CN117503828A - 一种防治阿尔茨海默症的组合物及其应用 - Google Patents
一种防治阿尔茨海默症的组合物及其应用 Download PDFInfo
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- CN117503828A CN117503828A CN202311461136.8A CN202311461136A CN117503828A CN 117503828 A CN117503828 A CN 117503828A CN 202311461136 A CN202311461136 A CN 202311461136A CN 117503828 A CN117503828 A CN 117503828A
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Abstract
本发明提供了一种防治阿尔茨海默症的组合物及其应用,属于阿尔茨海默症治疗技术领域。该组合物包含肉苁蓉总苷和大麻二酚,以及药学上可接受的载体,其中肉苁蓉总苷50~80重量份、大麻二酚10~40重量份。本发明证实了肉苁蓉总苷和大麻二酚组成的组合物较单纯肉苁蓉总苷或单纯大麻二酚具有更好的防治阿尔茨海默症作用,组分均来源于天然产物,长期使用无不良反应和毒副作用,值得推广应用。
Description
技术领域
本发明涉及阿尔茨海默症治疗技术领域,特别涉及一种防治阿尔茨海默症的组合物及其应用。
背景技术
阿尔茨海默病(Alzheimer disease,AD)即老年性痴呆,是中枢神经系统退行性病变,主要特征表现为痴呆和大脑中神经元细胞损伤导致的认知功能下降、日常生活能力减弱、记忆力减退,并且随着病情的加重,甚则出现精神行为症状,严重威胁老年人身体健康和生活质量。据国际阿尔茨海默病协会报道,目前全球约有4600万AD患者,预计到2050年将升至1.32亿人。我国AD患病率占所有痴呆类型的62%。
阿尔茨海默症的具体发病机制目前尚未完全研究透彻,只是存在多种假说,包括胆碱能神经元假说、β淀粉样蛋白毒性假说、Tau蛋白假说、胰岛素假说、自由基损伤假说等。针对AD现代医学仍然没有明确的治疗方法,临床治疗AD的药物主要包括胆碱酯酶抑制剂、N-甲基-D-门冬氨酸(NDMA)受体拮抗剂、改善脑代谢/循环药物及神经保护剂等,但上述药物单一靶点的治疗对于阿尔茨海默症这种复杂疾病很难奏效,存在疗效不确切、毒副作用大、口服吸收差等缺点,不适宜长期服用。
随着人口老龄化的逐步加剧,AD患者数逐年增加,已成为重大的医学和社会问题。但基于AD的发病机制复杂、病因不明等原因,迄今为止仍未有防治AD的特效药。天然植物的有效成分或其提取有效部位,可通过多作用途径或多作用靶点来治疗或减缓该类疾病的发生和发展。因此治疗AD的天然植物药具有一定的优势和潜力,对于现阶段国民健康具有重要意义。但天然植物来源的单一有效成分的活性有限,对于治疗阿尔茨海默症这种复杂疾病很难奏效,另外简单提取的中药组合药物受有效成分含量限制,不能完全发挥协同增效作用,因此急需开发安全、高效的防治阿尔茨海默症的天然药物组合物。
发明内容
