CN109170891A - 一种改善记忆力的组合物及其制备方法与应用 - Google Patents
一种改善记忆力的组合物及其制备方法与应用 Download PDFInfo
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- CN109170891A CN109170891A CN201811113708.2A CN201811113708A CN109170891A CN 109170891 A CN109170891 A CN 109170891A CN 201811113708 A CN201811113708 A CN 201811113708A CN 109170891 A CN109170891 A CN 109170891A
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Abstract
本发明涉及医药技术领域，提供一种改善记忆力的组合物及其制备方法与应用。一种改善记忆力的组合物，其包括烟酰胺单核苷酸、牛磺酸、磷脂酰丝氨酸、人参皂苷PPD、人参皂苷Rh2、硫酸软骨素、熊去氧胆酸、燕窝酸、s‑腺苷蛋氨酸、γ‑氨基丁酸、虾青素、葡萄籽提取物、焦谷氨酸酯。该改善记忆力的组合物对提高脑供氧量，加速大脑血液循环，提高记忆力具有很大的功效，且处方简单，价格便宜。本发明还提供该改善记忆力的组合物的其制备方法与应用。
Description
技术领域
本发明涉及医药技术领域，尤其涉及一种改善记忆力的组合物及其制备方法与应用。
背景技术
记忆是人脑对经历过的事物的反映。我们见过的人或物、听过的声音、嗅过的气味、品尝过的味道、触摸过的东西、思考过的问题、体验过的情绪和情感等都会在头脑中留下痕迹，并在一定条件下呈现出来，这就是记忆。日常生活中，如发现自己近期记忆力大不如从前，常记不住事，丢三落四、忘记刚刚做过的事情等，这就是我们常说的记忆力减退，在医学上，称为“健忘”。记忆力衰退是多因素的，如老年人的大脑衰老退化，小儿的营养不良等多种情况。目前，市场上的改善记忆力的保健食品多是由鱼油(主要成分EPA、DHA)、卵磷脂、氨基酸等组成。虽说上述各保健食品在技术上各有独到之处，并对记忆力衰退的某些方面具有一定的保健作用，但总体来说，普遍存在如下不足：1、防止记忆力衰退的效果不显著。2、只是具有一定的保健作用，提高记忆力效果不明显。3、配方较单一，很难具有多方面协同作用，不能同时具有增强大脑功能、延缓大脑衰老、提高人体免疫能力、改善失眠健忘、神经衰弱、老年痴呆症状和提高智力的的功效。
国内外防治记忆力障碍或减退的药物有很多，如目前临床常用的奥拉西坦和吡拉西坦等，它们均是通过改善脑部代谢，来达到增强记忆，提高学习能力但目的。但是，这些化学药物或多或少都有人们接受不了的不良反应，而且目前仅用于脑损伤及引起的神经功能缺失、记忆与智能障碍的治疗，无法对普遍的记忆力下降人群用药。目前国内外市场上也有一些健脑补脑的产品，但是大多数存在效果不佳或成份复杂的缺陷。
发明内容
本发明的目的在于克服上述现有技术的缺点，提供一种改善记忆力的组合物及其制备方法与应用。
为解决上述技术问题，发明采用如下所述的技术方案。一种改善记忆力的组合物，其包括如下组分：
优选地，所述改善记忆力的组合物还包括1-10重量份的原料药，所述原料药包括远志、菟丝子、猪牙皂、知母、酸枣仁、小茴香、叶酸中的一种或几种。
优选地，所述原料药至少包括远志、菟丝子、猪牙皂、知母、酸枣仁、小茴香、叶酸中的四种。
