Fipronil ntsiav tshuajyog ib qho tshuaj tua kab muaj zog raws li cov tshuaj phenylpyrazole. Cov txheej txheem tseem ceeb ntawm cov tshuaj no yog nyob rau hauv nws cov kev xaiv heev cuam tshuam nrog rau -aminobutyric acid (GABA) receptors nyob rau hauv kab hauv nruab nrab paj hlwb, ua rau ntau dhau ntawm cov kab mob hauv lub paj hlwb thiab ua rau tuag taus. Cov ntsiav tshuaj no tsuas yog siv rau hauv kev kho tsiaj kho tsiaj rau cov tsiaj txhu xws li dev thiab miv, rau kev tiv thaiv thiab tswj cov kab mob sab nraud xws li dev mub thiab zuam. Ib co formulations kuj siv tau rau tej kev ua liaj ua teb tshuaj tua kab. Thaum siv nws, yuav tsum tau ua raws li cov lus qhia meej ntawm cov tsiaj thiab qhov hnyav, thiab cov kws kho tsiaj yuav tsum tau ua raws li cov lus qhia. Txoj kev tswj hwm feem ntau yog qhov ncauj. Nws yog ib nqi sau cia hais tias cov tshuaj no muaj ib tug tseem ceeb toxicity rau tib neeg lub cev thiab tsis yog ib tug tib neeg tshuaj. Kev noj tshuaj tsis haum tuaj yeem ua rau muaj kev phom sij hnyav xws li xeev siab, ntuav, mob plab, mob taub hau, convulsions, thiab lwm yam, thiab txawm tias muaj kev phom sij rau lub neej. Yog li ntawd, nws yog ib qho tseem ceeb uas yuav tsum nruj me ntsis cais nws los ntawm cov tshuaj tseem ceeb hauv tsev thiab xyuas kom cov me nyuam tsis tuaj yeem nkag mus rau nws. Thaum lub sij hawm tom qab noj tshuaj tsiaj, nws raug nquahu kom txwv kev sib cuag nrog cov me nyuam mos thiab cov me nyuam me kom txo tau qhov kev pheej hmoo ntawm qhov seem.
|
|
|
| Fipronil Spot On | Compound Fipronil thiab Praziquantel Spot On Solution (Fipronil + Methopren + Acetaminobamectin + Praziquantel) |
Compound Fipronil Drops (Fipronil + Methoprene) |
| TSI: 0.5ml DOG: (1) 0.67ml: 2-10kg (2) 1.34ml: 10-20kg (3) 2.68ml: 20-40kg (4) 4.02ml: 40-60kg |
(1) 0.3ml (2) 0.9ml 1ml:83mg+100mg+4mg+83mg |
CAT: 0.5ml: 50mg +60mg DOG: 1ml: 100mg+90mg (1) 0.67ml (2) 1.34ml (3) 2.68ml (4) 4.02 ml |
Fipronil hmoov COA
Kev txiav txim siab ntawm cov khoom xyaw tshuaj nquag (API)
Cov khoom siv tshuaj nquag (API) ntawmFipronil ntsiav tshuaj(fluofenidone ntsiav tshuaj) yog fluofenidone. Kev tswj kom zoo ntawm cov khoom no yuav tsum tau txiav txim siab los ntawm ntau yam xws li raw khoom purity, impurity tswj, stability kev tshawb fawb, txoj kev validation, thiab batch sib xws, thiaj li yuav ua kom muaj kev ruaj ntseg, ua tau zoo thiab stability ntawm cov tshuaj.