为了解决上述问题,本发明的目的在于提供一种防治阿尔茨海默症的组合物及其应用。本发明针对现有用于治疗阿尔茨海默症的药物副作用大、长期使用后疗效变差等问题,提供一种效果明确且安全的的治疗阿尔茨海默症的组合物,以满足可以适合长期服用并能够预防或改善阿尔茨海默症的需求。
本发明的发明人经过大量筛选和深入研究,发现将肉苁蓉总苷和大麻二酚组合使用,显示出良好的阿尔茨海默症治疗效果,协同发挥治疗阿尔茨海默症,比单独应用肉苁蓉总苷和大麻二酚效果更显著,从而完成了本发明。本发明的组合物,可以应用于制备用于治疗阿尔茨海默症的药物,或者以预防和治疗为目的的功能性食品。
本发明提供一种防治阿尔茨海默症的组合物,该组合物由以下重量份的原料组成:肉苁蓉总苷:50~80重量份;大麻二酚:10~40重量份。
优选的,组合物由以下重量份的原料组成:肉苁蓉总苷75重量份、大麻二酚25重量份。
进一步的,所述的肉苁蓉总苷中有效物质的含量不小于80wt%。
进一步的,所述的大麻二酚中有效物质的含量不小于80wt%。
进一步的,所述的肉苁蓉总苷是从管花肉苁蓉和/或荒漠肉苁蓉中提取得到。
优选的,所述的肉苁蓉总苷是从管花肉苁蓉中提取。
进一步的,所述的肉苁蓉总苷的制备方法包括以下步骤:
将肉苁蓉药材粉碎,然后加水(液料比为7~9:1)进行煎煮得到提取液,进行2~3次,每次0.5~1.5h,之后过滤所有的提取液并合并,进行减压加热浓缩得到浓缩液,然后将浓缩液进行柱状层析洗脱,用水,20%乙醇和70%乙醇进行洗脱,最后收集70%乙醇的洗脱液,并对洗脱液浓缩干燥,最终得到肉苁蓉总苷。
进一步的,所述的肉苁蓉总苷是以苯乙醇苷类为有效成分,其它成分包括松果菊苷、毛蕊花糖苷、2′-乙酰基毛蕊花糖苷、肉苁蓉苷C、肉苁蓉苷D、异毛蕊花糖苷、管花苷B、管花苷E、盐生肉苁蓉苷D、盐生肉苁蓉苷E中的一种或多种。
进一步的,所述的大麻二酚制备过程包括:
将工业大麻花叶粉碎,加入70~80wt%乙醇水溶液(液料比为15~25:1)回流提取2~4次得到提取液,每次0.5~1.5h,之后过滤所有的提取液并合并,进行减压加热浓缩得到浓缩液,对浓缩液使用正己烷(浓缩液的2~3倍体积)进行萃取,取上层溶液经分子蒸馏,正庚烷结晶,过滤干燥,得到大麻二酚。
进一步的,所述防治阿尔茨海默症组合物的使用剂量,应根据病人的年龄、体重、健康状况及剂型的不同而定,组合物推荐的使用剂量为5~20mg/kg/d,但是由于本发明的原料成分均有着很强的安全性,本领域的技术人员可以根据个体需要,适当增加有效用量。
优选的,所述组合物使用剂量为10mg/kg/d。
本发明所提供的组合物在制备用于防治阿尔茨海默症的药物中的应用。
本发明所提供的组合物在食品领域的应用。
在本发明的一种实施方式中,所述防治阿尔茨海默症药物包括但不限于:片剂、胶囊剂、口服液、口含剂、颗粒剂、丸剂、散剂、膏剂、丹剂、混悬剂、粉剂、栓剂、软膏剂、硬膏剂、霜剂、喷雾剂、滴剂、贴剂、滴丸剂。
优选的,所述防治阿尔茨海默症药物为胶囊剂、颗粒剂、片剂、口服液、糖浆剂。
具体可选的,所述防治阿尔茨海默症药物为片剂、胶囊剂。
在本发明的一种实施方式中,所述防治阿尔茨海默症药物是由上述的肉苁蓉总苷和大麻二酚的组合物和药学上可用载体、辅料组成。
