CN113663008A - 一种改善记忆功能/缓解视疲劳的组合物及其制备方法和应用 - Google Patents
一种改善记忆功能/缓解视疲劳的组合物及其制备方法和应用 Download PDFInfo
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- CN113663008A CN113663008A CN202110936402.2A CN202110936402A CN113663008A CN 113663008 A CN113663008 A CN 113663008A CN 202110936402 A CN202110936402 A CN 202110936402A CN 113663008 A CN113663008 A CN 113663008A
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Abstract
本发明属于药物/保健食品制备技术领域,具体涉及一种改善记忆功能/缓解视疲劳的组合物及其制备方法和应用。该组合物按重量百分比计包括漆黄素/漆黄素复合物10‑50%、α‑亚麻酸2‑15%、叶黄素2‑15%、原花青素2‑15%、VB1 2‑10%、VB12 2‑10%、蓝莓10‑50%、枸杞10‑50%、桑椹10‑50%;所述漆黄素复合物为磷脂复合物或漆黄素纳米结晶或漆黄素‑环糊精复合物中的一种或多种。该组合物能明显改善记忆功能和明显缓解受试者的视疲劳,使用者的眼酸痛、眼胀、畏光、食物模糊、眼干涩、异物感等症状有明显改善。
Description
技术领域
本发明属于药物/保健食品制备技术领域,具体涉及一种基于漆黄素/漆黄素复合物的改善记忆功能/缓解视疲劳的组合物及其制备方法和应用。
背景技术
很多动物大脑内侧的海马区负责掌控记忆,进入海马区的信息依靠“长时程增强”机制形成记忆。“长时程增强”是一种快速建立且持久作用的突触反应性增强,被认为是学习、记忆的神经基础。长期的高糖高脂肪饮食,长期处于焦虑、学习紧张,压力过大的情况,容易使大脑海马区产生炎症,久而久之就会对海马区功能产生损伤,从而影响记忆力。学生和白领群体由于学习压力和工作压力大,用眼时间长,普遍存在视疲劳现象。特别是长期存在视疲劳状态,也会导致记忆力下降或减退。漆黄素是一种抑制炎症反应的化合物,能有效抑制海马区炎症,防止海马区损伤,使与“长时程增强”有关的细胞内分子活动活跃起来,从而提高记忆力。如果同时改善记忆力和缓解视疲劳可以起到事半功倍的效果。漆黄素具有提高记忆力的功效,但是水溶性差,生物利用度低,要服用较大的剂量才会起效,而且对于学习压力巨大的学生想提高记忆力,如果仅单纯缓解海马区炎症提高其功能,而不同时缓解视疲劳,将很难达到预期效果的,现有技术单独改善记忆力或缓解视疲劳的效果不理想。
发明内容
有鉴于此,本发明在于提供一种改善记忆功能/缓解视疲劳的组合物。
所述改善记忆功能/缓解视疲劳的组合物按重量百分比计包括漆黄素/漆黄素复合物10-50%、α-亚麻酸2-15%、叶黄素2-15%、原花青素2-15%、VB1 2-10%、VB12 2-10%、蓝莓10-50%、枸杞10-50%、桑椹10-50%;所述漆黄素复合物为磷脂复合物或漆黄素纳米结晶或漆黄素-环糊精复合物中的一种或多种,所述漆黄素磷脂复合物的制备方法包括:将漆黄素和磷脂按重量比1:1-4溶于有机溶剂中,加热进行反应,所述漆黄素重量浓度为5-80mg/ml。
优选地,所述磷脂为卵磷脂、脑磷脂、肌醇磷脂或磷脂酸中的一种或多种。
优先地,所述有机溶剂为四氢呋喃、乙醇、甲醇、三氯甲烷、二氯甲烷、乙酸乙酯中的一种或多种。