优选地，所述改善记忆力的组合物还包括1-10重量份的辅料，所述辅料包括尼泊金复合酯、富马酸、磷酸盐、木糖醇、微晶纤维素、失水山梨醇脂肪酸酯、硬脂酸镁、交联羧甲基纤维素钠、氢氧化镁、预胶化淀、硫酸钙、气相二氧化硅、乳糖中的一种或几种。
优选地，所述辅料至少包括尼泊金复合酯、富马酸、磷酸盐、木糖醇、微晶纤维素、失水山梨醇脂肪酸酯、硬脂酸镁、交联羧甲基纤维素钠、氢氧化镁、预胶化淀、硫酸钙、气相二氧化硅、乳糖中的三种。
优选地，所述烟酰胺单核苷酸、人参皂苷PPD、人参皂苷Rh2之间的重量比优选为3-7：2-5：5-7。
一种改善记忆力的组合物的制备方法，按照上述改善记忆力的组合物的各组分及配比配好并均匀混合。
优选地，所述改善记忆力的组合物的制备方法还包括烟酰胺单核苷酸的制备；所述烟酰胺单核苷酸的制备为：以烟酰胺、ATP和木糖为原料，在烟酰胺磷酸核糖转移酶、核糖磷酸焦磷酸激酶、核糖-5-磷酸异构酶、核酮糖-3-磷酸异构酶、木酮糖激酶以及木糖异构酶的催化作用下发生反应，制得所需的烟酰胺单核苷酸。
优选地，所述烟酰胺单核苷酸的制备包括：将ATP、木糖混合，并加入 MgCl2溶液、KCl溶液及Tris-HCl缓冲液，调pH至7.5-8.0；然后加入核糖磷酸焦磷酸激酶，核糖-5-磷酸异构酶，核酮糖-3-磷酸异构酶，木酮糖激酶及木糖异构酶进行初次反应，分离得到初次反应液后再加入烟酰胺、ZnCl2溶液、 Tris-HCl缓冲液及烟酰胺磷酸核糖转移酶继续反应，即得烟酰胺单核苷酸粗产品溶液，进而提取得到所需的烟酰胺单核苷酸。
一种改善记忆力的组合物的应用，将上述的改善记忆力的组合物用于制备保健品。
本发明的有益效果在于：
(1)本发明所述组分的各物质间协同作用，对提高脑供氧量，加速大脑血液循环，提高记忆力具有很大的功效，且处方简单，价格便宜。此药物组合物是发明人在长期的实践中对中医方术结合现代工艺精心研制的结果，对改善记忆力具有明显的治疗效果，临床观察，其治疗效果达97.5％，制剂的原生药材均为植物药，为药物的安全性提供了最佳的保障，也为中药治疗高脂血症的药物研发开辟了新天地。
(2)本发明在上述方中添加PPD、人参皂苷Rh2，这两个成分具有改善学习记忆能力的作用，这主要与PPD、人参皂苷Rh2改善脑部血液供应有关，其对氧自由基的清除也是其改善大脑学习记忆能力的机理之一，上述方协以PPD、人参皂苷Rh2，对大脑记忆能力的改善作用更强。
(3)发明人在传统配方的基础上，首次提出加用烟酰胺单核苷酸(NMN) 和PPD、人参皂苷Rh2等明确的有效成分的理论，并以该理论为指导思想，通过大量药理实验。现有报道中，NMN、PPD、Rh2三者仅仅单独作为原料被使用，目前尚未检索到任何将三者共同使用制备的组合物，本发明中西医理论相呼应，加入各类特定的辅料的引入能够显著提高方中其它药材对改善记忆力具有促进效果，以上几个组分产生了协同增效作用，通过调配使得各个组分的功效得到了1+1＞2的技术效果。
(4)本发明克服了目前食品行业中改善记忆力的食品的空缺，特别是可以替代药物的提高记忆力的保健品的空缺。
具体实施方式
为使本领域的普通技术人员更加清楚地理解发明的目的、技术方案和优点，以下通过实施例对发明做进一步的阐述。
实施例一
一种改善记忆力的组合物，其包括如下组分：
优选地，所述改善记忆力的组合物，其包括如下组分：
其中，所述烟酰胺单核苷酸、人参皂苷PPD、人参皂苷Rh2之间的重量比优选为3-7：2-5：5-7，最优为5：4：6。
在一些优选的实施例中，所述的改善记忆力的组合物还包括1-10重量份的原料药，所述原料药包括远志、菟丝子、猪牙皂、知母、酸枣仁、小茴香、叶酸中的一种或几种。更好的是，所述原料药至少包括远志、菟丝子、猪牙皂、知母、酸枣仁、小茴香、叶酸中的四种。具体的，所述原料药由远志、菟丝子、知母、小茴香、叶酸组成。