进一步的,所述药学上可用的载体包括但不限于:甘露醇、山梨醇、焦亚硫酸钠、亚硫酸氢钠、硫代硫酸钠、盐酸半胱氨酸、巯基乙酸、蛋氨酸、维生素C、EDTA二钠、一价碱金属的碳酸盐、醋酸盐、磷酸盐或者水溶液、盐酸、醋酸、硫酸、磷酸、氨基酸、氯化钠、氯化钾、乳酸钠、木糖醇、麦芽糖、葡萄糖、果糖、右旋糖苷、淀粉、蔗糖、甘露糖醇、硅衍生物、纤维素及其衍生物、藻酸盐、明胶、聚乙烯吡咯烷酮、甘油、吐温80、琼脂、碳酸钙、碳酸氢钙、表面活性剂、聚乙二醇、环糊精、磷脂类材料、高岭土、滑石粉、硬脂酸钙、硬脂酸镁。
进一步的,所述辅料包括但不限于:包含溶剂、抛射剂、增溶剂、助溶剂、乳化剂、着色剂、黏合剂、崩解剂、填充剂、润滑剂、润湿剂、渗透压调节剂、稳定剂、助流剂、矫味剂、防腐剂、助悬剂、包衣材料、芳香剂、抗黏合剂、整合剂、渗透促进剂、pH值调节剂、缓冲剂、增塑剂、表面活性剂、发泡剂、消泡剂、增稠剂、包合剂、保湿剂、吸收剂、稀释剂、絮凝剂与反絮凝剂、助滤剂以及释放阻滞剂。
本发明与现有技术相比,具有如下优点及有益效果:
(1)组合物来源,有一定中医和现代药效学研究基础;
肉苁蓉为列当科植物肉苁蓉Cistanche deserticola Y.C.Ma或管花肉苁蓉Cistanche tubulosa(Schenk)Wight的干燥带鳞叶的肉质茎,主要分布于我国西北地区,被称为“沙漠人参”,被列为上品,其性温,味甘、咸,归肾、大肠经,有补肾阳、益精血、润肠便的功效。可用于肾阳不足、精血亏虚所致的阳痿、不孕、腰膝酸软、筋骨无力、肠燥便秘等症。肉苁蓉总苷为补肾阳、提高免疫功能、抗老年痴呆症的活性成分,是从肉苁蓉中提取得到的一类由咖啡酸、糖基和苯乙醇苷元这3个部分构成的化合物,包括松果菊苷、毛蕊花糖苷、2′-乙酰基毛蕊花糖苷、肉苁蓉苷C、肉苁蓉苷D、异毛蕊花糖苷、管花苷B、管花苷E、盐生肉苁蓉苷D、盐生肉苁蓉苷E等,具有益精填髓、延缓衰老和健脑益智等多种功效。其作用机制主要包括:①抗氧化、清除自由基、提高突触可塑性;②抑制抑制神经炎症、减缓海马衰退有关。
几千年来,大麻作为药用植物在历代本草均有详细的记载,《本草纲目》中记载大麻“治健忘及金疮内漏”,现代研究表明,大麻素参与记忆、学习、免疫等多种生理过程,具有保护神经元、促进神经再生等作用。大麻二酚(cannabidiol,CBD)是从大麻花叶中萃取的一种非成瘾性的高附加值的酚类物质,具有抗癫痫、抗痉挛、抗焦虑、抗炎等药理作用,与古代本草记载相吻合。目前,以色列、美国、英国等国家已用其做原料并开发出多种特效药品和化妆品。大麻二酚在治疗老年痴呆症方面也有记载,但其单独使用的治疗效果并不理想。
(2)通过实验动物模型,首创性的发现组合物治疗阿尔茨海默症的药效,保证了本发明产品使用的效果。
(3)大麻二酚已经作为用于治疗儿童癫痫的药物,部分国家允许含大麻二酚的大麻提取物作为食品及食品配料,另外肉苁蓉的药食两用试点工作正在开展,因此本发明组合物的安全性已经得到认可,适合长期使用。
(4)本发明解决现有技术中阿尔茨海默症状无特效药,现有药物毒副作用大问题,具有明显增强记忆改善认知的作用,且安全性好,对于改善记忆和预防阿尔茨海默症具有重大意义。
具体实施方式
原料来源
以下实施例以及对比例中所使用的肉苁蓉总苷和大麻二酚均为云南工麻生物科技有限公司自行制备;肉苁蓉购自西安昊轩生物科技有限公司,工业大麻花叶产自云南工麻生物科技有限公司。
