CN1654041A - 老鹰茶水提取物总黄酮在制备调血脂药物中的应用 - Google Patents
老鹰茶水提取物总黄酮在制备调血脂药物中的应用 Download PDFInfo
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Abstract
本发明涉及老鹰茶水提取物总黄酮在制备调血脂药物中的应用。老鹰茶水提取物总黄酮具有明显的降低血清甘油三酯作用。其优点是：采用口服给药，服用方便，毒副作用小，长期服药无危害；疗效确切，作用于多个环节，适用于各型高脂血症；可根据需要开发为药品和保健品。
Description
技术领域
本发明涉及老鹰茶总黄酮的用途，确切地说是在制药领域中的应用。
背景技术
老鹰茶是我国江南农村的一种传统饮料，千百年来深受人们的喜爱和欢迎，原因在于原料丰富，加工简单，便于保管，饮用方便，而且是一种无毒、无污染的纯天然饮料。近年来，由于环境受到一定程度的污染，人们回归自然的意识不断增加，这种纯天然饮料越来越受到人们的青睐。为了认识和了解这一野生自然资源，更好的开发与利用，现将老鹰茶的研究与开发现状综述如下。
老鹰茶的植物学分类：属于樟科、木姜子属、毛豹皮樟，俗称“白茶”，也叫老阴茶。学名Litsea coreana Levc.vav.是一种常绿小乔木或乔木。常生长在海拔1000米左右的低山常绿阔叶林中，分布在四川、贵州、安徽、云南、湖南和江西等地。
当年生枝紫褐色或绿色，有卷曲柔毛，皮孔黄褐色或绿色，第二年枝秃净。芽卵行，鳞片外绿色或黄褐色绢毛。
叶革质、互生、椭圆形、狭椭圆形或倒卵状椭圆形，先端渐尖或突尖，基部锲形，长5-15cm，宽1.5-5.cm，背面灰白色，有卷曲柔毛，有时秃净，侧脉6-10条，叶柄长0.5-1.5cm，有毛。在自然环境下，年萌发新芽2轮，4-5月为春芽，8-9月为秋芽，以春芽产量为高。
花，腊黄色、花序无梗，数个簇生在叶腋，总苞外有短毛，每序有花4-8朵，花朵直径4-5mm。
果，近球状(有长椭圆形和倒椭圆形)，直径约6mm，果梗粗壮，长0.5-0.8mm，有毛，果托扁平膨大，有宿存的花被裂片。花期8-9月，果期次年5-8月。
种子，由一层较薄的果皮包裹，种子坚硬，有蜡质。种子直径约6mm。
老鹰茶中含有丰富的氨基酸，总含量为0.82％，8种人体必需氨基酸齐全，含量以亮氨酸最高，赖氨酸次之，蛋氨酸最低，这和绿茶相似，其中蛋氨酸含量还略高于绿茶。在非必需氨基酸中，以谷氨酸含量最高，其次是天冬氨酸和精氨酸，与绿茶相比无明显差异。从氨基酸总量上看，绿茶的氨基酸高于老鹰茶，其主要原因是绿茶中特有茶氨酸的含量高，茶氨酸在一定程度上反映绿茶与老鹰茶的口感差异，另一方面也说明绿茶原植物与老鹰茶植物有不同的氨基酸代谢类型。
老鹰茶富含多种矿物质元素，其中钾(K)、磷(P)、钙(Ca)、镁(Mg)、钠(Na)、锌(Zn)、铁(Fe)、硒(Se)都是人体必需的营养元素，尤其是锌(Zn)、铁(Fe)、硒(Se)元素含量高于绿茶，对造血、健脑有较好作用。更值得一提的是有害元素铅的含量明显低于绿茶。
老鹰茶含有的水溶性维生素主要是Vc、VB1和VB2，其含量比绿茶稍低，可能与加工过与代谢途径等因素有关。
老鹰茶中总黄酮(TF，total flavonoid)含量远高于绿茶，绿茶只有1.22％左右，而老鹰茶可高达3.45％，已经确定的有山柰酚(kaempferol)，山柰酚-3-O-β-D-葡萄糖苷(kaempferol-3-O-β-D-glucopyranoside)，槲皮素-3-O-β-D-葡萄糖苷(quercetin-3-O-β-D-glucopyranoside)。
