高速逆流色谱技术制备石杉碱甲单体

目的从千层塔植物提取物中分离制备石杉碱甲单体。方法利用高速逆流色谱技术,通过寻找合适的两相溶剂体系及工艺参数,研究及讨论石杉碱甲分离制备的新方法。结果以n-Hexane/n-BuOH/H2O(4∶1∶5,V/V/V)为两相溶剂体系,在优化的工艺参数条件下,利用高速逆流色谱技术,获得了单体纯度为98.6%(HPLC)的石杉碱甲单体。结论利用高速逆流色谱技术成功地从千层塔植物提取物中分离制备了纯度高于98%的石杉碱甲单体。     

石杉碱甲治疗多梗死性痴呆20例

目的; 观察石杉碱甲治疗多梗死性痴呆(MID)的临床疗效.方法;20例MID患者均口服石杉碱甲150 μg,bid,连服6周为1个疗程.结果;治疗后患者认知功能MMSE评分(15.92±5.9)分,较治疗前(10.98±4.9)分显著提高(P＜0.05),认知功能改善的总有效率70.0%,其中显效率25.0%,有效率45.0%.结论;石杉碱甲对MID患者的认知功能障碍有一定的改善作用.     

高效液相色谱法测定石杉碱甲片的含量

采用高效液相色谱法测定石杉碱甲片的含量。固定相为μＢｏｎｄａｐａｋ Ｃ１８，流动相为乙腈－０．０２ｍｏｌ／Ｌ磷酸二氢钾溶液（１２：８８），以对乙酰氨基酚为内标，石杉碱甲浓度在１０￣５０ｍｇ／Ｌ范围内与峰面积呈良好的线性关系，平均回收率为９９．９３％，ＲＳＤ为０．４１％（ｎ＝９）。     

光学活性石杉碱甲的不对称全合成

２－甲氧基－６－羟基－７，８－二氢－５－喹啉羧酸甲酯（２）与２－甲基丙烯醛的不对称Ｍｉｃｈａｅｌ反应是石杉碱甲全合成的关键一步。在０．１当量奎宁的存在下，（２）与２－甲基丙烯醛在室温反应１０ｄ，得到收率大于９０％的立体异构体混合物（３），将（３）甲磺酰化后，再进行消除反应，得到（５Ｓ，９Ｒ）（＋）－（５），总收率约为５０％，对映体过量百分率（ｅｅ值）约为５２％，如果以０．１当量奎尼丁作催化剂，得到约为４０％ｅｅ的（５Ｒ，９Ｓ）－（－）－（５）．最后从（５Ｓ，９Ｒ）－（＋）－（５）得到（－）－石杉碱甲。     

Bivalent ligands derived from Huperzine A as acetylcholinesterase inhibitors

The naturally occurring alkaloid Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor that has been used for centuries as a Chinese folk medicine in the context of its source plant Huperzia Serrata. The potency and relative safety of HupA rendered it a promising drug for the ameliorative treatment of Alzheimer's disease (AD) vis-à-vis the "cholinergic hypothesis" that attributes the cognitive decrements associated with AD to acetylcholine deficiency in the brain. However, recent evidence supports a neuroprotective role for HupA, suggesting that it could act as more than a mere palliative. Biochemical and crystallographic studies of AChE revealed two potential binding sites in the active-site gorge of AChE, one of which, the "peripheral anionic site" at the mouth of the gorge, was implicated in promoting aggregation of the beta amyloid (Abeta) peptide responsible for the neurodegenerative process in AD. This feature of AChE facilitated the development of dual-site binding HupA-based bivalent ligands, in hopes of concomitantly increasing AChE inhibition potency by utilizing the "chelate effect", and protecting neurons from Abeta toxicity. Crystal structures of AChE allowed detailed modeling and docking studies that were instrumental in enhancing the understanding of underlying principles of bivalent inhibitor-enzyme dynamics. This monograph reviews two categories of HupA-based bivalent ligands, in which HupA and HupA fragments serve as building blocks, with a focus on the recently solved crystallographic structures of Torpedo californica AChE in complex with such bifunctional agents. The advantages and drawbacks of such structured-based drug design, as well as species differences, are highlighted and discussed.     