在一些优选的实施例中，所述的改善记忆力的组合物还包括1-10重量份的辅料，所述辅料包括尼泊金复合酯、富马酸、磷酸盐、木糖醇、微晶纤维素、失水山梨醇脂肪酸酯、硬脂酸镁、交联羧甲基纤维素钠、氢氧化镁、预胶化淀、硫酸钙、气相二氧化硅、乳糖中的一种或几种。更好的是，所述辅料至少包括尼泊金复合酯、富马酸、磷酸盐、木糖醇、微晶纤维素、失水山梨醇脂肪酸酯、硬脂酸镁、交联羧甲基纤维素钠、氢氧化镁、预胶化淀、硫酸钙、气相二氧化硅、乳糖中的三种。具体的，所述辅料由尼泊金复合酯、富马酸、微晶纤维素、失水山梨醇脂肪酸酯、硬脂酸镁、交联羧甲基纤维素钠、预胶化淀、气相二氧化硅、乳糖组成。
实施例二
一种改善记忆力的组合物的制备方法，按照实施例一中所述改善记忆力的组合物的各组分及配比配好并均匀混合。
在一些优选的实施例中，所述的改善记忆力的组合物的制备方法还包括烟酰胺单核苷酸的制备；所述烟酰胺单核苷酸的制备为：以烟酰胺、ATP和木糖为原料，在烟酰胺磷酸核糖转移酶、核糖磷酸焦磷酸激酶、核糖-5-磷酸异构酶、核酮糖-3-磷酸异构酶、木酮糖激酶以及木糖异构酶的催化作用下发生反应，制得所需的烟酰胺单核苷酸。
优选地，所述烟酰胺单核苷酸的制备包括：将ATP、木糖混合，并加入 MgCl2溶液、KCl溶液及Tris-HCl缓冲液，调pH至7.5-8.0；然后加入核糖磷酸焦磷酸激酶，核糖-5-磷酸异构酶，核酮糖-3-磷酸异构酶，木酮糖激酶及木糖异构酶进行初次反应，分离得到初次反应液后再加入烟酰胺、ZnCl2溶液、 Tris-HCl缓冲液及烟酰胺磷酸核糖转移酶继续反应，即得烟酰胺单核苷酸粗产品溶液，进而提取得到所需的烟酰胺单核苷酸。
具体的，烟酰胺单核苷酸制备方法为：
向反应釜中加入底物溶液，含30mmol/L的ATP、30mmol/L的木糖、 20mmol/L的MgCl2、10mmol/L的KC1以及100mmol/L的Tris-HCl缓冲液，调pH至7.5-8.0。然后加入以下催化用酶：核糖磷酸焦磷酸激酶6g/L底物溶液，核糖-5-磷酸异构酶10g/L底物溶液，核酮糖-3-磷酸异构酶l.lg/L底物溶液，木酮糖激酶10g/L底物溶液，木糖异构酶10g/L底物溶液。搅拌均匀后进行反应，反应过程中持续搅拌(搅拌速度50rpm)，控制反应温度为35℃，维持pH值为 7.5-8.0。
待上述反应进行4h后，分离出反应液，并将反应液送入另一反应釜中，再向反应液中加入60mmol/L的烟酰胺、30mmol/L的ZnCl2、100mmol/L的Tris-HCl 缓冲液以及烟酰胺磷酸核糖转移酶15g/L底物溶液，搅拌均匀后继续反应，反应过程中持续搅拌(搅拌速度50rpm)，控制反应温度为35℃，维持pH值为 7.5-8.0，再反应4h后即得烟酰胺单核苷酸粗产品溶液(含烟酰胺单核苷酸 12mmol/L)，再经过滤、纯化、干燥后即得烟酰胺单核苷酸成品。
下面提供几种具体的制备方法
制备方法1：
首先将干燥好的原辅料分别过30-80目筛，使颗粒度分布均匀，流动性更好，原辅料保持干燥，然后将筛选好的原料进行配比称重，加水在25-40℃下充分搅拌混匀后升温至50℃搅拌1小时后，得到组合物。
制备方法2：
首先将干燥好的原辅料分别过60目筛，使颗粒度分布均匀，流动性更好，原辅料保持干燥，然后将筛选好的原料进行配比称重，同时加入相关辅料，搅拌均匀。将混合好的样品在制粒机中进行制粒，并进行烘干而后进行整粒。随后放入到压片机，调节压片机参数，进行压片，理论片重为500mg，最后进行薄膜包衣、检验和包装。
制备方法3：
