通痹舒筋丸的毒理学安全性研究

A study on toxicological safety of Tongbi Shujin Wan

目的:探讨通痹舒筋丸的安全性,为通痹舒筋丸的安全用药提供参考。方法:通过大鼠经口给予通痹舒筋丸6个月毒性试验,对试验动物进行大体解剖学观察和脏器病理切片观察,并测血液学及血液生化学指标。结果:1.大体观察结果显示,动物各脏器肉眼观察未见外形异常,表面未见充血、瘀血、肿胀、渗出、粘连等变化,胸腔、腹腔、盆腔等未见渗液、充血、出血、粘连等变化。2.病理切片显微检查结果显示,(1)连续给药6个月,对照组动物肝小叶结构正常;高剂量组可见肝细胞轻度肿胀,伴轻度炎症反应;中剂量组和低剂量组未见异常。恢复期高剂量组均未见肝细胞损伤和炎症反应。(2)连续给药6个月,对照组肾脏结构正常;高剂量组部分动物肾皮质近曲小管上皮细胞轻度水样变性,雌雄动物间无明显差异;中剂量组和低剂量组未见异常。恢复期高剂量组的肾脏均未见损伤。(3)连续给药6个月,高剂量组的个别动物肺间质可见轻度炎症,与对照组相比未见明显差异,属动物偶发的组织形态学改变,与药物毒性无关。(4)连续给药6个月,恢复期对照组、高剂量组的其余脏器未见与受试药毒性有关的病变。3.实验室检查结果显示:(1)连续给药6个月,高剂量组有2只大鼠WBC偏高,无异常高值,PLT总体明显高于正常值高限;停药恢复2周后高剂量组2只大鼠WBC趋于正常;PLT总体仍明显高于正常值高限,但所有大鼠血液生化检测值与对照组检测值无明显异常。(2)连续给药6个月,高剂量组有1只大鼠BUN明显高于正常值高限;停药恢复2周后所有大鼠血液生化检测值与对照组检测值无明显异常。结论:高剂量组(12.0g生药/kg/d)给药量相当于成人(60kg体重)临床用药量(0.1667g生药/kg/d)的71.98倍;中剂量组(7.2g生药/kg/d)给药量相当于成人临床用药量的43.19倍;低剂量组(4.2g生药/kg/d)给药量相当于成人临床用药量的25.19倍。通痹舒筋丸的临床使用剂量无明显毒副作用,具有可靠的安全性。

Objective： The safety of TongbiShujin Wan was explored, for reference to application. Methods： The rats were treated with TongbiShujin Wan by oral administration for 6 months. The animals were subjected to gross anatomical and histopathological observation. And hematology and blood biochemical indicators were tested. Results： The results of general observation showed that there was no abnormalities in the viscera, without congestion, coagulation, swelling, exudation, adhesion and so on. There was also no change in the pleural, abdominal, pelvic, and so on. In pathological microanalysis examination, the liver lobules were normal in the control group at continuous administration for 6 months, and the liver cells were mildly swollen and mild infammation in the high dose treatment group. No abnormality was observed in the middle and low dose treatment group. There was no hepatocyte injury and infammatory response in the recovery period in the high dose group. When continuous administration for 6 months, the control group had normal renal structure. The animals in the high dose treatment group were mild water sample degeneration in renal cortex proximal tubule epithelial cells. There was no signifcant diference between the male and female animals. No abnormality was observed in the middle and low dose treatment group. There was no kidney damage in the recovery period in the high dose treatment group. The administration time is the same as above. The individual animals in the high dose group can be seen mild interstitial pneumonia, with no signifcant diference with the control group. And this was the animal＇s occasional histomorphological changes, and the drug toxicity has nothing to do. In the same method of medication, the toxicity of the drug involved in the rest of the organs in the recovery period in the control group and the high dose treatment group was not observed. In laboratory tests, continuous administration for 6 months, there were 2 rats in the high dose treatment group with high WBC, no abnormally high value, PLT was generally higher than the normal upper limit; in 2 weeks of recovery, the WBC of two rats in the high dose treatment group becamenormal; PLT overall was still signifcantly higher than the normal high limit; but all the blood biochemical test values showed no signifcant abnormalities compared with the control group. Continuous administration for 6 months, in the high dose treatment group, 1 rat BUN was signifcantly higher than the normal high limit; in 2 weeks of recovery, the blood biochemical test value of all rats was not signifcantly diferent from that in the control group. Conclusion： The dose in the high dose treatment group was equivalent to 71.98 times of the clinical dose in adult （60kg body weight）; The dose in the middle dose treatment group （7.2g crude drug/kg/d） is equivalent to 43.19 times in the adult clinical dose; The dose in the low dose treatment group （4.2g crude drug/kg/d） is equivalent to 25.19 times in adult clinical dosage. TongbiShujin Wan did not fnd obvious side efects, with reliable safety.