Object To phosphorylate 7-OH of A ring of puerarin molecules for enhancing their water solubility,and then to compare with puerarin from hemorheology impact in hyperlipidemia rats.Methods The target products were obtained by puerarin reacting with acetic anhydride to give full-protected Puerarin, then selectively deprotected 7-OAc with imidazol, phosphorylation of 7-OH, deprotection of Bn, cation resin exchange purification and recrystallization in methanol, successively. Their structures were confirmed by spectral analysis. To investigate solubility of puerarin and puerarin monophosphate in water. SD rats were divided into blank control group: distilled water, 20 mL/kg, ig. ; model group: distilled water, 20 mL/kg, ig; YuFengNingXinPian positive drug control group: 200 mg/kg, ig. ; puerarin group: 400 mg/kg, ig.; puerarin monophosphate derivatives group: 510 mg/kg, ig. First of all, each animal was administrated for 5 consecutive days. In addition to the blank control group, other groups were administrated by subcutaneous injection of epinephrine 0.08 mL/100 g 1h after administration on the fourth day. In the middle time of the two injections, rats were wetted in cold water, placed in fridge for 10 min at 4℃ and fasted. Next morning, 1 h after administration, drawn blood was used for determination of 12 parameters such as high shearrate blood viscosity, low shearrate blood viscosity, plasma viscosity and so on.Results The puerarin monophosphate derivatives were obatined and have apparently greater solubility than puerarin. Compared with the model, both puerarin and sodium puerarin-7- phosphate decrease related parameters of hemorheology in acute hyperlipidemia rats. Of which, Sodium Puerarin-7 phosphate has the most obvious effect(P<0.01). Conclusions Sodium Puerarin-7 phosphate has greater water solubility, and can dramatically decrease related parameters of hemorheology in acute hyperlipidemia rats.%目的：将葛根素分子A环7位上的羟基进行磷酸酯化衍生，以期提高其水溶性，并对比葛根素及葛根素单磷酸酯盐衍生物对高血脂大鼠血液流变学的影响。方法葛根素在醋酐条件下生成全乙酰保护的葛根素，再在咪唑条件下选择性脱除7位上的乙酰保护基，然后与氯代亚磷酸二苄酯反应，最后脱苄基保护，得到目标产物，产物经阳离子交换树脂处理、甲醇重结晶纯化分离，产物结构经波谱解析鉴定；分别测定葛根素及葛根素单磷酸酯盐在水中的溶解度；SD大鼠分为空白对照组：蒸馏水，20 mL/kg，ig；模型组：蒸馏水，20 mL/kg，ig；愈风宁心片阳性药物对照组：200 mg/kg，ig；葛根素组：400 mg/kg，ig；葛根素单磷酸盐衍生物组：510 mg/kg，ig。首先对各组动物连续灌胃5 d，除空白对照组外，其它组于第4天给药1 h后，再皮下注射肾上腺素0.08 mL/100 g。4 h后再注射1次，在两次注射肾上腺素期间的中间时间点，将大鼠用冷水浸湿，在4℃冰箱中放置10 min，处置后禁食，次晨给药1 h后取血检测全血高切黏度、全血低切黏度、血浆黏度等12项指标。结果得到葛根素单磷酸酯盐衍生物：葛根素-7-磷酸酯钠，葛根素单磷酸酯盐在水中的溶解度明显高于葛根素；与模型组比较，葛根素和葛根素-7-磷酸酯钠均能显著改善急性高脂血症大鼠血液流变学相关指标，其中葛根素-7-磷酸酯钠的作用较其它药物更为明显（P＜0.01）。结论葛根素-7-磷酸酯钠具有较好的水溶性；能更加显著地改善急性高脂血症大鼠血液流变学相关指标。
展开▼
