CN113648292A - 四氢姜黄素在制备提高记忆力的药物或保健品中的用途 - Google Patents
四氢姜黄素在制备提高记忆力的药物或保健品中的用途 Download PDFInfo
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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Abstract
本发明提供了四氢姜黄素在制备提高记忆力的药物或保健品中的用途。本发明还提供了一种四氢姜黄素的固体分散体及其制备方法和用途。通过药效学证明,本发明四氢姜黄素具有明显提高记忆功能,在同等剂量下,药效显著优于姜黄素。
Description
本申请是对申请号为201810468409.4,申请日为2018年05月16日的发明专利申请提出的分案申请。
技术领域
本发明涉及四氢姜黄素的新用途,具体是在制备提高记忆力的药物或保健品中的用途。
背景技术
记忆障碍指个人处于一种不能记住或回忆信息或技能的状态,有可能是由于病理生理性的或情境性的原因引起的永久性或暂时性的记忆障碍。记忆包括识记、保持、再现,与神经心理功能有密切关系。根据神经生理和生化研究将记忆分为瞬时记忆(分、秒之内)短时记忆(几天)和长时记忆(月、年)。记忆和遗忘是伴随的,遗忘有时间规律和选择性。新近识记的材料遗忘最快,逐渐发展到远事遗忘,曾经引起高度注意的事情较难忘记。
姜黄(RhizomaCurcumaeLongae)为姜科植物姜黄(CurcumaeLongae L.)的干燥根茎,主产于日本、美国、非洲、中国等地,在印度用于调味、食品防腐、美容并入药。姜黄的化学成分主要为姜黄素类及挥发油两大类,此外尚有糖类、甾醇等。姜黄素类主要有姜黄素(Curcumin)、去甲氧基姜黄素(demethoxycurcumin)及双去甲氧基姜黄素(bisdemethoxycurcumin)。姜黄素作为姜黄根茎中的一种主要有效成分,具有抗炎、抗氧化、消除氧自由基、保护肝脏、抗纤维化等多种药理作用,受到国内外广泛的关注。姜黄素在体内迅速代谢为葡萄糖醛酸结合物、硫酸结合物、二氢姜黄素、四氢姜黄素及六氢姜黄素,而二氢与六氢又转化为四氢姜黄素。
四氢姜黄素(Tetrahydrocurcumin,THC)作为姜黄素在体内代谢过程中产生的最为活跃和主要的代谢产物,亦受到国内外广泛关注。研究表明四氢姜黄素具有保肝、抗肿瘤、抗氧化、降血糖、降血脂等药理活性。未见四氢姜黄素可以改善记忆力的报道。
发明内容
本发明的目的是提供四氢姜黄素在制备提高记忆力的药物或保健品中的用途。
本发明提供了四氢姜黄素作为唯一活性成分在制备提高记忆力的药物或保健品中的用途。
进一步地,所述的药物是改善记忆获得障碍、提高记忆力的药物,所述患有学习记忆障碍的疾病包括有阿尔兹海默症、老年痴呆、糖尿病脑病、脑小血管病、血管性痴呆、帕金森病、亨延顿病、癫痫、抑郁症等。
进一步地,所述的药物能升高脑组织CHAT蛋白含量、降低Aβ蛋白含量、降低PS1蛋白含量和/或保护神经元。
进一步地,所述的药物是由四氢姜黄素作为唯一活性成分,加入药学上可接受的辅料或辅助性成分制备成药学上常用的制剂。
进一步地,所述的制剂是固体分散体。
本发明还提供了一种四氢姜黄素固体分散体,它是由如下重量配比的原辅料制备而成:
四氢姜黄素1份、水溶性载体材料1~20份、协同剂0.1~15份;
其中,所述的水溶性载体材料选自聚乙二醇、泊洛沙姆、聚乙烯吡咯烷酮中的一种或几种;协同剂选自多元醇、卵磷脂、吐温中的一种或一种以上的混合物。
进一步地,所述的多元醇为乙二醇、丙二醇、丙三醇中的一种或一种以上的混合物;所述的吐温为吐温20、吐温40、吐温60、吐温65、吐温80、吐温85中的一种或一种以上的混合物。
