劉夢,于彭城,徐寒梅.蛋白多肽類藥物長效化技術(shù)研究進展[J].藥學進展,2019,43(03):209-216.
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蛋白多肽類藥物長效化技術(shù)研究進展
劉夢于 彭城 徐寒梅
中國藥科大學江蘇省合成多肽藥物發(fā)現(xiàn)與評價工程研究中心
摘要：近年來,蛋白多肽類藥物因在治療疾病方面具有顯著的優(yōu)點,普遍受到研究者的青睞;另一方面,蛋白多肽類藥物半衰期一般較短,影響患者用藥順應性。結(jié)合蛋白多肽類藥物藥動學特點,總結(jié)蛋白多肽類藥物長效化方法的研究進展,主要包括氨基酸替代、定點修飾突變、通過基因手段與其他蛋白融合、糖基化、環(huán)化、與聚合物綴合、釘合肽,以及新劑型開發(fā)等方法,希望能對藥物研發(fā)工作者有所幫助。
關(guān)鍵詞： 蛋白多肽類藥物;藥動學特點;長效化技術(shù);
專輯： 醫(yī)藥衛(wèi)生科技
專題： 藥學
分類號： R96
文章目錄
1 蛋白多肽類藥物藥動學特點
1.1 吸收
1.2 分布
1.3 代謝和消除
2 改善蛋白多肽類藥物半衰期的方式
2.1 氨基酸替代
2.2 定點修飾突變
2.3 通過基因手段與其他蛋白融合
2.4 糖基化
2.5 環(huán)化
2.6 與聚合物綴合
2.6.1 PEG化學修飾
2.6.2 非結(jié)構(gòu)化可生物降解蛋白綴合
2.6.3 PAS綴合
2.6.4 羥乙基化淀粉綴合
2.7 釘合肽
2.8 藥物傳遞系統(tǒng)開發(fā)
3 結(jié)語
劉夢,于彭城,徐寒梅.蛋白多肽類藥物長效化技術(shù)研究進展[J].藥學進展,2019,43(03):209-216.
[ 作者介紹 ] 徐寒梅：中國藥科大學教授，博士生導師，江蘇省合成多肽藥物發(fā)現(xiàn)與評價工程研究中心主任，國家藥典委員會委員，中組部“萬人計劃”入選者。多年從事多肽藥物的研究，帶領(lǐng)團隊自主設計合成了多個多肽藥物、轉(zhuǎn)讓了 4 個 1 類多肽新藥，有 2 個已經(jīng)進入臨床研究。近 5 年在國內(nèi)外發(fā)表學術(shù)論文 80 余篇，SCI 論文 35 篇；主編及參編論著各 1 部，主編教材 1 部；申請發(fā)明專利及軟件著作權(quán)共 35 項 ( 其中國際專利 5 項 )，獲得授權(quán) 15 項。近年來，先后帶領(lǐng)團隊主持了：國家自然科學基金，國家“863”高科技發(fā)展計劃，國家“十一五”、“十二五”、“十三五”重大新藥創(chuàng)制科技重大專項多項，江蘇省校企合作前瞻性研究等項目。2014 年獲得江蘇省醫(yī)藥科技獎一等獎（排名第一），曾獲得科技部創(chuàng)新創(chuàng)業(yè)人才、南京市領(lǐng)軍人才、科技創(chuàng)業(yè)家等稱號。
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劉夢,于彭城,徐寒梅.蛋白多肽類藥物長效化技術(shù)研究進展[J].藥學進展,2019,43(03):209-216.
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