Zeng F B, Lu B, Yang H, Deng X X
School of Pharmacy, West China University of Medical Sciences, Chengdu.
Yao Xue Xue Bao. 1996;31(2):132-7.
The effect of ligustrazine hydrochloride (LTH) on depressing pulmonary artery hypertension has been proved in recent studies. In an attempt to prepare a lung targeting dosage form, ligustrazine hydrochloride gelatin microspheres (LTH-GMS) were prepared by the method of emulsion process, using 2:1 as the weight ratio of LTH to gelatin. The preparation technique was optimized and the appearance, particle size and size distribution, LTH content, in vitro release, stability, and in vivo distribution of LTH-GMS were studied. The results showed that the mean diameter of LTH-GMS measured by Coulter counter was 12.65 microns, 87.5% of the microspheres ranging from 5 to 24.9 microns. The average content of LTH in LTH-GMS was 16.49% +/- 0.49% (n = 3) with an average extent of entrapment of about 89% and the LTH-GMS were stable for three months when stored in refrigerator or at room temperature. The release profile in vitro (pH 7.8-8.0 phosphate buffer) can be described by first-order kinetic equation. The release t1/2 of LTH when given LTH-GMS was about 6 times as much as that of original LTH. The relative distribution percentage of LTH-GMS in lung when determined 20 min after iv administration to mice was significantly higher than those of LTH-GMS in other tissues and blood, and was about 6 times as much as that of the LTH solution control group in lung under the same conditions.
近年来的研究已证实盐酸川芎嗪（LTH）对降低肺动脉高压有作用。为制备肺靶向剂型，采用乳化法制备了盐酸川芎嗪明胶微球（LTH - GMS），LTH与明胶的重量比为2:1。对制备工艺进行了优化，并研究了LTH - GMS的外观、粒径及粒径分布、LTH含量、体外释放、稳定性和体内分布。结果表明，用库尔特计数器测得LTH - GMS的平均直径为12.65微米，87.5%的微球粒径在5至24.9微米之间。LTH - GMS中LTH的平均含量为16.49%±0.49%（n = 3），平均包封率约为89%，LTH - GMS在冰箱或室温下储存三个月稳定。体外释放曲线（pH 7.8 - 8.0磷酸盐缓冲液）可用一级动力学方程描述。给予LTH - GMS时LTH的释放t1/2约为原LTH的6倍。小鼠静脉给药20分钟后测定，LTH - GMS在肺中的相对分布百分比显著高于其在其他组织和血液中的分布百分比，且在相同条件下约为LTH溶液对照组肺中分布百分比的6倍。
