一种新型杜仲冲剂的生产工艺研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
杜仲(Eucommia ulmiodes Oliv.)为单属科单种属植物,其皮和叶中含有多种药用成分,如绿原酸、黄酮、桃叶珊瑚苷,多种维生素、氨基酸,丰富的矿物质铁、钙、钾、锌、镁、硒等天然植物微量元素,具有调节血压、血脂和血糖,抗氧化、抗衰老及抗肿瘤,增强免疫力,减肥美容等保健作用。本研究对杜仲有效成分提取工艺进行了深入的研究,优化了提取工艺,提取出了富含生物活性物质的浸膏。在此基础上,研究了杜仲冲剂的造粒工艺,为新型杜仲保健品和药品的开发提供理论依据。研究结果如下:
     一、杜仲叶有效成分提取工艺
     以杜仲叶中的生物活性物质绿原酸和总黄酮为指标,利用响应面法优化提取杜仲叶中的工艺参数。在分析单因素的基础上,以绿原酸和总黄酮的得率为响应值,以乙醇浓度(%)、提取温度(℃)、提取时间(h)、料液比为考察因素,并采用响应面设计实验方法优化提取工艺,其最优条件为乙醇浓度55%、提取温度63℃、提取时间2.2h、料液比为1:13。在此条件下,绿原酸和总黄酮的得率分别达0.81%和0.51%。
     二、杜仲冲剂的制备工艺
     通过一系列的单因素试验选择不同的矫味剂、赋型剂、润湿剂,并从实际生产中常用的制粒方法湿法制粒、快速搅拌制粒、流化喷雾制粒中选择快速搅拌制粒为主要的制粒方法。以粒度不合格率为响应值,确定最佳提取工艺参数为:甜菊糖苷用量为杜仲提取物的0.78%、β-环状糊精与药粉质量之比为6,乙醇浓度为65%,乙醇用量(L)与药粉量(kg)比例为l︰6,干燥温度为70℃,在此条件下,杜仲冲剂的颗粒不合格率为仅为6.12%。
     通过本课题的研究,得到了完整的一套杜仲冲剂制备工艺:杜仲叶经除尘、除杂,并于105℃杀青10min后晾干,粉碎,加入55%乙醇,乙醇用量(L)与杜仲叶(kg)比例为13︰1,在63℃的温度下提取2.2 h后,在60℃下浓缩、干燥,得到杜仲提取物干粉,粉碎,加用量为杜仲提取物干粉的0.78%的甜菊糖苷、6倍于其他药粉重量的β-环状糊精、并加入浓度为65%的乙醇,乙醇用量(L)与药粉量(kg)比例为l︰6,混合均匀后,倒入快速搅拌制粒机中制粒,而后在70℃下进行干燥,时间为20 min,成型后即为杜仲冲剂。
Eucommia ulmiodes Oliv. is a plant species with mono genus and family. The bark has been a traditional Chinese medicine for thousands of years. Modern scientific research has confirmed that the functional constituents in the leaf are similar to the bark. Based on this finding, the leaf has been listed in China Pharmacopoeia with therapeutic effects similar to the bark. The leaf contains a variety of medicinal ingredients, such as chlorogenic acid, flavonoids, aucubin, vitamin, amino acids, and minerals. The medical functions of the leaf include regulating blood pressure, lipids and glucose, anti-oxidation, anti-aging, anti-tumor, enhancing immunity, beautifying skin and anti-obesity.
     In order to make health-care products from the leaves of E. ulmoides, an experiment was conducted on the optimization of the extraction parameters of active ingredients the granulation process of the extracts which are rich in functional constituents. The results are as follows.
     1. Extraction of active ingredients of leaves of Eucommia ulmoides
     Response surface methodology (RSM) was employed to optimize the extraction parameters of chlorogenic acid and flavonolds from the leaves of E. ulmoides. Based on one-factor experiment, the effects of four independent variables, namely the concentration of ethanol (%) extraction temperature (°C), time (h) and the ratio of material to solvent on the extraction yields of chlorogenic acid and flavonoids were investigated, and then the response surface analysis was used to optimize conditions. The optimal extraction parameters were: ethanol concentration: 55%, extraction temperature: 63°C, time of extraction: 2.2h and material to solvent 1:13 according to the response surface analysis. Under these conditions, the extraction yields of chlorogenic acid and flavonoids were 0.81%, 0.51% respectively.