Tswj ntawm raw khoom purity
Lub purity ntawm fipronil ncaj qha cuam tshuam rau kev ua tau zoo ntawm cov khoom kawg. Cov khoom siv raw yuav tsum ua kom tau raws li cov qauv ntawm cov tshuaj pharmacopoeia, nrog rau purity ntawm ntau dua lossis sib npaug li 99.5% thiab ib qho impurity tsawg dua lossis sib npaug li 0.1%. Thaum lub sijhawm tsim khoom, cov neeg muag khoom yuav tsum tau ua tib zoo xaiv, thiab txhua pawg ntawm cov khoom siv raw yuav tsum tau kuaj xyuas HPLC kom ntseeg tau tias cov ntsiab lus ntawm cov khoom tseem ceeb ua tau raws li cov qauv. Piv txwv li, cov tshuaj npe ntawm fipronil yog (RS)-5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfonylpyrazole-3-cyanate. Cov tshuaj chlorine atoms thiab trifluoromethyl pawg hauv nws cov qauv molecular yuav tsum tau lees paub los ntawm nuclear magnetic resonance (NMR) thiab huab hwm coj spectrometry (MS) kom tsis txhob txo qis kev ua haujlwm vim qhov txawv txav.
Impurity Control thiab Limit Setting
Cov kev txwv impurity yuav tsum raug txiav txim raws li cov ntaub ntawv kev nyab xeeb thiab kev ua tau zoo los ntawm API. Cov impurities uas yuav raug qhia thaum lub sij hawm tsim cov fipronil muaj xws li hluavtaws intermediates (xws li 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethyl phenyl) pyrazole), incompletely reacted raw cov ntaub ntawv (xws li trifluoruchyl sulfonide cov khoom), fipronil). Kev sim degradation yuam kev (xws li raug lub teeb, kub, thiab cov av noo siab) yuav tsum tau ua kom simulate impurity tsim, thiab HPLC-UV lossis HPLC-MS cov tswv yim yuav tsum tau siv rau kev tshawb nrhiav. Qhov kev txwv rau ib qho impurity yuav tsum tau teem caij tsawg dua lossis sib npaug li 0.5% thiab rau tag nrho cov impurities tsawg dua lossis sib npaug li 1.5%. Piv txwv li, fipronil yuav tsim sulfoxide-hom impurities nyob rau hauv acidic tej yam kev mob, thiab cov ntsiab lus ntawm cov impurities yuav tsum tau tswj los ntawm kev kho tus nqi pH.
Kev tshawb fawb txog kev ruaj ntseg
Kev tshawb fawb txog kev ruaj ntseg yog qhov tseem ceeb rau kev ntsuas lub txee lub neej ntawm APIs nyob rau hauv ntau yam mob. Kev ntsuas nrawm (40℃/ 75% RH, 6 lub hlis) thiab qhov ntev - kuaj lub sijhawm (25℃/ 60% RH, 24 lub hlis) yuav tsum tau saib xyuas cov ntsiab lus tsis tu ncua, kev sib cais, thiab kev hloov pauv hauv impurities. Piv txwv li, fipronil tuaj yeem decompose nyob rau hauv qhov kub thiab txias los tsim hydrogen fluoride. Cov ntsiab lus fluoride ion yuav tsum tau kuaj pom siv ion chromatography kom ntseeg tau tias nws tsis dhau qhov kev nyab xeeb. Tsis tas li ntawd, qhov cuam tshuam ntawm cov khoom ntim khoom (xws li aluminium foil blister ntim) ntawm kev ruaj ntseg ntawm API yuav tsum tau kawm kom tsis txhob degradation vim noo noo permeability los yog lub teeb raug.
Kev Tshawb Fawb Txog Kev Tshawb Fawb
Qhov tseeb ntawm cov txheej txheem tshawb pom ncaj qha cuam tshuam rau kev tswj cov txiaj ntsig zoo. Nws yog ib qho tsim nyog yuav tsum tau ua raws li cov txheej txheem tshuaj ntsuam xyuas xws li HPLC thiab UV, suav nrog qhov tshwj xeeb (tseem ceeb los ntawm kev sim degradation rau kev sib cais ntawm impurities los ntawm lub ntsiab ncov), linearity (R² Ntau dua lossis sib npaug rau 0.999), precision (RSD Tsawg dua lossis sib npaug rau 2%), qhov tseeb (rov qab tus nqi 98%), thiab qhov sib piv ntawm 4% 2; fluctuates los ntawm ± 5%, nws tseem ua tau raws li qhov yuav tsum tau ua). Piv txwv li, rau kev txiav txim siab ntawm cov ntsiab lus fipronil, C18 chromatographic kem yog siv, nrog acetonitrile- dej (muaj 0.1% formic acid) raws li theem ntawm lub xov tooj ntawm tes, thiab qhov ntsuas wavelength yog 280 nm. Kev sib cais ntawm txoj kev no rau fipronil thiab paub impurities yuav tsum tau txheeb xyuas.
