CN112500383A - 一种提高秦皮乙素转移率的二丁颗粒提取工艺 - Google Patents
一种提高秦皮乙素转移率的二丁颗粒提取工艺 Download PDFInfo
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Abstract
本发明属于中药提取技术领域,涉及一种提高秦皮乙素转移率的二丁颗粒提取工艺,包括以下步骤:等比例取紫花地丁、半边莲、蒲公英、板蓝根四味药材,加入10~12倍量的pH为9~10的碱水溶液,加热煎煮1~3次,每次1~2h,滤过,合并滤液,浓缩,离心,上清液制成1g/mL的药液。本发明首次采用碱水溶液对二丁颗粒进行提取,使得秦皮乙素的转移率大大提高,可充分利用药材资源,降低生产成本。
Description
技术领域
本发明属于中药提取技术领域,涉及一种提高秦皮乙素转移率的二丁颗粒提取工艺。
背景技术
二丁颗粒是2015版《中国药典》收载的常用中药成方制剂,由紫花地丁、半边莲、蒲公英和板蓝根4味中药经加热提取制得的颗粒剂,具有清热解毒的功效,用于治疗火热毒盛所致的热疖痈毒、湿热黄疸、外感风热、咽喉肿痛、风热火眼等。
二丁颗粒方中紫花地丁、蒲公英(黄花地丁)苦寒,清热解毒,消痈为君药;板蓝根解毒利咽,消肿为臣药;半边莲甘淡渗利为佐使,可使热随小便而出,又兼具消肿解毒之功效。诸药合用,力专而雄,实为清热解毒之重剂。研究表明,秦皮乙素为紫花地丁主要有效成分之一,具有明显的抗炎、抑菌、镇痛、抗氧化、抗肿瘤和免疫调节等作用,且2015版《中国药典》收载的二丁颗粒选用秦皮乙素作为其质量控制指标,因此,秦皮乙素提取率的高低对二丁颗粒的药效尤为重要。
秦皮乙素为黄酮类化合物,化学名为6,7-二羟基香豆素,其结构为香豆素类七叶内酯,溶于热乙醇、甲醇和稀碱溶液,微溶于水、乙醇、乙酸乙酯,不溶于乙醚和氯仿,传统的提取工艺一般采用水做为提取溶剂,但普遍提取率不高,造成药材资源的浪费。
2017年张石宇等人发表的《二丁颗粒的水提醇沉工艺研究》,仍以传统的水煎煮法制备中药液,采用醇沉法进行精制,通过正交实验得出:影响精制结果的因素为浓缩浓度和乙醇浓度,旨在为二丁颗粒的剂型改良提供理论依据,与本发明的构思不同。
发明内容
本发明的目的在于提供一种提高秦皮乙素转移率的二丁颗粒提取工艺,首次采用碱水溶液对二丁颗粒进行提取,使得秦皮乙素的转移率大大提高,可充分利用药材资源,降低生产成本。
为实现上述目的,本发明采用以下技术方案:
本发明提供一种提高秦皮乙素转移率的二丁颗粒提取工艺,包括以下步骤:等比例取紫花地丁、半边莲、蒲公英、板蓝根四味药材,加入10~12倍量的pH为9~10的碱水溶液,加热煎煮1~3次,每次1~2h,滤过,合并滤液,浓缩,离心,上清液制成1g/mL的药液。
在一个技术方案中,提取工艺包括以下步骤:等比例取紫花地丁、半边莲、蒲公英、板蓝根四味药材,加入12倍量的pH为10的碱水溶液,加热煎煮3次,每次1.5h,滤过,合并滤液,浓缩,离心,上清液制成1g/mL的药液。
在一个技术方案中,提取工艺包括以下步骤:等比例取紫花地丁、半边莲、蒲公英、板蓝根四味药材,加入10倍量的pH为10的碱水溶液,加热煎煮2次,每次2h,滤过,合并滤液,浓缩,离心,上清液制成1g/mL的药液。
在上述技术方案中,所述碱水溶液由无机碱性试剂配制而成,所述无机碱性试剂选自氢氧化钠或氢氧化钙。
相比现有技术,本发明的有益效果在于:
本发明首次采用碱水溶液对二丁颗粒进行提取,二丁颗粒的指标性成分秦皮乙素属于香豆素类化合物,具有内酯环,能被碱液水解开环生成顺邻羟基桂皮酸盐溶于碱液,酸化后内酯环环合,香豆素类成分即可游离析出,用乙醚等亲脂性有机溶剂萃取得到。碱液提取使得秦皮乙素的转移率大大提高,可充分利用药材资源,降低生产成本。本发明采用正交实验设计,以浸膏得率和秦皮乙素的转移率的综合评分为评价指标对提取工艺进行优化,优选出最佳提取工艺,并进行工艺验证,确保提取工艺条件准确可靠,安全、经济,适用于大规模生产。
