CN106265503A - A kind of high stability diclazuril suspension and preparation method thereof - Google Patents
A kind of high stability diclazuril suspension and preparation method thereof Download PDFInfo
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- CN106265503A CN106265503A CN201610697568.2A CN201610697568A CN106265503A CN 106265503 A CN106265503 A CN 106265503A CN 201610697568 A CN201610697568 A CN 201610697568A CN 106265503 A CN106265503 A CN 106265503A
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- diclazuril
- suspension
- slow
- high stability
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- ZSZFUDFOPOMEET-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-[2,6-dichloro-4-(3,5-dioxo-1,2,4-triazin-2-yl)phenyl]acetonitrile Chemical compound C1=CC(Cl)=CC=C1C(C#N)C1=C(Cl)C=C(N2C(NC(=O)C=N2)=O)C=C1Cl ZSZFUDFOPOMEET-UHFFFAOYSA-N 0.000 title claims abstract description 58
- 229960000248 diclazuril Drugs 0.000 title claims abstract description 58
- 239000000725 suspension Substances 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000008187 granular material Substances 0.000 claims abstract description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 18
- 229920001661 Chitosan Polymers 0.000 claims abstract description 12
- 239000011780 sodium chloride Substances 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 7
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 7
- 239000013530 defoamer Substances 0.000 claims abstract description 7
- 239000002270 dispersing agent Substances 0.000 claims abstract description 7
- 239000000375 suspending agent Substances 0.000 claims abstract description 7
- -1 polyoxyethylene Polymers 0.000 claims description 17
- 238000003756 stirring Methods 0.000 claims description 14
- 238000002156 mixing Methods 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 6
- 235000006708 antioxidants Nutrition 0.000 claims description 6
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- NWGKJDSIEKMTRX-MDZDMXLPSA-N Sorbitan oleate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(O)C1OCC(O)C1O NWGKJDSIEKMTRX-MDZDMXLPSA-N 0.000 claims description 3
- 241001122767 Theaceae Species 0.000 claims description 3
- 229930003427 Vitamin E Natural products 0.000 claims description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 3
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 claims description 3
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 claims description 3
- 235000004515 gallic acid Nutrition 0.000 claims description 3
- 229940074391 gallic acid Drugs 0.000 claims description 3
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 229920000128 polypyrrole Polymers 0.000 claims description 3
- 235000019165 vitamin E Nutrition 0.000 claims description 3
- 229940046009 vitamin E Drugs 0.000 claims description 3
- 239000011709 vitamin E Substances 0.000 claims description 3
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims 2
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 claims 1
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims 1
- 229960003742 phenol Drugs 0.000 claims 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 7
- 241001465754 Metazoa Species 0.000 abstract description 6
- 210000000936 intestine Anatomy 0.000 abstract description 5
- 210000002784 stomach Anatomy 0.000 abstract description 5
- 241000287828 Gallus gallus Species 0.000 description 10
- 208000003495 Coccidiosis Diseases 0.000 description 8
- 206010023076 Isosporiasis Diseases 0.000 description 8
- 230000001165 anti-coccidial effect Effects 0.000 description 8
- 238000012360 testing method Methods 0.000 description 7
- 230000037396 body weight Effects 0.000 description 5
- 239000002775 capsule Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- 230000036528 appetite Effects 0.000 description 3
- 235000019789 appetite Nutrition 0.000 description 3
- 231100000915 pathological change Toxicity 0.000 description 3
- 230000036285 pathological change Effects 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 2
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 150000008442 polyphenolic compounds Chemical class 0.000 description 2
- 235000013824 polyphenols Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 244000144977 poultry Species 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 241000272525 Anas platyrhynchos Species 0.000 description 1
- 241000272814 Anser sp. Species 0.000 description 1
- 235000010894 Artemisia argyi Nutrition 0.000 description 1
