CN103156867B - 预防或治疗淀粉样β肽相关疾病或状况的医药组合物 - Google Patents
预防或治疗淀粉样β肽相关疾病或状况的医药组合物 Download PDFInfo
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- CN103156867B CN103156867B CN201210548516.0A CN201210548516A CN103156867B CN 103156867 B CN103156867 B CN 103156867B CN 201210548516 A CN201210548516 A CN 201210548516A CN 103156867 B CN103156867 B CN 103156867B
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- solvent
- polar solvent
- water
- isoacteoside
- benzyl carbinol
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Abstract
一种含有类叶升麻苷与异类叶升麻苷的医药组合物，其能够抑制一淀粉样β肽生成、累积或聚集，于是可以用于预防或治疗与一淀粉样β肽相关的一疾病或状况，其中异类叶升麻苷对该类叶升麻苷的重量比为4:1至1:4。
Description
技术领域
本发明系有关于一种用于预防或治疗一种与淀粉样β肽相关性疾病或状况之医药组合物，其含有作为有效成分的类叶升麻苷与异类叶升麻苷，该有效成分能够抑制淀粉样β肽生成、累积或聚集。
背景技术
美国专利7,087,252B2揭示了一种从管花肉苁蓉(Cistanche tubulosa (Schenk)Wight)的肉质茎所制备之含25-50wt%松果菊苷(echinacoside)及5-15wt%类叶升麻苷(acteoside)的制剂，其可用于抗老年痴呆症(senile dementia)。异类叶升麻苷及多种其它苯乙醇苷类(phenylethanoid glycosides) 已知被包含于该制剂中。
申请人前于WO 2011/157059A1揭示了异类叶升麻苷或其医药学上可接受盐于抑制淀粉样β肽生成、累积或聚集之用途，以及其于制备预防或治疗淀粉样β肽相关之疾病或状况的药物之用途。
美国专利7,087,252B2及WO 2011/157059A1的全部内容通过参考方式被并入本案。
于本申请案中发明人延续WO 2011/157059A1的研究并获得一相关的发明成就。
发明内容
有鉴于淀粉样β肽和其聚集体，容易于生物体内引发各种疾病或状况，因此本发明之一目的为提供一种抑制淀粉样β肽生成、累积或聚集的医药组合物，其可作为食品、饮品、咀嚼物、贴片、皮肤保养品或其他的一添加剂。本发明之另一目的则提供一种预防或治疗淀粉样β肽相关之疾病或状况的医药组合物。
本发明的又一目的为提供一种医药组合物于制备预防或治疗淀粉样β肽相关之疾病或状况的药物之用途。
依本发明内容所完成的一种预防或治疗与一淀粉样β肽相关之一疾病或状况的医药组合物包含作为有效成分的类叶升麻苷与异类叶升麻苷，其中异类叶升麻苷对该类叶升麻苷的重量比为4:1至1:4。
较佳的，该医药组合物中的异类叶升麻苷对该类叶升麻苷的重量比为 4:1至2:3。
较佳的，该医药组合物不含有松果菊苷。
较佳的，该医药组合物能够抑制该淀粉样β肽的生成、累积或聚集。
较佳的，该医药组合物能够抑制该淀粉样β肽细胞外的生成、累积或聚集。
较佳的，该医药组合物能够抑制该淀粉样β肽导致神经元的损伤或凋亡，进而保留、改善或恢复学习与记忆能力。
较佳的，该与淀粉样β肽相关之疾病或状况为阿滋海默氏症、轻度认知障碍、路易氏体失智症、唐氏症、荷兰型类淀粉变性症、关岛帕金森氏症-失智症复合症、大脑淀粉样血管病、包涵体肌炎、额颞叶型失智症、年龄相关性黄斑变性或皮克病。
较佳的，该医药组合物是用于治疗阿滋海默氏症。
较佳的，该医药组合物是用于避免或延迟一生物体罹患阿滋海默氏症。
较佳的，该医药组合物对人体的有效剂量系相当于每日每公斤体重0.2 毫克至4毫克之该有效成分。
较佳的，该医药组合物包含一种萃取自植物的苯乙醇苷制剂作为该有效成分的来源，其中该制剂包含类叶升麻苷与异类叶升麻苷为主要的苯乙醇成分，且异类叶升麻苷的含量大于该类叶升麻苷。
