CN102198099A - Toltrazuril suspension and preparation method thereof - Google Patents
Toltrazuril suspension and preparation method thereof Download PDFInfo
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- CN102198099A CN102198099A CN 201110121095 CN201110121095A CN102198099A CN 102198099 A CN102198099 A CN 102198099A CN 201110121095 CN201110121095 CN 201110121095 CN 201110121095 A CN201110121095 A CN 201110121095A CN 102198099 A CN102198099 A CN 102198099A
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- toltrazuril
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- OCINXEZVIIVXFU-UHFFFAOYSA-N 1-methyl-3-[3-methyl-4-[4-(trifluoromethylthio)phenoxy]phenyl]-1,3,5-triazinane-2,4,6-trione Chemical compound CC1=CC(N2C(N(C)C(=O)NC2=O)=O)=CC=C1OC1=CC=C(SC(F)(F)F)C=C1 OCINXEZVIIVXFU-UHFFFAOYSA-N 0.000 title claims abstract description 78
- 229960000898 toltrazuril Drugs 0.000 title claims abstract description 77
- 239000000725 suspension Substances 0.000 title claims abstract description 73
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 239000000203 mixture Substances 0.000 claims description 23
- 239000002671 adjuvant Substances 0.000 claims description 10
- 229960001031 glucose Drugs 0.000 claims description 8
- 239000000375 suspending agent Substances 0.000 claims description 8
- -1 hydroxypropyl Chemical group 0.000 claims description 7
- 229920001285 xanthan gum Polymers 0.000 claims description 5
- 229940082509 xanthan gum Drugs 0.000 claims description 5
- 235000010493 xanthan gum Nutrition 0.000 claims description 5
- 239000000230 xanthan gum Substances 0.000 claims description 5
- 229930006000 Sucrose Natural products 0.000 claims description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- WQZGKKKJIJFFOK-DVKNGEFBSA-N alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-DVKNGEFBSA-N 0.000 claims description 2
- 239000000470 constituent Substances 0.000 claims description 2
- 229960004793 sucrose Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 11
- 239000003651 drinking water Substances 0.000 abstract description 8
- 235000020188 drinking water Nutrition 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 7
- 238000002156 mixing Methods 0.000 abstract description 6
- 239000003960 organic solvent Substances 0.000 abstract description 6
- 239000000463 material Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 238000010521 absorption reaction Methods 0.000 abstract description 3
- 239000007788 liquid Substances 0.000 abstract description 2
- 230000000144 pharmacologic effect Effects 0.000 abstract description 2
- 230000008569 process Effects 0.000 abstract description 2
- 238000003860 storage Methods 0.000 abstract description 2
- 230000002411 adverse Effects 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 239000000843 powder Substances 0.000 description 21
- 238000012360 testing method Methods 0.000 description 20
- 241000287828 Gallus gallus Species 0.000 description 17
- 235000013330 chicken meat Nutrition 0.000 description 17
- 239000006185 dispersion Substances 0.000 description 17
- 230000001165 anti-coccidial effect Effects 0.000 description 10
- 239000002775 capsule Substances 0.000 description 10
- 241000252983 Caecum Species 0.000 description 8
- 210000004534 cecum Anatomy 0.000 description 8
- 238000007689 inspection Methods 0.000 description 8
- 238000013112 stability test Methods 0.000 description 8
- 208000003495 Coccidiosis Diseases 0.000 description 7
- 206010023076 Isosporiasis Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 241000223932 Eimeria tenella Species 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 230000036528 appetite Effects 0.000 description 6
- 235000019789 appetite Nutrition 0.000 description 6
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 6
- 230000004584 weight gain Effects 0.000 description 6
- 235000019786 weight gain Nutrition 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- 239000000273 veterinary drug Substances 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 241000223924 Eimeria Species 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 244000144977 poultry Species 0.000 description 4
- 235000013594 poultry meat Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 241000224483 Coccidia Species 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 210000003608 fece Anatomy 0.000 description 3
- 238000000386 microscopy Methods 0.000 description 3
- 210000003250 oocyst Anatomy 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003224 coccidiostatic agent Substances 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 210000003746 feather Anatomy 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- KMUONIBRACKNSN-UHFFFAOYSA-N potassium dichromate Chemical compound [K+].[K+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KMUONIBRACKNSN-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000004215 spore Anatomy 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 241000272205 Columba livia Species 0.000 description 1