(1)配制内容物：首先将干燥好的原辅料分别过60目筛，原辅料保持干燥，然后将筛选好的原料进行配比称重，同时加入相关辅料，均和均匀。
(2)软胶囊体制备：现将甘油和水加入溶胶罐中，随后分别加入明胶和相关辅料，搅拌，真空脱气，制得软胶囊体。
(3)制备胶囊：将上述配制好的内容物和软胶囊体经过压丸、定型干燥、洗丸、晾丸、捡丸和包装等步骤，制得软胶囊。
制备方法4：
S1：取可选组分碎成粗颗粒，加5倍量70％乙醇加热回流提取2h，滤过；药渣再加3倍量70％乙醇加热回流提取1h，滤过，滤液合并，回收乙醇并减压浓缩至60℃下相对密度1.35～1.40的稠膏，备用；
S2：将步骤1所得的产物加7倍量的水，加热回流提取挥发油4h，分取分层的挥发油，备用；药渣和药液粗滤，滤液离心分离，上清液和药渣分别保存备用；
S3：取必选组分与S2步骤得到的挥发油后药渣合并，加水煎煮提取二次，第一次加18倍量水提取2h，第二次加12倍量水提取1h，粗滤，滤液离心分离，两次提取的上清液与S2步骤得到的提取挥发油后的上清液合并，减压浓缩至 60℃下相对密度1.35～1.40的稠膏，备用；
S4：取糊精、微粉硅胶，混匀，加入到上述S1步骤得到的水提浓缩稠膏与 S3步骤得到的醇提浓缩稠膏中，充分搅拌均匀，铺层，真空干燥，粉碎，加入糊精，喷入S2步骤得到的挥发油，过筛，混匀，装入胶囊。
实施例三
一种改善记忆力的组合物的应用，将实施例一中所述改善记忆力的组合物用于制备保健品。
下面提供具体的实施例并进行实验
一、制备改善记忆力的组合物
实施例1
各组分为：
其中，原料药由远志、菟丝子、知母、小茴香、叶酸组成；辅料由尼泊金复合酯、富马酸、微晶纤维素、失水山梨醇脂肪酸酯、硬脂酸镁、交联羧甲基纤维素钠、预胶化淀、气相二氧化硅、乳糖组成。烟酰胺单核苷酸采用以下方法制备：
向反应釜中加入底物溶液，含30mmol/L的ATP、30mmol/L的木糖、 20mmol/L的MgCl2、10mmol/L的KC1以及100mmol/L的Tris-HCl缓冲液，调 pH至7.5-8.0。然后加入以下催化用酶：核糖磷酸焦磷酸激酶6g/L底物溶液，核糖-5-磷酸异构酶10g/L底物溶液，核酮糖-3-磷酸异构酶l.lg/L底物溶液，木酮糖激酶10g/L底物溶液，木糖异构酶10g/L底物溶液。搅拌均匀后进行反应，反应过程中持续搅拌(搅拌速度50rpm)，控制反应温度为35℃，维持pH值为 7.5-8.0。
待上述反应进行4h后，分离出反应液，并将反应液送入另一反应釜中，再向反应液中加入60mmol/L的烟酰胺、30mmol/L的ZnCl2、100mmol/L的Tris-HCl 缓冲液以及烟酰胺磷酸核糖转移酶15g/L底物溶液，搅拌均匀后继续反应，反应过程中持续搅拌(搅拌速度50rpm)，控制反应温度为35℃，维持pH值为 7.5-8.0，再反应4h后即得烟酰胺单核苷酸粗产品溶液(含烟酰胺单核苷酸 12mmol/L)，再经过滤、纯化、干燥后即得烟酰胺单核苷酸成品。
实施例2
与实施例1的区别在于：
各组分为：
实施例3
与实施例1的区别在于：
各组分为：
实施例4
与实施例1的区别在于：
各组分为：
二、效果检测
1、小鼠跳台试验跳台法的实验装置为一长方形反射箱，其长径被黑色塑料板隔为若干区间，底部铺以间距为5mm的铜栅，可通适当的电流(32V交流电)。每个小的区间有一个高和直径均为4.5cm的小平台。实验时，首先将小鼠放在铜栅上，当铜栅通电时，跳在铜栅上的小鼠受到电击，其正常反应是躲避电击跳上平台，大多鼠有可能再次或多次跳下平台受到电击,受到电击时又会迅速跳回平台。如此训练5min，并记录每只鼠受到电击的次数(错误次数)，以此为学习成绩。24h后重新测验，此次测验时，首先将鼠放在跳台上，记录第一次跳下的时间(潜伏期)、受电击的动物数和5min内的错误次数，以此反映记忆保持情况。