     2. Development of Eucommia granules
     Firstly, optimal additives were screened from different flavoring agents, excipients, and wetting agents. Then preferable method of granulation was selected from three conventional methods, namely, fast stirring granulation, wet granulation, rapid mixing granulation, and fluidized spraying granulation. Failure rate of particle size was investigated and then the response surface analysis was used to optimize conditions. The optimal extraction parameters were: 0.78% stevia,β-cyclodextrin to powder: 6, 65% ethanol concentration, ratio of ethanol (L) to the powder volume (kg) 1:6, drying temperature of 70°C, in these conditions, Eucommia granules failure rate of particles size was as low as 6.12%.
     Based on the results mentioned above, a completed flow of making Eucommia granules were proposed as Eucommia leaf after de-dusting, cleaning, and drying 10 min at 105°C, grinding, added 55% ethanol, and the ratio of ethanol (L) to Eucommia leaf (kg) 13:1, and extracted at 63°C about 2.2h, next, concentrated and dried at 60°C. After grinding, the Eucommia leaf extract powder added 0.78% stevioside, theβ-cyclodextrin which was 6 times of the weight of other powder, then continued to add 65% ethanol, and concentration of ratio of ethanol (L) to the powder volume (kg) l:6, after mixing, granulated into the machine the rapid mixing granulation, and then dried under 70°C, 20 minutes.
引文
成军,赵玉英,崔育新,程铁明. 2000.杜仲叶黄酮类化合物的研究.中国中药杂志, 25(5): 284~286
    成红砚,陈菊,杨春. 2008.等离子发射光谱法测定杜仲中的微量元素.贵州地质, 25(3): 239~241
    陈晓娟,周春山,魏巍. 2006.杜仲叶中绿原酸和黄酮不同提取方法的比较.中国生化药物杂志, 27(1): 38~40
    董娟娥,梁宗锁. 2006.杜仲叶酸性多糖提取分离及含量测定.林业科学, 42(10): 59~63
    董娟娥,马柏林,仝小林,刘丽,薛雪琴. 2002.提高杜仲叶中主要活性物质提取率的研究.西北林学院学报, 17(1): 64~67
    高桥周七. 1997.杜仲叶提取物对胶原蛋白合成的促进作用.首届国际杜仲学术会议论文集.中国林业出社, 159-167.
    管淑玉,苏薇薇. 2003.杜仲化学成分与药理研究进展.中药材, 26 (2): 124~129
    国家药典委员会. 2004.中华人民共和国药典:一部(M).北京:化学工业出版社: 1114~1151
    郭美丽,周燕平,冯碹. 2008.杜仲籽油辅助降血脂作用实验研究,中国预防医学杂, 9(7): 677~678.