- 241001391944 Commicarpus scandens Species 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 208000001140 Night Blindness Diseases 0.000 description 1
- AYDQIZKZTQHYIY-UHFFFAOYSA-N OC(=O)C1(C)CC(C(O)=O)=CC=C1 Chemical compound OC(=O)C1(C)CC(C(O)=O)=CC=C1 AYDQIZKZTQHYIY-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 235000009392 Vitis Nutrition 0.000 description 1
- 241000219095 Vitis Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000009360 aquaculture Methods 0.000 description 1
- 244000144974 aquaculture Species 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 208000027503 bloody stool Diseases 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000004490 capsule suspension Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 208000035861 hematochezia Diseases 0.000 description 1
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- 230000000968 intestinal effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
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- 229960005486 vaccine Drugs 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses toltrazuril suspension, which belongs to the field of veterinary medicines and comprises the following components in percentage by mass: 2.5 to 15 percent of toltrazuril, 15.0 to 30.0 percent of suspending aid, and 65.0 to 82.5 percent of auxiliary materials. The invention also discloses the preparation method of the suspension. The suspension is administrated by mixing with drinking water, the use is convenient, the suspension is suitable for mass administration, and the labor force and materials are saved; the dosage is accurate, the toltrazuril disperses uniformly in water, and the concentration of the medicine is uniform; the absorption of the toltrazuril is desirable, the effectiveness is quick, and the bioavailability is high; in addition, compared with liquid preparation, the toltrazuril suspension is very stable and maintains a dry state constantly in a process from production to storage, and the package is sealed to prevent the suspension from contact with moisture and air. The suspension does not contain organic solvent, so the possibility of adverse pharmacological effect that may be produced by the organic solvent is lowered and the safety is high.
Description
Technical field
The invention belongs to the veterinary drug preparation field, be specifically related to a kind of Toltrazuril dry suspension and preparation method thereof.
Background technology
The common coccidiosis of veterinary clinic mainly is that the coccidiosis by Eimeria causes.Animal body can produce immunity rapidly after the contact cause of disease, and produces the protectiveness that infects again, so coccidiosis only breaks out in growing animal mostly.Yet, there is not cross immunity between each worm kind of Eimeria, be easy to break out the coccidiosis that causes by different worm kinds.Modern scale and enclosed aquaculture model more make this life cycle short, make disease be difficult to control, conventional chemoprophylaxis, sterilization and vaccine epidemic prevention effect very weak (favour is numerous etc. Chinese animal health .29-30 (2010)).
Toltrazuril (English name is Toltrazuril), having another name called hundred balls clear (Baycox), toltrazuril, methyl triazon, many piperazines pearl profit or toltrazuril etc., is that Bayer A.G is in the Triazinone of the exploitation eighties in 20th century, the coccidiostat of animal specific.Chemical name is 1-[3-methyl-4-(4-trifluoromethylthio-phenoxy group)-phenyl]-the 3-methyl isophthalic acid, 3,5-triazine-2,4,6-triketone, chemical molecular formula are C
18H
14F
3N
3O
1S, molecular weight is 425.4, and white crystalline powder almost is not soluted in water, be slightly soluble in ethanol, be dissolved in ethyl acetate, N, organic solvents such as dinethylformamide (DMF), dimethyl sulfoxide (DMSO), oxolane (THF), diethyl carbonate, toluene, triethanolamine.Toltrazuril anticoccidial spectrum is wide, and the anticoccidial effect is strong, and toxicity is low, is difficult for producing drug resistance, and various Eimerias are had efficiently.Toltrazuril can be killed the multiple protozoon that comprises coccidiosis, wherein tender, heap type, murder by poisoning, Bu Shi, 6 kinds of topmost Eimerias such as huge and gentle are all had efficiently, the anticoccidial index is all above 180, belong to efficient coccidiostat (.Parasitol Research.75 (1) such as Mehlhorn H., 64-66 (1988)), be mainly used in poultry such as chicken, rabbit, Columba livia, piglet coccidium infection (Guo Teng. veterinary drug and feed additive .7,16-18 (2002)).