进一步地,前述的固体分散体是由如下重量配比的原辅料制备而成:
四氢姜黄素1份、聚乙二醇4000 2~12份、吐温80 0.5~10份。
本发明还提供了一种制备前述的固体分散体的方法,它包括如下步骤:
(1)按配比称取原辅料;
(2)取四氢姜黄素和水溶性载体材料、协同剂,采用溶剂法或融熔法,制备固体分散体即可。
本发明还提供了前述的固体分散体的检测方法,它采用高效液相色谱法进行检测,包括如下步骤:
a、对照品溶液的制备:精密称取四氢姜黄素对照品适量,加流动相制成每1ml含10μg的溶液,即得;
b、供试品溶液的制备:精密称取本品内容物150mg,置10ml容量瓶中,精密加入流动相定容,摇匀,超声处理1~10分钟,取出,放至室温,再精密吸取1ml至10ml量瓶中,流动相定容,0.45μm微孔滤膜过滤,滤液即为供试品溶液;所述超声功率不低于100W,频率不小于40kHz;
测定法:分别精密吸取对照品溶液与供试品溶液各5~15μl,注入液相色谱仪,测定;
c、色谱条件与系统适应性试验:用十八烷基硅烷键合硅胶为填充剂,乙腈:0.02%~1%磷酸或冰醋酸溶液=30~60:70~40为流动相,检测波长为280nm,理论塔板数按四氢姜黄素计算应不低于1000~3000。
综上,通过药效学证明,本发明四氢姜黄素具有明显提高记忆功能,在同等剂量下,药效显著优于姜黄素,临床应用前景优良。
显然,根据本发明的上述内容,按照本领域的普通技术知识和惯用手段,在不脱离本发明上述基本技术思想前提下,还可以做出其它多种形式的修改、替换或变更。
以下通过实施例形式的具体实施方式,对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
附图说明
图1为小鼠大脑皮层HE染色。
图2为小鼠大脑海马HE染色。
具体实施方式
本发明具体实施方式中使用的原料、设备均为已知产品,通过购买市售产品获得。
实施例1、四氢姜黄素/PEG/吐温80固体分散体
表1.四氢姜黄素/PEG/吐温80固体分散体的投料配比
制备方法:采用熔融法制备。按表1组分比例投料,称取PEG4000、吐温80于70~80℃加热至完全熔融,加入四氢姜黄素,搅匀,继续加热至四氢姜黄素完全溶解,迅速放入冰水浴中冷却固化,粉碎过即得四组四氢姜黄素/PEG/吐温80固体分散体。
实施例2、四氢姜黄素/泊洛沙姆188/吐温80固体分散体
表2.四氢姜黄素/泊洛沙姆188/吐温80固体分散体的投料配比
制备方法:采用熔融法制备。按表2组分比例投料,称取泊洛沙姆188、吐温80于70~80℃加热至完全熔融,加入四氢姜黄素,搅匀,继续加热至四氢姜黄素完全溶解,迅速放入冰水浴中冷却固化,粉碎过即得四组四氢姜黄素/泊洛沙姆188/吐温80固体分散体。
以下通过具体药效学试验证明本发明的有益效果。
试验例1、四氢姜黄素(THC)和姜黄素(Cur)改善东莨菪碱损伤的记忆获得障碍小鼠的学习记忆功能
1、实验方法
(1)实验动物昆明小鼠,雄性,4周龄,购自四川省中医药科学院。
(2)药物用量及分组:正常对照、辅料对照组、模型组、四氢姜黄素固体分散剂(THC)组(200mg/kg)、姜黄素固体分散剂组(200mg/kg),每组各12只动物。
给药方式:采用实验前给药,灌胃给药,0.1ml/10g体重/天,受试样品总给予时间35天,Morris水迷宫实验训练期间(总共10日)继续给样。正常对照组以同等体积蒸馏水灌胃,辅料对照组和模型组灌胃同等体积的溶媒。
(3)测定指标
