芩术安胎散的毒性和临床安全性试验研究

试验通过对芩术安胎散的急性毒性、亚慢性毒性和临床安全性进行研究，为芩术安胎散对家猫先兆性流产的预防与治疗提供参考。急性毒性试验：制备芩术安胎散药液，取6周龄健康昆明小白鼠60只，随机分为5组，每组12只，第1~4组的给药剂量分别为6 000、4 800、3 840和3 072 mg/kg，对照组给予等量纯净水，10 d内观察有无中毒和死亡，计算半数致死量（LD₅₀）；另取6周龄健康昆明小白鼠20只，随机分为2组：试验组给予2.0 g/mL芩术安胎散药液，18 h内灌服3次，每次0.8 mL，对照组给予等量纯净水，给药后饲养7 d，计算最大耐受量（MTD）。亚慢性毒性试验：24只7周龄SD雌性大鼠随机均分为高、中、低剂量组和对照组，在30 d内，每日分别给予4 800、2 400和1 200 mg/kg芩术安胎散，对照组以等量纯净水进行灌胃，每日观察和记录各组大鼠的精神状态、有无中毒症状和死亡；第31天对各组大鼠称重、采血，进行血液学检测，剖检各组大鼠，观察主要脏器有无病变并制作病理切片。临床安全性试验：选取2~5岁健康雌性家猫20只，适应性饲养10 d，随机分组，每组5只，分别为低剂量组（1倍临床推荐剂量：1.15 g/kg）、中剂量组（3倍临床推荐剂量：3.45 g/kg）、高剂量组（5倍临床推荐剂量：5.75 g/kg）及空白对照组，将药物置于胶囊内，口服给药，空白对照组给予空胶囊，每日1次，连续给药7 d，每日观察各组家猫食欲、精神状态及排便情况，于第8天对各组家猫进行静脉采血，检测血常规和血液生化指标。结果显示，急性毒性试验无小鼠死亡，LD₅₀>6 000 mg/kg；小鼠对芩术安胎散的最大耐受量为240 g/kg，表明该受试药物无明显毒性。在亚慢性毒性试验中，各组大鼠的生长发育情况、血常规指标、脏器系数与对照组相比均无显著差异（P>0.05）；高、中剂量组与低剂量组、对照组相比血清总胆固醇含量显著下调（P<0.05），除此之外的生化指标均无显著差异（P>0.05）。病理剖检和组织切片观察结果显示，高剂量组大鼠主要组织器官与对照组相比无明显异常。在临床安全性试验中，不同剂量组家猫精神状态、被毛光泽度、粪便情况均正常，血液学指标与对照组相比差异均不显著（P>0.05）。本试验结果表明，中药芩术安胎散无明显毒性，家猫按临床推荐剂量使用是安全的。

Study on Toxicity and Safety Evaluation of Qinzhu Antai Powder

This study was aimed to investigate the acute toxicity, sub-chronic toxicity and clinical safety of Qinzhu Antai powder, and provide basis for its application for prevention and treatment of domestic cats threatened miscarriage. Acute toxicity test:Qinzhu Antai powder was prepared, sixty 6 weeks old healthy Kunming mice were randomly divided into 5 groups. The doses of groups 1-4 were 6 000, 4 800, 3 840 and 3 072 mg/kg, respectively, and the control group was given the same volume of purified water. After 10 days of feeding, the poisoning symptoms and mortality were observed, and the median lethal dose (LD₅₀) was calculated. Twenty 6 weeks old healthy mice were randomly divided into two groups:The experimental group was given 2.0 g/mL solution 3 times within 18 hours, 0.8 mL each time, and the control group was given the same volume purified water for 7 days, and the maximum tolerance dose (MTD) and tolerance multiple were calculated. Sub-chronic toxicity test:Twenty-four 7 weeks old female SD rats were randomly divided into high, middle and low dose groups and control group, the daily intragastric doses of Qinzhu Antai powder were 4 800, 2 400 and 1 200 mg/kg, respectively, the control group was given the same volume of pure water and fed rats for 30 days, the mental state, poisoning symptoms and mortality of rats in each group were observed and recorded every day. On the 31st day, the rats in each group were weighed and blood samples were collected for hematological examination, the pathological changes of the major organs were observed and pathological sections were made. Clinical safety test:Twenty 2-5 years old healthy female domestic cats were selected and fed adaptively for 10 days. They were randomly divided into 4 groups, the Qinzhu Antai powder dosage was 1, 3 and 5 times of the recommended clinical dose of domestic cats, respectively:1.15 g/kg in low dose group, 3.45 g/kg in middle dose group and 5.75 g/kg in high dose group. The drug was given orally once a day for 7 days. The blank control group was given empty capsule, and the appetite, mental state and defecation of domestic cats in each group were observed every day. Venous blood samples were collected from domestic cats in each group on the 8th day, and blood routine indexes and blood biochemical indexes were detected. The results showed that there was no death in mouse in acute toxicity test, LD₅₀>6 000 mg/kg, the MTD of Qinzhu Antai powder in mouse was 240 g/kg, indicating that the drug was no-toxic. In the sub-chronic toxicity test, there was no significant difference in growth, organ coefficient and blood routine index between each dose and control groups (P>0.05). The content of serum total cholesterol in high and middle dose groups was significantly lower than that in low dose and control groups (P<0.05). There was no significant difference in other biochemical indexes (P>0.05). The results of pathological examination and tissue section observation showed that there was no obvious abnormality in the main tissues and organs of high dose group compared with control group. In the clinical safety test, the mental state, coat glossiness and feces of domestic cats in different dose groups were normal, there were no significant difference in hematological indexes with control group (P>0.05). The results indicated that Qinzhu Antai powder had no obvious toxicity, according to the recommended clinical dose used for domestic cats were safety.