A & Aanyama a anthu opanda phokoso a matrix opanda kanthu kwa bionalelytical njira ndi bioanalytical njira yotsimikizika

1 Iphase Zinthu

2 black biomatrix

Mitundu yosiyanasiyana yaMa Meriological Matrict, kuphatikizapo magazi opusa, seramu, plasma, nchito ya, Mkaka, mkodzo, ndowe, m'matumbo, ma visceral, nthabwala zamadzi, zotupa zamtundu wathanzi kapena zopangidwa bwino zopangidwa ngati matrictogion ngati matrict opanda kanthu.

Kufunikira kugwiritsa ntchito matricform obisika pamaphunziro

In Kafukufuku Wogulitsa Mankhwala, matrix opanda kanthu ndi mwala wapadera wokhazikitsa ndi kutsimikizikaNjira Zakusanthula Zachilengedwe. Pogwiritsa ntchito matrict opanda vuto kapena nyama zoyeserera, ofufuza amatha kuphika molondola miyezo yosiyanasiyana, kuwunikira zitsanzo, chidwi, kutsimikizira kudalirika kwa zotsatira za kuchuluka kwa mankhwala osokoneza bongo.

4 njira yachilengedwe yotsimikizika ndi kukhazikitsa ndi kugwiritsa ntchito matsix opanda kanthu

Ponena za mafomu a FDA / EMA, kukhazikitsidwa ndi kutsimikizika kwa njira zachilengedwe matrix, matrictoological matrict amafunikira kugwiritsidwa ntchito potsimikizira kuti njira yotsimikizika ndi yotsimikizika. Makamaka mu LC - Kusanthula kwa MS / MS, kusiyana mu matrix zigawo kuchokera kumagawo osiyanasiyana kumatha kukhudza kwambiri a maoniza. Matrix opanda kanthu amagwiritsidwa ntchito pokonzekera mfundo zodziwika bwino, kukonza zitsanzo zamagetsi pofufuza zakuda, kulondola, kukhazikika, kusokonezeka, zotsatira za kusokoneza, etc. Njira zosokoneza. Kusankha ndi matrix zotsatira za njira yodziwika kumafunikira zofunikira kwambiri ku matrix opanda kanthu.

Ma prenarios 5 a Bile opanda kanthu matrix pakukula kwa mankhwala

Matrix oundana (Kuyesedwa Bile Matrix)Ndi njira yopanga yomwe imagwirizana ndi zigawo zachilengedwe ndipo imagwiritsidwa ntchito popanga mankhwala osokoneza bongo, toxicology, komanso kusanthula kwachilengedwe.Bile MatrixAli ndi mtengo wofunikira pakugwiritsa ntchito mankhwala otsatirawa: Pharmacokinetic (PK) maphunziro a hepatobiliary dongosolo la mankhwala osokoneza bongo, mankhwala a Hepatot Unics, ndi MS / MS).

6 hepatobiliary dongosolo mankhwala

Kukula kwa mankhwala a hepatobiliary, matrix opanda kanthu kumathandizanso gawo losasinthika monga chokhazikika mu dongosolo la phala mu phala ku pharmacokineticn mu phala.

6.1 Yesetsani kuchuluka kwa bile

Kafukufuku wa hepatointenal Kufalikira: Bile ndi imodzi mwa njira zofunika kwambiri za kuchuluka kwa mankhwala osokoneza bongo ndi ma metabolites. Pogwiritsa ntchito matrix a bile, kusintha kwa mankhwala osokoneza bongo ku Bile kumatha kuwunika ngati akubwezeretsedwa kudzera mu matumbo a hepatic kufalitsidwa.

Mankhwala a Bile Chidance Recrence: Mankhwala omwe amapangidwa mwamphamvu kudzera mu bile (monga ma statins ndi maantibayotiki ena), bile yopanga (yopanda bile) ingakuthandizeni kukhala ndi vuto la dosing.

6.2 Phunzirani zotsatira za bile acid pa mankhwala oyamwa

Zovuta Zosintha: Bile Adids imatha kulimbikitsa kuwonongeka ndi matumbo a mavitamini D. Bile Bile imathamangire ma bile acid a acid ndikuwunika momwe amathandizira pakugwiritsa ntchito bioavailability.

