CN114668813A - 黄精和白刺组合物在调节血糖血脂方面的应用 - Google Patents
黄精和白刺组合物在调节血糖血脂方面的应用 Download PDFInfo
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- CN114668813A CN114668813A CN202210371097.1A CN202210371097A CN114668813A CN 114668813 A CN114668813 A CN 114668813A CN 202210371097 A CN202210371097 A CN 202210371097A CN 114668813 A CN114668813 A CN 114668813A
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- nitraria tangutorum
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- polygonatum sibiricum
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明公开了一种黄精和白刺组合物在调节血糖血脂方面的应用。本发明根据中医药理论和糖尿病发病机制,充分利用植物资源,在黄精和白刺降血糖、降血脂功效的研究基础上,将二者结合使用,通过大量的药理实验,应用正交实验法筛选出黄精和白刺组合的最佳配比和制备工艺。实验结果表明,黄精和白刺在最佳配比下具有很好的协同增强效果,具有较强的α‑葡萄糖苷酶抑制活性,可以显著降低高血糖、高血脂模型小鼠的血糖、总胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白(HDL‑C)、低密度脂蛋白(LDL‑C)的水平,显示出了非常好的降血糖降血脂功效,且具有很高的安全性。
Description
技术领域
本发明涉及一种植物组合物,具体涉及黄精和白刺组合物在调节血糖和血脂方面的新应用途径。
背景技术
白刺(Nitraria)为蒺藜科(Zygophyllceae)的多分枝、耐盐碱、旱生型低矮灌木,具有耐干旱,抗高温、保水力强等生理特性。我国的白刺果资源丰富,分布广泛,在我国西北沙漠、华北、东北沿海地区,张家口坝上、天津、沧州等地都有野生。据统计,柴达木盆地的白刺分布在海拔3000米以上无污染的地区,每年可产白刺果6~10万吨,具有巨大的开发价值。现代药理研究表明,白刺果具有降血糖、抗氧化、抗疲劳等多种功效。
黄精为百合科(Liliaceae)黄精属Polygonatum Mill.多年生草本植物,全球有60余种,主要分布于北温带和北亚热带,我国有31种,广泛分布于除南方热带以外的广大地区。《中国药典》2015年版记载黄精为滇黄精P.kingianum Coll.et Hemsl.、黄精P.sibiricum Red.或多花黄精P.cyrtonemaHua的干燥根茎;甘、平;归脾、肺、肾经;具有补气养阴、健脾、润肺、益肾的作用;用于脾胃气虚、体倦乏力、胃阴不足、口干食少、肺虚燥咳、劳嗽咳血、精血不足、腰膝酸软等。黄精在抗衰老、调节免疫力、调血糖、改善记忆力、抗肿瘤、抗菌等方面显示出潜在的药用价值。
目前治疗2型糖尿病的药物主要有促胰岛素分泌剂(磺脲类)、胰岛素增敏剂(双胍类、噻唑烷二酮类)、胰岛素及其类似物等,以上药物降糖效果显著,但不良反应严重。中药作用温和,不良反应少。目前,已经公开了一些含黄精或者白刺的降血糖药物。专利“CN201811487687-具有辅助降血糖功能的组合物及其应用”公开了一种含黄精的降糖组合物,该组合物基础成分为黄芪、黄精、蜂胶粉和吡啶甲酸铬,并额外添加了三七,具有更好的降血糖效果。但黄芪、黄精、蜂胶、铬、三七这几种成分均被现代研究表明具有一定的降血糖功效(参考已公开文献如下:李存亮.黄芪治疗糖尿病作用机制和临床应用研究进展[J].