成骨诱导剂缓释凝胶的研制及凝结性能  

Preparation and property study of sustained-release osteoinductive gel

作　　者：吕冬梅 罗永华 万孝龙 曾春玉 李玲 何芸 Lv Dongmei;Luo Yonghua;Wan Xiaolong;Zeng Chunyu;Li Ling;He Yun(Orofacial Reconstruction and Regeneration Laboratory,Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of Oral and Maxillofacial Surgery,Hospital of Stomatology,Southwest Medical University,Luzhou 646000,Sichuan Province,China)

机构地区：[1]西南医科大学口颌面修复重建和再生实验室,四川省泸州市646000 [2]西南医科大学附属口腔医院口腔颌面外科,四川省泸州市646000

出　　处：《中国组织工程研究》2019年第34期5447-5453,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学青年项目(11702231)，项目负责人：何芸;四川省医学会项目(S16079)，项目负责人：何芸;四川省人力资源与社会保障厅(201864)，项目负责人：何芸;国家级、省级、校级大学生创新创业训练计划项目(201816032054)，项目负责人：何芸;西南医科大学项目(2016014)，项目负责人：何芸~~

摘　　要：背景:探索一种简单、方便、效果明显并广泛适用的局部缓释药物系统,局部应用于拔牙创,促进拔牙创愈合、减少牙槽嵴的萎缩和吸收是目前的一个研究热点。目的:通过检测凝胶性状、凝结时间和凝胶黏度,药物累积释放率,探究以聚乳酸-羟基乙酸共聚物为载体、成骨诱导剂为有效药物的成骨诱导剂缓释凝胶的各成分最佳配比。方法:按照正交设计简单对比法,检测N-甲基-2吡咯烷酮与三乙酸甘油酯体积比(5∶5,6∶4,7∶3,8∶2,9∶1)、聚乳酸-羟基乙酸共聚物质量分数(20%,30%,35%,40%,45%,50%)、成骨诱导剂体积分数(5%,10%,15%,20%,25%,30%)对凝胶凝固时间、凝胶黏度、凝胶凝结后状态和药物累积释放率的影响。采用单因素方差分析凝胶各组分不同比例配方的凝固时间和凝胶黏度,双因素方差分析不同时间的药物释放量。结果与结论:①当成骨诱导剂含量为10%、聚乳酸-羟基乙酸共聚物质量分数为20%时,随着N-甲基-2吡咯烷酮的增多与三乙酸甘油酯的减少,凝胶的流动性增加、凝结时间缩短、凝结硬度减小、黏度减小,在相同时间下的药物累积释放率增大;N-甲基-2吡咯烷酮与三乙酸甘油酯体积比为5∶5的凝胶性状与凝胶性能较好;②当N-甲基-2吡咯烷酮与三乙酸甘油酯体积比为5∶5、成骨诱导剂体积分数为10%时,随着聚乳酸-羟基乙酸共聚物质量分数的增加,凝胶的流动性减小、凝结时间缩短、黏度增大、凝结硬度增加,相同时间下的药物累积释放量减少;聚乳酸-羟基乙酸共聚物质量分数为40%的凝胶性状与性能较好;③当N-甲基-2吡咯烷酮与三乙酸甘油酯体积比为5∶5、聚乳酸-羟基乙酸共聚物质量分数为40%时,如果成骨诱导剂体积分数大于20%,凝胶遇水无凝结;如果成骨诱导剂体积分数小于20%,各组凝胶凝结时间相似,质均软,相同时间下的药物累积释放量减少;成骨诱导剂体积分数为1BACKGROUND:Local application of sustained-release osteoinductive medicine to improve the healing of socket and reduce the absorption of alveolar bone after tooth extraction has been receiving increasing attention.OBJECTIVE:To investigate the best ratio of each component of the poly(lactic-co-glycolic acid(PLGA)loaded sustained-release osteoinductive gel form the perspectives of the properties,coagulation time,viscosity of the gel and the cumulative drug release rate.METHODS:The orthogonal design method was used to investigate the effect of N-methyl-2-pyrrolidone(NMP)to glycerol triacetate(GTA)ratio(5∶5,6∶4,7∶3,8∶2,9∶1),PLGA mass fraction(20%,30%,35%,40%,45%,50%),and osteoinductive gel content on the properties,coagulation time and viscosity of the gel and the cumulative drug release rate.One-way analysis of variance was used to explore the differences among different groups in the viscosity and coagulation time of the gel.Two-way analysis of variance was used to explore the differences among different groups in the cumulative drug release rate.RESULTS AND CONCLUSION:(1)When osteoinductive gel content was 10%and PLGA mass fraction was 20%,as NMP increased and GTA decreased,gel fluidity increased,coagulation time was shortened,coagulation hardness was reduced,viscosity was reduced,and the cumulative drug release rate during the same time was increased.The gel property and performance was encouraging when the NMP to GTA ratio was at 5∶5.(2)When the NMP to GTA ratio was at 5∶5,the volume fraction of osteoinductive gel was 10%,with the mass fraction of PLGA content increased,gel fluidity was reduced,coagulation time was shortened,viscosity was increased,and gel hardness was increased,the cumulative drug release rate during the same time was decreased.The gel property and performance was encouraging when GLGA content was 40%.(3)When the NMP to GTA ratio was at 5∶5,the volume fraction of osteoinductive gel was 40%,when the volume fraction of osteogenic inducer was greater than 20%,no coagulation occurred

关 键 词：成骨诱导剂 PLGA 骨再生 缓释剂 拔牙创愈合 黏度 凝结时间 药物载体 释放 

分 类 号：R459.9[医药卫生—治疗学] R782.12[医药卫生—临床医学]