At present, the dosage form of Toltrazuril medicine mainly contain pre-mixing agent, solid pulvis (Qi Wenwen etc. Chinese veterinary drug magazine .43 (4), 34-37 (2009)), solution (CN1839845A), microemulsion (CN101336901A), suspension (patent CN101491497A) etc.The Toltrazuril consumption is little, and the pre-mixing agent mixing is inhomogeneous, the dispersion of dispersant medicine is inhomogeneous causes the poultry absorption inhomogeneous easily, thereby makes curative effect reduction or indivedual poultry produce toxic and side effects because of Excessive Intake.Solution is all the organic solvent hydrotropy at present, and causing has certain pollution to environment, and causes cost of supplementary product to raise, and medicine was separated out easily when this dosage form was used for livestock and fowl drinking water simultaneously.Microemulsion and suspension preparation cost are higher, there is certain limitation in clinical expansion.Therefore, need low, stable high, evident in efficacy, the eco-friendly dosage form of a kind of cost.
Summary of the invention
At the problem that existing Toltrazuril dosage form exists, the object of the invention is to provide a kind of Toltrazuril dry suspension, and this dry suspension adds water and can be made into suspension, convenient drug administration, good effect and environmental friendliness.
Another purpose of the present invention is to provide the preparation method of above-mentioned Toltrazuril dry suspension.
Realize that technical scheme of the present invention is as follows:
A kind of Toltrazuril dry suspension of the present invention, its constituent and mass percent thereof are: Toltrazuril 2.5～15%, suspending agent 15.0～30.0%, adjuvant 65.0～82.5%.
The mass percent of Toltrazuril is preferably 5～10% described in the above-mentioned Toltrazuril dry suspension.
The mass percent of suspending agent is preferably 20～30% described in the above-mentioned Toltrazuril dry suspension.
The mass percent of adjuvant is preferably 70～80% described in the above-mentioned Toltrazuril dry suspension.
Suspending agent described in the above-mentioned Toltrazuril dry suspension is one or both combination of hydroxypropyl emthylcellulose or xanthan gum etc.
The viscosity coefficient of described hydroxypropyl emthylcellulose is 100,000,150,000 or 200,000; Its viscosity coefficient is preferably 200,000.
Adjuvant described in the above-mentioned Toltrazuril dry suspension is one or more combination of oral glucose, anhydrous glucose or sucrose etc.
The preparation method of above-mentioned Toltrazuril dry suspension comprises that the adjuvant with Toltrazuril and equivalent mixes mix homogeneously; Add suspending agent then, mix homogeneously; Equivalent increases progressively the adjuvant that adds remainder again, and mix homogeneously promptly gets the Toltrazuril dry suspension.
Among the present invention each component all can be on market open purchase.
The using method of Toltrazuril dry suspension of the present invention: by the drinking-water administration, promptly add water and make suspension solution, poultry freely drink water or gavage.
Compare with other dosage forms of existing Toltrazuril, advantage that the present invention has and beneficial effect: (1) is compared with pre-mixing agent, dry suspension of the present invention carries out administration by drinking-water, easy to use, and be suitable for colony's administration, use manpower and material resources sparingly, having avoided searches for food to descend after the animal morbidity influence influence of medicine absorption; And overcome pre-mixing agent and mixed inequality, different chicken intake differences, the shortcoming that uncertain therapeutic efficacy is fixed with feedstuff.(2) dry suspension dispensing dosage of the present invention is accurate, and after the present invention dropped in the water, Toltrazuril was uniformly dispersed in water, water Chinese medicine concentration homogeneous.(3) dry suspension good absorbing of the present invention, rapid-action, bioavailability is high.(4) compare Toltrazuril dry suspension good stability of the present invention with liquid preparation.From produce storage process, be in drying regime all the time, and package encapsulation, avoid contacting with air with dampness.(5) dry suspension of the present invention does not contain organic solvent, has avoided the issuable bad pharmacological action of organic solvent, and is safe, belongs to environmentally friendly.(6) preparation method of the present invention is used conventional equipment, and method is simple.