较佳的，该制剂包含12-32%类叶升麻苷及26-46%的异类叶升麻苷，以该制剂的重量为基准。
较佳的，该植物为一管花肉苁蓉。
较佳的，该制剂系经过一包含以下步骤的方法所制备：
a)将该管花肉苁蓉的肉质茎以一第一极性溶剂加予萃取；
b)将步骤a)获得的萃取物于浓缩后加到装有疏水大孔隙聚合物的柱中，使得苯乙醇苷吸附在聚合物上；
c)用第二极性溶剂作为流动相流洗液洗脱该柱以除去游离的化合物，而实质上大部份的苯乙醇苷仍然吸附在聚合物上；以及
d)用第三极性溶剂将苯乙醇苷从聚合物上洗脱下来，得到含有苯乙醇苷的洗脱液，其中第一极性溶剂为水、甲醇、乙醇、水与甲醇的混合溶剂、或水与乙醇的混合溶剂；第二极性溶剂为水；及第三极性溶剂为甲醇、乙醇、水与甲醇的混合溶剂、或水与乙醇的混合溶剂，且该第三极性溶剂与第二极性溶剂相比极性较低；
e)将步骤d)获得的含有苯乙醇苷的洗脱液浓缩再溶于水中，所得到的水溶液与一大孔树脂接触使得其中的苯乙醇苷吸附在大孔树脂上；及
f)依序以一第四极性溶剂和一第五极性溶剂分别对该大孔树脂进行洗脱，其中该第五极性溶剂的极性较该第四极性溶剂为低，使得以该第四极性溶剂洗脱而得的洗脱液不含有类叶升麻苷与异类叶升麻苷，而以该第四极性溶剂洗脱而得的洗脱液仅包含类叶升麻苷与异类叶升麻苷，其中第四极性溶剂及第五极性溶剂为水与甲醇的混合溶剂、或水与乙醇的混合溶剂。
较佳的，该第四极性溶剂为25~35%乙醇水溶液，而该第五极性溶剂则为35~45%乙醇水溶液。
为让本发明之上述和其他目的、特征、和优点能更明显易懂，下文特举出实施例，并配合所附图式，作详细说明。
附图说明
图1显示药物A(类叶升麻苷)、I(异类叶升麻苷)、C(控制组，不含药物)及不同比例之A与I的医药组合物对Aβ1-40在细胞外累积的影响。
图2显示显示药物A(类叶升麻苷)、I(异类叶升麻苷)、C(控制组，不含药物)及不同比例之A与I的医药组合物对Aβ1-42寡聚化的影响。
具体实施方式
许多由淀粉样β肽引发的疾病均具有一种共通的特征-淀粉样β肽聚集体的形成。这些淀粉样β肽聚集体可以例如纤维或斑块的形态出现，并且沉淀在生物体的系统、器官、组织或体液中，进而引发各种疾病或状况。如能有效抑制淀粉样β肽的生成、累积或聚集，应可避免淀粉样β肽形成聚集体而引发的各种疾病或状况，其应可作为有效预防或治疗淀粉样β肽相关疾病或状况的方式之一。
所述“预防”意指避免或延迟疾病或状况在生物体中出现，而所述“治疗”则指减缓或阻止疾病或状况的发展，又或者使生物体的状况回复至较佳或正常的状态。
所述“淀粉样β肽相关性疾病或状况”指此疾病或状况的发生通常与淀粉样β肽的生成、累积或聚集相关，且尤其指此疾病或状况的发生为淀粉样β肽所导致。而当在具有某种疾病或状况之一定比例上的生物体上发现有淀粉样β肽的不正常生成、累积或聚集现象时，亦可认为此疾病或状况为淀粉样β肽相关。另外，当淀粉样β肽的聚集处与疾病或状况所发生的病理特征影响位置相近时，亦可认为此疾病或状况为淀粉样β肽相关。
在下列实施例中，利用表一所提供之测试样品进行Aβ试验，并且与未加入任何测试样品处理的对照组(Vehicle)进行比较。
表一：进行试验之样品
实施例一：神经瘤母细胞株之培养
将原生型(wild type)人类神经瘤母细胞SH-SY5Y培养于Eagle’s Minimumessential Medium(EMEM)/Ham’s F12 medium(1:1混合物)(含 10%FBS,10units/mlpenicillin,10μg/ml Streptomycin)中，而原生型小鼠神经瘤母细胞Neuro-2a则培养于minimum essential medium(MEM)培养基 (含10%FBS,10units/ml penicillin,10μg/mlStreptomycin)中。
实施例二：各样品对Aβ1-40于细胞外的累积测试
将实施例一中的原生型人类神经瘤母细胞SH-SY5Y之培养基置换成化学成份培养基(EMEM/F12medium(Cat.No.12500-062),Hepes 5mM,葡萄糖0.6%,NaHCO33mM,麸酰胺2.5mM,胰岛素25μg/ml,Transferin 100μg/ml,Progestrone 20nM,Putrescine 60μM,亚硒酸钠(Sodium selenite) 30nM,Heparin 2μg/ml)。每个井(well)具有1x105个SH-SY5Y细胞，而培养基体积为300μl。30分钟后，将表一中所示之测试样品分别以50μg/ml 的总浓度加入至不同井中处理24小时，接着以Human Aβ1-40Immunoassay kits(Catalog#KHB3482Invitrogen)分析各井之培养基中的Aβ1-40含量。