肉苁蓉总苷制备过程包括:粉碎肉苁蓉药材,然后加8倍药材重量的纯净水,煎煮两次,每次1h,过滤后合并水提取液,减压加热回收溶剂浓缩,然后装填入D101大孔吸附树脂柱,用蒸馏水,20%乙醇和70%乙醇分三次洗脱,收集70%乙醇洗脱液,浓缩并干燥得到肉苁蓉总苷。
大麻二酚制备过程包括:工业大麻花叶粉碎,然后加20倍药材重量的80wt%乙醇回流提取两次,每次1h,过滤后合并后,减压加热回收溶剂浓缩,2倍药材量正己烷萃取,上层轻相经分子蒸馏,正庚烷结晶,过滤干燥得到大麻二酚。
肉苁蓉总苷中有效物质的含量≥80wt%,大麻二酚中有效物质的含量≥80wt%。
实施例1
一种含有肉苁蓉总苷、大麻二酚组合物,该组分组合物由下述按质量比计的组分制备而成:肉苁蓉总苷50重量份和大麻二酚10重量份。将各组分混匀,即得。
实施例2
一种含有肉苁蓉总苷、大麻二酚组合物,该组分组合物由下述按质量比计的组分制备而成:肉苁蓉总苷80重量份和大麻二酚10重量份。将各组分混匀,即得。
实施例3
一种含有肉苁蓉总苷、大麻二酚组合物,该组分组合物由下述按质量比计的组分制备而成:肉苁蓉总苷75重量份和大麻二酚25重量份。将各组分混匀,即得。
实施例4
一种含有肉苁蓉总苷、大麻二酚组合物,该组分组合物由下述按质量比计的组分制备而成:肉苁蓉总苷50重量份和大麻二酚40重量份。将各组分混匀,即得。
实施例5
一种含有肉苁蓉总苷、大麻二酚组合物,该组分组合物由下述按质量比计的组分制备而成:肉苁蓉总苷80重量份和大麻二酚40重量份。将各组分混匀,即得。
对比例1
本对比例与实施例1的区别在于:将肉苁蓉总苷替换成等重量份数的大麻二酚。
对比例2
本对比例与实施例1的区别在于:将大麻二酚替换成等重量份数的肉苁蓉总苷。
对比例3
一种含有肉苁蓉总苷、大麻二酚组合物,该组分组合物由下述按质量比计的组分制备而成:肉苁蓉总苷20重量份和大麻二酚40重量份。将各组分混匀,即得本对比例的药物组合物。
对比例4
一种含有肉苁蓉总苷、大麻二酚组合物,该组分组合物由下述按质量比计的组分制备而成:肉苁蓉总苷50重量份和大麻二酚5重量份。将各组分混匀,即得本对比例的药物组合物。
实施例10药物制剂制备
1、片剂
以重量份数计,包括的组方为:肉苁蓉总苷75份、大麻二酚25份、淀粉100份、硬脂酸镁8份、滑石粉2份。将各种物料进行过80目筛,然后混合均匀,压片,分装即可。
2、颗粒剂
以重量份数计,包括的组方为:肉苁蓉总苷75份、大麻二酚25份、甘露醇50份、麦芽糊精100份、二氧化硅10份、三氯蔗糖6份。将各种物料进行过80目筛,然后混合均匀,制粒,分装即可。
3、胶囊剂
以重量份数计,包括的组方为:肉苁蓉总苷75份、大麻二酚25份、麦芽糊精100份、硬脂酸镁10份。将各种物料进行过80目筛,然后混合均匀,装胶囊即可。
实施例11测试试验
1.肉苁蓉总苷含量测定
准确称量松果菊苷对照品10mg,加入50%甲醇,定容至100mL容量瓶内。分别量取0.2mL、0.4mL、0.6mL、0.8mL、1.0mL置于10mL容量瓶中,加50%甲醇至刻度。配制不同浓度(以C表示)的标准溶液,在378nm波长处测定标准品溶液的吸光度A,绘制标准曲线。取实施例样品,按上述稀释方法操作,于378nm处测定吸光度,按标准曲线计算得肉苁蓉总苷含量。