The specific embodiment:
The invention will be further described below by specific embodiment, but protection scope of the present invention is not limited to following examples.
The preparation of embodiment 1 Toltrazuril dry suspension
With Toltrazuril (Hubei Longxiang Pharmaceutical Co., Ltd, lot number 201012181, down with) 25g join anhydrous glucose (Weifang Ecological Medicine Industry company limited, lot number 20101221, down with) among the 25g, mix homogeneously; Add xanthan gum (Shanghai Hang Seng chemical industry company limited, lot number are 20101115, down together) 150g then, add at twice, add 50g for the first time, mix homogeneously adds 100g again, mix homogeneously; Add anhydrous glucose 800g again, add at twice, add 200g for the first time, add 600g behind the mix homogeneously again, mix homogeneously promptly makes Toltrazuril dry suspension 1000g.
The preparation of embodiment 2 Toltrazuril dry suspension
Toltrazuril 50g is joined among oral glucose (Shijiazhuang City China battalion associating Fructus Vitis viniferae sugar refinery, the specification 25kg/ bag) 50g mix homogeneously; Add xanthan gum 200g then, mix homogeneously; Add oral glucose 700g again, add at twice, add 300g for the first time, add 400g behind the mix homogeneously again, mix homogeneously promptly gets Toltrazuril dry suspension 1000g.
The preparation of embodiment 3 Toltrazuril dry suspension
Toltrazuril 100g is joined among the anhydrous glucose 100g mix homogeneously; Add viscosity coefficient then and be 200,000 hydroxypropyl emthylcellulose 250g, mix homogeneously; Add anhydrous glucose 550g again, add at twice, add 250g for the first time, mix homogeneously adds 300g for the second time, and mix homogeneously promptly gets Toltrazuril dry suspension 1000g.
The preparation of embodiment 4 Toltrazuril dry suspension
Toltrazuril 150g is joined among sucrose (Shanghai Xi Run chemical industry company limited, specification the is the 50kg/ bag) 150g mix homogeneously; Add viscosity coefficient then and be 200,000 hydroxypropyl emthylcellulose 100g and xanthan gum 100g, mix homogeneously; Add sucrose 500g again, add at twice, add 250g for the first time, add 250g more for the second time, mix homogeneously promptly gets Toltrazuril dry suspension 1000g.
The settling volume of embodiment 5 Toltrazuril dry suspension of the present invention is than test
(1) dry suspension of test material: embodiment 1,2,3,4.
(2) test method: with reference to 14 pages of appendix of " People's Republic of China's veterinary drug allusion quotation " version in 2005.Suspensoid for oral administration is according to following method inspection, and the settling volume ratio should be not less than 0.90.
Inspection method: apparatus plug graduated cylinder is got test sample 50mL, close plug, and firmly jolting is 1 minute, writes down the beginning height H of suspended matter
0, left standstill 3 hours, write down the final height H of suspended matter.The ratio that dry suspension is stipulated down in each kind item adds the water jolting, answers homodisperse, and checks the settling volume ratio according to last method.
