Txij li thaum cov tshuaj metabolizing enzyme kev ua ub no maj mam txo nrog lub sijhawm ntev ntawm vitro incubation, cov qauv hauv vitro metabolism muaj kev txwv xws li lub sij hawm luv luv, tsis tshua muaj metabolic hloov dua siab tshiab thiab siab qis qis ntawm kev kuaj pom (qhov ntau qhov txwv qis ntawm CLint assay yog 2.5 μL / ( min · 106 hlwb)), uas tsis tuaj yeem maj mam ntsuas cov tshuaj metabol.[1]. Lub caij no,hepatocytes muaj ntau enzymes xav tau rau oxidation, txo, hydrolysis thiab dimerization tshwm sim piv raudaim siab microsomes, thiab nyob rau hauv vitro systems, ntau yam tshiab qauv zoo li yuav optimized raws li covhepatocyte system thiab ntxiv mimic nyob rau hauv vivo ib puag ncig kom ncua kev khaws cia ntawm enzyme kev ua hauvhepatocytes, thiab lub sijhawm ntev ntawm lub sijhawm incubation muab qhov ua tau los saib xyuas cov metabolism hauv kev hloov pauv ntawm cov tshuaj qeeb metabolizing.[1,2].
Raws li qhov no, IPHASE, ua tus thawj coj hauv cov tshuaj lom neeg rau kev tshawb fawb hauv vitro, tau ua haujlwm rau HepatoMax ™ System thiab HepatoCon ™ Media System raws li kev tshawb fawb ntawm cov thawj cov hepatocytes thiab stromal hlwb ntawm ntau hom, suav nrog tib neeg, liab, canine, nas, thiab nas, thiab lwm yam. siv HepatoMax ™ Media System thiab HepatoMax ™ Cov Txheej Txheem tseem ceeb ntawm tib neeg.hepatocytes ua piv txwv, thiab ob lub tshuab tau teeb tsa rau kev txiav txim siab ntawm kev ua haujlwm thiab metabolic stability ntawm cov enzyme tshwj xeeb thiab kev nce hauv cov lus teb tus nqi ntawm cov tshuaj tolbutamide ntawm 10 hnub thiab 7 hnub los txheeb xyuas cov kab ke. Metabolite nce tus nqi teb ntawm 10 hnub thiab kev ua haujlwm thiab kev ruaj ntseg ntawm cov enzyme tshwj xeeb ntawm 7 hnub tau txiav txim siab kom siv tau cov tshuab.
- (1) Ob qhov txheej txheem kev lees paub tshuaj siv tau zoo yog raws li hauv qab no:
IPHASE-HepatoMax™yog ib qho kev coj noj coj ua ntawm cov kab lis kev cai ntawm cov pob zeb khov kho thawj tib neeg hepatocytes thiab stromal hlwb. Tib neeg cov hepatocytes tau resuscitated thiab incubated nrog stromal hlwb nyob rau hauv HepatoP ™ nruab nrab rau 3 hnub los pib tshuaj ntsuam xyuas cov tshuaj, thiab cov metabolism hauv cov tshuaj tau ua nyob rau hauv serum-free HepatoDo™ nruab nrab, uas yog replenished nkaus xwb nrog cov tshuaj tsis hloov qhov nruab nrab. Tag nrho ntawm 4, 72, 168 thiab 240 teev tom qab kev tswj hwm tshuaj, tus nqi ntxiv ntawm cov tshuaj metabolites tau txiav txim siab rau kev tshuaj xyuas.
IPHASE-HepatoCon™, ntawm qhov tod tes, yog ib txoj hauv kev rau kev cog qoob loo khov rau cov tib neeg cov kab mob hepatocytes hauv HepatoCon ™ nruab nrab. Tom qab resuscitation thawj tus tib neeghepatocytes, kev tshuaj xyuas kev tswj hwm tshuaj tau ua tiav tom qab 3 hnub ntawm kab lis kev cai hauv HepatoCon ™ nruab nrab ib leeg, thiab lub sijhawm tom ntej ntawm kev tswj hwm, kab lis kev cai thiab cov txheej txheem ntsuas tau zoo ib yam li HepatoMax ™ system.