优选地,所述反应的反应时间为1-5h,反应温度为30-60℃。
在某些具体实施例中,所述漆黄素磷脂复合物的制备方法包括:以四氢呋喃、乙醇、甲醇、三氯甲烷、二氯甲烷、乙酸乙酯等中的一种为反应溶剂,漆黄素和卵磷脂进行反应,反应时间为1-5h,反应温度为30-60℃,反应物质量浓度为5-80mg/ml,反应物投料按重量比为漆黄素:卵磷脂=1:1-4。
进一步,所述漆黄素纳米结晶的制备方法包括:将稳定剂溶于水后与漆黄素混合研磨;所述稳定剂为聚维酮K30、共聚维酮S630、十二烷基硫酸钠、泊洛沙姆188、卵磷脂、吐温80、没食子酸丙酯(PG)中的一种或多种;所述漆黄素与所述稳定剂的重量比为1:0.1-1。
优选地,所述漆黄素纳米结晶的粒径为100-950nm。
优选地,所述研磨是在研磨机里进行研磨20-360min。
优选地,研磨后得到的漆黄素纳米混悬液用喷雾干燥或冷冻干燥进行得到漆黄素纳米结晶。
优选地,漆黄素纳米混悬液在干燥前加入5%的甘露醇。
在某些具体实施例中,所述漆黄素纳米结晶的制备方法包括:采用聚维酮K30(PVPK30)、共聚维酮S 630、十二烷基硫酸钠(SDS)、泊洛沙姆188(P188)、卵磷脂、吐温80、没食子酸丙酯(PG)等中的一种或几种与含1-15%的漆黄素悬浮液混合,在研磨机里进行研磨20-360min得到粒径为100-950nm的漆黄素纳米混悬液,用喷雾干燥或冷冻干燥进行得到漆黄素纳米结晶。
进一步,所述漆黄素纳米结晶的制备还可以使用反溶剂沉淀法。
在某些具体实施例中,所述反溶剂沉淀法包括:将稳定剂微晶纤维素溶解于水中,并置于磁力搅拌器上搅拌,作为水相;然后将漆黄素15mg溶于无水乙醇中,作为有机相,之后将有机相在持续搅拌下快速加入水相中,继续搅拌10-15min,放入冷冻干燥机里先预冻24h,再进行干燥得到漆黄素纳米结晶。
进一步,所述漆黄素-环糊精复合物的制备方法包括:将漆黄素与环糊精加入水中振荡、离心得上清液;所述环糊精为α-环糊精、β-环糊精、γ-环糊精、麦芽糖基-β-环糊精、羟丙基-β-环糊精中的一种或多种;所述漆黄素与环糊精的重量比为1:1-10。
进一步,所述振荡具体为在25-60℃的水浴中振荡3h-72h。
进一步,将所述上清液进行喷雾干燥或冷冻干燥,得到固体为漆黄素-环糊精复合物。
进一步,在所述上清液干燥前加入5%的甘露醇。
在某些具体实施例中,所述漆黄素-环糊精复合物的制备方法包括:将漆黄素与了α-环糊精(α-CD)、β-环糊精(β-CD)、γ-环糊精(γ-CD)、麦芽糖基-β-环糊精(M-β-CD)、羟丙基--β-CD(HP-β-CD)加入一定量纯水中,并在25-60℃的水浴中振荡3h-72h,离心,上清液进行喷雾干燥或冷冻干燥,得到固体为漆黄素-环糊精复合物。
本发明目的在于还提供一种包括前述的改善记忆功能/缓解视疲劳的组合物的药物/保健食品。
进一步,所述改善记忆功能/缓解视疲劳药物/保健食品还包括辅料,所述辅料为微晶纤维素、可溶性淀粉、预胶化淀粉、糊精、乳糖、甘露醇中的一种或多种;所述漆黄素复合物与辅料重量比为1:0.2-2。
进一步,所述改善记忆功能/缓解视疲劳药物/保健食品是先将所述漆黄素/漆黄素复合物与所述辅料混合制剂,然后与所述α-亚麻酸、叶黄素、原花青素、VB1、VB12、蓝莓、枸杞、桑椹混合。
进一步,所述改善记忆功能/缓解视疲劳药物/保健食品为胶囊或片剂或微丸或颗粒剂制剂。
本发明目的在于还提供一种改善记忆功能的方法,该方法是通过使用前任一所述的组合物或前任一所述的改善记忆功能/缓解视疲劳保健食品。
