[关键词]
[摘要]
目的 从制剂分析角度进行中药注射剂与生物化学注射剂配伍稳定性研究。方法 注射用血栓通(冻干)(XST)分别与注射用脑蛋白水解物(Ⅲ)、小牛血清去蛋白注射液以及骨瓜提取物注射液按临床实际条件进行联合使用,采用2,4-二硝基氟苯(DNFB)柱前衍生HPLC法,测定配伍生物化学制剂中16种氨基酸含量。并以2015版《中国药典》为依据,检查配伍7 h内溶液渗透压、不溶性微粒、粒径、pH值、澄明度、颜色等各项制剂分析指标变化情况,综合评价药物配伍联合使用稳定性变化。结果 XST与3种生物化学药物配伍在7 h内各指标(渗透压、pH值及颜色、澄明度)均保持稳定。与小牛血清去蛋白注射液配伍在生理盐水(NS)和5%葡萄糖注射液(5% GS)中粒径波动均较大,但在NS中配伍1 h内粒径值保持稳定;与骨瓜提取物注射液配伍7 h后,在NS输液基质中,甘氨酸含量略有升高、亮氨酸含量略有下降;在5% GS输液基质中,不溶性微粒数值随时间呈增长趋势,但仍处于合格范围内。结论 建议临床XST与小牛血清去蛋白注射液配伍选用NS作为药物溶媒,现用现配,并慢速滴入,观察患者情况;使用XST与骨瓜提取物注射液配伍时建议选用5% GS作为输液剂基质即配即用;为中药注射剂质量再评价和临床合理应用提供理论参考。
[Key word]
[Abstract]
Objective The stability of compatibility between traditional Chinese medicine injection and biochemical injection was studied from the perspective of preparation analysis. Methods Xueshuantong Injection (lyophilized) (XST) respectively with Cerebroprotein Hydrolysate for Injection (Ⅲ), Deproteinised Calf Blood Serum Injection, and Guguatiquwu Injection according to the clinical used in combination with actual conditions, 2, 4-dinitrofluorobenzene pre-column derivative HPLC method was used, the determination of compatibility of 16 kinds of amino acids in biological chemicals. Based on the 2015 edition of the Chinese pharmacopoeia, the changes in the analytical indexes of various preparations including osmotic pressure, insoluble particles, particle size, pH value, clarity and color within seven hours of compatibility were examined, and the changes in the stability of drug compatibility combined with use were comprehensively evaluated. Results All indexes (osmotic pressure, pH value, color and clarity) of the three biochemical drugs compatible with XST remained stable for seven hours. The particle size of XST and Deproteinised Calf Blood Serum Injection fluctuated greatly in NS and 5% GS, but remained stable within one hour. After seven hours of compatibility between XST and Guguatiquwu Zhusheye, glycine content increased slightly and leucine content decreased slightly in 0.9% sodium chloride injection (NS) infusion matrix. In 5% GS infusion matrix, the insoluble particle value increased with time, but was still in the qualified range. Conclusion The stability changes of drug compatibility were evaluated from the perspective of preparation analysis, and the results suggested that NS should be used as the drug solvent for XST and deproteinized calf serum injection, which was currently used and prepared, and slowly dripped into the solution;5% GS should be selected as the infusion matrix for the clinical compatibility of XST and Guguatiquwu Zhusheye. This study provides theoretical reference for the re-evaluation of the quality of traditional Chinese medicine injections and the rational clinical application.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金面上项目(81873191);天津市科技计划项目:中药组分库构建关键技术的建立(20ZYJDJC00120)