2.大麻二酚含量检测
色谱条件色谱柱:InertSustain C18柱(4.6x250 mm,5μm;流速:1.0mL/min;检测波长:220nm;进样量:10μL;柱温:30℃;以甲醇:水(85:15)为流动相进行等度洗脱。在此色谱条件下,取CBD对照品和实施例样品分别进样分析。
3.稳定性测试
将实施例1~4制得的组合物于温度40℃±2℃、相对湿度75%±5%的条件下放置6个月,每个月观测片剂的外观性状变化,理化指标含量变化(肉苁蓉总苷含量和大麻二酚含量),结果分别见表1~2。检测结果可知本发明工艺组合物肉苁蓉总苷含量和大麻二酚含量稳定,未发生显著性变化。
表1实施例各组加速试验期间肉苁蓉总苷含量变化
表2实施例各组加速试验期间大麻二酚含量变化
4.改善记忆作用的实验研究
4.1实验方法
4.1.1AD实验动物模型的建立和动物处理
模式动物品系选择SPF级ICR小鼠,健康,雄性,体重为22g~25g,由辽宁长生生物技术有限公司提供。按照《中国动物管理条例》标准饲养动物和执行动物实验,适应性喂养2周后体重24~28g。实验分组分为正常对照组、AD模型组、阳性药组、实施例1~4给药组、对比例1~~4给药组,总共11组,每组10只。
除了正常对照组,采用β-淀粉样蛋白(具体为Aβ1-40,购于Sigma公司)注射至海马诱导小鼠为AD小鼠的建模方法进行建模方式。具体为:小鼠腹腔注射5%水合氯醛溶液麻醉,用量为6.7μl/g。麻醉后继而固定于脑立体定位仪上。待小鼠四肢对夹钳无反应后,固定小鼠于定位仪小鼠适配器上。剔去小鼠头部毛发,备皮,进行碘酒消毒,之后将小鼠颅骨暴露,并用镊子去掉皮下骨膜层,暴露前后囟、找到人字缝和矢状缝。此时需利用定位针进行定位,确定前后囟高度一致,矢状缝在一条直线上。然后用定位针确定侧脑室注射位置,在前囟后2.46mm,矢状缝两侧旁开2.0mm处做好标记,使用10μl微量注射器自颅骨表面垂直进针2mm。注射针吸入Aβ1-40,对照组双侧每侧侧脑室缓慢注射3μl生理盐水,AD组和阳性药物组双侧每侧侧脑室缓慢注射3μl(3.4ug/μl)老化的Aβ1-40(1μL/min),原处留针约5min使溶液完全吸收后,然后拔出注射针。最后消毒并将小鼠表皮缝合,大腿肌肉注射庆大霉素1mg/kg。
正常对照组、AD模型组灌胃生理盐水,每天一次,阳性药组灌胃盐酸美金刚3mg/kg/d,按人体口服推荐量的10倍作为给药剂量,实施例和对比例的给药组在受试药物配制好后给小鼠灌胃100mg/kg受试物,(使用剂量参考“肉苁蓉总苷对SAMP8小鼠学习记忆能力及突触可塑性的影响”,以及EPIDIOLEX(大麻二酚)口服溶液使用说明书)连续给药21天后开展下述实验。
4.1.2AD学习与记忆行为测试
通过跳台试验和Morris水迷宫实验开展学习能力和记忆能力测试。
4.1.2.1跳台试验
跳台装置为一个20cm×20cm×30cm的长方体,底面放置一个可供小鼠站立的绝缘橡胶平台并通以36V电流。该实验连续进行2天,第1天为学习训练阶段,先将小鼠放置在跳台测试箱内自由活动3min适应环境后,将小鼠放置在绝缘平台上,底部铜栅通电连续刺激300秒,小鼠受电击后跳上平台躲避电击,若小鼠不跳上平台,则由实验操作人员手动指引到绝缘平台上;第2天为测试阶段,将小鼠放置在绝缘平台上,然后使底部铜栅通电,将小鼠第一次跳下平台的时间记录为潜伏期,300秒内跳下平台的次数记录为错误次数,若300秒小鼠未跳下平台,则潜伏期记录为300秒。停止给予受试物继续饲养,5天后进行消退实验。
