两种苦参素缓释剂型制备及其相对生物利用度研究.docVIP

两种苦参素缓释剂型的制备及其相对生物利用度研究 摘要 目的：制备苦参素缓释微丸和缓释片，并研究其Beagle犬体内的相对生物利用度。方法：采用离心造粒技术，选用Eudragit RS30D 作为包衣材料制成膜控缓释微丸，同时制备了骨架型缓释片，用HPLC 法测定Beagle犬口服苦参素缓释微丸和缓释片、市售普通胶囊(参比制剂) 后不同时间血浆中的浓度，计算药物动力学参数及相对生物利用度。结果：实验研究表明自制缓释微丸的相对生物利用度103.1%；自制缓释片相对生物利用度117.6%两种自制缓释制剂与市售胶囊生物等效 Preparation of the sustained-release systems of kushenin and study on the relative bioavailability ABSTRACT: OBJECTIVE To prepare kushenin sustained-release pellets and sustained-release tablets, and to study the bioavailability of these two preparations in beagle dogs. METHODS The pellets were prepared and coated using the centrifugation coating ＆ granulating equipment. Eudragit RS30D was used as the coating material. And HPMC was used as the matrix of the sustained-release tablet. HPLC was selected to determine the concentration of the active drug-oxymatrine and its metabolite-matrine in plasma. The pharmacokinetic parameters and relative bioavailability were calculated comparing with conventional capsules. RESULTS The relative bioavailability of oxymatrine in sustained release pellets and sustained release tablets analyzed by non-compartment model theory were 103.1% and 117.6%，respectively. CONCLUSIONS Two formulations are both bioequivalent with the conventional capsules. Keywords: pharmaceutics; sustained-release pellets; sustained-release tablets; oxymarine; matrine; bioavailability 苦参素（kushenin）是从天然植物苦豆子（Sophora alopecuroides L）和苦参（Sophora flavescens Ait）中提取的生物碱，是以氧化苦参碱(oxymatrine，OM)为主并含有少量氧化槐果碱的混合碱。此外，苦参碱（matrine，M）为豆科植物苦参的根及广豆根的有效活性成分，它的药理活性与OM类似，二者在一定条件下可以转化，已有文献报道，OM在胃肠道菌群的作用下可被等分子还原成M。 Oxymatrine，OM Matrine，M 目前，苦参素已经被确定为治疗病毒性肝炎重点推广工程药物，它能够明显抑制乙肝病毒感染，具有抑制病毒生长繁殖的作用。苦参素目前大量应用于临床，但国内外上市的苦参素制剂主要有软胶囊、输液、速释胶囊、注射剂和片剂，尚无缓释制剂。由于其体内消除半衰期较短（1.5～2h），现有的剂型已经远远不能适合于临床需要，对于慢性乙型肝炎患者而言，开发一日一次或两次的缓释制剂是很有必要的。本文参照市售胶囊“博尔泰力胶囊”（剂量：每日三次，每次2~3粒，100mg/粒）针对不同患者，制备了体外释放12小时的苦参素缓释片和缓释微丸并进行了苦参素缓释片、缓释微丸的相对生物利用度和体内外相关性研究。氧化苦参碱对照品中国药品生物制品检定所苦参素、苦参素胶囊（宁夏博尔泰力药业股份有限公司）；微晶纤维素（MCC）（江苏常熟