The Study On The Material Base And Preparation Of Pulsatilla Chinensis For Schistosomiasis

Schistosomiasis is a serious damage parasitic diseases, which is epidemic in tropical and subtropical zone. But praziquantel is the only effective drug in clinic, which can not accommodate with the Schistosomiasis control. In our prophase research, Pulsatilla chinensis has an effictive drug against Schistosomiasis, but the material basis and the mechanism of action are not clear. The exploitation of antischistosomal drugs have been restrained. So the text is about the new drug againt Schistosome based on the components of traditional Chinese medicine. Through the study on structure-activity and toxic-activity relationship, the material basis of Pulsatilla chinensis againt Schistosomiasis could be screened. And on the aim of improving the bioavailability, we could get the effective and safe drug againt Schistosomiasis through the stuty on the absorption of pulchinenoside. The dissertation is summarized as follows:1. the study on the structure-activity relationship about pulchinenosideOn the base of the understood of pulchinenoside, the structure-activity relationship can be summarized through the study on the drug against Schistosomiasis in vitro.The results are①It is vital for anti-schistomiasis activity to the C-28Carboxyl free of the P. chinensis.②It makes a difference for antischistomiasis activity to the C-3of sugar chain and connection order of the P. chinensis.③The type of aglycone also affect the anti-schistomiasis activity, found that the Oleanolic acid has the more activity than hederagenin.The four pulchinenosides BP-SJ-7、 BP-SJ-3、BP-SJ-9、 BP-SJ-10have been screened in vitro. Polypide is becoming swell and inflexible, the clarity descend, epidermis inflamed and epidermis damaged after exproused in drug.BP-SJ-9together with other components have the concurrency action through isobolographic analysis2. The study on the extract of pulchinenoside against schistosome in vitro and in vivo Based On the material basis of the extract, the extract of pulchinenoside have been screened according to the activity against schistosome, the result is BTW3has difference with the others. The effecitve and characteristic have been identified through the extrace against imago, schistosomula and the schistosomes of decreased parziquantel sensitivity in virto and in vivo.The results are the drug have concentration dependent against schistosome in virto and in vivo. The criticality anthelminthic concentration is male schistosome24μg/mL, femal schistosome32μg/mL, schistosomula32μg/mL, and the schistosomes of decreased parziquantel sensitivity48μg/mL。 Criticality is shrinking, retortion, and epidermis is swelling on the40times mirror. On the100times mirror, epidermis is swelling, Tissue is porosity, intestinal tract is swelling, bending and distribution is confusion. Under the ultrastructural organization, the pleat of tegument is disappeared, becoming the trabs or lump, and mastoid is intumescing and transfiguring. The intine spine and hollow of gynecophoral canal is disappeared.The effective dosage is400mg/kg in vivo. And the ratio is above65%to1、3、7、14、21、28、35day-old schistosomes, but they are not significant difference. Under the ultrastructural organization, the pleat of tegument is disappeared, becoming the trabs or lump, and mastoid is intumescing and transfiguring. The intine spine and hollow of gynecophoral canal is disappeared. But the change of tegument and gynecophoral canal are not obvious.3. The study on the absorption characteristic of pulchinenosideEstablishing the absorption model of pulchinenoside based on the active constitutent of pulchinenoside against the schistosome. Through comparing the study on the absorption characteristic of the2pulchinenoside, they have differences in absorption. They could have other sorbefacient constitutent.The absorption of constitutents is moderately, and they are not significant difference. The absorption of pulchinenoside B3、B10, B11are saturated, but the pulchinenoside BD、 B7are passive diffusion. The absorption rate is increasing after adding P-glucoprotein inhibitor. So pulchinenoside could be P-glucoprotein inhibitor.4. The screening on the preparation of pulchinenosideThe physico-chemical property of the extract determine the dosage form design. Pulchinenoside is subacidity, and the dissolution ability is the best in subalkaline environment. The ability is B7(?)B3(?)B10(?)B11(?)BD in all solvent. They are all stabilization in gastric enzyme and trypsogen in12h. And they are all stabilization in high temperature and glare, but the hygroscopicity is powerful. According to the absorption characteristic and physico-chemical property, we design three different type preparation. Gum Acacia design is low toxicity, and the ratio is above70%after Oral Drug Administration.5. the pharmacodynamics study on the Gum Acacia design of pulchinenosideStudying the potency on the Gum Acacia design of pulchinenoside, the result is the ratio of decreasing worms is above65%to different stages after300mg/kg Oral Drug Administration. But they are not significant difference. The usage of different designs is still increasing the ratio of decreasing worms.