CN115137068A - 一种降尿酸的组合物及其应用 - Google Patents
一种降尿酸的组合物及其应用 Download PDFInfo
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- CN115137068A CN115137068A CN202210771744.8A CN202210771744A CN115137068A CN 115137068 A CN115137068 A CN 115137068A CN 202210771744 A CN202210771744 A CN 202210771744A CN 115137068 A CN115137068 A CN 115137068A
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Abstract
本发明公开了一种降尿酸的组合物及其应用,组合物活性成分的原料为:薏苡仁、百合、茯苓、桑叶、木瓜、绿茶、核桃仁、菊苣和葛根。组合物中的原料为常用的食品,具有良好的安全性。薏苡仁利水渗湿、百合消炎止痛,多味来自食用原料的活性成分共同作用,具有良好的降尿酸作用,同时具有较佳的口感。本发明一些实例的固体饮料,结合中药现代制剂工艺等现代技术对降尿酸固体饮料的生产工艺进行改进,得到了口感优良、质量稳定、功能性优于普通固体饮料的降尿酸固体饮料,并且成本低,携带、运输、贮存方便。
Description
技术领域
本发明属于天然产物领域,具体涉及一种降尿酸的组合物及其应用。
背景技术
尿酸高是人体内有一种叫做嘌呤的物质因代谢发生紊乱,致使血液中尿酸增多而引起的一种代谢性疾病。人体内尿酸每日的生成量和排泄量大约是相等,生成量是由食物和体内自行合成,排泄途径则是由肠道和肾脏排泄。临床上正常的尿酸值,男性为149~416μMol/L,女性为89~357μMo1/L。
但无论对痛风患者还是尿酸高的肾病患者来说,把尿酸控制在正常值是远远不够的。如果要避免大量尿酸沉积在关节和肾脏,保护肾功能,把尿酸控制在300μMol/L以下是比较理想的,而420μMol/L为正常的血尿酸上限值。
痛风的病理基础是高尿酸血症,当血液中尿酸浓度高于正常时,就会以尿酸盐结晶的方式析出,沉积在关节、心血管、肾脏和胰腺等处,通常首先表现为突发性关节红肿热痛。高尿酸血症患者体内的尿酸盐结晶在关节滑膜、滑囊、软骨及其他组织中沉积,引起反复发作性炎性疾病,称之为痛风,表现为痛风性急性关节炎、慢性关节炎、痛风石和关节畸形、痛风性肾病等。随着人们的生活水平不断日益提高,不论男女老少,人们在饮食和生活习惯上面有了更多的选择,所以很多不好的饮食和生活习惯日益增长,加上生活和工作的压力大,身体抵抗力变差,我国患痛风的人群也日益趋向年轻化,所以使控制尿酸的水平成为了必要。
中药治疗痛风是以清热利湿、活血通络、利尿排酸为指导原则,然而作为日常降尿酸使用并不适宜,一方面是长期使用药物会带来一定的副作用,另一方面,中药的使用也不够方便。
开发一种安全性高、效果良好的组合物,具有非常重要的意义。
发明内容
本发明的目的在于克服现有技术的至少一个不足,提供一种降尿酸的组合物及其应用。
本发明所采取的技术方案是:
本发明的第一个方面,提供:
一种组合物,其活性成分的原料为:薏苡仁、百合、茯苓、桑叶、木瓜、绿茶、核桃仁、菊苣和葛根。
在一些组合物的实例中,其活性成分的原料质量组成为:薏苡仁50~80份、百合15~28份、茯苓16~30份、桑叶7~12份、木瓜7~12份、绿茶2~8份、核桃仁2~8份、菊苣16~30份、葛根16~30份。
在一些组合物的实例中,所述活性成分为原料的水提物。
本发明的第二个方面,提供:
一种固体饮料,由辅料和功效成分组成,所述功效成分为本发明第一个方面所述的组合物。
