CN113144043A - 一种预防和改善记忆力减退和老年痴呆的组合物及其制备方法和应用 - Google Patents
一种预防和改善记忆力减退和老年痴呆的组合物及其制备方法和应用 Download PDFInfo
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- 239000002904 solvent Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
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Abstract
本发明涉及医药保健领域,具体涉及一种预防和改善老年痴呆和记忆力减退的组合物及其制备方法和应用。组合物按重量份包括:蛹虫草提取物:0.5‑10重量份;黑枸杞提取物:1‑15重量份;白果提取物:0.5‑10重量份;槐米提取物:1‑15重量份;γ‑氨基丁酸:0.5‑10重量份;磷脂酰丝氨酸:1‑15重量份;姜黄素:0.5‑10重量份;复合益生菌粉:0.5‑15重量份。本发明精选上述几种组分组合和进行特定的配比,运用补肾、行气活血、营养大脑、抗炎和调理胃肠道菌群来进行组方,制备而成预防和改善记忆力减退、老年痴呆的组合物。
Description
技术领域
本发明涉及医药保健领域,具体涉及一种预防和改善老年痴呆和记忆力减退的组合物及其制备方法和应用。
背景技术
2020人口普查表明,我国65岁人口达到了1.76亿,按照5.9%的发病率计算,目前我国老年痴呆病人已经超过了1000万,这给国家及家庭带来了沉重的负担,随着我国人口老龄化的到来,患有老年痴呆或轻度症状的人口将超过2000 万,记忆力减退、老年痴呆症状的问题日益明显。
抗老年痴呆的药物主要是包括以下两方面:
第一方面,改善患者认知功能的药物,临床上常用的包括乙酰胆碱酯酶抑制剂,有盐酸多奈哌齐、石杉碱甲、卡巴拉汀,这一类药物可以有效提高大脑内乙酰胆碱的水平、加强突触传递、改善患者的认知功能。临床上有时候还使用一些改善脑代谢的药物,比如说奥拉西坦胶囊、胞磷胆碱钠片、脑蛋白水解物片。还使用具有调节谷氨酸活性作用的药物,如美金刚;
第二方面,控制患者精神症状的药物,因为在老年痴呆的某一个阶段,会出现精神方面的症状,比如说患者会有幻觉、妄想、抑郁、焦虑等,可以给患者使用帕罗西汀、舍曲林、奥氮平这些药物。
然而现有药物的副作用都较大,不适合日常使用。
发明内容
本发明的目的之一,是针对背景技术中的问题,提供一种能够日常保健食用的预防和改善记忆力减退、老年痴呆的组合物。
本发明的目的之二,是针对背景技术中的问题,提供一种预防和改善记忆力减退、老年痴呆的组合物的制备方法。
本发明的目的之三,是针对背景技术中的问题,提供一种预防和改善记忆力减退、老年痴呆的组合物的应用。
本发明的第一技术目的是通过以下技术方案得以实现的:
一种预防和改善记忆力减退、老年痴呆的组合物,按重量份包括:
蛹虫草提取物:0.5-10重量份
黑枸杞提取物:1-15重量份
白果提取物:0.5-10重量份
槐米提取物:1-15重量份
γ-氨基丁酸:0.5-10重量份
磷脂酰丝氨酸:1-15重量份
姜黄素:0.5-10重量份
复合益生菌粉:0.5-15重量份。
本发明选用特定比例的蛹虫草提取物和黑枸杞提取物组合物进行补肾;特定比例的γ-氨基丁酸和磷脂酰丝氨酸组合物增强记忆,营养大脑;特定比例的白果提取物、纳米包裹的姜黄素和槐米提取物组合进行活血抗炎和抗菌;特定比例的复合益生菌粉调理胃肠道菌群,清理慢性炎症滋生地。本发明首先从引起记忆力减退的诱因上进行预防,选用特定比例的白果提取物、纳米包裹的姜黄素、槐米提取物以及复合益生菌粉进行活血抗炎、抗菌、调理胃肠道菌群、清理慢性炎症滋生地,由内而外、由下而上对人体进行全面的身体调理,首先提高人体免疫力,预防因身体衰弱引起的神经衰弱和脑供血不足;然后同时选用特定组分比例的物质进行补肾和营养大脑。本发明精选上述几种组分组合和进行特定的配比,运用补肾、行气活血、营养大脑、抗炎和调理胃肠道菌群来进行组方,制备而成预防和改善记忆力减退、老年痴呆的组合物。
作为优选,所述姜黄素为纳米包裹的姜黄素。
作为优选,所述复合益生菌粉包括植物乳杆菌N13、乳酸片球菌CCFM7902、嗜酸乳杆菌、长双歧杆菌BL21和/或两歧双歧杆菌。
