Tun da miyagun ƙwayoyi metabolizing ayyukan enzyme sannu a hankali ya ragu tare da tsawaita lokacin shiryawa in vitro, ƙirar in vitro na al'ada na al'ada suna da iyakancewa kamar gajeriyar lokacin shiryawa, ƙaramin juzu'i na rayuwa da ƙarancin ƙarancin ganowa (ƙananan ƙarancin ƙimar CLint assay shine 2.5 μL / (min · 106 sel)), wanda ba zai iya yin hasashen ainihin magungunan CLint a hankali a hankali ba.[1]. A halin yanzu,hepatocytes suna da ƙarin enzymes da ake buƙata don hadawan abu da iskar shaka, raguwa, hydrolysis da halayen dimerization idan aka kwatanta dahanta microsomes, kuma in vitro tsarin, da yawa novel model ayan a inganta bisa gahepatocyte tsarin kuma ya kara yin kwaikwayon yanayin in vivo don tsawaita riƙe aikin enzyme a cikihepatocytes, kuma tsawaita lokacin shiryawa yana ba da damar sa ido kan isassun canji na rayuwa na jinkirin ƙwayoyin metabolizing.[1,2].
Dangane da wannan, IPHASE, a matsayin jagora a cikin nazarin halittu don bincike a cikin vitro, ya fara aikin HepatoMax ™ System da Tsarin Watsa Labarai na HepatoCon ™ dangane da nazarin hepatocytes na farko da ƙwayoyin stromal na nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan nau'ikan, gami da ɗan adam, biri, canine, bera, linzamin kwamfuta, da sauransu.hepatocytes a matsayin misali, kuma an saita tsarin biyu don ƙayyade aiki da kwanciyar hankali na rayuwa na takamaiman nau'in enzyme da haɓaka ƙimar amsawar metabolites na miyagun ƙwayoyi tolbutamide a kwanaki 10 da kwanaki 7 don tabbatar da tsarin. Metabolite yana haɓaka ƙimar amsawa a cikin kwanaki 10 kuma aiki da kwanciyar hankali na rayuwa na takamaiman nau'ikan enzyme a cikin kwanaki 7 an ƙaddara don inganta tsarin.
- (1) Tsarin al'adun tabbatar da magunguna na tsari guda biyu sune kamar haka:
IPHASE-HepatoMax™tsarin al'adu ne na daskararre bangon hepatocytes na farko na ɗan adam da ƙwayoyin stromal. An sake farfado da hepatocytes na farko na ɗan adam kuma an haɗa su tare da ƙwayoyin stromal a cikin HepatoP™ matsakaici na tsawon kwanaki 3 don fara gwajin sarrafa magunguna, kuma an gudanar da metabolism na maganin a cikin magani - matsakaicin HepatoDo™ kyauta, wanda aka sake cika shi da magani kawai ba tare da canza matsakaici ba. Jimlar sa'o'i 4, 72, 168 da 240 bayan gudanar da magani, an ƙaddara ƙimar da aka ƙara na metabolites na miyagun ƙwayoyi don bincike.
IPHASE-HepatoCon™, a daya bangaren, tsari ne na al'ada daskararre adherent primary hepatocytes na mutum a cikin HepatoCon™ matsakaici. Bayan farfado da mutum na farkohepatocytes, an gudanar da gwajin sarrafa magunguna bayan kwanaki 3 na al'ada a cikin HepatoCon ™ matsakaici kadai, kuma lokacin gudanarwa na gaba, tsarin al'ada da hanyoyin tantancewa iri ɗaya ne da na tsarin HepatoMax™.
A halin yanzu, don tabbatar da daidaito da tsauri na sakamakon, IPHASE ta aiwatar da matsakaicin matsakaici (cell - kyauta) da kuma kula da kwayar cutar stromal a lokaci guda, tare da maimaitawa guda uku, kuma sakamakon ya nuna cewa.IPHASE-HepatoMax™ kumaIPHASE-HepatoCon™ Tsarin ya samar da martani mai ƙarfi na metabolite mai ƙarfi daga rana ta 3 zuwa gaba, kuma duka biyun sun nuna ƙimar juzu'i mai ƙarfi.
- (2) Metabolism na miyagun ƙwayoyi ya dogara ne akan hepatocyteCYP450tsarin enzyme, kuma ana iya auna ayyukansa don bincika mafi kyau.
TheIPHASE-HepatoMax™ kumaIPHASE-HepatoCon™ tsarin yana da kyakkyawan aiki.
IPHASE ta kafa nau'i hudu na matsakaicin iko (babu sel), HepatoMax™, HepatoCon™ da ƙwayoyin stromal. Amfani da bango - madaidaicin ɗan adam na farkohepatocytes a matsayin misali, metabolite yana ƙara ƙimarSaukewa: CYP1A2, Saukewa: CYP2B6kumaSaukewa: CYP3A4An tabbatar da su a ranakun 0, 3 da 7 bayanhepatocytefarfadowa na kwanaki 3 ta amfani da finasteride, bupropion da midazolam a matsayin abubuwan da ake amfani da su, bi da bi. Metabolite karuwa dabi'u ya nuna cewa duka biyuIPHASE-HepatoMax™ kumaIPHASE-HepatoCon™ Tsarin ya nuna aikin enzyme mai aiki ta rana ta 7, yana haɓaka haɓakar ƙwayar cuta ta yau da kullun.
- (3) Baya ga tabbatar da aikin enzyme, ingantaccen kwanciyar hankali na rayuwa shima muhimmin mataki ne kuma wanda ba makawa a cikin ingantacciyar amfani da samfuran in vitro.
IPHASE ya kafa nau'i uku na HepatoMax™, HepatoCon ™ da sel stromal don ƙayyade kwanciyar hankali na Tolbutimide a cikin tsawon sa'o'i 80 ta amfani da hepatocytes na farko na mutum a matsayin misali, wanda aka gudanar kwanaki 3 bayan farfadowa na farko.hepatocytes, kuma sakamakon ya nuna cewa duka biyunIPHASE-HepatoMax™ kumaIPHASE-HepatoCon™ Tsarukan biyun sun nuna ingantaccen aikin kawar da rayuwa a cikin mafi tsayin ƙimar lokacin tantancewa.
A taƙaice, IPHASE, a matsayin jagorar in vitro bio-reagents, ta haɓakaIPHASE HepatoMax™ kumaIPHASE HepatoCon™ in vitro model dangane da bango - shafi na farko mutum, biri, canine, bera da linzamin kwamfutahepatocytes and stromal cells of various genera, with excellent metabolic turnover, active enzyme activities and powerful metabolic clearance activities, which offer new choices for our customers to develop low-clearance drugs, and are an indispensable partner to realize drug discovery! TheIPHASE HepatoMax™ kumaIPHASE HepatoCon™ Samfuran in vitro suna ba da ingantacciyar ƙimar canjin rayuwa, ayyukan enzyme mai aiki da kuma ayyukan share fage mai ƙarfi, samar da sabbin zaɓuɓɓuka don abokan ciniki don haɓaka ƙananan ƙwayoyi masu tsafta, kuma su ne muhimmin abokin tarayya a gano magunguna!
Magana:
[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. Hanyar ba da labari ga sabon labari don ƙayyadaddun ƙaƙƙarfan ƙimar sharewa[J]. Magungunan ƙwayar cuta da halin da ake ciki, 2012, 40 (9): 1860-1865.
Lokacin aikawa: 2024-07-19 17:20:41