| Depressing the gastrointestinal side effect of aspirin and increasing the stability of Eugenol, Aspirin Eugenol Ester (AEE) was synthesized. To offer experimental basis and rationale on its clinical exploitation and application, the toxicology and pharmacodynamics of AEE were researched initially. The paper includes five major contents as follows:Fever model induced by yeast was established in rabbits.The antipyretic effects was observed, and then the rats were executed to assay both arginine vasopressin (AVP) content in the ventral septal area (VSA) and cyclic adenosine monophosphate (cAMP) levels of hypothalami and blood plasma by enzyme linked immunosorbent assay (ELISA). The results indicated that the antipyretic effects of AEE were quick-acting and lasting longer time with significant differences. AEE reduced the levels of AVP in the ventral septal area (VSA) and the cAMP in the hypothalami of fever rats significantly.The sub-acute aging model induced by D-galactose was established in Kunming rats. Then the heart, liver and serum of rats were collected to assay both lipofuscins levels and malondialdehyde (MAD) content by fluorescence spectrophotometer. The results showed that AEE can significantly reduce the content of lipofuscins and MDA in heart, liver and blood of aging Kunming rats, and with dose effect.Wister rats were divided randomly into four groups: including control group, aspirin group, eugenol group and AEE group. Rats in each group were given medicines respectively once daily for 14d.Then a half of rats in each group were killed after taking blood from femoral artery, the rest were stopped being given medicines for one more week, then taking blood to observe differences in the rats blood by automatic blood analyzer and automatic biochemical analyzer. The results showed that the effects of AEE on rats blood was littler than Aspirin, and capacity of AEE to reduce the contents of triglyceride and total cholesterol on rats blood went beyond Aspirin and Eugenol.80 adults of Wistar rats(clean class) were randomly divided into four groups to investigate the subchronic toxicity of AEE. Three AEE doses of 50 mg/kg, 1000 mg/kg and 2000 mg/kg and one control dose were administered to rats. The results indicated that no rats were dead in each dose group. Some negative effects on metabolism were investigated in high dose group, and there were no significant toxic effect of AEE in the low dose group.The suppositories were prepared by semi-synthetic fatty acid glyceride. Quality controls of the appearance, colour, lustre, weight, melts variable time limit and local irritation of suppositories were made, and the content of AEE was assayed by HPLC (High Performance Liquid Chromatography).The results showed that the preparation technology of AEE suppositories is feasible and reliable. Quality test criterion for AEE suppositories conforms to the standard of Chinese Pharmacopeias.The above experimental results show that AEE has a greater antipyretic activity than aspirin and eugenol, which may be related with the production of the AVP in the ventral septal area (VSA) and blood plasma and the cAMP in the hypothalami of fever rats. As with aspirin and eugenol, AEE has obvious antioxidant capacity. A low dose of AEE is non-toxic to the body, and had higher medicinal value. Because of reasonable and simple preparation method, explicit quality control standards, good stability, antipyretic effects, non-excitant, non-adverse reaction, successful clinical curative effects observation, AEE suppositories can be used for clinical application practically. |
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