实验及分组：按照实施例1-4制备得到的组合物为实验组1-4，市售亦贝安软胶囊为实验组5，实施例1的空白囊壳材料为实验组6。每组10只小鼠。小鼠适应环境后每只鼠按照25mg/kg计量灌胃，对照组给予0.1ml生理盐水灌胃。给药前和给药24小时后分别进行跳台试验。
结果如下表所示
2、临床试验将实施例1的组合物按照1200mg每次，每日3次给出30-40 岁成年人，连续7天，分为两组每组10人，对照组给予空白对照，进行盲测。记录试验前后记忆情况，结果实验组自感记忆力明显改善，对照组没有明显变化。
以上所述仅是本发明的优选实施方式，本发明的保护范围并不仅局限于上述实施例，凡属于本发明思路下的技术方案均属于本发明的保护范围。应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理前提下的若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
Claims (10)
1.一种改善记忆力的组合物，其特征在于：其包括如下组分：
2.如权利要求1所述的改善记忆力的组合物，其特征在于：还包括1-10重量份的原料药，所述原料药包括远志、菟丝子、猪牙皂、知母、酸枣仁、小茴香、叶酸中的一种或几种。
3.如权利要求2所述的改善记忆力的组合物，其特征在于：所述原料药至少包括远志、菟丝子、猪牙皂、知母、酸枣仁、小茴香、叶酸中的四种。
4.如权利要求1所述的改善记忆力的组合物，其特征在于：还包括1-10重量份的辅料，所述辅料包括尼泊金复合酯、富马酸、磷酸盐、木糖醇、微晶纤维素、失水山梨醇脂肪酸酯、硬脂酸镁、交联羧甲基纤维素钠、氢氧化镁、预胶化淀、硫酸钙、气相二氧化硅、乳糖中的一种或几种。
5.如权利要求4所述的改善记忆力的组合物，其特征在于：所述辅料至少包括尼泊金复合酯、富马酸、磷酸盐、木糖醇、微晶纤维素、失水山梨醇脂肪酸酯、硬脂酸镁、交联羧甲基纤维素钠、氢氧化镁、预胶化淀、硫酸钙、气相二氧化硅、乳糖中的三种。
6.如权利要求1-5任一项中所述的改善记忆力的组合物，其特征在于：所述烟酰胺单核苷酸、人参皂苷PPD、人参皂苷Rh2之间的重量比优选为3-7：2-5：5-7。
7.一种改善记忆力的组合物的制备方法，其特征在于：按照权利要求1中所述改善记忆力的组合物的各组分及配比配好并均匀混合。
8.如权利要求7所述的改善记忆力的组合物的制备方法，其特征在于：还包括烟酰胺单核苷酸的制备；
所述烟酰胺单核苷酸的制备为：以烟酰胺、ATP和木糖为原料，在烟酰胺磷酸核糖转移酶、核糖磷酸焦磷酸激酶、核糖-5-磷酸异构酶、核酮糖-3-磷酸异构酶、木酮糖激酶以及木糖异构酶的催化作用下发生反应，制得所需的烟酰胺单核苷酸。
9.如权利要求8所述的改善记忆力的组合物的制备方法，其特征在于：所述烟酰胺单核苷酸的制备包括：将ATP、木糖混合，并加入MgCl2溶液、KCl溶液及Tris-HCl缓冲液，调pH至7.5-8.0；然后加入核糖磷酸焦磷酸激酶，核糖-5-磷酸异构酶，核酮糖-3-磷酸异构酶，木酮糖激酶及木糖异构酶进行初次反应，分离得到初次反应液后再加入烟酰胺、ZnCl2溶液、Tris-HCl缓冲液及烟酰胺磷酸核糖转移酶继续反应，即得烟酰胺单核苷酸粗产品溶液，进而提取得到所需的烟酰胺单核苷酸。
10.一种改善记忆力的组合物的应用，其特征在于：将权利要求1中所述改善记忆力的组合物用于制备保健品。
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