本发明结合老年痴呆的中西医病理病机,运用补肾、行气活血、营养大脑、抗炎和调理胃肠道菌群来进行组方。本发明精选上述几种组分组合和进行特定的配比,制备而成预防和改善记忆力减退、老年痴呆的组合物,且吸收快、无毒副作用,具有较高的食用安全性、可长期服用。
本发明的第二技术目的是通过以下技术方案得以实现的:
一种预防和改善记忆力减退、老年痴呆的组合物的制备方法,其具体包括以下步骤:
(1)按重量份准备以下原料:
蛹虫草提取物:0.5-10重量份
黑枸杞提取物:1-15重量份
白果提取物:0.5-10重量份
槐米提取物:1-15重量份
γ-氨基丁酸:0.5-10重量份
磷脂酰丝氨酸:1-15重量份
姜黄素:0.5-10重量份
复合益生菌粉:0.5-15重量份;
(2)按比例将白果提取物、姜黄素、槐米提取物混合均匀,得到第一混合物; (3)按比例将复合益生菌粉加入第一混合物中混合均匀形成第二混合物;
(4)按比例将蛹虫草提取物和黑枸杞提取物加入第二混合物中混合均匀形成第三混合物;
(5)按比例将γ-氨基丁酸和磷脂酰丝氨酸加入第三混合物中混合均匀,得到组合物。
本发明按比例不同阶段混合制备不同的混合物,最终得到本发明预防和改善记忆力减退、老年痴呆的组合物,可以使各组分的功能效果得到最大协同发挥。
作为优选,所述步骤(4)按比例将蛹虫草提取物和黑枸杞提取物加入第二混合物中混合均匀处理形成第三混合物。
作为优选,所述蛹虫草提取物,虫草多糖的含量不低于1900mg/L、虫草腺苷的含量不低于45mg/L;
其制备方法包括以下步骤:
步骤1:将蛹虫草与液态二氧化碳混合,压力40MPa~60MPa保持2h~3h后,制得第一中间产物;
步骤2:将所述第一中间产物粉碎至粒径为0.005mm~0.02mm,加入氢氧化钠水溶液调节pH值为6~7,经固液分离,得第一沉淀与第一液体,收集所述液体为第二中间产物;
步骤3:将所述沉淀加入氢氧化钠水溶液调节pH值为6~7,经固液分离,得第二沉淀与第二液体,将所述第二液体与第二中间产物混合,浓缩得浓缩液;
步骤4:将所述浓缩液在温度80~90℃,真空度-0.03~-0.05MPa,浓缩至固形物含量至70%~85%Brix(w/w),得到富含生物活性物质的蛹虫草提取物。
虫草多糖是由甘露糖、虫草素、腺苷、半乳糖、***糖、木糖精、葡萄糖、岩藻糖组成的多聚糖。虫草腺苷主要包括尿嘧啶、腺嘌呤、腺嘌呤、次黄嘌呤、鸟嘌呤、腺嘌呤等。虫草多糖、虫草腺苷属于蛹虫草活性成分,具有抗提高免疫力的功能,此外还具有抗菌、消炎、调节内分泌***及增强机体免疫能力等作用。
蛹虫草本身直接进行活性物质的提取方法仍存在着提取效率低、提取过程对活性物质破坏严重的问题。本发明的蛹虫草活性物质提取方法,提取效率高,能减少提取过程对活性物质的破坏,有助于将本发明的蛹虫草提取物与黑枸杞提取物混合到第二混合物中发挥作用,对预防、改善记忆力减退、老年痴呆有很好的帮助。
作为优选,所述黑枸杞提取物制备包括选取黑枸杞,然后进行以下步骤:
(1)将干燥的黑枸杞置于管式加热炉内进行加热破壁处理;管式加热炉以 5-10℃/min的速度升温至85-95℃,处理时间为20-25min,加热过程中通入氮气作为保护气;
(2)将破壁处理后的黑枸杞置于乙醇水溶液中浸泡处理,得到黑枸杞乙醇混合溶液;
(3)将获得的黑枸杞乙醇混合溶液置于微波萃取仪中,进行第一次浸出萃取,萃取时间为2-4min,获得黑枸杞第一提取液;微波萃取仪的频率为 1000-1500MHz,功率为850-950W;
(4)将第一提取液静置5-10min,置于微波萃取仪中,进行第二次萃取,萃取时间为4-6min,获得黑枸杞第二提取液;微波萃取仪的频率为700-900MHz,功率为300-400W;
(5)将第二提取液静置8-10min,自然冷却至室温;然后置于离心机中,离心分离收集上清液;
(6)将所述上清液添加保护剂聚乙二醇先冷却至0~3℃,再冷冻至-25℃以下,在真空冷冻干燥器中进行干燥,干燥24h以上,得到黑枸杞提取物。
