[Rationality evaluation of Shuanghuanglian Injection combined with Ampicillin Sodium for Injection based on sequential analysis].

The lack of rationality evaluation method for drug combination has long restricted its clinical application. In view of this, this study took Shuanghuanglian Injection as model drug and established a "physical-chemical-biological" sequential analysis method, which is expected to provide clues for improving the safety and effectiveness of clinical drug combination. With the methods of insoluble particle testing, isothermal titration calorimetry(ITC), and real time cellular analysis(RTCA), the rationality of Shuanghuanglian Injection combined with Ampicillin Sodium for Injection was assessed. The results showed that the number of insoluble particles>10 µm in the solution of the combination met the standard of Chinese Pharmacopoeia, while the number of insoluble particles>25 µm did not meet the standard. ITC detection demonstrated that the change of Gibbs free energy(ΔG) was less than 0 during the fusion process, indicating that the process was spontaneous and enthalpy-driven reaction. Therefore, the interaction between the two was mainly chemical reaction, and the internal substances may change. RTCA found that Shuanghuanglian Injection alone and Ampicillin Sodium for Injection alone basically had no inhibitory effect on the growth of HEK293 T cells, while the combination of the two suppressed the growth of HEK293 T cells, suggesting that the combination was toxic to HEK293 T cells. This study showed that Shuanghuanglian Injection and Ampicillin Sodium for Injection reacted, yielding toxicity. This suggested that the two should not be combined for application. With the "physical-chemical-biological" sequential analysis, the molecular interaction of drugs was clarified. The method can be further applied for evaluating the rationality of other Chinese and western medicine injections.