2012-09-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105726522B (en) | Magnolol is killing application and its preparation in fish parasitic protozoa | |
| CN105566353A (en) | Compound and preparation method thereof | |
| CN103341114A (en) | Application of amomum tsao-ko oil in preparation of drugs for treating bacterial infectious diseases | |
| CN102671199B (en) | Dissolving agent capable of dissolving diclazuril and ethopabate simultaneously and anticoccidial medicinal composition | |
| CN104055731B (en) | A kind of coccidiostat fluoroadenine solution and preparation method thereof | |
| CN105412089A (en) | Application of compound VS1 in preparation of anti-non-small cell lung cancer medicine | |
| CN102697757A (en) | Application of p-hydroxy benzylidene acetone in preparation of drugs for preventing and/or treating encephalopathy | |
| CN112592367A (en) | Magnolol derivative and preparation method and application thereof | |
| CN105878179A (en) | Preparation method and application of florfenicol solution | |
| KR101242535B1 (en) | Method of producing composite for curing and preventing coccidium | |
| RU2320352C2 (en) | Method for treating subclinical mastitis in cows | |
| CN105267148B (en) | A kind of sulfaclozine soluble powder and preparation method thereof | |
| CN102000100A (en) | Anticoccidiosis nano suspension and preparation method thereof | |
| BRPI0414191A (en) | substituted thienoimidazoles, process for their preparation, their use as a medicine or diagnosis as well as a medicine containing them | |
| US10016387B2 (en) | Method for treating melanoma | |
| CN106580994A (en) | Enrofloxacin hydrochloride composition and liquid medicine, and preparation methods thereof | |
| Chunduri et al. | Comparative study of Phytal originated B17s and medicinal importance | |
| CN102697788B (en) | Compound lactic acid levofloxacin oral liquid and preparation process thereof | |
| CN112587533A (en) | Application of honokiol derivative in preparation of medicine for preventing and/or treating bovine mastitis | |
| CN104523722A (en) | Medicine composition for treating neuropathic pains | |
| CN116019168A (en) | Application of silymarin in preparation of chicken feed or anti-chicken coccidiosis medicine | |
| CN110269860A (en) | A kind of drug for treating cancer | |
| CN105311007B (en) | Application of the naganol in anticoccidial drugs thing is prepared | |
| BR102014031535A2 (en) | pharmaceutical formulation and process for obtaining an oral solution containing praziquantel and oral solution containing praziquantel thus obtained | |
| CN108904556A (en) | A kind of Thesium chinese extract powder is used to promote the purposes of children's skeleton development |
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 | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130918 Termination date: 20140115 |