Popeza mankhwala osokoneza bongo amachepetsa pang'onopang'ono ndi kuchuluka kwa mitundu ya vitro, mwachikhalidwe cha Vint[1]. Pakalipano,hepatocyteali ndi ma enzyme ambiri omwe amafunikira oxidation, kuchepetsa, hydrolysis ndi kumvetsetsa zomwe zimachitika poyerekeza ndimicroolumes, komanso mu machitidwe a Vitro, mitundu yambiri yazithunzi imakonda kutengera kutengerahepatocyte dongosolo ndi kutsanzira mopitilira muyeso wa vivo kuti apitilize kuwongolera kwa enzyme ntchitohepatocytes, ndipo kutalika kwa nthawi ya makulitsidwe kumapereka mwayi wowunikira zokwanira kagayidwe ka kakitala wa mankhwala osachedwa[1,2].
Poona izi, Iphase, monga mtsogoleri wopangira kafukufuku wa vitro, wachita upainiya wa Hepatocy ™ wamunthuhepatocyteMonga chitsanzo, ndipo machitidwe onsewo adakhazikitsidwa kuti atsimikizire kuti ntchitoyi ndi kukhazikika kwa mitundu ya enzyme ndi kuchuluka kwa mankhwala a tolbutamide pa masiku 10 ndi masiku 7 kuti muwonetsetse makina. Metabolite imawonjezera phindu pa masiku 10 ndi ntchito kukhazikika kwa mitundu ina ya enzyme masiku 7 inali yotsimikiza kutsimikizira machitidwe.
- (1) Njira ziwiri zothandizira chikhalidwe cha chikhalidwe cha mankhwala ndi motere:
Iphase - hepatomax ™ndi CO - Chikhalidwe Chikhalidwe cha oundana owundana kwambiri ndi ma hepatocytes aumunthu ndi maselo ozungulira. Choyambirira cha hepatocytes chimakhala chosinthika ndikuphatikizidwa ndi maselo ozungulira mu hepatop ™, ndipo kagayidwe ka mankhwalawa adayamba ku serumon ™ Farmuent, omwe adawerengedwa ndi sing'angayo. Pafupifupi 4, 72, 168 mpaka maola angapo pambuyo pa makonzedwe, mtengo womwewo wowonjezedwa wa metabolites unatsimikizika kuti usanthule.
Iphase - Hepatocon ™Komabe, kumbali inayo, ndi kachitidwe kopenyerera ma hepatocytes oyambira a hepatocy ™. Pambuyo pokana munthu woyambahepatocyteS, bungwe loyang'anira mankhwala lidachitika pambuyo pa masiku atatu a chikhalidwe ku hepatocon ™ payekha, ndipo njira yotsatirira ndi njira yofananira ndi omwe ali panjira ya hepatox.
Pakadali pano, kuonetsetsa kuti zotsatira zake, Iphase adachita zowongolera (cell - kuwongolera miyala) nthawi imodzi, ndipo zotsatira zake zidawonetsa kutiIphase - hepatomax ™ ndiIphase - Hepatocon ™ Makina adatulutsa yankho la peak metabol kuyambira pa tsiku 3 lopitilira, ndikuti onse adawonetsa kuchuluka kwa chipata cha metabolic.
- (2) Mankhwala olimbitsa thupi amadalira kwambiri hepatocyteCyp450Makina a enzyme, ndipo ntchito yake imatha kuyesedwa kuti muwerenge bwino.
AIphase - hepatomax ™ ndiIphase - Hepatocon ™ Makina ali ndi ntchito yabwino.
Iphase adakhazikitsa mitundu inayi ya kuwongolera kwapakatikati (maselo), hepatoxx ™, hepatocron ™ ndi maselo a stromal. Kugwiritsa Ntchito Khoma - Amprete OrgehepatocyteMwachitsanzo, metabolite imawonjezera mikhalidwe yaCyp1a2, Cyp2b6ndiCyp3a4adatsimikiziridwa tsiku la 0, 3 ndi 7 pambuyohepatocytekuchira kwa masiku atatu pogwiritsa ntchito finasteride, bupropion ndi midazolam ngati gawo lapansi, motsatana. Makina owonjezera metabolite adawonetsa kuti onsewoIphase - hepatomax ™ ndiIphase - Hepatocon ™ Makina adawonetsa ntchito ya ezzyme tsiku ndi tsiku, nthawi zonse amalimbikitsa mankhwala osokoneza bongo.
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Iphase adakhazikitsa magulu atatu a Hepatotoxx ™, hepatocon ™ ndi stromal cell kuti adziwe kukhazikika kwa ma tolbutyhepatocytes, ndipo zotsatira zake zidawonetsa kuti onsewoIphase - hepatomax ™ ndiIphase - Hepatocon ™ Makina onsewa adawonetsa chiwongola dzanja cha metabolic chokwanira pamtengo wautali kwambiri.
Mwachidule, monga mtsogoleri, monga mu vitro bio - Zodzikongoletsera, zayambaIphase hepatomax ™ ndiIphase hepatocon ™ Mu mitundu ya vitronce yotengera khoma - ntchito yoyamba, nyani, canine, rat ndi mbewahepatocyteMaselo a mitundu yosiyanasiyana ya geora yosiyanasiyana, yomwe ili ndi enzyme yogwira ntchito ndi zochitika zamphamvu za meyibolic, zomwe zimapereka zisankho zatsopano kwa makasitomala athu kuti azikhala otsika! AIphase hepatomax ™ ndiIphase hepatocon ™ Mu mitundu ya Vitro imapereka mitengo yazosintha za metabolic, yogwira ntchito yamphamvu ya metabolic, ndikupatsa njira zatsopano kwa makasitomala kuti azikhala otsika - mankhwala osokoneza bongo, ndipo ndi mnzake wofunika pakupanga mankhwala!
Kunena:
[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. 中国药科大学学报, 2019 (2): 152 - 160.
[2] DI L, TOPUP P, Obach R s, et al. Njira yolumikizira yofananira kuti mudziwe zochepa - Mfundo za Clearance [j]. Metabolism ndi mawonekedwe, 2012, 40 (9): 1860 - 1865.
Post Nthawi: 2024 - 07 - 19 17:20:0:41