老鹰茶中挥发油成分：老鹰茶经过常压水蒸气蒸馏提取老鹰茶的挥发性成分，得到浅黄色油状液体，香味浓郁，出油率0.1％左右。经色谱和质谱分析，鉴定出32种成分(其中萜类化合物及其衍生物20种)，已鉴定的含量占挥发油组成的95％，主要成分是正奎醛(decanal)含量为71.53％；其次是10-烯-十一醛(10-undecenal)，含量为5.02％；壬醛(n-nonaldehyde)，含量3.58％；正十二酸乙烯酯(dodecanoic acid，ethenyl ester)，含量2.63％。香味的主要成分为萜类，其中主要是分子量为204的萜类。
老鹰茶中还含有多糖、皂甙、生物碱、多酚和天然色素等。
另外，尤其值得一提的是，与绿茶相比，老鹰茶的化学成分不含咖啡碱物质，无兴奋作用，不影响睡眠，这对需要控制咖啡碱摄入的人更是一种良好的选择。
老鹰茶(Litsea coreana Levc.vav)在我国江南广大农村饮用由来已久，深受广大劳动人民的喜爱，但仅仅作为一种饮料。近年来，四川、贵州等地进行了一些开发和利用，但也仅限于粗加工，还没有充分认识到它的药理功能，它所潜在的药理作用机制更无前人探讨。根据文献报道，长期饮用有防馊、防腐、消暑解渴、消食化积、解毒、消肿利尿，明目、健胃、益思的作用。
本发明的目的在于提供老鹰茶总黄酮的新用途，即在制药中的新应用。
实际上，本发明提供了老鹰茶水提取物总黄酮在制备高脂血症药物中的应用。
随着人类寿命的延长，生活水平的不断提高，高脂血症(hyperlipidmia)的发病率在逐年上升，并且是心血管疾病的重要诱发因素，具有很高的致残率和致死率，严重威胁着人类的健康。据保守估计，高脂血症的患者近三亿，而我国就有将近四千万。世界卫生组织已将防治这一类疾病列为全球人类健康的重要问题之一。
近年来，治疗高脂血症的药物发展很快，但存在不良反应多或价格昂贵的缺点。治疗高脂血症的药物主要有：
1、胆酸络合剂主要用于IIa型高脂蛋白血症的治疗。其不良反应主要为胃肠道反应。
2、HMG-CoA还原酶抑制剂主要用于IIa和IIb型高脂蛋白血症的治疗。其不良反应较少，主要是肝功能异常。且价格昂贵，不易被患者所接受。
3、烟酸类可以用于II、III、IV、V型高脂蛋白血症等。其不良反应较多：皮肤潮红、瘙痒以及胃肠道反应等。
4、苯氧酸类临床应用于IIb、III、IV、V型高脂蛋白血症。其不良反应较少，主要是胃肠道反应，但价格昂贵，不易被患者所接受。
老鹰茶水提取物总黄酮的制备：称取老鹰茶叶，溶媒提取后，经过水溶和滤过，然后经大孔吸附树脂吸附，再经醇洗脱、减压浓缩后，经过真空干燥，得到总黄酮，得率约为4％，总黄酮含量大于50％。
药理学实验研究结果表明，老鹰茶水提取物总黄酮对脂肪乳剂所诱导的高脂血症性大鼠有明显降低血清TG、以上各指标均优于阳性对照药烟酸和山楂精。使用方法：口服。
老鹰茶水提取物总黄酮的主要优点：
1、采用口服给药，服用方便，毒副作用小，长期服药无危害。
2、疗效确切，作用于多个环节，适用于各型高脂血症。
3、可根据需要开发为药品和保健品。
为了更好地理解本发明的实质，下面将用老鹰茶总黄酮的药理实验及结果来说明其在制药领域中的新用途。
老鹰茶水提取物总黄酮对高脂血症大鼠作用实验如下：
1、材料与方法
1.1主要药物与试剂
老鹰茶水提取物总黄酮(自制)，烟酸片(上海九福药业有限公司，批号：030701)，山楂精(宁夏启元药业有限公司，批号：02029433)，胆固醇(中国医药(集团)上海化学试剂公司，AR级，批号：F20030410)；脱氧胆酸钠(北京双旋微生物培养基制品厂，批号：20030617)；丙基硫氧嘧啶(上海复星朝晖药业有限公司，批号：030505)；吐温80(蚌埠化学试剂厂，符合药用标准，批号：20030602)；1-2丙二醇(淮南市化学试剂厂，AR级，批号：20021020)；猪油自制。TG、TC测定试剂盒购自北京福瑞生物工程公司。
1.2主要仪器
电子天平FA2004(上海精天天平厂)、79HW-1恒温磁力搅拌器(江苏金坛市金城国胜实验仪器厂)、722紫外分光光度计(上海分析仪器厂制造)。
1.3实验动物
Spague-Dawlay(SD)大鼠70只，雌雄各半，体重180-200g，由安徽医科大学实验动物中心提供(皖医实动准第02号)。