Mankhwala Bile Acid Kugwirizana: Mankhwala ena (monga Liraglutide) amatha kupikisana ndi Bile Acid

6.3 Kuwunika kwa chiopsezo cha hepatotoxicity ndi cholestasis

Mankhwala osokoneza bongo a cholestasis: bile yopanga mphamvu amatha kusanthula mikhalidwe ngati bile duct yotsekeka komanso hyperbilirubinemia, ndipo amagwiritsidwa ntchito kuwona ngati mankhwala osokoneza bongo a bile.

Kusanthula Kwa Biomeker: Powonjezera zigawo zina monga bilirubin, bile acids, ndi kutupa, zomwe zimapangitsa kuti mankhwala osokoneza bongo azitha kunenedweratu.

6.4 zabwino komanso zabwino zobwezeretsanso bile yachilengedwe

Pothana ndi vuto la kuchuluka kwa mabizinesi: Bile yachilengedwe imayenera kupezeka kudzera mu njira zowonongera monga bile dutet caheterization, pomwe bile imakonzekereratu kuti isakhale ndi malire.

Kusagwirizana: Kuphatikizika kwa matrix (chomangika matrix) ndikowongolera, ndikuchepetsa kukhudzidwa kwa kusiyana kwamunthu pazinthu zachilengedwe pazinthu zoyeserera.

6.5 Thandizani chitukuko cha LC - MS / MS Herologicals Sectucs

Matrix Hertection: Kupanga kwa bile bile (mchere wambiri bile Bile yopanga matrix (omangika Bile Matrix) amatha kupereka maziko, kungoyang'ana njira yokopa ndi kulondola.

7 Mtanda Wamtundu wa Minda

Kuphatikizika kwa bile kumasiyana kwambiri pakati pa nyama zosiyanasiyana (makoswe, agalu, anyani), ndi bile yopanga amatha kusinthanso mitundu ya mitundu ndikuwongolera kutanthauzira kwa data.

7.1 Cynomolgus Bale (NHP bile)

Bile ya cynomolgus nyani imakhala yofanana ndi ya anthu malinga ndi kapangidwe kake (monga bsep, mrp2)

7.2 Galu wagalu bile

The phospholpolip yomwe ili mu Beagle Bile ili yokwera, ndikupanga kukhala koyenera kuphunzira bolodi ya bile ndi bile mchere umadalira mankhwala osokoneza bongo. Komabe, kusiyana kwa Bile Acid pakati pakati pa Beagle ndipo anthu amafuna fanizo la matriction.

7.3 Strat bile

Kuchulukitsa kwa Bile Makoswe ndi kwakukulu (~ 1 ml / nthawi), komwe kumagwiritsidwa ntchito kwambiri kwa chizolowezi cha hepatotic kufalitsidwa ndi maphunziro a mankhwala a hepatotoxity. Komabe, ziyenera kudziwitsidwa kuti bilirubin ya bilirubin ingasokoneze LC - MS / MS.

7.4 ICR / CD - mbewa 1 bile

CD - mbewa 1 imakhala ndi voliyumu yaying'ono ya bile (50 - 200 μ l, njira za FXR / PXR yomwe imafunikira kuti musinthe.

7.5 C57BL / 6 mbewa bile

C57BL / 6 Mouse imagwiritsidwa ntchito mu mitundu ya metabolic, ndipo kusintha kwa mabilo awo kumatha kuwonetsa zochitika zathanzi, zomwe zimafuna kugwiritsa ntchito matrix a bile kuti azilinganiza matenda.

Mitundu yomwe ili pamwambapa imayenera kuphatikizidwa ndi matrix a bile kuti aziwongolera mitundu ya mitundu ndikukweza mitanda yamiyala ya LC - MS / MS Njira.

Mapeto

Matrix ochita masewera olimbitsa thupi, monga chida chofunikira kwambiri pakusintha kwa bile bile. Pogwiritsa ntchito kapangidwe ka mitundu yosiyanasiyana yamitundu yosiyanasiyana (monga agalu a cynomolbulbus, makoswe, cd -

Ndi chitukuko cha mankhwala olondola, matrix ochita bwino amaphatikiza zigawo zolimbitsa thupi ndi zamagetsi kuti musinthe chiwindi ndi ma ndulu.

Mawu ofunikira:Kusanthula kopanda tanthauzo, kusanthula kwa matrix, bile

Kuchulidwa

LI T, Chiang Jy. Bile acid signal mu metabolic matenda ndi mankhwala. Phalcol Rev. 2014 Oct; 66 (4): 948 - 83. Doi: 10,1124 / PR.113.008201. PMID: 250733467; PMCID: PMC4180336.