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基于在体单向肠灌流模型探究去氢骆驼蓬碱衍生物HM-Y-A的肠吸收特性 被引量:2
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作者 高惠静 王鑫 +3 位作者 李玉玲 卡地尔亚·库尔班 赵军 陈蓓 《中南药学》 CAS 2023年第3期607-611,共5页
目的考察去氢骆驼蓬碱衍生物(HM-Y-A)在小肠不同肠段、不同条件下的吸收特性,探究HM-Y-A的吸收机制。方法采用大鼠在体单向肠灌流模型结合HPLC测定法,考察不同肠段、不同药物浓度、不同pH值及P-糖蛋白抑制剂对HM-Y-A吸收参数(K_(a)和P_(... 目的考察去氢骆驼蓬碱衍生物(HM-Y-A)在小肠不同肠段、不同条件下的吸收特性,探究HM-Y-A的吸收机制。方法采用大鼠在体单向肠灌流模型结合HPLC测定法,考察不同肠段、不同药物浓度、不同pH值及P-糖蛋白抑制剂对HM-Y-A吸收参数(K_(a)和P_(app))的影响。结果HM-Y-A在小肠各段均有吸收,最佳吸收肠段是十二指肠和空肠;随着药物浓度升高,吸收参数K_(a)和P_(app)不断降低,低浓度与中、高浓度间差异具有统计学意义(P<0.05);在pH 6.4和7.4时K_(a)和P_(app)显著增高(P<0.05);加入P-糖蛋白抑制剂前后,吸收参数差异无统计学意义。结论HM-Y-A在小肠全段均有吸收,在十二指肠和空肠吸收较好;吸收机制可能以主动吸收或促进扩散为主;药物在偏碱性条件下吸收较好;HM-Y-A可能不是P-gp的底物。 展开更多
关键词 去氢骆驼蓬碱衍生物 在体单向肠灌流 吸收特性
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Effects of 1-(2-chlorine)-phenyl-9-butyl-β-carboline(DH-330)on Cystic Echinococcosis in Mice in vivo
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作者 Huijing GAO Xin WANG +2 位作者 cartiera kurban Aniwanr METIkurban Bei CHEN 《Medicinal Plant》 CAS 2022年第3期39-42,共4页
[Objectives]The paper was to evaluate the in vivo treatment efficacy of harmine derivative 1-(2-chloro)phenyl-9-butyl-β-carboline(DH-330)on mice cystic echinococcosis(CE).[Methods]Kunming mice were injected intraperi... [Objectives]The paper was to evaluate the in vivo treatment efficacy of harmine derivative 1-(2-chloro)phenyl-9-butyl-β-carboline(DH-330)on mice cystic echinococcosis(CE).[Methods]Kunming mice were injected intraperitoneally into the protoscoleces and infected with secondary infection for 8 months to prepare CE model.The successfully modeled mice were randomly divided into 6 groups according to their body weight:model group,control-1,-2 groups and experimental-L,-M,-H groups,with 10 mice in each group.The model group was given distilled water and control-1,-2 groups were given 50 mg/kg albendazole and harmine,respectively.The experimental-L,-M,-H groups were given 25,50 and 100 mg/kg DH-330.After 8 weeks of intragastric administration,the mice were dissected and vesicles were taken,and the differences of cyst weight were compared.The ultrastructure changes of cysts were observed by transmission electron microscope(TEM).The histopathology of cysts and liver were observed by hematoxylin-eosin(HE)staining method.[Results]The cyst weight of model group,control-1,-2 groups and experimental-L,-M,-H groups were(34.38±4.32),(11.38±2.37),(15.89±1.31),(16.22±2.30),(11.69±2.95)and(9.78±1.14)g,respectively.Compared between drugs group and model group,the difference was significant(all P<0.05);compared between experimental-H group and harmine group,the difference was significant(P<0.05).Except for the model group and experimental-L group,all other groups can damage the hydatid nuclei,which lead to cell lysis and nucleoli disappear.Experimental groups can improve inflammatory cells infiltration in liver and vesicle.[Conclusions]DH-330 can reduce the cysts weight of CE mice,inhibit the growth of hydatid,and improve the inflammation of the liver and vesicles,showing a good resistance against Echinococcus granulosus,or may become an effective new drug against hydatid disease. 展开更多
关键词 Harmine derivative Cystic echinococcosis Cyst weight Transmission electron microscope HISTOPATHOLOGY
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去氢骆驼蓬碱在大鼠体内代谢产物与代谢途径的UPLC-Q-TOF-MS分析
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作者 卡地尔亚·库尔班 王长虹 +3 位作者 徐楠 徐勤伟 滕亮 高惠静 《中国实验方剂学杂志》 CAS CSCD 北大核心 2024年第11期202-209,共8页
目的:采用超高效液相色谱-四极杆-飞行时间质谱法(UPLC-Q-TOF-MS)鉴定去氢骆驼蓬碱在大鼠体内的代谢产物,探究去氢骆驼蓬碱单剂量灌胃给药后在大鼠体内代谢产物分布差异,并推测其代谢途径。方法:SD大鼠单剂量(40 mg·kg^(-1))灌胃... 目的:采用超高效液相色谱-四极杆-飞行时间质谱法(UPLC-Q-TOF-MS)鉴定去氢骆驼蓬碱在大鼠体内的代谢产物,探究去氢骆驼蓬碱单剂量灌胃给药后在大鼠体内代谢产物分布差异,并推测其代谢途径。方法:SD大鼠单剂量(40 mg·kg^(-1))灌胃给予去氢骆驼蓬碱,收集给药后血浆、胆汁、尿液和粪便样品,经处理后运用UPLC-Q-TOF-MS进行分析,采用ACQUITY UPLCTMHSS T3色谱柱(2.1 mm×100 mm,1.8μm),乙腈(A)-0.1%甲酸水溶液(B)为流动相进行梯度洗脱(0~2 min,5%A;2~9 min,5%~35%A;9~9.5 min,35%~100%A;9.5~12 min,100%A;12~12.5 min,100%~5%A;12.5~14 min,5%A),质谱采用电喷雾离子化源(ESI),正离子检测模式,扫描范围m/z 50~1 200。根据得到的化合物相对保留时间、准分子离子峰及特征碎片离子等信息,与文献数据进行比较,鉴定去氢骆驼蓬碱体内代谢产物,并推测其代谢途径。结果:在大鼠血浆、胆汁、尿液和粪便中共鉴定出去氢骆驼蓬碱及其相关代谢产物42个,其中血浆中27个,胆汁中17个,尿液中26个,粪便中13个。涉及的代谢途径包括单羟基化、双羟基化、去甲基化、葡萄糖醛酸化及硫酸化等。结论:去氢骆驼蓬碱可在大鼠体内发生Ⅰ相和Ⅱ相代谢反应,原型药物在体内代谢较快,代谢产物主要经肾脏排泄,可为去氢骆驼蓬碱的药效学和物质基础研究提供参考依据。 展开更多
关键词 去氢骆驼蓬碱 超高效液相色谱-四极杆-飞行时间质谱法(UPLC-Q-TOF-MS) 代谢产物 代谢途径 血浆 胆汁 尿液
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