1.4动物实验
SD大鼠在本实验室饲养一周后，按体重随机分为7组(每组10只)：正常对照组；模型组；给药组分别给予老鹰茶总黄酮80、40、20mg·kg-1·d-1三个剂量；烟酸组(120mg·kg-1·d-1)，山楂精组(0.5片·kg-1·d-1)。大鼠高脂血症性脂肪肝的复制参照刘明[1]的方法，加以改进。除正常组外，各组每天上午灌脂肪乳剂(10ml·kg-1·d-1)，下午给予相应的药物，正常组予以等量的蒸馏水灌胃。于1周后，断尾取血，测定血清脂质；3周后，放血处死动物，测定血清脂质。
1.5观察指标及测定方法
1.5.1一般情况
实验前，实验后每周称体重1次，观察食欲行为、粪便、毛发及动物死亡情况；实验结束时处死动物称量体重。
1.5.2粪便脂质变化
于实验开始后第3天用代谢笼(每笼1只)收集大鼠72小时的粪便，低温烤干后用生理盐水制成20％的匀浆，3000r/min离心15min，提取上清夜，用酶法测定TG、TC含量。
1.5.3血清生化
血清TG、TC、AST、ALT、SOD、MDA、GLU测定按试剂盒规范操作。
1.6统计学处理
计量资料mean±SD表示，各组间实验数据的比较采用两样本均数的t检验，P＜0.05有显著性差异。
2.结果
2.1一般情况
实验中各组体重无明显差异，但有少数大鼠出现腹泻现象。在实验第19天模型组死亡1只。(见表1)。
表1各组体重的变化(
x±s，n＝10)
| 组别 | 实验前 | 体重(g) | ||
| 1W | 2W | 3W | ||
| 正常组模型组烟酸组山楂精组大剂量组中剂量组小剂量组 | 191±9192±7190±6195±5193±6185±9190±8 | 195±12200±11198±13199±6201±10194±8201±5 | 203±11211±15204±12205±10208±13201±12209±12 | 210±15200±17216±14220±12213±13215±14221±13 |
**p＜0.01，与正常组比较，##p＜0.01，与模型组比较
2.2粪便脂质变化
粪便匀浆TG、TC用酶法测定，模型组TG比正常组显著升高，烟酸组、烟酸组、中剂量组及大剂量组与模型组相比明显降低；模型组TC比正常组显著升高，而给药组与模型组之间无显著性差异，各给药组之间也无显著性差异(见表2)。
表2各组粪便脂质变化(
x±s，n＝10)
| 组别 | TG mmol·l-1 | TC mmol·l-1 |
| 正常组模型组烟酸组山楂精组大剂量组中剂量组小剂量组 | 0.27±0.040.46±0.14**0.81±0.19##0.78±0.12##1.05±0.36#1.04±0.43##0.47±0.12 | 0.63±0.060.83±0.15**0.96±0.240.98±0.220.95±0.240.78±0.060.77±0.09 |
**p＜0.01，与正常组比较，##p＜0.01，与模型组比较
2.3血清脂质变化
每次采血后离心，血清放入-70℃冰箱保存备用。末次采血后离心取血清连同第一次同时用酶法测定。模型组TG明显比正常组升高，烟酸组、山楂精组、中剂量组及大剂量组与模型组相比明显降低。模型组TC明显比正常组升高，而给药组均无降低TC作用(见表3)。
表3各组血清脂质动态变化(
x±s，n＝10)
| 组别 | TG mmol·l-1 | TC mmol·l-1 | ||
| 1W | 3W | 1W | 3W | |
| 正常组模型组烟酸组山楂精组大剂量组中剂量组小剂量组 | 0.49±0.130.64±0.15*0.42±0.09##0.46±0.07##0.40±0.05##0.29±0.16##0.65±0.32 | 0.46±0.120.69±0.18**0.51±0.09#0.42±0.12##0.44±0.08##0.57±0.170.62±0.12 | 134±0.242.13±0.40**1.79±0.322.00±0.332.22±0.362.31±0.302.02±0.41 | 1.48±0.432.75±0.55**2.77±0.183.15±0.832.79±0.653.16±0.512.94±0.33 |
