Sezvo mishonga inogadzirisa enzyme mabasa ichiderera zvishoma nezvishoma nekuwedzera kwenguva ye in vitro incubation, tsika dzemu vitro metabolism dzine zvisingakwanisi zvakadai senguva pfupi yekuisa, kushanduka kwemasabolism uye yakaderera muganho wekuona (yehuwandu hushoma hwemuganhu weCLint assay ndeye 2.5 μL / ( min · 106 masero)), iyo isingagoni kugadzirisa zvinodhaka zvishoma nezvishoma[1]. Zvichakadaro,hepatocytes ine mamwe ma enzymes anodiwa kune oxidation, kuderedza, hydrolysis uye dimerization maitiro zvichienzaniswachiropa microsomes, uye in vitro masisitimu, akawanda mamodheru mamodheru anowanzo kuve akagadziridzwa zvichienderana nehepatocyte system uyezve kutevedzera in vivo nharaunda kuti uwedzere kuchengetwa kwe enzyme chiitiko mukatihepatocytes, uye kurebesa kwenguva yekufukidzira kunopa mukana wekutarisa yakakwana metabolic shanduko yeinononoka metabolizing zvinodhaka.[1,2].
Tichifunga izvi, IPHASE, semutungamiri mune biological reagents for in vitro research, yakapayona iyo HepatoMax™ System uye HepatoCon™ Media System zvichibva pakudzidza kweadherent primary hepatocytes uye stromal masero emarudzi akasiyana-siyana, anosanganisira vanhu, tsoko, canine, gonzo, uye mbeva, nezvimwewo. Iyo HepatoMax™ System uye HepatoCon the Mediadherenthepatocytes semuenzaniso, uye ese ari maviri masisitimu akagadzirirwa kugadzwa kwechiitiko uye kugadzikana kwemetabolism yemhando dzakasiyana dzee enzyme uye kuwedzera kwekupindura kukosha kwematabolites emushonga tolbutamide pamazuva gumi nemazuva manomwe kuti aone masisitimu. Metabolite inowedzera kukosha kwekupindura pamazuva e10 uye basa uye kugadzikana kwemetabolism yemhando dzakasiyana dze enzyme pamazuva e7 zvakatsunga kusimbisa masisitimu.
- (1) Iwo maviri akarongeka ekugadzirisa zvinodhaka tsika maitiro ndeaya anotevera:
IPHASE-HepatoMax™ico - tsika sisitimu yechando yakavharwa nemadziro ekutanga emunhu hepatocytes uye stromal masero. Primary human hepatocytes yakadzorerwa uye yakabatanidzwa ne stromal cells muHepatoP ™ yepakati kwemazuva 3 kuti itange kushandiswa kwezvinodhaka zvinodhaka, uye metabolism yemishonga yakaitwa mu serum - free HepatoDo ™ medium, iyo yakazadzwa chete nemushonga pasina kuchinja svikiro. Huwandu hwe4, 72, 168 uye 240 maawa mushure mekutonga kwezvinodhaka, kukosha kwakawedzerwa kwemishonga metabolites kwakatemwa kuongororwa.
IPHASE-HepatoCon™, kune rumwe rutivi, igadziriro yekurima yakaomeswa nechando inonamatira yekutanga hepatocytes muHepatoCon™ medium. Mushure mekusimudzira munhu wekutangahepatocytes, chirongwa chekutonga zvinodhaka chakaitwa mushure memazuva e3 etsika muHepatoCon ™ pakati pega, uye nguva yakatevera yehutungamiri, tsika yemagariro uye nzira yekuongorora yakanga yakafanana neyeHepatoMax ™ system.
