Ko te Linaclotide he peptide cyclic e 14 nga waikawa amino, e toru o enei he cysteine e hanga ana i nga here disulfide.Ko te Linaclotide te hangahanga ki nga peptides endogenous guanylin me te uroguanylin, he hononga taiao o te kaiawhina guanylate cyclase C (GC-C).Ko te kaiwhiwhi GC-C e whakaatuhia ana i runga i te mata maramara o nga pūtau epithelial intestinal, kei reira te whakahaere i te rerenga wai me te motireti intestinal.Ka herea te Linaclotide ki te kaiwhakawhiwhi GC-C me te tino hononga me te motuhake, ka whakahohe ma te whakanui ake i nga taumata intracellular o te cyclic guanosine monophosphate (cGMP).Ko te cGMP te kaikawe tuarua e takawaenga ana i nga momo urupare pūkoro, penei i te chloride me te hunanga bicarbonate, te whakangā uaua maeneene, me te whakarereke mamae.Ka mahi a Linaclotide ki roto i te kopa gastrointestinal, kaore e uru ki roto i te arai toto-roro, ka pa ranei ki te punaha nerve matua.Ka whakaputa ano hoki a Linaclotide i te metabolite kaha, MM-419447, he rite nga ahuatanga rongoa ki te linaclotide.Ko te linaclotide me tona metabolite he aukati ki te whakahekenga proteolytic e nga enzymes intestinal, a ka whakakorehia te nuinga kaore i whakarereketia i roto i nga feces (MacDonald et al., Drugs, 2017).
Na roto i te whakahohe i te GC-C receptor, ka whakanuia e te linaclotide te hunanga o te wai ki roto i te lumen intestinal, e whakangawari ana i te kumete me te whakahaere i nga kohanga whekau.Ko te Linaclotide hoki ka whakaheke i te whakaraeraetanga o te visceral me te mumura e pa ana ki te irritable bowel syndrome (IBS) me etahi atu mate gastrointestinal.Ko te Linaclotide te whakarereke i nga mahi o te punaha nerve enteric me nga nociceptors koroni, he neurons mohio e tuku tohu mamae mai i te whekau ki te roro.Ka whakaitihia e Linaclotide te whakaaturanga o nga ira e pa ana ki te mamae, penei i te matū P me te calcitonin gene-related peptide (CGRP), me te whakanui ake i te whakaputanga o nga kaiwhakawhiwhi opioid, e takawaenga ana i te analgesia.Ka whakaiti hoki a Linaclotide i te tukunga o nga cytokine pro-inflammatory, penei i te interleukin-1 beta (IL-1β) me te tumor necrosis factor alpha (TNF-α), me te whakanui ake i te tukunga o nga cytokines anti-inflammatory, penei i te interleukin-10 (IL). -10) me te whakarereke i te take tipu beta (TGF-β).Ko enei paanga o te linaclotide te whakapai ake i nga tohu o te mate pukupuku me te mamae o te puku i roto i nga turoro me te IBS, te mate pukupuku tawhito ranei (Lembo et al., The American Journal of Gastroenterology, 2018).
Kua whakaatuhia he whai hua me te pai o te Linaclotide i roto i te maha o nga whakamatautau haumanu e pa ana ki nga turoro whai CC, IBS-C ranei.I roto i enei whakamatautau, ka whakapai ake te linaclotide i nga tikanga whekau, penei i te auau o te kue, te rite, me te whakaoti;te whakaiti i te mamae o te puku me te mamae;me te pai ake o te oranga me te pai o te manawanui.I whakaatu ano a Linaclotide i tetahi tohu haumaru pai, me te korere ko te tino kino kino.Ko te mate o te mate pukupuku i whakawhirinaki ki te horopeta me te nuinga o te waa he ngawari ki te ngawari te taumahatanga.He rite tonu etahi atu kino ki te placebo, he iti ranei te auau.Kaore he kino kino, he mate ranei i kiihia ki te maimoatanga linaclotide (Rao et al., Clinical Gastroenterology and Hepatology, 2015).
Ko te Linaclotide he rongoa hou me te whai hua mo nga turoro me te CC me te IBS-C kaore i pai te whakautu ki nga maimoatanga tikanga.Ka mahi ma te peehi i nga mahi a nga peptides endogenous e whakahaere ana i te mahi intestinal me te rongo.Ka taea e Linaclotide te whakapai ake i nga tikanga whekau, te whakaiti i te mamae o te puku, me te whakapai ake i te oranga o enei turoro.
Whakaahua 1. Te mamae o te puku / te mamae o te puku me te tohu IBS mo te awhina i nga kaiwhakautu i ia wiki mo te wiki 12., 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 i roto i te irritable bowel syndrome me te paopao: He whakamatautau matapōkere Wāhanga 3 i Haina me etahi atu rohe. Journal of Gastroenterology me te Hepatology, 33: 980–989. doi: 10.1111/jgh.14086.)
He kaihanga polypeptide matou i Haina, he maha nga tau o te wheako pakeke ki te hanga polypeptide.Ko Hangzhou Taijia Biotech Co., Ltd. he kaihanga ngaio polypeptide raw rauemi, ka taea te whakarato i nga mano tini o nga rauemi polypeptide, ka taea hoki te whakarite kia rite ki nga hiahia.Ko te kounga o nga hua polypeptide he pai rawa atu, a ka taea e te parakore te tae ki te 98%, kua mohiohia e nga kaiwhakamahi puta noa i te ao.Nau mai ki te korero ki a matou.