表3实施例各组对小鼠跳台试验中潜伏期的影响(x±SE)
注:与对照组比较▲P<0.05,▲▲P<0.01;与模型组比较,*P<0.05,**P<0.01;与实施例相比,#P<0.05,##P<0.01。
由表3试验结果显示,与对照组相比,AD模型组小鼠的跳台潜伏期明显减少(P<0.01),错误次数明显增加(P<0.01)。实施例1~4组较AD模型组潜伏期明显延长(P<0.01),错误次数明显降低(P<0.01)。结果表明,本发明对小鼠的认知障碍有明显改善作用。对比例1~4组较实施例1~4组潜伏期明显减少(P<0.05,P<0.01),错误次数明显增加(P<0.01),说明按照本发明组合物配方效果好,可更好地提高AD模型小鼠的学习记忆能力,且组合物原料和比例缺一不可。
4.1.2.1Morris水迷宫实验
包括潜伏期实验和穿台实验
所谓潜伏期实验,是指每只小鼠测试中从同一个位置入水,须有实验人员辅助小鼠缓慢入水。为了保证小鼠游泳上台环境尽量相同,注意补水保持平台距离水面2cm,小鼠入水后开始计时,记录小鼠在120秒内找到平台的时间即逃避潜伏期,若小鼠在120秒内未找到平台则其逃避潜伏期为120秒,每只小鼠训练完毕后不论是否找到平台均将之放于平台上学15秒。数据采集和处理采用Morris水迷宫图像自动监视处理系统完成。时间越短表明记忆改善效果越好。
所谓穿台实验,是指在前5天水迷宫潜伏期测试之后,第6天撤去水迷宫中的平台,记录小鼠入水后的运动轨迹,与平台位置相交一次记为一次穿台,记录每只小鼠120秒内穿台总次数,次数越多说明记忆改善效果越好。
每只小鼠在前5天在各个象限入水4次,总共落水20次,将最终将得到的时间值汇总取平均值并四舍五入,作为该只小鼠的最终潜伏期,第6天每只小鼠在各个象限入水4次,将得到的4个数字取平均值,为该只小鼠的穿台次数。
如表4结果所示,在水迷宫实验中,模型组与对照组相比错误次数明显增多,模型组小鼠平均到达终点平台的潜伏期显著增加,其全程游泳时间延长,造模成功。阳性药组和实施例1~4组小鼠错误次数明显减少,其游泳时间缩短。对比例组与实施例组相比,相对于AD模型显现了一定记忆改善效果,但没有实施例组效果明显,药效具有显著性差异。
表4 Morris水迷宫实验各组小鼠的逃避潜伏期与平台穿越次数
组别 | 逃避潜伏期(s) | 平台穿越次数 |
对照组 | 26.25±3.72 | 3.46±0.54 |
AD模型组 | 48.41±5.10▲▲ | 0.84±0.31▲▲ |
阳性药组 | 28.85±4.20 | 3.46±0.65 |
实施例1药组 | 30.62±4.65** | 3.85±1.12** |
实施例2药组 | 28.33±3.62** | 4.25±0.85** |
实施例3药组 | 27.12±4.58** | 3.83±0.52** |
实施例4药组 | 29.58±4.39** | 3.35±0.65** |