(3.1)Morris水迷宫实验-定为航行:给药25天后,开始做水迷宫实验,将小鼠面向池壁放入圆形水池中(直径为120cm,高为50cm,水池水深为30cm,离池顶边10cm),水池中一个圆形平台(平台表面设计有一些粗纹便于小鼠抓稳)直径约为6.5cm,高度29cm,藏匿于1cm的水面之下。池水用染料染成白色,记录小鼠找平台的时间(逃避潜伏期)。如果在90s内未找到平台,由试验者将其引上平台,停留5s后放回饲养笼,逃避潜伏期记录为90s。
(3.2)Morris水迷宫实验-空间探索试验:于定位航行结束后次日上午撤除平台,动物在平台正对面位置入水,记录60s的游泳轨迹,测量动物在平台所在象限停留时间及游泳行程。记录穿越原平台的次数。
(3.3)水迷宫训练前10min,除正常对照组外,其余各组腹腔注射东莨菪碱3mg/kg,整个训练和测试期间每天持续给予东莨菪碱。
(3.4)水迷宫实验结束后,取小鼠脑组织,采用免疫组织化学法进行染色后对小鼠海马组织光镜下观察,确定胆碱乙酰转移酶(CHAT)、乙酰胆碱酯酶(AchE)、脑内乙酰胆碱(Ach)表达强弱。
2、实验结果
由表3可见,与对照组比较,模型组在造模后第8、9和10天,小鼠找到平台的时间明显延长(P<0.05,P<0.01);与模型组比较,THC组小鼠在造模后第10天找到平台的时间明显缩短(P<0.01),Cur组小鼠在造模后第10天找到平台的时间缩短(P<0.05),显示THC和Cur可以明显改善东莨菪碱小鼠的学习记忆能力。
注:模型组与正常组相比,*P<0.05,**P<0.01;其余组与模型组相比,△P<0.05,△△P<0.01。
由表4可见,与对照组比较,模型组在造模后第11天的空间探索实验中,小鼠在平台的滞留时间、有效区域运动时间和在第一象限滞留时间均明显缩短,(P<0.01);与模型组比较,THC组小鼠在有效区域运动时间和在第一象限的滞留时间都明显延长(P<0.01),Cur组小鼠在有效区域运动时间和在第一象限的滞留时间都明显延长(分别是P<0.05,P<0.01),显示THC和Cur可以明显改善东莨菪碱小鼠的空间探索记忆能力。
注:模型组与正常组相比,*P<0.05,**P<0.01;其余组与模型组相比,△P<0.05,△△P<0.01。
表5统计结果显示,与辅料对照组相比,模型组组小鼠脑组织CHAT蛋白含量明显降低,具有非常显著的统计学意义(P<0.01)。与模型组相比,THC组小鼠脑组织CHAT蛋白含量显著升高,具有非常显著的统计学意义(P<0.01),Cur组小鼠脑组织CHAT蛋白含量升高,具有显著的统计学意义(P<0.05)。
注:模型组与辅料组相比,*P<0.05;THC组与模型组相比,△P<0.05△△P<0.01。
实验结果证明,本发明四氢姜黄素可以有效明显改善记忆获得障碍,提高记忆力,在同等剂量下,药效显著优于姜黄素,临床应用前景优良。
试验例2、四氢姜黄素(THC)改善D-半乳糖联合三氯化铝损伤的记忆获得障碍小鼠的学习记忆功能
1、实验方法
(1)将4周龄的雄性昆明小鼠随机分为正常对照、辅料对照组、模型组、四氢姜黄素固体分散剂(THC)(200mg/kg)组,每组各12只动物。
采用实验前给药,灌胃给药,0.1ml/10g体重/天,受试样品总给予时间35天,Morris水迷宫实验训练期间(总共10日)继续给样。正常对照组以同等体积蒸馏水灌胃,辅料对照组和模型组灌胃同等体积的溶媒。
实验性AD造模采用ig AlCl3(20mg/kg)联合ip D-半乳糖(120mg/kg)。每日灌胃给予AlCl3:0.1ml/10g体重,腹腔注射D-半乳糖:0.1ml/20g体重。正常对照组小鼠ig等体积MilliQ水(0.1ml/10g体重)和ip等体积生理盐水(0.1ml/20g体重),连续造模70天。
