复方治疗慢性肾衰海洋新药的初步研究

该论文在褐藻多糖硫酸酯已有研究工作的基础上,参考中药治肾病领域有关文献,结合中医药理论,组方成治疗慢性肾衰复方海洋新药-复方褐藻多糖硫酸酯,并进行了复方褐藻多糖硫酸酯的部分药学、初步药效学和急性毒性试验的研究.

Based on the study of fucoidan and the documents on prevention and treat of chronic renal failure(CRF) as well as the theory of traditional Chinese medicine, the formula is formed by fucoidan and Dll extract which is called fufang fucoidan. In this thesis part of pharmcy.pharmcodynamics and acute mice toxicity of fufang fucoidan were studied.The results are as following: Microwave technique was applied to study the extraction process of EK from DM by the orthogonal test design which was used to arrange sequent experiments and the methods of microwave extraction and traditional extraction were compared.The results are that microwave extraction method is superior to the traditional decocting method and equivalent to the alcohol refluxing method. Microwave extraction method is efficient,simple,and rapid for extraction of active compounds of medicinal herb. The I1PLC method to determine DMA and DHS and the complexometric titralion to determine RZ from DH extract were developed.The methods have good precision and arc highly specific,and they are suitable to determine the active compounds of DH extract. Adenine-induced CRF model in rats was prepared successfully and applied to evaluate the preliminary phanncodynamics of fufang fucoidan for CRF. On treatment with fufang fucoidan, the level of urea nitrogen and creatinine in the serum showed a significant decrease, fu therm ore, administration of fufang fucoidan markedly increase the urinary excretion of both urea nitrogen and creatinine and significantly reduced the amount of urinary protein. In addition, the renal pathotnorphological examination showed that the dilatation degree of renal tubules abated and the amount of glomerulus with nearly normal histomorphology increased after the treatment. These results indicate that fufang fucoidan could improve markedly the biochemical indexs both in blood and urine and the pathomorphological changes of renal tissue in rats with CRF, Moreover,the experimental study also demonstrated that therapeutic efficacy of high-proportion fufang fucoidan is the best and superior to individual fucoidan or DH extract. Maximum toletrance dose(MTD) was tested by po administration of fufang fucoidan in KM mice because LD50 could not be determined in acute mice toxicity test. MTD is ≥ 10g/kg and no obvious sign of acute toxicity was observed. Administration of fufang fucoidan had no influence on the body weight and food intake of female mice, whereas it had marked influence on the body weight and food intake of male mice which could produce a significant increase of body weight and food intake.No mice died during the 14 testing days. Abnormal changes did not observed by anatomising mice.