本发明采用管式加热炉对黑枸杞进行破壁,以氮气作为保护气体可以避免花青素等物质高温氧化,特定的升温速率、时间和温度控制为黑枸杞的破壁提供了一个稳定的环境,能够使花粉均匀有效地受热破壁;后续的微波萃取使黑枸杞粉细胞进一步膨胀破壁,细胞中的花青素可以和溶剂充分接触、进而溶解,可以大幅度提高提取效率,提高总花青素得率。相比于传统的微波提取方法,本发明方法采用先高后低的两次功率微波萃取,在第一阶段采用较高的功率和微波频率,可在花青素快速浸出阶段进一步提升花青素萃出效率,在第二阶段采用相对较低的功率和微波频率,可降低对提取液中已浸出花青素的热降解作用;为了防止花青素氧化,本发明在获得上清液后也采用两步法,先进行冷却,再进行冷冻,对其中的花青素进行保护处理,从而获得稳定花青素含量的黑枸杞提取物。
本发明微波法制备黑枸杞提取物,提取效率高;本发明黑枸杞提取物中的花青素提取率为88.5%以上,而传统方法花青素提取率只有50%左右;本发明提取不仅优于传统的微波提取方法,而且优于现有的浸泡提取和超声提取方法。
作为优选,所述白果提取物制备包括先选取白果,加入固体总质量2.5-3.5 倍的65~75%乙醇,在萃取压力为15-20MPa、萃取温度为50-60℃条件下进行超临界CO2萃取1.5-2小时,最后经挥干制得干浸膏,并粉碎得白果提取物备用。
作为优选,所述槐米提取物制备包括按比例选取槐米,加入固体总质量 2.5-3.5倍的浓度为65~75%的乙醇回流提取一次,且提取用时0.5~1小时,然后再将经乙醇提取后的槐米残渣用浓度为65~75%的乙醇再回流提取一次,且提取用时0.5~1小时,最后经挥干制得干浸膏,并粉碎备用。所述乙醇浓度是指体积比V/V。
作为优选,所述纳米包裹的姜黄素的制备包括:
①提取:将姜黄粉碎,加入4-8wt%的碱水提取,得碱水提取液;
②脱脂:往碱水提取液中加入乙酸甲酯,搅拌萃取1-2小时后,静置1-2 小时,分出有机层;
③酸沉:将提取液用碳酸调节pH至1-2,使姜黄素析出,过滤,干燥至恒重,得到姜黄素粗品;
④精制:将姜黄素粗品用异丙醇溶解,过滤,往滤液中加入去离子水,2-4℃冷冻析晶3-5小时,过滤,干燥,得到姜黄素;
⑤包裹:将姜黄素与甲氧基聚乙二醇-聚己内酯按质量比1:6-8混合溶于丙酮中,超声1-2min,室温条件下旋转蒸发制成贴壁薄膜,在60-70℃条件下缓慢旋转水化,微孔滤膜过滤除去未包载的姜黄素,制成纳米粒溶液;将所得纳米粒溶液冻干即得纳米包裹的姜黄素粉末。
本发明的纳米包裹姜黄素不含有其他助剂,聚己内酯的甲氧基聚乙二醇为两亲性聚合物,聚乙二醇段不易脱落,水环境中可以覆盖在纳米粒表面,增强纳米粒的亲水性,减少网状内皮***摄取的速度和程度,延长体内的循环时间,提高生物利用度,进而提高活血抗炎和抗菌性能,尤其是提高了组合物的抗炎抗菌性能,从而提高组合物延缓记忆力衰退功能。
本发明的第三技术目的是通过以下技术方案得以实现的:
一种预防和改善记忆力减退、老年痴呆的组合物的应用,具体是将该组合物用于制备胶囊、压片糖果或固体饮料。
作为优选,所述组合物用于制备胶囊时,每粒胶囊含组合物300-600mg。
作为优选,所述组合物用于制备压片糖果时,每颗压片糖果含组合物 300-600mg。
作为优选,所述组合物用于制备固体饮料时,每袋固体饮料含组合物 300-600mg。
综上所述,本发明的有益效果:
1、本发明选用特定比例的蛹虫草提取物和黑枸杞提取物组合物进行补肾;特定比例的γ-氨基丁酸和磷脂酰丝氨酸组合物增强记忆,营养大脑;特定比例的白果提取物、纳米包裹的姜黄素和槐米提取物组合进行活血抗炎和抗菌;特定比例的复合益生菌粉调理胃肠道菌群,清理慢性炎症滋生地。本发明首先从引起记忆力减退的诱因上进行预防,选用特定比例的白果提取物、纳米包裹的姜黄素、槐米提取物以及复合益生菌粉进行活血抗炎、抗菌、调理胃肠道菌群、清理慢性炎症滋生地,由内而外、由下而上对人体进行全面的身体调理,首先提高人体免疫力,预防因身体衰弱引起的神经衰弱和脑供血不足;然后同时选用特定组分比例的物质进行补肾和营养大脑。本发明精选上述几种组分组合和进行特定的配比,运用补肾、行气活血、营养大脑、抗炎和调理胃肠道菌群来进行组方,制备而成预防和改善记忆力减退、老年痴呆的组合物;
2、本发明的蛹虫草活性物质提取方法,提取效率高,能减少提取过程对活性物质的破坏,有助于将本发明的蛹虫草提取物与黑枸杞提取物混合到第二混合物中发挥作用,对预防、改善记忆力减退、老年痴呆有很好的帮助;
3、本发明的纳米包裹姜黄素不含有其他助剂,聚己内酯的甲氧基聚乙二醇为两亲性聚合物,聚乙二醇段不易脱落,水环境中可以覆盖在纳米粒表面,增强纳米粒的亲水性,减少网状内皮***摄取的速度和程度,延长体内的循环时间,提高生物利用度,进而提高活血抗炎和抗菌性能,尤其是提高了组合物的抗炎抗菌性能,从而提高组合物延缓记忆力衰退功能。