人类神经瘤母细胞SH-SY5Y会累积Aβ于细胞外的培养基中，而图1 显示SH-SY5Y井分别经各测试样品处理后，Aβ1-40于培养基中的含量百分比，其系以未加入任何测试样品处理的对照组(C)为比较基准。结果显示为平均值±标准误差，而对照组和测试样品组间之统计差异标示为：***表示P<0.001。
参考图1所示，测试样品A(类叶升麻苷)减少培养基中的Aβ1-40含量约10%，测试样品A:I 40:10(类叶升麻苷40μg/ml+异类叶升麻苷10 μg/ml)则减少培养基中的Aβ1-40含量约22%，而其余测试样品则减少培养基中的Aβ1-40含量约80%。图1结果显示类叶升麻苷+异类叶升麻苷=30 μg/ml+20μg/ml；20μg/ml+30μg/ml；及10μg/ml+40μg/ml异类叶升麻苷(D)的测试样品，与异类叶升麻苷50μg/ml的测试样品具有显著降低 Aβ1-40于细胞外累积的极佳活性。
实施例三：各测试样品对Aβ1-42寡聚化的实验
将干燥的Human Aβ1-42自冰箱取出平衡至室温，加入 1,1,1,3,3,3-Hexa-fluro-2-propanol(HFIP)溶解Aβ1-42至浓度为1mM，而之后在室温下静置1小时。以Hamilton注射器将上述Aβ1-42/HFIP容易进行分装，并且以氮气将HFIP吹干，接着存放于-20°C。将HFIP处理后的 Aβ1-42以PBS溶解，并分别以浓度50μg/ml的测试样品A-D且于4℃下振荡处理24小时，以制备Aβ1-42之寡聚物(oligomer)，并利用thioflavine T结合荧光(Ex=450nm,Em=482nm)以分析Aβ1-42的寡聚化程度。
图2显示表1中的测试样品分别对Aβ1-42寡聚化(oligomerization)的影响，结果以百分比显示，并以未加入任何测试样品处理的对照组(C)为基准。图2结果显示表1中的各测试样品均具有抑制Aβ1-42寡聚化的活性，其中以类叶升麻苷+异类叶升麻苷=30μg/ml+20μg/ml；20μg/ml+30 μg/ml；及10μg/ml+40μg/ml异类叶升麻苷(D)的测试样品，与异类叶升麻苷50μg/ml的测试样品对降低Aβ1-42的寡聚化具有较佳的活性，进而可抑制Aβ形成纤维丝或老年斑块。
综合上述结果，异类叶升麻苷及类叶升麻苷的医药组合物可作为抑制 Aβ生成、累积或聚集之有效成份，预计此医药组合物可有效抑制Aβ导致神经元的损伤或凋亡，以进而保留、改善或恢复学习与记忆能力。此外，根据上述结果，此医药组合物可用于预防或治疗Aβ相关疾病或状况。
所述Aβ相关疾病或状况可包含但不限于阿滋海默氏症、轻度认知障碍、路易氏体失智症、唐氏症、荷兰型类淀粉变性症、关岛帕金森氏症- 失智症复合症、大脑淀粉样血管病、包涵体肌炎、额颞叶型失智症、年龄相关性黄斑变性、皮克病以及其他。另，所述Aβ虽以Aβ中最大量的Aβ1-40 或具有高度纤维形成性的Aβ1-42为例，然亦可包含其他胺基酸片段。
图1及2的结果显示异类叶升麻苷具有较佳的活性，但在实际应用上，异类叶升麻苷为一种含糖分子，不易以化学合成方式制备。以植物来源获得高纯度异类叶升麻苷的成本亦极高。由于图1及2的结果亦显示类叶升麻苷和异类叶升麻苷的混合物作为淀粉样β肽抑制剂具有可比拟于纯异类叶升麻苷的活性，因此假使一医药组合物可包含适当组成比的类叶升麻苷和异类叶升麻苷，则可在兼顾经济效益和医疗功效等实际应用面考量上，将此医药组合物用于代替纯化之异类叶升麻苷于预防或治疗淀粉样β肽相关的疾病或状况。
在本发明的下列实施例中，首先参考美国专利案US7,087,252所述制备含有苯乙醇苷的管花肉苁蓉制剂之方法，其包括下列步骤：a)将管花肉苁蓉的地下部分(肉质茎)以一第一极性溶剂加予萃取；b)将步骤a)获得的萃取物加到装有疏水大孔隙聚合物的柱中，使得苯乙醇苷被吸附在聚合物上；c)用第二极性溶剂作为流动相流洗液洗脱该柱以除去游离的化合物，而实质上大部份的苯乙醇苷仍然吸附在聚合物上；以及d)用第三极性溶剂将苯乙醇苷从聚合物上洗脱下来，得到含有苯乙醇苷的洗脱液，该第三极性溶剂与第二极性溶剂相比极性较低。