中国现代药物应用,2011,5(24):3.;齐斌.黄精降血糖活性成分的提取,分离及结构鉴定.江南大学.;CHENG Xiao-yu,程晓雨,ZHANG Jiang-lin,等.蜂胶降血糖作用及其分子机制研究进展[C]//中国养蜂学会中国蜂产品协会.中国养蜂学会中国蜂产品协会,2016.;周保学,周定.铬(Ⅲ)与高血糖和高血脂研究进展[J].哈尔滨师范大学自然科学学报,1999,15(6):4.;黄春燕,梁洁,唐红珍.三七降血糖和降血脂的药理研究及临床应用进展[J].大众科技,2016,18(5):4.),因此将这几种常见降糖药物组合使用,降血糖功效应是可预见的,公开内容中并没有将组合物与各药物单一使用时的降糖效果进行对比,无法体现出药物组合带来的增益效果。
中药之间的配伍并非是几种药的随机组合,也并非几种药的单纯累积增加,由于中药配伍前后以及不同配伍比例剂量的物质基础与效应不同,因此药物配伍比例不同以及剂量的加减都会导致药物间相互作用的增强或减弱。现有公开文件多是将已经研究表明具有降糖功效的药物组合一起,并没有对药物之间相互作用进行研究,没有探究能充分发挥药效的最佳比例和最佳制备方法,可能会有药效减弱并造成药材浪费的风险。
发明内容
本发明所要解决的问题是,针对上述现有技术中的缺点,提出创新方案,尤其是探究黄精和白刺在降血糖功效应用上的相互作用,提高黄精或白刺单一植物在降血糖或降血脂方面的功效,开发二者组合应用最优途径。本发明采用单因素结合正交实验法,通过大量实验筛选出黄精或白刺的最佳配比,确定组合物的制备工艺。
为解决上述问题,本发明采用的方案如下:黄精和白刺组合物在调节血糖血脂方面的应用。
进一步,所述黄精和白刺组合物在调节血糖血脂方面的应用,其特征在于,黄精和白刺组合物为黄精和白刺的提取物。
进一步,所述黄精和白刺组合物在调节血糖血脂方面的应用,其特征在于,所述黄精和白刺组合物中黄精和白刺的质量比为4:1~1:4。
进一步,所述黄精和白刺组合物在调节血糖血脂方面的应用,其特征在于,所述黄精和白刺组合物中黄精和白刺的质量比为3:1、1:1或1:2。
一种具有调节血糖血脂作用的黄精和白刺组合物在药剂、食品、饮料中的应用。
一种用于调节血糖和血脂的黄精和白刺组合物的制备方法,其特征在于,包括如下步骤,黄精切片,白刺干果破碎,二者按比例混合后加水,经过超声提取,过滤后滤渣重复超声提取,合并滤液,并向滤液中加入复合酶进行酶解,待酶解后灭酶,最后经过浓缩制得黄精和白刺组合物。
进一步,所述用于调节血糖和血脂的黄精和白刺组合物的制备方法,其特征在于,初次超声提取加入10倍于黄精和白刺质量的水,并在75℃下超声提取90min,过滤后向料渣中再加入8倍的水重复超声提取一次,过滤出料渣后合并两次滤液;所述复合酶为质量比为1:1:1的果胶酶:淀粉酶:中性蛋白酶,酶解时间为2h,而后煮沸灭酶,最后浓缩至药材浓度为1g/mL。
黄精和白刺组合物可以和药学或食品接受的载体制成胶囊剂、片剂或制成口服液、饮料、固体饮料等多种形式的产品。黄精和白刺组合物制成口服液或饮料时,先将黄精和白刺组合物提取液稀释到适当倍数,通过0.25μm滤膜澄清,加山梨酸钾防腐后灌装灭菌得到黄精和白刺口服液或功能性饮料。黄精和白刺组合物制成固体饮料时,向黄精和白刺组合物提取液中加入麦芽糊精或可溶性淀粉,然后喷雾干燥得固体饮料。黄精和白刺组合物制成片剂时,向固体饮料中加入硬脂酸镁,混匀后压制而成。
本发明的技术效果如下:本发明公开了一种黄精和白刺组合物在调节血糖血脂方面的应用。本发明根据中医药理论和糖尿病发病机制,充分利用植物资源,在黄精和白刺降血糖、降血脂功效的研究基础上,首次将二者结合使用,通过大量的药理实验,应用正交实验法筛选出黄精和白刺组合的最佳配比和制备工艺。实验结果表明,黄精和白刺在最佳配比下具有很好的协同增效的功效,具有较强的α-葡萄糖苷酶抑制活性,可以显著降低高血糖、高血脂模型小鼠的血糖、TC、TG、HDL-C以及LDL-C的水平,显示出了非常好的降血糖降血脂功效,且具有很高的安全性。
