金钗石斛眼用温敏凝胶的制备及评价  

Preparation and evaluation of thermosensitive ophthalmic gel of Dendrobium nobile Lindl.

作　　者：陈莉 吴玉梅 王森 熊永爱 吕佳佳 刘永鸿 申志林 谭道鹏 Chen Li;Wu Yumei;Wang Sen;Xiong Yongai;Lv Jiajia;Liu Yonghong;Shen Zhilin;Tan Daopeng(School of Pharmacy,Zunyi Medical University,Zunyi Guizhou 563099,China)

机构地区：[1]遵义医科大学药学院,贵州遵义563099

出　　处：《遵义医科大学学报》2021年第6期730-735,共6页Journal of Zunyi Medical University

基　　金：贵州省中医药管理局中医药、民族医药科学技术项目(NO:QZYY-2020-041);遵义市科技计划项目(NO:遵市科合社字(2017)12);贵州省教育厅重点领域项目(NO:黔教科合KY字[2021]049);贵州省科技支撑计划项目(NO:黔科合支撑[2019]2953,黔科合支撑[2019]2961)。

摘　　要：目的制备金钗石斛眼用温敏凝胶并对其体外性质、兔眼房水药动学、眼部刺激性和稳定性进行评价。方法按照眼用制剂的要求及温敏凝胶的特性检查测定其pH、黏度、胶凝温度、胶凝时间、体外溶蚀及释药行为;采用雄性新西兰兔双眼给药并在不同时间点取房水,考察其药动学特征;采用新西兰兔眼部单次和多次给药评价其眼部刺激性;将样品置于60℃和-20℃考察其耐热、耐寒稳定性;采用气相色谱法进行石斛碱定量分析。结果金钗石斛温敏凝胶的pH为6.65±0.15,黏度为(230.01±1.74)mPa·s,加人工泪液前、后的胶凝温度分别为26±0.2℃和36±0.2℃,胶凝时间仅需24±1.5 s,体外释放速度与程度几乎与凝胶的溶蚀过程同步,两者均遵循零级动力学方程。经眼部给药后,石斛碱可迅速穿过角膜进人房水(T_(max)=0.17±0.07 h)、达到峰浓度(C_(max)=24.53±6.42μg/mL),并在1 h后药物浓度降至C_(max)的2.22%,药动学过程整体表现出吸收快、消除快(t_(1/2)=0.75±0.11 h)的特点。实验建立的气相色谱条件专属性和线性良好,精密度和回收率较高,适用于石斛碱样品的含量测定。结论金钗石斛温敏凝胶性质适宜、眼部吸收迅速,提示金钗石斛经眼部给药发挥治疗作用具有一定的可行性。Objective To prepare the thermosensitive ophthalmic gel of Dendrobium nobile Lindl.and evaluate its properties,pharmacokinetics in aqueous humors of rabbit eyes,ocular irritation and stability.Methods The pH,viscosity,gelling temperatures and time,erosion and drug release behavior of the gel were determined according to the requirements of ophthalmic preparations and the properties of thermosensitive gel.The pharmacokinetic characteristics were investigated by collecting aqueous humor samples of rabbits at different time points.The ocular irritation was evaluated by single-dose and multiple-dose administration to rabbits’eyes.The thermal-resistant and cold-resistant stabilities were investigated at 60℃and-20℃,respectively.The contents of Dendrobium alkaloids were analyzed by Gas Chromatography.Results The pH of the gel was 6.65±0.15,viscosity(230.01±1.74)mPa·s,the gelling temperatures before and after adding artificial tears were(26±0.2)℃and(36±0.2)℃,and the gelling time was 24±1.5 seconds,meeting the requirements of ophthalmic use.The release rate and degree were synchronized with the erosion process of the gel,following the zero-order kinetics.The pharmacokinetic parameters displayed a good tissue permeability after ocular administration with the gel,which could quickly pass through the cornea into aqueous humor(T_(max)=0.17±0.07 h),reach the highest concentration(C_(max)=24.53±6.42μg/mL),and then decrease to 2.22%of C_(max) after 1 hour,characterized by the fast absorption and quick elimination(t_(1/2)=0.75±0.11 h).The established Gas Chromatographic conditions were suitable for the content analysis of Dendrobium alkaloids with good specificity,linearity,precision and recovery.Conclusion The in vitro properties of the Dendrobium Nobile thermosensitive gel were suitable to meet the requirements of ophthalmic preparation,and quickly absorbed through the cornea.All the results suggested the feasibility for Dendrobium Nobile to exert its therapeutic effects by ocular administration.

关 键 词：金钗石斛 眼用温敏凝胶 体外性质 房水药动学 眼部刺激性 稳定性 

分 类 号：R944.9[医药卫生—药剂学]