在一些固体饮料的实例中,所述辅料选自选自矫味剂、产气剂、增稠剂。
在一些固体饮料的实例中,所述矫味剂选自罗汉果甜苷、甜菊糖苷、甘草甜素、阿斯巴甜。
在一些固体饮料的实例中,所述产气剂为碳酸氢钠。
在一些固体饮料的实例中,所述稠剂选自麦芽糊精。
在一些固体饮料的实例中,所述辅料由碳酸氢钠、罗汉果甜苷和麦芽糊精组成。
在一些固体饮料的实例中,固体饮料的质量组成包括功效成分2~6份、碳酸氢钠0.25~0.35份、罗汉果甜苷0.5~1.5份,麦芽糊精添加量为所述功效成分的0.5~3.5倍,所述功效成分为干浸膏。
本发明的第三个方面,提供:
本发明第一个方面所述组合物在制备降尿酸组合物中的应用。
在一些应用的实例中,所述降尿酸组合物的类型选自饮料、食品添加剂、糖果、糕点。
本发明的有益效果是:
本发明的组合物采用药食同源的中药材进行科学组方,薏苡仁味甘淡,性凉,入脾、胃、肺三经,具利水渗湿,健脾止泻、排脓,解毒散结的功效。主治水肿,脚气,小便不利,脾虚泄泻,湿痹拘挛,肺痈,肠痈;赘疣,癌肿,其利水渗湿作用可将组织上的尿酸盐结晶析回血液中,通过尿液将更多的尿酸排出体外,有效的净化血液,降低血尿酸。其中,薏苡仁中的游离型多酚和结合性多酚。现代药理研究表明,薏苡仁具有抗氧化、抗炎、降血糖、抗肿瘤、调节免疫等功效,它可通过抑制C5a和白细胞三烯B4抑制多种核白细胞的趋化作用,从而改善关节炎症状,而且安全,无毒副作用。百合,含有丰富的秋水仙碱,能迅速减轻炎症,有效止痛,对痛风发作所致的急性炎症有辅助治疗作用;茯苓可以解毒、除湿、利关节从而有降尿酸的作用;桑叶有利尿消肿、解毒、提高机体免疫力等作用。木瓜可清热化湿,能够使邪气排出体外,从而导致尿酸水平下降。菊苣,具有清热解毒,利尿消肿,健胃等功效。葛根有解肌退热,透疹,生津止渴,升阳止泻之功。多味来自食用原料的活性成分共同作用,具有良好的降尿酸作用。活性成分来源为长期使用的食品,安全性佳。
本发明一些实例的固体饮料,结合中药现代制剂工艺等现代技术对降尿酸固体饮料的生产工艺进行改进,得到了口感优良、质量稳定、功能性优于普通固体饮料的降尿酸固体饮料,并且成本低,携带、运输、贮存方便。
通过对本发明的固体饮料开展了体外和体内斑马鱼降尿酸功效评价实验,并进行了阳性对照,以体外XOD活性抑制率、斑马鱼尿酸强度为评价指标进行实验。体外实验表明,固体饮料对黄嘌呤氧化酶(XOD)的抑制率是14.6±0.737,表明本固体饮料具有降低斑马鱼尿酸水平的作用。体内实验表明,与正常对照比,模型组尿酸含量明细增高(p<0.05),阳性药物别嘌呤醇(200μM)与固体饮料(1 mg/mL)均能显著降低尿酸含量(p<0.05)。实验结果表明,固体饮料具有降低斑马鱼尿酸水平的作用。
附图说明
图1是固体饮料对斑马鱼尿酸含量的影响。
图2是不同组小鼠的血尿酸含量变化情况。
图3是不同组小鼠的踝关节HE染色结果。
图4是不同组小鼠的肝组织HE染色结果。
图5是不同组小鼠的肾组织HE染色结果。
图6是不同组小鼠的踝关节IHC染色结果。
具体实施方式
薏苡仁为禾本科植物薏苡Coix lacryma-jobi L.var.ma-yuen(ROman.)Stapf的干燥成熟种仁。
百合为百合科植物卷丹Lilium lancifolium Thunb.、百合Lilium browniiF.E.Brown var.viridulum Baker 或细叶百合Lilium Pumilum DC.的干燥肉质鳞叶。
茯苓为多孔菌科真菌茯苓Poria cocos(Schw.)Wolf的干燥菌核。
桑叶为桑科植物桑Morns alba L.的干燥叶。
木瓜为蔷薇科植物贴梗海棠Chaenomeles speciosa(Sweet)Nakai的干燥近成熟果实。
