基于生物热动力学的注射剂无菌检查新方法研究

A novel method for testing sterility of injections based on biothermodynamics

为弥补药典常规无菌检查方法周期长、灵敏度低、易误判等局限,尝试建立基于生物热动力学的注射剂无菌检测新方法。依据微生物生长代谢过程中存在热量变化的普遍现象,采用生物热动力学法,以微生物生长速率k≥0及热功率差值Pi-P0大于3倍基线噪音为评价指标,检测其热量变化规律以考察新建方法对无菌检查方法学要求菌株及注射剂实际样本中微生物的检测效力。结果显示,新建方法可在10 h内检出规定的革兰阳性菌、革兰阴性菌和真菌,且灵敏度均小于100 CFU·mL-1;同时在不同灭菌处理的注射剂实际样本中(复方茵陈注射液、注射用双黄连粉针、复方曲安奈德混悬型注射液)成功应用。研究提示,生物热动力学法用于注射剂无菌检查具有快速、灵敏等技术优势,有望为常规无菌检查方法带来有益的补充。

This study aims at trying to establish a novel method of sterility test for injections based on biothermodynamics, in order to overcome the deficiencies of routine sterility tests such as long detecting cycle, low sensitivity and prone to misjudgments. A biotherrnodynamics method was adopted to rapidly detect the microorganism contamination of injections by monitoring the heat metabolism during the growth of microbe. The growth rate equal to or greater than zero and the heat power difference of Pi and P0 with three folds higher than the noise of baseline were chosen as indexes to study the heat change rule of microbe. In this way, the effectiveness of the new method to detect strains required by conventional sterility test or in injection samples was also investigated. Results showed that the Gram-positive bacteria, Gram-negative bacteria and fungi demanded by sterility testing methodology could be detected by biothermodynamics method within 10 hours, with the sensitivity lower than 100 CFU ·mL^-1. Meanwhile, this method was successfully applied to the sterility test of Compound Yinchen injection （FFYC）, Shuanghuanglian powder injection （SILL） and Compound Triamcinoloneinjection （TAND） which were sterilized with different degrees. Therefore, the biothermodynamics method, with advantages of fast detection and high sensitivity, could be a complementary solution for conventional sterility tests.