- 241000252983 Caecum Species 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241000223932 Eimeria tenella Species 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 229930191564 Monensin Natural products 0.000 description 1
- GAOZTHIDHYLHMS-UHFFFAOYSA-N Monensin A Natural products O1C(CC)(C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CCC1C(O1)(C)CCC21CC(O)C(C)C(C(C)C(OC)C(C)C(O)=O)O2 GAOZTHIDHYLHMS-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- JQYYTCRAWVKTHZ-UHFFFAOYSA-N N1CCNCC1.[Cl] Chemical compound N1CCNCC1.[Cl] JQYYTCRAWVKTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 241000287882 Pavo Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- KQXDHUJYNAXLNZ-XQSDOZFQSA-N Salinomycin Chemical compound O1[C@@H]([C@@H](CC)C(O)=O)CC[C@H](C)[C@@H]1[C@@H](C)[C@H](O)[C@H](C)C(=O)[C@H](CC)[C@@H]1[C@@H](C)C[C@@H](C)[C@@]2(C=C[C@@H](O)[C@@]3(O[C@@](C)(CC3)[C@@H]3O[C@@H](C)[C@@](O)(CC)CC3)O2)O1 KQXDHUJYNAXLNZ-XQSDOZFQSA-N 0.000 description 1
- 239000004189 Salinomycin Substances 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 244000030166 artemisia Species 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 208000027503 bloody stool Diseases 0.000 description 1
- 239000004490 capsule suspension Substances 0.000 description 1
- 210000004534 cecum Anatomy 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000003224 coccidiostatic agent Substances 0.000 description 1
- 238000005868 electrolysis reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 208000035861 hematochezia Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- RWVUEZAROXKXRT-VQLSFVLHSA-N maduramicin Chemical compound O1[C@@H](C)[C@H](OC)[C@@H](OC)C[C@H]1O[C@@H]1[C@H]([C@@]2(C)O[C@H](CC2)[C@@]2(C)O[C@]3(O[C@@H]([C@H](C)[C@@H](O)C3)[C@@H](C)[C@H]3[C@@H]([C@@H](OC)[C@H](C)[C@@](O)(CC(O)=O)O3)OC)CC2)O[C@@H]([C@@H]2[C@H](C[C@@H](C)[C@@](C)(O)O2)C)C1 RWVUEZAROXKXRT-VQLSFVLHSA-N 0.000 description 1
- 229950006915 maduramicin Drugs 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 229960005358 monensin Drugs 0.000 description 1
- GAOZTHIDHYLHMS-KEOBGNEYSA-N monensin A Chemical compound C([C@@](O1)(C)[C@H]2CC[C@@](O2)(CC)[C@H]2[C@H](C[C@@H](O2)[C@@H]2[C@H](C[C@@H](C)[C@](O)(CO)O2)C)C)C[C@@]21C[C@H](O)[C@@H](C)[C@@H]([C@@H](C)[C@@H](OC)[C@H](C)C(O)=O)O2 GAOZTHIDHYLHMS-KEOBGNEYSA-N 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 210000003250 oocyst Anatomy 0.000 description 1
- 210000004681 ovum Anatomy 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229960001548 salinomycin Drugs 0.000 description 1
- 235000019378 salinomycin Nutrition 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Inorganic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Dispersion Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a kind of high stability diclazuril suspension and preparation method thereof, described diclazuril suspension is made up of following parts by weight component: diclazuril slow-releasing granules 10 ~ 20 parts, suspending agent 3 ~ 5 parts, dispersant 1 ~ 3 part, defoamer 1 ~ 2 part, 1 ~ 3 part of sodium chloride, antioxidant 0.8 ~ 1.2 part and 66.8 ~ 82.7 parts of water；Described diclazuril slow-releasing granules preparation method is as follows: chitosan is dissolved in obtained solution A in 3wt% aqueous acetic acid, is added by diclazuril in solution A, after being uniformly mixed, and spray-dried prepared diclazuril slow-releasing granules.Diclazuril suspension provided by the present invention has preferable low-temperature stability, stable performance after storing a year, conveniently comes into operation；Having slow release effect, reducing medicine stimulates animal intestines and stomach simultaneously.
Description
Technical field
The present invention relates to a kind of veterinary drug preparation, particularly relate to a kind of high stability diclazuril suspension and preparation side thereof
Method.
Background technology
Diclazuril (Diclazuril) belongs to triazine benzene acetonitrile compound, has another name called Dick pearl profit, spirit of killing, carves power fowl, is
The coccidiostat of new generation that the eighties is developed by Janssen pharmaceutical factory of Belgium.Chemical name is 2,6-bis-chloro-2-(4-chlorine
Benzene)-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazine-2 (3H)-yls) benzene acetonitrile, is also chlorine piperazine phenethyl cyanogen.Molecular formula is
C17H9Cl3N4O2, molecular weight is 407.64.This medicine is off-white color or pale yellow powder, almost odorless, at N, N-dimethyl formyl
In amine (DMF) the most molten, slightly soluble in oxolane (THF), the most insoluble in water, ethanol, fusing point is 291-297 DEG C.