    郭孝武,吉晓芹. 2003.杜仲叶中总黄酮物质超声提取的研究.西北植物学报, 23(11): 1984~1987
    候立新. 1996.中药制剂中新型甜味剂的选用.中成药, 18(4): 6~7
    贾征,黄文,薛安. 2008.杜仲叶黄酮的提取及抗脂质过氧化和红细胞保护作用研究.食品研究与开发, 29(5): 46~49
    康桢,吴卫华,王俊杰,欧阳冬生. 2007.桃叶珊瑚苷及其苷元的药理研究进展.中国中药杂志, 32(24): 2585~2587
    兰小艳,黄敏,张学俊. 2009b.杜仲叶中绿原酸醇提法的工艺研究.中国农学通报, 25(18): 84~88
    兰小艳,张学俊,龚桂珍. 2009a.杜仲叶中绿原酸的研究进展.中国农学通报, 25(21): 86~89
    冷水江. 2001.新型矫昧剂在制药业应用前景广阔.中国化工报, 10(25) : 6~7
    李军. 2005.β-环糊精在中药制剂中的应用.药学专论, 14(6) : 26~27
    刘静,濮智颖,李爱玲,赵红岩,阎红蕾.杜仲叶黄酮降血脂及抗氧化作用的研究.安徽农业科学,38(11): 5631~5632
    刘军海,裘爱泳. 2004.大孔吸附树脂提取纯化杜仲叶绿原酸的研究.山东医药, 44(23):2~3
    刘军海,裘爱泳,任惠兰. 2008.正交实验优化杜仲叶中桃叶珊瑚甙提取工艺.食品研究与开发, 1(29): 99~102
    刘国荣,邱立朋,周延萌,辛晓明,高允生. 2010.杜仲多糖对糖尿病小鼠降血糖作用及其机制研究. 泰山医学院学报, 31(9): 659~661
    刘耕陶. 1988.氧自由基与抗氧化剂,中国药理通报, 4(6): 324~327
    刘艳杰,项荣武. 2007.星点设计效应面法在药学试验设计中的应用.中国现代应用药学杂志, 12(24): 455~457
    李小安,夏前明,王秉文,袁秉祥,康军. 2009.杜仲叶浸膏粉抗衰老作用的研究,西部医学, 21(6): 904~906
    李晓瑜. 2002甜菊糖苷的安全性研究进展.国外医学.卫生学分册, 29(5) : 291~296
    李竹,晏媛,李青. 2004.杜仲的药理活性研究进展,中国药事, 18(2): 131~132
    娄丽杰,陈百泉,杜红岩,付建敏,杜兰英,李钦. 2009.杜仲雄花茶对高脂乳剂小鼠血脂水平的影响.河南大学学报(医学版), 28(4): 273~275
    吕琳,孙燕荣,徐伟,刘叔文,饶进军,吴曙光. 2007.杜仲提取物抗HIV活性成分的分离鉴定, 31(6): 847~850
    彭婕,钱之玉,刘同征. 2003.京尼平苷和西红花酸保肝利胆作用的比较.中国新药杂志, 12(2):105
    彭密军,钟世安,周春山,董朝清,雷启福. 2004.大孔吸附树脂分离纯化杜仲中活性成分.离子交换与吸附, 20(1): 13~22
    戚向阳,陈维军,张声华,彭光华. 2002.杜仲粉的药理作用及其有效成分特性研究,中国食品学报, 2(4): 42~45.
    孙燕荣,董俊兴,吴曙光. 2004.中药杜仲抗HIV作用的实验研究,解放军预防医学杂志, 22(2):847~850
    唐栩. 2006. 26种黄酮类天然活性成分的药理研究进展.中药材, 27 (1): 46~54 .
    王俊丽,陈王铃,朱宝成. 1994.杜仲氨基酸成分的研究.河北大学学报(自然科学版), 14(2): 80~82
    尉芹,蒂谦平,马希汉. 2001a.杜仲叶中绿原酸的提取工艺条件研究.林产化学与工业, 21(4): 27~32
    尉芹,韩建国,董娟娥,马希汉. 2008.不同炮制方式对中药材杜仲叶品质的影响.中国中药杂志, 33(1): 85~87
    尉芹,王冬梅,马希汉,张康健. 2001b.杜仲叶总黄酮含量测定方法研究.西北农林科技大学学报(自然科学版), 29(5): 119~123
    肖培根. 2001.新编中药志, 1卷北京:化学工业出版社: 259
    谢文利,李宏捷,晋玉章. 2008.京尼平苷的降血糖作用研究.武警医学院学报, 17(7): 580~581
    辛晓明,王大伟,赵娟,王浩,费洪荣,董峰,高允生. 2009.杜仲总多糖抗肿瘤作用的实验研究.医药导报, 28(6): 719~721
    薛程远,曲范仙,刘辉. 1998.杜仲叶乙醇提取物对小鼠免疫功能的影响,甘肃中医学院学报, 15(3): 50~52
    许激扬,宋妍,季晖. 2006.杜仲木脂素化合物舒张血管作用机制.中国中药杂志,31(23): 1976~1978
    姚新生. 1996.天然药物化学.北京:人民卫生出版社(第二版): 286~289
    尹莲,魏鲁霞. 2000.杜仲微量元素与药用功效关系探讨.实用中药杂志, 16(1): 42
    袁其朋,赵会英,齐宪荣. 2005.现代药物制剂技术.北京:化学工业出版社:7~47
    于学玲. 1992.杜仲皮和叶营养成分的分析.中草药, 23(3): 161
    张康健,董娟娥,马柏林. 2002b.杜仲次生代谢部位差异性的研究.林业科学, 38(6): 12~16
    张健康,王蓝,马柏林等. 2002a.中国杜仲次生代谢物.上海:科学出版社: 3~16
    张康健,赵毅德,董娟娥. 2005.风靡全球的杜仲健康新理念.杨凌:西北农林科技大学出版社:12~13
    赵德义,高锦明,许爱遐,董娟娥,张康健. 2003.杜仲黄酮指纹图谱研究.西北植物学报, 23(11): 1988~1990
    赵德义,徐爱遐,张博勇. 2005.杜仲籽油与紫苏籽油脂肪酸组成的比较研究.西北植物学报, 25(1): 10191~10193
