注射剂中不溶性微粒的测定及其对微循环功能的影响

Determination of Insoluble Particles in Injection and the Effects on Microcirculation Function

目的：考察注射剂中不溶性微粒的差异,并研究其对微循环功能的影响。方法：以盐酸氨溴索注射剂为模型药物,采用显微镜计数法和光子相关光度法检测4个厂家盐酸氨溴索注射剂中不溶性微粒的数量和分布。取大鼠复制肢体缺血再灌注（LIR）大鼠模型,实验分为模型组与正常组,每组再分为8小组,每小组10只,依次尾iv给予生理盐水、4个厂家的盐酸氨溴索注射剂和粒径为0.5、2.5、25μm的聚苯乙烯微球,给药量为250μl。正常大鼠依次记为CN、CA、CB、CC、CD、CE、CF、CG组,模型大鼠依次记为RN、RA、RB、RC、RD、RE、RF、RG组。给药后20 min检测各组大鼠肠系膜微静脉血流速度（BFVV）和微静脉管径（DV）。结果：4个厂家的盐酸氨溴索注射剂中不溶性微粒数量均符合《中国药典》规定,但0.5-2.5μm的不溶性微粒数量间差异具有统计学意义（P〈0.05）。在正常状态下,与CN组比较,除CG组外其余各组大鼠BFVV明显减小,CB、CD、CE、CF组大鼠DV明显增加,差异具有统计学意义（P〈0.01）,其中CE、CF、CG组微循环效果与粒径大小呈负相关。在LIR状态下,与RN组比较,其余各组大鼠BFVV明显减小,RB、RD组大鼠DV明显减小,差异具有统计学意义（P〈0.01）。结论：4个厂家盐酸氨溴索注射剂中不溶性微粒数量虽然均符合《中国药典》规定,但小粒径的不溶性微粒数量存在一定差异;不溶性微粒对微循环功能有不同程度的影响,且在LIR状态下影响更显著。

OBJECTIVE：To evaluate the difference of insoluble particles in injections and study its effects on microcirculation function. METHODS：The Ambroxol hydrochloride injection（AHI）was model drug. The number and distribution of insoluble particles from 4 manufacturers were determined by microscope counting method and photon correlation photometry. The limbs ischemia-reperfusion（LIR）rats model were established. The experiments were divided into model group and normal group,each divided into 8 little groups,10 in each little group. In turn the rats were tail iv given physiological saline,AHI from 4 manufacturers,polystyrene microspheres of 0.5,2.5,25 μm. The dose was 250 μl. The normal rats were marked as CN,CA,CB,CC,CD,CE,CF,CG group. The LIR model rats were marked as RN,RA,RB,RC,RD,RE,RF,RG group. The mesenteric microcirculation blood flow velocity of venule（BFVV）and diameter of venule（DV）were determined after 20 minutes of administration. RESULTS：The numbers of insoluble particles of AHI from 4 manufacturers were conformed to the requirement of Chinese Pharmacopoeia,but there were significantly differences among the numbers of insoluble particles in 0.5-2.5 μm（P0.05）. In normal conditions,compared with CN group,the BFVV of rats in other groups were significantly decreased except for CG group,and DV of rats were significantly increased in CB,CD,CE and CF groups. There were significant differences（P〈0.01）,and results of CE,CF and CG groups were negatively correlated with the particle size. In the LIR conditions,compared with RN group,the BFVV of rats was significantly decreased in other groups,and the DV of rats were significantly decreased in RB and RD groups. There were significant differences（P〈0.01）. CONCLUSIONS：Though the numbers of insoluble particles of AHI from 4 manufacturers are all conformed to the requirement of Chinese Pharmacopoeia,there are certain differences among the number of insoluble particles with small diameter. The insoluble particles have different effect on the microcirculation function,and it appears significantly under the condition of LIR.