CAJ | 학술논문

目的:合成系列具有功能侧基,用于偶联抗癌药或避孕疫苗等生物活性物质的生物医用聚酯-聚氨基酸共聚物,用做靶向肿瘤治疗或免疫避孕的药物控制释放载体.方法:合成功能性单体3-苄氧羰基乙基吗啉-2,5-二酮(BEMD),在辛酸亚锡的作用下通过开环聚合与ε-己内酯共聚,经催化氢化反应脱除苄氧保护基团,获得功能侧基为羧丙基的聚(ε-己内酯)-CO-(乙醇酸-alt-L-谷氨酸)(PCGG)共聚物.核磁共振氢谱、凝胶渗透色谱、差示扫描量热仪、水接触角测定等手段表征共聚物;3T3成纤维细胞初步考察共聚物的细胞毒性.结果:所得单体的纯度在99.7%以上;共聚物的共聚组成与单体投料比基本一致,随着BEMD投料比的增加,共聚物的分子量减小;随着BEMD在共聚物中共聚组成的增加,聚合物熔点降低,亲水性增强;短期的体外细胞毒性考察表明所得聚合物均无细胞毒性.结论:通过调控不同聚合条件可合成具有不同物理性能的PCGG共聚物,有望在共聚物的羧基侧基上偶联抗癌药或避孕疫苗等生物活性分子,用做靶向肿瘤治疗或免疫避孕的药物载体.
목적:합성계렬구유공능측기,용우우련항암약혹피잉역묘등생물활성물질적생물의용취지-취안기산공취물,용주파향종류치료혹면역피잉적약물공제석방재체.방법:합성공능성단체3-변양탄기을기마람-2,5-이동(BEMD),재신산아석적작용하통과개배취합여ε-기내지공취,경최화경화반응탈제변양보호기단,획득공능측기위최병기적취(ε-기내지)-CO-(을순산-alt-L-곡안산)(PCGG)공취물.핵자공진경보、응효삼투색보、차시소묘량열의、수접촉각측정등수단표정공취물;3T3성섬유세포초보고찰공취물적세포독성.결과:소득단체적순도재99.7%이상;공취물적공취조성여단체투료비기본일치,수착BEMD투료비적증가,공취물적분자량감소;수착BEMD재공취물중공취조성적증가,취합물용점강저,친수성증강;단기적체외세포독성고찰표명소득취합물균무세포독성.결론:통과조공불동취합조건가합성구유불동물이성능적PCGG공취물,유망재공취물적최기측기상우련항암약혹피잉역묘등생물활성분자,용주파향종류치료혹면역피잉적약물재체.
Objective:To synthesize a series of biomedical polyester-co-poly (amino acid) copolymers with functional side groups for conjugation of anti-cancer drugs or bioactive agents such as contraceptive polypoptides, which would be used as controlled release drug carriers for targeted oncotherapy or immunocon-traception. Methods:Functional cyclic monomer of 3-[(benzyloxycarbonyl) ethyl] morpholine-2,5-di-one (BEMD) was synthesized and then copolymerized with ε-caprolactone through ring-opening polymeri-zation catalyzed by stannous octoate. After removing the protective benzyloxy groups via catalytic hydrogena-tion, poly(ε-caprolactone)-co-[(glycolic acid)-alt-(L-glutamic acid)]s (PCGG) with functional side carboxylic groups were obtained and characterized by means of <'1>H-NMR, GPC, DSC and water con-tact angle measurement. The cytotoxicity of the copolymers was evaluated by culturing the 3T3 cells on their films in vitro within short period. Results:The purity of BEMD was beyond 99.7%. The mole fraction of the BMED units in the eopolyners was nearly equal to the monomer feed molar ratio and the molecular weight of the eopolymers was decreased with the increasing of the amount of BMED in the copolymerization. The crys-tal melting temperature of the copolymers was decreased with the increasing of the content of L-glutamic acid and inversely the hydrophilieity was increased. No cytotoxicity of the copolymers was found in the in vitro evaluated period. Conclusion:PCGG copolymers with different physical properties could be synthesized by varying different polymerization parameters. The side carboxylic groups of the copolymers could be used to conjugate anti-cancer drugs for targeted oncotherapy or contraceptive polypoptides for immunocontraception.