具体实施方式
以下具体实施例仅仅是对本发明的解释,其并不是对本发明的限制,本领域技术人员在阅读完本说明书后可以根据需要对本实施例做出没有创造性贡献的修改,但只要在本发明的权利要求范围内都受到专利法的保护。下面对本发明进行详细说明。
实施例1:
一种预防和改善记忆力减退、老年痴呆的组合物的制备方法,其具体包括以下步骤:
(1)按重量份准备以下原料:
蛹虫草提取物:0.5重量份
黑枸杞提取物:1重量份
白果提取物:0.5重量份
槐米提取物:1重量份
γ-氨基丁酸:0.5重量份
磷脂酰丝氨酸:1重量份
姜黄素:0.5重量份
复合益生菌粉:15重量份;
(2)按比例将白果提取物、姜黄素、槐米提取物混合均匀,得到第一混合物;
(3)按比例将复合益生菌粉加入第一混合物中混合均匀形成第二混合物;
(4)按比例将蛹虫草提取物和黑枸杞提取物加入第二混合物中混合均匀形成第三混合物;
(5)按比例将γ-氨基丁酸和磷脂酰丝氨酸加入第三混合物中混合均匀,得到组合物。
所述蛹虫草提取物,虫草多糖的含量不低于1900mg/L、虫草腺苷的含量不低于45mg/L;
其制备方法包括以下步骤:
步骤1:将蛹虫草与液态二氧化碳混合,压力40MPa保持2h后,制得第一中间产物;
步骤2:将所述第一中间产物粉碎至粒径为0.005mm,加入氢氧化钠水溶液调节pH值为6,经固液分离,得第一沉淀与第一液体,收集所述液体为第二中间产物;
步骤3:将所述沉淀加入氢氧化钠水溶液调节pH值为6,经固液分离,得第二沉淀与第二液体,将所述第二液体与第二中间产物混合,浓缩得浓缩液;
步骤4:将所述浓缩液在温度80℃,真空度-0.03MPa,浓缩至固形物含量至 70%Brix(w/w),得到富含生物活性物质的蛹虫草提取物。
其中,黑枸杞提取物制备包括选取黑枸杞,然后进行以下步骤:
(1)将干燥的黑枸杞置于管式加热炉内进行加热破壁处理;管式加热炉以 5℃/min的速度升温至85℃,处理时间为20-25min,加热过程中通入氮气作为保护气;
(2)将破壁处理后的黑枸杞置于乙醇水溶液中浸泡处理,得到黑枸杞乙醇混合溶液;
(3)将获得的黑枸杞乙醇混合溶液置于微波萃取仪中,进行第一次浸出萃取,萃取时间为2min,获得黑枸杞第一提取液;微波萃取仪的频率为1000MHz,功率为850W;
(4)将第一提取液静置5min,置于微波萃取仪中,进行第二次萃取,萃取时间为4min,获得黑枸杞第二提取液;微波萃取仪的频率为700MHz,功率为300W;
(5)将第二提取液静置8min,自然冷却至室温;然后置于离心机中,离心分离收集上清液;
(6)将所述上清液添加保护剂聚乙二醇先冷却至0℃,再冷冻至-25℃以下,在真空冷冻干燥器中进行干燥,干燥24h以上,得到黑枸杞提取物。
其中,白果提取物制备包括先选取白果,加入固体总质量2.5倍的65%乙醇,在萃取压力为15MPa、萃取温度为50℃条件下进行超临界CO2萃取1.5小时,最后经挥干制得干浸膏,并粉碎得白果提取物备用。
其中,槐米提取物制备包括按比例选取槐米,加入固体总质量2.5倍的浓度为65%的乙醇回流提取一次,且提取用时0.5小时,然后再将经乙醇提取后的槐米残渣用浓度为65%的乙醇再回流提取一次,且提取用时0.5小时,最后经挥干制得干浸膏,并粉碎备用。
实施例2:
一种预防和改善记忆力减退、老年痴呆的组合物的制备方法,其具体包括以下步骤:
(1)按重量份准备以下原料:
蛹虫草提取物:10重量份
黑枸杞提取物:15重量份
白果提取物:10重量份
槐米提取物:15重量份
γ-氨基丁酸:10重量份
磷脂酰丝氨酸:15重量份
姜黄素:10重量份
复合益生菌粉:0.5重量份;
(2)按比例将白果提取物、姜黄素、槐米提取物混合均匀,得到第一混合物; (3)按比例将复合益生菌粉加入第一混合物中混合均匀形成第二混合物;
(4)按比例将蛹虫草提取物和黑枸杞提取物加入第二混合物中混合均匀形成第三混合物;
(5)按比例将γ-氨基丁酸和磷脂酰丝氨酸加入第三混合物中混合均匀,得到组合物。
蛹虫草提取物,虫草多糖的含量不低于1900mg/L、虫草腺苷的含量不低于 45mg/L;
其制备方法包括以下步骤:
