I-Linaclotide yi-peptide ye-cyclic equkethe i-14 amino acids, ezintathu zazo ziyi-cysteine ezenza iibhondi ze-disulfide.I-Linaclotide inxulumene nesakhiwo se-endogenous peptides guanylin kunye ne-uroguanylin, eziyi-ligands zendalo ze-guanylate cyclase C (GC-C) receptor.I-GC-C i-receptor ibonakaliswe kwi-luminal surface yeeseli ze-epithelial zamathumbu, apho ilawula ukukhutshwa kwamanzi kunye ne-intestinal motility.I-Linaclotide ibophelela kwi-GC-C ye-receptor enobudlelwane obuphezulu kunye neenkcukacha, kwaye isebenze ngokunyusa amanqanaba e-intracellular ye-cyclic guanosine monophosphate (cGMP).I-cGMP sisithunywa sesibini esidibanisa iimpendulo ezahlukeneyo zeselula, ezifana nekloride kunye ne-bicarbonate secretion, ukuphumla kwemisipha egudileyo, kunye nokuguqulwa kweentlungu.I-Linaclotide isebenza kwindawo kwindawo yesisu, kwaye ayifuni ukungena kumqobo wegazi-ingqondo okanye ichaphazele inkqubo ye-nervous central.I-Linaclotide iphinda ivelise i-metabolite esebenzayo, i-MM-419447, eneempawu ezifanayo ze-pharmacological kwi-linaclotide.Zombini i-linaclotide kunye ne-metabolite yayo iyamelana nokuthotywa kwe-proteolytic ngama-enzymes amathumbu, kwaye ikhutshwe ngokukodwa ingatshintshi kwi-feces (MacDonald et al., Iziyobisi, i-2017).
Ngokusebenzisa i-GC-C receptor, i-linaclotide inyusa ukukhutshwa kwamanzi kwi-lumen yamathumbu, eyenza i-stool ibe lula kwaye iququzelele ukuhamba kwamathumbu.I-Linaclotide ikwanciphisa i-visceral hypersensitivity kunye nokuvuvukala okuhambelana nesifo se-bowel syndrome (IBS) kunye nezinye izifo zesisu.I-Linaclotide imodareyitha umsebenzi wenkqubo ye-nervous ye-enteric kunye ne-colonic nociceptors, eziyi-neurons ze-sensory ezihambisa iimpawu zentlungu ukusuka emathunjini ukuya kwingqondo.I-Linaclotide inciphisa ukubonakaliswa kwee-genes ezinxulumene neentlungu, ezifana ne-substance P kunye ne-calcitonin ye-peptide ehlobene ne-gene (CGRP), kwaye yandisa ukubonakaliswa kwe-opioid receptors, edibanisa i-analgesia.I-Linaclotide iphinda inciphise ukukhululwa kwe-cytokines e-pro-inflammatory, efana ne-interleukin-1 beta (IL-1β) kunye ne-tumor necrosis factor alpha (TNF-α), kwaye yandisa ukukhululwa kwe-cytokines ezichasayo, ezifana ne-interleukin-10 (IL) -10) kunye nokuguqula ukukhula kwe-beta (TGF-β).Ezi ziphumo ze-linaclotide ziphucula iimpawu zokuqunjelwa kunye neentlungu zesisu kwizigulane ezine-IBS okanye ukuqhina okungapheliyo (Lembo et al., I-American Journal of Gastroenterology, 2018).
I-Linaclotide ibonakaliswe ukuba iyasebenza kwaye inyamezeleke kakuhle kwiimvavanyo ezininzi zekliniki ezibandakanya izigulane ezine-CC okanye i-IBS-C.Kwezi zilingo, i-linaclotide iphucule imikhwa yamathumbu, njengokuphindaphinda kwesitulo, ukuhambelana, kunye nokuphelela;ukunciphisa intlungu yesisu kunye nokukhathazeka;kunye nomgangatho wobomi ophuculweyo kunye nokwaneliseka kwesigulana.I-Linaclotide ikwabonakalise iprofayili yokhuseleko encomekayo, kunye norhudo sesona siganeko sibi sixhaphakileyo.Isiganeko sorhudo sasixhomekeke kwithamo kwaye ngokuqhelekileyo siphakathi ukuya phakathi kobunzima.Ezinye iziganeko ezimbi zazifana ngokubanzi ne-placebo okanye ziphantsi ngamaxesha amaninzi.Akukho ziganeko ezimbi kakhulu okanye ukufa okubangelwa unyango lwe-linaclotide (Rao et al., I-Clinical Gastroenterology kunye ne-Hepatology, i-2015).
I-Linaclotide iyinoveli kunye neyeza elisebenzayo kwizigulane ezine-CC kunye ne-IBS-C ezingakhange ziphendule kakuhle kunyango oluqhelekileyo.Isebenza ngokulinganisa isenzo se-peptides engapheliyo elawula ukusebenza kwamathumbu kunye nokuziva.I-Linaclotide inokuphucula imikhwa yamathumbu, inciphise iintlungu zesisu, kwaye iphucule umgangatho wobomi kwezi zigulana.
Umzobo 1. Intlungu yesisu / isisu esibuhlungu kunye ne-IBS degree of relief responders weekly responders over the 12-weeks., 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, kunye ne-Lim, S. (2018) i-Linaclotide kwi-syndrome ye-bowel syndrome kunye nokuqunjelwa: iSigaba se-3 sovavanyo olungahleliwe e-China nakweminye imimandla. Ijenali yeGastroenterology. kunye neHepatology, 33: 980–989. doi: 10.1111/jgh.14086.)
Singumenzi wepolypeptide eTshayina, esineminyaka eliqela yamava aqolileyo kwimveliso yepolypeptide.I-Hangzhou Taijia Biotech Co., Ltd. yingcali yomenzi we-polypeptide ekrwada, enokubonelela amashumi amawaka ezinto ezikrwada ze-polypeptide kwaye inokwenziwa ngokweemfuno.Umgangatho weemveliso ze-polypeptide ugqwesileyo, kwaye ukucoceka kunokufikelela kwi-98%, eye yaqatshelwa ngabasebenzisi emhlabeni wonke.
