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为筛选适宜的注射用增溶辅料、减少注射剂不良反应的发生,以嗜热四膜虫BF5为模式生物,建立基于微量量热技术的注射用增溶辅料生物安全性评价方法.恒温28℃时,监测不同注射用增溶辅料(泊洛沙姆188、吐温80、吐温20、聚乙二醇600、聚乙二醇400)干预嗜热四膜虫BF5生长代谢的热谱曲线,抽提生物热动力学特征参数进行量化评价.结果表明,在不同浓度的上述增溶辅料干预下,嗜热四膜虫BF5生长速率常数(k)、5%抑制浓度(IC5)、最大输出功率(P1,P2)、达峰时间(T1,T2)和发热量(Q)呈现规律性变化;且k与增溶辅料浓度间的线性关系良好(r>0.9),IC5依次是泊洛沙姆188为2.18mg/mL,聚乙二醇600为1.35mg/mL,吐温80为1.07mg/mL,聚乙二醇400为0.58mg/mL,吐温20为0.045mg/mL.主成分分析表明,参数k,P1和Q能够较好体现热谱曲线整体信息,可用于增溶辅料生物安全性的量化评价.这也得到综合评价结果的印证,即在相同浓度下,泊洛沙姆188对嗜热四膜虫BF5生长代谢毒性较小,而吐温20毒性较大.
In order to screen suitable solubilization excipients for injection and reduce the incidence of adverse reactions of injection, the biosafety evaluation method of solubilization adjuvant for injection based on microcalorimetry was established by using Tetrahymena thermophila BF5 as model organism. The thermodynamic profiles of growth and metabolism of Tetrahymena thermophila BF5 were monitored with different solubilization adjuvants for injection (poloxamer 188, Tween 80, Tween 20, polyethylene glycol 600 and polyethylene glycol 400) The biological thermodynamic parameters were quantified and evaluated.The results showed that the growth rate constants (k), 5% inhibitory concentration (IC5), maximum output power ( P1, P2), the peak time (T1, T2) and the calorific value (Q) showed regular changes, and the linear relationship between k and solubilization excipients was good Was 2.18 mg / mL, polyethylene glycol 600 was 1.35 mg / mL, Tween 80 was 1.07 mg / mL, polyethylene glycol 400 was 0.58 mg / mL, and Tween 20 was 0.045 mg / mL. The principal component analysis , Parameters k, P1 and Q can better reflect the overall information of the thermal spectrum curve, which can be used to quantify the biosafety of solubilization excipients. , I.e. at the same concentration, growth and metabolism Poloxamer 188 less toxic Tetrahymena thermophila BF5, and Tween 20 greater toxicity.