KIM, SEUNG SU,金承洙,LIM, SE YOUNG,林世荣,林世榮,JUNG, SUNG YOUB,郑圣烨,鄭聖燁,KWON, SE CHANG,权世昌,權世昌
申请号：
TW101150930
公开号：
TWI666219B
申请日:
2012.12.28
申请国别(地区):
TW
年份:
2019
代理人:
摘要：
The present invention relates to a glucagon-like peptide-2 (GLP-2) conjugate comprising native GLP-2 or its derivative and an immunoglobulin Fc fragment being covalently linked via a non-peptidyl polymer, wherein the native GLP-2 or its derivative has a thiol group introduced at its C-terminal end, and one end of the non-peptidyl polymer is linked to an amino acid residue of the GLP-2 other than the N-terminal amino group thereof； a method for preparing the GLP-2 conjugate； a pharmaceutical composition comprising the same； and a method for treating or preventing intestinal disease, intestinal injury, or gastrosia by using the same. Since the GLP-2 conjugate of the present invention has a remarkably increased binding affinity to a GLP-2 receptor, it shows a prolonged in vivo half-life and an improved in vivo durability and stability. Thus, the GLP-2 conjugate of the present invention can be administered at a remarkably low dose and exhibit an improvement in drug compliance without fluctuation in blood glucose level. Accordingly, the long-acting GLP-2 conjugate of the present invention can be effectively used for preventing or treating intestinal disease, intestinal injury, or gastrosis.本發明係關於一種類升糖素胜肽-2(GLP-2)接合物，包含經由非胜肽聚合物共價性連接之原始GLP-2或其衍生物與免疫球蛋白Fc片段，其中該原始GLP-2或其衍生物之C-端具有硫醇基，以及該非胜肽聚合物之一端連接至除了GLP-2之N-末端胺基以外之GLP-2的胺基酸殘基；一種製備該GLP-2接合物之方法；一種包含該GLP-2接合物之醫藥組成物；以及一種使用該GLP-2接合物以治療或預防腸疾病、腸損傷或胃酸過多(gastrosia)之方法。由於本發明GLP-2接合物具有顯著增加之GLP-2受體結合親和力，顯示延長體內半衰期並增進體外耐久性與穩定性。因此，本發明GLP-2接合物可以相當低之劑量給藥，並展現增進之藥物依從性，而不使血糖濃度波動。因此，本發明之長效性GLP-2接合物可有效用於預防或治療腸疾病、腸損傷或胃酸過多。