在某些具体实施例中,小鼠的服用的剂量≥20mg/kg漆黄素,优选为≥40mg/kg漆黄素,更优选为≥80mg/kg漆黄素。
本发明目的在于还提供一种缓解视疲劳的方法,该方法是通过使用前任一所述的组合物或前任一所述的改善记忆功能/缓解视疲劳保健食品。每日2次,每次2粒,口服,连续食用60天。
本发明中,术语“mg/kg漆黄素”为:1kg的服用者服用1mg漆黄素,如果是服用本发明中的漆黄素复合物或者保健食品,则要进行相应的折算。
本发明中,所涉及的“重量”“时间”“重量比”“重量百分数”“粒径”等表明物理或化学性质的数值,不包括由于仪器误差和操作误差导致的数值差,即是说由于仪器误差和操作误差导致的数值差范围也在本发明技术方案之中。
本发明中,所涉及的“搅拌”“混合”“干燥”等化学工艺术语,指的就是本领域常规技术人员的操作,即是说若是换成不同的术语相同的工艺也属于本发明的技术方案。
本发明中,术语“重量浓度”为固体在液体中的比例,包括溶于溶剂和不溶于溶剂的部分,单位为w/v。
本发明中,使用的“甘露醇”均为赋形剂,不会对产品产生影响疗效的影响。
本发明中,术语“提取物”为一般释意,即对相关中药进行提取、浓缩、干燥得到的提取物。
本发明有益效果在于:
本发明提供的改善记忆功能/缓解视疲劳的组合物能明显改善记忆功能和明显缓解受试者的视疲劳,使用者的眼酸痛、眼胀、畏光、食物模糊、眼干涩、异物感等症状有明显改善。
本发明提供的改善记忆功能/缓解视疲劳的组合物能同时改善记忆功能和缓解视疲劳具有协同效应,对两方面功能的改善同时具有增强作用。
具体实施方式
所举实施例是为了更好地对本发明进行说明,但并不是本发明的内容仅局限于所举实施例。所以熟悉本领域的技术人员根据上述发明内容对实施方案进行非本质的改进和调整,仍属于本发明的保护范围。
实施例1漆黄素纳米结晶的制备
研磨法:将4%的泊洛沙姆188(P 188)和0.5%的共聚维酮S 630溶于50ml纯化水中,搅拌至完全溶解,加入1%的没食子酸丙酯(PG),搅拌至完全溶解,备用。取该混合溶液46g,漆黄素4g,加入研磨罐中,加入研磨球,研磨200min后,过筛分离出漆黄素纳米混悬液,加入5%的甘露醇,放入冷冻干燥机里先预冻24h,再进行干燥得到漆黄素纳米结晶。
反溶剂沉淀法:将稳定剂微晶纤维素溶解于水中,并置于磁力搅拌器上搅拌,作为水相;然后将漆黄素15mg溶于无水乙醇中,作为有机相,之后将有机相在持续搅拌下快速加入水相中,继续搅拌10-15min,加入5%的甘露醇,放入冷冻干燥机里先预冻24h,再进行干燥得到漆黄素纳米结晶。
测定漆黄素纳米结晶冻干品在磷酸盐缓冲液(pH=6.8)的溶解度。分别吸取磷酸盐缓冲液(pH=6.8),0.5%吐温80溶液,向其中加入过量的漆黄素和漆黄素纳米结晶冻干品,连续涡旋震荡48h后,离心后取上清液2mL,用0.22μm微孔滤膜过滤,释放介质稀释后测定其吸光度,计算出溶解度如表1。
表1漆黄素和漆黄素纳米结晶在水中的溶解度
实施例2漆黄素磷脂复合物的制备
将300mg漆黄素和1.2g大豆卵磷脂溶于30ml四氢呋喃,在40℃下,回流磁力搅拌反应2h。反应结束后将反应液减压蒸馏除去反应溶剂,加入适量三氯甲烷,抽滤,将滤液继续减压蒸馏除去三氯甲烷,40℃真空干燥3h,得到漆黄素磷脂复合物固体。复合物在正辛醇和水中的溶解度见表2。
表2漆黄素及其磷脂复合物在正辛醇和水中的溶解度
实施例3漆黄素-环糊精复合物的制备
将0.286漆黄素与1.38gβ-环糊精(β-CD)加入25ml纯水中,并在30℃的水浴中振荡72h,离心,得上清液,加入5%的甘露醇,放入冷冻干燥机里先预冻24h,再进行干燥得到漆黄素/环糊精复合物。复合物在水中的溶解度见表3。