步骤1:将蛹虫草与液态二氧化碳混合,压力50MPa保持2.5h后,制得第一中间产物;
步骤2:将所述第一中间产物粉碎至粒径为0.01mm,加入氢氧化钠水溶液调节pH值为6.5,经固液分离,得第一沉淀与第一液体,收集所述液体为第二中间产物;
步骤3:将所述沉淀加入氢氧化钠水溶液调节pH值为6.5,经固液分离,得第二沉淀与第二液体,将所述第二液体与第二中间产物混合,浓缩得浓缩液;
步骤4:将所述浓缩液在温度85℃,真空度-0.04MPa,浓缩至固形物含量至 75%Brix(w/w),得到富含生物活性物质的蛹虫草提取物。
黑枸杞提取物制备包括选取黑枸杞,然后进行以下步骤:
(1)将干燥的黑枸杞置于管式加热炉内进行加热破壁处理;管式加热炉以 8℃/min的速度升温至90℃,处理时间为23min,加热过程中通入氮气作为保护气;
(2)将破壁处理后的黑枸杞置于乙醇水溶液中浸泡处理,得到黑枸杞乙醇混合溶液;
(3)将获得的黑枸杞乙醇混合溶液置于微波萃取仪中,进行第一次浸出萃取,萃取时间为3min,获得黑枸杞第一提取液;微波萃取仪的频率为1200MHz,功率为900W;
(4)将第一提取液静置8min,置于微波萃取仪中,进行第二次萃取,萃取时间为5min,获得黑枸杞第二提取液;微波萃取仪的频率为800MHz,功率为350W;
(5)将第二提取液静置9min,自然冷却至室温;然后置于离心机中,离心分离收集上清液;
(6)将所述上清液添加保护剂聚乙二醇先冷却至2℃,再冷冻至-25℃以下,在真空冷冻干燥器中进行干燥,干燥24h以上,得到黑枸杞提取物。
白果提取物制备包括先选取白果,加入固体总质量3倍的70%乙醇,在萃取压力为18MPa、萃取温度为56℃条件下进行超临界CO2萃取1.8小时,最后经挥干制得干浸膏,并粉碎得白果提取物备用。
槐米提取物制备包括按比例选取槐米,加入固体总质量2.5倍的浓度70%的乙醇回流提取一次,且提取用时0.8小时,然后再将经乙醇提取后的槐米残渣用浓度为70%的乙醇再回流提取一次,且提取用时0.8小时,最后经挥干制得干浸膏,并粉碎备用。
实施例3:
一种预防和改善记忆力减退、老年痴呆的组合物的制备方法,其具体包括以下步骤:
(1)按重量份准备以下原料:
蛹虫草提取物:5重量份
黑枸杞提取物:8重量份
白果提取物:6重量份
槐米提取物:10重量份
γ-氨基丁酸:5重量份
磷脂酰丝氨酸:7重量份
姜黄素:7重量份
复合益生菌粉:9重量份;
(2)按比例将白果提取物、姜黄素、槐米提取物混合均匀,得到第一混合物;
(3)按比例将复合益生菌粉加入第一混合物中混合均匀形成第二混合物;
(4)按比例将蛹虫草提取物和黑枸杞提取物加入第二混合物中混合均匀形成第三混合物;
(5)按比例将γ-氨基丁酸和磷脂酰丝氨酸加入第三混合物中混合均匀,得到组合物。
蛹虫草提取物,虫草多糖的含量不低于1900mg/L、虫草腺苷的含量不低于 45mg/L;
其制备方法包括以下步骤:
步骤1:将蛹虫草与液态二氧化碳混合,压力60MPa保持3h后,制得第一中间产物;
步骤2:将所述第一中间产物粉碎至粒径为0.02mm,加入氢氧化钠水溶液调节pH值为7,经固液分离,得第一沉淀与第一液体,收集所述液体为第二中间产物;
步骤3:将所述沉淀加入氢氧化钠水溶液调节pH值为7,经固液分离,得第二沉淀与第二液体,将所述第二液体与第二中间产物混合,浓缩得浓缩液;
步骤4:将所述浓缩液在温度90℃,真空度-0.05MPa,浓缩至固形物含量至 85%Brix(w/w),得到富含生物活性物质的蛹虫草提取物。
黑枸杞提取物制备包括选取黑枸杞,然后进行以下步骤:
(1)将干燥的黑枸杞置于管式加热炉内进行加热破壁处理;管式加热炉以 10℃/min的速度升温至95℃,处理时间为25min,加热过程中通入氮气作为保护气;
(2)将破壁处理后的黑枸杞置于乙醇水溶液中浸泡处理,得到黑枸杞乙醇混合溶液;
(3)将获得的黑枸杞乙醇混合溶液置于微波萃取仪中,进行第一次浸出萃取,萃取时间为4min,获得黑枸杞第一提取液;微波萃取仪的频率为1500MHz,功率为950W;
(4)将第一提取液静置10min,置于微波萃取仪中,进行第二次萃取,萃取时间为6min,获得黑枸杞第二提取液;微波萃取仪的频率为900MHz,功率为 400W;
(5)将第二提取液静置10min,自然冷却至室温;然后置于离心机中,离心分离收集上清液;
