反相高效液相色谱法测定血浆中多奈哌齐浓度

 目的建立反相高效液相色谱法测定人血浆中多奈哌齐浓度。方法采用美国Waters公司680型高效液相色谱仪,486紫外可变波长检测器,YMC-PackODS(150mm×3.9mm,5μm)色谱柱，柱温62℃，以CH-3OH-0.01mol·L^-1NH4H2PO4=65∶35(pH7.50)为流动相，甲泼尼龙做内标，在314nm波长处检测。结果标准曲线线性范围1.00～20.00μg·L^-1；萃取回收率71.6%～76.0%；加样回收率99.8%～108.9%；日内RSD为2.7%～10.3%，日间RSD为1.8%～9.9%。结论本方法快速、灵敏、准确、简便，可用于多奈哌齐血药浓度测定和药动学及生物利用度研究。     

盐酸多奈哌齐透过小鼠血脑屏障的动态研究

目的　了解多奈哌齐透过小鼠血脑屏障的转运机制。方法　采用反相高效液相色谱法及Integrationplot法定量解析 ,以多奈哌齐在脑内浓度 (cb)对血浆中浓度 (cp)比值 (Kp)为纵轴 ,血浆中浓度曲线下面积对血浆中浓度比 (AUC/cp)为横轴 ,通过计算机模拟软件进行Integrationplot并求出药物流入脑内的速度常数 (K1)及排出速度常数 (K2 )的比值 ,以此定量反映药物移行入脑的过程。结果　Integrationplot所得结果为抛物线 ,K1(mL·s-1g-1) =0 .0 0 12 1± 0 .0 0 0 16 ,K2 (s-1) =0 .0 0 2 2 7± 0 .0 0 0 37,K1/K2 =0 .5 4 1,当AUC/cP 值在 2 0 0 0s左右时 ,KP 值达到稳定状态。显示多奈哌齐在初期向脑内快速转运 ,后期多奈哌齐的脑内转运和泵出逐渐达到平衡状态。结论　脑内存在着运载多奈哌齐排出脑组织的载体     

复方海蛇胶囊联合盐酸多奈哌齐治疗阿尔茨海默病临床观察

目的探讨复方海蛇胶囊(RSC)联合盐酸多奈哌齐治疗阿尔茨海默病(AD)的有效性及安全性。方法 96例AD患者随机分为RSC组30例、盐酸多奈哌齐组32例和联合用药组34例,RSC组给予复方海蛇胶囊口服;盐酸多奈哌齐组给予盐酸多奈哌齐口服;联合用药组同时口服复方海蛇胶囊和盐酸多奈哌齐;连续用药6个月。观察3组患者治疗前后智能状态量表(MMSE)、日常生活能力量表(ADL)、认知次级量表(ADAS-Cog)、痴呆程度评定量表(CDR)以及副反应量表(TESS)评定情况。结果治疗后各组MMSE评分均大于治疗前(P<0.05),ADL、ADAS-Cog、CDR评分均小于治疗前(P均<0.05);3组不良反应发生率比较无显著性差异(P>0.05)。结论复方海蛇胶囊联合盐酸多奈哌齐治疗AD安全、有效,疗效优于单一药物,且不良反应发生率低。     

金钱草颗粒剂质量标准的研究

目的探讨金钱草颗粒剂的质量标准。方法采用TLC对金钱草颗粒剂处方中的柴胡、延胡索及大黄进行定性鉴别;采用HPLC对其主药金钱草中的槲皮素进行定量分析。结果该方法定性鉴别薄层色谱特征明显,专属性强;样品中槲皮素在1.8960～30.3360μg·mL-1内线性关系良好（r=0.9998）,平均回收率为97.73%,RSD=1.34%。结论用该方法作定性、定量分析简便、快速、专属性强,可有效控制制剂的质量。     

A systematic review of the efficacy of donepezil hydrochloride combined with nimodipine on treating vascular dementia