表3漆黄素和漆黄素/环糊精复合物在水中的溶解度
样品 | 溶解度mg/ml |
漆黄素 | 0.15 |
漆黄素/环糊精复合物 | 1.32 |
实施例4复方胶囊1制备
将15份漆黄素与10份的微晶纤维素进行混合,制粒,用30目筛进行过筛和整粒,用真空干燥方法烘干颗粒,温度35℃,烘干至水分低于7%。将所制得25份漆黄素颗粒与2份α-亚麻酸、5份叶黄素、10份原花青素、2份VB1、2份VB12、14份枸杞提取物、20份蓝莓提取物、20份桑椹提取物进行混合,灌装胶囊。
实施例5复方胶囊2制备
将30份漆黄素纳米结晶与10份的微晶纤维素进行混合,制粒,用30目筛进行过筛和整粒,用真空干燥方法烘干颗粒,温度35℃,烘干至水分低于7%。将所制得40份漆黄素颗粒与6份α-亚麻酸、5份叶黄素、10份原花青素、2份VB1、2份VB12、10份枸杞提取物、15份蓝莓提取物、10份桑椹提取物进行混合,灌装胶囊。
实施例6复方胶囊3制备
将20份漆黄素磷脂复合物与20份的微晶纤维素进行混合,制粒,用30目筛进行过筛和整粒,用真空干燥方法烘干颗粒,温度35℃,烘干至水分低于7%。将所制得40份漆黄素颗粒与5份α-亚麻酸、8份叶黄素、5份原花青素、5份VB1、5份VB12、12份枸杞提取物、10份蓝莓提取物、10份桑椹提取物进行混合,灌装胶囊。
实施例7复方胶囊4制备
将15份漆黄素磷脂复合物与15份的微晶纤维素进行混合,制粒,用30目筛进行过筛和整粒,用真空干燥方法烘干颗粒,温度35℃,烘干至水分低于7%。将所制得30份漆黄素颗粒与8份α-亚麻酸、5份叶黄素、5份原花青素、8份VB1、8份VB12、10份枸杞提取物、10份蓝莓提取物、16份桑椹提取物进行混合,灌装胶囊。
实施例8复方胶囊改善记忆功能验证
(1)实验动物及其分组
采用SPF级昆明雌性小鼠,体重18g-22g。动物饲养室温度20-25℃,湿度为40-70%。60只小鼠随机分为5组,每组12只,即空白对照组、模型组、低剂量组(含20mg/kg漆黄素)、中剂量组(含40mg/kg漆黄素)、高剂量组(含80mg/kg漆黄素),各受试物组灌胃给予相应的药物,空白对照组灌胃给予纯化水,均为10ml/kg。
(2)跳台实验
末次给样后1h(或次日)开始训练。将动物放入反应箱内(台上、台下)适应环境3min,然后将动物放置反应箱内的铜栅上,立即通以36V的交流电。动物受到电击,其正常反应是跳回平台(绝缘体),以躲避伤害性刺激。多数动物可能再次或多次跳至铜栅上,受到电击又迅速跳回平台上,小鼠训练5min,24h后进行重测验,将小鼠放在平台上,记录各鼠第一次跳下平台的潜伏期、各鼠3min内电击次数,如小鼠5min内未跳下平台,潜伏期按300s计算。
受试样品对记忆障碍模型小鼠的影响:除空白对照组外,模型组、给药组小鼠腹腔注射东莨菪碱造模10min后,进行跳台实验训练。先将小鼠放入跳台箱中适应环境3min,适应期间不通电,随后将小鼠放在安全平台上,并接通36V交流电,如果小鼠跳下平台,受到电击后跳回平台为正确反应,小鼠训练5min,24h后再次进行检测,直接将小鼠放在安全平台上并接通电源,记录小鼠第一次跳下平台时间即为潜伏期,并记录小鼠跳下平台点击次数。如小鼠5min内未跳下平台,潜伏期按300s计算。
结果见表4,与空白对照组比较,模型组小鼠跳台潜伏期明显缩短(P<0.01);与模型组比较,低剂量组、中剂量组、高剂量组均可显著延长跳台潜伏期(P<0.01)。与空白对照组比较,模型组小鼠错误次数增加(P<0.01);与模型组比较,低剂量组、中剂量组、高剂量组均可显著减少错误次数(P<0.05或P<0.01)。因此可判定此实验结果为阳性。