Batch Consistency Control
Batch sib xws yog lub hauv paus rau kev ua kom lub uniformity ntawm cov tshuaj zoo. Nws yog ib qho tsim nyog los saib xyuas cov txheej txheem tseem ceeb (xws li kev nplawm nrawm thiab ntim ntim hauv cov dej ntub dej) hauv lub sijhawm tiag tiag siv cov txheej txheem tshuaj ntsuam xyuas (PAT), thiab sib txuas ze ntawm -infrared spectroscopy (NIR) rau online nrhiav pom cov khoom ya raws thiab kev sib xws. Piv txwv li, thaum lub ntsiav tshuaj nias theem, qhov sib txawv ntawm cov ntsiav tshuaj hnyav (± 3%), hardness (8-10 kg / cm²), thiab lub sij hawm disintegration (tsawg dua los yog sib npaug li 15 feeb) yuav tsum tau tswj. Cov ntaub ntawv sib txawv yuav tsum tau txheeb xyuas siv cov txheej txheem kev tswj xyuas kev txheeb cais (SPC) cov kab kos kom kho qhov ntsuas tam sim kom tsis txhob muaj qhov sib txawv.
Kev tswj hwm thiab kev txhawb nqa cov ntaub ntawv tshawb fawb
Cov qauv zoo ntawm API yuav tsum ua raws li cov cai ntawm kev cai hauv tsev thiab thoob ntiaj teb. Piv txwv li, Suav Pharmacopoeia qhia meej cov kev cai ntawm cov khoom, kev txheeb xyuas, kev ntsuam xyuas (xws li kev soj ntsuam impurity, residual solvents) thiab cov ntsiab lus txiav txim siab ntawm fipronil. Tib lub sijhawm, ICH cov lus qhia (xws li Q3D elemental impurities, Q6A cov qauv zoo) yuav tsum raug xa mus rau hauv kev tsim cov kev txwv ntawm impurities. Ntxiv mus, kev tshawb fawb toxicological (xws li mob toxicity, genotoxicity) yuav tsum tau ua los ntsuas kev nyab xeeb ntawm API, muab kev tshawb fawb hauv paus rau cov qauv zoo.
Pharmacodynamic xeem
Mechanism of Drug Effect
Fipronil ntsiav tshuajyog ib qho dav -spectrum insecticide belongs rau chav kawm phenylpyrazole. Nws lub luag haujlwm tseem ceeb ntawm kev ua haujlwm yog xaiv los tiv thaiv -aminobutyric acid (GABA) receptor nyob rau hauv kab, thaiv cov tshuaj chloride ion raws thiab cuam tshuam nrog kev ua haujlwm ntawm lub hauv paus paj hlwb. Cov ntaub ntawv sim qhia tias nws tus nqi IC50 rau GABA receptor nyob rau hauv kab laum yog 30 nM, uas yog qis dua 1600 nM hauv nas, qhia tias muaj zog lub hom phiaj ntawm cov kab paj hlwb. Tsis tas li ntawd, fipronil tuaj yeem thaiv cov glutamate tshwj xeeb-gated chloride ion channels (GluCls) tshwj xeeb rau cov kab. Cov channel no tsis muaj nyob hauv cov tsiaj nyeg, piav qhia ntxiv txog nws cov tshuaj lom neeg tsawg rau tib neeg thiab tsiaj.