具体实施方式
以下实施例用于说明本发明,但不用来限定本发明的保护范围。若未特别指明,实施例中所用技术手段为本领域技术人员所熟知的常规手段。下述实施例中的试验方法,如无特别说明,均为常规方法。
实施例一
1.1仪器与试剂:LC-1260高效液相色谱仪(美国安捷伦);KQ5200B型超声波清洗器(昆山市超声仪器有限公司);GZX-9140MBE电热鼓风干燥箱(上海博讯实业有限公司医疗设备厂);十万分之一分析天平(MS205DU,梅特勒-托利多);TD5Z低速离心机(湖南凯达科学仪器有限公司);秦皮乙素(批号:110741-201708,纯度:99.9%)购自中国食品药品检定研究院;紫花地丁、半边莲、蒲公英、板蓝根购自河南禹州药材市场,经检验均符合2015版《中国药典》一部该药材项下的有关规定。
1.2方法
1.2.1对照品溶液的制备:精密称取秦皮乙素对照品9.30mg,置100mL量瓶中,加甲醇溶解并定容至刻度,摇匀,得0.093mg/mL的对照品储备液。精密吸取该对照品储备液2mL置10mL量瓶中,加甲醇定容至刻度,摇匀,即得18.60μg/mL的对照品溶液。
1.2.2二丁颗粒浸膏的制备:等比例取紫花地丁、半边莲、蒲公英和板蓝根4味药材共50g,放入2000mL圆底烧瓶中,用1%氢氧化钠调节水为pH值为8的稀碱溶液,加入10倍量的稀碱溶液,煎煮2次,每次1h,滤过,合并滤液,浓缩,离心,上清液定容至50mL制成1g/mL的药液,得浸膏。
1.2.3供试品溶液的制备:精密量取本品2mL,置25mL量瓶中,加入甲醇适量,超声处理(功率250W,频率50kHz)30分钟,放冷,加甲醇定容至刻度,摇匀,滤过,精密量取续滤液2mL置10mL量瓶中,加甲醇定容至刻度,摇匀,即得。
1.2.4色谱条件:ODS2 C18(4.6mm′250mm,5μm);流动相:甲醇-水-冰醋酸(20:80:0.4,V/V/V);检测波长:353nm;流速:1mL/min;进样量:10μL;理论板数按秦皮乙素峰计算应不低于3000。
1.2.5方法学考察
1.2.5.1线性关系考察:精密量取秦皮乙素对照品储备溶液0.8、1.2、1.6、2.0、2.4、2.8mL置10mL量瓶中,加甲醇定容至刻度,摇匀,分别制成质量浓度为7.44、11.16、14.88、18.60、22.32、26.04μg/mL的对照品系列溶液。精密吸取上述对照品系列溶液各10μL,进样测定,记录峰面积,以秦皮乙素对照品的峰面积(Y)对秦皮乙素的进样浓度(X)进行线性回归,得回归方程Y=0.0241X+0.6297(r=0.9991),表明秦皮乙素在7.44~26.04μg/mL的范围内线性关系良好。
1.2.5.2精密度试验:精密吸取秦皮乙素对照品溶液(18.60μg/mL)10μL,重复进样6次,记录峰面积,计算其RSD为0.51%,表明仪器精密度良好。
1.2.5.3稳定性试验:精密吸取同一供试品溶液10μL于0、2、4、6、8、10、12h分别进样测定,记录峰面积,计算其RSD为0.72%,表明供试品溶液在12h内稳定性良好。
1.2.5.4重复性试验:取同一批浸膏,按供试品溶液的制备方法制备6份样品,进样测定,记录峰面积,结果显示秦皮乙素的平均含量为2.42mg/mL,RSD为1.03%,表明该方法重复性良好。
1.2.5.5加样回收率试验:分别量取2mL已知含量(每毫升含秦皮乙素约2.42毫克)浸膏6份,分别按照相等浓度加入一定量的秦皮乙素对照品,混合均匀,按供试品溶液的制备方法进行处理,精密吸取10μL,进样测定,计算加样回收率为98.19%,RSD为1.44%。
1.2.6提取工艺优化