Computing formula: settling volume ratio=H/H
0
(3) result:
The suspendible situation of the dry suspension of table 1 embodiment 1 and settling volume are than the test result
| Project | The suspendible situation | H 0(mL) | H(mL) | The settling volume ratio |
| 1min | Good dispersion | 50 | 50 | 1 |
| 30min | Good dispersion | 50 | 48 | 0.98 |
| 1h | Good dispersion | 50 | 47.5 | 0.95 |
| 3h | Good dispersion | 50 | 46 | 0.92 |
The suspendible situation of the dry suspension of table 2 embodiment 2 and settling volume are than the test result
| Project | The suspendible situation | H 0(mL) | H(mL) | The settling volume ratio |
| 1min | Good dispersion | 50 | 50 | 1 |
| 30min | Good dispersion | 50 | 48 | 0.96 |
| 1h | Good dispersion | 50 | 48 | 0.96 |
| 3h | Good dispersion | 50 | 47 | 0.94 |
The suspendible situation of the dry suspension of table 3 embodiment 3 and settling volume are than the test result
| Project | The suspendible situation | H 0(mL) | H(mL) | The settling volume ratio |
| 1min | Good dispersion | 50 | 50 | 1 |
| 30min | Good dispersion | 50 | 48 | 0.96 |
| 1h | Good dispersion | 50 | 47.5 | 0.95 |
| 3h | Good dispersion | 50 | 47 | 0.94 |
The suspendible situation of the dry suspension of table 4 embodiment 4 and settling volume are than the test result
| Project | The suspendible situation | H 0(mL) | H(mL) | The settling volume ratio |
| 1min | Good dispersion | 50 | 50 | 1 |
| 30min | Good dispersion | 50 | 48 | 0.96 |
| 1h | Good dispersion | 50 | 47.5 | 0.95 |
| 3h | Good dispersion | 50 | 46 | 0.92 |
By data in the above table 1,2,3 and 4 as can be known, the settling volume of the suspension solution of embodiment 1,2,3 and the preparation of 4 dry suspension meets the regulation of suspensoid than greater than 0.90, uses when being fit to animal drinking-water.
The stable contrast test of embodiment 6 Toltrazuril dry suspension of the present invention and solution
In order to measure this stability of formulation, (commodity are called the ball Brunswick to the Toltrazuril dry suspension of embodiment 1, embodiment 2, embodiment 3, embodiment 4 and commercially available toltrazuril solution according to the requirement of " veterinary drug stability test technical specification ", Baoding Jizhong Pharmaceutical Co., Ltd., specification is to contain Toltrazuril 2.5g in every 100mL solution, and product batch number is 20100528) carry out the accelerated test of following condition.Embodiment 1, embodiment 2, embodiment 3, embodiment 4 described dry suspension are added water and make suspension, put into temperature and be 40 ℃, relative humidity and be 75% calorstat, the sampling respectively in the 0th, 1,2,3,6 month, and observe character respectively and measure content, result of the test is as follows:
The Toltrazuril dry suspension stability test result of table 5 embodiment 1
| Project | Character | The settling volume ratio | Content (%) |
| 0 month | Off-white powder | 0.92 | 2.55 |
| January | Off-white powder | 0.93 | 2.55 |
| February | Off-white powder | 0.93 | 2.53 |
| March | Off-white powder | 0.92 | 2.50 |
| June | Off-white powder | 0.92 | 2.48 |
The Toltrazuril dry suspension stability test result of table 6 embodiment 2
| Project | Character | The settling volume ratio | Content (%) |
| 0 month | Off-white powder | 0.94 | 5.07 |
| January | Off-white powder | 0.94 | 5.06 |
| February | Off-white powder | 0.94 | 5.03 |
| March | Off-white powder | 0.93 | 4.99 |
| June | Off-white powder | 0.94 | 4.95 |
The Toltrazuril dry suspension stability test result of table 7 embodiment 3
| Project | Character | The settling volume ratio | Content (%) |
| 0 month | Off-white powder | 0.94 | 10.10 |
| January | Off-white powder | 0.93 | 10.08 |
| February | Off-white powder | 0.94 | 10.03 |
| March | Off-white powder | 0.93 | 9.95 |
| June | Off-white powder | 0.93 | 9.87 |
The Toltrazuril dry suspension stability test result of table 8 embodiment 4
| Project | Character | The settling volume ratio | Content (%) |
| 0 month | Off-white powder | 0.93 | 15.12 |
| January | Off-white powder | 0.93 | 15.10 |
| February | Off-white powder | 0.92 | 15.05 |
| March | Off-white powder | 0.94 | 14.95 |
| June | Off-white powder | 0.93 | 14.83 |
The toltrazuril solution stability test result of table 9 commercially available 2.5%
| Project | Character | Content |
| 0 month | Light yellow thickness settled solution | 2.51 |
| January | Light yellow thickness settled solution | 2.48 |
| February | Faint yellow thickness settled solution | 2.45 |
| March | Faint yellow thickness settled solution | 2.40 |
| June | Dark yellow thickness settled solution | 2.33 |
From the accelerated test result, the Toltrazuril suspension of embodiment 1,2,3,4 is at accelerated stability test in the phase, character does not all change, settling ratio is all greater than 0.9, content does not have significant change, and all other indexs meet the requirements, and commercially available 2.5% toltrazuril solution is at accelerated stability test in the phase, solution colour deepens, and content has reduced by 7.17%.The solution that Toltrazuril dry suspension preparation of the present invention is described is more stable.
