CN107823295A - 栀子花在制备改善睡眠障碍或改善记忆力减退或通便或提高免疫力药物或保健食品中应用 - Google Patents
栀子花在制备改善睡眠障碍或改善记忆力减退或通便或提高免疫力药物或保健食品中应用 Download PDFInfo
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Abstract
本发明公开了栀子花在制备改善睡眠障碍或改善记忆力减退或通便或提高免疫力药物或保健食品中应用。所制备的栀子花本身是栀子花的花初期的花或花蕾或花盛期的花或花衰期的花的阴干花或晒干花，或所制备的栀子花本身是新鲜栀子花的花初期的花或花蕾或花盛期的花或花衰期的花的冷冻干燥花蕾或冷冻干燥花。所制备栀子花的原料组分本身是上述栀子花总提物上大孔吸附树脂的水洗脱部位或30％乙醇洗脱部位或70％乙醇洗脱部位或95％乙醇洗脱部位或冷冻干燥花蕾的粉末或冷冻干燥花的粉末，上述栀子花制备的原料组分具有改善记忆功能减退功能疗效或改善睡眠障碍功能疗效或润肠通便功能疗效或提高免疫力功能疗效。
Description
技术领域
本发明涉及栀子花在制备改善睡眠障碍或改善记忆力减退或通便或提高免疫力药物或保健食品中应用，属于中医药制备技术领域。
背景技术
栀子花来源主要为茜草科栀子属植物栀子Gardenia jasminoides Ellis.的花或茜草科栀子属所有已知植物的花，更具体为新鲜栀子花的花初期的花或花蕾或花盛期的花或花衰期的花、新鲜栀子花蕾冷冻干燥花蕾或新鲜栀子花冷冻干燥花。栀子花性寒味甘苦，入肺、肝经，可药食用两用。栀子花含黄酮、单萜、二萜、三萜、果胶、鞣质、氨基酸、微量元素等成分类型，特别是黄酮类、单萜类、二萜类和三萜为其花的营养价值成分或活性成分类型，如含藏红花素、栀子苷、栀子花酸A、栀子花酸B、乙酸苄酯、乙酸芳樟酯，特别是黄酮类化合物5，7-dihydroxyl-3′，4′，5′-trimethoxyflavone、5，7，4′-trihydroxyl-6-methoxyflavone、5，7，4′-trihydroxyl-8-methoxyflavone、5，7，3′-trihydroxyl-8，4′，5′-trimethoxyflavone、5-hydroxyl-6，7，3′，4′，5′-pentamethoxyflavone、5，3′-dihydroxyl-7，4′，5′-trimethoxyflavone、5-hydroxyl-7，3′，4′，5′-tetramethoxyflavone、3，5，6，4′-tetrahydroxy-3′，5′-dimethoxyflavone、5，7，3′，4′，5′-pentame-thoxyflavone等。栀子花具有泻火除烦，清热利尿，凉血解毒功效。现代药理研究具有镇静安神、缓解疲劳功能。栀子花为药食两用，加工后成为饭桌上的美味佳肴。人们在栀子开花季节，把新鲜栀子花用水泡茶喝或当蔬菜炒着吃，也有把栀子花和大米一起煮粥吃。栀子花鲜汤、栀子花炒竹笋、栀子花炒韭菜等菜肴不但味道鲜美，颇佳能够起到清热凉血、化痰止咳、宽肠通便的作用。栀子花药用价值和保健作用已被认可，但是泡茶、爆炒、煎煮等传统工艺栀子花都是经过高温烹制营养成分被高温破坏，挥发性营养价值成分容易流失。栀子为江西道地药材，其花在保健食品中应用有待进一步系统研究完善，将有助于地方经济的发展。
发明内容
本发明目的是提供栀子花在制备改善睡眠障碍或改善记忆力减退或通便或提高免疫力药物或保健食品中应用。
本发明采用了下述技术方案。
栀子花原料组分的制备方法如下：