对比例1 | 36.36±4.31# | 2.40±0.42# |
对比例2 | 35.18±3.35# | 2.21±0.33## |
对比例3 | 34.42±2.88# | 2.6±0.36# |
对比例4 | 34.71±3.53# | 2.12±0.26## |
注:与对照组比较▲P<0.05,▲▲P<0.01;与模型组比较,*P<0.05,**P<0.01;与实施例1相比,#P<0.05,##P<0.01。
上述动物实验显示实验组的组合物显示了在治疗阿尔茨海默病中具有良好的应用前景,即,本发明的组合物具有治疗或者预防阿尔茨海默症的活性,可以用于制备治疗和预防阿尔茨海默症的药物或者功能性食品。
以上所提供的实施例并非用以限制本发明所涵盖的范围,所描述的步骤也不是用以限制其执行顺序。本领域技术人员结合现有公知常识对本发明做显而易见的改进,亦落入本发明权利要求书所界定的保护范围之内。
Claims (10)
1.一种防治阿尔茨海默症的组合物,其特征在于,组合物由以下重量份的原料组成:肉苁蓉总苷:50~80重量份;大麻二酚:10~40重量份。
2.根据权利要求1中所述的组合物,其特征在于,组合物是由以下重量份的原料组成:肉苁蓉总苷75重量份、大麻二酚25重量份。
3.根据权利要求1中所述的组合物,其特征在于,所述的肉苁蓉总苷是从管花肉苁蓉和/或荒漠肉苁蓉中提取得到。
4.根据权利要求1中所述的组合物,其特征在于,所述的肉苁蓉总苷的制备方法包括以下步骤:
将肉苁蓉药材粉碎,然后加液料比为7~9:1的水进行煎煮得到提取液,进行2~3次,每次0.5~1.5h,之后过滤所有的提取液并合并,进行减压加热浓缩得到浓缩液,然后将浓缩液进行柱状层析洗脱,用水,20%乙醇和70%乙醇进行洗脱,最后收集70%乙醇的洗脱液,并对洗脱液浓缩干燥,最终得到肉苁蓉总苷。
5.根据权利要求1中所述的组合物,其特征在于,所述的肉苁蓉总苷是以苯乙醇苷类为有效成分,其它成分包括松果菊苷、毛蕊花糖苷、2′-乙酰基毛蕊花糖苷、肉苁蓉苷C、肉苁蓉苷D、异毛蕊花糖苷、管花苷B、管花苷E、盐生肉苁蓉苷D、盐生肉苁蓉苷E中的一种或多种。
6.根据权利要求1中所述的组合物,其特征在于,所述的大麻二酚制备过程包括:
将工业大麻花叶粉碎,加入液料比为15~25:1的70~80wt%乙醇水溶液回流提取2~4次得到提取液,每次0.5~1.5h,之后过滤所有的提取液并合并,进行减压加热浓缩得到浓缩液,对浓缩液使用体积是浓缩液的2~3倍的正己烷进行萃取,取上层溶液经分子蒸馏,正庚烷结晶,过滤干燥,得到大麻二酚。
7.权利要求1~6任一项所述的组合物在制备用于防治阿尔茨海默症的药物中的应用。
8.根据权利要求7中所述的应用,其特征在于,所述的用于防治阿尔茨海默症的药物包括:片剂、胶囊剂、口服液、口含剂、颗粒剂、丸剂、散剂、膏剂、丹剂、混悬剂、粉剂、栓剂、软膏剂、硬膏剂、霜剂、喷雾剂、滴剂、贴剂、滴丸剂。
9.根据权利要求7中所述的应用,其特征在于,所述防治阿尔茨海默症药物是由所述防治阿尔茨海默症的组合物和药学上可用载体、辅料组成。
10.权利要求1~6任一项所述的组合物在食品领域中的应用。
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