公开(公告)号：KR100778633B1

公开(公告)日：2007-11-28

申请号：KR1020070036246

申请日：2007-04-13

Applicant: 성균관대학교산학협력단

Inventor： 이강춘 ,  채수영 ,  신한종

IPC: C07D495/04 ,  A61K31/4188

Abstract: A biotin and biotin polyethylene glycol-linked GLP-1 derivative is provided to be usefully used for preventing or treating diseases caused by excessive secretion of insulin, lowering of glucose in plasma, inhibition of stomach or intestine motion, inhibition of an empty stomach or intestine, or inhibition of food intake, type 2 diabetes, obesity and irritable colon syndrome. A GLP-1 derivative in which biotin and biotin-polyethylene glycol are selectively linked to No. 26 lysine residue and No. 34 lysine residue is represented by the formula(2), wherein the biotin-polyethylene glycol is represented by the formula(1) having a molecular weight of 3,400. A method for preparing the GLP-1 derivative comprises the steps of: (a) adding biotin, biotin-polyethylene glycol and GLP to a buffer solution and an organic solvent to be subject to reaction; (b) storing the reaction mixture obtained from the step(a) under a certain temperature for a certain period of time; (c) removing non-reacted reaction products after the reaction completion of the step(b); and (d) isolating GLP-1 in which the biotin and biotin-polyethylene glycol are linked from the non-reacted products-removed products and purifying them. A pharmaceutical composition for preventing or treating diabetes or obesity comprises the biotin and biotin polyethylene glycol-linked GLP-1 derivative.

Abstract translation: 提供生物素和生物素聚乙二醇连接的GLP-1衍生物可用于预防或治疗由胰岛素过量分泌引起的疾病，血浆中葡萄糖降低，抑制胃或肠运动，抑制空腹或肠 ，或抑制食物摄入，2型糖尿病，肥胖症和肠易激综合征。 生物素和生物素 - 聚乙二醇与26号赖氨酸残基和34号赖氨酸残基选择性连接的GLP-1衍生物由式（2）表示，其中生物素 - 聚乙二醇由式（1 ），分子量为3400。 制备GLP-1衍生物的方法包括以下步骤：（a）将生物素，生物素 - 聚乙二醇和GLP加入缓冲溶液和有机溶剂进行反应; （b）将从步骤（a）获得的反应混合物在一定温度下储存一定时间; （c）在步骤（b）的反应完成后除去未反应的反应产物; 和（d）分离其中生物素和生物素 - 聚乙二醇与未反应的产物去除产物连接的GLP-1并纯化。 用于预防或治疗糖尿病或肥胖症的药物组合物包括生物素和生物素聚乙二醇连接的GLP-1衍生物。