石杉碱甲的临床应用研究进展

石杉碱甲(HupA)是一种选择性作用于脑部的可逆性胆碱酯酶抑制剂。近年来,大量研究证明,它在治疗阿尔茨海默病、早老性痴呆、血管性痴呆以及改善学生的学习与记忆能力、脑外伤性记忆功能和认知功能损害等方面有一定的作用。笔者检索相关文献,旨在分析、总结石杉碱甲的临床疗效。     

石杉碱甲片溶出度方法的建立

目的：建立石杉碱甲片的溶出度检查方法。方法：以盐酸溶液（9→1000）100mL为溶出介质,转速为50r·min^-1,取样时间为30min。采用溶出度第三法测定。结果：石杉碱甲在0．13—1．02μg·mL^-1的浓度范围内,线性关系良好。线性方程为：A=103．95C-0．15（γ=1．0）;平均回收率为99．0％（RSD=2．0％）;6批样品30min平均溶出度均在80％以上。结论：本方法简便、准确、重现性好,可用于石杉碱甲片的质量控制。     

石杉碱甲联合美金刚治疗老年性痴呆的临床观察

目的：探讨石杉碱甲联合美金刚治疗老年性痴呆（AD）临床疗效。方法：随机抽取某院门诊及住院老年性痴呆患者42例（年龄69±4.5岁）,分为对照组（20例）,给予石杉碱甲（商品名：哈伯因）及一般常规治疗;试验组（22例）给予石杉碱甲联合美金刚治疗,并给予所有患者简易精神量表（MMSE）、日常生活功能量表（ADL）及神经精神科问卷（NPI）评分,治疗18周后再复查量表评分,用统计学分析方法对终点时两组量表分值作组间对照分析。结果：经组间对照t检验分析结果显示,对照组和试验组MMSE、ADL、NPI有显著性差异（P〈0.05）。结论：石杉碱甲联合美金刚治疗老年性痴呆治疗显效,较单纯应用石杉碱甲对患者的认知功能、日常生活能力及精神行为异常疗效有明显提高。     

Huperzine A reverses scopolamine- and muscimol-induced memory deficits in chick

AIM: To study the effects of huperzine A on disruption of spatial memory induced by scopolamine (a muscarinic antagonist) and muscimol (a GABAA agonist) in passive avoidance task. METHODS: One-trial passive avoidance task was used to investigate the effects of huperzine A. The avoidance rate was used to evaluate memory retention. RESULTS: Both scopolamine (100 ng) and muscimol (50 ng), injected intracranially 5 min before training, resulted in a decreased avoidance rate. Huperzine A (25 ng), injected intracranially 15 min before training, reversed memory deficits induced by scopolamine and muscimol at 30 min after training, and this reversal persisted at least 1 h. The improving effects of huperzine A exhibited a bell-shaped dose-response curve. CONCLUSION: Huperzine A improved the process of memory formation not only by acting as a highly potent and selective inhibitor of AChE, but also by antagonizing effects mediated through the GABAA receptor.     

高效液相色谱法测定石杉碱甲胶囊溶出度

目的 建立石杉碱甲胶囊溶出度的高效液相色谱 方法 . 方法 以盐酸溶液（9→1 000）100 mL为溶出递质,转速为35 r•min^-1,取样时间为30 min,采用溶出度第三法测定. 结果 石杉碱甲在0.13～1.02 μg•mL^-1的浓度范围内,线性关系良好. 线性方程为：A＝103.95C-0.15 （r＝1.000 0）;平均回收率为98.0%（RSD＝0.7%）;4批样品30 min平均溶出度均＞80%. 结论 该 方法 简便、准确、重现性好,可用于石杉碱甲胶囊的质量控制.     

石杉碱甲片治疗阿耳茨海默病的临床疗效

目的；观察石杉碱甲片治疗阿耳茨海默病（ＡＤ）临床疗效。方法：选择符合ＩＣＤ－１０诊断标准的４１例ＡＤ患者，随机给其中治疗组（２３例）投用石杉碱甲０．１５ｍｇｂｉｄ对照组（１８例）投用砒啦西坦１．２ｇｂｉｄ，８ｗｋ为一疗程，疗前，疗后分别进行韦工记忆量表（ＷＭＳ）和简明智力量表（ＭＭＳＥ）的检测和评分比较，结果：两组治疗前，后ＷＭＳ的记忆商（ＭＱ）和ＭＭＳＥ总评分，自身比较有显著性差异（治疗组Ｐ〈０     

石杉碱甲与吡硫醇治疗多梗死性痴呆的比较

目的：研究石杉碱甲对多梗死性痴呆的疗效。方法：治疗组多梗死性痴呆５０例（男性３９例，女性１１例，年龄６６±ｓ８ａ）服用石杉碱甲片１００μｇ，ｔｉｄ，４ｗｋ为一个疗程。另４７例（男性３７例，女性１０例，年龄６４±９ａ）服用吡硫醇片０．２ｇ，ｔｉｄ，作为对照组。结果：治疗组总有效率为６６％，对照组为３８％（Ｐ＜０．０５）。结论：石杉碱甲对多梗死性痴呆有效。     

石杉碱甲磷脂原位凝胶的制备及其在大鼠体内的药动学研究

目的 制备石杉碱甲磷脂原位凝胶(PSE-H)并研究其在大鼠体内的药动学.方法 采用直接载药法制备PSE-H,建立石杉碱甲(Hup A)血浆样品的分析方法,研究不同剂量制剂及制剂中Hup A油酸复合物的形成对PSE-H药动学特征的影响.结果 PSE-H在体内持续释放Hup A达15 d.将Hup A制备成油酸复合物可降低制剂中药物的突释作用;随着制剂重量的增加,缓释作用增强,突释作用降低.结论 通过直接载药法制备PSE-H,方法简便可行,Hup A在体内持续释放达15 d,有望成为可生产的缓控释新剂型.     