Diclazuril is novel, efficient, low toxicity anticoccidial drug, is widely used in various coccidiosis.Chicken coccidiosis is chickling
Regular incidence and endanger extremely serious, chickling sickness rate more than 15 ages in days is the highest, and mortality rate may be up to more than 80%, and recover
Chick growth is obstructed, and can not recover for a long time, gives the poultry loss that industrial belt is come the hugest.The various coccidiosiss of chicken are had by diclazuril
Having good prevention effect, the treatment to the various coccidiosis of turkey, duck, goose, peafowl, Carnis Coturnicis japonicae, rabbit etc. is the most notable simultaneously.If
Uniformly adding 1 gram of diclazuril in feedstuff per ton, just energy 100% controls the outburst of coccidiosis.This medicine belongs to nonionic and resists
Coccidiosis medicine, it and monensin, Salinomycin, the anticoccidial drug of Maduramicin plasma type polyether antibiotics and other synthesis
Anticoccidial drug all without cross-resistance, be that current consumption is minimum, anticoccidial spectrum is the widest, need not drug withdrawal before butchering, and uses
A kind of novel against-coccidia medicine of safety.China's veterinary clinic is applied for many years, Ye Shi China poultry husbandry anticoccidial main
Means and first-line drug.
Diclazuril hangs mixed liquid and has the feature of taking convenience, but the stability of existing outstanding mixed liquid is not good enough, easily by temperature
Impact, additionally, stimulate animal intestines and stomach substantially, affects its appetite and the speed of growth.
Summary of the invention
Hang the stability of mixed liquid to improve existing diclazuril, reducing it stimulates animal intestines and stomach, and the present invention provides
A kind of high stability diclazuril suspension, still has preferable stability, and has preferable slow release effect under low temperature, right
Gastrointestinal irritability is low.
The present invention solves the technical scheme that problem used:
A kind of high stability diclazuril suspension, is made up of following parts by weight component: diclazuril slow-releasing granules 10
～20 parts, suspending agent 3～5 parts, dispersant 1～3 parts, defoamer 1～2 parts, sodium chloride 1～3 parts, antioxidant 0.8～1.2 parts
With water 66.8～82.7 parts；
Described diclazuril slow-releasing granules preparation method is as follows:
Chitosan is dissolved in obtained solution A in 3wt% aqueous acetic acid, diclazuril is added in solution A, stirring mixing
After Jun Yun, spray-dried prepared diclazuril slow-releasing granules.Use diclazuril slow-releasing granules, increase ground gram by chitosan
The slow-release function of pearl profit suspension, reduces medicine to animal intestines and stomach zest.Chitosan is the most positively charged, sodium chloride
Addition add the electrolysis performance of suspension, decrease suspension low temperature flocculability, improve suspension stability.
As preferably, described suspending agent is Polyethylene Glycol, polypyrrole alkanone or Carboxymethyl cellulose sodium.
As preferably, described dispersant is polyoxyethylene sorbitan monooleate dehydration or sorbester p17.
As preferably, described defoamer is polyoxyethylene polyoxy propanol amidogen ether, polypropylene glycerol aether, polyoxypropylene polyoxy
Ethylene Glycol ether or polydimethylsiloxane.
As preferably, described antioxidant is tea polyphenols, gallic acid or vitamin E.
As preferably, the mass ratio of described chitosan, aqueous acetic acid and diclazuril is 10～15:100:20～25.
Invention also provides a kind of method preparing high stability diclazuril suspension, comprise the steps:
(1) chitosan is dissolved in obtained solution A in 3wt% aqueous acetic acid, diclazuril is added in solution A, stirring
After mix homogeneously, spray-dried prepared diclazuril slow-releasing granules.
(2) diclazuril slow-releasing granules, suspending agent, dispersant and water are added in reaction vessel, in 800～1200 turns/
Stir 8～10 minutes mix homogeneously under point mixing speed, add defoamer, sodium chloride and antioxidant in 400～600 turns/
Divide and stir 15～20 minutes under mixing speed.