Pharmacodynamic Experiment Design
Kawm thiab pab pawg
Qhov kev sim siv cov neeg laus noj qab nyob zoo dev thiab miv ua qauv. Lawv tau muab faib ua pawg tswj hwm dawb paug, pawg qauv, pawg tswj zoo (avermectin), thiab qis / nruab nrab / siab- koob tshuaj Fipronil pawg (0.67 mg / kg, 1.34 mg / kg, 2.68 mg / kg) raws li lub cev hnyav thiab poj niam txiv neej. Tus naj npawb ntawm cov tsiaj hauv txhua pab pawg yuav tsum tau ua kom tau raws li cov ntaub ntawv teev tseg (cov dev Ntau dua lossis sib npaug rau 6, miv Ntau dua lossis sib npaug rau 8) txhawm rau txo qhov cuam tshuam ntawm tus kheej qhov sib txawv ntawm cov txiaj ntsig.
Txoj kev tswj hwm thiab koob tshuaj
Kev tswj hwm yog nyob rau hauv daim ntawv ntawm cov tshuaj pleev. Cov kua tau sib npaug ntawm qhov chaw sib tshuam ntawm tus dev lub xub pwg lossis nraub qaum ntawm tus miv lub caj dab kom tsis txhob licking. Cov koob tshuaj tau teem raws li cov txiaj ntsig ntawm qhov kev sim ua ntej -. Qhov nruab nrab - pawg koob tshuaj (1.34 mg / kg) muaj 98.7% tua cov dev mub hauv 24 teev thiab 100% hauv 48 teev; LT50 ntawm zuam yog 6.2 teev thiab LT90 yog 12.5 teev, uas yog qhov zoo dua li pawg tswj hwm zoo (avermectin, LT50 yog 8.9 teev, LT90 yog 18.3 teev). Cov pab pawg tsawg - koob tshuaj (0.67 mg / kg) muaj 85.3% tua tus nqi hauv 24 teev, qhia txog koob tshuaj - nyob ntawm cov nyhuv.
Pharmacodynamic Observation Indicators
Direct indicators: Lub sij hawm tuag (LT50, LT90) ntawm dev mub thiab zuam thiab 24-teev thiab 48-teev tua tus nqi.
Indirect indicators: Tsiaj coj cwj pwm saib (xws li khawb zaus), daim tawv nqaij liab, qhov hnyav hloov.
Cov ntsuas kev nyab xeeb: ntshav niaj hnub, lub siab thiab lub raum ua haujlwm (ALT, AST, creatinine), kuaj cov ntaub so ntswg (siab, lub raum, spleen).
Pharmacodynamic Experiment Results
Insecticidal nyhuv
Qhov nruab nrab - pawg koob tshuaj (1.34 mg / kg) muaj 98.7% tua cov dev mub hauv 24 teev thiab 100% hauv 48 teev; LT50 ntawm zuam yog 6.2 teev thiab LT90 yog 12.5 teev, uas yog qhov zoo dua li pawg tswj hwm zoo (avermectin, LT50 yog 8.9 teev, LT90 yog 18.3 teev). Cov pab pawg tsawg - koob tshuaj (0.67 mg / kg) muaj 85.3% tua tus nqi hauv 24 teev, qhia txog koob tshuaj - nyob ntawm cov nyhuv.
Kev soj ntsuam kev nyab xeeb
Thaum lub sij hawm sim, tsis muaj kev tuag los yog muaj kev cuam tshuam loj heev tshwm sim hauv ib pawg ntawm cov tsiaj. Hauv qhov siab - pab pawg koob tshuaj (2.68 mg / kg), 1 tus dev tau pom qhov luv luv salivation (< 30 minutes), which might be related to the alcohol component in the drug carrier. There was no significant difference in blood routine, liver and kidney function indicators compared with the blank control group (P > 0.05), and no liver or kidney damage was found in the tissue pathological examination.