现代药理学研究表明,黄精和白刺均具有一定的降血糖和降血脂功效,但二者配伍使用的研究比较少。中药之间的配伍并非是两味药的随机组合,也并非两味药的单纯累积增加,由于中药配伍前后以及不同配伍比例剂量的物质基础与效应不同,因此药物配伍比例不同以及剂量的加减都会导致药物间相互作用的增强或减弱。
本发明将黄精与白刺配伍使用,首次发现二者结合使用就有增强调节血糖功效的能力,进一步通过正交实验法,确定了黄精和白刺配伍最优比例和制备工艺,进一步实验结果表明,黄精和白刺组合物除调节血糖外还有明显的降血脂功效。
附图说明
图1不同比例黄精和白刺组合物对α-葡萄糖苷酶活性的抑制能力。
图2黄精和白刺组合物对人体餐后血糖的影响。
具体实施方式
下面结合附图对本发明做进一步详细说明。
实施例1黄精和白刺组合物在调节血糖血脂方面的应用:
1.1实验方法
1.1.1黄精和白刺组合物的制备
首先将黄精切成2mm薄片,白刺干果经钢磨压碎,然后将二者按1:0、4:1、3:1、2:1、1:1、1:2、1:3、1:4、0:1的比例均匀混合,加入10倍的水在75℃下超声提取90min,过滤后向料渣中再加入8倍的水重复超声提取一次,过滤出料渣后合并两次滤液,滤液中加入复合酶(果胶酶:淀粉酶:中性蛋白酶=1:1:1)酶解2h后煮沸灭酶,最后浓缩至药材浓度为1g/mL,冷藏备用。
1.1.2α-葡萄糖苷酶活性抑制能力测定
提取液抑制α-葡萄糖苷酶活性实验:分为抑制剂组与对照组。抑制剂分别为黄精和白刺组合物及阿卡波糖。向抑制剂组分别加入400μL抑制剂及400μLα-糖苷酶(1U)。抑制剂对照组分别加入400μL抑制剂及400μL磷酸盐缓冲液(pH 7.0);空白组分别加入400μL磷酸盐缓冲液及400μLα-糖苷酶(1U),空白对照组中加入800μL磷酸盐缓冲液(pH7.0),于37℃反应20min。之后向每组中加入100μLpNPG(100mmol/L)于37℃反应40min。最后以1.5mLNaOH溶液(1.0mol/mL)以停止反应的进行,于410nm处测各组的吸光度值。抑制率计算公式为:
式中:A1为抑制剂组吸光度值;A2为抑制剂对照组吸光度值;A3为空白组吸光度值;A4为空白对照组吸光度值。
1.1.3黄精和白刺组合物对高血糖小鼠降糖实验
取180只昆明种健康小鼠,雌雄各半,适应饲养3天。采用尾部静脉注射四氧嘧啶,注射剂量70mg/kg。3天后测定空腹血糖,血糖值>15mmol/L的小鼠为高血糖小鼠,总计110只。将110只小鼠随机分成11组,每组10只,分别为空白组,阿卡波糖组,组合物组。灌胃给药,阿卡波糖给药剂量为5mg/kg(小鼠体重),黄精和白刺组合物给药剂量为1g/kg,每天给药1次,在给药第6天、第9天采取尾静脉抽血,血糖仪测定空腹血糖值。
1.1.4正交实验法优化黄精和白刺组合物的制备工艺
正交实验以黄精:白刺(质量比)、提取时间、提取温度为自变量,α-葡萄糖苷酶活性抑制率为因变量,按以下因素水平表进行:
表1正交实验因素水平表
1.1.5黄精和白刺组合物稳定人体餐后血糖实验
20名健康志愿者,男女各半,年龄在25~35岁之间,无糖尿病史。测试前,所有志愿者空腹10h以上,测定一次志愿者空腹血糖。然后给每个志愿者100g白面包,其中10名志愿者在服用白面包时同时服用5mL组合物,另外10名志愿者在服用白面包时同时服用5mL水,服用完毕后在30min、60min、90min、120min、150min后测定一次血糖,绘制餐后血糖变化曲线。
1.2实验结果
1.2.1α-葡萄糖苷酶活性抑制能力测定
不同黄精和白刺组合物抑制α-葡萄糖苷酶活性的实验结果如图1所示,当黄精:白刺为1:1时,抑制率最高,达到了89.64%,其次是3:1和1:2,抑制率分别达到了87.68%和85.23%。除黄精:白刺为4:1时抑制率(81.45%)比单一白刺抑制率(82.37%)略低以外,其他各比例对α-葡萄糖苷酶活性的抑制率均超过单一的黄精或者白刺,因此黄精和白刺组合具有一定的协同增强效果。
1.2.2黄精和白刺组合物对高血糖小鼠降糖实验结果
