The present invention relates to an effective method of preparation of copolymers of N-(2-hydroxypropyl) methacrylamide (HPMA) and methacryloylaminoacylhydrazide, suitable for binding of drugs containing a keto group, for pH-controlled drug release. The method comprises the steps: a) providing of the monomers of the linear statistical copolymer; b) RAFT polymerisation of monomers of the linear statistical copolymer; c) introduction of hydrazide groups, and simultaneous in situ modification of the end groups of the linear statistical copolymer, optionally, binding a biologically active molecule to the ends of the polymer chain. The present invention further relates to a method of preparation of a conjugate of the linear statistical copolymer with a drug by means of a pH-sensitive hydrolysable hydrazone bond.
本发明涉及一种有效的制备N-(2-羟丙基)甲基
丙烯酰胺(H
PMA)和甲基
丙烯酰胺基酰
肼的共聚物的方法,适用于结合含有酮基的药物,用于pH控制药物释放。该方法包括以下步骤:a)提供线性统计共聚物的单体;b)线性统计共聚物单体的RAFT聚合;c)引入
肼基团,并同时原位修饰线性统计共聚物的末端基团,可选择地将
生物活性分子结合到聚合物链的末端。本发明还涉及一种通过pH敏感可
水解的
肼酮键制备线性统计共聚物与药物的共轭物的方法。