Sezvo iyo mishonga mishonga ye enzyme zviitiko zvishoma nezvishoma inoderera neyekuwedzera kweVitro kuiswa kwesimba[1]. Zvichakadaro,hepatocytes ane akawanda enzymes anodikanwa kuti oxidation, kuderedza, hydrolysis uye dimerisization maitiro achienzaniswa nechiropa microsomes, uye muVitro Systems, akawanda marudzi mazhinji anowanzove akagadzirirwa kubva panehepatocyte System uye kumwezve kutevedzera iyo muVivo nharaunda yekununura kuchengetedza kweiyo enzyme chiitiko muhepatocytes, uye kusarudzika kweiyo nguva yekushongedza inopa mukana wekutarisa zvakakwana metariro ekushandurwa kwetabolic yekudzora mishonga yekuita[1,2].
Tichifunga izvi, Iphase, semutungamiri wezvivakwa zvekushanduka kweVitro munhuhepatocytes semuenzaniso, uye masisitimu ese akaiswa mukutsunga kwechiitiko uye metabolic kugadzikana kwemhando dze enzyme eMetabolices yeiyo madhiri emushonga mumazuva gumi uye mazuva manomwe kuti uone masisitimu. Metabolite anowedzera mhinduro pamazuva gumi uye zviitiko uye metabolic kugadzikana kwemhando dze enzyme mumazuva manomwe aive akatsunga kusimbisa masisitimu.
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Iphase - Hepatomax ™Iro CO - Tsika yetsika yetsika yakarongedzwa yakadzvanywa primary vanhu hepatocytes uye stromal masero. Yokutanga Hepatocytes yakadzoserwa uye yakavezwa neStomal masero muHepatiop ™ mazuva matatu ekutanga muSerum - Specium yeSepatodo Yakazara ye4, 72, 168 uye maawa makumi maviri nemana mushure mekutungamira kwezvinodhaka, kukosha kwakawedzerwa kwezvinodhaka metabolites kwakatsunga kuongororwa.
Ifase - Hepatocon ™, kune rumwe rutivi, isirimu yetsika yechando yakaromina chando chinomiririra vanhu hepatocytes muHepatocon ™ yepakati. Mushure mekudzosera iyo yekutanga munhuhepatocyteS, iyo mishonga yezvinodhaka inoitwa mushure memazuva matatu emazuva matatu muHepatocon ™ nguva yekutonga, tsika idzo uye iya leaday yaive yakafanana neye hepatomax ™ system.
Zvichakadaro, kuve nechokwadi chekuti kurerutsa uye kuomarara kwemhedzisiro, Iphose vakaita svutugadzike repakati (SEPECE CROPL (Cell Control Control panguva imwe chete, nekudzora nhatu, uye mhedzisiro yacho yakaratidza kutiIphase - Hepatomax ™ uyeIfase - Hepatocon ™ Systems yakaburitsa Peak yakasimba metabolite kubva pazuva rechitatu zvichienda mberi, uye kuti ivo vaviri vakaratidza metabolic turnover rate.
- (2) mrabolism inodhaka inonyanya kutsamira paHepatocyteCyp450Enzyme system, uye chiitiko chacho chinogona kuyerwa kuti uongorore zviri nani.
The theIphase - Hepatomax ™ uyeIfase - Hepatocon ™ Systems ine yakanaka yekushanda.
Iphase gadzira zvikamu zvina zvemhando yepamusoro (hapana masero), hepatomax ™, hepaton ™ uye stromal masero. Kushandisa Wall - Inhere Pritalary Munhuhepatocytes semuenzaniso, metabolite anowedzera tsika dzeCyp1a2, Cyp2b6uyeCyp3a4vakasimbiswa pazuva 0, 3 ne7 mushurehepatocyteKudzoreredza kwemazuva matatu uchishandisa kugutsa, Bupropion uye midazolam seSubstrates, zvichiteerana. Metabolite kuwedzera tsika kwakaratidza kuti zvese zviri zviviriIphase - Hepatomax ™ uyeIfase - Hepatocon ™ Systems yakaratidza kushanda kweiyo enzyme zuva rechinomwe, zvinogara zvichisimudzira zvakajairika metabolism.
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Iphase gadzira zvikamu zvitatu zveHepatomaxhepatocytes, uye mhedzisiro yakaratidza kuti zveseIphase - Hepatomax ™ uyeIfase - Hepatocon ™ Systems ese airatidza kusimba metabolic clearance zviitiko mukati mekukosha kwakareba kweiyo leary nguva.
MuPummary, Ifase, semutungamiri muVitro Bio - Refaasts, yakagadziraIfase Hepatomax ™ uyeIphae Hepatocon ™ muVitro Models Kubva pamadziro - Akashandiswa Pakutanga Munhu, Monkey, Canine, Rat uye mbevahepatocyteS uye stromal masero akasiyana eStera, ane metazolic turnver, anoshanda enzicme zviitiko uye anopa sarudzo nyowani kuti vatengi vedu vakudzwe kudiki - muropa zvisina kukodzera kuziva kuwanikwa kwezvinodhaka! The theIfase Hepatomax ™ uyeIphae Hepatocon ™ MuVitro Models inopa yakanaka metabolic tates
Reference:
[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. Nzira yeLove yeLoury yekuona yakaderera - clearance tsika [j]. Metabolism uye mafungiro, 2012, 40 (9): 1860 - 1865.
Post Nguva: 2024 - 07 - 19 17: 20:30