表4小鼠跳台实验中潜伏期和错误次数(X±SD)
组别 | 动物数量(只) | 潜伏期(s) | 错误次数 |
空白对照组 | 12 | 195.50±13.63 | 2.08±1.62 |
模型组 | 12 | 139.25±25.32 | 5.42±4.15 |
低剂量组 | 12 | 166.30±20.26 | 1.67±1.68 |
中剂量组 | 12 | 178.76±18.37 | 1.33±1.56 |
高剂量组 | 12 | 189.62±15.18 | 1.25±1.63 |
(3)水迷宫实验
设对照组、低剂量组、中剂量组和高剂量组。给受试物30天后开始进行水迷宫实验。训练期间继续给予受试物。每天训练一次,连续5天。第一天训练前将小鼠放在梯子附近,使其自动爬上3次,以后每次训练前将小鼠放在梯子附近,使其自动爬上1次。第一天训练时,用挡板在A处挡死,从A点开始进行训练;第二天加长路程从B处开始,此路程训练3天,至80%的动物在2min内达到终点;第五天从起点开始训练,将小鼠放在起点,记录从起点到达终点的所需的时间和发生错误的次数。最后以5天的中学习成绩进行评价(即各组5天到达终点的总时间、总错误次数和各组2min内到达终点的动物数)。由表5可知,经连续给予小鼠不同剂量的胶囊30天,各剂量组的小鼠到达终点的时间以及到达终点前的错误次数明显少于对照组,各剂量组小鼠2min内到达终点的数量均高于对照组,且成剂量依赖关系。表明本发明的复方胶囊具有明显改善记忆力的作用。
表5水迷宫实验
实施例9复方胶囊缓解视疲劳功能验证
(1)实验方法与分组
受试对象:选择18-65岁成人,长期用眼,视力易疲劳者。排除患有感染性,外伤性眼部疾患者;进行眼部手术不足3个月者;患有角膜、品体、玻璃体、眼底病变等内外眼疾患者;患有心血管、脑血管、肝、肾、造血***等疾病者;妊娠或哺乳期妇女、过敏体质患者;短期内服用与受试功能有关的物品,影响到对结果的判定者;长期服用有关治疗视力的药物,保健品或使用其他治疗方法未能终止者;不符合纳入标准,未按规定食用受试物者,或资料不全等影响功效或安全性判断者。
试验设计与分组:采用自身和组间两种对照设计。根据随机、双盲的要求进行分组,分组时根据症状及视力检查情况,使试食组和对照组的症状及视力水平均衡。同时要考虑年龄、性别等因素,使两组具有可比性。试食试验结束时每组受试者人数不少于50例。
受试物剂量和使用方法:试食组服用复方胶囊(按实施例6制备),每日2次,每次2粒,口服。对照组服用安慰剂。受试物服用时间为连续60天。受试者在试食期间停止服用有关改善视力的药物或其他保健品。
(2)功效判定
眼酸痛、眼胀、畏光、视物模糊、眼干湿、异物感、流泪,全身不适8种症状中有3种改善,且其他症状无恶化即判定症状改善。计算两组症状改善例数和两组症状改善有效率。症状改善有效率(%)计算方法为症状改善例数试食例数×100。将两组症状改善有效率进行统计学检验。有表6可知,与对照组相比,试食组的眼酸痛、眼胀、畏光、视物模糊、眼干湿、异物感、流泪,全身不适等症状的改善率显著提高。表明本发明的复方胶囊具有明显的缓解视疲劳的作用。
表6复方胶囊对视疲劳主要症状的改善情况
最后说明的是,以上实施例仅用以说明本发明的技术方案而非限制,尽管参照较佳实施例对本发明进行了详细说明,本领域的普通技术人员应当理解,可以对本发明的技术方案进行修改或者等同替换,而不脱离本发明技术方案的宗旨和范围,其均应涵盖在本发明的权利要求范围当中。
Claims (10)