The invention have the benefit that
Diclazuril suspension provided by the present invention has preferable low-temperature stability, stable performance after storing a year,
Conveniently come into operation；Having slow release effect, reducing medicine stimulates animal intestines and stomach simultaneously.
Detailed description of the invention
Below in conjunction with specific experiment embodiment, the present invention is described in further detail.
Embodiment 1
(1) 12g chitosan is added 100g 3wt% aqueous acetic acid, after mix homogeneously, then be added thereto to 20g ground gram
Pearl profit, spray-dried prepared 31.2g diclazuril slow-releasing granules.
(2) by 15g diclazuril slow-releasing granules, 4g cetomacrogol 1000,2g polyoxyethylene sorbitan monooleate dehydration
Add in reaction vessel with 74g water, under 1000 revs/min of mixing speeds, stir 9 minutes mix homogeneously, add 1g polyoxyethylene
Polyoxy propanol amidogen ether, 3g sodium chloride and 1g vitamin E stir 15 minutes under 500 revs/min of mixing speeds.
Produce without precipitation after preserving 1 year under gained diclazuril suspension room temperature, have good stability.
Embodiment 2
(1) 10g chitosan is added 100g 3wt% aqueous acetic acid, after mix homogeneously, then be added thereto to 22g ground gram
Pearl profit, spray-dried prepared 31.4g diclazuril slow-releasing granules.
(2) 10g diclazuril slow-releasing granules, 3g polypyrrole alkanone, 1g sorbester p17 and 82.7g water are added reaction vessel
In, under 800 revs/min of mixing speeds stir 10 minutes mix homogeneously, add 1.5g polypropylene glycerol aether, 1g sodium chloride and
0.8g gallic acid stirs 20 minutes under 400 revs/min of mixing speeds.
Produce without precipitation after preserving 1 year under gained diclazuril suspension room temperature, have good stability.
Embodiment 3
(1) 15g chitosan is added 100g 3wt% aqueous acetic acid, after mix homogeneously, then be added thereto to 25g ground gram
Pearl profit, spray-dried prepared 38.6g diclazuril slow-releasing granules.
(2) by 20g diclazuril slow-releasing granules, 5g Carboxymethyl cellulose sodium, 3g polyethenoxy sorbitan list oleic acid
Ester and 66.8g water add in reaction vessel, stir 8 minutes mix homogeneously, add 2g poly-two under 1200 revs/min of mixing speeds
Methylsiloxane, 2g sodium chloride and 1.2g tea polyphenols stir 18 minutes under 600 revs/min of mixing speeds.
Produce without precipitation after preserving 1 year under gained diclazuril suspension room temperature, have good stability.
Embodiment 4 animal experiment
By 14 ages in days test chickling by only weighing after, select whose body weight difference healthy chicken within 10g, be divided into four
Group, often group 20, respectively organize test chicken through crop artificial vaccination Eimeria Tenella egg capsule suspension 1.0ml (containing tender Chinese mugwort
U.S. ear coccidiosis Sporulated Oocysts 1.0 × 105Individual), to select one group to do blank group, be not administered, other three groups of every days use implements
Example 1-3 gained diclazuril suspension is administered, and dosage is 5mg/kg (diclazuril actual content mg/ chicken body weight kg), is used in conjunction
Seven days, observe every day and record the situations such as test chicken spirit, appetite.Test the 4th day and start to check feces every day, record bloody stool feelings
Condition, until slaughtering.Testing the 7th day and carry out a gram excrement egg capsule counting, within the 8th day, cut open inspection, emphasis checks caecum lesion, according to pathological changes standard
Score.
Effect judges: observe chicken spirit, appetite, record survival rate, weightening finish and body weight increase rate, lesion score value, ovum
Capsule count value, carries out synthetic determination by calculating medicine anticoccidial index (ACI) etc..
Anticoccidial index (ACI)=(body weight increase rate+survival rate) × 100-(pathological changes value+egg capsule value)
Anticoccidial index ＞ 180 is efficient；160～180 is middle effect；120～160 is poor efficiency；Less than 120 is invalid.
Each test group is shown in Table 1 to the therapeutic effect of coccidium infection chicken.