Background:Vascular dementia (VaD) is a comprehensive syndrome related to the damage of cognitive function and various cerebral vascular illnesses. VaD is also generally recognized as the second most common type of dementia after Alzheimer disease, contributing to 30% of the dementia population in Asia and developing countries. The ability of donepezil hydrochloride and nimodipine had been respectively proven in improving cognitive function in vascular dementia. However, whether the combined application of both drugs contribute to better efficacy remains as a research hotspot. Studies had shown definite satisfactory result with such combination, however evidence-based evaluation of the efficacy is still lacking. Therefore, meta-analysis is employed in this study to evaluate the efficacy and safety of using donepezil hydrochloride combined with nimodipine in treating VaD to provide references for clinical treatments. The efficacy of donepezil hydrochloride combined with nimodipine on treating vascular dementia is systematically reviewed to provide evidence-based references for clinical applications.Methods:Both Chinese and English databases were searched from the start till August, 2020 for any RCT regarding the combined use of the 2 drugs in treating vascular dementia. Two investigators would later evaluate and screened out research and data based on an improved Jaded scale. Software Rev Man 5.3.0 was employed to carry out meta-analysis on clinical effificacy, mini-mental state examination (MMSE) ratings, activity of daily living (ADL) ratings, and clinical dementia scale (CDR) ratings.Results:Donepezil hydrochloride combined with nimodipine had demonstrated satisfactory efficacy on the treatment of vascular dementia. Improvements were namely spotted on MMSE scale, ADL scale, and CDR scale, with the utmost efficacy by 12 weeks after intervention.Conclusions:Donepezil hydrochloride combined with nimodipine had good efficacy in the treatment of patients with vascular dementia, mainly in terms of improving the Simple MMSE scores, the ability to use daily living scale (ADL) scores and the CDR, and the best results were obtained after 12 weeks of intervention. Such conclusion should be cautiously evaluated.     

盐酸多奈哌齐片人体生物等效性研究

目的进行试验制剂盐酸多奈哌齐片与参比制剂安理申的生物等效性试验,为新药报批及其临床应用提供试验依据.方法用单剂双交叉试验,健康志愿者18名,分别于试验当日晨空腹一次口服试验制剂盐酸多奈哌齐片和参比制剂安理申10mg,采用高效液相色谱法测定盐酸多奈哌齐经时血浓度.结果试验制剂盐酸多奈哌齐片和参比制剂主要药代动力学参数t1/2(β)分别为(54.28±10.14)h和(53.53±9.919)h,Tpeak分别为(3.50±1.15)h和(3.0±1.125)h,Cmax分别为(87±17)ng/mL和(99±23)ng/mL,AUC0～t分别为(2719±1124)ng/mL·h和(3127±1299)ng/mL·h,AUC0～∞分别为(3072±1324)ng/mL·h和(3525±1517)ng/mL·h.试验制剂盐酸多奈哌齐片相对生物利用度为(103.34±14.29)%.结论盐酸多奈哌齐片与参比制剂安理申具有生物等效性,为生物等效制剂.     

盐酸多奈哌齐联合脑脉通治疗老年痴呆的作用机制研究

目的探讨盐酸多奈哌齐联合脑脉通治疗老年痴呆的作用机制。方法选择无特定病原体(SPF)级健康雄性SD大鼠50只作为研究对象,随机分为空白组、模型组、盐酸多奈哌齐组、脑脉通组与联合用药组,每组10只。除空白组外,其余各组采用皮下注射D-半乳糖和聚集肽Aβ25~35制备老年痴呆大鼠模型。建模成功后,盐酸多奈哌齐组给予盐酸多奈哌齐0.85 mg/(kg·d)灌胃,脑脉通组给予脑脉通复方制剂1.50 g/(kg·d)灌胃,联合用药组同时给予盐酸多奈哌齐和脑脉通灌胃,空白组和模型组给予生理盐水2.50 mL/(kg·d)灌胃,持续灌胃8周。分别于给药前、给药1周、3周、5周和8周时测定血清糖萼损伤标志物(Syndecan-1、硫酸乙酰肝素)水平。于给药8周后处死各组大鼠,观察各组大鼠脑组织形态,检测脑组织匀浆中白细胞介素(IL)-6、IL-1及肿瘤坏死因子-α(TNF-α)含量和脑源性神经营养因子(BDNF)、神经生长因子(NGF)蛋白表达水平。结果与模型组比较,盐酸多奈哌齐组、脑脉通组和联合用药组脑组织海马神经细胞排列恢复一定的规律性,数量增多。与模型组比较,盐酸多奈哌齐组、脑脉通组与联合用药组炎性因子水平均降低(P<0.05或P<0.01)。与模型组比较,盐酸多奈哌齐组和脑脉通组BDNF、NGF表达水平差异均无统计学意义(P>0.05),联合用药组BDNF、NGF表达水平升高(P<0.01)。与模型组比较,盐酸多奈哌齐组和脑脉通组在灌胃5周时,联合用药组在灌胃3周时,血清Syndecan-1和硫酸乙酰肝素水平降低(P<0.05)。结论盐酸多奈哌齐与脑脉通联合用药对老年痴呆大鼠的改善作用可能是通过保护血管内皮糖萼、抑制炎症反应,进而修复海马神经组织和提高神经营养因子水平实现的。