(6)将所述上清液添加保护剂聚乙二醇先冷却至3℃,再冷冻至-25℃以下,在真空冷冻干燥器中进行干燥,干燥24h以上,得到黑枸杞提取物。
白果提取物制备包括先选取白果,加入固体总质量3.5倍的75%乙醇,在萃取压力为20MPa、萃取温度为50-60℃条件下进行超临界CO2萃取2小时,最后经挥干制得干浸膏,并粉碎得白果提取物备用。
槐米提取物制备包括按比例选取槐米,加入固体总质量3.5倍的浓度为75%的乙醇回流提取一次,且提取用时1小时,然后再将经乙醇提取后的槐米残渣用浓度为75%的乙醇再回流提取一次,且提取用时1小时,最后经挥干制得干浸膏,并粉碎备用。
实施例4
同实施例1,不同的是姜黄素为纳米包裹的姜黄素。
其中,纳米包裹的姜黄素的制备包括:
①提取:将姜黄粉碎,加入4wt%的碱水提取,得碱水提取液;
②脱脂:往碱水提取液中加入乙酸甲酯,搅拌萃取1小时后,静置1小时,分出有机层;
③酸沉:将提取液用碳酸调节pH至1,使姜黄素析出,过滤,干燥至恒重,得到姜黄素粗品;
④精制:将姜黄素粗品用异丙醇溶解,过滤,往滤液中加入去离子水,2℃冷冻析晶3小时,过滤,干燥,得到姜黄素;
⑤包裹:将姜黄素与甲氧基聚乙二醇-聚己内酯按质量比1:6混合溶于丙酮中,超声1min,室温条件下旋转蒸发制成贴壁薄膜,在60℃条件下缓慢旋转水化,微孔滤膜过滤除去未包载的姜黄素,制成纳米粒溶液;将所得纳米粒溶液冻干即得纳米包裹的姜黄素粉末。
实施例5
同实施例2,不同的是姜黄素为纳米包裹的姜黄素。
其中,纳米包裹的姜黄素的制备包括:
①提取:将姜黄粉碎,加入8wt%的碱水提取,得碱水提取液;
②脱脂:往碱水提取液中加入乙酸甲酯,搅拌萃取2小时后,静置2小时,分出有机层;
③酸沉:将提取液用碳酸调节pH至2,使姜黄素析出,过滤,干燥至恒重,得到姜黄素粗品;
④精制:将姜黄素粗品用异丙醇溶解,过滤,往滤液中加入去离子水,4℃冷冻析晶5小时,过滤,干燥,得到姜黄素;
⑤包裹:将姜黄素与甲氧基聚乙二醇-聚己内酯按质量比1:8混合溶于丙酮中,超声2min,室温条件下旋转蒸发制成贴壁薄膜,在70℃条件下缓慢旋转水化,微孔滤膜过滤除去未包载的姜黄素,制成纳米粒溶液;将所得纳米粒溶液冻干即得纳米包裹的姜黄素粉末。
实施例6
同实施例3,不同的是姜黄素为纳米包裹的姜黄素。
其中,纳米包裹的姜黄素的制备包括:
①提取:将姜黄粉碎,加入5wt%的碱水提取,得碱水提取液;
②脱脂:往碱水提取液中加入乙酸甲酯,搅拌萃取1.5小时后,静置1.5 小时,分出有机层;
③酸沉:将提取液用碳酸调节pH至1.5,使姜黄素析出,过滤,干燥至恒重,得到姜黄素粗品;
④精制:将姜黄素粗品用异丙醇溶解,过滤,往滤液中加入去离子水,3℃冷冻析晶4小时,过滤,干燥,得到姜黄素;
⑤包裹:将姜黄素与甲氧基聚乙二醇-聚己内酯按质量比1:7混合溶于丙酮中,超声1.5min,室温条件下旋转蒸发制成贴壁薄膜,在65℃条件下缓慢旋转水化,微孔滤膜过滤除去未包载的姜黄素,制成纳米粒溶液;将所得纳米粒溶液冻干即得纳米包裹的姜黄素粉末。
实施例7
同实施例1,不同的是蛹虫草提取物、黑枸杞提取物、白果提取物、槐米提取物、姜黄素均为市场上普通购得。
实施例8
同实施例2,不同的是蛹虫草提取物、黑枸杞提取物、白果提取物、槐米提取物、姜黄素均为市场上普通购得。
实施例9
同实施例3,不同的是蛹虫草提取物、黑枸杞提取物、白果提取物、槐米提取物、姜黄素均为市场上普通购得。
对比例1
同实施例1,不同的是,按重量份准备以下原料:
蛹虫草提取物:0.3重量份
黑枸杞提取物:0.8重量份
白果提取物:0.3重量份
槐米提取物:0.7重量份
γ-氨基丁酸:0.5重量份
磷脂酰丝氨酸:1重量份
姜黄素:0.5重量份
复合益生菌粉:18重量份;
将以上物质直接混合均匀。
对比例2
同实施例2,不同的是,按重量份准备以下原料:
蛹虫草提取物:12重量份
黑枸杞提取物:17重量份
白果提取物:11重量份
槐米提取物:1重量份
γ-氨基丁酸:0.5重量份
磷脂酰丝氨酸:1重量份
姜黄素:0.5重量份
复合益生菌粉:18重量份;
将以上物质直接混合均匀。
对比例3
同实施例3,不同的是本实施例预防和改善记忆力减退、老年痴呆的组合物中不含蛹虫草提取物和姜黄素。
对比例4
同实施例4,不同的是本实施例预防和改善记忆力减退、老年痴呆的组合物中不含黑枸杞提取物、γ-氨基丁酸和复合益生菌粉。