Lub caij no, txhawm rau kom ntseeg tau qhov tseeb thiab nruj ntawm cov txiaj ntsig, IPHASE tau ua qhov kev tswj nruab nrab (cell - dawb) thiab kev tswj hwm ntawm tes stromal tib lub sijhawm, nrog peb qhov rov ua dua, thiab cov txiaj ntsig tau pom tias covIPHASE-HepatoMax™ thiabIPHASE-HepatoCon™ cov kab ke tsim muaj zog tshaj plaws metabolite teb los ntawm hnub 3 mus ntxiv, thiab tias lawv ob leeg pom muaj zog metabolic turnover tus nqi.
- (2) Cov tshuaj metabolism feem ntau yog nyob ntawm lub hepatocyteTSI 450enzyme system, thiab nws cov haujlwm tuaj yeem ntsuas tau zoo dua.
CovIPHASE-HepatoMax™ thiabIPHASE-HepatoCon™ systems muaj kev siv tau zoo.
IPHASE teeb tsa plaub pawg tswj nruab nrab (tsis muaj hlwb), HepatoMax™, HepatoCon™ thiab stromal hlwb. Siv phab ntsa-adherent thawj tib neeghepatocytes ua piv txwv, cov metabolite nce nqi ntawmCYP1A2, CYP2B 6thiabCYP3A4tau txheeb xyuas hnub 0, 3 thiab 7 tom qabhepatocyterov qab rau 3 hnub siv finasteride, bupropion thiab midazolam ua cov substrates, feem. Metabolite nce qhov txiaj ntsig tau pom tias ob qho tib siIPHASE-HepatoMax™ thiabIPHASE-HepatoCon™ Cov kab ke pom kev ua haujlwm enzyme los ntawm hnub 7, tsis tu ncua txhawb cov tshuaj metabolism hauv ib txwm.
- (3) Ntxiv rau qhov kev siv tau ntawm kev ua haujlwm enzyme, zoo metabolic stability kuj yog ib qho tseem ceeb thiab indispensable kauj ruam nyob rau hauv validating cov nqi hluav taws xob nyob rau hauv vitro qauv.
IPHASE teeb tsa peb pawg ntawm HepatoMax ™, HepatoCon ™ thiab stromal hlwb los txiav txim siab cov metabolism hauv kev ruaj ntseg ntawm Tolbutimide nyob rau lub sijhawm ntawm 80 teev siv cov tib neeg cov kab mob hepatocytes ua piv txwv, uas tau tswj hwm 3 hnub tom qab resuscitation thawj zaug.hepatocytes, thiab cov txiaj ntsig tau pom tias ob qho tib siIPHASE-HepatoMax™ thiabIPHASE-HepatoCon™ cov tshuab ob leeg tau pom tias muaj zog metabolic tshem tawm kev ua haujlwm nyob rau hauv qhov ntev tshaj plaws ntawm lub sijhawm ntsuas.
Hauv cov ntsiab lus, IPHASE, ua tus thawj coj hauv vitro bio-reagents, tau tsimIPHASE HepatoMax™ thiabIPHASE HepatoCon ™ in vitro qauv raws phab ntsa - siv thawj tib neeg, liab, canine, nas thiab nashepatocytes thiab stromal hlwb ntawm ntau yam genera, nrog zoo heev metabolic turnover, active enzyme kev ua si thiab muaj zog metabolic clearance kev ua ub no, uas muaj kev xaiv tshiab rau peb cov neeg muas zaub los tsim tsawg - clearance tshuaj, thiab yog ib tug indispensable khub kom paub txog tshuaj nrhiav pom! CovIPHASE HepatoMax™ thiabIPHASE HepatoCon ™ Cov qauv hauv vitro muab cov txiaj ntsig zoo ntawm cov metabolic hloov pauv, cov haujlwm enzyme nquag thiab muaj zog metabolic tshem tawm cov haujlwm, muab cov kev xaiv tshiab rau cov neeg siv khoom los tsim cov tshuaj qis - tshem tawm cov tshuaj, thiab yog tus khub tseem ceeb hauv kev tshawb nrhiav tshuaj!
Siv:
[1]阮婷婷, 鞠武建, 熊海伟, 等.低清除率药物的代谢稳定性预测模型研究进展[J].中国药科大学学报, 2019(2):152-160.
[2] Di L, Trapa P, Obach R S, et al. Ib txoj kev tshiab relay rau kev txiav txim siab qis - clearance qhov tseem ceeb [J]. Drug metabolism and disposition, 2012, 40(9): 1860-1865.
Hnub tim: 2024-07-19 17:20:41