Study On Long - Term Toxicity

Purpose: This experiment rats were given Tongmai-Jiangzhuo dry extract long-term orally, whether of toxicity, determine safe dosage range of indicators based on observation. Assess Tongmai-Jiangzhuo dry extract security, provide a basis for further clinical medicine. Material and method:After the purchase of rats fed normally observed one week, according to the weight, sex were randomly divided into four groups: control group; the low-dose group; middle dose group; high dose group. N = 60, male and female. Daily oral administration of low-dose group for the test crude drug 5g / kg / d, the daily dose of oral administration of the test 15 g crude drug / kg / d, daily oral administration of high-dose group for the test 30 g crude drug / kg / d. Given saline control group was given the same volume of saline. 2 times a day, six days a week dosing, Sunday withdrawal. Weighed by the calculation of weekly dosage administered the test. Test 26 weeks, wherein the administration period is 24 weeks, two weeks recovery period. Mid-week dosing was 12; the end of 24 weeks of administration; recovery for 26 weekends. Each issue of random number of rats were sacrificed approximately 1/3. Continuous observations general index, food intake, body weight. Each issue hematology blood test rats were sacrificed finger, blood chemistry 15 Index 10. After removal dissected rat brain, heart and other tissues and organs. Among them, weighed(wet weight) and calculate the brain, heart and other 12 organizations, organs and organ coefficient. After necropsy observe brain, heart and other organs in general changed. Light microscopy of rat brain, heart and other 32 organizations, pathological organ, and to analyze. Results: 1. All rats in the test cycle. All the animals were not significantly change the state of the general index. Test animal deaths occur, due to both anatomic confirmed orally and record, no drug-related deaths. 2. rat food intake, body weight gradually increasing regularity occasional fluctuations were no obvious changes in drug-related. 3. The blood test showed that, compared with the same period of the same sex in the control group, the experimental results show that the mid and high dose groups statistical male white blood cell count and lymphocyte count increased(P <0.05), suggesting infection in rats during this time. Return to normal when the experimental stage. Mid and late recovery in the presence of certain indicators have significant differences, but no biological and clinical significance. Other blood parameters were not significantly changed. 4. biochemical detection and control rats of the same sex the same period compared to some indicators appear statistically significant mid and late recovery period, but no biological and clinical significance. Other indicators of blood chemistry students did not change significantly. 5. drawn animals in each group were sacrificed systematic autopsy found: All the animals are well developed, the mouth, nose, eyes, ears, no abnormal secretions, organs(brain, heart, liver, spleen, lung, kidney, adrenal gland, thymus, testis, epididymis, uterus, ovaries, etc.) to the naked eye no obvious morphological changes. Compared with the control group of the same sex the same period, the mid-tongmai Jiangzhuo dose group and high dose group was significantly increased liver index(P <0.01), and the end of the recovery period did not change significantly. Some indicators appear three times significant differences, but no biological and clinical significance. There were no significant changes in other indicators. 6. Histopathological observations, in addition to the middle dose group and high dose groups the late part of the animal outside and saw a small amount of tissue sections of sinusoidal endothelial cell proliferation and inflammatory cells, detect normal recovery period after stopping the remaining animals, such as heart and kidney solid organ no obvious abnormalities. Gastrointestinal and other hollow organs found no significant mucosal necrosis, inflammatory cell infiltration, proliferation and other pathological changes. Bone marrow smears showed no abnormalities. Conclusion: Tongmai-Jiangzhuo dry extract no significant long-term toxicity and delayed toxicity, good security, in accordance with the recommended clinical dose should be used long-term with a certain degree of security.