上述步骤a)的第一极性溶剂可例如为水、或水与乙醇的混合溶剂。步骤c)的第二极性溶剂为水。步骤d)的第三极性溶剂则可例如包含甲醇、乙醇、水与甲醇的混合溶剂、或水与乙醇的混合溶剂，而第三极性溶剂较佳为水与乙醇的混合溶剂。
本发明提供了一种进一步纯化方法，其系直接将上述含苯乙醇苷的管花肉苁蓉制剂经进一步纯化，以得到仅含有类叶升麻苷与异类叶升麻苷之苯乙醇苷的医药组合物。此进一步纯化方法包括步骤：e)将含有多种苯乙醇苷的管花肉苁蓉制剂以大孔树脂进行纯化；f)依序以第四极性溶剂与第五极性溶剂分别对大孔树脂进行洗脱，其中第四极性溶剂的极性较第五极性溶剂为低，使经由第五极性溶剂洗脱而出的苯乙醇苷大抵仅包含类叶升麻苷与异类叶升麻苷。在一较佳实施例中，第四极性溶剂可例如为25~35% 乙醇水溶液，而第五极性溶剂则可例如为35~45%乙醇水溶液。
较佳的，该疏水大孔隙聚合物及大孔树脂为交联聚芳族物质，更佳的为交联的聚苯乙烯，或交联的苯乙烯和二乙烯苯共聚物，例如D-101型或 AB-8型的材料。
将上述经第五极性溶剂洗脱后的洗脱液进行浓缩或干燥，即可直接得到实质上仅含异类叶升麻苷与类叶升麻苷之苯乙醇苷的医药组合物。
实施例四：仅含有异类叶升麻苷与类叶升麻苷之苯乙醇苷的医药组合物
将管花肉苁蓉药材10kg，切成饮片，加8倍量水浸泡1小时后煎煮提取2小时，过滤，滤液备用。药渣再加6倍量水煎煮提取2次，每次1 小时，过滤。合并三次滤液，减压浓缩至比重1.10(50℃)，加乙醇至含醇量达60%，冷藏12小时，倾出上清液，将残留的悬浊液过滤，合并上清液和滤液，减压浓缩并回收乙醇至比重1.10(50℃)，得提取浸膏。
将提取浸膏6kg加1倍量水加热溶解，徐徐注入已处理好的大孔吸附树脂柱内，先用水洗脱，收集药材4倍量水洗脱液备用；再用40%乙醇洗脱，收集药材5倍量40%乙醇洗脱液备用。将水洗脱液再注入大孔吸附树脂柱中，先用药材3倍量水洗脱，弃去水洗脱液；再用40%乙醇洗脱，收集药材4倍量40%乙醇洗脱液备用。合并2次40%乙醇洗脱液，浓缩，干燥，即得含有苯乙醇苷的制剂1107g。
以高效液相色谱法测定，溶剂A:含0.1%甲酸的乙腈(acetonitrile, CAN)，溶剂B:含0.1%甲酸的MQ-H2O，柱:Agilent Zorbax SB-C18柱,2.1 x150mm,5μm；流速:0.3ml/min；UV波长:333nm。上述苯乙醇苷制剂中的松果菊苷、类叶升麻苷以及异类叶升麻苷之含量，经计算后所得之结果分别为33.6wt%、3.65wt%以及6.05wt%。
将200公克上述含苯乙醇苷的制剂溶于800克水中，以一溶液形式流经大孔树脂以便进行纯化。接着依序先后分别以30%乙醇和40%乙醇进行洗脱。在薄层析片(聚酰胺(Polyamide))以UV 365nm检测个别的洗脱液，其中30%乙醇的洗脱液中未包含类叶升麻苷与异类叶升麻苷，而40%乙醇的洗脱液中则仅包含类叶升麻苷与异类叶升麻苷之苯乙醇苷23.6g。在此实施例中，所测得洗脱液中的类叶升麻苷为22.5wt%，而异类叶升麻苷为36.4wt%。
虽然本发明已以数个较佳实施例揭露如上，然其并非用以限定本发明，任何熟习此技艺者，在未脱离本发明所揭示之精神下所完成之等效改变或修饰，均应包含在下述之权利要求内。
Claims (1)
1.一种仅含有类叶升麻苷与异类叶升麻苷的苯乙醇苷的医药组合物的制备方法，其中异类叶升麻苷对类叶升麻苷的重量比为4:1至2:3，所述制备方法包含以下步骤：
a)将管花肉苁蓉的肉质茎以一第一极性溶剂加予萃取；
b)将步骤a)获得的萃取物于浓缩后加到装有疏水大孔隙聚合物的柱中，使得苯乙醇苷吸附在聚合物上；
c)用第二极性溶剂作为流动相流洗液洗脱该柱以除去游离的化合物，而实质上大部分的苯乙醇苷仍然吸附在聚合物上；以及
d)用第三极性溶剂将苯乙醇苷从聚合物上洗脱下来，得到含有苯乙醇苷的洗脱液，其中第一极性溶剂为水、甲醇、乙醇、水与甲醇的混合溶剂、或水与乙醇的混合溶剂；第二极性溶剂为水；及第三极性溶剂为甲醇、乙醇、水与甲醇的混合溶剂、或水与乙醇的混合溶剂，且该第三极性溶剂与第二极性溶剂相比极性较低；
e)将步骤d)获得的含有苯乙醇苷的洗脱液浓缩再溶于水中，所得到的水溶液与一大孔树脂接触使得其中的苯乙醇苷吸附在大孔树脂上；及
f)依序以一第四极性溶剂和一第五极性溶剂分别对该大孔树脂进行洗脱，其中该第五极性溶剂的极性较该第四极性溶剂为低，使得以该第四极性溶剂洗脱而得的洗脱液不含有类叶升麻苷与异类叶升麻苷，而以该第五极性溶剂洗脱而得的洗脱液仅包含类叶升麻苷与异类叶升麻苷；其中该第四极性溶剂为25～35％乙醇水溶液，而该第五极性溶剂则为35～45％乙醇水溶液。
