Linaclotide yog cyclic peptide uas muaj 14 amino acids, peb ntawm cov cysteines uas tsim cov disulfide bonds.Linaclotide muaj feem cuam tshuam nrog endogenous peptides guanylin thiab uroguanylin, uas yog ntuj ligands ntawm guanylate cyclase C (GC-C) receptor.GC-C receptor yog qhia nyob rau ntawm lub luminal nto ntawm lub plab hnyuv epithelial hlwb, qhov uas nws tswj cov kua secretion thiab txoj hnyuv motility.Linaclotide khi rau GC-C receptor nrog siab affinity thiab tshwj xeeb, thiab activates nws los ntawm kev ua kom cov qib intracellular ntawm cyclic guanosine monophosphate (cGMP).cGMP yog tus xa xov thib ob uas kho ntau cov lus teb ntawm tes, xws li tshuaj chloride thiab bicarbonate tso tawm, ua kom cov leeg du, thiab kho qhov mob.Linaclotide ua haujlwm hauv zos hauv plab hnyuv, thiab tsis nkag mus rau hauv cov ntshav-hlwb thaiv lossis cuam tshuam rau hauv nruab nrab cov hlab ntsha.Linaclotide kuj tsim cov metabolite nquag, MM-419447, uas muaj cov tshuaj zoo sib xws rau linaclotide.Ob leeg linaclotide thiab nws cov metabolite tuaj yeem tiv thaiv kev degradation proteolytic los ntawm plab hnyuv enzymes, thiab tsuas yog tshem tawm tsis hloov pauv hauv cov quav (MacDonald li al., Tshuaj, 2017).
Los ntawm kev ua kom lub GC-C receptor, linaclotide ua rau kom cov kua dej tso rau hauv cov hnyuv lumen, uas ua rau cov quav mos thiab ua kom lub plab zom mov.Linaclotide kuj tseem txo cov visceral hypersensitivity thiab o uas cuam tshuam nrog kev chim siab plob tsis so tswj (IBS) thiab lwm yam kab mob hauv plab.Linaclotide modulates cov haujlwm ntawm lub paj hlwb enteric thiab colonic nociceptors, uas yog cov neurons hnov mob uas xa cov cim mob ntawm plab mus rau lub hlwb.Linaclotide txo qis qhov kev qhia ntawm cov noob caj ces mob, xws li tshuaj P thiab calcitonin gene-related peptide (CGRP), thiab ua rau kom muaj kev nthuav tawm ntawm opioid receptors, uas kho mob analgesia.Linaclotide kuj txo cov kev tso tawm ntawm cov cytokines pro-inflammatory, xws li interleukin-1 beta (IL-1β) thiab qog necrosis factor alpha (TNF-α), thiab ua rau kom tso tawm cov tshuaj tiv thaiv cytokines, xws li interleukin-10 (IL. -10) thiab kev loj hlob zoo tshaj beta (TGF-β).Cov teebmeem ntawm linaclotide no txhim kho cov tsos mob ntawm cem quav thiab mob plab hauv cov neeg mob uas muaj IBS lossis cem quav (Lembo li al., American Journal of Gastroenterology, 2018).
Linaclotide tau pom tias ua tau zoo thiab ua tau zoo nyob rau hauv ntau qhov kev sim tshuaj uas cuam tshuam nrog cov neeg mob CC lossis IBS-C.Hauv cov kev sim no, linaclotide txhim kho lub plab zom mov, xws li quav zaus, sib xws, thiab ua tiav;txo qhov mob plab thiab tsis xis nyob;thiab txhim kho lub neej zoo thiab kev txaus siab rau tus neeg mob.Linaclotide kuj tau pom tias muaj kev nyab xeeb zoo, nrog rau kev mob raws plab yog qhov tshwm sim tsis zoo tshaj plaws.Qhov tshwm sim ntawm raws plab yog nyob ntawm koob tshuaj thiab feem ntau me me mus rau nruab nrab ntawm qhov hnyav.Lwm cov xwm txheej tsis zoo feem ntau zoo ib yam li cov placebo lossis tsawg zaus.Tsis muaj qhov tshwm sim tsis zoo lossis kev tuag raug suav tias yog kev kho mob linaclotide (Rao li al., Clinical Gastroenterology thiab Hepatology, 2015).
Linaclotide yog cov tshuaj tshiab thiab zoo rau cov neeg mob CC thiab IBS-C uas tsis tau teb zoo rau cov kev kho mob ib txwm muaj.Nws ua haujlwm los ntawm kev ua raws li qhov kev txiav txim ntawm endogenous peptides uas tswj txoj hnyuv ua haujlwm thiab hnov qab.Linaclotide tuaj yeem txhim kho lub plab zom mov, txo qhov mob plab, thiab txhim kho lub neej zoo rau cov neeg mob no.
Daim duab 1. Kev mob plab / plab tsis xis nyob thiab IBS qib ntawm kev pab cuam rau cov neeg teb txhua lub lim tiam dhau 12 lub lis piam., cov placebo;, 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) Linaclotide in irritable bowel syndrome with constipation: Phase 3 randomized trial in China and other regions. thiab Hepatology, 33: 980–989. doi: 10.1111/jgh.14086.)
Peb yog cov chaw tsim khoom polypeptide hauv Suav teb, nrog ntau xyoo ntawm kev paub tab hauv kev tsim cov polypeptide.Hangzhou Taijia Biotech Co., Ltd. yog lub chaw tsim khoom ntawm polypeptide raw khoom, uas tuaj yeem muab tau kaum tawm txhiab tus polypeptide raw cov ntaub ntawv thiab tuaj yeem kho raws li kev xav tau.Qhov zoo ntawm cov khoom polypeptide yog qhov zoo heev, thiab qhov purity tuaj yeem ncav cuag 98%, uas tau lees paub los ntawm cov neeg siv thoob plaws ntiaj teb. Zoo siab txais tos los tham nrog peb.