1.改善记忆功能/缓解视疲劳的组合物,其特征在于,所述组合物按重量百分比计包括漆黄素/漆黄素复合物10-50%、α-亚麻酸2-15%、叶黄素2-15%、原花青素2-15%、VB1 2-10%、VB12 2-10%、蓝莓提取物10-50%、枸杞提取物10-50%、桑椹提取物10-50%;所述漆黄素复合物为磷脂复合物和/或漆黄素纳米结晶或漆黄素-环糊精复合物中的一种或多种;所述漆黄素磷脂复合物的制备方法包括:将漆黄素和磷脂按重量比1:1-4溶于有机溶剂中,加热进行反应,所述漆黄素重量浓度为5-80mg/ml。
2.根据权利要求1所述的组合物,其特征在于,所述磷脂为卵磷脂、脑磷脂、肌醇磷脂或磷脂酸中的一种或多种。
3.根据权利要求1所述的组合物,其特征在于,所述反应的反应时间为1-5h,反应温度为30-60℃。
4.根据权利要求1所述的组合物,其特征在于,所述漆黄素纳米结晶的粒径为100-950nm。
5.根据权利要求1所述的组合物,其特征在于,所述漆黄素纳米结晶的制备方法包括:将稳定剂溶于水后与漆黄素混合研磨;所述稳定剂为聚维酮K30、共聚维酮S630、十二烷基硫酸钠、泊洛沙姆188、卵磷脂、吐温80、没食子酸丙酯(PG)中的一种或多种;所述漆黄素与所述稳定剂的重量比为1:0.1-1。
6.改善记忆功能/缓解视疲劳药物/保健食品,其特征在于,所述改善记忆功能/缓解视疲劳药物/保健食品包括权利要求1-4任一所述的组合物和药理学可接受或食品可接受的辅料,所述漆黄素复合物与所述辅料重量比为1:0.2-2。
7.根据权利要求5所述的改善记忆功能/缓解视疲劳药物/保健食品,其特征在于,其制备方法包括:先将所述漆黄素/漆黄素复合物与所述辅料混合制剂,然后与所述α-亚麻酸、叶黄素、原花青素、VB1、VB12、蓝莓提取物、枸杞提取物、桑椹提取物混合。
8.根据权利要求6所述的改善记忆功能/缓解视疲劳药物/保健食品,其特征在于,所述改善记忆功能/缓解视疲劳药物/保健食品为胶囊或片剂或微丸或颗粒剂制剂。
9.一种改善记忆功能的方法,其特征在于,利用权利要求1-3任一所述的组合物或权利要求5-7任一所述的改善记忆功能/缓解视疲劳保健食品进行改善。
10.一种缓解视疲劳的方法,其特征在于,利用权利要求1-3任一所述的组合物或权利要求5-7任一所述的改善记忆功能/缓解视疲劳保健食品进行缓解。
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103494134A (zh) * | 2013-08-28 | 2014-01-08 | 沈阳农业大学 | 一种缓解视力疲劳蓝莓含片及其制作方法 |
CN104256827A (zh) * | 2014-10-17 | 2015-01-07 | 山东禹王制药有限公司 | 一种改善视力的口服液及其制备方法 |
-
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103494134A (zh) * | 2013-08-28 | 2014-01-08 | 沈阳农业大学 | 一种缓解视力疲劳蓝莓含片及其制作方法 |
CN104256827A (zh) * | 2014-10-17 | 2015-01-07 | 山东禹王制药有限公司 | 一种改善视力的口服液及其制备方法 |
Non-Patent Citations (2)
Title |
---|
陈虹霞,等: "漆树黄酮类化合物研究进展", 《天然产物研究与开发》 * |
黄远英: "越橘叶黄素酯软胶囊缓解视疲劳的保健作用", 《四川生理科学杂志》 * |
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