石杉碱甲缓释贴片Ⅰ期临床耐受性试验研究

目的 观察健康受试者使用石杉碱甲缓释贴片的安全性及耐受性.方法 40例健康志愿者随机分为单次给药组(n=28)和多次给药组(n=12),单次给药组设2、4、6、9和12 mg共5个剂量组,多次给药组设9和12 mg两个剂量组.观察并记录各组不良反应.结果 单次和多次给药组各发生不良反应10和5例,均为轻度.结论 石杉...     

Huperzine A in rat plasma and CSF following intranasal administration

This paper presents to investigate the levels of Huperzine A in plasma and CSF of rats after three different kinds of administrations and to find out whether intranasal administration is the best route to transfer the drug into the CNS. The drugs of two doses (167 and 500 microg/kg) were administered to male Sprague-Dawley rats intravenously, intranasally and intragastricly, respectively. Series plasma and cerebrospinal fluid (CSF) samples were collected from femoral artery and cisterna magna for 6h. The drug concentrations were determined by HPLC-fluorescence method. The AUC(plasma) and the AUC(CSF) of intranasal administration were 90.3% and 127.7% in low dose group (167 microg/kg) and 91.3% and 69.4% in high dose group (500 microg/kg) compared with intravenous administration. The AUC(plasma) and the AUC(CSF) of intragastric administration were 98.9% and 52.1% in high dose group (500 microg/kg) compared with intravenous administration.     

石杉碱甲的大鼠鼻黏膜吸收研究

目的研究治疗早老性痴呆症药物石杉碱甲的鼻黏膜吸收特性。方法采用石杉碱甲进行大鼠鼻腔灌流实验,测定循环液中药物浓度。结果随着石杉碱甲的浓度增加(0.125~0.75mg/mL),其吸收速度呈线性增加(r=0.995)。在pH值5.5~7.5内,随pH值的升高,其吸收速度增加。结论石杉碱甲的鼻黏膜吸收良好,其吸收程度与药液的浓度和pH值有较好的相关性。     

石杉碱甲-玉米醇溶蛋白微球释放特性的研究

目的建立石杉碱甲-玉米醇溶蛋白微球体外释放的测定方法,并考察载药微球的体外释放特性及影响因素。方法采用高效液相色谱法,色谱条件:色谱柱:ODS-C18色谱柱(4.6 mm×250 mm,5μm);流动相:pH2.5磷酸盐缓冲液-乙腈(86∶14,V/V);检测波长:310 nm;流速:1.0 mL·min-1;柱温:25℃;进样量:20μL。将石杉碱甲载药微球加以不同的释放介质,在摇床中振荡,定时取样并补以新鲜介质,高效液相色谱法测定石杉碱甲的累积释放率,并用不同释药模型对水为介质的释放结果进行拟合。结果建立的高效液相色谱法符合方法学要求,分别以零级、一级、Higuchi以及Ritger-Peppas方程对以水为介质的释药曲线进行拟合,相关系数分别为0.693 8、0.902 5、0.964 6和0.954 7。介质的pH和离子强度不同,药物的释放结果不同。结论石杉碱甲-玉米醇溶蛋白微球在水中的释放符合Higuchi模型,微球中药物的释放机制以扩散为主。不同的pH和离子强度主要是分别通过影响石杉碱甲的溶解度和玉米醇溶蛋白的相对疏水性来影响石杉碱甲从微球中的释放速率。     

石杉碱甲免疫层析试纸条的研制

目的 利用胶体金免疫层析技术建立一种快速检测石杉碱甲的方法。方法 采用柠檬酸三钠还原法制备胶体金颗粒,标记抗石杉碱甲单克隆抗体并于4 ℃保存。石杉碱甲和羊抗鼠二抗分别结合于硝酸纤维膜上,依次将硝酸纤维素膜、金标垫、样品垫、吸水纸组装于PVC底板上,切割成胶体金试纸条。结果 石杉碱甲快速检测试纸条的灵敏度为15 μg·mL^-1,检测时间为5 min,特异性高,批内和批间重复性良好。结论 该法操作简单,使用方便,可用于现场快速检测石杉碱甲。