Linaclotide inonzi cyclic peptide ine 14 amino acids, matatu acho ari macysteine anoumba disulfide bonds.Linaclotide ine hukama kune endogenous peptides guanylin uye uroguanylin, ayo ari echisikigo ligands eiyo guanylate cyclase C (GC-C) receptor.Iyo GC-C receptor inoratidzwa pane luminal pamusoro peiyo intestinal epithelial masero, kwainogadzirisa secretion yemvura uye intestinal motility.Linaclotide inosungira kuGC-C receptor ine hukama hwepamusoro uye hutsanana, uye inoimisa nekuwedzera intracellular mazinga ecyclic guanosine monophosphate (cGMP).cGMP mutumwa wechipiri anoyananisa akasiyana cellular mhinduro, senge chloride uye bicarbonate secretion, yakatsetseka tsandanyama kuzorora, uye marwadzo modulation.Linaclotide inoshanda munharaunda munharaunda yegumbo, uye haipindi muropa-brain barriers kana kukanganisa iyo yepakati tsinga system.Linaclotide inogadzirawo inoshanda metabolite, MM-419447, ine yakafanana pharmacological properties kune linaclotide.Ose ari maviri linaclotide uye metabolite ayo anopesana nekuora kweproteolytic nema enzymes emudumbu, uye anonyanya kubviswa asina kuchinjwa mutsvina (MacDonald et al., Zvinodhaka, 2017).
Nekuita iyo GC-C receptor, linaclotide inowedzera kuburitswa kwemvura mumatumbo lumen, iyo inopfavisa chituru uye kufambisa ura.Linaclotide inoderedzawo visceral hypersensitivity uye kuzvimba izvo zvinosanganiswa neakatsamwa bowel syndrome (IBS) uye mamwe matambudziko emudumbu.Linaclotide inogadzirisa basa re enteric nervous system uye colonic nociceptors, iyo inonzi sensory neurons inotumira zviratidzo zvinorwadza kubva mudumbu kusvika kuuropi.Linaclotide inoderedza kutaura kwemajini ane hukama nemarwadzo, akadai sechinhu P uye calcitonin gene-related peptide (CGRP), uye inowedzera kutaura kweopioid receptors, iyo inopindirana analgesia.Linaclotide inoderedzawo kusunungurwa kwepro-inflammatory cytokines, yakadai se interleukin-1 beta (IL-1β) uye tumor necrosis factor alpha (TNF-α), uye inowedzera kusunungurwa kwe-anti-inflammatory cytokines, yakadai se interleukin-10 (IL). -10) uye kushandura kukura chinhu beta (TGF-β).Izvi zvinokonzerwa nelinaclotide zvinovandudza zviratidzo zvekudzivirira uye kurwadziwa kwepamuviri kune varwere vane IBS kana kusingaperi kuvimbiswa (Lembo et al., The American Journal of Gastroenterology, 2018).
Linaclotide yakaratidzwa kuva inoshanda uye inoshivirirwa zvakanaka mune akati wandei miedzo yekiriniki inosanganisira varwere vane CC kana IBS-C.Mumiyedzo iyi, linaclotide yakavandudza ura hutsika, senge stool frequency, consistency, uye kukwana;kuderedza marwadzo emimba uye kusagadzikana;uye kuwedzera kwehupenyu hwehupenyu uye kugutsikana kwemurwere.Linaclotide yakaratidzawo yakanakira kuchengetedzwa chimiro, manyoka ari iwo anonyanya kuipa chiitiko.Kuitika kwemanyoka kwaienderana nedosi uye kazhinji kupfava kusvika pakati pekuomarara.Zvimwe zviitiko zvakashata zvaiwanzofanana ne placebo kana kuderera muhuwandu.Hapana zviitiko zvakakomba zvakashata kana kufa kwakakonzerwa nekurapa linaclotide (Rao et al., Clinical Gastroenterology uye Hepatology, 2015).
Linaclotide inyowani uye inoshanda mushonga kune varwere vane CC uye IBS-C vasina kupindura zvakanaka kune zvakajairwa marapirwo.Inoshanda nekutevedzera maitiro eendogenous peptides inodzora intestinal basa uye kunzwa.Linaclotide inogona kuvandudza marara, kuderedza marwadzo emudumbu, uye kuwedzera hupenyu hwevarwere ava.
Mufananidzo 1. Kurwadziwa kwepamuviri / kusagadzikana kwepamuviri uye IBS dhigirii yekuyamura vanopindura vhiki nevhiki pamusoro pe12-vhiki., 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, uye Lim, S. (2018) Linaclotide mune inogumbura bowel syndrome ine constipation: A Phase 3 randomized trial muChina nedzimwe nzvimbo. Journal of Gastroenterology. uye Hepatology, 33: 980–989. doi: 10.1111/jgh.14086.)
Isu tiri mugadziri wepolypeptide muChina, tine makore akati wandei ehunyanzvi mukugadzira polypeptide.Hangzhou Taijia Biotech Co, Ltd inyanzvi yepolypeptide mbishi kugadzira, iyo inogona kupa makumi ezviuru zvepolypeptide mbishi zvinhu uye inogona zvakare kugadzirwa zvinoenderana nezvinodiwa.Hunhu hwezvigadzirwa zvepolypeptide hwakanakisa, uye kuchena kunogona kusvika 98%, iyo yave ichizivikanwa nevashandisi pasi rese.Welcome to consult us.