(一)采用冷冻干燥工艺将采摘的新鲜栀子花的花初期的花或花蕾或花盛期的花或花衰期的花置于冰柜温度于零下5℃～零下40℃硬化结冰后，置于冷冻真空干燥机内温度于零下5℃～零下50℃，真空度为1～999pa的条件下，冷冻真空干燥6～48小时，其水分含量小于5％，得新鲜栀子花冷冻干燥的花蕾或冷冻干燥的花。
(二)栀子花药材粉碎成粗粉，用0-100％乙醇浸泡0.5-2小时，4-12倍量溶剂加热回流提取2-4次，每次1-3小时，过滤，合并滤液。上述滤液与45-80℃减压浓缩得浸膏，用水稀释至0.5-1.5g生药材/ml，直接上大孔吸附树脂AB-8型或D-101型或HPD-400或各种型号大孔吸附树脂富集，依次用水洗脱、30％乙醇水洗脱、70％乙醇水洗脱、95％乙醇水洗脱，得水洗脱部位、30％乙醇水洗脱部位、70％乙醇水洗脱部位、95％乙醇水洗脱部位，各洗脱部位在45-80℃减压回收溶剂至乙醇适量浓度，用冷冻干燥法或喷雾干燥进行干燥，收集冻干粉或喷雾干燥粉，即得。
前述方法制备的栀子花原料组分可用于制备改善睡眠障碍或改善记忆力减退或润肠通便或提高免疫力药物或保健食品。所述药物或保健食品包括口服液、胶囊、片剂、泡腾片、粉针剂、水针剂、注射剂、雾化剂、微乳剂、凝胶剂、纳米制剂或各种已知剂型制剂或各种可接受剂型制剂，所述药物还包括各种单方制剂和复方制剂。
本发明的优点是：提供了栀子花原料组分的制备方法，所得栀子花原料组分可用于制备改善睡眠障碍或改善记忆力减退或润肠通便或提高免疫力药物或保健食品。
提供了栀子花具体新用途和新功效。
发现了栀子的新的药用部位，栀子花的花蕾，特别是冷冻干燥的栀子花的花蕾，其含有未受外界其他因素影响的花蜜。
具体实施方式
下面结合实施例对本发明作进一步描述：
实施例1
新鲜栀子花的冷冻干燥花蕾的制备方法如下：采用冷冻干燥工艺将采摘清洗后的新鲜栀子花的花蕾2000克置于冰柜温度于零下35℃硬化结冰后，置于冷冻真空干燥机内温度于零下45℃，真空度为8pa的条件下，冷冻真空干燥12小时，其水分含量小于5％，得新鲜栀子花冷冻干燥的花蕾。
实施例2
将实例1中得到的新鲜栀子花冷冻干燥的花蕾应用粉碎机打粉，过药典的6号筛，得100目新鲜栀子花冷冻干燥花蕾的粉末。
实施例3
栀子花水洗脱部位、30％乙醇水洗脱部位、70％乙醇水洗脱部位、95％乙醇水洗脱部位的原料组分的制备方法：将实例2中的100目新鲜栀子花冷冻干燥花蕾的粉末，用70％乙醇水或95％乙醇水浸泡1小时，10倍量溶剂加热回流提取3次，每次1.5小时，过滤，合并滤液。上述滤液于45℃减压浓缩得70％乙醇水浸膏或95％乙醇水浸膏，用水混悬70％乙醇水浸膏或95％乙醇水浸膏至0.5-1.2g生药材/ml，经过AB-8型大孔吸附树脂富集，依次用水、30％乙醇水、70％乙醇水、95％乙醇水洗脱，得到各洗脱部位，各洗脱部位在45℃减压回收溶剂至乙醇适量浓度，用冷冻干燥法或喷雾干燥进行干燥，收集冻干粉或喷雾干燥粉，即得栀子花水洗脱部位、30％乙醇水洗脱部位、70％乙醇水洗脱部位、95％乙醇水洗脱部位的原料组分。
实施例4
本发明从动物因素诱发性与生理性脑衰老的记忆力减退出发，将睡眠障碍(SleepDisorder，SD，其使脑部气络异常或紊乱内生毒邪至“毒损脑络”)和Aβ蛋白等多因素引起的生理性脑衰老的记忆力减退相结合，利用睡眠剥夺致睡眠障碍及鼠脑室一次性注射Aβ淀粉样蛋白制作睡眠障碍生理性脑衰老记忆力减退(Sleep Disorder-factors'PhysiologicalBrain Aging Memory Subside，SDPBAMS,)模型，简称SDAD模型。