【作者】 马宇辉；

【导师】 赵继全； 王义明；

【作者基本信息】 河北工业大学 ， 化学工艺， 2004， 硕士

【摘要】 灯盏花素是从菊科短葶飞蓬属植物短葶飞蓬Erigerm breviscapus(Vant.)Hand.-Mazz中提取出来的黄酮类有效成分，主要为灯盏甲素和乙素的混合物，其中灯盏乙素含量占95％以上。作为一种新型的活血化瘀中药，灯盏花素具有疗效好、用途广、不良反应少等优点，临床上主要用于治疗脑梗死、冠心病、心绞痛等。 本论文以灯盏花素为研究对象，建立了紫外分光光度法用于灯盏花素基本性质以及灯盏花素制剂含量的测定，并对其基本的理化性质进行了考察；建立了高效液相色谱法(HPLC)用于灯盏花素稳定性的研究，发现温度、pH值对其稳定性有显著影响；还建立了动物血浆中灯盏乙素浓度的HPLC测定方法，用于体内药代动力学的研究。 为了满足预防和治疗心脑血管性疾病长期用药的临床需求，达到减少服药次数、降低毒副作用和提高生物利用度的目的，将灯盏花素制成了肠溶缓释胶囊。为检查研制的药品质量，选择了目前中药质量控制中常用的高效液相色谱法建立了该药物的质量标准，包括鉴别、检查、含量测定和体外释放度测定等多项指标。 在分别静脉给予灯盏花素，灌胃给予灯盏花素普通片和灯盏花素肠溶缓释胶囊后，研究了犬血浆中灯盏乙素的血药浓度变化及药代动力学过程。灯盏花素肠溶缓释胶囊和灯盏花素片的血药浓度-时间曲线符合双室开放模型。在测定的时间范围内灯盏花素肠溶缓释胶囊的药时曲线较普通片剂的血药浓度变化平稳，达峰时间和半衰期均延长，具有明显的缓释特性。与静脉给药比较，灯盏花素肠溶缓释胶囊的绝对生物利用度达到76.79％，灯盏花素片的绝对生物利用度为50.38％；与普通片比较相对生物利用度达到152.95％，自制缓释胶囊的生物利用度明显高于参比制剂(市售普通片)。体内外相关性研究表明灯盏花素肠溶缓释胶囊的体内吸收与体外释放度有很好的相关性，可以用体外的释放度数据表征其体内的吸收。 同时，本论文还对灯盏花素的代谢产物进行了初步研究，将灯盏花素原料药分别在家犬的胃液和肠液中进行温孵；同时将其在碱性条件下进行水解。采用液相色谱-离子阱质谱技术检测灯盏花素在体液温孵条件下的代谢产物和碱性条件下的水解产物。体液中的酶水解产物和碱液中的化学水解产物的色谱和质谱行为一致，证明体内外代谢具有相关性，得到相同的代谢产物。灯盏乙素主要代谢途径为野黄芩苷脱去糖分子变为苷元。更多还原

【Abstract】 Breviscapine were the flavonoids extracted from Erigeron breviscapus (Vant.) Hand-Mazz. Breviscapine were mainly the mixture of 4’-hydroxy- β-D-pyangluconate methyl ester and scutellarin and the content of the latter was about 95 percent. As a new type of Chinese proprietary medicines, which can promote blood circulation to remove blood stasis, breviscapine showed characteristics of good curative effects, wide uses and less side-effects. Breviscapine is efficacious in the treatment of cerebral infraction, coronary heart disease, angina pectoris.In this paper, the study on breviscapine was reported. Ultraviolet spectrophotometry method was established for the study of physic chemical properties and drug content. The physiochemical properties were observed. High performance liquid chromatography with vv detection was established for studying the stability of breviscapine. Results demonstrated that temperature and PH value had significant influence on its stability. A reversed-phase high performance liquid chromatography method was established for determination if scutellarin in animals plasma which was used for the pharmacokinetics study.To meet clinical need for long time use of drugs for prevent and treatment of cardiovascular disease and cerebrovascular disease, to attain the aim of reducing times of administration and side-effects, briviscapine sustained-release capsules dissolved in intestines were prepared through the technique of sustained-release microgranules. The HPLC method was developed to control the quality of sustained-release pellets.The plasma concentrations and pharmacokinetic parameters compared after vein administration of breviscapine and oral administration of normal tablet and sustained-release capsules dissolved in intestines respectively. The results showed that plasma concentration-time profile after coral administration of normal tablet and sustained-released capsules were both fitted in with two compartment model. The absolute bioavailability of sustained-release capsules dissoloved in intestine were calculated to be 76.79% and that ofcommon tablets were 50.38%. Compared with the normal tablet, the eliminative speed of capsules reduced more slowly. The relative bioavailability was 152.95%. The result showed that breviscapine sustained-release capsules dissolved in intestines was not bioequivalent with the reference preparation (normal tablet). At the same time, metabolites of breviscapine were researched. The breviscapine was incubated in dogs’ gastric juice and intestinal juice respectively. The sample was examined by means of HPLC/MS and found the main metabolic product. Two-phase hydrolysis method was used to determined the hydrolysates of breviscapine in vitro. The two kind of product got from different method were the same. The decomposed course of breviscapine in vivo was consistent with that in vitro.更多还原