*p＜0.05，**p＜0.01，均与正常组比较；#p＜0.05，##p＜0.01，均与模型组比较
2.4血清ALT、AST、SOD、MDA的变化
末次采血后离心取血清ALT、AST用赖氏法测定，MDA用BTA法测定，SOD用黄嘌呤氧化酶法测定、GLU用葡萄糖氧化酶法测定。模型组ALT、MDA、GLU明显比正常组升高；中剂量组及大剂量组ALT、AST与模型组相比明显降低，大剂量组MDA与模型组相比明显下降，山楂精组、大剂量组GLU与模型组相比明显下降。(见表4)。
表4各组血清ALT、AST、MDA、SOD的变化(
x±s，n＝10)
| 组别 | ALTU·l-1 | ASTU·l-1 | MDAn mol·ml-1 | SODU·ml-1 | GLU mmol·l-1 |
| 正常组模型组烟酸组山楂精组大剂量组中剂量组小剂量组 | 8.18±2.5253.40±31.94**31.33±9.8050.50±17.7927.23±12.11#25.44±8.46#28.07±10.86 | 48.12±21.9662.60±21.1753.19±13.7951.87±14.7241.21±18.79#39.47±16.22#46.23±14.16 | 15.16±2.4919.62±5.32*20.64±6.1421.62±7.0014.25±4.29#15.18±5.2223.10±7.15 | 186.79±24.64173.53±43.06207.86±33.43208.56±26.88184.68±16.37160.52±61.51177.70±27.24 | 6.35±1.769.46±2.87*7.27±1.726.24±1.66#5.74±1.72##7.34±2.867.75±1.78 |
*p＜0.05，**p＜0.01，均与正常组比较；#p＜0.05，##p＜0.01，均与模型组比较
3.结论
老鹰茶水提取物总黄酮具有明显的降低血清甘油三酯作用。
老鹰茶水提取物总黄酮物理性状
该品为深黄色粉末，易吸潮，水溶性较差，易溶于乙醇，无特殊气味。
老鹰茶水提取物总黄酮临床推荐剂量：600～1200mg/d，口服，分3次服用。
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1、老鹰茶水提取物总黄酮在制备调血脂药物中的应用。
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104336775A (zh) * | 2013-07-26 | 2015-02-11 | 江西中烟工业有限责任公司 | 一种老鹰茶提取物及其制备方法以及该提取物在卷烟中的应用 |
| CN114470037A (zh) * | 2022-03-04 | 2022-05-13 | 重庆医科大学 | 老鹰茶提取物在防治肥胖和肠道菌群失调中的应用 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104336775A (zh) * | 2013-07-26 | 2015-02-11 | 江西中烟工业有限责任公司 | 一种老鹰茶提取物及其制备方法以及该提取物在卷烟中的应用 |
| CN114470037A (zh) * | 2022-03-04 | 2022-05-13 | 重庆医科大学 | 老鹰茶提取物在防治肥胖和肠道菌群失调中的应用 |
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