由表2可知,造模后的空白组小鼠在分组6天和9天后空腹血糖依然处于一个较高值,甚至有轻微上升趋势,而治疗组小鼠的血糖水平明显降低,黄精:白刺为3:1、2:1、1:1和1:2时降血糖功效更好,这与α-葡萄糖苷酶活性抑制实验的结论基本相符,因此α-葡萄糖苷酶活性抑制能力的测定可作为黄精和白刺组合物降糖功效的参考指标。
表2黄精和白刺组合物对高血糖小鼠的降糖效果
注:“*”表示与空白组对比有显著差异(p<0.05)。
1.2.3正交实验结果
表3正交实验设计表及实验结果
由表3所示,对正交实验结果进行直观分析,三个因素对α-葡萄糖苷酶活性抑制的影响强度顺序依次是B>C>A,即提取温度>提取时间>黄精:白刺(质量比),最佳组合为A2B3C3,即黄精:白刺(质量比)为1:1,提取温度为75℃,提取时间为90min时,组合物对α-葡萄糖苷酶活性抑制作用最强。这与前面的实验结果一致,在这个条件下组合物对α-葡萄糖苷酶活性抑制率达到了89.64%,高于正交实验中任何一个实验组结果,且在降低高血糖小鼠实验中表现出非常好的降血糖效果,因此确定组合物黄精:白刺(质量比)为1:1,提取温度为75℃,提取时间为90min。
1.2.4黄精和白刺组合物稳定人体餐后血糖实验结果
照1.2.3中最佳工艺制作黄精和白刺组合物用于实验,结果如图2所示,组合物能明显降低人体餐后血糖的峰值,并使得血糖上升及下降的幅度变缓,表明黄精和白刺组合物具有明显的稳定人体餐后血糖的能力。
实施例2黄精和白刺组合物在调节血糖血脂方面的应用:
2.1黄精和白刺组合物对高脂小鼠血脂的影响
2.1.1实验方法
60只大鼠在实验室适应性饲养1周,称重后将大鼠分为6组,每组10只。空白组饲喂基础饲料和蒸馏水,模型组饲喂高脂饲料(80%基础饲料+10%猪油+10%鸡蛋黄)和蒸馏水,阳性对照组饲喂高脂饲料和绿茶提取物(茶叶加10倍热水在80℃超声30min,反复提取三次后合并滤液浓缩至茶叶浓度为1g/mL),黄精和白刺组合物实验组分为低剂量组(高脂饲料加灌胃组合物0.5g/kg)、中剂量组(高脂饲料加灌胃组合物1g/kg)、高剂量组(高脂饲料加灌胃组合物1.5g/kg)。处理28天后在大鼠眼底静脉采血,采血后使用肝素抗凝,2000r/min离心10min后取上清液冷藏保存待测,血清中TG、TC、HDL-C、LDL-C均使用试剂盒测定。
2.1.2实验结果
黄精和白刺组合物对大鼠血脂的影响结果如表4所示,与高血脂组相比,低、中、高剂量组组合物的TC、TG、LDL-C、HDL-C均显著降低,与阳性对照组没有明显区别,表明黄精和白刺组合物具有明显的降血脂功效。
表4黄精和白刺组合物对大鼠血脂的影响
Claims (7)
1.黄精和白刺组合物在调节血糖血脂方面的应用。
2.根据权利要求1所述黄精和白刺组合物在调节血糖血脂方面的应用,其特征在于,黄精和白刺组合物为黄精和白刺的提取物。
3.根据权利要求1所述黄精和白刺组合物在调节血糖血脂方面的应用,其特征在于,所述黄精和白刺组合物中黄精和白刺的质量比为4:1~1:4。
4.根据权利要求1所述黄精和白刺组合物在调节血糖血脂方面的应用,其特征在于,所述黄精和白刺组合物中黄精和白刺的质量比为3:1、1:1或1:2。
5.一种具有调节血糖血脂作用的黄精和白刺组合物在药剂、食品、饮料中的应用。
6.一种具有调节血糖和血脂功效的黄精和白刺组合物的制备方法,其特征在于,包括如下步骤,黄精切片,白刺干果破碎,二者按比例混合后加水,经过超声提取,过滤后滤渣重复超声提取,合并滤液,并向滤液中加入复合酶进行酶解,待酶解后灭酶,最后经过浓缩制得黄精和白刺组合物。
7.根据权利要求6所述具有调节血糖和血脂功效的黄精和白刺组合物的制备方法,其特征在于,初次超声提取加入10倍于黄精和白刺质量的水,并在75℃下超声提取90min,过滤后向料渣中再加入8倍的水重复超声提取一次,过滤出料渣后合并两次滤液;所述复合酶为质量比为1:1:1的果胶酶:淀粉酶:中性蛋白酶,酶解时间为2h,而后煮沸灭酶,最后浓缩至药材浓度为1g/mL。
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