(2)测定指标
Morris水迷宫实验-定为航行:给药25天后,开始做水迷宫实验,将小鼠面向池壁放入圆形水池中(直径为120cm,高为50cm,水池水深为30cm,离池顶边10cm),水池中一个圆形平台(平台表面设计有一些粗纹便于小鼠抓稳)直径约为6.5cm,高度29cm,藏匿于1cm的水面之下。池水用染料染成白色,记录小鼠找平台的时间(逃避潜伏期)。如果在90s内未找到平台,由试验者将其引上平台,停留5s后放回饲养笼,逃避潜伏期记录为90s。
Morris水迷宫实验-空间探索试验:于定位航行结束后次日上午撤除平台,动物在平台正对面位置入水,记录60s的游泳轨迹,测量动物在平台所在象限停留时间及游泳行程。记录穿越原平台的次数。
水迷宫实验结束后,取小鼠脑组织,HE染色观察小鼠海马和皮层的细胞损伤病变程度,免疫组织化学法染色后观察小鼠海马组织中β-淀粉样蛋白(Aβ,Amyloidβ-peptide)、淀粉蛋白前β-分解酶1(BACE)、早老蛋白-1(Presenilin-1,PS1)表达的强弱。
2、实验结果
由表6可见,与对照组比较,模型组在水迷宫实验的第10天,小鼠找到平台的时间明显延长,运动总距离明显增加,具有显著的统计学意义(P<0.05,P<0.01);与模型组比较,THC组小鼠在造模后第10天找到平台的时间明显缩短(P<0.01),运动总距离明显减少(P<0.01),具有显著的统计学意义。显示THC可以明显改善D-半乳糖联合三氯化铝损伤小鼠的学习记忆能力。
注:模型组与正常组相比,*P<0.05,**P<0.01;其余组与模型组相比,△P<0.05,△△P<0.01。
表7统计结果显示,与对照组相比,模型组小鼠脑组织Aβ蛋白含量明显升高,具有显著的统计学意义(P<0.01)。与模型组相比,THC组小鼠脑组织Aβ蛋白含量明显降低,具有显著统计学意义(P<0.01)。
注:模型组与辅料组相比,*P<0.05;THC组与模型组相比,△P<0.05△△P<0.01。
表8统计结果显示,与正常对照组相比,模型组小鼠脑组织PS-1蛋白含量明显升高,具有显著的统计学意义(P<0.01)。与模型组相比,THC组小鼠脑组织PS-1蛋白含量降低,具有统计学意义(P<0.05)。
注:模型组与辅料组相比,*P<0.05;THC组与模型组相比,△P<0.05△△P<0.01。
表9统计结果显示,与正常对照组相比,模型组小鼠脑组织BACE蛋白含量明显升高,具有显著的统计学意义(P<0.01)。与模型组相比,THC组小鼠脑组织BACE蛋白含量无明显差异,不具有统计学意义。
注:模型组与辅料组相比,*P<0.05;THC组与模型组相比,△P<0.05△△P<0.01。
如图1和图2所示,小鼠大脑皮层HE染色和海马HE染色结果显示,正常对照组:脑组织被膜完整,皮质层各个细胞层排列整齐有序、形态结构较正常、染色清晰,神经纤维排列致密,海马结构完整,神经元排列整齐,细胞数量未见减少或增加,其中1例(1/6)海马DG区神经元出现少量的坏死,细胞呈三角形,染色较深。溶媒模型组:脑组织被膜完整,皮质层各个细胞层排列整齐、染色清晰,神经纤维排列致密,其中4例(4/6)脑组织大脑皮层细胞排列紊乱、皮层和海马区域分别可见少量的椎体细胞坏死。模型组:本组中5例(5/6)大脑组织的海马区域均可见数量不等的椎体细胞坏死,细胞呈三角形,染色较深;大脑皮层细胞排列紊乱,可见少量的小胶质细胞增生。THC组:本组中有2(2/6)例大脑皮层可见少量的椎体细胞坏死,海马区域细胞排列整齐,未见细胞增生或减少,其余组织大脑皮层和海马区域细胞排列整齐,未见异常。
实验结果证明,本发明四氢姜黄素可以有效升高脑组织CHAT蛋白含量、降低Aβ蛋白含量、降低PS1蛋白含量和/或保护神经元,改善记忆获得障碍,提高记忆力。