检验项目:菌落总数、大肠杆菌、霉菌和酵母计数、沙门氏菌、志贺氏菌、溶血性链球菌、金黄色葡萄球菌。经检测,组合物中各物料之间配伍使用符合微生物标准。
采用专利“CN201610649982.6(CN106237235B)一种增强记忆力的中药组合物及其制备方法和应用”的测试方法将实施例1-9以及对比例1-4的组合物产品对各实验小组的小鼠分别进行给药,并对小鼠进行水迷宫法测试。
水迷宫法测试受试物对正常小鼠学习记忆的影响,实验结果分析如表1。
表1水迷宫成绩分析
由表1可见,与空白对照组相比,受试物剂量组的小鼠游完全程所需的时间明显缩短,错误次数明显减少。且本发明实施例4-6组合物的小鼠水迷宫成绩优于实施例1-3,给药实施例1-3组合物的小鼠水迷宫成绩优于实施例7-9,给药实施例7-9组合物的小鼠水迷宫成绩优于对比例1-4。
使用方法:成人每次2~4粒,小儿每次1粒,每日三次,温开水送服。
急性毒性试验:小鼠口服该制剂1g/kg,相当于成人口服的100倍,未出现死亡和反应。
典型病例:
病例1:
林某某,男,35岁,IT工程师。2001年6月以来,出现头晕脑胀、神态疲惫、丢三落四,自感记忆力显著减退。使用本发明组合物产品,10天见效,20 天显效,50天症状全部消失。
病例2:
姚某某,男,54岁,工人;两月前出现反应迟钝。经服用本发明组合物产品10天,症状明显改善,连续服用30天症状全部消失。
病例3:
应某某,女,16岁,某中学学生。由于繁重的学习,导致压力过大,经常是疲劳状态,上课打哈欠,记忆力减退。服本发明药7日,症状明显改善,连服 20天,症状完全消失,精力充沛。
预防记忆力衰退、改善记忆力功能性检验
1.样品:实施例1制得的胶囊,服用剂量为每天一粒,即每天0.6g。
2.受试对象:受试者未接受过类似测试,短期内未服用与改善记忆力功能有关的物品,尽可能考虑到文化水平,年龄等因素,进行均衡性试验。服用受试样品前后均对受试者进行一次记忆商的测试。把受试者分为三组,青年组20人,年龄16-25岁,中年组20人,年龄26-45岁,老年组20人,年龄46-65岁。
3.试食方法:每人每天一粒实施例1制得的胶囊,连续服用30天。
4.结果:
试食者在食用本产品前后一般情况等检查,身体状况未见异常,表面试食本品无不良影响。
青年组试食者普遍上课注意力集中,思维变得更加敏捷,大脑不容易疲劳,考试焦虑情绪减少,成绩普遍提高,试食前后结果显示:试食者试食后的视觉再认、联想学***均提高了25%。
中年组的试食者的睡眠质量普遍有积极的改善效果,生活情绪稳定,改善健忘的症状,试食前后结果显示:试食者试食后的视觉再认、联想学***均提高了10%。
老年组的试食者精神状态普遍比以前好,身体各项指标都较健康,有效地预防老年痴呆,试食前后结果显示:试食者试食后的视觉再认、联想学***均提高了2.5%。
本具体实施例仅仅是对本发明的解释,其并不是对本发明的限制,本领域技术人员在阅读完本说明书后可以根据需要对本实施例做出没有创造性贡献的修改,但只要在本发明的权利要求范围内都受到专利法的保护。
Claims (10)
1.一种预防和改善记忆力减退、老年痴呆的组合物,其特征在于按重量份包括:
蛹虫草提取物:0.5-10重量份
黑枸杞提取物:1-15重量份
白果提取物:0.5-10重量份
槐米提取物:1-15重量份
γ-氨基丁酸:0.5-10重量份
磷脂酰丝氨酸:1-15重量份
姜黄素:0.5-10重量份
复合益生菌粉:0.5-15重量份。
2.根据权利要求1所述的一种预防和改善记忆力减退、老年痴呆的组合物,其特征在于:所述姜黄素为纳米包裹的姜黄素。
3.根据权利要求1所述的一种预防和改善记忆力减退、老年痴呆的组合物,其特征在于:所述复合益生菌粉包括植物乳杆菌N13、乳酸片球菌CCFM7902、嗜酸乳杆菌、长双歧杆菌BL21和/或两歧双歧杆菌。
4.一种根据权利要求1-3任一项所述预防和改善记忆力减退、老年痴呆的组合物的制备方法,其特征在于具体包括以下步骤:
(1)按重量份准备以下原料:
蛹虫草提取物:0.5-10重量份
黑枸杞提取物:1-15重量份
白果提取物:0.5-10重量份
槐米提取物:1-15重量份
γ-氨基丁酸:0.5-10重量份
磷脂酰丝氨酸:1-15重量份
姜黄素:0.5-10重量份
复合益生菌粉:0.5-15重量份;
