I-Linaclotide iyi-peptide ye-cyclic equkethe ama-amino acid ayi-14, amathathu awo angama-cysteine akha amabhondi e-disulfide.I-Linaclotide ihlobene ngokwesakhiwo nama-peptide e-endogenous guanylin kanye ne-uroguanylin, okungama-ligand emvelo we-guanylate cyclase C (GC-C) receptor.I-GC-C receptor ivezwa endaweni ekhanyayo yamaseli e-epithelial yamathumbu, lapho ilawula ukukhishwa koketshezi kanye nokuhamba kwamathumbu.I-Linaclotide ibophezela kumamukeli we-GC-C ngokuhambisana okuphezulu nokucaciswa, futhi iyenze isebenze ngokwandisa amazinga e-intracellular e-cyclic guanosine monophosphate (cGMP).I-cGMP yisithunywa sesibili esixhumanisa izimpendulo zeselula ezihlukahlukene, njenge-chloride ne-bicarbonate secretion, ukuphumula kwemisipha ebushelelezi, nokuguqulwa kobuhlungu.I-Linaclotide isebenza endaweni emgudwini wamathumbu, futhi ayingeni emgodleni wegazi nobuchopho noma ithinte isimiso sezinzwa esimaphakathi.I-Linaclotide iphinde ikhiqize i-metabolite esebenzayo, i-MM-419447, enezici ezifanayo ze-pharmacological ze-linaclotide.Kokubili i-linaclotide kanye ne-metabolite yayo imelana nokuwohloka kwe-proteolytic ngama-enzyme amathumbu, futhi ikhishwa ikakhulukazi ingashintshiwe endle (MacDonald et al., Izidakamizwa, 2017).
Ngokuvula i-GC-C receptor, i-linaclotide inyusa ukukhishwa koketshezi kulume lwamathumbu, okuthambisa indle futhi kube lula nokuphuma kwamathumbu.I-Linaclotide iphinde yehlise ukuzwela kwe-visceral nokuvuvukala okuhlotshaniswa nesifo samathumbu esicasulayo (IBS) nezinye izifo zesisu.I-Linaclotide ishintsha umsebenzi wesimiso sezinzwa ze-enteric kanye ne-colonic nociceptors, okuyi-neurons yezinzwa ezidlulisela izimpawu zobuhlungu kusuka emathunjini kuya ebuchosheni.I-Linaclotide yehlisa ukuvezwa kwezakhi zofuzo ezihlobene nobuhlungu, njenge-substance P kanye ne-calcitonin ehlobene ne-peptide ehlobene nofuzo (CGRP), futhi ikhuphule ukubonakaliswa kwama-opioid receptors, alamula i-analgesia.I-Linaclotide iphinde yehlise ukukhululwa kwama-cytokines abangela ukuvuvukala, njenge-interleukin-1 beta (IL-1β) kanye ne-tumor necrosis factor alpha (TNF-α), futhi ikhuphule ukukhululwa kwama-cytokines aqeda ukuvuvukala, njenge-interleukin-10 (IL). -10) kanye ne-beta yesici sokukhula esishintshayo (TGF-β).Le miphumela ye-linaclotide ithuthukisa izimpawu zokuqunjelwa kanye nobuhlungu besisu ezigulini ezine-IBS noma ukuqunjelwa okungapheli (Lembo et al., The American Journal of Gastroenterology, 2018).
I-Linaclotide ikhonjiswe ukuthi iyasebenza futhi ibekezelelwa kahle ezivivinyweni ezimbalwa zomtholampilo ezibandakanya iziguli ezine-CC noma i-IBS-C.Kulezi zivivinyo, i-linaclotide ithuthukise imikhuba yamathumbu, njengokuvama kwesitulo, ukungaguquguquki, nokuphelela;ukunciphisa ubuhlungu besisu nokungakhululeki;kanye nezinga lempilo elithuthukisiwe kanye nokwaneliseka kwesiguli.I-Linaclotide iphinde yakhombisa iphrofayili yokuphepha evumayo, kanti isifo sohudo siyisigameko esibi esivame kakhulu.Izehlakalo zohudo zazincike kumthamo futhi ngokuvamile zithambile kuye kumaphakathi ngobukhulu.Ezinye izehlakalo ezimbi ngokuvamile zazifana ne-placebo noma imvamisa ephansi.Azikho izehlakalo ezimbi kakhulu noma ukufa okubangelwa ukwelashwa kwe-linaclotide (Rao et al., I-Clinical Gastroenterology and Hepatology, 2015).
I-Linaclotide iyinoveli futhi umuthi osebenzayo weziguli ezine-CC kanye ne-IBS-C ezingazange zisabele kahle ekwelashweni okujwayelekile.Isebenza ngokulingisa isenzo sama-peptide endo native alawula ukusebenza kwamathumbu kanye nomuzwa.I-Linaclotide ingathuthukisa imikhuba yamathumbu, inciphise ubuhlungu besisu, futhi ithuthukise izinga lempilo yalezi ziguli.
Umfanekiso 1. Ubuhlungu besisu / ukungaphatheki kahle kwesisu kanye ne-IBS degree yokukhululeka kwabaphenduli bamasonto onke phakathi neviki le-12., indawo ye-placebo;, i-linaclotide 290 μg.
(Yang, Y., Fang, J., Guo, X., Dai, N., Shen, X., Yang, Y., Sun, J., Bhandari, BR, Reasner, DS, Cronin, JA, Currie, MG, Johnston, JM, Zeng, P., Montreewasuwat, N., Chen, GZ, and Lim, S. (2018) I-Linaclotide ku-bowel syndrome ecasulayo nokuqunjelwa: Isigaba sesi-3 sokuhlola okungahleliwe e-China nakwezinye izifunda. I-Journal of Gastroenterology kanye ne-Hepatology, 33: 980–989. doi: 10.1111/jgh.14086.)
Singumkhiqizi we-polypeptide e-China, esineminyaka eminingana yokuhlangenwe nakho okuvuthiwe ekukhiqizeni i-polypeptide.I-Hangzhou Taijia Biotech Co., Ltd. ingumkhiqizi wezinto ezingavuthiwe ze-polypeptide, enganikeza amashumi ezinkulungwane zezinto zokusetshenziswa ze-polypeptide futhi ingenziwa ngokwezifiso ngokwezidingo.Izinga lemikhiqizo ye-polypeptide lihle kakhulu, futhi ubumsulwa bungafinyelela ku-98%, okuye kwaqashelwa abasebenzisi emhlabeni wonke.Siyakwamukela ukuthi uxhumane nathi.