Embodiment 6 Toltrazuril dry suspension of the present invention are to the clinical trial of tender eimeria tenella disease
(1) test material
(1) trial drug: the Toltrazuril dry suspension that present embodiment 1 is prepared is dissolved in water before interim and makes suspension solution.
(2) control drug: commercially available 2.5% toltrazuril solution (Baoding Jizhong Pharmaceutical Co., Ltd. produces, and commodity are called the ball Brunswick, and specification is to contain Toltrazuril 2.5g in every 100mL solution, and product batch number is 20100528).
(3) coccidian oocyst: spore Eimeria tenella egg capsule, parasite teaching and research room of Agricultural University Of Nanjing provides, and 2.5% potassium dichromate is stored in 4 ℃ of refrigerators standby.
(4) experimental animal: the AA chicken, under strictness isolation condition, raise, the chicken full-valence pellet feed of feeding, drinking water is fresh tap water.
(2) test method
(1) artificial challenge: the laboratory cage is raised 16 200 of age in days AA chickens be divided into four groups, 50 every group, each is organized chicken body weight and health status etc. and is close to suitable.Except that negative control group, each is organized test chicken and (contains Eimeria tenella spore egg capsule 5 * 10 through crop artificial vaccination Eimeria Tenella egg capsule suspension 0.5mL
4Individual) specifically divide into groups and handle to see Table 10.
Grouping of table 10 test chicken and processing method
(2) test method: artificial vaccination Eimeria Tenella egg capsule begin administration on the same day, and be recorded as first day of treatment.Embodiment 1 and medicine matched group pass through the drinking-water administration with 25mg/kg dosage, logotype two days, and concrete dosage and administration time see Table 10.Observe every day and situations such as record test chicken spirit, appetite.Began to check feces on the 4th day, every day, bloody stool heap number respectively organized in record, till cuing open extremely on the 9th day.The 6th day begins to collect every group feces, checks the egg capsule sum that every group of chicken discharged.Inspection was catched and killed, weighs, cutd open to all chickens in the 9th day.Emphasis is checked caecum lesion when cuing open inspection, scores according to the pathological changes standard, caecum is digested respectively by component make homogenate then, to calculate every group of every night blindness intestinal egg sac number.
Effect is judged: observe chicken spirit, appetite, record survival rate, weightening finish and the relative weight gain rate, lesion score value, egg capsule count value, anticoccidial index (ACI) etc. carry out synthetic determination.
Anticoccidial index (AC)=(the relative weight gain rate+survival rate) * 100-(pathological changes value+egg capsule value)
Anticoccidial index＞180 are efficient; 160～180 is middle effect; 120～160 is poor efficiency; Be invalid below 120.
(3) result of the test
(1) negative control group: chicken all survives, and the mental status is good, appetite is fine, and feather is glossy, and feces is normal, the no egg capsule of excrement inspection, and the relative weight gain rate is 100%, the anticoccidial index is 200.