综上,本发明四氢姜黄素可以有效提高记忆力,改善记忆获得障碍,为临床改善记忆获得障碍提供了一种新的选择。
Claims (10)
1.四氢姜黄素作为唯一活性成分在制备提高记忆力的药物或保健品中的用途。
2.根据权利要求1所述的用途,其特征在于:所述的药物是改善记忆获得障碍、提高记忆力的药物。
3.根据权利要求2所述的用途,其特征在于:所述的药物能升高脑组织CHAT蛋白含量、降低Aβ蛋白含量、降低PS1蛋白含量和/或保护神经元。
4.根据权利要求1-3任一项所述的用途,其特征在于:所述的药物是由四氢姜黄素作为唯一活性成分,加入药学上可接受的辅料或辅助性成分制备成药学上常用的制剂。
5.根据权利要求4所述的用途,其特征在于:所述的制剂是固体分散体。
6.一种四氢姜黄素固体分散体,其特征在于:它是由如下重量配比的原辅料制备而成:
四氢姜黄素1份、水溶性载体材料1~20份、协同剂0.1~15份;
其中,所述的水溶性载体材料选自聚乙二醇、泊洛沙姆、聚乙烯吡咯烷酮中的一种或几种;协同剂选自多元醇、卵磷脂、吐温中的一种或一种以上的混合物。
7.根据权利要求6所述的固体分散体,其特征在于:所述的多元醇为乙二醇、丙二醇、丙三醇中的一种或一种以上的混合物;所述的吐温为吐温20、吐温40、吐温60、吐温65、吐温80、吐温85中的一种或一种以上的混合物。
8.根据权利要求7所述的固体分散体,其特征在于:它是由如下重量配比的原辅料制备而成:
四氢姜黄素1份、聚乙二醇4000 2~12份、吐温80 0.5~10份。
9.一种制备权利要求6~8任一项所述的固体分散体的方法,其特征在于:它包括如下步骤:
(1)按配比称取原辅料;
(2)取四氢姜黄素和水溶性载体材料、协同剂,采用溶剂法或融熔法,制备固体分散体即可。
10.权利要求6~8任一项所述的固体分散体的检测方法,它采用高效液相色谱法进行检测,包括如下步骤:
a、对照品溶液的制备:精密称取四氢姜黄素对照品适量,加流动相制成每1ml含10μg的溶液,即得;
b、供试品溶液的制备:精密称取本品内容物150mg,置10ml容量瓶中,精密加入流动相定容,摇匀,超声处理1~10分钟,取出,放至室温,再精密吸取1ml至10ml量瓶中,流动相定容,0.45μm微孔滤膜过滤,滤液即为供试品溶液;所述超声功率不低于100W,频率不小于40kHz;
测定法:分别精密吸取对照品溶液与供试品溶液各5~15μl,注入液相色谱仪,测定;
c、色谱条件与系统适应性试验:用十八烷基硅烷键合硅胶为填充剂,乙腈:0.02%~1%磷酸或冰醋酸溶液=30~60:70~40为流动相,检测波长为280nm,理论塔板数按四氢姜黄素计算应不低于1000~3000。
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Non-Patent Citations (4)
Title |
---|
KWOK KIN CHENG等: "Highly Stabilized Curcumin Nanoparticles Tested in an In Vitro Blood–Brain", 《THE AAPS JOURNAL》 * |
廖利等: "四氢姜黄素的研究进展", 《世界科学技术-中医药现代化》 * |
梁艳红: "四氢姜黄素β-环糊精包和物的制备方法研究", 《化学工程与装备》 * |
赵苗等: "姜黄素对阿尔茨海默病模型小鼠记忆获得和巩固障碍的影响", 《湖北科技学院学报(医学版)》 * |
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