The table 1 each test group therapeutic effect table to coccidium infection chicken
| Group | Survival rate (%) | Body weight increase rate (%) | Pathological changes value | Egg capsule value | ACI |
| Blank group | 60 | 57.23 | 35.3 | 45 | 36.93 |
| Embodiment 1 | 99 | 95.35 | 7.50 | 5 | 181.85 |
| Embodiment 2 | 100 | 96.28 | 6.82 | 6 | 183.46 |
| Embodiment 3 | 99 | 95.78 | 7.23 | 7 | 180.55 |
By table 1 it can be seen that the diclazuril suspension prepared by the present invention has significantly healing to chicken coccidiosis
Effect.
Above example is only in order to illustrate technical scheme and unrestricted, although preferred by referring to the present invention
Invention has been described for embodiment, it should be appreciated by those of ordinary skill in the art that can in form and carefully
On Jie, it is made various change, the protection domain limited without departing from claims of the present invention.
Claims (8)
1. a high stability diclazuril suspension, it is characterised in that described diclazuril suspension is by following parts by weight
Component forms: diclazuril slow-releasing granules 10 ~ 20 parts, suspending agent 3 ~ 5 parts, dispersant 1 ~ 3 part, defoamer 1 ~ 2 part, sodium chloride 1 ~
3 parts, antioxidant 0.8 ~ 1.2 part and 66.8 ~ 82.7 parts of water；
Described diclazuril slow-releasing granules preparation method is as follows:
Chitosan is dissolved in obtained solution A in 3wt% aqueous acetic acid, diclazuril is added in solution A, be uniformly mixed
After, spray-dried prepared diclazuril slow-releasing granules.
2. high stability diclazuril suspension as claimed in claim 1, it is characterised in that described suspending agent is poly-second two
Alcohol, polypyrrole alkanone or Carboxymethyl cellulose sodium.
3. high stability diclazuril suspension as claimed in claim 1, it is characterised in that described dispersant is polyoxyethylene
Arlacel-80 or sorbester p17.
4. high stability diclazuril suspension as claimed in claim 1, it is characterised in that described defoamer is polyoxyethylene
Polyoxy propanol amidogen ether, polypropylene glycerol aether, polyoxyethylene polyoxypropylene glycerin ether or polydimethylsiloxane.
5. high stability diclazuril suspension as claimed in claim 1, it is characterised in that described antioxidant is that tea is many
Phenol, gallic acid or vitamin E.
6. high stability diclazuril suspension as claimed in claim 1, it is characterised in that described chitosan, acetic acid are water-soluble
The mass ratio of liquid and diclazuril is 10 ~ 15:100:20 ~ 25.
7. the method for high stability diclazuril suspension described in preparation claim 1-6 any one, it is characterised in that described
Preparation method comprises the steps:
(1) chitosan is dissolved in obtained solution A in 3wt% aqueous acetic acid, diclazuril is added in solution A, stirring mixing
After Jun Yun, spray-dried prepared diclazuril slow-releasing granules.
8. diclazuril slow-releasing granules, suspending agent, dispersant and water are added in reaction vessel by (2), in 800 ~ 1200 revs/min
Stir 8 ~ 10 minutes mix homogeneously under mixing speed, add defoamer, sodium chloride and antioxidant and stir in 400 ~ 600 revs/min
Mix and stir 15 ~ 20 minutes under speed.
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| CN109394697A (en) * | 2018-11-30 | 2019-03-01 | 合肥中龙神力动物药业有限公司 | A kind of diclazuril sustained release preparation and preparation method thereof for preventing and treating chicken coccidiosis of rabbit |
| CN113797347A (en) * | 2021-10-21 | 2021-12-17 | 广东温氏大华农生物科技有限公司 | Water-oil two-phase cosolvent and preparation method and application thereof |
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| CN108186561A (en) * | 2018-03-12 | 2018-06-22 | 石家庄市金元康牧药业有限公司 | A kind of solution of diclazuril and preparation method thereof |
| CN109394697A (en) * | 2018-11-30 | 2019-03-01 | 合肥中龙神力动物药业有限公司 | A kind of diclazuril sustained release preparation and preparation method thereof for preventing and treating chicken coccidiosis of rabbit |
| CN113797347A (en) * | 2021-10-21 | 2021-12-17 | 广东温氏大华农生物科技有限公司 | Water-oil two-phase cosolvent and preparation method and application thereof |
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