(2) positive controls: infected behind the coccidian oocyst the 3rd day, appetite obviously goes down, and occurs that feather is fluffy, fear of cold, has loose bowels and symptom such as hemafecia.The 4th day dead 10, the 5th, 6,8 day each dead 2.Cut open inspection and see the caecum enlargement, black purple is cut open, and blood clot and blood and slime are arranged in the enteric cavity, and a large amount of coccidian oocysts are arranged in the microscopy caecum.This group sickness rate is 100%, and mortality rate is 50%, and the relative weight gain rate is 25.8%, and the anticoccidial index is 37.5, and lesion score value and egg capsule count value all are higher than other each group.
(3) medicine matched group: duration of test does not have chicken death, and spirit, appetite is more normal, and cut open inspection and do not see caecum lesion, non-ball worm egg capsule in the microscopy caecum, the relative weight gain rate 90%, the anticoccidial index is 180.
(4) test group (embodiment 1 dry suspension): the test group chicken does not have death, and the most chicken spirit of duration of test, appetite are better, and cut open inspection and do not see caecum lesion, non-ball worm egg capsule in the microscopy caecum, the relative weight gain rate is 95%, the anticoccidial index is 195.
As can be seen from the above results, Toltrazuril dry suspension of the present invention has efficient effect to tender eimeria tenella, and it can kill the polypide of stage of development in the coccidiosis life cycle all cells, and to coccidiosis cure rate height, the chicken protective rate is reached 100%.Recommended dose is freely drunk for according to 25mg/kg the Toltrazuril dry suspension is sneaked in the drinking-water.
Claims (9)
1. a Toltrazuril dry suspension is characterized in that its constituent and mass percent thereof are: Toltrazuril 2.5～15%, suspending agent 15.0～30.0%, adjuvant 65.0～82.5%.
2. according to the described Toltrazuril dry suspension of claim 1, the mass percent that it is characterized in that described Toltrazuril is 5～10%.
3. according to the described Toltrazuril dry suspension of claim 1, the mass percent that it is characterized in that described suspending agent is 20～30%.
4. according to the described Toltrazuril dry suspension of claim 1, the mass percent that it is characterized in that described adjuvant is 70～80%.
5. according to the arbitrary described Toltrazuril dry suspension of claim 1～4, it is characterized in that described suspending agent is one or both combination of hydroxypropyl emthylcellulose or xanthan gum.
6. according to the described Toltrazuril dry suspension of claim 5, the viscosity coefficient that it is characterized in that described hydroxypropyl emthylcellulose is 100,000,150,000 or 200,000.
7. according to the described Toltrazuril dry suspension of claim 6, the viscosity coefficient that it is characterized in that described hydroxypropyl emthylcellulose is 200,000.
8. according to the described Toltrazuril dry suspension of claim 5, it is characterized in that described adjuvant is one or more combination of oral glucose, anhydrous glucose or sucrose.
9. the preparation method of the described Toltrazuril dry suspension of claim 1 is characterized in that comprising that the adjuvant with Toltrazuril and equivalent mixes mix homogeneously; Add suspending agent then, mix homogeneously; Equivalent increases progressively the adjuvant that adds remainder, mix homogeneously again.
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| CN102973507A (en) * | 2012-08-23 | 2013-03-20 | 郑州后羿制药有限公司 | Chicken coccidiosis treatment liposome and preparation method thereof |
| CN103142487A (en) * | 2013-03-22 | 2013-06-12 | 黑龙江大学 | High-content toltrazuril soluble powder, as well as preparation method and application thereof |
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| CN101450044A (en) * | 2008-12-29 | 2009-06-10 | 天津瑞普生物技术股份有限公司 | Anti-coccidium suspension agent containing nicarbazin and preparation technique thereof |
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| CN101450044A (en) * | 2008-12-29 | 2009-06-10 | 天津瑞普生物技术股份有限公司 | Anti-coccidium suspension agent containing nicarbazin and preparation technique thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973507A (en) * | 2012-08-23 | 2013-03-20 | 郑州后羿制药有限公司 | Chicken coccidiosis treatment liposome and preparation method thereof |
| CN103142487A (en) * | 2013-03-22 | 2013-06-12 | 黑龙江大学 | High-content toltrazuril soluble powder, as well as preparation method and application thereof |
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