苦豆子粉末有效成分释放与仔猪体内药动学研究  

Study on the Release of Active Ingredients of Sophora Alopecuroides Powder and Pharmacokinetics in Piglets

作　　者：张天宇 闫琰 吴永超 唐星[1] 于淼[1] ZHANG Tianyu;YAN Yan;WU Yongchao;TANG Xing;YU Miao(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;Shenyang Weijia Biotechnology Co.,Ltd.,Shenyang 110027,China)

机构地区：[1]沈阳药科大学药学院,沈阳110016 [2]沈阳伟嘉生物技术有限公司,沈阳110027

出　　处：《宁夏医科大学学报》2025年第2期181-188,共8页Journal of Ningxia Medical University

基　　金：中央引导地方科技发展资金区域创新体系建设项目(2023JH6/100400001)。

摘　　要：目的比较苦豆子粗粉与超微粉中总生物碱在体外的释放情况及4种生物碱(氧化苦参碱、槐定碱、槐果碱、金雀花碱)在仔猪体内的药动学规律,探究两者生物利用度的差异。方法取苦豆子粗粉(D90≈150μm)和超微粉(D90<25μm)。采用自身对照法,以苦豆子中主要成分总生物碱为指标,利用紫外分光光度法分别测定苦豆子粗粉与超微粉不同时间点总生物碱溶出的量,比较两者体外释药差异;将20头仔猪随机分为两组,分别单次给予苦豆子粗粉和超微粉,给药后采用液相色谱-质谱联用仪(LC-MS/MS)测定血浆中氧化苦参碱、槐定碱、槐果碱与金雀花碱浓度,计算末端消除速率、末端消除半衰期、达峰时间、最大血药浓度(C_(max))、药时曲线下面积(AUC)、一阶矩药时曲线下面积(AUMC)与平均驻留时间。结果超微粉与粗粉组有效成分各个时间点的累计释放量差异均有统计学意义(P均<0.01);在酸中苦豆子超微粉累计释放量在0~90 min时两者差异有统计学意义(P<0.01),随着时间延长,累计溶出率与普通粉趋于一致;氧化苦参碱与金雀花碱两者曲线具有相似性;苦豆子超微粉中氧化苦参碱、槐定碱、槐果碱、金雀花碱在仔猪体内的C_(max)分别为粗粉的1.33、1.18、1.12和1.21倍(P均<0.05);苦豆子超微粉氧化苦参碱、槐定碱、槐果碱、金雀花碱在仔猪体内的AUC_(0-t)分别为苦豆子粗粉的1.59、1.50、1.23和1.36倍。槐定碱的AUC_(0-t)与AUC_(0-inf)在超微粉组和普通粉组间差异均有统计学意义(P均<0.05);其余超微粉组药动学参数与普通粉组间差异均无统计学意义(P均>0.05)。结论苦豆子经超微粉碎后,其有效成分的释放程度可得到极大提升,生物利用度有所提高。Objective To compare the in vitro release of total alkaloids in coarse powder and ultrafine powder of Sophora alopecuroides,as well as the pharmacokinetics of four alkaloids(oxymatrine,sophoridine,sophocarpine and cytisine)in piglets,and then explore the difference of bioavailability between them.Methods Sophora alopecuroides were crushed properly,to obtain coarse powder(D90≈150μm)by sieving through 100 meshes.The coarse powder was further processed using an air jet mill to obtain ultrafine powder(D90<25μm).Employing the self-control method,the total alkaloids of Sophora alopecuroides were used as the index to determine the dissolution amounts in water and 0.1 mol·L^(-1)hydrochloric acid at different time points using ultraviolet and visible spectrophotometry.Subsequently,the cumulative release rate was calculated,and the differences in in vitro drug release were compared.20 piglets were randomly divided into two groups,the first group was treated with coarse powder,and the second group was treated with ultrafine powder.Both groups were administered the same dose in terms of active ingredients.Following administration,blood samples were collected at predetermined time points for analysis.Following the treatment of plasma by the protein precipitation method,the concentrations of four ingredients in plasma were determined using liquid chromatography-mass spectrometry(LC-MS/MS).The data were processed by DAS 2.1.1 statistical software,and the terminal elimination rate,terminal elimination half-life,peak time,maximum plasma concentration,area under the drug-time curve(AUC),area under the first moment curve(AUMC)and average residence time were calculated by non-compartment model statistical moment.Results There were significant differences in the cumulative release of active components between ultrafine powder group and coarse powder group in pure water(P all<0.01).The cumulative release of ultrafine powder of Sophora alopecuroides in acid was significantly different from that of 0-90 min(P<0.05),and with the ext

关 键 词：苦豆子 超微粉 生物碱 药物动力学 

分 类 号：R969.1[医药卫生—药理学]