Zvichakadaro, kuti ive nechokwadi chechokwadi uye kuomarara kwemhedzisiro, IPHASE yakaita yepakati control (sero - yemahara) uye stromal cell control panguva imwe chete, ine kudzokorora katatu, uye mhedzisiro yakaratidza kutiIPHASE-HepatoMax™ uyeIPHASE-HepatoCon™ masisitimu akaburitsa yakasimba peak metabolite mhinduro kubva pazuva 3 zvichienda mberi, uye kuti ivo vese vakaratidza yakasimba metabolic shanduko mwero.
- (2) Mishonga metabolism inonyanya kutsamira pane hepatocyteCYP450enzyme system, uye basa rayo rinogona kuyerwa kuti riongorore zviri nani.
TheIPHASE-HepatoMax™ uyeIPHASE-HepatoCon™ masisitimu ane mashandiro akanaka.
IPHASE yakamisa zvikamu zvina zvepakati kudzora (hapana masero), HepatoMax™, HepatoCon™ uye stromal masero. Kushandisa wall-adherent primary humanhepatocytes semuenzaniso, iyo metabolite inowedzera kukosha kweCYP1A2, CYP2B6uyeCYP3A4dzakasimbiswa pazuva 0, 3 uye 7 pashurehepatocytekupora kwemazuva matatu uchishandisa finasteride, bupropion uye midazolam sema substrates, zvichiteerana. Metabolite kuwedzera kukosha kwakaratidza kuti ese ari maviriIPHASE-HepatoMax™ uyeIPHASE-HepatoCon™ masisitimu airatidza anoshanda enzyme chiitiko nezuva rechinomwe, achisimudzira zvakajairika zvinodhaka metabolism.
- (3) Pamusoro pekusimbiswa kwechiitiko che enzyme, kugadzikana kwakanaka kwemetabolism zvakare inhanho yakakosha uye yakakosha mukusimbisa kushandiswa kwemamodhi mu vitro.
IPHASE yakagadzira mapoka matatu eHepatoMax™, HepatoCon™ uye stromal masero kuti aone kugadzikana kwemetabolism yeTolbutimide kwemaawa 80 uchishandisa adherent primary human hepatocytes semuenzaniso, iyo yaishandiswa mazuva 3 mushure mekumutswa kwekutanga.hepatocytes, uye mhedzisiro yakaratidza kuti ese ari maviriIPHASE-HepatoMax™ uyeIPHASE-HepatoCon™ masisitimu ese ari maviri airatidza yakasimba metabolic clearance chiitiko mukati mehurefu hwakareba hwenguva yeassay.
Muchidimbu, IPHASE, semutungamiri in vitro bio-reagents, yakagadziraIPHASE HepatoMax™ uyeIPHASE HepatoCon™ in vitro modhi yakavakirwa pamadziro - yakashandiswa yekutanga munhu, tsoko, canine, gonzo uye mbevahepatocytes uye stromal masero emarudzi akasiyana-siyana, ane yakanakisa metabolic kuchinja, inoshanda enzyme zviitiko uye zvine simba metabolic clearance zviitiko, izvo zvinopa sarudzo nyowani kune vatengi vedu kugadzira yakaderera- yekubvisa zvinodhaka, uye uri mudiwa akakosha kuwana kuwanikwa kwezvinodhaka! TheIPHASE HepatoMax™ uyeIPHASE HepatoCon™ in vitro modhi inopa yakanakisa metabolic turnover rates, inoshingaira enzyme zviitiko uye yakasimba metabolic clearance zviitiko, zvichipa sarudzo nyowani kune vatengi kugadzira yakaderera - yekubvisa zvinodhaka, uye mudiwa akakosha mukuwanikwa kwezvinodhaka!
Reference:
[1]阮婷婷,鞠武建,熊海伟,等.大清除率药物的代谢稳定性预测模型研究进中展展[J]. 2019(2):152-160.
[2] Di L, Trapa P, Obach R S, nevamwe. Inovhero relay nzira yekuona yakaderera-yekucheneswa tsika[J]. Zvinodhaka metabolism uye maitiro, 2012, 40(9): 1860-1865.
Nguva yekutumira: 2024-07-19 17:20:41