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| TWI650131B (zh) * | 2014-07-03 | 2019-02-11 | 杏輝藥品工業股份有限公司 | 管花肉蓯蓉萃取物之用於製備保護眼部細胞之藥品或食品用途 |
| CN104922137B (zh) * | 2015-06-04 | 2018-07-31 | 苏州大学 | 苯乙醇苷类化合物Torenoside B的新用途 |
| KR102018085B1 (ko) * | 2017-12-06 | 2019-09-04 | 김좌진 | 악테오사이드를 함유하는 뇌종양 치료 및 전이 억제용 약학 조성물 |
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| CN111632058A (zh) * | 2020-06-24 | 2020-09-08 | 新疆医科大学 | 毛蕊花糖苷在制备预防和治疗神经退行性疾病药物中的应用 |
| CN112225766A (zh) * | 2020-10-27 | 2021-01-15 | 杏辉天力（杭州）药业有限公司 | 一种由肉苁蓉萃取物中富集及分离苯乙醇苷类化合物的方法 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1526400A (zh) * | 2003-03-04 | 2004-09-08 | 杭州天力药业有限公司 | 来源于管花肉苁蓉的含有苯乙醇苷的制剂及其制备方法和用途 |
| CN1721425A (zh) * | 2004-07-16 | 2006-01-18 | 北京华医神农医药科技有限公司 | 一种从肉苁蓉药材中提取、分离松果菊苷的方法 |
| CN101411753A (zh) * | 2008-12-04 | 2009-04-22 | 闫明 | 列当提取物、列当总苷和列当多糖及其制备方法和用途 |
| CN101797307A (zh) * | 2010-04-09 | 2010-08-11 | 广州中医药大学 | 一种含苯乙醇苷的枇杷叶紫珠提取物及其制备方法 |
| EP2397144A1 (en) * | 2010-06-16 | 2011-12-21 | Sinphar Tian-li Pharmaceutical Co., Ltd. (Hangzhou) | Use of Isoacteoside in Preventing or Treating Amyloid Beta Peptide-Associated Diseases or Conditions, and Method for Inhibiting Formation, Accumulation or Aggregation of Amyloid Beta Peptides |
| CN102670631A (zh) * | 2011-12-01 | 2012-09-19 | 河南科技大学 | 一种四楞麻总苯乙醇苷组合物、制备方法及应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100500584B1 (ko) * | 2002-08-12 | 2005-07-12 | 경희대학교 산학협력단 | 신경성장인자와 유사 작용을 갖는 육종용 추출물 및 이를함유하는 조성물 |
| KR100514076B1 (ko) * | 2003-01-10 | 2005-09-13 | 주식회사 엘컴사이언스 | 페닐에타노이드 유도체를 포함하는 퇴행성 뇌신경계질환의 예방 및 치료용 조성물 |
| TW200416036A (en) * | 2003-02-18 | 2004-09-01 | Sinphar Pharmaceutical Co Ltd | Medicinal preparation containing phenylethanoid glycosides extracted from herbaceous plant, cistanche tubulosa (schenk.) wight, process of making the same, and uses of the same |