应用睡眠障碍生理性脑衰老记忆力减退(SDAD)模型大鼠对栀子花制备的原料组分为新鲜栀子花冷冻干燥花蕾的粉末及其30％乙醇水洗脱部位、70％乙醇水洗脱部位和95％乙醇水总提取物进行药理活性筛选，通过行为学(Morris水迷宫)测定和生理生化相应指标的测定与检测，实验证实新鲜栀子花冷冻干燥花蕾的粉末及其30％乙醇水洗脱部位、70％乙醇水洗脱部位和95％乙醇水总提取物能使睡眠障碍生理性脑衰老记忆力减退(SDAD)模型大鼠缩短潜伏期、增加过台次数，延长在第四象限逗留时间。同时，新鲜栀子花冷冻干燥花蕾的粉末及其95％乙醇水总提取物能使睡眠障碍生理性脑衰老记忆力减退(SDAD)模型大鼠自主活动减少，从而起到清心除烦，延缓脑衰老，改善睡眠，抗抑郁等多种功能。其对由睡眠障碍和Aβ纤丝形成聚集等多因素引起的睡眠障碍生理性脑衰老的记忆力减退(SDAD)具有辅助改善记忆功能，进一步证实栀子花制备的原料组分具有改善睡眠障碍或改善记忆力减退功能疗效。
1材料
1.1动物 SPF级健康SD雄性大鼠，体质量300-350g，由湖南斯莱克景达实验动物有限公司提供，许可证号：SCXK(湘)2009-0004。饲养条件：温度20-22℃，喂以大鼠标准饲料，自由饮水。
1.2栀子花的原料组分与试剂 由实例1、实例2和实例3得到的栀子花原料组分为100目新鲜栀子花冷冻干燥花蕾的粉末及其95％乙醇水总提取物和95％乙醇水总体物上大孔吸附树脂的30％乙醇水洗脱部位以及70％乙醇水洗脱部位。D-半乳糖(Sigma公司，批号Lot#SLBD5369V)；Aβ1-40(Sigma公司，批号052M4801V)。
1.3仪器 ZS-B型脑立体定位仪、Morris水迷宫视频分析系统(北京众实迪创科技发展有限责任公司)，Forma-86C ULT超低温冰箱(美国赛默飞)，Allegra64R高速冷冻离心机(美国贝克曼库尔特)，UV-1800型紫外-可见分光光度计(日本岛津公司)。
2方法
2.1动物分组和动物模型的建立 将110只健康SD雄性大鼠随机分为空白组、睡眠障碍生理性脑衰老记忆力减退(Sleep Disorder-factors'Physiological Brain AgingMemory Subside，SDAD)模型组、盐酸多奈哌齐组、栀子花95％乙醇水总提取物中剂量组、栀子花95％乙醇水总提取物高剂量组、栀子花30％乙醇水洗脱部位中剂量组、栀子花30％乙醇水洗脱部位高剂量组、栀子花70％乙醇水洗脱部位中剂量组、栀子花70％乙醇水洗脱部位高剂量组、新鲜栀子花冷冻干燥花蕾的粉末中剂量组、新鲜栀子花冷冻干燥花蕾的粉末高剂量组，共11组，每组10只大鼠。
睡眠障碍生理性脑衰老记忆力减退(SDAD)模型的建立：各实验组先利用改良多平台水环境法进行睡眠剥夺3周得睡眠障碍易发生理性脑衰老记忆力减退大鼠。之后，取未死亡状态良好的睡眠障碍易发生理性脑衰老记忆力减退病变大鼠再脑内注射凝聚态Aβ25-35得睡眠障碍生理性脑衰老记忆力减退(SDAD)整体动物模型。
空白组不予处理；模型组与各给药组分别按上述造模方法予以处理。模型组于脑内注射手术前14天开始灌胃2％吐温-80水溶液至手术后7天截止给药，共21天，每天1次。各给药组于睡眠剥夺第2周开始即手术前14天开始连续灌胃给药至手术后7天截止给药，共给药21天，每天1次。
2.2 Morris水迷宫实验 预先在水池里注入清水使水面高出平台1-2cm，水温控制在24士2℃左右。水池内壁涂有黑漆，每次测试前须向水池内加入适量黑色墨水，水池共分为4个象限。将平台放在第四象限中间，在其他三个象限任选一点面向水池池壁将大鼠放入水中，试验历时5天，每天上午每个象限各测试一次，每次测试1min。若大鼠在1min之内尚未找到平台，则将大鼠拿到平台上并使它在上面站15s，若大鼠在l min之内找到平台，也让其在平台上站15s，方结束一次训练，如此训练4天。在第5天，将平台移走，每只大鼠游l min，记录每只大鼠第一次经过原平台的时间(潜伏期)，每只大鼠在l min内经过平台的次数、游过的总距离以及在原平台所在象限及其它三个象限内逗留的时间，计算出在第四象限游泳的时间(t4)占整个游泳时间(t总)的百分比。
