[Animal modeling] - Animal experimental evaluation on the safety pharmacology of Tanreqing injection

  Objective To observe the effects of Tanreqing injection on cardiovascular system, respiratory system of Beagle dogs and central nervous system of ICR mice, and to provide experimental data for its safety in clinical use.

  Methods Twenty four Beagle dogs, half male and half female, were randomly divided into low dose (2.5 mL stock solution/kg), medium dose (5.0 mL stock solution/kg), high dose (10.0 mL stock solution/kg) Tanreqing injection group and solvent control group according to body mass, with 6 dogs in each group; Under anesthesia, the drug was injected into the inferior cutaneous cephalic vein on the medial side of the right forelimb, and the blood pressure, heart rate, electrocardiogram and respiration were measured before administration, 40 min and 80 min after administration, and 5, 10, 20, 30, 60, 90, 120, 150, 180, 210 and 240 min after administration. 160 ICR mice, half male and half female, of which 60 mice were randomly divided into low dose (3.6 mL stock solution/kg), medium dose (6.25 mL stock solution/kg), high dose (12.5 mL stock solution/kg) Tanreqing injection group, solvent control group and positive control group according to body weight. After tail vein injection, the general behavior and white hair activity of the mice were observed; For 50 mice of the same group, the coordinated movement at different time points after administration was measured; The synergistic effect of pentobarbital sodium at subthreshold sleep dose after administration was determined in another 50 mice of the same group.

  Results Compared with the solvent control group at the same time point and before self administration, there was no significant difference in systolic blood pressure, mean arterial pressure, electrocardiogram and respiratory rate of Beagle dogs in each dose group of Tanreqing injection (P>0.05), and there was significant difference in diastolic blood pressure and heart rate at individual time points (P<0.05 or P<0.01), but there was no significant dose or time effect correlation. After administration, the spontaneous activity of ICR mice in the high-dose group decreased at all time points (P<0.05, P<0.01 or P<0.001), while the coordinated exercise rating increased significantly at 30, 50 and 90 min after administration (P<0.05, P<0.01 or P<0.001).

  Conclusion Under the experimental conditions, a single intravenous injection of Tanreqing injection has no significant effect on the cardiovascular and respiratory systems of Beagle dogs; The high dose Tanreqing injection has certain effects on the central nervous system of ICR mice, mainly manifested by the reduction of spontaneous activity and the disorder of coordinated movement, which may be related to the main effective ingredient bear bile powder.