    赵咏梅,李发荣,杨建雄, 2005.连翘苷对营养性肥胖小鼠减肥作用的研究.陕西中医, 26(6): 602
    曾建春,樊粤光,刘建仁,曾意荣,李显彭,易春智. 2009.杜仲含药血清诱导骨髓间充质干细胞定向分化的实验研究,时珍国医国药, 20(29): 2136~2138
    郑旭煦,邵承斌,江澜. 2005.芦丁对单纯性肥胖大鼠血糖和脂代谢紊乱的调节作用.华西药学杂志, 20(2): 11.
    周捷,章蕴毅,张建文,徐晗,陈道峰. 2006.中药杜仲对补体系统的作用,复旦学报(医学版),33(1):101~106
    Deyama T, Nishibe S, Nakazawa Y. 2001. Constituents and pharmacological effects of Eucommia and Siberian ginseng. Acta Pharmacologica Sinica, 22(12): 1057~1070
    Ghodke S K, Ananthanarayan L, Rodrigues L. 2009. Use of response surface methodology to investigate the effects of milling conditions on damaged starch, dough stickiness and chapatti quality. Food Chemistry, 11(2): 1010~1015
    Gonda R, Tomoda M, Shimizu N. 1990. An acidic polysaccharide having acticity on the reticuluoendothelial system from the bark of Eucommia ulmoides. Chem Parma Bull, 38(7): 1966~1969
    Gow C Y,Chiu L H. Inhibitory effects of Du-zhong (Eucommia uhoides Oliv.) against low-density lipoprotein oxidative modification. Food Chemistry, 77(4): 449~456
    Joglekar A M, May A T. 1987. Product excellence through design of experiments. Cereal Foods World, 32(12): 857~868
    Lee W C, Yusof S, Hamid N S A. 2006. Optimizing conditions for hot water extraction of banana juice using response surface methodology (RSM). Journal of Food Engineering, 75: 473~479
    Liew S L, Ariff A B, Raha A R. 2005. Optimization of medium composition for the production of a probiotic microorganism, Lactobacillus rhamnosus, using response surface methodology. International Journal of Food Microbiology, 102: 137~142
    Nath A, Chattopadhyay P K. 2007. Optimization of oven toasting for improving crispness and other quality attributes of ready to eat potato-soy snack using response surface methodology. Journal of Food Engineering, 80: 1282~1292
    Nishibe, Kinoshita H, Takeda H. 1990. Phenolic compounds from stem bark of A canthopanax senticosas and their pharmacological effect in chronic swimming stressed rats. Chem Pharm Bull, 38(6):1767~1765.
    Redd L V A, Wee Y J, Ryu H M. 2008. Optimization of alkaline protease production by batch culture of Bacillus sp.RKY3 through Plackett-Burman and response surface methodological approaches. Bioresourse Technology, 99(7): 2242~2249
    Yen G C, Hsieh C L. 2002. Inhibitory effects of Du-zhong (Eucommia ulmoides Oliv.) against low-density lipoprotein oxidative modification. Food Chemistry, 6(23): 449~456

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700