采用正交试验优化二丁颗粒的提取工艺,分别选用稀碱溶液的pH值、液料比、提取时间、提取次数4个因素,每个因素选3个水平如表1所示,利用L9(34)正交表进行试验设计,以浸膏得率和秦皮乙素的转移率的综合评分为评价指标,根据L9(34)正交表进行试验,因素水平设计见表1,试验结果见表2,方差分析见表3。
表1 L9(34)正交试验因素水平表
表2 L9(34)正交试验结果
表3方差分析
注:临界值F0.05(2,2)=19.00,*P<0.05
综合评分计分法:分别以秦皮乙素的含量最大值和浸膏得率最大值为参照,对数据进行归一化法分析,秦皮乙素的转移率、浸膏得率的权重系数分别为0.6、0.4。综合评分=(秦皮乙素转移率/秦皮乙素最大转移率)×0.6+(浸膏得率/浸膏最大得率)×0.4。
根据正交试验结果分析可知,各因素对综合评分的影响为A>D>B>C,稀碱溶液的pH值对综合评分的影响具有显著性。最佳提取工艺条件为A3B2C1D3,即稀碱溶液的pH值为10,液料比为12,提取时间为1h,提取次数为3次。根据预实验的结果,稀碱溶液的pH值过高,经加热煎煮,秦皮乙素的转移率反而降低,可能是由于秦皮乙素的开环产物顺邻羟基桂皮酸盐在碱液中长时间加热会异构为反邻羟基桂皮酸盐,酸化后不能环合成原来的内酯环所致。
1.2.7工艺验证
取等比例的紫花地丁、半边莲、蒲公英和板蓝根4味药材共50g,放入2000mL圆底烧瓶中,用1%氢氧化钠调节水为pH值为10的稀碱溶液,加入12倍量的稀碱溶液,煎煮3次,每次1h,滤过,合并滤液,浓缩,离心,上清液定容至50mL。同法制备3批浸膏,测定浸膏得率和秦皮乙素的转移率。结果见表4。
表4工艺验证结果
由工艺验证结果可知,在最佳工艺条件下,二丁颗粒的浸膏得率平均为28.66%,秦皮乙素的转移率平均为82.61%,表明该工艺条件稳定,重复性良好,适合工业化大规模生产。
同时,另取等量的3份药材,采用药典方法水提做对照,在最佳工艺条件下测定浸膏得率和秦皮乙素的转移率,结果见表5。
表5水提对照试验结果
由表4和表5的结果可知,碱水溶液对二丁颗粒的提取效果,与水提工艺相比,浸膏得率差别不太明显,但秦皮乙素的转移率却提高了21.85%。
另取等量的3份药材,采用葡甲胺配制碱水溶液,在最佳工艺条件下,测定浸膏得率为29.12%,秦皮乙素的转移率为59.40%。可见,采用有机碱配制的碱水溶液对二丁颗粒的提取效果,远低于采用无机碱水溶液对二丁颗粒的提取效果,甚至低于水提的提取效果。
以上所述之实施例,只是本发明的较佳实施例而已,仅仅用以解释本发明,并非限制本发明实施范围,对于本技术领域的技术人员来说,当然可根据本说明书中所公开的技术内容,通过置换或改变的方式轻易做出其它的实施方式,故凡在本发明的原理上所作的变化和改进等,均应包括于本发明申请专利范围内。
Claims (4)
1.一种提高秦皮乙素转移率的二丁颗粒提取工艺,其特征在于,包括以下步骤:等比例取紫花地丁、半边莲、蒲公英、板蓝根四味药材,加入10~12倍量的pH为9~10的碱水溶液,加热煎煮1~3次,每次1~2h,滤过,合并滤液,浓缩,离心,上清液制成1g/mL的药液。
2.根据权利要求1所述的一种提高秦皮乙素转移率的二丁颗粒提取工艺,其特征在于,包括以下步骤:等比例取紫花地丁、半边莲、蒲公英、板蓝根四味药材,加入12倍量的pH为10的碱水溶液,加热煎煮3次,每次1.5h,滤过,合并滤液,浓缩,离心,上清液制成1g/mL的药液。
3.根据权利要求1所述的一种提高秦皮乙素转移率的二丁颗粒提取工艺,其特征在于,包括以下步骤:等比例取紫花地丁、半边莲、蒲公英、板蓝根四味药材,加入10倍量的pH为10的碱水溶液,加热煎煮2次,每次2h,滤过,合并滤液,浓缩,离心,上清液制成1g/mL的药液。
4.根据权利要求1或2或3所述的一种提高秦皮乙素转移率的二丁颗粒提取工艺,其特征在于,所述碱水溶液由无机碱性试剂配制而成,所述无机碱性试剂选自氢氧化钠或氢氧化钙。
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