2.3自主活动测试：将小动物自主活动检测装置与MP-100生理实验信号采集分析系统相连，随机在每个装置内放1只大鼠，每次检测前让动物在装置内适应5min，检测室内保持安静，防止对大鼠的活动产生影响。记录各组大鼠20min内的自主活动次数和自主活动时间，并称量大鼠的体重变化。
2.4统计方法 采用SAS软件分析，实验数据用x±s表示，单因素方差分析实验的数据。P＜0.05为有统计学意义。
3结果
3.1栀子花原料组分对睡眠障碍生理性脑衰老记忆力减退(SDAD)模型大鼠Morris水迷宫实验的影响
与空白组比较，模型组大鼠潜伏期延长、过台次数减少，在第四象限逗留时间短，差异显著(P＜0.01)；与模型组比较，给药盐酸多奈哌齐组、栀子花原料组分各组能缩短潜伏期、增加过台次数，在第四象限逗留时间和距离延长(P＜0.05或P＜0.01)，说明各给药组治疗有效，提示栀子花原料组分(尤其是栀子花30％乙醇水洗脱部位组、新鲜栀子花冷冻干燥花蕾的粉末组、新鲜栀子花冷冻干燥花蕾粉末的95％乙醇水总提取物组)效果明显，具有改善记忆功能减退的功能疗效。结果见表1。
表1栀子花原料组分各部位对SDAD模型大鼠空间探索试验结果
与模型组比较：*P<0.05，**P<0.01
3.2栀子花原料组分对睡眠障碍生理性脑衰老记忆力减退(SDAD)模型大鼠自主活动行为学试验结果
与空白组比较，模型组大鼠自主活动次数减少(睡眠障碍、心神不宁、焦虑紧张不安、痴呆症状表现，大鼠毛色凌乱、行为焦躁并有一定攻击性)，体重增加缓慢，差异显著(P＜0.01)；与模型组比较，栀子花原料组分各部位能使模型动物的活动次数增加(疏肝和胃、理气解郁、改善睡眠功能、缓解疲劳功能，给药后的大鼠毛色光滑平整、性情温和)，体重增加明显(P＜0.05或P＜0.01)，说明栀子花原料组各部位对SDAD模型大鼠效果明显，尤其是新鲜栀子花冷冻干燥花蕾的粉末和栀子花95％乙醇总提取物效果最优。新鲜栀子花冷冻干燥花蕾的粉末因其含有花粉具有改善胃肠道功能(通便)，特别是青少年多动症、改善胃肠道功能(厌食症)并增加体重。见结果见表2和表3。
表2栀子花原料组分各部位对SDAD模型大鼠自主活动行为学试验结果
与模型组比较：*P<0.05，**P<0.01
表3栀子花原料组分各部位对SDAD模型大鼠体重变化分析结果
Claims (8)
1.栀子花在制备改善睡眠障碍或改善记忆力减退或通便或提高免疫力药物或保健食品中应用，其特征在于：栀子花制备的原料组分本身是栀子花总提物上大孔吸附树脂的水洗脱部位或30％乙醇水洗脱部位或70％乙醇水洗脱部位或95％乙醇水洗脱部位或栀子花粉碎的粉末或栀子花总提取物，上述栀子花制备的原料组分具有改善记忆功能减退或改善睡眠障碍或润肠通便或提高免疫力的功能疗效。
2.根据权利要求1中所述的栀子花在制备改善睡眠障碍或改善记忆力减退或通便或提高免疫力药物或保健食品中应用，其特征在于：栀子花来源主要为茜草科栀子属植物栀子Gardenia jasminoides Ellis.的花或茜草科栀子属所有已知植物的花，更具体为栀子花的花初期的花或花蕾或花盛期的花或花衰期的花的阴干花或晒干花，或新鲜栀子花的花初期的花或花蕾或花盛期的花或花衰期的花的冷冻干燥花蕾或冷冻干燥花。