绿茶采取茶树Camellia sinensis (L.) O. Ktze.的新叶或芽,未经发酵,经杀青、整形、烘干等工艺而制作得到,含有的茶多酚、儿茶素、叶绿素、咖啡碱、氨基酸、维生素等营养成分。
核桃仁为胡桃科植物胡桃Juglans regia L.的干燥成熟种子。秋季果实成熟时采收,除去肉质果皮,晒干,再除去核壳及木质隔膜。
菊苣为维吾尔族习用药材。为菊科植物毛菊苣Cichori-um glandulosum Boiss.et Huet或菊苣Cichorium intybus L.的干燥地上部分或根。
葛根为豆科植物野葛Pueraria lobata(Willd.)Ohwi的干燥根。
下面结合实例,进一步说明本发明的技术方案。
浸膏的制备
按组成称取原料,10倍水煎煮1h,重复煎煮1次,8倍水煎煮1h,合并滤液,过滤,浓缩,干燥,所得干浸膏打粉,过60目筛备用。
固体饮料的制备
麦芽糊精、碳酸氢钠、罗汉果甜苷按比例量加入到干浸膏中;将物料充分混匀后,将物料充分混匀后,用80%乙醇制软材,过16目筛,置于60℃鼓风干燥箱干燥5~6h(水分含量在5%以下),过20目筛,得固体颗粒。
不同实施例活性成分的原料组成及固体饮料组成如表1所示:
表1
表1中,用量均以重量份计。
下面结合实验,进一步说明本发明的技术方案。
以下实验中,如无特别说明,所使用的固体饮料为实施例1固体饮料。
降尿酸药理实验:
1.实验目的
利用体外和体内斑马鱼实验评价固体饮料的降尿酸作用
1.1评价指标
①体外XOD活性抑制率
②斑马鱼尿酸强度。
2.实验方法
2.1产品对XOD活性的体外抑制
以黄嘌呤为底物,通过酶标仪检测产品XOD抑制活性。反应设置共6组:空白组、酶反应组、固体饮料组、固体饮料对照组、阳性药物组、阳性药物对照组。每组总体积为200μL,XOD抑制剂别嘌呤醇(1 mg/mL)作为阳性对照,各组的组成如表2所示。
表2
空白组:黄嘌呤(2 mM)+磷酸盐缓冲液;
酶反应组:黄嘌呤+黄嘌呤氧化酶(XOD 0.1 U/mL)+磷酸盐缓冲液;
固体饮料组:黄嘌呤+XOD+固体饮料溶液(10μg/mL);
固体饮料对照组:黄嘌呤+固体饮料溶液 +磷酸盐缓冲液;
阳性药物组:黄嘌呤+XOD+别嘌呤醇;
阳性药物对照组:黄嘌呤+别嘌呤醇+磷酸盐缓冲液。
37℃,避光预孵15 min后,通过加入50μL XOD 引发反应(XOD 需要在37℃下预孵30 min以稳定酶活),混合均匀,37℃,反应15min后,在295 nm处测定吸光度。
抑制率(%)=(1- [A3-A4] / [A1-A2])×100%,
其中A1、A2、A3、A4分别代表酶反应组、空白组、抑制剂组和对照组在295nm处的吸光度。
固体饮料对高尿酸血症斑马鱼尿酸水平的影响
选取5dpf 斑马鱼。评价固体饮料对斑马鱼的存活率影响,结果表明1 mg/mL及以下浓度的固体饮料对5dpf斑马鱼存活率没有影响,且不会造成畸形等影响。将5dpf分成4组:正常对照组、模型对照组、阳性药物别嘌呤醇(2 mM)和固体饮料组(1 mg/mL)。其中正常对照组未摄入氧嗪酸钾(200 μM)和黄嘌呤(10 μM ),模型对照组、阳性对照组和固体饮料组都摄入了等量的氧嗪酸钾和黄嘌呤建立急性高尿酸血症模型(氧嗪酸钾和黄嘌呤通过溶解到养鱼用水中的方式摄入到斑马鱼体内)。固体饮料组在摄入氧嗪酸钾和黄嘌呤的同时浸泡在固体饮料溶液中,阳性药物组在摄入氧嗪酸钾和黄嘌呤的同时浸泡在固体饮料溶液中。一段时间后,用尿酸检测试剂盒检测斑马鱼体内尿酸水平。
3. 结果分析
3.1 固体饮料体外对尿酸含量的影响
体外实验表明,固体饮料对黄嘌呤氧化酶(XOD)的抑制率是14.6±0.737。
3.2 固体饮料对斑马鱼尿酸含量的影响
如图1所示,与正常对照比,模型组尿酸含量明细增高(p<0.05),阳性药物别嘌呤醇(200μM)与固体饮料(1 mg/mL)均能显著降低尿酸含量(p<0.05)。结果表明,固体饮料具有降低斑马鱼尿酸水平的作用。