| EP1736167B1 (en) * | 2005-06-20 | 2018-03-21 | I.R.B. Istituto Di Ricerche Biotecnologiche S.r.l. | Extracts obtained from cell line cultures from Syringa vulgaris IRB-SV25/B (DMS:16857), their preparation and use |
| JP5410683B2 (ja) | 2008-02-19 | 2014-02-05 | 学校法人近畿大学 | カンカニクジュヨウから得られる肝保護剤及び抗ＴＮＦ−α作用剤 |
-
2012
- 2012-12-17 CA CA2859227A patent/CA2859227C/en active Active
- 2012-12-17 KR KR1020147018051A patent/KR102048289B1/ko active IP Right Grant
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- 2012-12-17 US US14/365,404 patent/US20150087606A1/en not_active Abandoned
- 2012-12-17 SG SG11201403265VA patent/SG11201403265VA/en unknown
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1526400A (zh) * | 2003-03-04 | 2004-09-08 | 杭州天力药业有限公司 | 来源于管花肉苁蓉的含有苯乙醇苷的制剂及其制备方法和用途 |
| CN1721425A (zh) * | 2004-07-16 | 2006-01-18 | 北京华医神农医药科技有限公司 | 一种从肉苁蓉药材中提取、分离松果菊苷的方法 |
| CN101411753A (zh) * | 2008-12-04 | 2009-04-22 | 闫明 | 列当提取物、列当总苷和列当多糖及其制备方法和用途 |
| CN101797307A (zh) * | 2010-04-09 | 2010-08-11 | 广州中医药大学 | 一种含苯乙醇苷的枇杷叶紫珠提取物及其制备方法 |
| EP2397144A1 (en) * | 2010-06-16 | 2011-12-21 | Sinphar Tian-li Pharmaceutical Co., Ltd. (Hangzhou) | Use of Isoacteoside in Preventing or Treating Amyloid Beta Peptide-Associated Diseases or Conditions, and Method for Inhibiting Formation, Accumulation or Aggregation of Amyloid Beta Peptides |
| CN102670631A (zh) * | 2011-12-01 | 2012-09-19 | 河南科技大学 | 一种四楞麻总苯乙醇苷组合物、制备方法及应用 |
Non-Patent Citations (5)
| Title |
|---|
| Acteoside protects human neuroblastoma SH-SY5Y cells against β-amyloid-induced cell injury;Hongquan Wang等;《Brain Research》;20090609;第1283卷;第139-147页 |
| 类叶升麻苷对东莨菪碱致小鼠学习记忆障碍的改善作用;林娟等;《中国中药杂志》;20121031;第37卷(第19期);第2956-2959页 |
| 紫珠的水溶性成分;鲁春华等;《中国天然药物》;20080531;第6卷(第3期);第176-178页 |
| 肉苁蓉的神经药理学研究进展;安春娜等;《中国药学杂志》;20110630;第46卷(第12期);第887-890页 |
| 苯乙醇苷类化合物的研究进展;吴培培等;《医药导报》;20111031;第30卷(第10期);第1316-1319页 |
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