3.根据权利要求2中所述的栀子花在制备改善睡眠障碍或改善记忆力减退或通便或提高免疫力药物或保健食品中应用，其特征在于：所制备的栀子花本身是新鲜栀子花的花初期的花或花蕾或花盛期的花或花衰期的花的冷冻干燥花蕾或冷冻干燥花，采用冷冻干燥工艺将采摘的新鲜栀子花的花初期的花或花蕾或花盛期的花或花衰期的花置于冰柜温度于零下5℃～零下40℃硬化结冰后，置于冷冻真空干燥机内温度于零下5℃～零下50℃，真空度为1～999pa的条件下，冷冻真空干燥6～48小时，其水分含量小于5％，得新鲜栀子花冷冻干燥的花蕾或冷冻干燥花。
4.根据权利要求1中所述栀子花在制备改善睡眠障碍或改善记忆力减退或通便或提高免疫力药物或保健食品中应用，其特征在于：栀子花原料组分的制备方法，将栀子花药材粉碎成粗粉，用0-100％乙醇浸泡0.5-2小时，4-12倍量溶剂加热回流提取2-4次，每次1-3小时，过滤，合并滤液。上述滤液与45-80℃减压浓缩得浸膏，用水稀释至0.5-1.5g生药材/ml，直接上大孔吸附树脂AB-8型或D-101型或HPD-400或各种型号大孔吸附树脂富集，依次用水洗脱、30％乙醇水洗脱、70％乙醇水洗脱、95％乙醇水洗脱，得水洗脱部位、30％乙醇水洗脱部位、70％乙醇水洗脱部位、95％乙醇水洗脱部位，各洗脱部位在45-80℃减压回收溶剂至乙醇适量浓度，用冷冻干燥法或喷雾干燥进行干燥，收集冻干粉或喷雾干燥粉，即得。
5.根据权利要求1-4中所述栀子花在制备改善睡眠障碍或改善记忆力减退或通便或提高免疫力药物或保健食品中应用，其特征在于：功能疗效为栀子花制备的原料组分为栀子花的花蕾或花盛期的花的阴干花或晒干花粉碎成40-100目的粉末，或新鲜栀子花的花蕾或花盛期的花的冷冻干燥花蕾或冷冻干燥花粉碎成40-100目的粉末，上述栀子花粉末含栀子花花粉或花蜜的主要营养成分，上述栀子花粉末主要含有多糖、氨基酸、微量元素、果胶、黄酮类活性成分、单萜类活性成分(环烯醚萜类活性成分)、二萜类活性成分和三萜类活性成分，上述栀子花粉末具有润肠通便或提高机体免疫力或改善记忆功能减退或改善睡眠障碍的功能疗效，上述栀子花粉末特别适用于治疗青少年多动症或厌食症，上述栀子花粉末具有强壮骨骼并增加骨密度。
6.根据权利要求1-5中所述栀子花在制备改善睡眠障碍或改善记忆力减退或通便或提高免疫力药物或保健食品中应用，其特征在于：栀子花制备的原料组分具有通便或提高免疫力功效，上述栀子花的总提取物上大孔吸附树脂的水洗脱部位，其水洗脱部位含栀子花花粉或花蜜的主要营养成分，其水洗脱部位主要含有多糖、氨基酸、微量元素和果胶，上述水洗脱部位具有润肠通便或提高机体免疫力的功能疗效，上述水洗脱部位特别适用于治疗青少年多动症或厌食症，上述水洗脱部位具有强壮骨骼并增加骨密度。
7.根据权利要求1-5中所述栀子花在制备改善睡眠障碍或改善记忆力减退或通便或提高免疫力药物或保健食品中应用，其特征在于：栀子花制备的原料组分具有改善记忆功能减退或改善睡眠障碍功能疗效，上述栀子花的总提取物及其总提取物上大孔吸附树脂的30％乙醇水洗脱部位或70％乙醇水洗脱部位或95％乙醇水洗脱部位，上述总提取物或30％乙醇水洗脱部位或70％乙醇水洗脱部位或95％乙醇水洗脱部位均具有改善记忆功能减退或改善睡眠障碍的功能疗效。
8.根据权利要求1中所述栀子花制备的原料组分在制备改善睡眠障碍或改善记忆力减退或通便或提高免疫力药物或保健食品中应用，其特征在于，所述药物或保健食品包括口服液、胶囊、片剂、泡腾片、粉针剂、水针剂、注射剂、雾化剂、微乳剂、凝胶剂、纳米制剂或各种已知剂型制剂或各种可接受剂型制剂，所述药物或保健食品还包括各种单方制剂和复方制剂。
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