Pharmacodynamic And Toxicological Study On Tong An Capsule

Tong An Capsule (TAC) has been as a hospital preparation in Lanzhou Institute of Liver Disease, Lanzhou Second People's Hospital and used to treat several kinds of pains. The Capsule is composed of eight traditional Chinese medicines, i.e., Herba Asari, Radix Aconiti Preparata, Radix Notoginseng, Radix Paeoniae Alba, etc. To evaluate its analgesic effect, action characteristic and toxicity and to provide scientific support for its clinical application, the pharmacodynamic and preliminary toxicological investigation were carried out.The analgesic effect of Tong An Capsule on different pain models was observed in mice and rats. In intragastrically administered (i.g.) groups, the writhing response induced by acetic acid in mice was inhibited, the latency of foot-licking on hotplate in mice, tail-flicking caused by radiant heat in rats, head-flicking induced by radiant heat in rabbits was prolonged and electric stimulation pain threshold was elevated after Tong An Capsule administration. The rat hind paw edema induced by carrageenin was obviously inhibited by intragastrical Tong An Capsule. In addition, the mouse spontaneous activity times were decreased and sleep mouse number induced by subliminal dose of pentobarbital sodium was increased in Tong An Capsule treated groups, indicating that Tong An Capsule possessed sedative activity in some degree. In intracerebroventricular (icv) administration groups with Tong An Capsule, the latency of tail-flicking induced by radiant heat was prolonged, suggesting that Tong An Capsule mainly exerted in role as a central analgesic.The acute toxicity test showed that the half lethal dose (LD₅₀) of Tong An Capsule i.g. in mice could not be acquired because too low toxicity and the limitation of concentration and volume of administered medicine. The maximal tolerance dose (MTD) of Tong An Capsule i.g. in mice was 22.4 g/kg, which is 498 times as much as the clinical dose of an adult.In the chronic toxicity test, the Tong An Capsule was intragastrically administered into rats with the dose of 1.35 g/kg, 2.70 g/kg and 4.05 g/kg, which is 30,60 and 90 times of the clinical dose of an adult, respectively, for three months followed by a 15-day convalescence period. The results showed that there was no remarkable difference in body weight, relative organ weights, hematological indices, serum biochemical parameters and the histopathologic change of main organs between the median dose group or low dose group and the control group. In high dose group, the decrease in body weight, content of total protein and albumin in serum was presented after three month exposure, but all were recovered after 15 days following cessation of administration, indicating that the toxic action was reversible and the no observed adverse effect level (NOAEL) was 2.70 g/kg.From the experiment results, we can infer that Tong An Capsule has obvious analgesic effect and low toxicity, and can be used as an effective and relative safe traditional Chinese medicine preparation for treatment of pains in clinic.