进一步的实验数据显示实施例2~5的固体饮料也可以降低斑马鱼尿酸含量,效果略弱于同浓度下实施例1。
急性痛风性关节炎模型:
取30只小鼠,分为空白组、对照组和固体饮料组。三组小鼠各有10只小鼠,空白组1-21 天生理盐水灌胃,正常饮食;对照组持续致高尿酸血饮食;固体饮料组1-21天持续致高尿酸血症饮食,第7-21天开始固体饮料灌胃。
在第0、7和21天取样,检测小鼠的血尿酸含量。
不同组小鼠的血尿酸情况如图2所示。从图2可知,空白组小鼠的血尿酸在实验期间基本保持稳定。而对照组和固体饮料组,在第7天时血尿酸含量已经显著升高,而固体饮料组小鼠,因为在第7天后给予了固体饮料灌胃处理,虽然依然是致高尿酸血症饮食,但是第21天的血尿酸基本已经恢复正常,与空白组无显著区别。对照组第21天的血尿酸基本和第7天持平。
高尿酸造模成功7天后关节腔注射尿酸钠,72小时后取材。
三组小鼠踝关节HE染色,结果如图3所示。空白组在见踝关节无明显炎症反应,关节周围滑膜组织形态基本正常,无明显细胞浸润性生长,关节间隙基本正常;模型组见关节结构肿胀,关节内、关节周围存在大量滑膜增生、炎症反应,部分炎症细胞浸润滑膜;固体饮料组可见部分踝关节稍肿胀,滑膜增生,但关节形态基本正常,可见部分结构炎症细胞增生、浸润(黑色箭头:炎症细胞)。
三组小鼠肝组织HE染色,结果如图4所示。结果显示肝细胞、肝窦及肝内血管未见明显异常。
三组小鼠肾组织HE染色,结果如图5所示。空白组在见肾小球、肾小管形态未见明显异常;模型组可见部分肾小球轻度萎缩;固体饮料组肾小球形态基本正常。
三组小鼠踝关节IHC( TNF-α )染色结果如图6所示。由图6可知,空白组关节腔内滑膜无明显TNF-α表达,关节间隙正常;模型组关机关节腔内滑膜可见增生,TNF-α在滑膜内部分表达,显示滑膜部分炎症反应状态;固体饮料组可见关节腔内滑膜轻度增生,可见少量TNF-α表达,炎症反应较轻。
以上是对本发明所作的进一步详细说明,不可视为对本发明的具体实施的局限。对于本发明所属技术领域的普通技术人员来说,在不脱离本发明构思的简单推演或替换,都在本发明的保护范围之内。
Claims (10)
1.一种组合物,其活性成分的原料为:薏苡仁、百合、茯苓、桑叶、木瓜、绿茶、核桃仁、菊苣和葛根。
2.根据权利要求1所述的组合物,其特征在于:其活性成分的原料质量组成为:薏苡仁50~80份、百合15~28份、茯苓16~30份、桑叶7~12份、木瓜7~12份、绿茶2~8份、核桃仁2~8份、菊苣16~30份、葛根16~30份。
3.根据权利要求1或2所述的的组合物,其特征在于:所述活性成分为原料的水提物。
4.一种固体饮料,由辅料和功效成分组成,其特征在于:所述功效成分为权利要求1~3任一项所述的组合物。
5.根据权利要求4所述的固体饮料,其特征在于:所述辅料选自选自矫味剂、产气剂、增稠剂。
6.根据权利要求5所述的固体饮料,其特征在于:所述矫味剂选自罗汉果甜苷、甜菊糖苷、甘草甜素、阿斯巴甜;和/或
所述产气剂为碳酸氢钠;和/或
所述稠剂选自麦芽糊精。
7.根据权利要求5所述的固体饮料,其特征在于:所述辅料由碳酸氢钠、罗汉果甜苷和麦芽糊精组成。
8.根据权利要求5所述的固体饮料,其特征在于:其质量组成包括功效成分2~6份、碳酸氢钠0.25~0.35份、罗汉果甜苷0.5~1.5份,麦芽糊精添加量为所述功效成分的0.5~3.5倍,所述功效成分为干浸膏。
9.权利要求1~3任一项所述组合物在制备降尿酸组合物中的应用。
10.根据权利要求9 所述的应用,其特征在于:所述降尿酸组合物的类型选自饮料、食品添加剂、糖果、糕点。
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