(2)按比例将白果提取物、姜黄素、槐米提取物混合均匀,得到第一混合物;
(3)按比例将复合益生菌粉加入第一混合物中混合均匀形成第二混合物;
(4)按比例将蛹虫草提取物和黑枸杞提取物加入第二混合物中混合均匀形成第三混合物;
(5)按比例将γ-氨基丁酸和磷脂酰丝氨酸加入第三混合物中混合均匀,得到组合物。
5.根据权利要求4所述预防和改善记忆力减退、老年痴呆的组合物的制备方法,其特征在于:所述蛹虫草提取物,虫草多糖的含量不低于1900mg/L、虫草腺苷的含量不低于45mg/L;
其制备方法包括以下步骤:
步骤1:将蛹虫草与液态二氧化碳混合,压力40MPa~60MPa保持2h~3h后,制得第一中间产物;
步骤2:将所述第一中间产物粉碎至粒径为0.005mm~0.02mm,加入氢氧化钠水溶液调节pH值为6~7,经固液分离,得第一沉淀与第一液体,收集所述液体为第二中间产物;
步骤3:将所述沉淀加入氢氧化钠水溶液调节pH值为6~7,经固液分离,得第二沉淀与第二液体,将所述第二液体与第二中间产物混合,浓缩得浓缩液;
步骤4:将所述浓缩液在温度80~90℃,真空度-0.03~-0.05MPa,浓缩至固形物含量至70%~85%Brix(w/w),得到富含生物活性物质的蛹虫草提取物。
6.根据权利要求4所述预防和改善记忆力减退、老年痴呆的组合物的制备方法,其特征在于:所述黑枸杞提取物制备包括选取黑枸杞,然后进行以下步骤:
(1)将干燥的黑枸杞置于管式加热炉内进行加热破壁处理;管式加热炉以5-10℃/min的速度升温至85-95℃,处理时间为20-25min,加热过程中通入氮气作为保护气;
(2)将破壁处理后的黑枸杞置于乙醇水溶液中浸泡处理,得到黑枸杞乙醇混合溶液;
(3)将获得的黑枸杞乙醇混合溶液置于微波萃取仪中,进行第一次浸出萃取,萃取时间为2-4min,获得黑枸杞第一提取液;微波萃取仪的频率为1000-1500MHz,功率为850-950W;
(4)将第一提取液静置5-10min,置于微波萃取仪中,进行第二次萃取,萃取时间为4-6min,获得黑枸杞第二提取液;微波萃取仪的频率为700-900MHz,功率为300-400W;
(5)将第二提取液静置8-10min,自然冷却至室温;然后置于离心机中,离心分离收集上清液;
(6)将所述上清液添加保护剂聚乙二醇先冷却至0~3℃,再冷冻至-25℃以下,在真空冷冻干燥器中进行干燥,干燥24h以上,得到黑枸杞提取物。
7.根据权利要求4所述预防和改善记忆力减退、老年痴呆的组合物的制备方法,其特征在于:所述白果提取物制备包括先选取白果,加入固体总质量2.5-3.5倍的65~75%乙醇,在萃取压力为15-20MPa、萃取温度为50-60℃条件下进行超临界CO2萃取1.5-2小时,最后经挥干制得干浸膏,并粉碎得白果提取物备用。
8.根据权利要求4所述预防和改善记忆力减退、老年痴呆的组合物的制备方法,其特征在于:所述槐米提取物制备包括按比例选取槐米,加入固体总质量2.5-3.5倍的浓度为65~75%的乙醇回流提取一次,且提取用时0.5~1小时,然后再将经乙醇提取后的槐米残渣用浓度为65~75%的乙醇再回流提取一次,且提取用时0.5~1小时,最后经挥干制得干浸膏,并粉碎备用。
9.根据权利要求4所述预防和改善记忆力减退、老年痴呆的组合物的制备方法,其特征在于:所述纳米包裹的姜黄素的制备包括:
①提取:将姜黄粉碎,加入4-8wt%的碱水提取,得碱水提取液;
②脱脂:往碱水提取液中加入乙酸甲酯,搅拌萃取1-2小时后,静置1-2小时,分出有机层;
③酸沉:将提取液用碳酸调节pH至1-2,使姜黄素析出,过滤,干燥至恒重,得到姜黄素粗品;
④精制:将姜黄素粗品用异丙醇溶解,过滤,往滤液中加入去离子水,2-4℃冷冻析晶3-5小时,过滤,干燥,得到姜黄素;
⑤包裹:将姜黄素与甲氧基聚乙二醇-聚己内酯按质量比1:6-8混合溶于丙酮中,超声1-2min,室温条件下旋转蒸发制成贴壁薄膜,在60-70℃条件下缓慢旋转水化,微孔滤膜过滤除去未包载的姜黄素,制成纳米粒溶液;将所得纳米粒溶液冻干即得纳米包裹的姜黄素粉末。
10.一种根据权利要求1-3任一项所述预防和改善记忆力减退、老年痴呆的组合物的应用,具体是将该组合物用于制备胶囊、压片糖果或固体饮料。
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