基于大鼠鼻腔灌流法筛选芍药苷经鼻给药制剂的吸收促进剂(1)
[摘要]该实验筛选了芍药苷经鼻给药制剂的吸收促进剂，建立了HPLC测定灌流液中芍药苷的方法，采用改良的大鼠鼻腔灌流模型，筛选吸收促进剂的种类和用量。为了避免鼻腔的分泌和吸收对灌流液体积的影响，采用体积校正法计算剩余药量，各时间点剩余药量的百分率取对数后与对应时间进行回归，回归直线的斜率即为吸收速度常数。结果显示，羟丙基-β-环糊精和水溶性氮酮能够显著提高芍药苷的鼻腔吸收，其中水溶性氮酮吸收速度常数最大，对芍药苷的促渗效果最好。当灌流液中水溶性氮酮的质量浓度由5 g·L-1逐渐升高为20 g·L-1时，吸收速度常数逐渐变大，20 g·L-1时达到峰值；当其质量浓度增加至30 g·L-1时，吸收速度常数变小，表明水溶性氮酮质量浓度为20 g·L-1时促渗效果最好。
[关键词]芍药苷； 大鼠鼻腔灌流； 吸收促进剂； 水溶性氮酮
[Abstract]This experiment was aimed to screen the absorption enhancer for intranasal administration preparations of paeoniflorin. In this study， HPLC method for determination of paeoniflorin in perfusion liquid was established and the improved model of nasal perfusion in rats was used to screen out the species and amounts of absorption enhancer. In order to avoid the influence of the secretion and absorption of nasal cavity on the volume of perfusion fluid， the residual dose was calculated by using the volume correction method. Linear regression was carried out between the logarithm to the percentage of the residual dose and the corresponding time， and the slope of the regression line was exactly the absorption rate constant. Experimental results showed that hydroxypropyl-β-cyclodextrin and water-soluble azone can significantly improve the nasal absorption of paeoniflorin. Furthermore， water-soluble azone had the highest absorption rate constant and the best promoting penetration effect on intranasal administration preparations of paeoniflorin. It was also found that when the mass concentration of water-soluble azone in the perfusion liquid increased from 5 g·L-1 to 20 g·L-1， the absorption rate constant was gradually increased and peaked at 20 g·L-1. When the mass concentration was increased to 30 g·L-1， the absorption rate constant was decreased， indicating that the best mass concentration of water-soluble azone was 20 g·L-1.
, 百拇医药
[Key words]paeoniflorin； nasal perfusion in rats； absorption enhancer； water-soluble azone
芍藥苷(paeoniflorin)是一种主要存在于毛茛科多年生宿根草本植物芍药Paeonia albiflora Pall.的根中的单萜类糖苷化合物，具有显著的镇痛、镇静、抗惊厥作用。此外，芍药苷还具有降温解热、抗炎、抗溃疡、抗氧化、抗凝血及调节血脂等作用[1]。近年来随着研究的深入，发现芍药苷亦可作用于神经系统，对老年痴呆、帕金森病和脑缺血损伤都有一定的治疗作用，但是芍药苷经口服进入人体后生物利用度较低，不利于发挥药效[2-5]。
研究表明存在着基于鼻腔到达中枢神经系统的通路，经鼻给药可绕过血脑屏障直接进入中枢神经系统，更好地发挥芍药苷在中枢的治疗作用[6]。芍药苷水溶性较大，不易被鼻黏膜吸收，通过添加吸收促进剂可以增加芍药苷对鼻黏膜的穿透作用。本研究通过大鼠鼻腔灌流法比较羟丙基-β-环糊精、丙二醇、水溶性氮酮对芍药苷的促渗作用，筛选出吸收促进剂的种类和较佳用量，为今后芍药苷经鼻给药制剂的研究提供实验依据[7]。, 百拇医药(朱智涛 潘金火 吴贤慧 蒋志涛)
[关键词]芍药苷； 大鼠鼻腔灌流； 吸收促进剂； 水溶性氮酮
[Abstract]This experiment was aimed to screen the absorption enhancer for intranasal administration preparations of paeoniflorin. In this study， HPLC method for determination of paeoniflorin in perfusion liquid was established and the improved model of nasal perfusion in rats was used to screen out the species and amounts of absorption enhancer. In order to avoid the influence of the secretion and absorption of nasal cavity on the volume of perfusion fluid， the residual dose was calculated by using the volume correction method. Linear regression was carried out between the logarithm to the percentage of the residual dose and the corresponding time， and the slope of the regression line was exactly the absorption rate constant. Experimental results showed that hydroxypropyl-β-cyclodextrin and water-soluble azone can significantly improve the nasal absorption of paeoniflorin. Furthermore， water-soluble azone had the highest absorption rate constant and the best promoting penetration effect on intranasal administration preparations of paeoniflorin. It was also found that when the mass concentration of water-soluble azone in the perfusion liquid increased from 5 g·L-1 to 20 g·L-1， the absorption rate constant was gradually increased and peaked at 20 g·L-1. When the mass concentration was increased to 30 g·L-1， the absorption rate constant was decreased， indicating that the best mass concentration of water-soluble azone was 20 g·L-1.
, 百拇医药
[Key words]paeoniflorin； nasal perfusion in rats； absorption enhancer； water-soluble azone
芍藥苷(paeoniflorin)是一种主要存在于毛茛科多年生宿根草本植物芍药Paeonia albiflora Pall.的根中的单萜类糖苷化合物，具有显著的镇痛、镇静、抗惊厥作用。此外，芍药苷还具有降温解热、抗炎、抗溃疡、抗氧化、抗凝血及调节血脂等作用[1]。近年来随着研究的深入，发现芍药苷亦可作用于神经系统，对老年痴呆、帕金森病和脑缺血损伤都有一定的治疗作用，但是芍药苷经口服进入人体后生物利用度较低，不利于发挥药效[2-5]。
研究表明存在着基于鼻腔到达中枢神经系统的通路，经鼻给药可绕过血脑屏障直接进入中枢神经系统，更好地发挥芍药苷在中枢的治疗作用[6]。芍药苷水溶性较大，不易被鼻黏膜吸收，通过添加吸收促进剂可以增加芍药苷对鼻黏膜的穿透作用。本研究通过大鼠鼻腔灌流法比较羟丙基-β-环糊精、丙二醇、水溶性氮酮对芍药苷的促渗作用，筛选出吸收促进剂的种类和较佳用量，为今后芍药苷经鼻给药制剂的研究提供实验依据[7]。, 百拇医药(朱智涛 潘金火 吴贤慧 蒋志涛)