Residual Effect Period Verification
Los ntawm kev sim tshuaj tua kab mob txhua lub limtiam, nws tau pom tias cov tshuaj muaj txiaj ntsig ntawm qhov nruab nrab - pawg koob tshuaj tau ntev li 4 lub lis piam, thiab tus nqi tua tau poob mus rau 89.2% nyob rau lub lim tiam 5, uas zoo ib yam nrog lub sijhawm qhia txog cov nyhuv seem (2-4 lub lis piam).
Pharmacodynamic Experiment Conclusion
Kev ua tau zoo
Fipronil ntsiav tshuajmuaj cov nyhuv tua sai thiab ua tau zoo ntawm cov dev mub thiab zuam sab nraud ntawm cov dev thiab miv. Qhov nruab nrab - pawg koob tshuaj (1.34 mg / kg) yog qhov koob tshuaj zoo tshaj plaws, ntsuas kev ua tau zoo thiab kev nyab xeeb.
Kev nyab xeeb
Ntawm cov koob tshuaj pom zoo, cov tsiaj tsis pom muaj kev cuam tshuam rau lub cev, thiab qhov kev pheej hmoo ntawm kev khaus hauv zos tsis tshua muaj, ua tau raws li qhov yuav tsum tau muaj ntawm kev nyab xeeb tshuaj veterinary.
Clinical tseem ceeb
Cov txiaj ntsig kev sim txhawb nqaFipronil ntsiav tshuajraws li ib qho ntawm cov tshuaj nyiam rau kev tiv thaiv thiab tswj cov kab mob sab nraud hauv cov tsiaj, tshwj xeeb tshaj yog rau cov kab tsuag uas tau tsim tawm tsam pyrethroids thiab carbamates.
FAQ
1. Cov ntsiav tshuaj Fipronil puas yog npaj rau tib neeg siv?
Tsis yog, tsis yog. Fipronil (fluvalinate) yog ib qho tshuaj tua kab zoo heev, feem ntau yog siv hauv kev ua liaj ua teb thiab chaw kho tsiaj. Nws yog nruj me ntsis txwv tsis pub rau tib neeg noj. Nws yog tshuaj lom heev rau tib neeg.
2. Nws lub hom phiaj tseem ceeb yog dab tsi?
Hauv kev lag luam kws kho tsiaj, nws tsuas yog siv rau kev tiv thaiv thiab tswj cov kab mob sab nraud hauv cov tsiaj xws li dev thiab miv, xws li dev mub thiab zuam. Nws feem ntau yog tsim los ua kua lossis tshuaj tsuag, thiab daim ntawv ntsiav tshuaj tsis tshua pom ntawm cov tsiaj.
3. Yuav ua li cas yog tias ib tug neeg tsis nco qab noj nws?
Nov yog qhov xwm txheej kho mob xwm txheej ceev. Kev tsis pom kev tuaj yeem ua rau muaj kuab lom. Cov tsos mob muaj xws li xeev siab, ntuav, mob taub hau, thiab qaug dab peg. Hauv qhov xwm txheej hnyav, nws tuaj yeem ua neej nyob - hem. Koj yuav tsum tam sim ntawd nqa cov ntim tshuaj nrog koj rau kev kho mob.
4. Dab tsi yog qhov tseem ceeb tshaj plaws uas yuav tsum nco ntsoov thaum siv nws?
Paub meej qhov txawv ntawm tib neeg cov tshuaj thiab cov tshuaj veterinary, thiab xyuas kom meej tias cov me nyuam tsis tuaj yeem ntsib nrog lawv. Tom qab siv cov tshuaj tsiaj, tsis txhob cia tus tsiaj nyob ze nrog cov me nyuam mos thiab cov me nyuam me. Ua raws li kws kho tsiaj cov lus qhia thiab siv cov tshuaj raws li tus tsiaj lub cev hnyav; txhob ua phem rau lawv.
Cim npe nrov: fipronil ntsiav tshuaj, lwm tus neeg, manufacturers, hoobkas, lag luam wholesale, yuav, nqe, tej, kev muag khoom